Correlation of transforming growth factor beta-1 gene polymorphisms C-509T and T869C and the risk of gastric cancer in China.
As an important cytokine that modulate the cell cycle, the involvement of transforming growth factor beta-1 (TGF-beta1) in carcinogenesis has been extensively studied for many years. Literatures have demonstrated that TGF-beta1 gene polymorphisms may alter the risk of various cancers, such as lung, prostate and breast. To investigate whether polymorphisms of the TGF-beta1 gene can modify the risk of gastric cancer, we conduct this hospital-based, case-control study. One hundred and sixty-seven cases and 193 gender, age-matched healthy controls were enrolled in this case-control study. TGF-beta1 polymorphisms C-509T and T + 869C were identified by PCR-RFLP and ARMS-PCR protocols, respectively. Significantly different distributions of both genes were demonstrated between the case and control. Variant genotypes -509CT, -509TT, +869TC and +869CC were associated with increased risk of gastric cancer (P = 0.001, OR = 2.54; P = 0.016, OR = 2.09; P < 0.001, OR = 3.46; P < 0.001, OR = 4.04, respectively). With haplotype analysis, wild type CT (-509C and +869T) led to a lower frequency in case than that in control (P < 0.001), while haplotype TC was more frequent in case than in control (P < 0.001). Multiple logistic regression analysis revealed that individuals with haplotype TC had an increased likelihood of developing gastric cancer (OR = 3.19, 95%CI = 1.72-5.90). Our findings imply that -509C > T and +869T > C gene polymorphisms in TGF-beta1 may be a critical risk factor of genetic susceptibility to gastric cancer in the Chinese population.


Neural networks applied to 12-lead electrocardiograms predict body mass index, visceral adiposity and concurrent cardiometabolic ill-health.
Obesity is associated with electrophysiological remodeling, which manifests as detectable changes on the surface electrocardiogram (ECG). To develop neural networks (NN) to predict body mass index (BMI) from ECGs and test the hypothesis that discrepancies between NN-predicted BMI and measured BMI are indicative of underlying adiposity and/or concurrent cardiometabolic ill-health. NN models were developed using 36,856 12-lead resting ECGs from the UK Biobank. Two architectures were developed for continuous and categorical BMI estimation (normal weight [BMI <25 kg/m2] vs overweight/obese [BMI ≥25 kg/m2]). Models for male and female participants were trained and tested separately. For each sex, data were randomly divided into 4 folds, and models were evaluated in a leave-1-fold-out manner. ECGs were available for 17,807 male and 19,049 female participants (mean ages: 61 ± 7 and 63 ± 8 years; mean BMI 26 ± 5 kg/m2 and 27 ± 4 kg/m2, respectively). NN models detected overweight/obese individuals with average accuracies of 75% and 73% for male and female subjects, respectively. The magnitudes of difference between NN-predicted BMI and actual BMI were significantly correlated with visceral adipose tissue volumes. Concurrent hypertension, diabetes, dyslipidemia, and/or coronary heart disease explained false-positive classifications (ie, calculated BMI <25 kg/m2 misclassified as ≥25 kg/m2 by NN model, P < .001). NN models applied to 12-lead ECGs predict BMI with a reasonable degree of accuracy. Discrepancies between NN-predicted and calculated BMI may be indicative of underlying visceral adiposity and concomitant cardiometabolic perturbation, which could be used to identify individuals at risk of cardiometabolic disease.


Labial adhesions in pubertal girls.
Labial adhesions after puberty are rare and are usually the result of chronic inflammation, urinary tract infection, hypoestrogenism or surgical procedures leading to vulval trauma. Sexual abuse leading to labial adhesions is extremely rare in girls who have attained menarche. Complete vulval fusion can rarely occur without any evidence of hypoestrogenism. We address this rare entity in three young pubertal girls wherein one had a history of genital trauma, the second had a history of surgical intervention due to urinary retention and the last one had a history of sexual abuse. All patients had history of genital trauma in common. Accepted management of this condition is adhesiolysis followed by application of estrogen cream in the postoperative period.


Antiemetic guidelines: are they being used?
Evidence-based guidelines are regarded as therapeutic standards for many medical interventions. However, implementation of such recommendations seems to be rather difficult. An international antiemetic guideline for the treatment of patients undergoing chemotherapy was issued by the Multinational Association of Supportive Care in Cancer in 1997 and has been in use ever since. However, for many reasons, the guideline has not been followed completely, despite the fact that if antiemetics are used in accordance with guidelines, efficacy is similar to that achieved in randomised controlled trials. Structural difficulties, patients characteristics, and other barriers, such as the individual acceptance of guidelines and education of physicians and nurses, could be crucial factors for successful implementation. Thus, better adherence to antiemetic guidelines can only be achieved through a complex and long-term process, consisting of efficient education, training, and monitoring of all individuals involved.


Flush exposure and injection immunization of rainbow trout to selected DNP conjugates.
Rainbow trout (Salmo gairdneri) were immunized by flush exposure or intraperitoneal injection with single doses of the following dinitrophenyl (DNP) conjugates: DNP-keyhole limpet hemocyanin (KLH), DNP-Ficoll, DNP-O-antigen (from the fish pathogen, Yersinia ruckeri), DNP-sheep red blood cells, or DNP-duck red blood cells. The immune response was demonstrated by the passive hemolytic plaque assay to show splenic antibody-producing cells (APC) 14 days after antigen administration. High numbers of splenic APC specific for the hapten were found when the conjugates DNP-KLH, DNP-Ficoll, and DNP-O-antigen were given by injection and when DNP-O-antigen was given by flush exposure. The heterologous red blood cells were relatively nonimmunogenic. When the immune response to the hapten and carrier could be measured--e.g., after immunization with the DNP-O-antigen--the numbers of APC were consistently higher for the hapten.


L-canavanine incorporation into vitellogenin and macromolecular conformation.
L-Canavanine is a potentially deleterious arginine antimetabolite whose toxicity is expressed in canavanine-sensitive organisms ranging from viruses to humans. Canavanine, a substrate for arginyl-tRNA synthetase, is incorporated into nascent polypeptide chains in place of arginine. This substitution results in the production of structurally aberrant, canavanyl proteins. Chemical, physical, and immunological studies of native and canavanine-containing vitellogenin obtained from female migratory locusts (Locusta migratoria migratorioides (Orthoptera] provide the first experimental evidence that canavanine can disrupt the tertiary and/or quaternary structure that yields the three-dimensional conformation unique to the protein. These findings enhance our understanding of the biochemical basis for canavanine's antimetabolic and potent insecticidal properties.


Epidemiologic assessment of trauma-independent skeletal pathology in non-passerine birds from museum collections.
Systematic survey of mammalian skeletons has revealed patterns of disease reproducible over geologic time. Systematic examination of non-passerine bird skeletons also reveals patterns of disease and identifies those disorders amenable to epidemiologic assessment. Neoplasia, infection, osteochondromatosis and gout are extremely rare, precluding phylogenetic comparisons--at least those based on macroscopic examination of skeletons. Osteoarthritis, paradoxically, is identified at sufficient population frequency for meaningful investigation.


Effect of aluminum on superoxide dismutase activity in the adult rat brain.
Male rats were treated daily with an intraperitoneal injection of 15 mg aluminum (Al chloride)/kg body weight for 17 d, in order to study the effects on superoxide dismutase (SOD) activities in the brain (cortex). No significant difference between control and treated animals was registered in the Cu/Zn and Mn SOD activities in the gray matter of the cortex. High Al levels were found in the plasma, the spleen, and the liver of the treated animals in comparison to the controls, but not in the cortex homogenates (gray matter). In addition, Al induced a significant decrease in food ingestion and weight gain.


Assessing the need for follow-up: the relationship of prognosis to posthospitalization adjustment.
Parents of children (N-64) hospitalized at a psychiatric hospital between the years 1971 and 1976 rated their child's adjustment in a number of behavioral areas. Problems in school, making friends, acting age-appropriately, and handling aggression were reported to be the major sources of difficulty for 40% of the former patients. No statistical relationship was found between clinicians' prognosis at discharge and children's post-hospitalization adjustment. The authors discuss some of the variables that mitigate against accurate outcome prediction and argue for the integration of an organized follow-up program into their treatment program.


Ultrasound characterization of the mastoid for detecting middle ear effusion: A preliminary clinical validation.
Ultrasound detection of middle ear effusion (MEE) is an emerging technique in otolaryngology. This study proposed using ultrasound characterization of the mastoid to noninvasively measure MEE-induced mastoid effusion (ME) as a new strategy for determining the presence of MEE. In total, 53 patients were enrolled (Group I: normal, n = 20; Group II: proven MEE through both otoscopy and tympanometry, n = 15; Group III: patients with MEE having effusions observed during grommet surgery, n = 18). A 2.25-MHz delay-line transducer was used to measure backscattered signals from the mastoid. The Nakagami parameter was estimated using the acquired signals to model the echo amplitude distribution for quantifying changes in the acoustic structures of mastoid air cells. The median Nakagami parameter and interquartile range were 0.35 (0.34-0.37) for Group I, 0.39 (0.37-0.41) for Group II, and 0.43 (0.39-0.51) for Group III. The echo amplitude distribution observed for patients with MEE was closer to Rayleigh distribution than that without MEE. Receiver operating characteristic (ROC) curve analysis further revealed that the area under the ROC was 0.88, sensitivity was 72.73%, specificity was 95%, and accuracy was 81.13%. The proposed method has considerable potential for noninvasive and comfortable evaluation of MEE.


Protectins: Their biosynthesis, metabolism and structure-functions.
Several lipoxygenase enzymes and cyclooxygenase-2 stereoselectively convert the polyunsaturated fatty acids arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and n-3 docosapentaenoic acid into numerous oxygenated products. Biosynthetic pathway studies have shown, during the resolution phase of acute inflammation, that distinct families of endogenous products are formed. These products were named specialized pro-resolving mediators, given their specialized functions in the inflammation-resolution circuit, enhancing the return of inflamed and injured tissue to homeostasis. The lipoxins, resolvins, protectins and maresins, together with the sulfido-conjugates of the resolvins, protectins and maresins, constitute the four individual families of these local mediators. When administrated in vivo in a wide range of human disease models, the specialized pro-resolving mediators display potent bioactions. The detailed and individual biosynthetic steps constituting the biochemical pathways, the metabolism, recent reports on structure-function studies and pharmacodynamic data of the protectins, are presented herein. Emphasis is on the structure-function results on the recent members of the sulfido conjugated protectins and further metabolism of protectin D1. Moreover, the members of the individual families of specialized pro-resolving mediators and their biosynthetic precursor are presented. Today 43 specialized pro-resolving mediators possessing pro-resolution and anti-inflammatory bioactions are reported and confirmed, constituting a basis for resolution pharmacology. This emerging biomedical field provides a new approach for drug discovery, that is also discussed.


