QT dispersion in sarcoidosis.
QT dispersion (QTd) is the maximal interlead difference in QT interval on surface 12-lead ECG. An increase in QTd is found in various cardiac diseases. Sarcoidosis augments inhomogeneity in ventricular repolarization by sarcoid granuloma, which significantly correlates with ventricular fibrillation. Changes in QTd in the course of sarcoidosis have not been investigated previously. The study included 35 patients with systemic sarcoidosis. The diagnosis of systemic sarcoidosis was made by biopsy. Thallium scintigraphy was performed in all patients with systemic sarcoidosis. Cardiac sarcoidosis was diagnosed in 16 patients based on abnormal thallium scintigraphy and normal coronary arteriography results. QTd, corrected QTd (cQTd), maximum QT (QTmax), maximum corrected QT (cQTmax), minimum QT, and minimum corrected QT intervals were measured. Twenty-four healthy subjects represented the control group for QT interval analysis. In the cardiac sarcoidosis group, mean QTd (+/- SD) was significantly greater than in the noncardiac sarcoidosis group and control group (49.50 +/- 10.86 ms, 28.14 +/- 11.02 ms, and 27.08 +/- 10.41 ms, respectively; p < 0.001). cQTd was significantly greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group and control group (53.17 +/- 10.44 ms, 30.61 +/- 10.94 ms, and 29.01 +/- 10.52 ms, respectively; p < 0.001). QTmax (440 +/- 15.01 ms, 409 +/- 14.86 ms, and 410 +/- 13.21 ms; p < 0.001) and cQTmax (449 +/- 16.31 ms, 417 +/- 12.51 ms, and 418 +/- 11.76, respectively; p < 0.001) were also significantly greater in patients with cardiac sarcoidosis. In a limited follow-up group (11 cardiac and 9 noncardiac sarcoidosis patients), the incidence of premature ventricular contraction (PVC) on ECG was greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group (36% and 0%, respectively; p < 0.05). A medium correlation existed between QTd and PVC (r = 0.331, p < 0.05). QTd, cQTd, QTmax, and cQTmax are prolonged in patients with cardiac sarcoidosis compared to the patients with noncardiac sarcoidosis and control subjects. The incidence of PVC on ECG was greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group.


Immunoparasitology: its contribution to development of new parasite vaccines.
Immunoparasitology--the study of the immunology of host-parasite relationships--can post some notable research successes over the past decade. Progress towards prophylactic molecularly-defined vaccines against human parasitic diseases such as falciparum malaria, schistosomiasis mansoni and cutaneous leishmaniasis, as well as economically-important veterinary parasites, has been good. However, new vaccines are not coming as easily as might be hoped mainly because of several deficiencies in knowledge on the immunology of host-parasite relationships and the unknown relevance of well-characterized model systems to real-life parasitic diseases. In some models, the immunology of resistance and the immunology of disease are understood in broad outline. The availability of isolated antigens and their epitopes has improved quantitation of host immune responses to various life cycle stages of parasites and enabled vaccination efficacy or diagnostic potential to be assessed. One of several major challenges facing the immunoparasitologist interested in vaccine development is overcoming genetically-based unresponsiveness to "oligoepitope", defined-antigen vaccines particularly at the level of helper TH and cytotoxic (Tc) T cells.


Accumulation of inactive p53 protein in oral squamous cell carcinoma: stabilization by protein interaction.
Our previous study showed that p53 protein is accumulated in >60% of cases of oral squamous cell carcinoma (OSCC) and its overexpression is related to poor prognosis. However, the mechanism behind this is still elusive. The present study attempts to dissect p53 alterations at various levels from gene to function in tumor biopsies to understand whether molecular alterations have any relationship with the accumulation of p53 protein in OSCC. Protein-stabilizing mutations were observed in only 13.8% of the samples. Neither p53 polymorphisms nor human papillomavirus (HPV) infection (<2%) has any major role in augmented expression of p53 protein. Analysis of the p53 transcript demonstrated that alteration in the level of p53 mRNA (10%) is not the major mechanistic cause for accumulation of p53 protein, and p21 transcript status showed that the overexpressed p53 protein is functionally inactive. Immunoprecipitation studies demonstrated that the known interactors of p53, such as MDM2 and HSP70, have no significant role in stabilizing p53 and the significant presence of some unknown interactors, sequestering p53, and leading to the aberrant accumulation of p53. Our study suggests that overexpression of inactive p53 protein could be manifested as a result of sequestering from degradation by an unknown interacting protein rather than by gene or transcript level of alteration.


The benign prostatic hyperplasia registry and patient survey: study design, methods and patient baseline characteristics.
To describe the design and baseline cohort characteristics of the Benign Prostatic Hyperplasia (BPH) Registry and Patient Survey, an ongoing, prospective, observational, disease registry documenting management practices and patient outcomes in men in the USA with lower urinary tract symptoms associated with BPH (LUTS/BPH) in actual clinical practice settings. Men with LUTS/BPH who were either untreated or treated with alpha(1)-adrenergic blockers (ABs), 5alpha-reductase inhibitors (5ARIs), a combination of these medications, or anticholinergics, and who met selection criteria, were enrolled at sites throughout the USA. At each visit, standardized forms and validated questionnaires were completed to assess the physicians' management practices and patients' clinical characteristics, sexual function, and health-related quality of life. At the close of recruitment (February 2005), 6909 men (mean age 66.0 years) were enrolled at 402 sites by urologists and primary-care physicians. Before enrolment, 49% of the men were managed with watchful waiting (WW), 21% with uroselective AB monotherapy, 11% with non-uroselective AB monotherapy, 6% with 5ARI monotherapy, 11% with AB + 5ARI, and 2% with anticholinergics. After enrolment, 42% were on WW and 26% were on selective AB monotherapy; changes in other management groups were minimal. Overall, 33% of the men had mild, 52% had moderate and 15% had severe LUTS. The most common comorbidities were hypertension (53%), high cholesterol (45%) and sexual dysfunction (36%). The BPH Registry and Patient Survey will provide information on physician management practices and outcomes of men with LUTS/BPH, while examining the effects of demographics, socio-economics, comorbidities, and medical therapies.


From dynamical systems with time-varying delay to circle maps and Koopman operators.
In this paper, we investigate the influence of the retarded access by a time-varying delay on the dynamics of delay systems. We show that there are two universality classes of delays, which lead to fundamental differences in dynamical quantities such as the Lyapunov spectrum. Therefore, we introduce an operator theoretic framework, where the solution operator of the delay system is decomposed into the Koopman operator describing the delay access and an operator similar to the solution operator known from systems with constant delay. The Koopman operator corresponds to an iterated map, called access map, which is defined by the iteration of the delayed argument of the delay equation. The dynamics of this one-dimensional iterated map determines the universality classes of the infinite-dimensional state dynamics governed by the delay differential equation. In this way, we connect the theory of time-delay systems with the theory of circle maps and the framework of the Koopman operator. In this paper, we extend our previous work [A. Otto, D. Müller, and G. Radons, Phys. Rev. Lett. 118, 044104 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.044104] by elaborating the mathematical details and presenting further results also on the Lyapunov vectors.


Eating behavior style predicts craving and anxiety experienced in food-related virtual environments by patients with eating disorders and healthy controls.
Eating behavior style (emotional, restrictive, or external) has been proposed as an explanation for the differences in response to food-related cues between people who overeat and those who do not, and has been also considered a target for the treatment of eating disorders (EDs) characterized by lack of control over eating and weight-related (overweight/obesity) conditions. The aim of this study was to analyze the relationship between eating behavior style and psychophysiological responses (self-reported food craving and anxiety) to food-related virtual reality (VR) environments in outpatients with bulimia nervosa (BN) and binge eating disorder (BED) and to compare them with healthy participants. Fifty-eight outpatients and 135 healthy participants were exposed to palatable foods in four experimental everyday real-life VR environments (kitchen, dining room, bedroom and café). During exposure, cue-elicited food craving and anxiety were assessed. Participants also completed standardized instruments for the study purposes. ED patients reported significantly higher levels of craving and anxiety when exposed to the virtual food than healthy controls. Eating behavior styles showed strong associations with cue-elicited food craving and anxiety. In the healthy group, external eating was the only predictor of cue-elicited craving and anxiety. In participants with BN and BED, external and emotional eating were the best predictors of cue-elicited craving and anxiety, respectively.


Operative and late coronary artery bypass grafting outcomes in matched African-American versus Caucasian patients: evidence of a late survival-Medicaid association.
This study sought to determine whether African-American versus Caucasian race is a determinant of early or late coronary artery bypass surgery (CABG) outcomes. African Americans are referred to CABG less frequently than Caucasians and Medicaid coverage is disproportionately common among those who are referred. How these factors affect the relative early and late CABG outcomes in these groups is incompletely elucidated. A retrospective cohort comparison of operative and 12-year outcomes for 304 African-American and 6,073 Caucasian consecutive patients who underwent isolated CABG (1991 to 2003) at an urban community hospital was used. Results were further confirmed in propensity-matched subgroups (n = 301 each). African Americans were younger (62 vs. 64 years, median), more were female (46% vs. 30%), more were on Medicaid (29% vs. 6.3%) and had more comorbidities. These differences were eliminated after matching. A total of 161 operative and 1,080 late deaths have been documented. Operative mortality was similar (African American versus Caucasian: 3.0% vs. 2.5%; p = 0.81). Unadjusted Kaplan-Meier survival at 1, 5, and 10 years (93.4%, 80.3%, and 66.1% vs. 94.8%, 86.5%, and 71.7%) was worse in African Americans (hazard ratio [HR] = 1.38; p = 0.004), but similar for matched groups (HR = 1.03; p = 0.97). After risk adjustment, race did not predict operative (odds ratio = 1.17; p = 0.69) or late (HR = 1.15; p = 0.28) mortality. However, Medicaid status (HR = 1.54; p < 0.005) predicted worse survival, which was verified in a case-matched Medicaid (n = 469) versus non-Medicaid analysis. The latter showed that in younger Medicaid patients without companion Medicare coverage, late mortality was nearly doubled (HR = 1.96; p = 0.003) with systematically increasing death hazard after the second year. African-American race per se is not associated with worse operative or late outcomes underscoring that CABG should be based on clinical characteristics only. Alternatively, Medicaid status, which is more prevalent among African Americans, is associated with worse late survival, especially in non-Medicare patients. Studies are needed to elucidate this late Medicaid-CABG outcome association.


