Constitutive expression of the antimicrobial peptide RNase 7 is associated with Staphylococcus aureus infection of the skin.
Staphylococcus aureus infections of the skin are a public health problem of growing importance. Antimicrobial peptides in human skin are believed to play an important role in innate defense against intruding pathogens. This study aimed to clarify whether their baseline expression influences the propensity of healthy individuals to develop S. aureus-positive skin infections. Using real-time polymerase chain reaction technique and a prospective case-control design, we determined the expression of messenger RNA coding for human beta-defensin 2 and 3 as well as RNase 7 in unaffected skin of 20 travelers returning with Staphylococcus aureus-positive skin infection (case patients) relative to levels in 40 matched control subjects. Expression of RNase 7 was found to be 64% higher in unaffected skin of control subjects, compared with unaffected skin of case patients (95% confidence interval, 17%-131%; P = .007). This association remained stable after controlling for S. aureus nasal carriage, smoking, level of accommodation, and history of allergy. No such association was present for human beta-defensin 2 or 3. In conjunction with the existing evidence from in vitro studies, these findings suggest that antimicrobial peptides found at high baseline levels in healthy skin, such as RNase 7, confer protection against S. aureus infection of the skin.


[Models of inter-group difference of the homeostasis system in patients with artificial heart valves and the set of laboratory parameters].
Patients with artificial heart valves (AHV) belong to a unique multi-component model of the homeostasis system presenting an interaction of activated coagulation processes and pharmacological effects, on the one hand, and genetic peculiarities functioning homeostatic mechanisms, on the other hand. The described method was evaluated on the basis of multi-factor mathematic analysis by information-metry. The data obtained provided for isolating the most information-dense laboratory indices and some genetic polymorphisms describing the shaping of continuous intravascular coagulation of stage III in AHV patients. The clinicians and laboratory experts are offered a practical instrument for the diagnosis (prognostication) of the above condition. It was proven as necessary to examine (by the morphofunctional method) the intravascular activation of platelets and to determine the D-dimer in the remote period after prosthesis of heart valves.


[Subacute toxicity of an amine-curing agent for epoxy resin].
Amine-curing agent for epoxy resin, bis(4-amino-3-methylcyclohexyl)methane, has been suspected of inducing toxic symptoms in man which resemble collagen disease such as scleroderma or polymyositis. We studied subacute toxicity of this agent by repeated oral administrations to rats. The agent was administered 25, 37.5, 50, 75 or 100 mg/kg per one dose, 8 times in 10 days or 17 times in 4 weeks or 20-22 times in 4 weeks. When administration had been completed, clinical biochemical tests and histopathological examinations were carried out. Animals of high dosage group showed suppression of body weight increase and loss of muscular strength of limbs in the administration period. By clinical biochemical tests, elevation of blood components from muscle (CPK, GOT, creatine) was noticed. Also, increase of monoamine oxidase and decrease of alkaline phosphatase were revealed. By histological examinations, skeletal muscle and choroid plexus of brain showed noticeable changes. In muscles of high dosage group, atrophy, degeneration and regeneration of muscle fibers were observed and an increase of fibroblasts was also seen. In choroid plexus, vacuolar changes in epithelial cells were observed, being clearly dose-dependent. No particular change was recognized in skin. Though scleroderma-like change was not observed in the skin histologically, our results suggest that this amine-curing agent was greatly associated with muscle symptoms in the workers who handled epoxy resin and that it was one of causative agents which induced toxic symptoms like those of collagen disease.


An effective method for monitoring tissue temperature using low-field MRI system.
This technical note describes an effective method for monitoring temperature based on the minimum curvature surface fitting (MCSF) referenceless proton resonance frequency shift (PRFs) at 0.35 T. Experimental tests on phantom, ex vivo porcine livers and human brain were conducted. A comparison study between the proposed method and a fiber optic temperature probe was conducted for microwave (MW) ablation. Experimental results showed that temperature root mean square error (RMSE) calculated by MCSF model were lower than those computed by high-order polynomial fitting. For ablation experiments, the temperature errors between temperature probe and MCSF method were all less than 2∘C.