Burst generation by electrically coupled network in the snail helisoma: analysis using computer simulation.
The effectiveness of electrical coupling between neurons as a mechanism for mediating single and repetitive bursts is investigated here using computer simulation. The cyberchron network in the snail Helisoma generates repetitive bursts controlling the animal's feeding behavior and served as the basic model for the simulation studies described in this paper. The action potential properties of individual neurons were modeled by the Rall equations describing generalized action potentials. Several properties of electrical coupling and its role in burst generation were demonstrated, including: (1) A neuron in an electrically coupled network can generate action potentials at a higher frequency than an isolated neuron with similar membrane properties due to the loading through the electrical junctions. However, the ability of electrically coupled neurons to generate high-frequency bursts of action potentials requires a concomitantly greater amount of driving current to overcome the junctional loading. (2) Temporal and spatial summation of synaptic input onto a neuron is maintained at its most effective level because the postsynaptic current is integrated across the long postsynaptic membrane time constant. (3) Initial simulations concentrated on a pair of electrically coupled neurons which were below threshold. Stimulation of one of the two neurons with a short pulse resulted in a reverberation or regenerative excitation between the two neurons. The reverberation terminated after a number of action potentials dependent on the specific model parameters. Similar results were obtained with a network containing a greater number (20) of model neurons if approximately one-half of the neurons were stimulated simultaneously. However, none of the cases studied produced more than a single discrete burst. (4) Simulations were also conducted on 20-neuron networks containing two subpopulations of model neurons differing in their values of coupling resistance and excitability. Some networks of this type required stimulation of only one cell to make the two subpopulations of model neurons reverberate with one another. Such simulations suggest the possibility that 'preferred' input pathways involving a small number of neurons would be capable of 'turning on' the activity of the entire network.


Lying to friends: Examining lie-telling, friendship quality, and depressive symptoms over time during late childhood and adolescence.
Lie-telling appears to peak during adolescence; however, previous research has not yet examined lie-telling frequency in adolescents' friendships. Increased lie-telling may be problematic given that honesty is crucial for trust within positive relationships, and more positive relationships lead to more positive well-being. The present study examined adolescents' lies to friends and longitudinal associations between lying, friendship quality, and depressive symptoms. Canadian adolescents (Time 1: N = 1313, Mage = 11.65, SD = 11.75, 50% male) reported how often they lied to their friends about their mental health/mood, possessions, romantic relationships, school, and to avoid spending time with them. Participants also completed measures of friendship quality and depressive symptoms. Participants completed these measures at two time points one year apart. Poorer friendship quality predicted more frequent lie-telling over time. Greater depressive symptoms predicted more frequent lie-telling over time, and more frequent lie-telling predicted greater depressive symptoms over time. Lies about mental health in particular were bidirectionally associated with both friendship quality and depressive symptoms over time. These findings highlight the developmental importance of lie-telling during adolescence. More negative friendships lead to greater lie-telling over time. Additionally, increased lie-telling predicted and is predicted by depressive symptoms, suggesting that lie-telling may be an important indicator of poor mental health.


Long-term cognitive complaint and post-concussive symptoms following mild traumatic brain injury: the role of cognitive and affective factors.
To determine whether neuropsychological test performance or affective factors predict long-term post-concussive symptoms and cognitive complaint following mild traumatic brain injury. Participants included 21 individuals with mild traumatic brain injury, 19 individuals with spinal injury but no injury to the brain and 20 neurologically-normal controls. All participants completed measures of post-concussive symptoms, cognitive complaint, depression, anxiety, and personality and were administered a variety of neuropsychological tests. The hypothesis that depression, anxiety and neuroticism would be better predictors of post-concussive symptoms than neuropsychological test performance for all three groups was supported. Contrary to expectations, however, neuropsychological test performance was a unique predictor of cognitive complaint for the mild traumatic brain injury group. It was concluded that long-term post-concussive symptoms are largely representative of psychological symptoms and not brain damage, but that genuine, albeit subtle, cognitive deficits also may be present for long-term periods following mild traumatic brain injury.


CircZNF609 promotes bladder cancer progression and inhibits cisplatin sensitivity via miR-1200/CDC25B pathway.
Circular RNAs (circRNAs) have been extensively studied in tumor development and treatment. CircZNF609 (hsa_circ_0000615) has been shown to serve as an oncogene in all kinds of solid tumors and may act as the novel biomarker in tumor diagnosis and therapy in tumor early diagnosis and therapy. However, the underlying character and mechanism of circZNF609 in cisplatin chemosensitivity and bladder cancer (BCa) development were unknown. The expression level of cell division cycle 25B (CDC25B), microRNA 1200 (miR-1200), and circZNF609 in BCa cells and tissues depended on quantitative real-time PCR (qRT-PCR). CDC25B protein level was assayed with Western blot. Functional assays in vitro and in vivo had been conducted to inspect the important role of circZNF609 on BCa progression and cisplatin chemosensitivity in BCa. RNA sequencing and online databases were used to predict the interactions among circZNF609, miR-1200, and CDC25B. Mechanistic exploration was confirmed by RNA pull-down assay, RNA fluorescence in situ hybridization (FISH) and Dual luciferase reporter assay. CircZNF609 expression was increased significantly in BCa cell lines and tissues. For BCa patients, increased expression of circZNF609 was correlated with a worse survival. In vitro and in vivo, enforced expression of circZNF609 enhanced BCa cells proliferation, migration, and cisplatin chemoresistance. Mechanistically, circZNF609 alleviated the inhibition effect on target CDC25B expression by sponging miR-1200. CircZNF609 promoted tumor growth through novel circZNF609/miR-1200/CDC25B axis, implying that circZNF609 has significant potential to act as a new diagnostic biomarker and therapeutic target in BCa. Enhancing cisplatin sensitivity is an important direction for bladder cancer management. 1. This research reveals that circZNF609 improves bladder cancer progression and inhibits cisplatin sensitivity by inducing G1/S cell cycle arrest via a novel miR-1200/CDC25B cascades. 2. CircZNF609 was confirmed associated with worse survival of bladder cancer patients. 3. CircZNF609 act as a prognostic biomarker for bladder cancer treatment.


Total aortic arch grafting for acute type A dissection: analysis of residual false lumen.
In surgery for acute type A dissection, an unresected dissection and residual false lumina are causes of the progression of aneurysms and ruptures. We grafted the ascending aorta and total arch, the maximum grafting possible through a median sternotomy alone, in all patients with type A dissection extending to the descending aorta, wherever initial tears existed in the arch. A total of 37 consecutive patients with acute type A dissection underwent ascending and total arch grafting between August 1994 and December 2000. Cerebral protection was achieved by selective cerebral perfusion. The distal anastomosis was conducted using the "Elephant Trunk" technique. Patent false lumina were evaluated using computed tomography 3 months after the operation. The hospital mortality was 8.1%. No major cerebral complications were observed. The incidence of residual thoracic patent false lumina was 26.5%. Univariate analyses showed Marfan syndrome and preoperative extension of false lumina to be statistically significant determinants of residual thoracic false lumina. On multivariate analysis, no other significant independent predictor of residual false lumina in the thoracic aorta was found. Outcomes of our strategy were satisfactory. However, residual thoracic false lumina could not be prevented in 26.5% of the patients. Thus, this extended operation is indicated in patients with initial tears in the aortic arch or distal arch, those with Marfan syndrome, and young patients with preoperative patent false lumina extending to the abdominal aorta.


Influence of acid-etching after grit-blasted on osseointegration of titanium dental implants: in vitro and in vivo studies.
Rough implant surfaces have shown improved osseointegration rates. In a majority of dental implants, the microrough surfaces are obtained by grit blasting and/or acid-etching. The aim of this contribution was to evaluate the effects of acid-etching, after the grit-blasted treatment in titanium dental implants, on surface wettability, surface energy, osteoblast responses and its osseointegration behavior. Four surfaces were studied: as-machined, acid-etched, micro-rough by grit-blasting and the combination grit-blasted surface with acid-etched. The surfaces with increasing roughness show more osteoblastic adhered cells. This effect was most pronounced on samples blasted and blasted with acid-etching. The roughness obtained by grit-blasting is the main factor in comparison with the acid etching treatment in the biological response. These results were confirmed in vivo tests and histological analysis. The results demonstrated that the combination of the grit-blasted and acid-etched accelerated lightly bone regeneration at the different periods of implantation in comparison with the grit-blasted implants.


Stimulation and inhibition of cellular functions by glucocorticoids. Correlations with rapid influences on chromatin structure.
The effect of media conditions on the glucocorticoid response has been examined in three types of cultured cells. In rat pituitary tumor cells (GC cells) growth hormone production was stimulated by glucocorticoids provided fresh culture media was present (enriched media conditions). In contrast, dexamethasone either failed to induce or deinduce growth hormone synthesis if added to cultures which had not received fresh media for 3 days (depleted media condition). With human skin fibroblasts, cortisol stimulated [3H]thymidine incorporation in the enriched condition but inhibited this response in the depleted condition. In mouse lymphoma (S49) cells the enriched media conditions significantly delayed the killing response to glucocorticoids (20% killing after 24 h versus 90% killing after 24 h for the depleted condition). Thus, the magnitude and in some cases, the direction of the glucocorticoid response are sensitive to the conditions to which the cells are exposed. In all three cell types the steroid also rapidly (detectable by 15 min, maximal by 2 h) altered chromatin structure as detected by a change in the number of initiation sites for Escherichia coli RNA polymerase assayed under cell-free conditions. This early nuclear response could be in a positive or negative direction and was also affected by the culture conditions; enriched media favored a positive or less negative effect on the initiation sites by the steroid, while depleted media favored a steroid-induced inhibition of this chromatin function. In S49 and GC cells the kinetics and magnitude of the change in chromatin closely followed receptor . glucocorticoid complex binding to nuclei while removal of dexamethasone from the culture media resulted in a rapid (t 1/2 = approximately 20 min) disappearance of the effect which paralleled loss of bound hormone from the nucleus. The glucocorticoid effect on chromatin was not observed in two lines of glucocorticoid-resistant mutant S49 cells. One line (R-) lacks detectable glucocorticoid receptors; the other line (Nti) has receptors that bind the hormone normally, but the receptor . glucocorticoid complexes bind more avidly to the nucleus. These results suggest that the receptor is involved in both the stimulatory and the inhibitory effects on chromatin. The findings in the Nti cells and of a slight lag between nuclear binding of receptors and initiation site alteration implies that some receptor property, in addition to nuclear binding per se, is responsible for the influence on chromatin. These results are discussed in terms of a model in which steroid hormones initiate their actions by influencing a reaction that modifies chromatin structure. The direction and magnitude of the reaction, and its effect on the expression of specific genes, are dictated by the metabolic state and differentiation of the cell.