Efficient combination of Wang-Landau and transition matrix Monte Carlo methods for protein simulations.
An efficient combination of the Wang-Landau and transition matrix Monte Carlo methods for protein and peptide simulations is described. At the initial stage of simulation the algorithm behaves like the Wang-Landau algorithm, allowing to sample the entire interval of energies, and at the later stages, it behaves like transition matrix Monte Carlo method and has significantly lower statistical errors. This combination allows to achieve fast convergence to the correct values of density of states. We propose that the violation of TTT identities may serve as a qualitative criterion to check the convergence of density of states. The simulation process can be parallelized by cutting the entire interval of simulation into subintervals. The violation of ergodicity in this case is discussed. We test the algorithm on a set of peptides of different lengths and observe good statistical convergent properties for the density of states. We believe that the method is of general nature and can be used for simulations of other systems with either discrete or continuous energy spectrum.


Progression of coronary artery calcification after kidney transplantation.
Calcification of coronary vessels progresses rapidly in hemodialysis (HD) patients and comprises a strong predictor of cardiovascular events. The aim of this prospective study was to evaluate the coronary artery calcification (CAC) in patients with end stage renal disease undergoing regular HD and to determine the effect of renal transplantation (RT) in the progression of CAC, using the Agatston technique for calcium scoring. The study included 20 patients with end-stage renal disease undergoing a regular HD treatment (16 males, 4 females) 54.1 ± 9.5 years old who had just received a renal transplant and 16 more HD patients (11 males, 5 females) 54.4 ± 13.8 years old as control group. The baseline evaluation showed a very high prevalence of CAC in both groups, which was positively correlated with age (p < 0.001) and CRP (p = 0.03). The second (follow-up) evaluation showed a significant slower progression of calcification after RT. In both groups, high calcium score values in the follow-up evaluation had a strong positive correlation with baseline calcium score (p < 0.001).


Highly Oxidized Platinum Nanoparticles Prepared through Radio-Frequency Sputtering: Thermal Stability and Reaction Probability towards CO.
Platinum-oxide nanoparticles were prepared through the radio-frequency (RF) discharge sputtering of a Pt electrode in an oxygen atmosphere. The structure, particles size, electronic properties, and surface composition of the RF-sputtered particles were studied by using transmission electron microscopy and X-ray photoelectron spectroscopy. The application of the RF discharge method resulted in the formation of highly oxidized Pt(4+) species that were stable under ultrahigh vacuum conditions up to 100 °C, indicating the capability of Pt(4+) -O species to play an important role in the oxidation catalysis under real conditions. The thermal stability and reaction probability of Pt(4+) oxide species were analyzed and compared with those of Pt(2+) species. The reaction probability of PtO2 nanoparticles at 90 °C was found to be about ten times higher than that of PtO-like structures.


Functional abdominal bloating.
Ten to 25% of healthy persons have bloating at some time or other. It is very common in those with the irritable bowel syndrome, constipation, or anorexia nervosa. Although the cause of functional bloating remains unknown, old explanations such as a low diaphragm, exaggerated lumbar lordosis, and psychiatric problems have been disproved. New suggestions on its etiology include recent weight gain, weak abdominal muscles, and retained fluid in loops of small intestine. No treatment is of proven benefit, but treatment by weight loss, exercise, and prokinetics should be studied.


Inotropic and vasoactive drug treatment of interleukin 2 induced hypotension in sheep.
The side effects associated with recombinant interleukin 2 administration, including systemic hypotension and a vascular leak syndrome, may limit therapy before reaching maximum doses of this innovative and promising treatment for cancer. In an attempt to reverse this hypotension without decreasing cardiac output and systemic oxygen delivery (DO2), we studied several inotropic agents, dobutamine, dopamine, amrinone, CaCl2, and a pure alpha-adrenergic vasoconstrictor, methoxamine. These were administered singly or in combination to sheep with chronically implanted arterial and pulmonary artery catheters following 24 h of 3 x 10(5) units/kg recombinant interleukin 2. Compared to baseline values, 24 h of recombinant interleukin 2 infusion caused a significant increase in cardiac output from 4.4 +/- 0.9 (SD) to 5.0 +/- 0.6 liters/min, a significant fall in systemic vascular resistance (SVR) from 21 +/- 7 to 15 +/- 5 units, a decrease in mean systemic blood pressure (SBP) from 88 +/- 9 to 78 +/- 6 mm Hg, and a decrease in left ventricular stroke work from 51.5 +/- 8 to 49 +/- 6 gram meters (P less than 0.05) without any change in DO2. Dopamine, dobutamine, and CaCl2 returned SBP to baseline values by increasing cardiac output without increasing SVR. Methoxamine increased SBP by increasing SVR, but cardiac output decreased significantly. A combination of 12 micrograms/kg/min of dopamine and 2 to 3 mg of methoxamine infused over 15 min resulted in an increase in SBP, cardiac output, and SVR to baseline values while maintaining DO2 and oxygen consumption (VO2). We suggest that this latter combination would be appropriate for clinical use since it returns physiological parameters to normal.


The effect of increasing glucose in CPD on the quality of stored blood.
Changes in quality of blood units containing one and a half or double amounts of glucose, stored at +4 degrees C for three weeks were analysed. An experimental preservative containing glucose and fructose (1 : 1) was also used. No other additives (purine or purine-nucleoside) were applied. A standard CPD preservative of the National Inst. of Haematology and Blood Transfusion was used as control. The pH, plasma free haemoglobin, K+ content, red blood cell (RBC) ATP and 2,3-DPG content, and RBC fragility index were determined in each sample. Increase of glucose concentration, the addition of fructose had a beneficial effect on blood pH, and on plasma free haemoglobin and K+ concentration. 150% glucose improved the 2,3-DPG maintenance in stored blood.


Wellbeing and chronic lung disease incidence: The Survey of Health, Ageing and Retirement in Europe.
Previous studies indicate that psychosocial factors can impact COPD prevalence. However, research into this association has predominantly focused on negative factors such as depression. The aim of this study was to examine whether high subjective wellbeing is associated with a lower risk of developing COPD. The sample consisted of 12,246 participants aged ≥50 years from the Survey of Health, Ageing and Retirement in Europe. We used Cox proportional hazards regression to examine the relationship between wellbeing (measured using the CASP-12) and incidence of COPD over a follow-up period of 9 years. There was a significant association between wellbeing and COPD risk. In age-adjusted analyses, a standard deviation increase in CASP-12 score was associated with a reduced risk of COPD; hazard ratios (95% confidence intervals) for men and women were 0.67 (0.60-0.75) and 0.80 (0.73-0.87) respectively. After additional adjustment for demographic and health behaviour variables, this association remained significant for men but not for women: the fully-adjusted hazard ratios were 0.80 (0.70-0.91) and 0.91 (0.82-1.03) respectively. Greater wellbeing is associated with a reduced risk of COPD, particularly in men. Future research is needed to establish whether gender reliably moderates this association.


[Analysis of the macrolide resistance gene in penicillin-resistant Streptococcus pneumoniae].
We examined the penicillin and macrolide resistance of 496 strains of Streptococcus pneumoniae (S. pneumoniae) isolated at Showa University Hospital from November 2004 to May 2005. According to the classification established by the Clinical and Laboratory Standards Institute, the ratio of penicillin susceptible S. pneumoniae (PSSP) was 25.8%, penicillin intermediate S. pneumoniae was 35.9% and penicillin resistant S. pneumoniae (PRSP) was 38.3%. The ratios of macrolide resistant S. pneumoniae were 85.3% for erythromycin and 76.2% for clarithromycin. S. pneumoniae strains were isolated mainly from pediatric patients, and the ratios of PRSP were similar between outpatients (39.8%) and inpatients (45.6%). We screened for mutations in pbp1a, pbp2b and pbp2x, and the retention rate of the macrolide resistance genes, ermB and mefA in 90 strains isolated in the same period. Seventy two strains had at least one mutation in the pbp genes. Interestingly, some of the penicillin susceptible strains had one or two pbp mutations, suggesting a progressive genetic acquirement of penicillin resistance. In screening for retention of the macrolide resistance genes, we found that 42 strains(46.7%) had ermB, 19 strains (21.1%) had mefA and 13 strains (14.4%) had both ermB and mefA. The possession of resistance genes and the minimal inhibitory concentration indicate that the resistance to erythromycin and clarithromycin were induced by ermB or mefA, and the resistance to clindamycin was induced only by ermB. Among the 72 strains with pbps mutations, 65 strains (90.3%) had ermB or mefA or both. Together, these results show that the strains with pbp mutations were being selected and, after acquiring the macrolide resistance gene, transform to multidrug resistant S. pneumoniae.


The effects of the dopamine D₃ receptor antagonist GSK598809 on attentional bias to palatable food cues in overweight and obese subjects.
The mesolimbic dopamine system plays a critical role in the reinforcing effects of rewards. Evidence from pre-clinical studies suggests that D₃ receptor antagonists may attenuate the motivational impact of rewarding cues. In this study we examined the acute effects of the D₃ receptor antagonist GSK598809 on attentional bias to rewarding food cues in overweight to obese individuals (n=26, BMI mean=32.7±3.7, range 27-40 kg/m²) who reported binge and emotional eating. We also determined whether individual differences in restrained eating style modulated the effects of GSK598809 on attentional bias. The study utilized a randomized, double-blind, placebo-controlled cross-over design with each participant tested following acute administration of placebo and GSK598809 (175 mg). Attentional bias was assessed by the visual probe task and modified Stroop task using food-related words. Overall GSK598809 had no effects on attentional bias in either the visual probe or food Stroop tasks. However, the effect of GSK598809 on both visual probe and food Stroop attentional bias scores was inversely correlated with a measure of eating restraint allowing the identification of two subpopulations, low- and high-restrained eaters. Low-restrained eaters had a significant attentional bias towards food cues in both tasks under placebo, and this was attenuated by GSK598809. In contrast, high-restrained eaters showed no attentional bias to food cues following either placebo or GSK598809. These findings suggest that excessive attentional bias to food cues generated by individual differences in eating traits can be modulated by D₃ receptor antagonists, warranting further investigation with measures of eating behaviour and weight loss.


