Fate of the herbicide isoxaflutole in the soil of corn fields.
The herbicide isoxaflutole 1 (5-cyclopropyl-4-isoxazolyl)[2- (methylsulfonyl)-4-(trifluoro-methyl)phenyl]-methanone) was applied pre-emergence at the rate of 125 g ha-1 on corn fields located in three sites different as to their soil texture and composition. In the 0-10 cm surface soil layer, the isoxaflutole soil half-life (soil dissipation kinetics of second order) was 9 days in sandy loam (Melle), 15 days in clay loam (Zevekote) and 18 days in loamy sand (Zingem) soil. The sum of the concentrations of isoxaflutole 1 and of its herbicide active metabolite diketonitrile 2 (2-cyano-3-cyclopropyl-1-(2-methylsulfonyl-4- trifluoromethylphenyl)propane-1,3-dione) had a soil half-life (dissipation kinetics of first order) of 45 days in sandy loam, and 63 days in the clay loam and loam sand soils. The soil metabolism of isoxaflutole thus generated, in the soil of field corn crops, a metabolite, the diketonitrile 2, which had an herbicide activity as high as the one of the parent isoxaflutole, and which much extended the herbicide protection given by isoxaflutole. At the crop harvest, isoxaflutole, the diketonitrile 2 and the acid 3 (2-methylsulfonyl-4-trifluoromethylbenzoic acid) were no more detected in soil. During the corn crops, isoxaflutole, and its metabolites diketonitrile 2 and acid 3 were never detected in the 10-15 et 15-20 cm surface soil layers, indicating the very low mobility of these compounds in soil.


Treatment of pulmonary sequestrations by means of endovascular embolization: future or fashion?
Bronchopulmonary sequestration is a rare malformation of the lower respiratory tract. Several methods of treatment have been described since the first publication. We present two cases of female adult patients with bronchopulmonary sequestration. In the first patient an unsuccessful attempt to treat the bronchopulmonary sequestration by means of arterial embolization is described. She was subsequently treated by means of surgical resection, which was the primary treatment for the second patient. Although endovascular techniques are becoming promising, in our opinion surgical resection remains the unique treatment for bronchopulmonary sequestration.


Developmental trends in vocal fundamental frequency of young children.
Fundamental frequency (F0) values are reported for 14 children between the ages of 11 and 25 months, an age period characterized by changes in physiological and linguistic development. Subjects were grouped into 3-month age intervals reflecting a continuum of physical development and were audiotape-recorded during spontaneous speech productions. Acoustic analysis of average F0 and F0 variability was performed. F0 variability was found to decrease as subject age increased, as did segment durations. The decrease in average F0 across the arbitrary age groups did not reach significance; however, when viewed within the overall developmental period and in comparison with data from other studies of younger and older children, average F0 during this age is consistent with a decreasing trend throughout early childhood.


Interaction Between Ropivacaine and a Self-Assembling Peptide: A Nanoformulation for Long-Acting Analgesia.
Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for several hours. In order to fulfill the clinic requirement for long-term analgesia, a long-acting ropivacaine nanocrystal formulation was fabricated through the interaction between ropivacaine and a self-assembling peptide. Transmission electron microscopy, dynamic light scattering, circular dichroism and fluorescence spectrometry were used to examine the structural changes caused by the interaction between ropivacaine and the peptide. Scanning electron microscopy, dynamic light scattering, Fourier transform infrared spectrometry, X-ray diffraction and optical microscopy were used to characterize the ropivacaine-peptide nanocrystal. In vitro drug release and pharmacokinetics study were conducted to evaluate the slow-release profile of the nanocrystal formulation. A rodent cutaneous trunci muscle reflex model was used to evaluate the nociceptive blockade effects, and histological analysis was used to evaluate the local toxicity. A rodent plantar incisional pain model was used to evaluate the analgesic effect. Soluble ropivacaine monomers interacted with the Q11 peptide through π-π stacking and remolded its self-assembling structure, leading to the formation of drug/peptide nanoparticles which could be mineralized to form drug/peptide nanocrystals by adjusting the pH. Under physiological condition, the nanocrystals could release free ropivacaine slowly. As evaluated in rodent models, the anesthetic and analgesic effects of this formulation were significantly extended without causing toxicity. Based on the interaction between ropivacaine and Q11, a controllable biomineralization process could be induced to obtain homogeneous nanocrystals, which could be used as an injectable long-acting analgesic formulation. This crystallization strategy utilizing the peptide-drug interaction also provided a promising pathway to fabricate long-acting formulations for many other small molecular drugs.


Rheumatology at the general practitioner/hospital interface: a study of prevalence and access to specialist care.
Four general practices with a combined population of 23,300 in the west of Scotland participated in a record research and questionnaire assessment of 551 patients with rheumatic diseases. The study describes the prevalence, levels of disability found, and the types of service used. Even with this number of patients it was not possible to detect any significant differences in disability levels, use of second line drugs, or aids/appliances when comparing practices with adequate or inadequate access to rheumatological facilities (general practitioner perception). General practice is an appropriate setting in which to investigate the effect of service provision, but larger studies will be needed to reach more definite conclusions.


Effects of acetazolamide on ventilatory, cerebrovascular, and pulmonary vascular responses to hypoxia.
Acute mountain sickness (AMS) may affect individuals who (rapidly) ascend to altitudes higher than 2,000-3,000 m. A more serious consequence of rapid ascent may be high-altitude pulmonary edema, a hydrostatic edema associated with increased pulmonary capillary pressures. Acetazolamide is effective against AMS, possibly by increasing ventilation and cerebral blood flow (CBF). In animals, it inhibits hypoxic pulmonary vasoconstriction. We examined the influence of acetazolamide on the response to hypoxia of ventilation, CBF, and pulmonary vascular resistance (PVR). In this double-blind, placebo-controlled, randomized study, nine subjects ingested 250 mg acetazolamide every 8 h for 3 d. On the fourth test day, we measured the responses of ventilation, PVR, and CBF to acute isocapnic hypoxia (20 min) and sustained poikilocapnic hypoxia (4 h). Ventilation was measured with pneumotachography. Hypoxia was achieved with dynamic end-tidal forcing. The maximum pressure difference across the tricuspid valve (DeltaPmax, a good index of PVR) was measured with Doppler echocardiography. CBF was measured by transcranial Doppler ultrasound. In normoxia, acetazolamide increased ventilation and reduced DeltaPmax, but did not influence CBF. The ventilatory and CBF responses to acute isocapnic hypoxia were unaltered, but the rise in DeltaPmax was reduced by 57%. The increase in DeltaPmax by sustained poikilocapnic hypoxia observed after placebo was reduced by 34% after acetazolamide, the ventilatory response was increased, but the CBF response remained unaltered. Acetazolamide has complex effects on ventilation, PVR, and CBF that converge to optimize brain oxygenation and may be a valuable means to prevent/treat high-altitude pulmonary edema.


[The first stages of ovum implantation in rats castrated before noon on the 5th day of gestation].
Ovariectomy performed on the 5th day of gestation before noon does not stop the first stages of ovoimplantation in the Rat. On the morning of the 6th day the reactivity to trypan blue is increased. Most of the blastocysts are well fixed in their implantation chamber. The closure of the uterine lumen is effective and the decidual reaction has developed around the blastocyst implantation chamber. These results are discussed and compared to morphological and physiological data. The hypotheses concerning the active role probably played by the blastocyst are also discussed.


Control of translation and mRNA degradation by miRNAs and siRNAs.
The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro RNAs (miRNAs) and short interfering RNAs (siRNAs) and can affect mRNA degradation and translation, as well as chromatin structure, thereby having impacts on transcription rates. In this review, we discuss possible mechanisms by which miRNAs control translation and mRNA degradation. An emerging theme is that miRNAs, and siRNAs to some extent, target mRNAs to the general eukaryotic machinery for mRNA degradation and translation control.


Evolution of sensitivity to fosfomycin at Jimenez Diaz Foundation.
The sensitivity to fosfomycin of more than 8,000 strains of bacteria isolated from products recevied by the laboratory between 1972 and 1974 has been studied. Some were studied by the dilution technique in a solid medium and the remainder was studied by diffusion. A single 50-mug disc was used and the strains inhibited by concentrations of less than 64 mug/ml or with inhibition halos of 15 mm diameter or more were considered sensitive. It is clear from this study that there are no significant changes in the sensitivity of the bacteria studied during the above-mentioned time, with the exception of a decrease in that of indole-positive Proteus, Providentia and Klebsiella.


Chronic toxicity studies with vigabatrin, a GABA-transaminase inhibitor.
The GABA-transaminase inhibitor, vigabatrin, has been shown to have a rather low degree of acute toxicity in several animal species. Oral administration of the drug at 1,000 mg/kg/day for 2-4 weeks caused decreased food consumption and weight loss with resultant prostration and death in both rats and dogs. Dosages of 200 mg/kg/day were tolerated for a year without clinical signs in dogs, although rats suffered reduced weight gains and convulsions after 3-4 months when given the drug in the diet. The convulsions continued to occur frequently throughout the one-yr study, but abated 3-4 months after cessation of treatment. The only consistent histopathologic evidence of toxicity in rats and dogs has been the finding of intramyelinic edema (microvacuolation) in the brain, most notably in certain areas of white matter (cerebellum, reticular formation and optic tract in rats and columns of fornix and optic tract in dogs). No lesions were found in the spinal cord or peripheral nervous system. It took several weeks for the microvacuolation to develop, even at high dosages, but it did not continue to progress thereafter, even though a slight effect was noted at dosages as low as 30-50 mg/kg/day after one yr of treatment. The intramyelinic edemia disappeared within a few weeks after treatment was withdrawn. No residual effects were observed in dogs, whereas rats exhibited swollen axons and microscopic mineralized bodies in the cerebellum. Monkeys exhibited no adverse clinical effects except for occasional loose stools at 300 mg/kg/day. After 16 months of oral treatment at 300 mg/kg/day any suggestion of intramyelinic edema was considered to be equivocal, and there was no evidence of any effect in the 50 or 100 mg/kg/day monkeys after 6 yr of treatment. Higher doses caused chronic diarrhea, thus limiting the dosage in this species. Vigabatrin was shown to be well absorbed in rat, dog and man, whereas dose-limited absorption occurred in the monkey. Metabolism is practically nil in all 4 species and the primary elimination pathway is by glomerular filtration. Because vigabatrin is an irreversible inhibitor of GABA-transaminase and the enzyme has a slow turnover rate, plasma levels of the drug are not indicative of its pharmacologic activity. For this reason cerebrospinal fluid levels of GABA and vigabatrin were evaluated, with considerable species differences being noted. The significance of these differences in relation to the differences in toxic response is discussed.