Selective inhibition of physiological late Na+ current stabilizes ventricular repolarization.
The physiological role of cardiac late Na+ current ( INa) has not been well described. In this study, we tested the hypothesis that selective inhibition of physiological late INa abbreviates the normal action potential (AP) duration (APD) and counteracts the prolongation of APD and arrhythmic activities caused by inhibition of the delayed rectifier K+ current ( IKr). The effects of GS-458967 (GS967) on the physiological late INa and APs in rabbit isolated ventricular myocytes and on the monophasic APs and arrhythmias in rabbit isolated perfused hearts were determined. In ventricular myocytes, GS967 and, for comparison, tetrodotoxin concentration dependently decreased the physiological late INa with IC50 values of 0.5 and 1.9 µM, respectively, and significantly shortened the APD measured at 90% repolarization (APD90). A strong correlation between inhibition of the physiological late INa and shortening of APD by GS967 or tetrodotoxin ( R2 of 0.96 and 0.97, respectively) was observed. Pretreatment of isolated myocytes or hearts with GS967 (1 µM) significantly shortened APD90 and monophasic APD90 and prevented the prolongation and associated arrhythmias caused by the IKr inhibitor E4031 (1 µM). In conclusion, selective inhibition of physiological late INa shortens the APD, stabilizes ventricular repolarization, and decreases the proarrhythmic potential of pharmacological agents that slow ventricular repolarization. Thus, selective inhibition of late INa may constitute a generalizable approach to stabilize ventricular repolarization and suppress arrhythmogenicity associated with conditions whereby AP or QT intervals are prolonged. NEW & NOTEWORTHY The contribution of physiological late Na+ current in action potential duration (APD) of rabbit cardiac myocytes was estimated. The inhibition of this current prevented the prolongation of APD in rabbit cardiac myocytes, the prolongation of monophasic APD, and generation of arrhythmias in rabbit isolated hearts caused by delayed rectifier K+ current inhibition.


Dynamic behavior of reversible oxygen migration in irradiated-annealed high temperature superconducting wires.
We use atomically resolved scanning transmission electron microscopy and electron energy loss spectroscopy to determine the atomic-scale structural, chemical and electronic properties of artificial engineered defects in irradiated-annealed high temperature superconducting wires based on epitaxial Y(Dy)BCO film. We directly probe the oxygen vacancy defects in both plane and chain sites after irradiation with 18-meV Au ions. The plane site vacancies are reoccupied during post-annealing treatment. Our results demonstrate the dynamic reversible behavior of oxygen point defects, which explains the depression and recovery of self-field critical current and critical temperature in irradiation-annealing process. These findings reveal the strong effect of oxygen vacancies in different sites on the superconductivity properties of irradiated Y(Dy)BCO film, and provide important insights into defects engineering of 2G HTS coil wires.


Optimal design of robust resilient automatic voltage regulators.
Uncertainties in the plant model parameters and perturbations in the controller gains imposed by implementation errors represent a challenge to ensure robust stability and controller non-fragility simultaneously. Optimal design of robust non-fragile proportional-integral-derivative (PID) controller is presented for an automatic voltage regulator (AVR). The PID design relies basically on Kharitonov theorem and optimization by future search algorithm (FSA). The proposed algorithm has low computational complexity and fast convergence rate because it utilizes both local and global search methods. Further, FSA can improve the exploration characteristic and prevent trapping in local optima by updating its random initial. The PID controller is optimized by FSA to cope with expected parametric uncertainties of the plant model and tolerate its gain perturbations such that robust stability and controller non-fragility are simultaneously met. An interval plant model is suggested to account for model uncertainties where only eight extreme plants derived by Kharitonov theorem are considered in design. FSA-based PID optimization is constrained by the stability conditions of Kharitonov's plants derived using Routh-Hurwitz. A new figure-of-demerit (FoD) based performance index is suggested to enforce simultaneous minimization of the time domain specifications. The suggested objective function is represented by a weighted sum of FoD of nominal response and the sum of reciprocals of the perturbation radii of PID gains. The output results of the recommended design are compared to that of artificial bee colony (ABC) algorithm and teaching-learning based optimization (TLBO) algorithm, multi-objective extremal optimization (MOEO), and non-dominated sorting genetic algorithm II (NSGA II). The results can confirm better response of the suggested technique measured up to other techniques where robustness and non-fragility are simultaneously ensured.


Arterial and end-tidal carbon dioxide partial pressure difference during prehospital anaesthesia in critically ill patients.
Normoventilation is crucial for many critically ill patients. Ventilation is routinely guided by end-tidal capnography during prehospital anaesthesia, based on the assumption of the gap between arterial partial pressure of carbon dioxide (PaCO2 ) and end-tidal carbon dioxide partial pressure (PetCO2 ) of approximately 0.5 kPa (3.8 mmHg). We retrospectively analysed the airway registry and patient chart data of patients who had been anaesthetised and intubated endotracheally by the prehospital critical care team and had their prehospital arterial blood gases analysed. Bland-Altman analysis was used to estimate the bias and limits of agreement. Altogether 502 patients were included in the study, with a median age of 58 years. The most common patient groups were post-resuscitation (155, 31%), neurological emergencies (96, 19%), intoxication (75, 15%) and trauma (68, 14%). The median of the gap between PaCO2 and PetCO2 was 1.3 kPa (interquartile range 0.7 to 2.2) (9.8 (5.3-16.5) mmHg). Mean bias of PetCO2 was -1.6 kPa/12.0 mmHg (standard deviation 1.7 kPa/12.8 mmHg) with 95% confidence limits of agreement -4.9 to 1.9 kPa (-36.8 to 14.3 mmHg). The gap was ≥ 1.0 kPa (>7.5 mmHg) in 297 (66%, 95% confidence interval 55 to 63) patients. Our results suggest that end-tidal capnography alone might not be an adequate method to achieve normoventilation for critically ill patients intubated and mechanically ventilated in prehospital setting. Thus, an arterial blood gas analysis might be useful to recognize patients with an increased gap between PaCO2 and PetCO2 .


Toxicity mechanism of Cu2+ ion individually and in combination with Zn2+ ion in characterizing the molecular changes of Staphylococcus aureus studied using FTIR coupled with chemometric analysis.
Copper and zinc have a high binding affinity with a Staphylococcus aureus bacterial community. This causes a change in the biomolecular composition of S. aureus. Our study aims at understanding the resistance mechanism of Cu and Zn either or in various combinations using FTIR and chemometric techniques. Zn toxicity resulted in a significant change in lipid content (3100-2800 cm-1) compared to Cu. A significant decrease in protein content is observed for Cu treatment in the amide region. The bio-concentration factor shows a higher value for Cu compared to Zn. The increase in band area of carbohydrates moieties 1059 cm-1 shows the secretion of EPS due to Cu toxicity. A significant change in nucleic acid compositions was noted in the region1200-900 cm-1 due to Zn treatment. Secondary structural change in protein shows β sheet formation. The result of the finding shows Cu has greater toxicity than Zn. Further toxicity effects were greatly enhanced for metal mixtures ratio (Cu:2Zn). This shows Zn exhibits synergism effect with Cu. The obtained ROC (receiver operating characteristic) curve area gives good reliability of the experiments. The study attempts to understand the mechanism of toxicity removal of Cu and Zn metal mixtures by bacterial population using FTIR coupled with chemometric techniques. Graphical abstract.


Purification and characterization of anthranilate synthase component I (TrpE) from Mycobacterium tuberculosis H37Rv.
The emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis is the main reason why tuberculosis (TB) continues to be a major health problem worldwide. It is urgent to discover novel anti-mycobacterial agents based on new drug targets for the treatment of TB, especially MDR-TB. Tryptophan biosynthetic pathway, which is essential for the survival of M. tuberculosis and meanwhile absent in mammals, provides potential anti-TB drug targets. One of the promising drug targets in this pathway is anthranilate synthase component I (TrpE), whose role is to catalyze the conversion of chorismate to anthranilate using ammonia as amino source. In order to get a deep understanding of TrpE, a study on purification and characteristic identification of TrpE is required. In this work, the putative trpE gene of M. tuberculosis H37Rv was expressed as a fusion protein with a 6x His-tag on the N-terminal (His-TrpE) in Escherichia coli. The recombinant TrpE protein was successfully purified and then its enzymatic characteristics were analyzed. The native TrpE without His-tag was obtained by removal of the N-terminal fusion partner of His-TrpE using enterokinase. It was found that N-terminal fusion partner had little influence on TrpE catalytic activity. In addition, the key residues related to enzyme catalytic activity and that involved in l-tryptophan inhibition were predicted in the structure of M. tuberculosis H37Rv TrpE. These results would be beneficial to the designing of novel anti-TB drugs with high potency and selectivity.


Ruptured thoracoabdominal aortic aneurysm treatment in the United States: 1988 to 1998.
Thoracoabdominal aortic aneurysm (TAAA) rupture usually results in death. The outcome remains poor for patients who reach the operating room. The objective of this investigation was to define contemporary surgical experience with ruptured TAAA in the United States. Patients and methods Clinical data derived from the Nationwide Inpatient Sample on patients who underwent repair of a ruptured TAAA from 1988 to 1998 were analyzed. Age, sex, race, nature of admission, comorbid conditions, and provider volume were abstracted from the database. In-hospital mortality, postoperative complications, and length of stay were the principal outcome measures. Three hundred twenty-one patients were identified for the study. Mean age was 71.5 years; men outnumbered women (63% vs 37%). Crude overall surgical mortality was 53.8% and did not improve over time. Operative mortality was most likely (51%) to occur within the first 24 hours postoperatively. Median length of stay for surviving patients was 16 days. Renal failure (28%) and cardiac complications (18%) were the most common complications. In a logistic regression model, age greater than 77 years was predictive of death (odds ratio [OR], 2.5; P =.005), and nonwhite race appeared protective (OR, 0.53; P =.013). Mortality after surgical treatment of ruptured TAAA is high. Surviving patients experience many postoperative complications and have lengthy hospital stays. Given the lack of significant improvement in contemporary surgical practice, new techniques of repair deserve the attention of clinicians.