Regulation of expression and trafficking of perforin-2 by LPS and TNF-α.
Perforin-2 is constitutively expressed in macrophages that are required for bacterial control. In this study, we found that perforin-2 is expressed in human macrophages with two isoforms: full-length perforin-2a and a splice variant, perforin-2b. Two isoforms show different subcellular distributions. Perforin-2a was predominantly localized to the membrane of endosome-like vesicles by a C-terminal transmembrane domain. In contrast, the short isoform perforin-2b lacking the transmembrane domain failed to localize to the membrane of vesicles. Furthermore, we determined that the pro-inflammatory stimuli LPS and TNF-α induced perforin-2a expression via the NF-κB pathway and triggered perforin-2a vesicles fusion with lysosomes. On the other hand, we detected the secretion of perforin-2b in response to LPS stimulation. Taken together, our data provide the evidence that membrane-bound and secretory isoforms of perforin-2 are present in human macrophages and may play important roles in immune defense.


Galilean resonances: the role of experiment in Turing's construction of machine intelligence.
In 1950, Alan Turing proposed his iconic imitation game, calling it a 'test', an 'experiment', and the 'the only really satisfactory support' for his view that machines can think. Following Turing's rhetoric, the 'Turing test' has been widely received as a kind of crucial experiment to determine machine intelligence. In later sources, however, Turing showed a milder attitude towards what he called his 'imitation tests'. In 1948, Turing referred to the persuasive power of 'the actual production of machines' rather than that of a controlled experiment. Observing this, I propose to distinguish the logical structure from the rhetoric of Turing's argument. I argue that Turing's proposal of a crucial experiment may have been a concession to meet the standards of his interlocutors more than his own, while his construction of machine intelligence rather reveals a method of successive idealizations and exploratory experiments. I will draw a parallel with Galileo's construction of idealized fall in a void and the historiographical controversies over the role of experiment in Galilean science. I suggest that Turing, like Galileo, relied on certain kinds of experiment, but also on rhetoric and propaganda to inspire further research that could lead to convincing scientific and technological progress.


Sutureless lamellar keratoplasty: a modified approach for fibrin glue application.
To report a case where fibrin glue was applied with a modified approach to secure the graft to the host bed in lamellar keratoplasty. One patient with epithelial membrane dystrophy, Salzmann nodular degeneration, and amyloid deposits in the cornea underwent lamellar keratoplasty by using fibrin glue. The glue components were applied separately: the fibrin component on the stromal bed and thrombin component on the stromal side of the lamellar graft. Tissue adhesion, corneal condition, and visual acuity were evaluated postoperatively. Best-corrected visual acuity 4 months after surgery was 20/30. The graft remained clear and well positioned 9 months after surgery. We report a case of visual acuity improvement and efficient adhesion of the lamellar graft after lamellar keratoplasty by using fibrin adhesive. The components of the glue can be applied separately, allowing more time to position the graft on the stromal bed.


Femara and the future: tailoring treatment and combination therapies with Femara.
Long-term estrogen deprivation treatment for breast cancer can, in some patients, lead to the activation of alternate cellular pathways, resulting in the re-emergence of the disease. This is a distressing scenario for oncologists and patients, but recent intensive molecular and biochemical studies are beginning to unravel these pathways, revealing opportunities for new targeted treatments. Far from making present therapies redundant, these new discoveries open the door to novel combination therapies that promise to provide enhanced efficacy or overcome treatment resistance. Letrozole, one of the most potent aromatase inhibitors, is the ideal candidate for combination therapy; indeed, it is one of the most intensively studied aromatase inhibitors in the evolving combinatorial setting. Complementary to the use of combination therapy is the development of molecular tools to identify patients who will benefit the most from these new treatments. Microarray gene profiling studies, designed to detect letrozole-responsive targets, are currently under way to understand how the use of the drug can be tailored more efficiently to specific patient needs.


Nutrition in the perioperative patient.
The association of malnutrition with surgical morbidity and mortality is well recognized. The question of whether this relationship is causal or simply an association in sick patients has been hotly debated. The field of nutrition support has grown out of the belief that correcting malnutrition will modify associated risks for poor outcome. It has been easier to substantiate this belief in some clinical situations than in others. The evidence for nutrition support during the perioperative period is reviewed and recommendations are made about where nutrition support is most useful and where it may be counterproductive. Some of the important unanswered questions about perioperative nutrition support are raised.


UK advanced practice nurses' experiences of the COVID-19 pandemic: a mixed-methods cross-sectional study.
The aim of the study was to understand the experiences of advanced practice nurses (APNs) in the UK during the 2020 COVID-19 pandemic, particularly in relation to safety, shortages and retention. A cross-sectional, mixed-methods survey. APNs in any UK setting. The survey was sent to an existing UK-wide cohort of APNs. 124 APNs responded (51%). UK-based APNs in this study reported shortages of staff (51%) and personal protective equipment (PPE) (68%) during the first 3 months of the coronavirus outbreak. Almost half (47%) had considered leaving their job over the same 3 months. Despite difficulties, there were reports of positive changes to working practice that have enhanced care. UK APNs report COVID-19-related shortages in staff and equipment across primary and secondary care and all regions of the UK. Shortages of PPE during a pandemic are known to be a factor in the development of mental health sequelae as well as a risk factor for increased turnover and retention issues. Half of APNs surveyed were considering a change in job. The UK risks a further crisis in staff morale and retention if this is not acknowledged and addressed. APNs also expressed concern about patients not receiving routine care as many specialties closed or reduced working during the crisis. However, there were also many examples of good practice, positive changes and innovation.


Prevalence and Influence of the -174 G/C Polymorphism in the Interleukin-6 Gene in Arboviruses Infections.
Dengue virus and Chikungunya virus are arboviruses that affect thousands of people worldwide annually. The mechanisms involved in viral pathogenesis still need to be better understood. Single nucleotide polymorphisms (SNPs) in immune genes may be involved in the protection, susceptibility, and/or progression of these diseases. This study was performed to investigate the SNP -174 G/C in the interleukin-6 (IL-6) gene in patients with dengue or chikungunya from Northeastern Brazil. A total of 581 blood samples were analyzed, of which 244 were part of the negative control group, genomic DNA was extracted, and the SNP was genotyped using real-time polymerase chain reaction (PCR). The data obtained were used to conduct statistical analyses of the genotype and allele frequencies. We suggest that the G/C genotype and C allele of the SNP -174 G/C in the IL-6 gene are related to protection against dengue in the studied population. No significant differences were observed in chikungunya patients. This is the first study that assessed the association of the SNP -174 G/C in patients with chikungunya. We identified the presence of the C allele as a protective factor against dengue in the studied population.


Efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory soft tissue sarcoma: a multicenter, phase 2 trial.
Anti-angiogenic agents have been reported to exert promising clinical activity for advanced soft tissue sarcoma (STS). Apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, is effective and safe for various solid tumors, but its role in STS remains unclear. The aim of this study was to explore the efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory STS. In this multicenter, single-arm, phase 2 trial, patients aged 18-70 years with untreated or chemotherapy-refractory STS were enrolled and received 500 mg apatinib per day. During treatment, patients were followed up with imaging every 8 weeks. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were objective response rate (ORR), overall survival (OS), and adverse events (AEs), which were graded following the National Cancer Institute common terminology criteria for AEs version 4.03. From June 2017 to October 2018, 53 patients were enrolled, 51 of whom received at least one dose of apatinib. Of the 53 patients, 41 (77.4%) had chemotherapy-refractory disease. The median follow-up was 13.3 months. The 6- and 12-month PFS rates were 46.8% and 25.2%, respectively, with a median PFS of 5.6 months [95% confidence interval (CI): 3.8-9.2 months]. The median PFS was 5.5 months for chemotherapy-refractory patients, 9.1 months for untreated patients, 13.9 months for patients with alveolar soft part sarcoma (ASPS), and 3.7 months for patients with clear cell sarcoma (CCS). The 12- and 24-month OS rates were 58.6% and 44.9%, respectively, with a median OS of 20.0 months (95% CI: 9.2-31.1 months). The median OS was 10.7 months for chemotherapy-refractory patients and not estimated for untreated, ASPS, nor CCS patients. In 50 evaluable patients, the ORR was 18.0% and the disease control rate was 86.0%. These results were similar to those of the per-protocol set. The most common grade 3 or 4 AEs included hypertension [30 (58.8%) of 51 patients], leukopenia [12 (23.5%)], proteinuria [8 (15.69%)], and hematuria [8 (15.69%)]. One patient died of unknown cause. This study suggested that apatinib might be effective and tolerable in patients with untreated or chemotherapy-refractory STS (NCT03064243).


[Pain in undernourished children: the mother's perception].
This qualitative study aimed to identify how mothers perceive pain in their undernourished children. Semistructured interviews were realized at the Institute for the Prevention of Malnutrition and Exceptionality--IPREDE (Fortaleza-Ceará-Brazil). Participants were mothers who accompanied their undernourished children. Data analysis revealed the following categories: Coming to the Institution; Pain description and How to take care of the pain. Society needs to take actions, in respect of citizens' rights and culture, with a view to reverting this picture of pain in undernourished children.


Design and Synthesis of AIE-Based Small-Molecule and Nanofibrous Film for Fluorescent Sensing Application.
Fluorescent sensors that respond to environmental conditions (temperature, pressure, and pH) have attracted widespread attention in recent years. Generally, traditional solid-state fluorescent materials tend to suffer from aggregation-induced quenching (ACQ) and difficulty of film forming, limiting their extensive applications. Therefore, researchers are focusing more and more attention on fluorescent sensors with aggregation-induced emission (AIE) effects. Herein, the article reports an AIE molecule (TPEBZMZ) containing tetraphenylethylene (TPE) and benzimidazole fragments. The fluorescence properties of TPEBZMZ in solution and aggregation states have been investigated, and the luminescence performance and aggregation structures of solid-state TPEBZMZ after force and acid treatments have been explored. The results show obvious AIE and fluorescent sensing properties of TPEBZMZ, presenting force- and acid-induced discolorations. Moreover, the TPEBZMZ-based fluorescent nanofibrous film is fabricated by electrospinning the solution of TPEBZMZ blended with polylactic acid (PLA), which shows a good nanofiber film structure and exhibits reversible acid-induced discoloration property, even with only 0.5 wt% TPEBZMZ. This work provides a simple strategy to achieve stimulus-responsive fluorescent film.