Plasma concentration and lipid composition of lipoproteins in lactating dairy cows fed control and high grain diets.
Six multiparous Holstein cows ranging from 7 to 19 wk postpartum were in a switchback design to determine effects of feeding high grain diets on lipoprotein concentration and composition in blood. Percents concentrate, alfalfa haylage, and corn silage of control and high grain diets were 50, 83; 25, 9; and 25, 8 dry matter. Milk yield (kg/day), milk fat percentage, and fat yield (g/day) averaged 27.7, 3.58, 997 and 30.2, 2.45, 729 for control and high grain treatments. Very low density, low density, and high density lipoproteins were isolated by gel filtration of total lipoproteins obtained by ultracentrifugation. Lipoprotein concentrations in blood plasma of cows fed the control or high grain diets were similar. Triglyceride, phospholipid, cholesterol, and cholesterol ester contents of each lipoprotein class were not altered by treatment. High grain feeding increased octadecadienoic fatty acid content of low density and high density lipoprotein cholesterol esters and decreased octadecenoic and octadecatrienoic acids. The trend was similar for the very low density lipoprotein fraction. Phospholipid octadecenoic acid decreased in all lipoprotein fractions but only significantly for high density lipoproteins. It is unlikely that differences in lipid composition of plasma lipoproteins caused alterations in lipoprotein metabolism leading to fat depression in this and other similar studies.


The C-Terminal Intact Forms of Periostin (iPTN) Are Surrogate Markers for Osteolytic Lesions in Experimental Breast Cancer Bone Metastasis.
Periostin is an extracellular matrix protein that actively contributes to tumor progression and metastasis. Here, we hypothesized that it could be a marker of bone metastasis formation. To address this question, we used two polyclonal antibodies directed against the whole molecule or its C-terminal domain to explore the expression of intact and truncated forms of periostin in the serum and tissues (lung, heart, bone) of wild-type and periostin-deficient mice. In normal bones, periostin was expressed in the periosteum and specific periostin proteolytic fragments were found in bones, but not in soft tissues. In animals bearing osteolytic lesions caused by 4T1 cells, C-terminal intact periostin (iPTN) expression disappeared at the invasive front of skeletal tumors where bone-resorbing osteoclasts were present. In vitro, we found that periostin was a substrate for osteoclast-derived cathepsin K, generating proteolytic fragments that were not recognized by anti-periostin antibodies directed against iPTN. In vivo, using an in-house sandwich immunoassay aimed at detecting iPTN only, we observed a noticeable reduction of serum periostin levels (- 26%; P < 0.002) in animals bearing osteolytic lesions caused by 4T1 cells. On the contrary, this decrease was not observed in women with breast cancer and bone metastases when periostin was measured with a human assay detecting total periostin. Collectively, these data showed that mouse periostin was degraded at the bone metastatic sites, potentially by cathepsin K, and that the specific measurement of iPTN in serum should assist in detecting bone metastasis formation in breast cancer.


Cutaneous Metastasis of Choriocarcinoma in 2 Male Patients: A Rare Presentation of an Aggressive Malignancy That Dermatopathologists Must Recognize.
Testicular choriocarcinoma needs to be considered in the differential diagnosis of cutaneous metastases in young adult men because of its propensity for early hematogenous dissemination. Furthermore, the diagnosis may not be suspected in many cases in which there is clinically no testicular enlargement. This highly aggressive germ cell tumor typically metastasizes to the liver, lungs, and brain. Skin metastasis is exceedingly rare with only 22 cases previously reported in the world literature. We herein report 2 additional cases: a 25-year-old man and a 32-year-old man, both of whom were treated for mixed germ cell tumors and developed multiple cutaneous metastases to the head.


Descriptive epidemiology of hemivertebrae, Hawaii, 1986-2002.
The intent of this study was to report on the epidemiology of hemivertebrae. Cases were derived from a population-based birth defects registry in Hawaii and comprised all infants and fetuses with hemivertebrae delivered during 1986-2002. Hemivertebrae rates per 10 000 births were determined for selected factors and comparisons made by calculating the rate ratio (RR) and 95% confidence interval (CI). Forty-two cases of hemivertebrae were identified, for a total rate of 1.33. Forty-one of the cases were live births, of which 26.83% expired within one year after delivery. Other major structural birth defects were found in 95.24% of the cases. The most frequent associated defect was scoliosis, affecting 54.76% of the cases. The rate among females was significantly lower than among males (RR 0.48, 95% CI 0.23-0.94). The rate was lower with maternal age > or =35 years (RR 0.50, 95% CI 0.10-1.57) and higher with birth weight < 2500 g (RR 5.96, 95% CI 2.84-11.90) and gestational age < 38 weeks (RR 3.94, 95% CI 2.01-7.64). The majority of hemivertebrae cases had other major structural birth defects. Hemivertebrae occurred predominantly among males and risk was lower with increased maternal age. Rates for hemivertebrae were higher with lower birth weight and gestational age. Further population-based research involving larger study populations are recommended to confirm these observations.