Comparison of peripheral arterial response to mental stress in men versus women with coronary artery disease.
There are profound gender-related differences in the incidence, presentation, and outcomes of coronary artery disease (CAD). These differences are not entirely explained by traditional cardiovascular risk factors. Nontraditional risk factors, such as psychological traits, have increasingly been recognized as important contributors to the genesis and outcomes of CAD. Mental stress induces significant peripheral arterial vasoconstriction, with consequent increases in heart rate and blood pressure. These changes are thought to underlie the development of myocardial ischemia and other mental stress-induced adverse cardiac events in patients with CAD. This study examined for gender-related differences in peripheral arterial response to mental stress in a cohort of patients with CAD using a novel peripheral arterial tonometric (PAT) technique. There were 211 patients (77 women; 37%) with a documented history of CAD and a mean age of 64 +/- 9 years. Patients were enrolled from August 18, 2004, to February 21, 2007. Mental stress was induced using a public speaking task. Hemodynamic and PAT measurements were recorded during rest and mental stress. The PAT response was calculated as a ratio of pulse wave amplitude during stress to at rest. PAT responses were compared between men and women. The PAT ratio (during stress to at rest) was significantly higher in women compared with men. Mean PAT ratio was 0.80 +/- 0.72 in women compared with 0.59 +/- 0.48 in men (p = 0.032). This finding remained significant after controlling for possible confounding factors (p = 0.037). In conclusion, peripheral vasoconstrictive response to mental stress was more pronounced in men compared with women. This finding may suggest that men have higher susceptibility to mental stress-related adverse effects. Additional studies are needed to determine the significance of this finding.


Locomotor activity in the ischemic gerbil.
Previous studies have shown that within 24 h after ischemic insult, gerbils exhibit an increase in locomotor activity. Because activity gradually diminishes to normal levels with repeated testing, it has been argued that this behavior represents a reversible or transient effect of ischemia. The present study challenged this notion by testing ischemic gerbils at a time when increased activity is not observed with repeated testing. Ischemic (5-min bilateral carotid occlusion) and sham gerbils were tested for 14 consecutive days after reperfusion in an open-field apparatus (n = 6/condition). As previously reported, ischemic gerbils exhibited a significant increase in activity (days 1 and 2) which returned to control levels with repeated testing (days 13 and 14). A second group of ischemic and sham gerbils (n = 6/condition) were tested only on days 13 and 14 after reperfusion. In contrast to those tested repeatedly, these ischemic gerbils displayed increased locomotor activity as compared with sham controls. In addition, gerbils in the repeated testing conditions were evaluated in a semi-novel testing environment on days 15 and 16 after surgery. The locomotor activity of ischemic gerbils significantly increased in response to the semi-novel environment. These results suggest that the effects of ischemia on locomotor activity are not limited to a brief period after occlusion and may represent a permanent deficit. In addition, as previously suggested, this behavior may represent a deficit in habituation or spatial mapping rather than motor hyperactivity.


Juvenile polyposis of infancy in a child with deletion of BMPR1A and PTEN genes: surgical approach.
Juvenile polyposis of infancy is the most severe and life-threatening form of juvenile polyposis. This disease typically presents in the first two years of life with gastrointestinal bleeding, diarrhea, inanition, and exudative enteropathy. In very few reports concerning this entity, a large deletion in the long arm of chromosome 10 (10q23), encompassing the PTEN and BMPR1A genes, was found. The authors report a case of delayed diagnosis of juvenile polyposis of infancy at 6 years of age. A 3.34 Mb long de novo deletion was identified at 10q23.1q23.31, encompassing the PTEN and BMPR1A genes. The disease course was severe with diarrhea, abdominal pain, inanition, refractory anemia, rectal bleeding, hypoalbuminemia, and exudative enteropathy. A sub-total colectomy, combined with intraoperative endoscopic removal of ileal and rectal stump polyps, was required for palliative disease control.


Inhibitory effects of hypo-osmotic stress on extracellular carbonic anhydrase and photosynthetic efficiency of green alga Dunaliella salina possibly through reactive oxygen species formation.
In this study, Dunaliella salina (D. salina) maintained in 30‰ salinity for more than two years was exposed to the salinities of 5‰, 10‰, 20‰, 30‰ (control) in order to investigate oxidative burst and it's possible connection with extracellular carbonic anhydrase (CA) under hypo-osmotic stress (low salinity). The results indicated that intracellular ROS contents increased significantly when cells were exposed to salinity of 5 and 10‰, and the increase also occurred at 20‰ salinity. The activity of extracellular CA and its gene (P60) expression decreased significantly when cells were exposed to salinity of 5-20‰. Data from H₂O₂ treatments hinted that ROS production was possibly one of the factors affecting CA, including enzyme activity and gene expression levels. Significant inhibition of effective quantum efficiency of PSII and photosynthetic oxygen evolution rate were observed with the increase of ROS production and decline of CA activities. Taken together, hypo-osmotic stresses could induce ROS production in D. salina, and CA enzyme activities and expression levels were consequently inhibited. As a result, algal photosynthesis and oxygen evolution were inhibited.


Cardiomyocyte injury induced by hemodynamic cardiac stress: Differential release of cardiac biomarkers.
We explored whether hemodynamic cardiac stress leads to a differential release of cardiomyocyte injury biomarkers, used in the diagnosis of acute myocardial infarction (AMI). In an observational international multicenter study, we enrolled 831 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. Hemodynamic cardiac stress was quantified by levels of B-type natriuretic peptide (BNP). Spearman's rho correlation was used to analyze the correlations between BNP and high-sensitivity cardiac troponin T (hs-cTnT), Siemens cTnI-Ultra (cTnI-ultra), CK-MB and Myoglobin. Patients were categorized according to the extent of hemodynamic cardiac stress as quantified by BNP tertiles. Among all patients, the positive pair-wise correlation with BNP was strongest with hs-cTnT and cTnI-ultra (r=0.58 and 0.50, respectively), moderate for Myoglobin (r=0.43), and weakest with CK-MB (r=0.25; p<0.001 for each). Similar pattern of correlations was also observed among AMI patients. Among patients diagnosed with non-cardiac cause of chest pain (n=385, 46%) and cardiac but non-coronary (n=109, 13%), BNP had significant positive correlations with hs-cTnT, cTnI-ultra and Myoglobin (p<0.05), but not with CK-MB (p=NS). A similar pattern of stronger correlation between BNP and hs-cTnT, cTnI-ultra and Myoglobin as compared to that with CK-MB was also observed within the higher BNP tertile range. There was no correlation between BNP and other biomarkers within the 1st BNP tertile group. Hemodynamic cardiac stress, as quantified by BNP, as a likely cause of cardiomyocyte injury, is more closely reflected by concentrations of hs-cTnT, cTnI-ultra and Myoglobin than CK-MB.


Pulmonary phosphatidic acid phosphatase. A comparative study of the aqueously dispersed phosphatidate-dependent and membrane-bound phosphatidate-dependent phosphatidic acid phosphatase activities of rat lung.
1. The properties of the aqueously dispersed phosphatidate-dependent phosphatidic acid phosphatase (EC 220.127.116.11) activities of rat lung have been studied in microsomal and cytosol preparations and compared with the properties of the membrane-bound phosphatidate-dependent activities. 2. The microsomal phosphatidic acid phosphatase displayed a prominent pH optimum at 6.5 with a minor peak which varied between 7.5--8 in different experiments. With the cytosol, the major activity was at the higher pH (7.5--8.0) but a distinct optimum was also observed at pH 6.0--6.5. With the membrane-bound substrate, a single broad optimum was observed between pH 7.4 and 8.0 with the cytosol and 6.5--7.5 with the microsomal fraction. 3. Subcellular fractionation studies revealed that the microsomal fraction possessed the greatest proportion of the total phosphatidic acid phosphatase activity and the highest relative specific activity. However, studies with marker enzymes indicated that the aqueously dispersed phosphatidate-dependent activity could be present in plasma membrane, lysosomes and osmiophilic lamellar bodies as well as in the endoplasmic reticulum. 4. The aqueously dispersed phosphatidic acid-dependent activities present in the microsomal and supernatant fractions were inhibited by Ca2+, Mn2+, F- and by high concentrations of Mg2+. In contrast to the membrane-bound phosphatidate-dependent activities, there was little Mg2+ stimulation and only a very slight inhibitory effect was noted with EDTA. A small EDTA-dependent Mg2+ stimulation could be observed with the microsomal fraction but only at the lower pH optimum (6.5). 5. The presence of a number of phosphate esters tended to stimulate rather than inhibit the microsomal activity, indicating that the hydrolase is relatively specific for lipid substrates. Marked inhibitions were noted with lysophosphatidic acid and phosphatidylglycerol phosphate. Phosphatidylcholine produced a slight inhibition. 6. The results indicate that the bulk of the aqueously dispersed phosphatidate-dependent phosphatidic acid phosphatase activities of rat lung microsomes and cytosol is not related to the activities observed with membrane-bound phosphatidate. The Mg2+-dependent hydrolase activities may be synonymous. However, unequivocal conclusions will only be possible when the polypeptide or polypeptides responsible for these activities can be purified.


Methane asphyxia. Coal mine accident investigation of distribution of gas.
Death from asphyxia due to substitution of air by methane gas may occur in coal mine by gas outburst. In such a case, it is required to determine methane gas contents from cadaveric blood and tissues for diagnosing cause of death and estimating conditions of the accident. The methane concentration in blood and tissue samples of 22 male victims by a gas outburst accident was measured by gas chromatography. The level of methane in the cardiac blood was in the range of 6.8-26.8 microliters/g. As a model of gas outburst in coal mine, rats were exposed experimentally to various concentrations of methane. Their course of death and methane distribution in the bodies were observed. From these findings, diagnostic criteria for asphyxia from substitution of air by methane are also discussed.