Data-Driven Synthetic Cell Factories Development for Industrial Biomanufacturing.
Revolutionary breakthroughs in artificial intelligence (AI) and machine learning (ML) have had a profound impact on a wide range of scientific disciplines, including the development of artificial cell factories for biomanufacturing. In this paper, we review the latest studies on the application of data-driven methods for the design of new proteins, pathways, and strains. We first briefly introduce the various types of data and databases relevant to industrial biomanufacturing, which are the basis for data-driven research. Different types of algorithms, including traditional ML and more recent deep learning methods, are also presented. We then demonstrate how these data-based approaches can be applied to address various issues in cell factory development using examples from recent studies, including the prediction of protein function, improvement of metabolic models, and estimation of missing kinetic parameters, design of non-natural biosynthesis pathways, and pathway optimization. In the last section, we discuss the current limitations of these data-driven approaches and propose that data-driven methods should be integrated with mechanistic models to complement each other and facilitate the development of synthetic strains for industrial biomanufacturing.


Annexins: from structure to function.
Annexins are a family of calcium-dependent phospholipid-binding proteins. They are abundant in the eukaryotic kingdom. Though structurally well investigated in the last twenty years the in vivo function of the annexins is still unclear. The determination of the crystal structure of human annexin V was the first milestone in the structural investigation of this protein family. Succeedingly, a variety of three-dimensional structures of annexin crystals as well as of membrane bound annexins were solved. They should provide tools to understand the in vivo function of the annexin family. Based on the structural knowledge mutagenesis studies and biophysical investigations were started to elucidate possible functions of annexins like membrane binding and ion channel activity.


Efficacy of bromocriptine versus breast binders as inhibitors of postpartum lactation.
Fifty postpartum patients were randomly given either bromocriptine (2.5 mg by mouth b.i.d. X 30 doses) or breast binders for inhibiting lactation. The breast binder group had a high incidence of symptoms (breast pain, engorgement, secretion) for the first week postpartum; these symptoms rapidly decreased by the second week. Bromocriptine successfully suppressed the breast problems in virtually all of the patients who took the drug correctly. Because of the high rate of side effects and a significant incidence of "rebound," the dosage of bromocriptine should probably be changed, and we recommend a revised dosage.


First description of cardiomyopathy syndrome (CMS)-related lesions in wild Atlantic salmon Salmo salar in Norway.
This report represents the first diagnosis of cardiomyopathy syndrome (CMS) in migrating, wild Atlantic salmon Salmo salar from 1 major river and off the coast of Norway. Previously, this disease has been diagnosed only in farmed Atlantic salmon. The possible significance of the disease in wild stocks of salmon is discussed.


Spatial Control of Gene Expression by Nanocarriers Using Heparin Masking and Ultrasound-Targeted Microbubble Destruction.
We developed a method to spatially control gene expression following nonviral delivery of DNA. This method includes surface-modifying DNA nanocarriers with heparin to inhibit passive gene transfer in both the target and the off-target tissues and using ultrasound-targeted microbubble destruction (UTMD) to selectively activate heparin-inhibited gene transfer at the target site. We observed that the engraftment of heparin onto the surface of cationic liposomes reduced off-target gene expression in the liver, a major site of nanoplex accumulation, by more than 700-fold compared to the nonheparinized PEGylated liposomes. We further observed that tumor-directed UTMD increased gene transfer with heparin-modified nanoplexes by more than 10-fold. This method augmented tumor-to-liver selectivity of gene expression by 4000-fold compared to controls. We conclude that heparinization of DNA nanocarriers in conjunction with localized activation of gene transfer by UTMD may enable greater spatial control over genetic therapy.


The potential of postbiotics as a novel approach in food packaging and biopreservation: a systematic review of the latest developments.
Metabolic by-products are part of the so-called postbiotics of probiotics and other beneficial microorganisms, particularly lactic acid bacteria, which have gained popularity as a feasible alternative to improving food quality and safety. Postbiotics in dry and liquid forms can be easily integrated into food formulations and packaging materials, exhibiting antimicrobial and antioxidant effects owing to the presence of multiple antimicrobials, such as organic acids, bacteriocins, exopolysaccharides and bioactive peptides. Postbiotics can thus control the growth of pathogens and spoilage microorganisms, thereby extending the shelf life of food products. Because of their ability to be easily manufactured without requiring extensive processing, postbiotics are regarded as a safer and more sustainable alternative to synthetic preservatives, which can have negative environmental consequences. Additionally, food manufacturers can readily adopt postbiotics in food formulations without significant modifications. This systematic review provides an in-depth analysis of studies on the use of postbiotics in the biopreservation and packaging of a wide range of food products. The review evaluates and discusses the types of microorganisms, postbiotics preparation and modification techniques, methods of usage in dairy products, meat, poultry, seafood, fruits, vegetables, bread, and egg, and their effects on food quality and safety.


Formation of a matter-wave bright soliton.
We report the production of matter-wave solitons in an ultracold lithium-7 gas. The effective interaction between atoms in a Bose-Einstein condensate is tuned with a Feshbach resonance from repulsive to attractive before release in a one-dimensional optical waveguide. Propagation of the soliton without dispersion over a macroscopic distance of 1.1 millimeter is observed. A simple theoretical model explains the stability region of the soliton. These matter-wave solitons open possibilities for future applications in coherent atom optics, atom interferometry, and atom transport.


Adherence to daily, oral TDF/FTC PrEP during periconception among HIV-exposed South African women.
Daily, oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) reduces HIV acquisition for African women. Adherence is key to efficacy and patterns of adherence can be highly variable in real-world settings. Using group-based trajectory modeling (GBTM), we sought to identify distinct patterns of periconception PrEP adherence and evaluate potential baseline predictors of such adherence trajectories. We conducted a single-arm longitudinal study for women aged 18-35 years living in Durban, South Africa with personal or partner plans for pregnancy with a partner with HIV or of unknown serostatus. Participants were offered safer conception counseling, including daily oral PrEP; women who initiated PrEP were given a bottle with an electronic pillcap that recorded when device opens. Weekly adherence to daily PrEP was modeled using GBTM with a censored normal outcome distribution as a function of weeks since PrEP initiation. The number and functional form of the adherence trajectory groups were primarily selected based on Bayesian information criteria (BIC) and confirmed by mean estimated probabilities of group membership. A multivariable version of the selected model assessed baseline predictors of membership in adherence trajectory groups. Overall mean (95% CI) adherence to PrEP was 63% (60%, 67%). We identified four groups of women with distinct patterns of adherence: (1) high (i.e., ≥6 doses per week) steady adherence throughout follow-up (22% of PrEP initiators); (2) moderate (i.e., 4-5 doses per week), but steady adherence (31%); (3) initially high, but consistently declining adherence (21%); and (4) initially moderate adherence, followed by a rapid decline and subsequent rebound (26%). In multivariable-adjusted analyses, older age was associated with membership in the high, steady adherence group as compared to the group identified with an adherence trajectory of initially high, then decline, and finally a rebound. GBTM is useful for exploring potential heterogeneity in longitudinal patterns of medication adherence. Although a large proportion of women in this study achieved high levels of adherence by electronic pillcap initially, far fewer women maintained these levels consistently. Knowledge of different adherence trajectories could be used to develop targeted strategies for optimizing HIV prevention during periconception.


Exogenous and endogenous nitric oxide donors improve post-ischemic tissue oxygenation in early pancreatic ischemia/reperfusion injury in the rat.
In pancreatic ischemia/reperfusion (IR) injury (IRI) the role of nitric oxide (NO) is not completely understood. Using a rat model of normothermic in situ IRI, the effect of endogenous and exogenous NO donors on post-ischemic tissue oxygenation and tissue damage was investigated. IR was induced by 2-hour normothermic in situ ischemia of a pancreatic tail segment pedunculated on the splenic vessels with 2 h of reperfusion in an untreated, an L-arginine- and a sodium-nitroprusside-treated group (Wistar rats, n = 7/group). Animals without ischemia served as controls. Tissue oxygenation (pO(2ti)) was monitored using a pO2-sensitive Clark-type electrode. Histological investigation was performed following a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). Plasma lipase was another marker of organ damage. The administration of L-arginine and sodium nitroprusside caused a significant amelioration of the decrease in pO2i) after reperfusion compared to IR animals (p < 0.05). Histological damage was also reduced in the NO donor groups (p < 0.05). After reperfusion, plasma lipase in the L-arginine-treated animals was significantly lower compared to IR and sodium nitroprusside (p < 0.05). The administration of both endogenous and exogenous NO donors is protective in IRI of the rat pancreas which can be seen by an improvement in post-ischemic tissue oxygenation which indicates better nutritive tissue perfusion, amelioration of the histological tissue injury and, in L-arginine animals, lower lipase levels. NO donors could be useful in the prevention and reduction of the pancreatic IRI.


Histological and ultrastructural observations of eosinophilic keratohyalin granules in filiform papillae of pig tongue.
Cells in filiform papillae of pig tongue possess distinct granules that stain with eosin but little or none with hematoxylin. This eosinophilia differs from the classically described basophilia of keratohyalin granules as is described in skin and keratinized oral mucosa of many species. At the ultrastructural level, electron-dense granules were observed in the cytoplasm and occasionally in the nuclei of cells within the papillae. The granules were round, oval or irregular in shape and varied in size and density. The ultrastructural characterization of these eosinophilic granules is the first reported in the literature.