Formal Synthesis of (-)-Quinagolide: Diastereoselective Ring Expansion via a Bicyclic Aziridinium Ion Strategy to Access the Octahydrobenzo[g]quinoline Architecture.
The diastereoselective formal synthesis of (-)-quinagolide, a D2 receptor agonist, has been achieved. The synthesis started from l-pyroglutamic acid and relied on utilization of (a) a stereospecific catalytic hydrogenation and diastereoselective Horner-Emmons-Michael cascade to obtain functionalized prolinate, (b) a Lewis acid mediated Pummerer cyclization to construct a tricyclic fused ring system, and (c) a diastereoselective ring expansion via a bicyclic aziridinium intermediate to access the required 3-substituted piperidine scaffold.


Immunotherapy of tumors with protein vaccine based on chicken homologous Tie-2.
Tie-2 is an endothelium-specific receptor tyrosine kinase known to play a key role in tumor angiogenesis. The present study explores the feasibility of immunotherapy of tumors by using a protein vaccine based on chicken Tie-2 as a model antigen to break the immune tolerance against Tie-2 in a cross-reaction between the xenogeneic homologous and self-Tie-2. In this study, a chicken homologous Tie-2 protein vaccine (chTie-2) and a corresponding mouse Tie-2 vaccine as a control were prepared and the antitumor effect of these vaccines was tested in two tumor models (murine B16F10 melanoma and murine H22 hepatoma). Immunotherapy with chTie-2 was found effective in two tumor models. Autoantibodies against mouse Tie-2 were detected in sera of mice immunized with chTie-2 through Western blot analysis and ELISA assay. Anti-Tie-2 antibody-producing B cells were detectable by ELISPOT. Histologic examination revealed that autoantibodies were deposited on the endothelial cells of tumor tissues. Purified immunoglobulins from chTie-2-immunized mice could induce the apoptosis of human umbilical vein endothelial cells in vitro. Importantly, adoptive transfer of purified immunoglobulins led to antitumor effect in vivo; apparently, angiogenesis was significantly inhibited in these tumors. Furthermore, the antitumor activity and production of autoantibodies could be abrogated by depletion of CD4+ T lymphocytes. Our findings may provide a vaccine strategy for cancer therapy and show the potential utilization of interference with Tie-2 pathway.


As the health insurance underwriting cycle turns: what next?
After twenty-five years of a consistent health insurance underwriting cycle, the pattern of insurer profitability changed greatly in the 1990s, raising speculation about the future. We conclude from interviews with industry experts that health plan competition and limits on plans' ability to predict costs will continue to drive a cycle, albeit one even more muted than it was in the 1990s because of changes in industry structure and forecasting improvements. Plans will price closer to cost trends and forego the more heated price competition that drove major losses in the past, reducing premium volatility but possibly leading to higher average premiums.


Right Ventricular Myocardial Infarction due to Right Coronary Artery Total Occlusion Originating From the Distal Left Circumflex Artery.
An isolated single coronary artery is rare but often associated with other congenital cardiac malformations and myocardial ischemia. We report a rare case of right ventricular myocardial infarction due to total occlusion of the right coronary artery originating from the distal left circumflex artery.


Bone graft substitutes in periodontal and peri-implant bone regeneration.
Regenerative medicine provides different therapy alternatives alongside gold standard autogenous grafts for the treatment of periodontal or peri-implant osseous defects. Continuing progress in the field of alloplastic bone substitutes has yielded promising solutions to the appropriate indications with the membrane technique either alone or in combination with enamel matrix derivatives. Their clinical outcomes, however, still require critical discussion.


Interactive Health Literacy and Symptom Self-management in Patients With Lung Cancer: A Critical Realist Analysis.
Patients with lung cancer experience multiple symptoms requiring self-management. Little is known about how self-management is influenced by interactive health literacy, defined as communicating with healthcare providers to obtain and process information. This study explored how interactive health literacy relates to symptom self-management among patients with lung cancer. A second aim explored how interactive health literacy might be integrated into the Individual and Family Self-management Theory. This study used a cross-sectional mixed-methods design. Quantitative data included demographics, the All Aspects of Health Literacy Scale, and the Memorial Symptom Assessment-Short Form. Qualitative data were collected using semistructured interviews. Data analysis followed a critical realist model. Twelve adults who recently received treatment for lung cancer reported an average of 14 symptoms that caused moderate distress. Average interactive health literacy of the sample was in the moderate range. Participants' experiences of self-management differed based on their interactive health literacy. A generative mechanism proposes that those with higher interactive health literacy who accessed online information used this information as a basis for engaging with providers regarding potential symptom self-management strategies. Interactive health literacy skills may play a role in patients' ability and confidence in symptom self-management through interactions with oncology providers. Further research should clarify the relationship between interactive health literacy, self-efficacy, and collaboration with oncology providers. The patient-provider relationship is a key factor influencing how patients obtain and process symptom self-management information. Oncology providers should implement patient-centered strategies to engage patients in symptom self-management.


Peripheral blood gene expression profiling for cardiovascular disease assessment.
Whole blood gene expression profiling has the potential to be informative about dynamic changes in disease states and to provide information on underlying disease mechanisms. Having demonstrated proof of concept in animal models, a number of studies have now tried to tackle the complexity of cardiovascular disease in human hosts to develop better diagnostic and prognostic indicators. These studies show that genomic signatures are capable of classifying patients with cardiovascular diseases into finer categories based on the molecular architecture of a patient's disease and more accurately predict the likelihood of a cardiovascular event than current techniques. To highlight the spectrum of potential applications of whole blood gene expression profiling approach in cardiovascular science, we have chosen to review the findings in a number of complex cardiovascular diseases such as atherosclerosis, hypertension and myocardial infarction as well as thromboembolism, aortic aneurysm, and heart transplant.


Distribution of CD8 T Cells and NK Cells in the Stroma in Relation to Recurrence or Metastasis of Nasopharyngeal Carcinoma.
The purpose of this study was to explore the expression and distribution of tumor-infiltrating immune cells (TIICs) and their relationship with recurrence and metastasis of nasopharyngeal carcinoma (NPC). The gene expression profiles of NPC were downloaded from GEO database (GSE53819 and GSE64634). The abundance of TIICs in NPC samples was calculated by the CIBERSORT algorithm, and TIICs with higher expression were screened in NPC. Then, we performed immunohistochemistry experiments to evaluate the expression of selected TIICs in 94 NPC samples from the Affiliated Hospital of Zunyi Medical University. We further explored the relationship between TIICs and recurrence and metastasis of NPC. The results based on the GEO database showed that the expression of CD8 T cells, NK cells, macrophages and plasma cells was higher than that in normal tissues. Immunohistochemistry results showed that CD8 T cells, NK cells, macrophages and plasma cells were mainly expressed in the stroma, and the expression of CD8 T cells and NK cells in the stroma of patients without recurrence or metastasis was significantly higher than that in patients with recurrence or metastasis of NPC. Kaplan-Meier analysis showed that patients with high CD8 T cells and high NK cells expression in the stroma had favorable recurrence or metastasis-free survival and overall survival (P<0.05). Univariate and multivariate Cox analyses indicated that CD8 T cells and NK cells in the stroma were independent factors for the recurrence or metastasis of NPC. The expression of CD8 T cells, NK cells, macrophages and plasma cells is significantly higher than that in normal tissues. Among them, the expression of CD8 T cells and NK cells is closely related to the recurrence and metastasis of NPC. They are independent factors affecting the recurrence and metastasis of NPC.


[Relationship between continuous renal replacement therapy and hypophosphatemia in critically ill children].
Objective: To investigate the incidence and prognosis of hypophosphatemia in critically ill children treated with continuous blood purification (CBP). Methods: The medical records of the critically ill patients, who were treated with CBP, admitted to pediatric intensive care unit (PICU) of Shanghai Children's Hospital from May 2014 to April 2017 were retrospectively analyzed. The serum phosphorus levels were tested before CBP, at 48-72 h during CBP, at the end of CBP and on the next day after CBP finished. Phosphorus supplement was given to the children with severe hypophosphatemia. Results: A total of 85 patients met the inclusion criteria. The serum phosphorus levels at the 4 indicated time points were (1.4±0.5), (0.7±0.3), (0.8±0.3), (0.9±0.4) mmol/L, respectively (F=45.21, P<0.05). Among the children, 66 cases (78%) had hypophosphatemia during CBP. The incidences of moderate and severe hypophosphatemia were 32 (48%) and 9 (14%), respectively. There were 41 patients with CBP replacement rates of (35-49) ml/(kg·h), while 44 patients with CBP replacement rates of 50-70 ml/(kg·h). There were significant differences at 48-72 h during CBP, the end of CBP and on the next day after CBP ((0.8±0.4) vs. (0.5±0.2), (1.0±0.3) vs. (0.6±0.2), and (1.1±0.4) vs. (0.8±0.2) mmol/L; t=7.672, 4.060, 14.440, P<0.05). Atotal of 9 cases were treated with sodium glycerophosphate. Among the 85 children, 24 (28%) patients died while 61 (72%) survived. There were no significant differences between the two groups in serum phosphorus levels at the indicated time points ((1.4±0.5) vs. (1.4±0.5), (0.7±0.3) vs. (0.7±0.3), (0.7±0.3) vs. (0.8±0.3), and (1.0±0.3) vs. (0.9±0.3) mmol/L, respectively, P>0.05). Conclusions: Hypophosphatemia is prone to occur during CBP, which probably related to the replacement rate. There was no significant relationship between hypophosphatemia and mortality in critically ill children after giving phosphorus supplementation.