Functional, physiological and subjective responses to concurrent neuromuscular electrical stimulation (NMES) exercise in adult cancer survivors: a controlled prospective study.
The primary aim of this study was to investigate the functional, physiological and subjective responses to NMES exercise in cancer patients. Participants with a cancer diagnosis, currently undergoing treatment, and an had an Eastern Cooperative Oncology Group (ECOG) performance status (ECOG) of 1 and 2 were recommended to participate by their oncologist. Following a 2-week, no-NMES control period, each participant was asked to undertake a concurrent NMES exercise intervention over a 4-week period. Functional muscle strength [30 s sit-to-stand (30STS)], mobility [timed up and go (TUG)], exercise capacity [6-min walk test (6MWT)] and health related quality of life (HR-QoL) were assessed at baseline 1 (BL1), 2-week post control (BL2) and post 4-week NMES exercise intervention (POST). Physiological and subjective responses to LF-NMES were assessed during a 10-stage incremental session, recorded at BL2 and POST. Fourteen participants [mean age: 62 years (10)] completed the intervention. No adverse events were reported. 30STS (+ 2.4 reps, p = .007), and 6MWT (+ 44.3 m, p = .028) significantly improved after the intervention. No changes in TUG or HR-QoL were observed at POST. Concurrent NMES exercise may be an effective exercise intervention for augmenting physical function in participants with cancer and moderate and poor functional status. Implications for cancer survivors: By allowing participants to achieve therapeutic levels of exercise, concurrent NMES may be an effective supportive intervention in cancer rehabilitation.


Antifertility effect of hydroalcoholic leaves extract of Michelia champaca L.: an ethnomedicine used by Bhatra women in Chhattisgarh state of India.
Michelia champaca L. (family: Magnoliaceae), commonly known as Champa [Hindi], is traditionally used for fertility regulation by the women of Chhattisgarh state in India. No scientific evidence regarding the antifertility effect of this plant is available till date. To study the anti-fertility effect of hydroalcoholic leaf extract of Michelia champaca Linn. in female rats. The antifertility activity of the extract (HAEMC) administered at dose levels (100 and 200mg/kg body weight, p.o.) was evaluated in two experimental animal models i.e. antiimplantation activity in female wistar rats and esterogenic/antiestrogenic activity in ovariectomized female rats. In anti-implantation activity, the extract (200 and 400mg/kg body weight, p.o.) was administered to female rats from 1 to 7 days of pregnancy and on 10th day, laprotomy was performed to count the no. of implants. For estrogenic/anti-estrogenic activity, ovariectomized female rats were administered with the extract at both the doses alone as well as along with 17α-ethinyl estradiol (1 μ/rat/day) for 7 consecutive days. On the 8th day, all animals were sacrificed and blood serum was further processed for the estimation of biochemical parameters such as estrogen level, alkaline phosphates, cholesterol, tryglycerides, total protein etc. The extract (HAEMC) showed significant (p<0.01) 49.95% and 71.03% antiimplantation activities at 100 and 200mg/kg doses respectively. The extract also exhibited significant (p<0.01) estrogenic activity as evidenced by increase in body weight, uterine weight, increased thickness and height of endometrium, vaginal cornification and significant (p<0.01) increase in estrogen, cholesterol, alkaline phosphate and triglycerides levels at higher dose when administered alone as well as along with ethinyl estradiol. Phytochemical screening showed the presence of steroids, flavonoids and alkaloids in the extract. Hydroalchoholic extract of Michelia champaca leaves possesses significant antifertility effect which might be due to the inhibition of implantation and estrogenic effect which in turn might be due to the presence of some phytoconstituents in the plant.


Piperine potentiates the effects of trans-resveratrol on stress-induced depressive-like behavior: involvement of monoaminergic system and cAMP-dependent pathway.
Stress can act as a precipitation factor in the onset of emotional disorders, particularly depression. Trans-resveratrol is a polyphenolic compound enriched in polygonum cuspidatum and has been found to exert antidepressant-like effects in our previous studies. In present study, we assessed the effects of trans-resveratrol used in combination with piperine, commonly known as a bioavailability enhancer, on chronic unpredictable mild stress-induced depressive-like behaviors and relevant molecular targets. Trans-resveratrol used alone reduced the immobility time of rats in the forced swimming test, with the maximal effects of trans-resveratrol around 60 % inhibition at the highest dose tested, 40 mg/kg. However, when a subthreshold dose of piperine, 2.5 mg/kg was used in combination with trans-resveratrol, the minimum effective dose of trans-resveratrol in reducing the immobility time was reduced to 20 mg/kg. Further evidence from neurochemical (monoamines in the frontal cortex and the hippocampus), biochemical (monoamine oxidase, MAO activities) and molecular biological (cAMP, PKA, CREB and BDNF) assays supported the findings in the behavioral studies. These results suggest that the co-treatment strategy with trans-resveratrol and piperine might be an alternative therapy that provides efficacious protection against chronic stress.


Global change research needs international collaboration.
Tackling the grand challenges of global climate change for the sustainability of ecological and societal systems requires data and expertise from Russia, the world's largest country that has the longest Arctic shoreline and the largest forest biome, peatland and permafrost zones. Academic relations and scientific collaborations with Russian scholars and institutions must continue despite the ensuing geopolitical crisis since 2022.


The silymarin composition… and why does it matter???
The extract from milk thistle (Silybum marianum (L.) Gaertn. (Asteraceae)), known as silymarin, contains a variety of flavonolignans and displays antioxidant, anti-inflammatory, immunomodulatory and hepatoprotective properties. As silybin is the main component of silymarin, the literature mainly focuses on this compound, ignoring all other components. This leads to problems in reproducibility of scientific results, as the exact composition of silymarin is often unknown and can vary to a certain degree depending on the processing, chemo-variety of the plant used and climatic conditions during the plant growth. There are studies dealing with the analytical separation and quantification of silymarin components as well as studies focused on silymarin content in clinically used drugs, in various plant parts, seasons, geographic locations etc. However, no comparison of detail flavonolignan profiles in various silymarin preparations is available to date. Also, as a result of the focus on the flavonolignans; the oil fraction, which contains linoleic, oleic and palmitic acids, sterols, tocopherol (vitamin E) and phospholipids, has been neglected. Due to all these factors, the whole plant is used e.g. as animal feed, the leaves can be eaten in salads and seed oil, besides culinary uses, can be also utilized for biodiesel or polymer production. Various HPLC separation techniques for the determination of the content of the flavonolignans have been vastly summarized in the present review.


An HPLC-UV method for the simultaneous quantification of vemurafenib and erlotinib in plasma from cancer patients.
Vemurafenib and erlotinib are two oral kinase inhibitors approved for the treatment of metastatic melanoma and advanced non-small cell lung cancer, respectively. In contrast with erlotinib, the single published method for analysis of vemurafenib in human plasma is based on mass spectrometry. The purpose of the present study was to develop an HPLC-UV method to simultaneously quantify these two drugs in plasma. Following liquid-liquid extraction, vemurafenib, erlotinib and sorafenib (internal standard) were separated isocratically on a C8 Xterra(®) MS using a mobile phase of glycine buffer (pH 9.0, 100mM)/acetonitrile (45:55, v/v). Samples were eluted at a flow rate of 0.9mL/min throughout the 12-min run. Dual UV wavelength mode was used, with vemurafenib and sorafenib monitored at 249nm, and erlotinib at 331nm. The calibration was linear in the range 1.25-100mg/L and 50-4000μg/L for vemurafenib and erlotinib, respectively. Inter- and intra-day precision was less than 6.7% and 6.6% for vemurafenib and erlotinib, respectively. This analytical method was successfully applied to assess the steady state plasma exposure of these drugs in cancer patients. This accurate method can be used in routine clinical practice to monitor vemurafenib or erlotinib concentrations in plasma from cancer patients.


Expression of PTEN, p27, p21 and AKT mRNA and protein in human BEL-7402 hepatocarcinoma cells in transplanted tumors of nude mice treated with the tripeptide tyroservatide (YSV).
The tripeptide, tyroservatide (YSV), has been previously shown to have antitumor effects through unknown mechanism. In the current study, we examined whether YSV modulates the protumorigenic PI3K pathway in human BEL-7402 hepatocarcinoma cells. BEL-7402 hepatocarcinoma was transplanted into the subcutaneous tissues of nude mice, and YSV, at varying doses, was administered. RT-PCR and Western blot were used to analyze the expression of PTEN, AKT, p21 and p27. YSV at doses of 80 microg/kg/day, 160 microg/kg/day and 320 microg/kg/day markedly inhibited the growth of human BEL-7402 hepatocarcinoma (p < 0.05). YSV increased mRNA and protein expression of the tumor-suppressor genes, PTEN, p21 and p27, and inhibited the mRNA and protein expression of the oncogene AKT. Furthermore, YSV administration was associated with dephosphorylation of both PTEN (which activates PTEN) and AKT (which inhibits AKT). These results are consistent with the possibility that YSV mediates inhibition of tumor growth through inhibition of the PI3K pathway and suggests that YSV should be explored for use as an antitumor agent for hepatocarcinoma.


The decision-making in dribbling: a video analysis study of U10 soccer players' skills and coaches' quality evaluation.
Dribbling is an important soccer skill that, when effective, allows players to overcome opponents. It can provide a strong tactical advantage; for this reason, all of its components (sprint, speed, and ball control) are fundamental to the development of young players. Dribbling can also be considered a decision-making process, and due to its characteristics, it is not always easy to study ecologically. Using a video analysis study, this research aimed to determine whether dribbling skills, specifically dribbling choice (i.e., decision-making), were related to U10 soccer players' quality. Several outcomes measures, divided into three categories, were taken during video analyses: (i) measures related to the efficacy of dribbling skill; (ii) measures related to the ability of players without the ball to support the player in possession; and (iii) measures related to ball circulation. These data were retrospectively assessed to whether the coaches had formed the teams in training through an implicit knowledge of the players' dribbling skills. The percentage of accurate dribbling (that is, the ability to perform correct passes after a successful dribble) was found to be the variable that coaches may have implicitly used in creating the three groups differentiated by technical skills (p < 0.05). In fact, this percentage was 12.9%, 24.0%, and 48.1% for the groups with lower, average, and higher technical skills, respectively. Overall, the results demonstrate that dribbling accuracy has an important weight in the coach's evaluation of the technical skills level of young soccer players.


A guide to CORNET for the construction of coexpression and protein-protein interaction networks.
To enable easy access and interpretation of heterogenous and scattered data, we have developed a user-friendly tool for data mining and integration in Arabidopsis thaliana, designated CORrelation NETworks (acronym CORNET), allowing browsing of microarray data, construction of coexpression and protein-protein interactions (PPIs), analysis of gene association and transcription factor (TF) regulatory networks, and exploration of diverse functional annotations. CORNET consists of three tools that can be used individually or in combination, namely, the coexpression tool, the PPI tool, and the TF tool. Different search options are implemented to enable the creation of networks centered around multiple input genes or proteins. Functional annotation resources are included to retrieve relevant literature, phenotypes, localization, gene ontology, plant ontology, and biological pathways. Networks and associated evidence of the majority of the currently available data types are visualized in Cytoscape. CORNET is available at https://bioinformatics.psb.ugent.be/cornet.