Analysis of particulate exposure during continuous drug infusion in critically ill adult patients: a preliminary proof-of-concept in vitro study.
In critically ill patients, drug incompatibilities frequently occur because of the number of drugs to be administered through a limited number of infusion lines. These are among the main causes of particulate contamination. However, little data is available to quantify particle exposure during simultaneous IV-drug infusion. The objective of this study was to evaluate the particulate matter potentially administered to critically ill patients. The particulate matter (between 1 μm and 30 mm) of infused therapies used in ICUs for patients suffering from either septic shock or acute respiratory distress syndrome was measured in vitro over 6 h using a dynamic image analysis device, so that both overall particulate contamination and particle sizes could be determined. Data is presented according to the recommendations of the European Pharmacopoeia (≥ 10 and 25 μm). For the six experimental procedures (continuous infusion of norepinephrine, midazolam, sufentanil, heparin, 5% glucose, binary parenteral nutrition and discontinuous administrations of omeprazole, piperacillin/tazobactam and fluconazole), the overall number of particles over the 6-h infusion period was 8256 [5013; 15,044]. The collected values for the number of particles ≥ 10 and 25 μm were 281 [118; 526] and 19 [7; 96] respectively. Our results showed that discontinuous administrations of drugs led to disturbances in particulate contamination. This work indicates the amount of particulate matter potentially administered to critically ill adult patients. Particulate contamination appears lower than previous measurements performed during multidrug IV therapies in children.


An Excel-based implementation of the spectral method of action potential alternans analysis.
Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results.


Attitudes and demands on medical statistical education during the COVID-19 pandemic among undergraduates-postgraduates-teachers: A cross-sectional study in eastern China.
Global coronavirus disease 2019 pandemic leads to the soaring demand for medical statistical applications, bringing a great challenge to medical education at universities worldwide. The purpose of our study is to investigate medical students and teachers attitudes and demands on statistical software education. A multi-city cross-sectional study was conducted in 2021 at medical universities in eastern China. Students and teachers were surveyed through online electronic questionnaires. We collected information on each participant attitudes and demands on medical statistical software usage experience. A total of 895 responses were collected using a validated questionnaire. Most students showed great interest in learning medical statistical software (undergraduates 91.9% vs post-graduates 97.8%, P < .01), thought that statistical software was important (undergraduates 99.2% vs post-graduates 94.7%, P < .01), highly relied on using the SPSS (undergraduates 52.9 % vs post-graduates 77.6%, P < .01) and R package, and felt difficulty in learning statistical software (undergraduates 82.7% vs post-graduates 98.4%, P < .01). Among teachers, the most commonly used statistical software was SPSS (91.2%), followed by the R package. Notably, very few students and teachers thought "Statistical software met needs" (from 21.8% of undergraduates to 8.8% of teachers). There were 75.4% of post-graduates and 96.5% of teachers who thought it was necessary for a university to offer an advanced statistical software curriculum such as the R package in the preferred teaching format of offline class as well as the combination of theory and software practice teaching. This study for the first time demonstrated that most medical undergraduates, post-graduates, and teachers in Anhui Province of eastern China were not satisfied with statistical software usage experience, calling for prompt adjustments to statistical software education in medical universities.


Barriers and facilitators for implementation of a national recommended specialty core-curriculum across UK medical schools: a cross-sectional study using an online questionnaire.
The National Health Service (NHS) Long-Term plan published in 2019 set out healthcare reforms to meet the healthcare demands of UK. Undergraduate specialty core-curricula like dermatology aligns well to the training needs of the future workforce but lacks representation, consistency and implementation. This study explores the barriers and facilitators influencing the implementation of a specialty-specific (dermatology) national core-curriculum across UK medical schools. A constructivist approach was used to develop an online questionnaire and data collected using mixed methodology. Undergraduate dermatology teaching leads across all UK medical schools. 30 out of 42 UK medical schools responded to the survey (71%). 16 out of 30 (53%) responders were unaware of the planned Medical Licensing Assessments (MLA) for all UK graduates in 2024-2025; 43% were unaware if dermatology was mapped to national standards; 50% were unsure if the dermatology was blueprinted on school curricula. Barriers to implementation included competing NHS service commitments, the specialty not seen as a priority and difficulty influencing curricula changes at school level. Facilitators included workforce planning and transparency in funding to support leadership in undergraduate education. Domains identified for curriculum implementation were: (1) awareness of the role of General Medical Council and the MLA, (2) medical education training for teaching leads, (3) lack of recognition and resources for leadership, (4) skills development to map, blueprint and assess specialty core-components, (5) medical school and specialty engagement. This study identifies the potential barriers and facilitators to specialty specific core-curricular implementation across UK medical schools. Lack of standardised training in medical education, time and resources undermine the role of specialty teaching leads as medical educators. Medical school engagement with specialties with mutual support would aid the forthcoming educational reforms.


A device for urologic post-surgical monitoring.
This article reports on the preliminary development of an instrument that is intended to monitor catheterized, post-TURP patients specifically to assist care-providers in the reduction of clot retention. The primary objective of the instrument is to detect conditions that indicate an alarm condition for which the probability of clot retention is considered to be high. In response to an alarm, intervention by means of increased irrigation flow rate or other action is expected. The density of outflow consisting of the mixture of irrigation fluid, urine, and blood from the prostate, is monitored optically. Multiple transducer sites along the catheter improve the monitoring by minimizing the effects of bubbles and particulates in the stream. Development of algorithms for processing the data have concentrated on the use of fuzzy logic in keeping with the linguistic descriptors used by medical experts. This allows the formulation of decision rules that mimic the knowledge base and syntax used by care providers who judge the conditions of the outflow and make decisions about the patient's condition and the optimum flow rate for irrigation fluid. A laboratory prototype has been completed and tested in vitro; a second-generation prototype has been designed in preparation for a clinical study.


Troponin I in atrial fibrillation with no coronary atherosclerosis.
A number of reports have raised the possibility that myocardial strain could be associated to increased plasma levels of troponin I. A 69-year-old, male, Caucasian, patient was admitted with prolonged chest pain and dyspnoea. The electrocardiogram showed atrial fibrillation with a ventricular rate of about 120 to 150/minute. After treatment with digoxin and amiodarone, the patient returned to sinus rhythm. An elevation in the plasma levels of troponin I was noted, with a maximum value of 0.66 ng/ml. Coronary angiography showed absence of coronary artery atherosclerotic lesions. Atrial fibrillation of recent onset and with a relatively high heart rate may be yet another situation in which acute myocardial strain could be the cause of the abnormal release of cardiac troponin I.


Retaining extracorporeal membrane oxygenation cannulae after extracorporeal support in the neonate: is it safe?
The retention of extracorporeal membrane oxygenation (ECMO) cannulae of ECMO is discontinued was originally developed to avoid reexploration of the neck in patients who may require a second course of ECMO. Because of the incidence, at the authors' institution, of thrombi noted on the ends of retained cannulae and their potential to cause significant morbidity, a critical review of this procedure was initiated. A telephone survey of 72 Extracorporeal Life Support Organization (ELSO) centers was conducted, and ELSO registry forms were requested for patients who had their cannulae retained. Twenty-four of these centers had performed the procedure of retaining ECMO cannulae. There were 324 neonatal and pediatric patients who had their cannulae retained, with 41 patients (12%) requiring a second course of ECMO and 17 of 41 (41%) surviving the second course. Twelve of the 24 ELSO centers that retain cannulae have reported complications. Analyses of the patients who had their cannulae retained showed that the three best predictors for requiring a second course of ECMO were the diagnosis of congenital diaphragmatic hernia (CDH) a high oxygenation index just before the initiation of ECMO, and a lengthy first ECMO course. The only difference between the survivors and nonsurvivors of the second course of ECMO was the length of the first ECMO course (P < .05). Five of the 25 patients who required two courses of ECMO had serious complications from their retained cannulae and all were nonsurvivors. The authors conclude that patients with retained ECMO cannulae are at high risk for developing thrombi, which can lead to severe embolic events. Therefore, the procedure of retaining cannulae should only be used in patients at high risk for requiring a second course of ECMO and not for the convenience of surgical availability to remove the cannulae.


Cancer Specific Long Noncoding RNAs Show Differential Expression Patterns and Competing Endogenous RNA Potential in Hepatocellular Carcinoma.
Long noncoding RNAs (lncRNAs) regulate gene expression by acting with microRNAs (miRNAs). However, the roles of cancer specific lncRNA and its related competitive endogenous RNAs (ceRNA) network in hepatocellular cell carcinoma (HCC) are not fully understood. The lncRNA profiles in 372 HCC patients, including 372 tumor and 48 adjacent non-tumor liver tissues, from The Cancer Genome Atlas (TCGA) and NCBI GEO omnibus (GSE65485) were analyzed. Cancer specific lncRNAs (or HCC related lncRNAs) were identified and correlated with clinical features. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in HCC. We found 177 cancer specific lncRNAs in HCC (fold change ≥ 1.5, P < 0.01), 41 of them were also discriminatively expressed with gender, race, tumor grade, AJCC tumor stage, and AJCC TNM staging system. Six lncRNAs (CECR7, LINC00346, MAPKAPK5-AS1, LOC338651, FLJ90757, and LOC283663) were found to be significantly associated with overall survival (OS, log-rank P < 0.05). Collectively, our results showed the lncRNA expression patterns and a complex ceRNA network in HCC, and identified a complex cancer specific ceRNA network, which includes 14 lncRNAs and 17 miRNAs in HCC.


[New model of the endocrine regulation of the female menstrual cycle].
Recent studies have modified remarkably our concepts regarding the hormonal control of the human menstrual cycle. The previously accepted hypothesis was mainly based on rat experiments. It postulated a single integrated hypothalamic-pituitary-ovarian feedback system directed by a "CNS clock". Primate investigations now suggest two interrelated, but separable functional elements, i.e. a hypothalamic-pituitary unit and a gonadal-pituitary unit. The continuous pulsatile, yet unvarying hypothalamic secretion of gonadotropin-releasing hormone (GnRH) facilitates a direct pituitary response to changing estrogen levels. Thus, GnRH plays only a permissive, albeit obligatory role, while an "ovarian clock" provides the critical signal for the cyclic surge of LH and FSH. "Physiological" substitution of exogenous GnRH may be used to treat gonadal dysfunction in women and men which is caused by pathologic changes of the amplitude and/or frequency of hypothalamic GnRH secretion. "Pharmacodynamic" administration of potent GnRH analogues promises to become an effective and safe method of contraception as well as a new approach in the treatment of endometrium and other estrogen-dependent dysfunctions.


An age apart: the effects of intergenerational contact and stereotype threat on performance and intergroup bias.
An experimental study examined the effect of intergenerational contact and stereotype threat on older people's cognitive performance, anxiety, intergroup bias, and identification. Participants completed a series of cognitive tasks under high or low stereotype threat (through comparison with younger people). In line with stereotype threat theory, threat resulted in worse performance. However, this did not occur if prior intergenerational contact had been more positive. This moderating effect of contact was mediated by test-related anxiety. In line with intergroup contact theory, more positive contact was associated with reduced prejudice and reduced ingroup identification. However this occurred in the high threat, but not low threat, condition. The findings suggest that positive intergenerational contact can reduce vulnerability to stereotype threat among older people.