[Electron microscopic observations on Pseudomonas cocovenenans].
A strain of food-poisoning bacterium has been isolated by Jin Jiexiang (1963) in China from the fermented cornflour that has gone bad. These pathogenic microorganism has been identified and named Pseudomonas by Zhao Naixin in 1988, which is the same species as P. cocovenenans. The characteristics of them were conformed to these of the species P. cepacia of section 2 of the genus Pseudomonas. In view of the fact that the fine structures of the above mentioned three strains of Pseudomonas have not been described yet, we decided to observe them with electron microscope. Results indicate there are many things in common among the three strains, such as: appearing short rods, 0.6-0.8 microns in diameter by 1.5-2.0 microns in length, one polar multiflagella; non-pili, non-capsules, non-endospores; containing intranuclear inclusions (electron-dense bodies or concentric laminae bodies), accumulating intracytoplasmic PHB granules; forming filaments, minicells and bizarrecells; producing extracellular cellulose-like materials by the three strains have not been reported previously.


Spinopelvic challenges in primary total hip arthroplasty.
There is no universal safe zone for cup orientation. Patients with spinal arthrodesis or a degenerative lumbar spine are at increased risk of dislocation. The relative contributions of the hip (femur and acetabulum) and of the spine (lumbar spine) in body motion must be considered together. The pelvis links the two and influences both acetabular orientation (i.e. hip flexion/extension) and sagittal balance/lumbar lordosis (i.e. spine flexion/extension). Examination of the spino-pelvic motion can be done through clinical examination and standard radiographs or stereographic imaging. A single, lateral, standing spinopelvic radiograph would be able to providemost relevant information required for screening and pre-operative planning. A significant variability in static and dynamic spinopelvic characteristics exists amongst healthy volunteers without known spinal or hip pathology. The stiff, arthritic, hip leads to greater changes in pelvic tilt (changes are almost doubled), with associated obligatory change in lumbar lordosis to maintain upright posture (lumbar lordosis is reduced to counterbalance for the reduction in sacral slope). Following total hip arthroplasty and restoration of hip flexion, spinopelvic characteristics tend to change/normalize (to age-matched healthy volunteers). The static spinopelvic parameters that are directly associated with increased risk of dislocation are lumbo-pelvic mismatch (pelvic incidence - lumbar lordosis angle >10°), high pelvic tilt (>19°), and low sacral slope when standing. A high combined sagittal index (CSI) when standing (>245°) is associated with increased risk of anterior instability, whilst low CSI when standing (<205°) is associated with increased risk of posterior instability. Aiming to achieve an optimum CSI when standing within 205-245° (with narrower target for those with spinal disease) whilst ensuring the coronal targets of cup orientation targets are achieved (inclination/version of 40/20 ±10°) is our preferred method.


Traumatic glenohumeral instability in athletes.
Traumatic glenohumeral instability represents a commonly encountered clinical scenario. Two case vignettes are presented along with an evidence-based review of epidemiology, pathophysiology, diagnosis, and treatment options.


Systematic grading of surgical complications in live liver donors according to Clavien's system.
The lack of consensus on how to evaluate surgical complications of donors in live donor liver transplantation (LDLT) and incoherence of cumulative data hampers efficient comparison of the outcome worldwide. We considered that the application of the internationally validated classification system introduced by Clavien in 2004 might be beneficial. Operative complications of 243 patients who underwent live donor hepatectomy for adult LDLT between January 1996 and October 2005 at the University of Tokyo were analyzed according to the system. Definitions for each grade in the system are: grade I, deviation from the normal postoperative course but without the need for therapy; grade II, complication requiring pharmacologic treatment; grade III, complication with the need for surgical, endoscopic or radiological intervention (IIIa/b: without/with the need for general anesthesia); grade IV, life-threatening complication requiring intensive care; grade V, death. Surgical morbidity was recognized in 67 donors (28%). No deaths occurred. The numbers of patients with complications were: grade I, 36 (15%); II, 10 (4%); IIIa, 12 (5%); IIIb, 9 (4%); IV, 0; V, 0. Six in IIIb underwent surgical repair for bile leakage. Clavien's system is simple and informative. It may serve as a common tool for the quality assessment in live liver donor surgery worldwide, and we propose its application whenever surgical complication of live donor is discussed.


Sonography of the adrenal glands: normal glands and small masses.
To evaluate sonographic imaging of the normal adrenal glands, anterior transverse and longitudinal scans were made on 200 patients who had no evidence of adrenal disease. In 78 additional patients who were suspected of having adrenal masses, anterior and posterior transverse and longitudinal scanning and longitudinal oblique scanning were done. Anterior transverse scanning proved to be the best single method of scanning the adrenal gland and small adrenal masses. The normal adrenal gland which is 3-6 mm thick and adrenal masses as small as 1.3 cm can be delineated. Although the frequency of visualizing normal adrenal glands (78.5% on the right and 44% on the left) with sonography is not as high as with CT, masses are more readily detected than the normal glands. The accuracy for detecting adrenal masses is very high, with a false-negative rate of only 3%. Sonography can be a useful screening test for many patients who are suspected of having adrenal masses. However, for obese patients the image is degraded and a higher false-positive rate (3.5%) is obtained. CT provides better resolution for such patients.


Relation of enzyme activity to local/global stability of murine adenosine deaminase: 19F NMR studies.
Adenosine deaminase (ADA, EC 188.8.131.52) is a ubiquitous (beta/alpha)8-barrel enzyme crucial for purine metabolism and normal immune competence. In this study, it was observed that loss of enzyme activity of murine ADA (mADA) precedes the global secondary and tertiary structure transition when the protein is exposed to denaturant. The structural mechanism for this phenomenon was probed using site-specific 19F NMR spectroscopy in combination with [6-19F]tryptophan labeling and inhibitor binding. There are four tryptophan residues in mADA and all are located more than 12 A from the catalytic site. The 19F NMR spectra of [6-19F]Trp-labelled mADA show that the urea-induced chemical shift change of 19F resonance of W161, one of the four tryptophan 19F nuclei, correlates with the loss of enzyme activity. The urea-induced chemical shift change of another 19F resonance of W117 correlates with the change of the apparent rate constant for the binding of transition-state analogue inhibitor deoxycoformycin to the enzyme. On the other hand, the chemical environment of the local region around W264 does not change significantly, as a consequence of perturbation by low concentrations of urea or substrate analog. The results indicate that different regions of mADA have different local stability, which controls the activity and stability of the enzyme. The results provide new insights into the relationship between the function of a protein and its conformational flexibility as well as its global stability. This study illustrates the advantage of 19F NMR spectroscopy in probing site-related conformational change information in ligand binding, enzymatic activity and protein folding.


Membrane association and multimerization of TcpT, the cognate ATPase ortholog of the Vibrio cholerae toxin-coregulated-pilus biogenesis apparatus.
The toxin-coregulated pilus (TCP) is one of the major virulence factors of Vibrio cholerae. Biogenesis of this type 4 pilus (Tfp) requires a number of structural components encoded by the tcp operon. TcpT, the cognate putative ATPase, is required for TCP biogenesis and all TCP-mediated functions. We studied the stability and localization of TcpT in cells containing in-frame deletions in each of the tcp genes. TcpT was detectable in each of the biogenesis mutants except the DeltatcpT strain. TcpT was localized to the inner membrane (IM) in a TcpR-dependent manner. TcpR is a predicted bitopic inner membrane protein of the TCP biogenesis apparatus. Using metal affinity pull-down experiments, we demonstrated interaction between TcpT and TcpR. Using Escherichia coli as a heterologous system, we investigated direct interaction between TcpR and TcpT. We report that TcpR is sufficient for TcpT IM localization per se; however, stable IM localization of TcpT requires an additional V. cholerae-specific factor(s). A LexA-based two-hybrid system was utilized to define interaction domains of the two proteins. We demonstrate a strong interaction between the cytoplasmic domain of TcpR and the N-terminal 100 amino acid residues of TcpT. We also demonstrated the ability of the C-terminal domain of TcpT to multimerize.


Comparative study of electron transfer reactions at the ionic liquid/water and organic/water interfaces.
The rates of electron transfer (ET) reactions at the water/ionic liquid (IL) interface have been measured for the first time using scanning electrochemical microscopy. The standard bimolecular rate constant of the interfacial ET between ferrocene dissolved in 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide and aqueous ferricyanide (0.4 M-1 cm s-1) was found to be approximately 30 times higher than the corresponding rate constant measured at the water/1,2-dichloroethane interface. The driving force dependence of the ET rate was investigated over a wide range of the interfacial potential drop values (>200 mV). The observed Butler-Volmer-type dependence is discussed in terms of the interfacial model. The ET was also probed at the interface between aqueous solution and the mixture of the IL and 1,2-dichloroethane. The mole fractions in this mixture were varied systematically to investigate the transition from the water/organic to the water/IL interface. The observed decrease in the rate constant with increasing mole fraction of 1,2-dichloroethane is in contrast with the previously reported direct correlation between the electrochemical rate constant and the diffusion coefficient of redox species in solution.


Prevalence of intimate partner violence among women presenting to an urban adult and paediatric emergency care department.
To determine the prevalence of intimate partner violence among women seeking emergency healthcare. Trained research assistants asked eligible adult women presenting to an urban emergency care department during randomly selected 4-hour time blocks to participate in a study about violence between partners. A structured interview was conducted that included a partner violence screen, identification of high risk, and lifetime prevalence. Culturally safe study protocols were developed that held women's and children's safety paramount. 174 women aged 16 to 88 years of age participated. Overall, 21% (95% CI=15.2%, 27.4%) of women screened positive for partner violence, and 44% (95% CI=36.9%, 51.7%) reported partner violence at some time in their adulthood. A large proportion of women were willing to answer sensitive questions regarding partner violence during an emergency visit. Rates of partner violence among women seeking healthcare were significant, and consistent with rates reported internationally. Healthcare providers have an opportunity to identify and intervene to assist women exposed to abuse by a partner.