Tobacco carcinogen NNK transporter MRP2 regulates CFTR function in lung epithelia: implications for lung cancer.
Lung cancer is the leading cause of cancer death in the United States. About 85% of all lung cancers are linked to tobacco smoke, in which more than 50 lung carcinogens have been identified and one of the most abundant is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The human lung epithelium constitutes the first line of defense against tobacco-specific carcinogens, in which apically-localized receptors, transporters, and ion channels in the airway may play a critical role in this native defense against tobacco smoke. Here we showed that multidrug resistance protein-2 (MRP2) and cystic fibrosis transmembrane conductance regulator (CFTR), two ATP-binding cassette (ABC) transporters, are localized to the apical surfaces of plasma membrane in polarized lung epithelial cells. We observed that there is a functional coupling between CFTR and MRP2 that may be mediated by PDZ proteins. We also observed the existence of a macromolecular complex containing CFTR, MRP2, and PDZ proteins, which might form the basis for the regulatory cooperation between these two ABC transporters. Our results have important implications for cigarette smoke-associated lung diseases (such as smoke-related emphysema, chronic obstructive pulmonary disease, and lung cancer).


Research on application of helmet wearing detection improved by YOLOv4 algorithm.
Aiming at the problem that the model of YOLOv4 algorithm has too many parameters and the detection effect of small targets is poor, this paper proposes an improved helmet fitting detection model based on YOLOv4 algorithm. Firstly, this model improves the detection accuracy of small targets by adding multi-scale prediction and improving the structure of PANet network. Then, the improved depth-separable convolution was used to replace the standard 3 × 3 convolution, which greatly reduced the model parameters without reducing the detection ability of the model. Finally, the k_means clustering algorithm is used to optimize the prior box. The model was tested on the self-made helmet dataset helmet_dataset. Experimental results show that compared with the safety helmet detection model based on Faster RCNN algorithm, the improved YOLOv4 algorithm has faster detection speed, higher detection accuracy and smaller number of model parameters. Compared with the original YOLOv4 model, the mAP of the improved YOLOv4 algorithm is increased by 0.49%, reaching 93.05%. The number of model parameters was reduced by about 58%, to about 105 MB. The model reasoning speed is 35 FPS. The improved YOLOv4 algorithm can meet the requirements of helmet wearing detection in multiple scenarios.


A computational study of astrocytic glutamate influence on post-synaptic neuronal excitability.
The ability of astrocytes to rapidly clear synaptic glutamate and purposefully release the excitatory transmitter is critical in the functioning of synapses and neuronal circuits. Dysfunctions of these homeostatic functions have been implicated in the pathology of brain disorders such as mesial temporal lobe epilepsy. However, the reasons for these dysfunctions are not clear from experimental data and computational models have been developed to provide further understanding of the implications of glutamate clearance from the extracellular space, as a result of EAAT2 downregulation: although they only partially account for the glutamate clearance process. In this work, we develop an explicit model of the astrocytic glutamate transporters, providing a more complete description of the glutamate chemical potential across the astrocytic membrane and its contribution to glutamate transporter driving force based on thermodynamic principles and experimental data. Analysis of our model demonstrates that increased astrocytic glutamate content due to glutamine synthetase downregulation also results in increased postsynaptic quantal size due to gliotransmission. Moreover, the proposed model demonstrates that increased astrocytic glutamate could prolong the time course of glutamate in the synaptic cleft and enhances astrocyte-induced slow inward currents, causing a disruption to the clarity of synaptic signalling and the occurrence of intervals of higher frequency postsynaptic firing. Overall, our work distilled the necessity of a low astrocytic glutamate concentration for reliable synaptic transmission of information and the possible implications of enhanced glutamate levels as in epilepsy.