Reconciliation of ontology and terminology to cope with linguistics.
To discuss the relationships between ontologies, terminologies and language in the context of Natural Language Processing (NLP) applications in order to show the negative consequences of confusing them. The viewpoints of the terminologist and (computational) linguist are developed separately, and then compared, leading to the presentation of reconciliation among these points of view, with consideration of the role of the ontologist. In order to encourage appropriate usage of terminologies, guidelines are presented advocating the simultaneous publication of pragmatic vocabularies supported by terminological material based on adequate ontological analysis. Ontologies, terminologies and natural languages each have their own purpose. Ontologies support machine understanding, natural languages support human communication, and terminologies should form the bridge between them. Therefore, future terminology standards should be based on sound ontology and do justice to the diversities in natural languages. Moreover, they should support local vocabularies, in order to be easily adaptable to local needs and practices.


Genetic variation of world soybean maturity date and geographic distribution of maturity groups.
The maturity date of soybean (Glycine max (L.) Merr.) is sensitive to photoperiod, which varies with latitude and growing seasons. The maturity group (MG) system, composed of 13 MGs, is a major approach in characterizing varieties' ecological properties and adaptable areas. A total of 512 world soybean varieties, including 48 MG checks, were tested at a major site (Nanjing, 32.04°N) with portions tested in supplementary sites (Heihe, 50.22°N; Mudanjiang, 44.60°N; Jining, 35.38°N and Nanning, 22.84°N) in China to explore the world-wide MG distribution. The maturity date of the world soybean varied greatly (75-201 d) in Nanjing. Along with soybeans disseminated to new areas, the MGs further expanded during the last 70 years from MG I-VII to the early MG 0-000 in the north continents and to the late MG VIII-X in the south continents with the growth period structure differentiated into two subgroups in each MG 0-VIII except V. The cluster analysis among MGs and subgroups using genome-wide markers validated the MG sequential emergence order and the subgroup differentiation in eight MGs. For future evaluation, in addition to one major site (Nanjing), one supplementary southern site (Nanning) and one supplementary northern site (Heihe) are sufficient.


Hypoglycorrhachia in pediatric patients.
Hypoglycorrhachia (abnormally low cerebro spinal fluid glucose content) eludes exact numerical definition, largely because of the dynamic equilibrium between blood and CSF glucose. A group of 181 pediatric patients with a CSF glucose less than 50 mg/100 ml or a CSF/blood glucose ratio less than 0.50 were studied. Hypoglycorrhachia was present in patients with bacterial meningitis, aseptic meningitis, meningeal carcinomatosis, subarachnoid hemmorrhage, and hypoglycemia. Markedly diminished CSF glucose values were seen primarily in patients with bacterial meningitis. Higher CSF/blood glucose ratios predominated in those with hypoglycemia and neonates with low-normal blood sugars. Following bacterial meningitis and hypoglycemia, aseptic meningitis (including five children with documented enterovirus meningitis and one with documented mumps meningitis) was the third most common cause of hypoglycorrhachia in children. When readily available, positive CSF viral cultures may allow early cessation of antibiotic therapy in two types of patients with meningitis and hypoglycorrhachia: (1) those receiving previous recent antibiotic therapy, and (2) those with CSF findings more typical of a bacterial meningitis.


[In vitro evaluation of chondrocytes combined with Wharton's jelly of human umbilical cord oriented scaffold].
To assess the role and effect of Wharton's jelly of human umbilical cord oriented scaffold on chondrocytes co-cultured in vitro. Chondrocytes from shoulder cartilage of adult New Zealand rabbits were isolated, cultured, amplified, and labelled using fluorescent dye PKH26. Cells were extracted from human umbilical cord tissue using wet-grinding chemical technology to prepare the Wharton's jelly of human umbilical cord oriented scaffold by freeze-drying and cross-linking technology. Second generation of chondrocytes were cultured with Wharton's jelly of human umbilical cord oriented scaffold. Inverted microscope and scanning electron microscope (SEM) were used to observe the cell distribution and adhesion on the scaffold; extracellular matrix secretion of the chondrocytes were observed by toluidine blue and safranin O staining. Cells distribution and proliferation on the scaffold were assessed by fluorescein diacetate-propidium iodide (FDA-PI) and Hoechst33258 staining. The viability of the in vitro cultured and PKH26 fluorescence labelled chondrocytes on the scaffold were assessed via fluorescence microscope. Inverted microscope showed that the cells cultured on the scaffold for 3 days were round or oval shaped and evenly distributed into space of the scaffold. SEM observation showed that large number of cultured cells adhered to the pores between the scaffolds and were round or oval shape, which aggregated, proliferated, and arranged vertically on longitudinally oriented scaffold at 7 days after culture. Histological observation showed that cells distributed and proliferated on the scaffold, and secreted large amount of extracellular matrix at 7 days. Scaffold could guide cell migration and proliferation, and could effectively preserve and promote the secretion of extracellular matrix. Cell viability assessments at 3 days after culture showed most of the adhered cells were living and the viability was more than 90%. PKH26 labelled chondrocytes were seen, which distributed uniformly along the pore of oriented scaffold, and exuberantly proliferated. Wharton's jelly of human umbilical cord oriented scaffold favors adhesion, proliferation, and survival of chondrocytes. It possesses a favorable affinity and cell compatibility. Thus, it is an ideal scaffold for cartilage tissue engineering.


Health and Safety Adoption from Use of a Risk Assessment Document on Irish Farms.
This article describes levels of implementation of occupational health and safety (OHS) controls on a sample of Irish farms following completion of a risk assessment document (RAD) made available as part of a statutory code of practice (COP) for the agriculture sector. The article describes the legislation mandating the COP and the operation of a prevention initiative (PI) among key stakeholders to develop and promote farmer use of the COP and RAD. RADs were collected for farmers (N = 475) and the number and type of OHS controls listed for action were tabulated. A farm audit of OHS standards and of implementation of controls listed for action in the RAD was undertaken among a randomly selected sample of farms (N = 94) where the RAD was completed. The study data indicates that farmers used the RAD to a limited extent, and that their focus in its use was on identifying physical rather than organizational controls. An association was found between farmers who actively implemented controls and positive OHS standards. Farm OHS standards were also associated with farmer attitude to OHS, farm enterprise, farmer age category, and work time needed to operate the farm. Overall, the study data suggests that standards of farm management are a crucial determinant of OHS standards. The study data also indicates that having knowledge of required OHS controls does not ensure implementation. Development of social learning in groups is considered as a significant means of increasing OHS farm adoption.


Toxicokinetic aspects of thallium poisoning. Methods of treatment by toxin elimination.
The elimination techniques which are used in the treatment of thallium poisoning are evaluated in toxicokinetic perspective. Prussian Blue therapy and forced diuresis are effective in the treatment of acute as well as subacute thallium intoxications. Both elimination techniques can be applied without danger from neurological side effects. Generally, the combined use of these techniques is recommended. Since obstipation as well as renal impairment are common in thallium poisoning, extracorporal elimination techniques are of additional importance. In particular, charcoal haemoperfusion has proven to be successful in the elimination of thallium from the body, especially in the early phase of the intoxication.


[THE IDENTIFICATION OF SUB-POPULATIONS OF B-LYMPHOCYTES OF PERIPHERAL BLOOD USING TECHNIQUE OF FLOW CYTOFLUOROMETRY IN HEALTHY INDIVIDUALS AND PATIENTS WITH RHEUMATOID DISEASES].
The study was carried out to apply technique of flow cytofluorometry for immunofenotyping of sub-populations of B-cells of peripheral blood in healthy persons and patients with rheumatoid diseases. The samples included 27 healthy donors, 16 patients with rheumatoid arthritis and 9 patients with systemic lupus erythematosus. The peripheral blood of all participants was analyzed for relative number of CD19+B-cells, total population of memory B-cells (CD19+CD27+); unswitched (CD19+IgD+CD27+) and switched (CD19+IgD- CD27+) memory B-cells, naive (CD19+IgD+CD27-) and transitory (CD19+IgD+CD10+CD38++CD27-) B-cells, plasmablasts (CD19+CD38+++IgD-CD27+CD20+) and long-lived plasmatic cells (CD19+CD138+). The sub-populations of B-cells were identified by technique of multicolor flow cytofluorometry using panel of monoclonal antibodies to surface membrane markers of B-lymphocytes. In normal state, relative number (median-Me; interquartile range 25-75 percentiles) of CD19+B-lymphocytes amounted to 9.1 (6.6-11.6)%; CD19+CD27+memory B-cells - 2.2 (1.6-3.3)%; unswitched and switched memory B-cells - 10 (6.4-12.7)% and 17.7 (14.9-27.0)%; naive B-cells - 65.8 (55.1-73.4)%; transitory B-cells - 0.1 (0.1-0.3)%; plasmablasts - 7.0 (5.0-9.4)%. The long-lived plasmatic cells in peripheral blood were absent. In patients with rheumatoid arthritis percentage of content of total population of memory B-cells were lower than in donors (1.6; 1.00-2.3%; p = 0.038). Under systemic lupus erythematosus was detected decreasing of number of naive B-cells (40.2; 19.7-58.2) and increasing of level of switched memory B-cells (34.2; 21.0-52.7) as compared with donors (p = 0.003 in both cases). The study established no reliable differences between healthy donors and patients with rheumatoid arthritis and systemic lupus erythematosus in the rest of sub-populations of B-lymphocytes. The developed technique of multi-parametric flow cytofluorometry can be recommended for studying homeostasis of B-cells of peripheral blood in healthy persons and patients with auto-immune rheumatoid diseases and also for evaluating and forecasting effectiveness of anti-B-cells therapy.