Unusual Occurrence of Incarceration and Breakage of the Coiled Shaft of the Intramedullary Reamer during Closed Intramedullary Nailing of Tibia.
Intramedullary (IM) nailing is a well-established method of treating closed tibia shaft fracture. We hereby describe an unusual incidence of the incarceration of the flexible IM reamer in the distal fracture fragment with breakage of the coiled shaft of the reamer in the proximal third of tibia during closed IM nailing. This case report highlights the usefulness of making a small window in the tibia to aid retrograde removal of incarcerated reamer. A 26-year-old male patient had road traffic accident and sustained a close fracture of the right distal 3rd tibia along with segmental fracture of the adjacent fibula. The tibia nailing was done under combined spinal and epidural anesthesia. The proximal tibia was approached by a midline incision with splitting of the patellar tendon. The reduction of the fracture fragments was done and the guide wire was inserted. The medullary canal was narrow and hence the initial reaming was started with the smallest available, that is, 8 mm reamer. After crossing the fracture site, we noticed that reamer coiled shaft got broken into multiple pieces in the medullary cavity at proximal 3rd tibia. The fracture site was exposed and a linear osteotomy was done in distal tibial fragment. Through this window, the broken reamer was pushed in the retrograde manner and was delivered out. Most of the broken metal pieces of the reamer shaft were removed with pituitary rongeur. An 8 mm solid IM nail was passed in antegrade manner across the fracture site and was locked distally and proximally. The operative wounds were irrigated and closure was done in layers. The patient was allowed partial weight bearing at 3 weeks post-surgery with gradually progressing to full weight bearing at 10 weeks after confirming clinical and radiological union. To handle this unusual occurrence one needs to stay calm, make a small window to aid retrograde removal of reamer and remove the fragmented pieces of the coiled shaft of the reamer. In tight medullary canal, it is desirable to have smaller diameter reamers, that is, 6 mm during the surgery.


The effect of message frames and CVD risk factors on behavioral outcomes.
To examine the interactive effects of message frames and CVD risk factors on women's knowledge, beliefs, efficacy, and behavioral intentions. In a randomized experiment, women (n = 395) read either a loss- or gain-framed heart disease prevention message to test differential effects by risk factor status. Messages significantly increased knowledge, self-efficacy and intervention efficacy beliefs, and behavioral intentions. Frames had significantly different effects on self-efficacy and behavioral intent to engage in detection behaviors by parental risk factor status. Further study is warranted to assess effects of frames on behavioral outcomes among women at elevated CVD risk.


Economics of central line--associated bloodstream infections.
Hospital-acquired infections add considerable morbidity and mortality to patient care. However, a detailed economic analysis of these infections on an individual case basis has been lacking. The authors examined both the hospital revenues and expenses in 54 cases of patients with central line-associated bloodstream infections (CLABs) over 3 years in 2 intensive care units and compared these financial data with patients who were matched for age, severity of illness on admission, and principal diagnosis. The average payment for a case complicated by CLAB was $64 894, and the average expense was $91733 with gross margin of -$26 839 per case and a total loss from operations of $1 449 306 in the 54 cases. The costs of CLABs and the associated complications averaged 43% of the total cost of care. The elimination of these preventable infections constitutes not only an opportunity to improve patient outcomes but also a significant financial opportunity.


Compression molding and tensile properties of thermoplastic potato starch materials.
The mechanical and melt flow properties of two thermoplastic potato starch materials with different amylose contents were evaluated. The materials were prepared by mixing starch, glycerol, and water, mainly in the weight proportions of 10:3:4.5. Compression molding was used to produce sheets/films with a thickness in the range of 0.3-1 mm. After conditioning at 53% relative humidity (RH) and 23 C, the glycerol-plasticized sheets with a higher amylose content (HAP) were stronger and stiffer than the normal thermoplastic starch (NPS) with an amylose content typical for common potato starch. The tensile modulus at 53% RH was about 160 MPa for the high-amylose material and about 120 MPa for the plasticized NPS. The strain at break was about 50% for both materials. The stress at break was substantially higher for the HAP materials than for the NPS materials, 9.8 and 4.7 MPa, respectively. Capillary viscometry at 140 C showed that the high-amylose material had a higher melt viscosity and was more shear-thinning than the NPS. Dynamic mechanical measurements indicated a broad transition temperature range for both types of starch material. The main transition peaks for glycerol-plasticized starch were located at about room temperature with the transition for the HAP material being at a somewhat higher temperature than that of the NPS material with a lower amylose content. It was also noted that the processing conditions used during the compression molding markedly affected the mechanical properties of the starch material.


Microsurgical phalloplasty: Anatomical study evaluating the use of the external pudendal vessels as recipients.
The inferior epigastric artery (IEA) is commonly used as a recipient vessel in microsurgical phalloplasty but its use can be associated with abdominal parietal complications (hernia, bulging). To preclude such complications and avoid involvement of the femoral artery, we assessed an external pudendal artery (EPA) as a recipient vessel. We studied the disposition of the external pudendal system and its general anatomy. Then we compared the external diameter of the EPA to that of the first branches of the femoral artery. The most important point was to determine the location of the EPA through a reference line to facilitate a surgical approach. We then illustrated this preliminary study with a clinical case to check the reliability of the identified landmarks. Ten adult cadavers were dissected. The arteries of interest were part of a system consisting of either a common trunk or a duplicated system. The branches of the pudendal system arose from either the femoral artery or the deep femoral artery. On a horizontal reference line passing through the two pubic tubercles, we observed that 83% of EPAs arose between the reference line and 3 cm below it, at the level of a vertical axis centered on the femoral artery. The EPA could be suitable as recipient vessel in phalloplasty owing to its location, size, and ease of dissection. Using it instead of the IEA precludes abdominal parietal complications and reduces scarring in the recipient area.


A self-administered version of a brief measure of suffering: first aspects of validity.
Measuring the impact of illness is important for several reasons. Recently, a new instrument was introduced using a pictorial approach in measuring the perception of suffering caused by illness: the Pictorial Representation of Illness Measure (PRISM). The aim of the present study was to introduce a self-administered version of PRISM and to provide some first data on its validity. A postal survey was conducted in subjects with the chronic depigmentation disorder vitiligo. Participants were members of the German vitiligo association. The response rate was 60.6%. Data of 333 respondents completing the PRISM were used for analysis. Besides illness-related measures, psychological variables were assessed with the following instruments: Satisfaction with Life Scale (SWLS), five-item version of the Mental Health Inventory, adaptation of the Skindex-29, a quality-of-life measure for skin diseases. Only 2.9% did not fill in the PRISM. Self-illness separation correlated as predicted with some illness-related variables. The distance was significantly larger in subjects whose depigmentation was no longer spreading. Significant correlations were also found with mental health (0.50), satisfaction with life (-0.28), perceived impairment of outward appearance (-0.65), and the Skindex subscales 'emotions' (-0.66) and 'functioning' (-0.67). Data suggest that PRISM can be self-administered. Measures of convergent validity confirm the usefulness of the new measure.


Plant-derived neurotoxic amino acids (beta-N-oxalylamino-L-alanine and beta-N-methylamino-L-alanine): effects on central monoamine neurons.
In the present study the subacute effects of beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) on CNS monoamine neurons in rats were investigated following intracisternal injections or local intracerebral administration into substantia nigra. In vitro effects of BOAA and BMAA on high-affinity synaptosomal uptake of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) were also examined. Intracisternal administration of BMAA decreased NA levels in hypothalamus, whereas no effects were seen on DA or 5-HT levels. Following intranigral injections of BOAA, NA levels tended to decrease in several regions, whereas the DA levels and the levels of DA metabolites were unaffected in all regions analyzed. Loss of tyrosine hydroxylase (TH) immunoreactivity in the intranigral injection sites and the presence of TH-immunoreactive pyknotic neurons near the borders of the injection sites were observed following both BOAA and BMAA treatments. Furthermore, substance P-immunoreactive terminals in substantia nigra pars reticulata were also found to have disappeared within the lesioned area following either BOAA or BMAA injections. Incubations with both BOAA and BMAA (10(-5) M) reduced high-affinity [3H]NA uptake in cortical synaptosomes to 69% and 41% of controls, respectively, whereas the striatal high-affinity [3H]DA uptake and the cortical high-affinity [3H]5-HT uptake were unaffected by BOAA or BMAA. The results demonstrate that both BOAA and BMAA can affect central monoamine neurons, although the potency and specificity of these substances on monoamine neurons when administered acutely into cerebral tissue or liquor cerebri seem to be low. However, the in vitro studies indicate selective effects of both compounds on NA neurons in synaptosomal preparations.


The time window of pet ownership exposure modifies the relationship of Environmental Tobacco Smoke with lung function: A large population-based cohort study.
There is a large body of evidence linking Environmental Tobacco Smoke (ETS) exposure with impaired lung function. However, it is not known whether exposure to pets modifies this relationship. To investigate if pet ownership changes the association between ETS exposure and lung function, a population-based sample of 7326 children, 7-14 years old, were randomly recruited from 24 districts in northeast China. Lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF) was measured by spirometry, while pet ownership time periods and ETS exposure were collected by questionnaire. Two-level regression analysis was done, with covariates controlled for. The results showed pet exposure in certain early lifetime windows modified the associations of ETS exposure on decreased lung function in children. Among children exposed to current ETS, those exposed to pets in utero had greater reductions in lung function (for instance: OR for reduced FVC (<85% predicted) = 10.86; 95% CI: 3.80-30.97) than those not exposed to pets in utero (OR = 2.32; 95% CI: 1.76-3.05) (pinteraction = 0.005). While, children exposed to current pet ownership reduced the lung function impairment induced by ETS exposure during the first 2 years of life and/or ETS exposure during pregnancy, especially for FVC impairment. For instance, OR (95%CI) for reduced FVC (<85% predicted) was 0.81 (0.56, 1.18) and 1.42 (1.15, 1.74), respectively, for children with or without current pet ownership exposed to ETS during the first 2 years of life (pinteraction = 0.010). Furthermore, pet type or number of pets did not significantly modify associations between ETS exposure and lung function. In conclusion, the timing of pet ownership modified associations between ETS exposure and lung function, pet ownership in utero and during the first 2 years of life significantly worsened the adverse impacts of passive smoking on lung function.