Recursive partitioning analysis of prognostic factors for survival in patients with advanced cancer.
To construct a predictive model for survival of patients referred to the Rapid Response Radiotherapy Program using recursive partitioning (RP). We analyzed 16 factors characterizing patients with metastases at first referral to the Rapid Response Radiotherapy Program for palliative radiotherapy in 1999 for their effect on survival. They included age, primary cancer site, site of metastases, weight loss (>or=10% during the past 6 months), Karnofsky performance status (KPS), interval from the first diagnosis of cancer to the first consultation at the Rapid Response Radiotherapy Program, analgesic consumption within the previous 24 h, and the nine symptom scores from the Edmonton Symptom Assessment Scale. We used RP to develop a predictive model of survival for patients referred in 1999, followed by temporal validation using patients referred in 2000, and external validation using patients referred in 2002 to another institution. The model was able to separate patients into three groups with different durations of survival that were defined by (1) KPS >60; (2) KPS <or=60 with bone metastases only; and (3) KPS <or=60 with other metastases. The model performed moderately well when applied to the validation sets, but a major limitation was that it led to an unequal distribution of patients, with a small proportion of patients in the intermediate group. We have demonstrated that RP can be used to predict the survival of patients with advanced cancer. However, this model has no advantages compared with our published prognostic models that use the survival prediction scores and number of risk factors.


Surface tension of nanoparticle dispersions unravelled by size-dependent non-occupied sites free energy versus adsorption kinetics.
The surface tension of dispersions presents many types of behaviours. Although some models, based on classical surface thermodynamics, allow partial interpretation, fundamental understanding is still lacking. This work develops a single analytical physics-based formulation experimentally validated for the surface tension of various pure nanoparticle dispersions, explaining the underlying mechanisms. Against common belief, surface tension increase of dispersions appears not to occur at low but rather at intermediate surface coverage, owed by the relatively large size of nanoparticles with respect to the fluid molecules. Surprisingly, the closed-form model shows that the main responsible mechanism for the various surface tension behaviours is not the surface chemical potential of adsorbed nanoparticles, but rather that of non-occupied sites, triggered and delicately controlled by the nanoparticles 'at a distance', introducing the concept of the 'non-occupancy' effect. The model finally invites reconsidering surface thermodynamics of dispersions and provides for criteria that allow in a succinct manner to quantitatively classify the various surface tension behaviours.


Incidence of Infective Endocarditis Among Patients With Tetralogy of Fallot.
Background Patients with tetralogy of Fallot (ToF) are considered at high risk of infective endocarditis (IE) as a result of altered hemodynamics and multiple invasive procedures, including pulmonary valve replacement (PVR). Data on the long-term risk of IE are sparse. Methods and Results In this observational cohort study, all patients with ToF born from 1977 to 2018 were identified using Danish nationwide registries and followed from date of birth until occurrence of first-time IE, emigration, death, or end of study (December 31, 2018). The comparative risk of IE among patients with ToF versus age- and sex-matched controls from the background population was assessed. Because of rules on anonymity, exact numbers cannot be reported if the number of patients is <4. A total of 1164 patients with ToF were identified and matched with 4656 controls. Among patients with ToF, 851 (73.1%) underwent early surgical intracardiac repair and 276 (23.7%) underwent PVR during follow-up. During a median follow-up of 20.3 years, 41 (3.5%) patients with ToF (comprising 24 [8.7%] with PVR and 17 [1.9%] without PVR) and <4 (<0.8%) controls were admitted with IE. The incidence rates of IE per 10 000 person-years were 22.4 (95% CI, 16.5-30.4) and 0.1 (95% CI, 0.01-0.7) among patients and controls, respectively. Moreover, PVR was associated with a further increased incidence of IE among patients with ToF (incidence rates per 10 000 person-years with and without PVR were 46.7 [95% CI, 25.1-86.6] and 2.8 [95% CI 2.0-4.0], respectively). Conclusions Patients with ToF are associated with a substantially higher incidence of IE than the background population. In particular, PVR was associated with an increased incidence of IE. With an increasing life expectancy of these patients, intensified awareness, preventive measures, and surveillance of this patient group are decisive.


A simple and reliable method for the detection of sialylation in complex/hybrid-type carbohydrate chains of glycoproteins by mixed lectins.
A practical and convenient method for discriminating between the presence and the absence of sialic acid in carbohydrate chains of glycoproteins was devised using paramagnetic beads and two lectins, Sambucus sieboldiana lectin (SSA) and Ricinus communis agglutinin (RCA120). The glycoproteins of transferrin or thyroglobulin were firstly captured to paramagnetic beads that were previously coated with corresponding antibody, and then the lectins of RCA120-biotin and SSA-FITC were bound to the glycoproteins on the paramagnetic beads. Finally, the fluorescence intensity of the beads was measured to determine the ratios of lectins RCA120-biotin/Cy5-streptavidin to SSA-FITC. The mixed lectins method showed bigger difference of the ratios between the presence and the absence of sialic acid, indicating higher discrimination efficiency than the ordinary non-mixed lectins method. Furthermore, statistical analysis by two-side t-test indicated that the mixed lectins method was more highly reliable than the ordinary non-mixed lectins method in discriminating between the presence and the absence of sialic acid. The reaction with the two lectins can be performed in a single tube and readily automated taking advantage of the use of paramagnetic beads.


Efficient removal of 2,6-xylidine precipitate using different agitation protocols: An in vitro field emission scanning electron microscopic study.
Any solution of chemical nature when combined will result in the formation of a precipitate, which in the root canal system will interfere with the hermetic seal. In clinical practice presence of any precipitate, especially carcinogenic in nature, should be eliminated. To evaluate whether final irrigation with different agitation protocols will remove the precipitate formed following lidocaine hydrochloride and sodium hypochlorite combination at the coronal, middle, and apical-root thirds. Forty-four uniradicular teeth were standardized at 17 mm. All specimens were injected with 2% lidocaine hydrochloride and 2.5% sodium hypochlorite, followed by mechanical instrumentation using rotary files. Further, specimens were arbitrarily divided into four groups (n = 11) based on the final irrigation protocol: Group 1: No irrigation; Group 2: Manual irrigation; Group 3: Mechanical irrigation; Group 4: Ultrasonic irrigation. Samples were sectioned and Field Field Emission Scanning Electron Microscopic (FESEM) analysis of the canal wall was done at coronal, middle, and apical thirds. FESEM images revealed occluded dentinal tubules with the presence of precipitate seen in all-thirds of each specimen. No irrigation protocol was successful in removing the precipitate formed; but when compared ultrasonic irrigation had the least precipitate seen at-coronal,-middle and apical thirds.


Selection of potential non-Sacharomyces probiotic yeasts from food origin by a step-by-step approach.
Due to healthcare is increasing in nowadays, the use of the commercial probiotics is in progress and each day they are more demanded. The challenge of this study is to identify yeast species for using as probiotic organisms. Thus, the research applied a step-by-step approach, to study the probiotic potential of non-Saccharomyces yeast strains. The 215 yeasts were isolated from different environments such as wineries, oil mills, brines cheeses, fermented vegetables and distilleries in previous works and were identified to strain level by RAPD-PCR technique resulting 108 different strains. A general screening was carried out to know the probiotic capability of the yeasts, following the next steps: study of the ability to resist and grow of the yeasts when they exposed to simulated in vitro digestion conditions and influence of time, temperature, pH and the presence of enzymes on the kinetic growth parameters (lag phase (λ), generation time (G), maximum OD (ODmax) and the specific growth rate constant (μmax)). The results made possible the selection of the 23% of the strains and they were assayed for knowing their capability of self-aggregation and hydrophobicity. Biofilm formation capacity and viability after simulated sequential salivary-gastric-intestinal digestion were then studied for the 10 best strains. Statistical analyses were applied in each step to make the selection. The final results showed that two yeasts, H. osmophila and P. kudriavzevii, were the most promising strains.


The expression of Cav3.1 on T-type calcium channels of rats with subarachnoid hemorrhage.
To study delayed cerebral vasospasm (DCVS) induced by subarachnoid hemorrhage (SAH), 60 healthy Sprague Dawley (SD) rats were randomly divided into 5 groups (12 rats in each group), namely sham operation group, blood injection model group, nimodipine group, flunarizine hydrochloride group, and normal group. Then, the physiological parameters were detected, and after the rats were killed under anesthesia, the degree of nerve injury, vasospasm as well as the therapeutic effect of drugs were evaluated by Western Blot (WB). Neurological impairment (NI), endothelial contraction and spasm were obvious in rats following blood injection. The expression of Cav3.1 on T-type calcium channels was significantly higher in the blood injection model group than in the sham operation group along with the normal group. Moreover, Cav3.1 mRNA was expressed in all groups. The Cav3.1 expression in blood injection model group and two drug groups were significantly higher than that in sham operation group and lower than that in blood injection model group. Vasospasm was improved in two drug groups, which indicated that calcium channel antagonists nimodipine and flunarizine hydrochloride had a certain therapeutic effect on DCVS in rats. The decrease in body weight and food intake of the two groups of rats treated with drugs decreased, and the delayed vasospasm was improved, but the expression of Cav3.1 was not changed significantly, indicating nimodipine and flunarizine hydrochloride had a therapeutic effect on delayed vasospasm in rats, but Cav3.1 expression on calcium channels was not affected.


Acute aortic dissection involving an aberrant right subclavian artery.
Although the aberrant right subclavian artery is the most common abnormality in aortic arch development, it is unusual to encounter this abnormality when repairing acute aortic dissection. We report a case of Stanford type A acute aortic dissection involving an aberrant right subclavian artery in a 45-year-old man. We used the elephant trunk procedure to surgically manage the intimal tear and aberrant right subclavian artery. This is, to our knowledge, the first report in Japan of surgical reconstruction of an aberrant right subclavian artery in conjunction with acute aortic dissection.