What are the differentiating clinical and MRI-features of enchondromas from low-grade chondrosarcomas?
To evaluate the role of clinical assessment, conventional and dynamic contrast-enhanced MRI in differentiating enchondromas from chondrosarcomas of long bone. The following clinical and MRI findings were assessed: age, gender, pain, pain attributable to lesion, tumour location, tumour length, presence, depth of endosteal scalloping, bone marrow oedema, soft tissue oedema, cortical destruction, periosteal reaction, bone expansion, macroscopic fat, calcification, soft tissue mass, haemorrhage, dynamic contrast-enhanced MRI. Clinical and MRI findings were compared with histopathological grading. Sixty patients with central chondroid tumours were included (27 enchondromas, 10 cartilaginous lesions of unknown malignant potential, 15 grade 1 chondrosarcomas, 8 high-grade chondrosarcomas). Pain attributed to lesion, tumour length, endosteal scalloping > 2/3, cortical destruction, bone expansion and soft tissue mass were differentiating features between enchondromas and grade 1 chondrosarcomas. Dynamic contrast-enhanced MRI could not differentiate enchondromas from grade 1 chondrosarcomas. Previously reported imaging signs of chondrosarcomas are useful in the diagnosis of grade 1 lesions but have lower sensitivity than in higher grade lesions. Deep endosteal scalloping is the most sensitive imaging sign of grade 1 chondrosarcomas. Pain due to the lesion is an important clinical sign of grade 1 chondrosarcomas. Dynamic contrast-enhanced MRI is not useful in differentiating enchondromas from grade 1 chondrosarcomas. • Differentiation of enchondroma from low-grade chondrosarcoma is challenging for radiologists and pathologists. • The utility of clinical assessment, conventional and dynamic contrast-enhanced MRI was uncertain. • Clinical assessment and conventional MRI aid in differentiating enchondromas from low-grade chondrosarcoma. • Dynamic contrast-enhanced MRI cannot differentiate enchondromas from grade 1 chondrosarcoma.


Augmentation of growth hormone secretion after testosterone treatment in boys with constitutional delay of growth and adolescence: evidence against an increase in hypothalamic secretion of growth hormone-releasing hormone.
The increase in pituitary GH secretion that occurs during mid-late puberty in boys follows an increase in circulating testosterone (T) concentration; the direct mechanism by which this occurs is unknown. We hypothesized that T increases GH secretion during puberty by augmenting hypothalamic output of GHRH. Using constant infusions of a GHRH antagonist, we tested this hypothesis in six early pubertal boys with constitutional delay of growth and adolescence who had a mean chronological age of 14.0 +/- 0.3 yr and mean bone age of 11.4 +/- 0.2 yr. Blood samples were obtained from subjects every 15 min for 24 h during the overnight infusion of normal saline (2000-0600 h) and again during the overnight infusion of GHRH antagonist (0.33 microg/kg/h) the following night. Subjects then received transdermal T (5-mg patch) for 12 h nightly and were studied again after 4 wk of treatment. Serum samples were assayed for GH and total ghrelin; the percent suppression of GH during GHRH antagonist infusion was calculated. Morning serum T rose from 0.44 +/- 0.09 to 4.43 +/- 0.74 microg/liter (P = 0.005). T treatment was associated with a 92.6% increase in mean nocturnal GH secretion area under the curve (830 +/- 177 to 1599 +/- 340 microg/24 h.liter). Infusion of GHRH-antagonist suppressed mean nocturnal GH area under the curve by 29.1% before T treatment (830 +/- 177 to 621 +/- 168 microg/24 h.liter), and by 29.4% after T treatment (1599 +/- 340 to 1182 +/- 249 microg/24 h.liter; P = 0.99). Somatotroph sensitivity to GHRH was tested with 0.1- and 1.0-microg/kg doses of GHRH-44 iv; GH response did not change with regard to T treatment. The mean 24-h concentration of total ghrelin was unchanged with regard to T treatment. In summary, nightly transdermal T administration in six boys with constitutional delay of growth and adolescence increased GH output almost 2-fold, whereas the degree of GH suppressibility by GHRH antagonist remained unchanged. We conclude that the T-associated augmentation of GH secretion during early puberty in boys is unlikely to involve an absolute increase in hypothalamic GHRH output.


Continuity and coordination in primary care: their achievement and utility.
Coordination is a hallmark of primary care. Efforts to improve primary care services should involve assessment of the extent to which coordination is achieved. Our study in three adult and three pediatric clinics demonstrates that existing information concerning patients' problems, therapies, tests, and referrals is often not recognized by primary care practitioners. Recognition of these types of information is better when the practitioner who provides follow-up care is the same from one visit to the next. Information about visits which were anticipated by the practitioner, and particularly the content of these visits, is often neglected. The largest deficit, however, is in recognition of both the occurrence and content of visits unanticipated by the primary care practitioner. Greater efforts to achieve better coordination of care, by improving either continuity of practitioner, communication among practitioners, or the information system, are required before this essential element of primary care becomes a reality.


Selectivity and Mechanism of Fengycin, an Antimicrobial Lipopeptide, from Molecular Dynamics.
Fengycin is a cyclic lipopeptide used as an agricultural fungicide. It is synthesized by Bacillus subtilis as an immune response against fungal infection and functions by damaging the target's cell membrane. Previous molecular dynamics simulations and experiments have led to the hypothesis that the aggregation of fengycins on the membrane surface plays a key role in cell disruption. Here, we used microsecond-scale all-atom molecular dynamics simulations to understand the specificity, selectivity, and structure of fengycin oligomers. Our simulations suggest that fengycin is more likely to form stable oligomers in model fungal membranes (phosphatidylcholine) compared to the model bacterial membranes (phosphatidylethanolamine:phosphatidylglycerol). Furthermore, we characterize the differences in the structure and kinetics of the membrane-bound aggregates and discuss their functional implications.


Early-Life Respiratory Syncytial Virus Infection, Trained Immunity and Subsequent Pulmonary Diseases.
Respiratory syncytial virus (RSV) is often the first clinically relevant pathogen encountered in life, with nearly all children infected by two years of age. Many studies have also linked early-life severe respiratory viral infection with more pathogenic immune responses later in life that lead to pulmonary diseases like childhood asthma. This phenomenon is thought to occur through long-term immune system alterations following early-life respiratory viral infection and may include local responses such as unresolved inflammation and/or direct structural or developmental modifications within the lung. Furthermore, systemic responses that could impact the bone marrow progenitors may be a significant cause of long-term alterations, through inflammatory mediators and shifts in metabolic profiles. Among these alterations may be changes in transcriptional and epigenetic programs that drive persistent modifications throughout life, leaving the immune system poised toward pathogenic responses upon secondary insult. This review will focus on early-life severe RSV infection and long-term alterations. Understanding these mechanisms will not only lead to better treatment options to limit initial RSV infection severity but also protect against the development of childhood asthma linked to severe respiratory viral infections.


Psychopharmacological profile of hydro-alcoholic extract of Euphorbia neriifolia leaves in mice and rats.
The leaf extract of E. neriifolia significantly reduced apomorphine-induced stereotypy in mice at all doses (100, 200, 400 mg/kg body weight) in mice and rats and was devoid of catalepsic effect thereby, suggesting specific dopaminergic receptor modulating activity. The extract (400 mg/kg) potentiated pentobarbitone-induced hypnosis. It showed protection against maximal electro-shock-induced convulsion at 400 mg/kg. E. neriifolia leaf extract had anxiolytic action at 400 mg/kg by increasing the percentage of time spent in open arm in elevated plus-maze. The extract did not reverse scopolamine-induced amnesia on elevated plus-maze. It increased transfer latency at 200 and 400 mg/kg and also in combination with scopolamine. These results indicated anti-anxiety, anti-psychotic and anti-convulsant activity of E. neriifolia leaf extract in mice and rats. Phytochemical study showed the presence of steroidal saponin, reducing sugar, tannins, flavonoids in the crude leaf extract


Dietary Patterns and Attention Deficit Hyperactivity Disorder Among Iranian Children: A Case-Control Study.
Associations between nutritional/dietary factors and mental disorders have been suggested. This study was conducted to assess the relation of major dietary patterns determined by factor analysis with attention-deficit/hyperactivity disorder (ADHD) in a group of Iranian preschool- and school-aged children. This case-control study was conducted with 500 preschool- and school-aged children (4-12 years old) matched by age and sex, in Isfahan, Iran. Dietary intake was identified by a 168-item questionnaire, and major dietary patterns were identified by factor analysis. The multivariable logistic regression is used for the association of dietary patterns with the diagnosis of ADHD. ADHD diagnosis was carried out with the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Two major dietary patterns were identified: healthy and Western. The healthy dietary pattern was rich in fruits, vegetables, vegetable oils, whole grains, legumes, and dairy products. The Western pattern was rich in processed meat, red meat, pizza, eggs, snacks, animal fat, hydrogenated fat, and salt. After controlling for potential confounders, children in the top quintile of the Western dietary pattern score had greater odds having ADHD, compared with those in the lowest quintile (odds ratio [OR] = 3.45; 95% confidence interval [CI], 1.17-18.3; ptrend = 0.03). The healthy pattern was inversely associated with ADHD (OR = 0.46; 95% CI, 0.38-0.91; ptrend = 0.01). A significant independent association was found between the Western dietary pattern and the odds of ADHD. The healthy dietary pattern was associated with lower odds of having ADHD. Prospective studies are needed to confirm these findings.


Serum levels of IL-2, IL-1 alpha, TNF-alpha, and soluble receptor of IL-2 in HIV-1-infected patients.
Serum levels of the interleukins (IL-1 alpha, IL-2), tumor necrosis factor-alpha (TNF-alpha), and soluble receptor of IL-2 (sIL-2R) were studied by enzyme-linked immunosorbent assay (ELISA) in 12 normal healthy controls and 52 HIV-1 seropositive patients. Results indicated that: (1) sIL-2R levels were significantly increased in most HIV-1 seropositive patients. This increase appeared to be correlated with low CD4 cell counts and with the presence of detectable levels of p25 antigen. Furthermore, initially high levels of sIL-2R appeared to be correlated with progression of disease. (2) IL-2 levels were found to be increased in about 43% of asymptomatic carriers (ASY) and subjects with lymphoadenopathy-associated syndrome (LAS) compared with 12% in the case of AIDS-related complex (ARC) and AIDS patients. (3) There was a positive correlation between serum levels of TNF-alpha and IL-1 alpha in nearly all patients. Detectable levels of both cytokines were found in 34% of ASY and LAS patients and only rarely were detectable in ARC and AIDS patients. (4) Sixteen patients in whom progression of disease was observed were studied initially and at the moment they upstaged. No significant modification of serum levels of the three cytokines and sIL-2R studied could be evidenced. It was concluded that sIL-2R could be a useful marker of disease activity and progression, though a prospective study is necessary. For IL-2, IL-1 alpha, and TNF-alpha, this study indicated the presence of variable alterations in serum levels in HIV-1-infected patients.