Mental health impact of COVID-19 on Saudi families and children with special educational needs and disabilities in Saudi Arabia: A national perspective.
The COVID-19 pandemic revealed a multidimensional impact on mental health due to health concerns, social distancing and lockdowns, job loss, and limits in institutional support. Accordingly, COVID-19 may disproportionally impact families with special educational needs and disabilities (SEND) due to the already high prevalence of mental health conditions in children with SEND and their parents. Hence, it is essential to determine the short-term impact of the pandemic on the mental health of families with SEND to identify their ongoing health, including psychological wellbeing and support needs. The current study examines the anxiety level and concerns of children with SEND and their parents living in Saudi Arabia. A cross-sectional national study design was utilized as a part of an international consortium using an online Arabic survey. Data were collected from the Ministry of Human Resources and Social Development beneficiaries from May to July 2020. The sample consisted of 1,848 parents of children with SEND aged between 1 and 18 years (mean = 9.66; SD = 4.31). A descriptive and bivariant analysis is reported. Parental worries on all those concerns when the pandemic started were significantly higher than before the pandemic, p < 0.050. Parental-perceived general anxiety had risen significantly across time, p < 0.001, and their perceived anxiety when the pandemic started exceeded their anxiety before the pandemic, p < 0.001. The general anxiety of children with SEND had risen significantly across time (from before the pandemic to when it had started to during the pandemic), p < 0.001. The children's general worries at the start of the pandemic had correlated significantly and positively with their anxiety, adaptive, maladaptive, and coping efficacies, and parental anxiety scores, p < 0.010 each. Anxiety levels were high in SEND and their caregivers before and during COVID-19. At the start of the pandemic, the anxiety, adaptive, maladaptive, coping efficacies, and parental anxiety scores of children with SEND were significantly and favorably correlated. These findings support the notion of SEND-specific anxiety and patterns of coping in SEND and their caregivers. The notion also attests to the institutional support required for this specifically vulnerable population during epidemics.


Three new serovars of Chlamydia trachomatis: Da, Ia, and L2a.
Three new Chlamydia trachomatis serovars were identified by several monoclonal antibodies in the microimmunofluorescence test and are proposed to be called Da, Ia, and L2a. Each was clearly distinguishable from the related serovars D, I, and L2. To date, 7, 41, and 4 isolates of the respective serovars have been identified. Each appears to be distributed worldwide. The findings meet previously established criteria for establishment of new serovars.


Prognostic Significance of the Nodal Ratio and Number of Positive Nodes in Patients With Squamous Cell Carcinomas of the Head and Neck.
The lymph node status has high prognostic relevance in head and neck squamous cell carcinoma (HNSCC). This study aimed to address the hypothesis that the number of positive nodes and the nodal ratio have a prognostic impact on survival in HNSCC. A retrospective analysis of 221 patients with HNSCC and clinical N+ status who underwent a neck dissection during primary surgery or after definitive radio(chemo)therapy was performed. The possible influence of age, sex, TNM stage, number of positive nodes and nodal ratio on survival was analyzed by univariate and multivariate Cox models and log-rank tests. On average, 30.1 lymph nodes were removed and 4.96 metastases were detected. The mean nodal ratio was 9.4%, the median nodal ratio was 5.3%. Multivariate analysis demonstrated a nodal ratio of ≥6-<12.5% [hazard ratio (HR)=2.33, 95% confidence interval (CI)=1.24-4.37; p=0.008] and of ≥12.5% (HR=2.86, 95% CI=1.40-5.84; p=0.004) compared to nodal ratio 0, number of positive nodes pN=1 compared to number of positive nodes=0 (HR=2.02, 95% CI=1.08-3.80. p=0.029), as well as N3 compared to N0 (HR=8.10, 95% CI=1.89-34.66; p=0.005), and Mx compared to M0 (HR of 2.76, 95% CI=1.59-4,79, p≤0.001) were of main importance for poor prognosis. Postoperative radio(chemo)therapy after surgery was associated with prolonged survival in multivariate analysis (HR=0.37, 95% CI=0.24-0.57; p≤0.001). The nodal ratio and number of positive nodes seem to have a high prognostic impact in patients with HNSCC and can be of value in identifying patients at high risk who warrant more aggressive therapy.


Bio-electrosprays: a novel electrified jetting methodology for the safe handling and deployment of primary living organisms.
Electrohydrodynamic jetting (EHDJ) which is also known as electrosprays (ES) has recently been elucidated as a unique electrified biotechnique for the safe handling and deployment of living organisms. This high intensity electric field driven jetting methodology is now referred to as "bioelectrosprays" (BES). Previously these charged jets have only been shown to jet-process immortalized cells which have undergone expected cellular behavior when compared with control cells. In this paper we demonstrate the ability to jet process primary living organisms in the stable conejetting mode. Finally the viability of the bio-electrosprayed living organisms has been assessed employing a flow cytometry approach which forms the discussion in this paper. Our findings further establish BES as a competing biotechnique, which could be employed for the deposition of primary living organisms according to a predetermined active cellular architecture. One day this could be used for the fabrication of viable tissues and organs for repair or replacement. These advanced studies carried out on BES have direct widespread applications ranging from developmental biology to regenerative and therapeutic medicine, which are a few amongst several other areas of study within the life sciences.


A model of lived experience leadership for transformative systems change: Activating Lived Experience Leadership (ALEL) project.
This discursive paper presents a lived experience leadership model as developed as part of the Activating Lived Experience Leadership (ALEL) project project to increase the recognition and understanding of lived experience leadership in mental health and social sectors. The model of lived experience leadership was formulated through a collaboration between the South Australian Lived Experience Leadership & Advocacy Network and the Mental Health and Suicide Prevention Research and Education Group. As one of the outcomes of the ALEL research project, this model incorporates findings from a two-year research project in South Australia using participatory action research methodology and cocreation methodology. Focus groups with lived experience leaders, interviews with sector leaders and a national survey of lived experience leaders provided the basis of qualitative data, which was interpreted via an iterative and shared analysis. This work identified intersecting lived experience values, actions, qualities and skills as characteristics of effective lived experience leadership and was visioned and led by lived experience leaders. The resulting model frames lived experience leadership as a social movement for recognition, inclusion and justice and is composed of six leadership actions: centres lived experience; stands up and speaks out; champions justice; nurtures connected and collective spaces; mobilises strategically; and leads change. Leadership is also guided by the values of integrity, authenticity, mutuality and intersectionality, and the key positionings of staying peer and sharing power. This model is based on innovative primary research, which has been developed to encourage understanding across mental health and social sectors on the work of lived experience leaders in seeking change and the value that they offer for systems transformation. It also offers unique insights to guide reflective learning for the lived experience and consumer movement, workers, clinicians, policymakers and communities.


The potential use of selective 5-HT2C agonists in treating obesity.
Activation of central 5-HT2C receptors as a strategy for appetite suppression and weight control is supported by animal pharmacology and human clinical studies. Considerable evidence comes from the weight-loss effects of fenfluramine, a non-selective 5-HT2C agonist. Advances in molecular pharmacology have led to an understanding of the effects of 5-HT2C receptor activation on food intake and satiety, in addition to providing insight into the causes of cardiac valvular insufficiency and pulmonary hypertension associated with the use of fenfluramine. However, clinically validated animal models of drug-induced disease and knowledge of the molecular mechanisms of these safety issues is lacking. For this reason, the development of selective 5-HT2C agonists for the treatment of obesity has remained a challenge.


[Occurrence of epistaxis in relation to seasonal factors].
A retrospective study of the occurrence of epistaxis in relation to seasonal factors--mean monthly air temperature and atmospheric pressure is presented. During three consecutive years a total of 18 625 patients were seen in the ENT Clinic: 1,357 (7.3%) were suffering from epistaxis (about 38 patients with epistaxis per month). The epistaxis appeared more frequently in men (60.1%), aged from 41 to 60 years (41.3%) The Increased occurrence of epistaxis was related to the low temperature period. The highest occurrence of epistaxis was observed during the cold season--between December and April (from 9.2 to 13.36% of all patients seen per month), suggesting the relationship between epistaxis and infections of the upper respiratory tract. No relation between epistaxis and mean monthly atmospheric pressure was observed.


No interaction of barrier-to-autointegration factor (BAF) with HIV-1 MA, cone-rod homeobox (Crx) or MAN1-C in absence of DNA.
Barrier-to-autointegration factor is a cellular protein that protects retroviral DNA from autointegration. Its cellular role is not well understood, but genetic studies show that it is essential and depletion or knockout results in lethal nuclear defects. In addition to binding DNA, BAF interacts with the LEM domain, a domain shared among a family of lamin-associated polypeptides. BAF has also been reported to interact with several other viral and cellular proteins suggesting that these interactions may be functionally relevant. We find that, contrary to previous reports, BAF does not interact with HIV-1 MA, cone-rod homeobox (Crx) or MAN1-C. The reported interactions can be explained by indirect association through DNA binding and are unlikely to be biologically relevant. A mutation that causes a premature aging syndrome lies on the previously reported MAN1-C binding surface of BAF. The absence of direct binding of BAF to MAN1-C eliminates disruption of this interaction as the cause of the premature aging phenotype.


Successful treatment of three synchronous primary malignant tumours-reflection on surgical, pathological and oncological aspects and decision making.
We report a case of a patient with triple synchronous primary malignancies (breast, colon, kidney) which has not been previously reported in the literature. A 70-year-old woman was diagnosed with invasive ductal carcinoma of the left breast with axillary lymph node metastasis. During the staging period, renal cell carcinoma on the left kidney and mucinous adenocarcinoma in the proximal colon were found. Since the breast tumour demonstrated favourable biology, aromatase inhibitor therapy had been started and simultaneous right colectomy and left nephrectomy was performed. Six months after the first diagnosis, left sector excision and axillary block dissection were performed. Adjuvant FEC chemotherapy was administered, followed by radiotherapy. During the 16-month follow-up period disease recurrence was not detected.