Croceicoccus gelatinilyticus sp. nov., isolated from a tidal flat sediment.
A novel Gram-staining-negative and short-rod-shaped bacterial strain designated as 1NDH52T was isolated from a tidal flat sediment and characterized using a polyphasic taxonomic approach. The predominant cellular fatty acids of strain 1NDH52T were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) and C14:0 2-OH; the major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid; the major respiratory quinone was Q-10. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 1NDH52T was closely related to type strains Croceicoccus sediminis S2-4-2 T (98.9%), Croceicoccus bisphenolivorans H4T (98.9%) and Croceicoccus pelagius Ery9T (98.7%). Phylogenomic analysis indicated that strain 1NDH52T formed an independent branch distinct from all type strains of this genus. The overall genome related indices including the digital DNA-DNA hybridization values, average nucleotide identities and average amino acid identities between strain 1NDH52T and the three close relatives above indicated that strain 1NDH52T should represent a novel genospecies. The genomic DNA G + C content was 62.6%. Strain 1NDH52T could produce carotenoids and its genome contained the complete carotenoids biosynthetic gene cluster. Based on the phenotypic and genotypic characteristics, strain 1NDH52T is concluded to represent a novel species of the genus Croceicoccus, for which the name Croceicoccus gelatinilyticus sp. nov., is proposed. The type strain of the species is 1NDH52T (= GDMCC 1.2381 T = KCTC 82668 T).


Resolution enhanced homonuclear carbon decoupled triple resonance experiments for unambiguous RNA structural characterization.
Large RNAs (>30 nucleotides) suffer from extensive resonance overlap that can seriously hamper unambiguous structural characterization. Here we present a set of 3D multinuclear NMR experiments with improved and optimized resolution and sensitivity for aiding with the assignment of RNA molecules. In all these experiments strong base and ribose carbon-carbon couplings are eliminated by homonuclear band-selective decoupling, leading to improved signal to noise and resolution of the C5, C6, and C1' carbon resonances. This decoupling scheme is applied to base-type selective 13C-edited NOESY, 13C-edited TOCSY (HCCH, CCH), HCCNH, and ribose H1C1C2 experiments. The 3D implementation of the HCCNH experiment with both carbon and nitrogen evolution enables direct correlation of 13C and 15N resonances at different proton resonant frequencies. The advantages of the new experiments are demonstrated on a 36 nucleotides hairpin RNA from domain 5 (D5) of the group II intron Pylaiella littoralis using an abbreviated assignment strategy. These four experiments provided additional separation for regions of the RNA that have overlapped chemical shift resonances, and enabled the assignment of critical D5 bulge nucleotides that could not be assigned using current experimental schemes.


Sex-Specific Clinical Outcomes of the PACT-HF Randomized Trial.
Transitional care may have different effects in males and females hospitalized for heart failure. We assessed the sex-specific effects of a transitional care model on clinical outcomes following hospitalization for heart failure. In this stepped-wedge cluster randomized trial of adults hospitalized for heart failure in Ontario, Canada, 10 hospitals were randomized to a group of transitional care services or usual care. Outcomes in this exploratory analysis were composite all-cause readmission, emergency department visit, or death at 6 months; and composite all-cause readmission or emergency department visit at 6 months. Models were adjusted for stepped-wedge design and patient age. Among 2494 adults, mean (SD) age was 77.7 (12.1) years, and 1258 (50.4%) were female. The first composite outcome occurred in 371 (66.3%) versus 433 (64.1%) males (hazard ratio [HR], 1.04 [95% CI, 0.86-1.26]; P=0.67) and in 326 (59.9%) versus 463 (64.8%) females (HR, 0.83 [95% CI, 0.69-1.01]; P=0.06) in the intervention and usual care groups, respectively (P=0.012 for sex interaction). The second composite outcome occurred in 357 (63.8%) versus 417 (61.7%) males (HR, 1.03 [95% CI, 0.85-1.24]; P=0.76) and 314 (57.7%) versus 450 (63.0%) females (HR, 0.81 [95% CI, 0.67-0.99]; P=0.037) in the intervention and usual care groups, respectively (P=0.024 for sex interaction). The sex differences were driven by a reduction in all-cause emergency department visits among females (HR, 0.66 [95% CI, 0.51-0.87]; P=0.003), but not males (HR, 1.10 [95% CI, 0.85-1.43]; P=0.46), receiving the intervention (P<0.001 for sex interaction). A transitional care model offered a reduction in all-cause emergency department visits among females but not males following hospitalization for heart failure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02112227.


Functional tunability from a distance: Rheostat positions influence allosteric coupling between two distant binding sites.
For protein mutagenesis, a common expectation is that important positions will behave like on/off "toggle" switches (i.e., a few substitutions act like wildtype, most abolish function). However, there exists another class of important positions that manifests a wide range of functional outcomes upon substitution: "rheostat" positions. Previously, we evaluated rheostat positions located near the allosteric binding sites for inhibitor alanine (Ala) and activator fructose-1,6-bisphosphate (Fru-1,6-BP) in human liver pyruvate kinase. When substituted with multiple amino acids, many positions demonstrated moderate rheostatic effects on allosteric coupling between effector binding and phosphoenolpyruvate (PEP) binding in the active site. Nonetheless, the combined outcomes of all positions sampled the full range of possible allosteric coupling (full tunability). However, that study only evaluated allosteric tunability of "local" positions, i.e., positions were located near the binding sites of the allosteric ligand being assessed. Here, we evaluated tunability of allosteric coupling when mutated sites were distant from the allosterically-coupled binding sites. Positions near the Ala binding site had rheostatic outcomes on allosteric coupling between Fru-1,6-BP and PEP binding. In contrast, positions in the Fru-1,6-BP site exhibited modest effects on coupling between Ala and PEP binding. Analyzed in aggregate, both PEP/Ala and PEP/Fru-1,6-BP coupling were again fully tunable by amino acid substitutions at this limited set of distant positions. Furthermore, some positions exhibited rheostatic control over multiple parameters and others exhibited rheostatic effects on one parameter and toggle control over a second. These findings highlight challenges in efforts to both predict/interpret mutational outcomes and engineer functions into proteins.


[Evaluation of users and health professionals on teleconsultation in primary care: A cross-sectional study].
To evaluate the perceptions and preferences of users and health professionals on teleconsultation in primary care. Cross-sectional study with a telephone survey of users and a face-to-face survey of professionals carried out at 2021. Urban primary health care. Random sample of users with teleconsultations in the last year, stratified by sex and age, and doctors and nurses from participating centres. Likert variables assessing teleconsultation according to consultation motives, preferences and related aspects. Descriptive analysis and comparison of proportions and means. Three hundred patients and 48 professionals answered the questionnaire. Both groups value positively the teleconsultation for the management of the electronic prescription (EP) (83% and 83%, respectively), sick leave (SL) (80% and 64%) and issues related to COVID-19 (71% and 58%). The positive assessment of teleconsultation decreases for the treatment of acute pathologies (47% and 25%) and chronic diseases (49% and 33%). Globally, people <70 years value teleconsultation more highly (P<.001), without differences between sexes. Users and professionals prefer face-to-face consultation for chronic diseases (82% and 83%) and acute pathologies (82% and 94%), and teleconsultation for EP (68.7% and 88.6%). 52% of users prefer face-to-face visits for SL compared to 29% of professionals (P<.05). Teleconsultation implementation has been well valued by both patients and professionals. The face-to-face visit is preferred for chronic and acute pathologies, especially in the elderly. It will be necessary to define in which cases teleconsultation is the best tool according to the characteristics of each population.


Effects of cadmium on glutathione synthesis in hepatopancreas of freshwater crab, Sinopotamon yangtsekiense.
Cadmium (Cd) is one of the most deleterious heavy metals in aquatic systems that could promote oxidative damage. To explore the effects of Cd exposure of a freshwater crab (Sinopotamon yangtsekiense) on hepatopancreatic glutathione (GSH) synthesis, crabs were exposed to the reagent with a dose range of 7.25-116.00 mg L(-1) for 48 h. The concentrations of GSH, oxidized glutathione (GSSG), NADPH and NADP(+), as well as the activities of enzymes involved in GSH synthesis, i.e. glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), gamma-glutamylcysteine synthetase (gamma-GCS) were determined. Progressive depletion of cellular GSH content was observed with the increasing of Cd concentrations, while the level of GSSG remained constant. In response to Cd exposure, crabs showed significant induction of G6PD and NADPH, however, only up to moderate exposures. GR activity remained at a steady level at all exposure concentrations. The activity of gamma-GCS was significantly positively correlated with the Cd concentration. These results suggested that GSH synthesis could be activated against reactive oxygen species induced by lower Cd exposure; under the higher Cd exposure conditions, an inhibition of NADPH-dependant redox cycling and de novo GSH synthesis led to significant decrease in GSH content.


Performance of the domestic Bt corn event expressing pyramided Cry1Ab and Vip3Aa19 against the invasive Spodoptera frugiperda (J. E. Smith) in China.
The invasive fall armyworm, Spodoptera frugiperda (J.E. Smith), has caused serious corn yield losses and increased the frequency of insecticide spraying on corn in Africa and Asia. Drawing lessons from the use of Bt corn to manage fall armyworm in the Americas, China released a certificate for the genetically modified corn event DBN3601T pyramidally expressing Cry1Ab and Vip3Aa19 for industrialization in 2021. Performance of the DBN3601T event against invasive fall armyworm in China was evaluated by plant tissue-based bioassays and field trials during 2019-2021. In the bioassays, tissues and organs of DBN3601T corn differed significantly in lethality to fall armyworm neonates in the order: leaf > husk > tassel and kernel > silk. In field trials, compared with non-Bt corn, DBN3601T corn greatly suppressed fall armyworm populations and damage; larval density, damage incidence, and leaf damage scores for DBN3601T corn were significantly lower than for non-Bt corn at different vegetative stages, and efficacy against larval populations during the 3 years ranged from 95.24% to 98.30%. A laboratory bioassay and 3-year field trials confirmed that DBN3601T corn greatly suppressed fall armyworm populations and has high potential as a control of this invasive pest, making it a key tactic for integrated management of fall armyworm in China. © 2022 Society of Chemical Industry.


The importance of farrowing to service interval in sows served during lactation or after shorter lactation than 28 days.
In a retrospective study, based on data from the national litter recording system, farrowing rate and litter size of sows served (inseminated or mated) during the lactation period (n = 574) or after a lactation period shorter than 28 days (n = 14,219) were analysed. The results were compared with the corresponding figures for sows with lactation length between 28 and 35 days and weaning to first service interval of 4 or 5 days (reference group; n = 41,741). The farrowing rate of the reference group was 80.9% and subsequent litter size was 13.7 total piglets born. Among sows served prior to weaning, the farrowing rates and litter sizes were significantly lower for those served earlier than 22 days post-farrowing compared to those served later (P < 0.05). Shorter lactations than 28 days and service within 10 days post-weaning led to lower farrowing rates than in the reference group (P < 0.01). Significant differences were seen after different lactation lengths. After correction for weaning to service interval, preceding litter size weaned, parity, breed and the interaction between parity and breed, litter size was significantly and positively associated with the preceding lactation length. The study shows that service within the first 3 weeks post-farrowing results in reduced reproductive performance.