Familial discoid lupus erythematosus associated with heterozygote C2 deficiency.
Two siblings with chronic discoid lupus erythematosus and several family members were found with heterozygous C2 deficiency. An association with histocompatibility markers HLA-B18 and HLA-Dw2 was demonstrated, and the slow allotype of factor B was present. Linkage studies in this family suggested a close linkage between the C2 deficiency gene and genes coding for B18, Dw2, and BfS antigens. One HLA-ACB/DBf recombinant was observed showing closer linkage between HLA-D and Bf than between HLA-B and Bf.


An Analysis of Maxillary Anterior Teeth Dimensions for the Existence of Golden Proportion: Clinical Study.
Appearance of the face is a great concern to everyone, as it is a significant part of self-image. The study analyzed the clinical crown dimensions of the maxillary anterior teeth with respect to their apparent mesiodistal widths, width-to-height ratio to determine whether golden proportion existed among the South Indian population. A total of 240 dentulous subjects were chosen for the study (120 males and 120 females) age ranging between 18 and 28 years. Full face and anterior teeth images of the subjects were made on specially designed device resembling a face-bow, mounted onto the wall under a standard light source. The width and height of the maxillary central incisors were measured on the stone casts using a digital caliper. The mean perceived maxillary lateral incisor to central incisor width ratio was 0.67 in males and 0.703 in females. The mean perceived maxillary canine to lateral incisor width ratio was 0.744 in males and 0.714 in females. The mean width-to-height ratio of the maxillary central incisor was 79.49% in males and 79.197% in females. The golden proportion was not found between perceived mesiodistal widths of maxillary central and lateral incisors and nor between perceived mesiodistal widths of maxillary lateral incisors and canines. In the majority of subjects, the width-to-height ratio of maxillary central incisor was within 75-80%. There are no statistically significant differences in maxillary anterior teeth proportions between males and females. The results may serve as guidelines for treatment planning in restorative dentistry and periodontal surgery.


Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway.
The present study aimed to investigate the role of semaphorin 4D (Sema4D) in bladder cancer cell proliferation and metastasis in vivo and in vitro. Effects of Sema4D modulation on cancer cell viability and clonogenic abilities were assessed by MTT assay and colony formation assay. Cell apoptosis, cell cycle analysis, transwell assays, and wound-healing assays were also assayed. A mouse model of bladder cancer was established to observe the tumorigenesis in vivo. Our data showed that Sema4D was 4-fold upregulated in clinical bladder cancer tissues relative to noncancerous ones and differentially expressed in bladder cancer cell lines. Knockdown of Sema4D in bladder cancer T24 and 5637 cells significantly decreased cell proliferation, clonogenic potential, and motility. On the contrary, overexpression of Sema4D in bladder cancer SV-HUC-1 cells significantly increased cell viability and motility. Concordantly, knockdown of Sema4D impaired while overexpression of Sema4D promoted bladder cancer cell growth rates in xenotransplanted mice. Cell cycle was arrested by modulation of Sema4D. Cell apoptotic rates and the mitochondrial membrane potentials were consistently increased upon knockdown of Sema4D in T24 cells and 5637 cells. Western blotting revealed that epithelial-mesenchymal transition was promoted by Sema4D. The PI3K/AKT pathway was activated upon Sema4D overexpression in SV-HUC-1 cells, while it was inactivated by knockdown of Sema4D in T24 cells. All these data suggest that Sema4D promotes cell proliferation and metastasis in bladder cancer in vivo and in vitro. The oncogenic behavior of Sema4D is achieved by activating the PI3K/AKT pathway.


Photovoltaic properties of new solar cell based on ideal cubic NaNbO3 thin films: a combined experimental and density functional theory study.
We explore the photovoltaic properties of a novel homojunction solar cell based on NNO(p)/NNO(n) perovskite by employing a combination of material synthesis, characterization and density functional theory calculations that are novel ideas compared to those previously reported in the literature. The band structure reveals that NaNbO3 introduces a n-type semiconductor. Moreover, using DFT calculation, we created n-NNO by a simple substitution in the O site by 4.16% fluorine atoms. Experimental and DFT calculation reveals that NNO perovskite exhibits a direct bandgap of ∼1.6 eV, with a slightly larger two other direct bandgaps of ∼2.13 and 3.24 eV. After extracting the necessary parameters, an electrical modelization of an n-NNO/p-NNO solar cell is performed by Maple software revealed that the cell conversion efficiency can reach 17% which presents a first path to identify a new solar cell based only on perovskite material.


Long-Term Assessment of the Cecal Intubation Rates in High-Performing Colonoscopists: Time for Review.
The cecal intubation rate (CIR) is one of the 3 priority indicators for quality in colonoscopy. Whether continuous measurement of CIR is useful in high performers is uncertain. At an academic center, we identified 16 physicians who performed at least 50 procedures over 6 consecutive years. We analyzed all colonoscopy procedures excluding those with poor/inadequate preparation or severe colitis for CIR trend over the years. We calculated the numbers needed to establish CIR over minimum threshold levels with 95% confidence. The overall CIR was 99.4%. None of the 16 physicians had a CIR <96.6% in any year. Sensitivity analyses including patients without intent to reach the cecum and inadequate bowel preparation had little impact on the results. Overall cecal photo documentation rate was 98.4%. No significant correlation was observed between procedure volume at our center and CIR (σ = -0.196, P = 0.483). Physicians with CIR ≥99% need to have only 24 examinations reviewed to establish CIR is >95%. Continuous measurement of CIR, at least in high performers, appears to be of limited value. Very high performers need to evaluate small number of cases to demonstrate that CIR is above the recommended thresholds.


Laboratory and field studies of Macrocyclops albidus (Crustacea: Copepoda) for biological control of mosquitoes in artificial containers in a subtropical environment.
The cyclopoid copepod Macrocyclops albidus (Jurine) was tested as a potential biological control agent of mosquitoes in laboratory microcosms, in controlled field conditions, and in a 22-mo field experiment using discarded tires. The predator was highly efficient in controlling mosquitoes in all three settings, reaching close to 90% reduction in larval survival under field conditions and exceeding the recommended predation rates for effective mosquito control in laboratory experiments. The predator was most effective on 1-4-d-old larvae. Alternate food and habitat structure significantly influenced the predation rates on mosquito larvae. Once established, the copepod was able to maintain reproducing populations in the field for the duration of the experiments. However, the predator failed to establish populations at four of the experimental field sites. Two of the failures can be attributed to characteristics of the individual tires, such as leaching chemicals, whereas the other two were probably due to site-specific factors. This copepod species is a promising candidate for control of mosquito larvae because it is a widespread and highly effective predator that is capable of establishing and maintaining populations under a wide variety of field conditions. Additionally, M. albidus is relatively easy to culture, maintain, and deliver to the target areas.


Lymph Node Transfer and Neolymphangiogenesis: From Theory to Evidence.
Vascularized lymph node transfer (VLNT) has proven to be a valuable treatment for patients with advanced stages of lymphedema. Although spontaneous neolymphangiogenesis has been advocated to explain the positive effects of VLNT, there is still a lack of supportive biological evidence. The aim of this study was to demonstrate the postoperative formation of new lymphatic vessels using histologic skin sections from the lymphedematous limb. Patients with lymphedema of the extremities who had undergone gastroepiploic vascularized lymph node flap surgery between January of 2016 and December of 2018 were identified. Full-thickness 6-mm skin-punch biopsy specimens were obtained from patients at identical sites of the lymphedematous limb during the VLNT surgical procedure (T0) and 1 year later (T1). The histologic samples were immunostained with anti-podoplanin/gp36 antibody. A total of 14 patients with lymph node transfer were included. At the 12-month follow-up, the mean circumference reduction rate was 44.3 ± 4.4 at the above-elbow/above-knee level and 60.9 ± 7 at the below-elbow/below-knee level. Podoplanin expression values were, on average, 7.92 ± 1.77 vessels/mm 2 at T0 and 11.79 ± 3.38 vessels/mm 2 at T1. The difference between preoperative and postoperative values was statistically significant ( P = 0.0008). This study provides anatomic evidence that a neolymphangiogenic process is induced by the VLNT procedure because new functional lymphatic vessels can be detected in close proximity to the transferred lymph nodes. Therapeutic, IV.


A Case-Based Analysis of Whether Living Related Donors Listed for Transplant Share ESRD Causes with Their Recipients.
Two recent studies reported increased risk of ESRD after kidney donation. In both, the majority of ESRD was seen in those donating to a relative. Confounding this observation is that, in the absence of donation, relatives of those with ESRD are at increased risk for ESRD. Understanding the pathogenesis and risk factors for postdonation ESRD is critical for both donor selection and counseling. We hypothesized that if familial relationship was an important consideration in pathogenesis, the donor and linked recipient would share ESRD etiology. We obtained information from the Organ Procurement and Transplantation Network (OPTN) on all living kidney donors subsequently waitlisted for a kidney transplant in the United States between January 1, 1996 and November 30, 2015, to determine (1) the donor-recipient relationship and (2) whether related donor-recipient pairs had similar causes of ESRD. We found that a significant amount of information, potentially available at the time of listing, was not reported to the OPTN. Of 441 kidney donors listed for transplant, only 169 had information allowing determination of interval from donation to listing, and only 99 (22% of the total) had information on the donor-recipient relationship and ESRD etiology. Of the 99 donors, 87 were related to their recipient. Strikingly, of the 87, only a minority (23%) of donor-recipient pairs shared ESRD etiology. Excluding hypertension, only 8% shared etiology. A better understanding of ESRD in donors requires complete and detailed data collection, as well as a method to capture all ESRD end points. This study highlights the absence of critical information that is urgently needed to provide a meaningful understanding of ESRD after kidney donation. We found that of living related donors listed for transplant, where both donor and recipient cause of ESRD is recorded, only a minority share ESRD etiology with their recipient.