Incidence and risk factors of non-device-associated pneumonia in an acute-care hospital.
To update current estimates of non-device-associated pneumonia (ND pneumonia) rates and their frequency relative to ventilator associated pneumonia (VAP), and identify risk factors for ND pneumonia. Cohort study. Academic teaching hospital. All adult hospitalizations between 2013 and 2017 were included. Pneumonia (device associated and non-device associated) were captured through comprehensive, hospital-wide active surveillance using CDC definitions and methodology. From 2013 to 2017, there were 163,386 hospitalizations (97,485 unique patients) and 771 pneumonia cases (520 ND pneumonia and 191 VAP). The rate of ND pneumonia remained stable, with 4.15 and 4.54 ND pneumonia cases per 10,000 hospitalization days in 2013 and 2017 respectively (P = .65). In 2017, 74% of pneumonia cases were ND pneumonia. Male sex and increasing age we both associated with increased risk of ND pneumonia. Additionally, patients with chronic bronchitis or emphysema (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.40-3.06), congestive heart failure (HR, 1.48; 95% CI, 1.07-2.05), or paralysis (HR, 1.72; 95% CI, 1.09-2.73) were also at increased risk, as were those who were immunosuppressed (HR, 1.54; 95% CI, 1.18-2.00) or in the ICU (HR, 1.49; 95% CI, 1.06-2.09). We did not detect a change in ND pneumonia risk with use of chlorhexidine mouthwash, total parenteral nutrition, all medications of interest, and prior ventilation. The incidence rate of ND pneumonia did not change from 2013 to 2017, and 3 of 4 nosocomial pneumonia cases were non-device associated. Hospital infection prevention programs should consider expanding the scope of surveillance to include non-ventilated patients. Future research should continue to look for modifiable risk factors and should assess potential prevention strategies.


Coloring Rate of Phenolphthalein by Reaction with Alkaline Solution Observed by Liquid-Droplet Collision.
Many important chemical reactions are induced by mixing two solutions. This paper presents a new way to measure rates of rapid chemical reactions induced by mixing two reactant solutions using a liquid-droplet collision. The coloring reaction of phenolphthalein (H2PP) by a reaction with NaOH is investigated kinetically. Liquid droplets of H2PP/ethanol and NaOH/H2O solutions are made to collide, which induces a reaction that transforms H2PP into a deprotonated form (PP(2-)). The concentration of PP(2-) is evaluated from the RGB values of pixels in the colored droplet images, and is measured as a function of the elapsed time from the collision. The obtained rate constant is (2.2 ± 0.7) × 10(3) M(-1) s(-1), which is the rate constant for the rate-determining step of the coloring reaction of H2PP. This method was shown to be applicable to determine rate constants of rapid chemical reactions between two solutions.


The Domain and Microstructure of Resin-Bonded Magnets.
This paper presents domain and structure studies of bonded magnets made from nanocrystalline Nd-(Fe, Co)-B powder. The structure studies were investigated using scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), Mössbauer spectroscopy and X-ray diffractometry. On the basis of performed qualitative and quantitative phase composition studies, it was found that investigated alloy was mainly composed of Nd2(Fe-Co)14B hard magnetic phase (98 vol%) and a small amount of Nd1.1Fe4B4 paramagnetic phase (2 vol%). The best fit of grain size distribution was achieved for the lognormal function. The mean grain size determined from transmission electron microscopy (TEM) images on the basis of grain size distribution and diffraction pattern using the Bragg equation was about ≈130 nm. HRTEM images showed that over-stoichiometric Nd was mainly distributed on the grain boundaries as a thin amorphous border of 2 nm in width. The domain structure was investigated using a scanning electron microscope and metallographic light microscope, respectively, by Bitter and Kerr methods, and by magnetic force microscopy. Domain structure studies revealed that the observed domain structure had a labyrinth shape, which is typically observed in magnets, where strong exchange interactions between grains are present. The analysis of the domain structure in different states of magnetization revealed the dynamics of the reversal magnetization process.


Mental Health and Well-Being in Mothers of Children With Rare Genetic Syndromes Showing Chronic Challenging Behavior: A Cross-Sectional and Longitudinal Study.
It is well documented that mothers of children with challenging behavior (CB) experience elevated levels of stress and that this persists over time, but less is known about the experience of mothers of children with rare genetic syndromes. This article describes 2 studies, 1 cross-sectional and 1 longitudinal, comparing well-being in mothers of children with Angelman, Cornelia de Lange and Cri du Chat syndrome who have either shown chronic CB ( n = 18) or low/no CB ( n = 26) in the preceding 7 years. The presence of chronic, long-term CB increased maternal stress but not depression or anxiety, and did not influence positive well-being. Stress relating specifically to their child's genetic syndrome reduced with age, highlighting the need for further exploration in this area.


Neural correlates of antinociception in borderline personality disorder.
A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. Case-control study. A university hospital. Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects. Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants. Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation. Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD. The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.


Professional relationships and power dynamics between urban community-based nurses and social work case managers: advocacy in action.
The purpose of this study was to explore how community-based case managers interface with their clients' healthcare providers and other community organizations as a function within their advocacy efforts. Case managers previously defined advocacy as occurring at individual, organizational, and community levels. The relationships they attempt to develop and maintain are consistent with case management ideology, yet this is a complex process to ensure care for vulnerable populations with many medical and socioeconomic needs. Community-based case management settings. In-depth qualitative interviews with a total of 20 nurse and social work case managers working in public housing, university-affiliated community nursing centers, local parishes, and community ministry. The case managers in this study reflected on how they interface with their clients, other healthcare providers, and community organizations on behalf of their clients. They reflect on the importance of trust and communication to facilitate this process. The advocacy work of case managers is influenced by the setting, others' perceptions of their knowledge and expertise, and power dynamics. Their ability to effectively advocate is greatly influenced by the strength of the relationships they forge. Advocacy for vulnerable clients is influenced by the existing relationship between case managers and their clients' healthcare providers. Case managers need to be persistent in their interactions with other providers to ensure that their clients have access to valuable community resources. Clear lines of communication should be established between case managers so that there is clarity around roles and expectations in service provision. Case managers should also participate in the mentoring of future health professions students so they may learn the application of advocacy work in community settings.


Proof of Concept Study: Investigating Force Metrics of an Intracorporeal Suturing Knot Task.
Mastering proper force manipulation in minimally invasive surgery can take many hours of practice and training. Improper force control can lead to necrosis, infection, and scarring. A force-sensing skin (FSS) has been developed, which measures forces at the distal end of minimal access surgeries' (MAS) instruments without altering the instrument's structural integrity or the surgical workflow, and acts as a minimally disruptive add-on to any MAS instrument. A proof of concept study was conducted using a FSS-equipped 5 mm straight-tip needle holder. Participants (n = 19: 3 novices, 11 fellows, and 5 staff surgeons) performed one intracorporeal suturing knot task (ISKT). Using participant task video footage, each participant's two puncture forces (each wall of the Penrose drain) and three knot tightening forces were measured. Force metrics from the three expertise groups were compared using analysis of variance (ANOVA) and Tukey's honest significance test with statistical significance assessed at P < .05. Preliminary ISKT force metric data showed differences between novices and more experienced fellows and surgeons. Of the five stages of the ISKT evaluated, the first puncture force of the Penrose drain seemed to best reflect the difference in skill among participants. The study demonstrated ISKT knot tightening and puncture force ranges across three expertise levels (novices, surgical fellows, and staff surgeons) of 0.586 to 6.089 newtons (N) and 0.852 to 2.915 N, respectively. The investigation of force metrics is important for the implementation of future force feedback systems as it can provide real-time information to surgeons in training and the operating theater.


Effect of periodontal treatment on tooth mobility.
The purpose of this study was to compare tooth mobility at different time periods during periodontal treatment and to relate changes in mobility to each method of treatment. Ninety-three patients (2421 teeth) with moderate to severe periodontitis were scored: (1) at initial examination, (2) 1 month following scaling, root planing, instruction in oral hygiene and preliminary occlusal adjustment, (3) 1 month after treatment with pocket elimination or reduction, curettage, modified Widman flap or scaling and root planing by the periodontist, and (4) 1 and 2 years following completed periodontal treatment. After initial nonsurgical treatment there was a significant decrease in tooth mobility. Tooth mobility increased temporarily after pocket reduction surgery but was not altered following curettage, modified Widman flap or scaling and root planing. Two years post-treatment there was a trend toward further decrease in tooth mobility with professional tooth cleaning every 3 months.


Energy intake and resting energy expenditure in adult male rats after early postnatal food restriction.
Both in man and in animal models, changes in food intake and body composition in later life have been reported after alterations in perinatal nutrition. Therefore, we hypothesised that early postnatal undernutrition in the rat induces permanent changes in energy balance. Food restriction (FR) during lactation was achieved by enlarging litter size to twenty pups, whereas control animals were raised in litters containing ten pups. Energy intake and resting energy expenditure were determined in adult males. Early postnatal FR resulted in acute growth restriction followed by incomplete catch-up in body weight, body length and BMI. At the age of 12 months, middle-aged FR males had significantly lower absolute resting energy expenditure (200 v. 216 kJ/24 h, P = 0.009), absolute energy intake (281 v. 310 kJ/24 h, P = 0.001) and energy intake adjusted for BMI (284 v. 305 kJ/24 h, P = 0.016) than controls, whereas resting energy expenditure adjusted for BMI did not differ significantly between the groups (204 v. 211 kJ/24 h, P = 0.156). The amount of energy remaining for other functions was lower in FR males (80 v. 94 kJ/24 h, P = 0.044). Comparable data were obtained at the age of 6 months. These results indicate that in rats energy balance can be programmed by early nutrition. A low early postnatal food intake appears to programme these animals for a low energy intake and to remain slender in adult life.