Identification of substance use disorders among pregnant women: A comparison of screeners.
The purpose of this study is to evaluate five self-report, non-proprietary questionnaires in the identification of substance use disorders [including alcohol, cannabis, opioids, and stimulants] among pregnant women. A total of 1220 pregnant women completed the NIDA Quick Screen, CRAFFT, Substance Use Risk Profile-Pregnancy (SURP-P), Wayne Indirect Drug Use Questionnaire (WIDUS), and the 5 Ps, as well as the MINI diagnostic interview for substance use disorders, which served as the reference standard. Measures of merit calculated for each screener included sensitivity, specificity, accuracy, and area under the receiver operating curve (AUROC). The participants were socioeconomically diverse, with a mean age of 29 years. Over 15% met diagnostic criteria for a substance use disorder. AUROCS for identifying any substance use disorder (including alcohol) ranged from a high of 0.75 for the CRAFFT (95% CI = 0.72-79) and 0.74 for the SURP-P (95% CI = 0.71-.78) to a low of 0.62 for the NIDA Quick Screen (95% CI = 0.59-.65). Overall accuracy of most tested measures was higher for identification of alcohol use disorders than for other substance use disorders (e.g., AUROCs for the CRAFFT and SURP-P for identifying alcohol use disorders were 0.78 and 0.77, respectively). The CRAFFT and SURP-P showed modest ability to identify substance use disorders among pregnant women. Future research is needed to develop an ideal questionnaire set in the complicated societal context which includes increasing rates of use and potential sanction.


Diagnostic and prognostic utility of methylation and protein expression patterns of myopodin in colon cancer.
Myopodin is an actin-binding protein believed to play a tumor suppressor role in several solid neoplasias. We evaluated the potential differential myopodin methylation and expression and their clinical relevance in colon cancer. The epigenetic silencing of myopodin by hypermethylation was tested in colon cancer cells (n = 5) before and after azacitidine treatment. Myopodin methylation status was evaluated by methylation-specific PCR in colon cancer cells and colorectal tissues (n = 210) grouped in a training set (n = 62) and two independent validation series (n = 100 and n = 48) collected at independent clinical settings. Myopodin expression patterns were analyzed by immunohistochemistry on tissue arrays. Myopodin hypermethylation correlated with gene and protein expression loss, being increased in vitro by azacitidine. Myopodin was frequently methylated in colon cancer cells (four out of five). Methylation rates were 90.3%, 70.0%, and 47.8% in the training and validation sets, respectively. Myopodin methylation rendered a diagnostic accuracy of 83.9% (p < 0.0005). Cytoplasmic myopodin expression was significantly higher in non-neoplastic biopsies compared to colon tumors (p < 0.0005). Loss of myopodin expression correlated with increasing tumor stage (p = 0.011), methylation (p = 0.005), and poor overall survival (p = 0.003). In the first validation set (n = 100), myopodin methylation predicted disease-free (p = 0.046) and overall survival (p = 0.031). In the second validation cohort, myopodin methylation and protein expression patterns predicted disease-specific (p = 0.012 and p = 0.001, respectively) and overall survival (p = 0.009 and p = 0.043, respectively). Thus, myopodin was revealed to be epigenetically modified in colon cancer. The diagnostic and prognostic clinical utility of myopodin methylation and expression patterns suggest considering their assessment for the clinical management of colon cancer patients.


Bio-mimetic mechanisms of natural hierarchical materials: a review.
Natural selection and evolution develop a huge amount of biological materials in different environments (e.g. lotus in water and opuntia in desert). These biological materials possess many inspiring properties, which hint scientists and engineers to find some useful clues to create new materials or update the existing ones. In this review, we highlight some well-studied (e.g. nacre shell) and newly-studied (e.g. turtle shell) natural materials, and summarize their hierarchical structures and mechanisms behind their mechanical properties, from animals to plants. These fascinating mechanisms suggest to researchers to investigate natural materials deeply and broadly, and to design or fabricate new bio-inspired materials to serve our life.


How to choose the surgical side when cerebral blood flow and cerebrovascular response are contradictory in bilateral moyamoya disease?: A case report.
Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive occlusion of the internal carotid artery and the secondary formation of collateral vessels. Bypass surgery is an effective treatment for MMD. Comprehensive evaluation of cerebral blood flow (CBF) and cerebrovascular response (CVR) is the common hemodynamic indication to surgery, the changes of which are usually identical. We reported a rare case of MMD in a 34-year-old pregnant woman with transient ischemic attacks (TIAs) for 1 month, manifesting as frequent weakness in right limbs for several minutes without obvious cause. The diagnostic digital subtraction angiography (DSA) examination revealed Suzuki Grade I in left side and Grade IV in right side under modified Suzuki scoring. No-hyperventilation test single-photon emission computed tomography (no-HVT SPECT) showed more decreased CBF in the right side of the brain, but HVT SPECT demonstrated a more impaired CVR on the left side. Comprehensively, which side should be operated on is confusing when the changes of CVR and CBF are inconsistent. The patient was diagnosed with bilateral MMD and underwent combined bypass surgery on the left side of the brain. The symptoms of admission were completely relieved after surgery and there were no further cerebrovascular events during the follow-up period of 4 months. CVR is a primary surgical indication of MMD, especially when the impairment of CVR and CBF are not consistent in the ipsilateral hemisphere. Meanwhile, HVT is the vital vasoactive challenges test for measuring CVR in MMD.


Simultaneous Mastopexy via Areola Excision to Correct Mild and Moderate Breast Ptosis.
Breast ptosis is one of the most common complaints in the clinical setting. Simultaneous mastopexy via areola excision involves a reliable modified aesthetic technique with distinctive features to correct mild and moderate pendulous breasts. The aim of this study is to determine whether the novel surgical approach is a safe and long-lasting technique for patients with breast ptosis. We performed a retrospective study of 48 patients who received simultaneous mastopexy through circumareolar excision and followed up for 12 months. Breast size, shape, fullness, symmetry, scar appearance, and sensitivity of nipple-areolar complex were evaluated. Patients were satisfied with upper pole fullness, symmetry and scar less appearance. There were no cases of NAC deformity or sensation loss, neither sever capsular contracture was observed. The new surgical technique, one-stage periareolar augmentation mastopexy, is a reliable and long-lasting operation for patients with mild and moderate breast ptosis. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


[Detection of anti-HEV IgG and analysis of partial HEV RNA sequence].
To investigate HEV infection in swine and the genotype relationship between swine and human HEV. Anti-HEV IgG antibody was detected in the sera of swine using enzyme linked immunoassay (EIA), and HEV RNA was amplified by reverse transcription nested polymerase chain reaction (RT-nPCR). The Vector NTI Suite 7 and TreeView softwares were used for nucleotide sequences phylogenetic analysis of HEV isolated from human and swine. The anti-HEV IgG positive rate was 16.67% (18/108). Among the 18 anti-HEV IgG positive sera, 2 sequences (11.11%, called S18 and S43, respectively) of HEV ORF1 (102-387bp) were amplified, with the identity of 99% between them. They had 76% to 77%, 78%, 76% to 79%, 85% to 86%, 77%, 80%, 79% and 75% - 79% homology at the nucleotide level with human HEV genotypes 1 to 8, respectively. One (S18) of them was also amplified out in ORF2 region (5,994-6 297bp) and showed 76% to 78%, 74%, 74% to 77%, and 85% to 94% identity with human HEV genotypes 1 to 4 at the nucleotide level, respectively. HEV sequences isolated from swine belong to human HEV genotype 4.


Differential regulation of the response to DNA damage in Ewing's sarcoma cells by ETS1 and EWS/FLI-1.
Ewing's sarcoma (EWS) cells contain levels of poly(ADP-ribose) polymerase (PARP) significantly higher than other eukaryotic cells. Previously, we cloned the PARP gene promoter region from EWS cells, showed that it contained multiple ETS-binding sites and demonstrated a positive regulation of PARP by ETS1. We now report that, contrary to ETS1, EWS/FLI-1, an aberrant ETS transcription factor present in most EWS cells, is a negative effector of PARP transcription. Because PARP levels have been associated with cellular resistance or sensitivity to genotoxic agents, we studied the effect of modifying PARP levels in EWS cells on their response to DNA damage by modulating the expression of ETS1 or EWS/FLI-1 using antisense methodology. Results show that stable down-regulation of ETS1 increases the resistance of EWS cells to various genotoxic agents, whereas down-regulation of EWS/FLI-1 has pro-apoptotic effects. Because down-regulation EWS/FLI-1 does not dramatically change PARP levels, these results suggest a direct effect for EWS/FLI-1 in the DNA damage response of EWS cells. Since expression of the aberrant fusion proteins by EWS cells is essential for maintaining their neoplastic phenotype, our results suggest that the use of antisense oligonucleotides in combination with chemotherapeutic agents or radiation may be doubly effective by causing both an increase in sensitivity to therapeutic agents and a simultaneous down-regulation, or reversion, of the neoplastic phenotype of EWS cells.


Slowing the Progression of Myopia in Children with the MiSight Contact Lens: A Narrative Review of the Evidence.
Myopia has become a major public health problem in the world due to the increase in its prevalence in the past few decades and due to sight-threatening pathologies associated with high myopia such as cataracts, glaucoma and especially myopic maculopathy. This article is a narrative review of the evidence that currently exists on a contact lenses (CLs) specifically designed to correct myopia and to slow its progression. To contextualise the topic we discuss the different classifications and definitions that have been used for myopia, the current burden of being myopic, and current treatment options to prevent and control its progression. There is evidence that exposure to sunlight reduces the risk of myopia onset and pharmacological treatment with atropine has been shown to be the most effective therapy for controlling its progression, followed by optical interventions such as CL fitting (orthokeratology or CLs specific for myopia control) designed to decrease retinal peripheral hyperopic defocus that seems to be the theory that suggests that axial elongation is driven by this defocus and explains why the eye continues to grow abnormally after emmetropisation and generates myopia. We will especially focus on MiSight CLs. MiSight is a daily replacement soft contact lens that has been clinically proven and approved by the US Food and Drug Administration (FDA) to control the progression of myopia in children. We analyse the optical design of MiSight CLs, as well as the results of the different efficacy and safety studies that led to the approval of the lens by the FDA. We also expose current knowledge gaps, limitations and future directions.