Comprehensive analysis of genetic and evolutionary features of the hepatitis E virus.
The hepatitis E virus (HEV) is the causative pathogen of hepatitis E, a global public health concern. HEV comprises 8 genotypes with a wide host range and geographic distribution. This study aims to determine the genetic factors influencing the molecular adaptive changes of HEV open reading frames (ORFs) and estimate the HEV origin and evolutionary history. Sequences of HEV strains isolated between 1982 and 2017 were retrieved and multiple analyses were performed to determine overall codon usage patterns, effects of natural selection and/or mutation pressure and host influence on the evolution of HEV ORFs. Besides, Bayesian Coalescent Markov Chain Monte Carlo (MCMC) Analysis was performed to estimate the spatial-temporal evolution of HEV. The results indicated an A/C nucleotide bias and ORF-dependent codon usage bias affected mainly by natural selection. The adaptation of HEV ORFs to their hosts was also ORF-dependent, with ORF1 and ORF2 sharing an almost similar adaptation profile to the different hosts. The discriminant analysis based on the adaptation index suggested that ORF1 and ORF3 could play a pivotal role in viral host tropism. In this study, we estimate that the common ancestor of the modern HEV strains emerged ~ 6000 years ago, in the period following the domestication of pigs. Then, natural selection played the major role in the evolution of the codon usage of HEV ORFs. The significant adaptation of ORF1 of genotype 1 to humans, makes ORF1 an evolutionary indicator of HEV host speciation, and could explain the epidemic character of genotype 1 strains in humans.


Surgical embolectomy in a 34-week pregnant woman with high risk pulmonary embolism and haemodynamic instability.
Pulmonary embolism represents the leading cause of maternal mortality in developed countries. The optimal treatment of high-risk pulmonary embolism with cardiovascular instability and at high hemorrhagic risk is still debated but surgical embolectomy represents an effective option. We describe the case of a 35-year-old woman in week 34 of pregnancy who was referred to our hospital because of exertional dyspnea and tachycardia and a few hours later became hypotensive and hypoxic. Pulmonary embolism was detected by performing an angio-computed tomography (CT) scan. After a successful cesarean section, emergent embolectomy was performed without inducing uterine hemorrhage. Both mother and the newborn recovered without postoperative sequelae.


Rapamycin-eluting Single and Double Stenting on Serum Markers in Coronary Bifurcation Lesions.
The objective of study was to compare effects of rapamycin-eluting single and double stenting on serum markers like high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in patients with coronary bifurcation lesions. It was an experimental study carried out from April 2016 to July 2017. One hundred and twenty-six patients were divided into two equal groups according to different treatment regimens. Group A was treated with rapamycin-eluting single stenting and group B with rapamycin-eluting double stenting. Three months after operation, hs-CRP, TNF-α, IL-6, IL-8 and MCP-1 levels in group B were lower than those in group A (p=0.010, p <0.001, p <0.001, p <0.001 and p <0.001, respectively). After one year of follow-up, rate of intrasegmental restenosis of branch vessels was higher in group A than in group B (p=0.011). Compared with rapamycin-eluting single stenting, rapamycin-eluting double stenting may regulate more effectively the above serum markers levels, reduce the incidence of intrasegmental restenosis of branch vessels.


Physicochemical and thermal characterization, and evaluation of a bacterial cellulose/Barhang gum-based dressing for wound healing.
The gram-negative bacterium of Gluconacetobacter xylinum is widely used to produce high-quality cellulose in the form of complex strips in microfiber bundles on a commercial scale. In this study, the film-forming potential of bacterial cellulose in combination with polyvinyl alcohol (PVA, 5 % w/v) and Barhang seed gum (BSG, 0.5 % w/v) loaded with summer savory (Satureja hortensis L.) essential oil (SSEO) to prepare a new wound dressing was investigated. The X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR), field emission-scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) surface area, in-vitro antibacterial, and in-vivo wound healing activities were performed to assess the structure, morphology, stability, and bioactivity of biocomposite films. Results showed that the SSEO incorporation into the polymeric matrix yielded smooth and transparent composite film with excellent thermal resistance. A significantly robust antibacterial activity against gram-negative bacteria by the bio-film was found. The healing process on mice models revealed that the SSEO-loaded composite film had a promising potential for wound healing associated with improved collagen deposition and reduced inflammatory response.


DNA methylation GrimAge acceleration in US military veterans with PTSD.
Epigenetic alterations in DNA methylation might mediate gene expression effects of trauma underlying PTSD symptoms, or effects of PTSD on related health problems. PTSD is associated with all-cause morbidity and premature mortality, suggesting accelerated biological aging. We measured genome-wide DNA methylation (Illumina MethylationEPIC BeadChip) in whole blood in a treatment study for combat-related PTSD - "PROGrESS", a multisite RCT comparing sertraline plus enhanced medication management (SERT + EMM), prolonged exposure (PE) therapy plus placebo (PE + PLB), and the combination (SERT + PE). DNA methylation was measured in 140 US military veterans who served in Iraq and/or Afghanistan (112 current PTSD cases enrolled in a PTSD treatment study and 28 veterans without PTSD history controls), and also 59 non-trauma exposed controls at baseline posttreatment (24 weeks after baseline). Increased DNA methylation GrimAge acceleration (p = 8.8e-09) was observed in patients with PTSD compared to a pooled control group (trauma exposed and non-trauma exposed), suggesting a higher risk of premature mortality in those with PTSD. There was no difference in GrimAge acceleration between combat trauma and non-trauma exposed controls. No treatment-related changes in GrimAge acceleration were found in within-subject comparisons of PTSD patients pre- to post-treatment.


Initial displacement as a risk factor for avascular necrosis of the femoral head in pediatric femoral neck fractures: a review of one hundred eight cases.
To evaluate the correlation between avascular necrosis (AVN) and the amount (severity) and direction (translation and angulation) of initial displacement of pediatric femoral neck fractures. We retrospectively reviewed 108 pediatric patients (mean age 10.3 ± 4.1 years) with femoral neck fractures. The amount of initial translation (T) and angulation (A) was measured on anteroposterior (AP; TAP% and AAP) and lateral (TL% and AL) radiographs. The direction of translation was determined on AP (medial or lateral) and lateral radiographs (anterior or posterior). Furthermore, the presence of a comminuted medial cortex on the AP pelvis radiograph was also recorded. Logistic regression analysis, receiver operating characteristic (ROC) curve analysis, student's t tests, and chi-square tests were used to evaluate the correlation between AVN and the severity and direction of displacement. Twenty-eight out of 108 hips (25.9%) developed AVN of the femoral head. Logistical regression analysis indicated that TAP%, TL%, AAP, and AL were risk factors for AVN (P < 0.05). The analysis of ROC curves found that TAP% over 37.4% and TL% over 29% were the cut-off values for an increased incidence of AVN; similarly, AAP over 8° and AL over 18.6° were the cut-off values for an increased incidence of AVN. The amount of initial translation is a better predictor of AVN than angulation is; fractures with posterior translation (P = 0.002) and/or medial comminution had a significantly higher incidence of AVN (P = 0.005). The mean diagnostic accuracy of translation (74-75%) was significantly higher than that of angulation (65-66%). Displacement severity and direction are important radiological parameters to be assessed in children with femoral neck fractures. Initial translation better predicts AVN than angulation does. Posterior translation and medial comminution are associated with an increased risk of AVN.


Delayed perihepatic abscess caused by Cutibacterium acnes following right partial hepatectomy.
We describe a case of a man in his 70s who presented with tachycardia and several weeks of right lower quadrant pain 3 months after partial right hepatectomy for hepatocellular carcinoma. Initial laboratory findings were significant for elevated C reactive protein and normal white cell count. CT revealed right pleural effusion and 5.8 cm fluid collection with air pocket adjacent to the surgical margin of the partial hepatectomy. Aspirate of the fluid collection grew Cutibacterium acnes Following percutaneous drainage and a short course of antibiotics, the patient recovered with eventual radiologic and symptomatic improvement. This, to the best of our knowledge, is one of two cases where C. acnes was involved in a possible delayed presentation of a surgical site infection after hepatic surgery.


Carotenoids from Cyanobacteria: Biotechnological Potential and Optimization Strategies.
Carotenoids are tetraterpenoids molecules present in all photosynthetic organisms, responsible for better light-harvesting and energy dissipation in photosynthesis. In cyanobacteria, the biosynthetic pathway of carotenoids is well described, and apart from the more common compounds (e.g., β-carotene, zeaxanthin, and echinenone), specific carotenoids can also be found, such as myxoxanthophyll. Moreover, cyanobacteria have a protein complex called orange carotenoid protein (OCP) as a mechanism of photoprotection. Although cyanobacteria are not the organism of choice for the industrial production of carotenoids, the optimisation of their production and the evaluation of their bioactive capacity demonstrate that these organisms may indeed be a potential candidate for future pigment production in a more environmentally friendly and sustainable approach of biorefinery. Carotenoids-rich extracts are described as antioxidant, anti-inflammatory, and anti-tumoral agents and are proposed for feed and cosmetical industries. Thus, several strategies for the optimisation of a cyanobacteria-based bioprocess for the obtention of pigments were described. This review aims to give an overview of carotenoids from cyanobacteria not only in terms of their chemistry but also in terms of their biotechnological applicability and the advances and the challenges in the production of such compounds.


Influence of entrepreneurship support programs on nascent entrepreneurial intention among university students in China.
This study aimed to investigate the impact of entrepreneurial educational support (NEES), entrepreneurial activities support (NEAS), and entrepreneurial commercialization support (NECS) on the nascent entrepreneurial intention (NEI) by mediating roles of entrepreneurial self-efficacy (NESE), opportunity recognition (OR), and the moderating effect of meaning in life (MLI). Data were gathered using a survey questionnaire from the 868 management, engineering, technical, and vocational institute students of China. The NEI model was analyzed using the partial least squares structural equation modeling through Smart-PLS software. The findings of the study reveal that NEES, NEAS, and NECS have a positive effect on NEI. Meanwhile, results indicate that NESE and OR partially mediate the relationship between entrepreneurship support programs and nascent entrepreneurial intention. Furthermore, the relationship between NESE and the NEI was insignificantly influenced by MLI, and the relationship between OR and the NEI was significantly moderated by MLI. Lastly, implications and limitations are also discussed in this article.


An alternative to the classical α-arylation: the transfer of an intact 2-iodoaryl from ArI(O₂CCF₃)₂.
The α-arylation of carbonyl compounds is generally accomplished under basic conditions, both under metal catalysis and via aryl transfer from the diaryl λ(3)-iodanes. Here, we describe an alternative metal-free α-arylation using ArI(O2CCF3)2 as the source of a 2-iodoaryl group. The reaction is applicable to activated ketones, such as α-cyanoketones, and works with substituted aryliodanes. This formal C-H functionalization reaction is thought to proceed through a [3,3] rearrangement of an iodonium enolate. The final α-(2-iodoaryl)ketones are versatile synthetic building blocks.


Activity of A-56268 (TE-031), a new macrolide, against Toxoplasma gondii in mice.
The activity of A-56268 (TE-031), a new macrolide, was tested in a murine model of acute toxoplasmosis. All control animals died in 8 +/- 1 days, while all mice treated with nine daily doses of A-56268 at 300 mg/kg, administered by gavage, survived. Moreover, 41.6% of the surviving mice were free from cerebral infection with Toxoplasma gondii, as assessed by brain subpassage. A-56268 is active against T. gondii in vivo, but further studies are needed to determine its usefulness in the treatment of human toxoplasmosis.


Genetic evidence for a temperature-sensitive lesion in the adenovirus 7 region of the PARA genome.
It has previously been shown that the helper adenovirus (Ad) present in the defective Ad 7-SV40 hybrid population is temperature-sensitive (ts) for replication in human cells. This study has shown that the replication of the defective hybrid virus (PARA) in green monkey kidney cells is also restricted at 40.5 percent. Complementation tests between the parental or transcapsidant PARA populations and SV40 or various Ad serotypes revealed that the ts lesion is located in the Ad region of the hybrid genome. Wild-type (wt) Ad type 7 and Ad type 21 were able to complement the replication of PARA while Ad type 31 was unable to do so. Complementation was more efficient after the PARA genome was transcapsidated to the wt isolates of helper Ad than during multiple infections with the parental hybrid population. The SV40 function which complements the replication of human adenoviruses in simian cells is not expressed by PARA at the nonpermissive temperature. However, the ts lesion does not affect the expression of SV40 functions coded for by PARA under other conditions, i.e., complementation of the replication of human adenoviruses in transformed monkey cells, and synthesis of T antigen in lytically infected or transformed cells. Although the exact nature of the mutated Ad 7 gene product is unknown, heat inactivation data suggest that it may be a structural protein.


The Impact of Acids Approved for Use in Foods on the Vitality of Haemonchus Contortus and Strongyloides Papillosus (Nematoda) Larvae.
The laboratory experiment described in this article evaluated the death rate of larvae of Haemonchus contortus (Rudolphi, 1803) nematodes of the Strongylida order and Strongyloides papillosus (Wedl, 1856) of the Rhabditida order under the impact of different concentrations of 8 flavouring acids and source materials approved for use in and on foods and in medicine (formic, wine, benzoic, salicylic, stearic, kojic, aminoacetic, succinic acids). Minimum LD50 for third stage larvae of (L3) S. papillosus was observed with salicylic and wine acids, for L3 H. contortus larvae - with formic acid. Minimum impact on all studied stages of development of nematodes was caused by stearic, kojic, aminoacetic and succinic acids: larvae did not die in the course of one day even at 1 % concentration of these substances. The best parameters of LD50 were observed for benzoic and formic acid. Further experiments on flavouring acids and source materials approved for use in and on foods and in medicines, and also their compounds, will contribute to developing preparations with a stronger impact on nematode larvae - parasites of the digestive tract of vertebrate animals and humans.


An integrated multi-omics analysis of topoisomerase family in pan-cancer: Friend or foe?
Topoisomerases are nuclear enzymes that get to the bottom of topological troubles related with DNA all through a range of genetic procedures. More and more studies have shown that topoisomerase-mediated DNA cleavage plays crucial roles in tumor cell death and carcinogenesis. There is however still a lack of comprehensive multi-omics studies related to topoisomerase family genes from a pan-cancer perspective. In this study, a multiomics pan-cancer analysis of topoisomerase family genes was conducted by integrating over 10,000 multi-dimensional cancer genomic data across 33 cancer types from The Cancer Genome Atlas (TCGA), 481 small molecule drug response data from cancer therapeutics response portal (CTRP) as well as normal tissue data from Genotype-Tissue Expression (GTEx). Finally, overall activity-level analyses of topoisomerase in pan-cancers were performed by gene set variation analysis (GSVA), together with differential expression, clinical relevancy, immune cell infiltration and regulation of cancer-related pathways. Dysregulated gene expression of topoisomerase family were related to genomic changes and abnormal epigenetic modifications. The expression levels of topoisomerase family genes could significantly impact cancer progression, intratumoral heterogeneity, alterations in the immunological condition and regulation of the cancer marker-related pathways, which in turn caused the differences in potential drugs sensitivity and the distinct prognosis of patients. It was anticipated that topoisomerase family genes would become novel prognostic biomarkers for cancer patients and provide new insights for the diagnosis and treatment of tumors.


Projective synchronization of two coupled excitable spiral waves.
Interaction of two identical excitable spiral waves in a bilayer system is studied. We find that the two spiral waves can be completely synchronized if the coupling strength is sufficiently large. Prior to the complete synchronization, we find a new type of weak synchronization between the two coupled systems, i.e., the spiral wave of the driven system has the same geometric shape as the spiral wave of the driving system but with a much lower amplitude. This general behavior, called projective synchronization of two spiral waves, is similar to projective synchronization of two coupled nonlinear oscillators, which has been extensively studied before. The underlying mechanism is uncovered by the study of pulse collision in one-dimensional systems.


Moving on from paediatric to adult health care: an initial evaluation of a transition program for young people with cystic fibrosis.
Although there are general guidelines for adolescents with chronic illnesses making the transition from paediatric to adult health care, there are few studies which evaluate transition programs. This cross-sectional study was a preliminary evaluation of a transition program for young people with cystic fibrosis. Study group and methods: A self-administered questionnaire was completed by a group of 'pre-transition' adolescents and their parents who had not moved on to adult health care and a 'post-transition' group who had moved on from the Children's Hospital at Westmead over a six year period. The questionnaire examined patient and parent concerns about adult health care, participation in steps of the transition process, satisfaction with transition and health related quality of life. Measures of disease severity (lung function tests and body mass index) were also included. 137 out of 220 (62%) eligible participants completed the questionnaire. In the pre-transition group, parents had more concerns compared to young people. There was no evidence of a significant difference between pre-transition and post-transition young people regarding degree of concern. Most people were satisfied with the transition program and posttransition patients and parents who completed more steps in the transition program described the overall transition process more positively. There was no evidence of a relationship between amount of participation in transition and measures of disease severity or quality of life.


Circannual testis and moult cycles persist under photoperiods that disrupt circadian activity and clock gene cycles in spotted munia.
We investigated whether circannual rhythms underlying annual testis maturation and moult cycles are independent of duration and frequency of the light period and circadian clock control in non-photoperiodic spotted munia. Birds were subjected to an aberrant light-dark (LD) cycle (3.5 h L:3.5 h D; T7, where T is the period length of the LD cycle) and continuous light (LL, 24 h L:0 h D), with controls on 12 h L:12 h D (T24, 24 h LD cycle). We measured the behavioural activity pattern of the birds and 24 h mRNA oscillations of circadian clock genes (bmal1, clock, per2, cry1, cry2) in the hypothalamus, the putative site of seasonal timing. Diurnal munia were rhythmic in behaviour with the period of the activity-rest cycle matched to T7 and T24, and became behaviourally arrhythmic with activity scattered throughout 24 h under LL. Similarly, exposure to 3.5 h L:3.5 h D and LL caused arrhythmicity in 24 h clock gene expression, suggesting disruption of internal circadian timing at the transcriptional level; a significant rhythm was found under 12 h L:12 h D. During an exposure of 80 weeks, munia showed two to three cycles of testis maturation and wing primaries moult under all photoperiods, although with a longer period under 12L:12D. Thus, the frequency of light period under 3.5 h L:3.5 h D or LL disrupted circadian clock gene cycles, but did not affect the generation of circannual testis and moult cycles. We conclude that the prevailing light environment and hypothalamic circadian gene cycles do not exert direct control on the timing of the annual reproductive cycle in spotted munia, suggesting independent generation of the circadian and circannual rhythms in seasonally breeding species.


Exercise-induced changes in pulmonary artery wedge pressure in adults post-Fontan versus heart failure with preserved ejection fraction and non-cardiac dyspnoea.
Despite their universal predisposition, diagnosing diastolic dysfunction in patients post-Fontan palliation is challenging. Our aim was to compare exercise haemodynamics between adults post-Fontan and patients with heart failure with preserved ejection fraction (HFpEF) and non-cardiac dyspnoea (NCD). Twenty-four adults (age ≥18 years) post-Fontan palliation with resting and exercise pulmonary artery wedge pressure (PAWP) measured during supine biking were identified. Forty-eight patients with HFpEF and 48 with NCD diagnosed at catheterization were selected for comparison. Mean age for Fontan patients was 30.3 ± 7.5 years; median ventricular ejection fraction was 52.5% (45-55.8), being <50% in 37.5%. Resting PAWP among Fontan patients was 10.2 ± 3.5 mmHg (>12 mmHg in 25%); PAWP was lower in Fontan patients than in HFpEF but higher than NCD. During exercise, PAWP was lower in the Fontan group than HFpEF (22.5 mmHg [19.3-28] vs. 28.2 ± 6.3; p = 0.0006) but higher than NCD (11.2 ± 4.2, p ≤ 0.0001). However, there were no differences in ΔPAWP/ΔQs between Fontan and HFpEF patients (4.0 [2.1-7.3] vs. 2.7 [1.6-4.4]; p = 0.10) with the ratio being higher post-Fontan than in NCD (0.6 [0.2-1.2]; p < 0.0001). ΔPAWP/ΔQs remained similar between HFpEF and Fontan patients even when those with ejection fraction <50% were excluded (2.7 [1.6-4.4] vs. 2.7 [1.0-5.8]; p = 0.97). There were no differences in ΔPAWP/ΔQs ratios between post-Fontan and HFpEF patients, supporting markedly abnormal single ventricle compliance despite lower resting and exercise PAWP. Therefore, exercise invasive haemodynamics may represent a novel tool for the diagnosis of diastolic dysfunction in Fontan patients.