Screen time usage among preschoolers aged 2-6 in rural Western India: A cross-sectional study.
We have evaluated screen time usage among preschool-aged (≤6 years) children in rural Western India. In addition, we have evaluated various lifestyle factors and their impact on the screen time of these children. English-medium schools in the locality were chosen based on convenience. A self-report survey requesting family information and screen usage information was distributed to the parents. Daily screen time was categorized as a three-category variable. Ordered logistic regression with multivariable regression was performed to examine the association of risk factors with screen time. Average screen time among the 379 (208 males, 171 female) children amounted to 2.7 hours (SD: 1.7), with average daily television screen time of 1.6 hours (SD: 1.1). Most children (87.2%) started screen use by the age of 3. Only 65 (17.2%) participants met AAP recommendation. Households with three devices and smartphone usage by mothers increased the odds of screen time by 60% and two-folds, respectively. Compared to weekdays, children had increased screen time exposure (3.5 vs 2.7 hours, P < 0.001), outdoor activity time (2.3 vs 1.6, P < 0.001), and reading hours (1.2 vs 1.1, P = 0.03) on weekends. No association was observed between screen time and mother's occupation. More than 80% of children exceeded the advised screen time with television and smartphone being the major contributors. This issue has to be dealt with at both individual and societal levels. Increased awareness about the high prevalence of inappropriate use of screen time use within the Indian context is needed to inspire attention and interventions for this emerging public health problem in India.


Competitive displacement of wild-type phospholamban from the Ca2+-free cardiac calcium pump by phospholamban mutants with different binding affinities.
Phospholamban (PLB) regulates the cardiac Ca(2+) pump (SERCA2a). To test how different species of PLB mutants compete to interact with the Ca(2+)-free, E2 conformation of SERCA2a, using the insect cell expression system, we examined how various exogenous PLB mutants regulated SER-20G-PLB, a chimeric WT-SERCA2a-Gly-WT-PLB construct, which retains a fully catalytic active Ca(2+)-pump and its intrinsically regulatory PLB-tether. Exogenous gain-of-function PLB mutants dominantly super-inhibited the WT-PLB-tethered SERCA2a. Further, in the Ca(2+)-free condition, co-expressed normal- or super-inhibitory PLB mutant with either engineered N30C or V49C residue cross-linked to Lys328 or V89C of SER-20G-PLB at the cytoplasmic or transmembrane domain, respectively, suggesting that these freely diffusing PLB mutants completely replaced the WT-PLB-tether and fit into the binding pocket previously occupied by WT-PLB. Micromolar Ca(2+) completely inhibited cross-linking, yielding a similar Ca(2+)-dependency regardless of the presence of the WT-PLB-tether. In contrast, the PLB mutant with the loss-of-function L31A mutation has decreased binding affinity for SERCA2a, thus cross-linking weakly to the WT-PLB-tethered SERCA2a, and only marginally affected the activity of SER-20G-PLB. Thus, there is a reversible equilibrium between different PLB mutants for binding to E2, in which PLB mutants possessing higher binding affinity for SERCA2a produce a more stable E2·PLB and lower Ca(2+) affinity.


[Anti-proliferation action of taurine on rat cardiac fibroblast through inhibiting protein kinase Calpha expression].
This project aimed to investigate the effect of taurine on cell cycle regulatory protein p27, Cyclin D1 and nuclear factor-kappa B (NF-kappaB) p65 in the proliferation of cultured neonatal rat cardiac fibroblast (CFb) induced by angiotensin II (Ang II), and to explore the effect of taurine on the signal transduction pathway in CFb proliferation. The cultured neonatal rat CFbs were isolated by trypsin digestion method. The proliferation of CFb was induced by Ang II and detected with thiazole blue (MTT) colorimetric assay. The protein expression of p-PKCalpha in cells was determined with Western blotting technology. The expression of p27 was analyzed by flow cytometry. The expression of Cyclin D1 was determined with the combination of immunocytochemical staining and image analysis software. The nuclear translocation of NF-kappaB p65 was determined with immunofluorescence staining. Among the concentrations ranged from 40 to 160 mmol L(-1), taurine significantly inhibited p-PKCalpha expression. Taurine increased p27 expression and inhibited the nuclear translocation of NF-kappaB p65 in CFb (P < 0.05, P < 0.01, respectively) by inhibition of p-PKCalpha expression. And PKC inhibitor (Che) could improve the inhibitory action of taurine on CFb proliferation. The effects of taurine on CFb proliferation might be due to inhibition of p-PKCalpha expression and p27 expression increase and the nuclear translocation of NF-kappaB p65 inhibition followed.


Impact of Clopidogrel on Clinical Outcomes in Patients with Staphylococcus aureus Bacteremia: a National Retrospective Cohort Study.
Activated platelets have known antimicrobial activity against Staphylococcus aureus. Accelerated clearance of platelets induced by S. aureus can result in thrombocytopenia and increased mortality in patients. Recent studies suggest that P2Y12 inhibition protects platelets from accelerated clearance. We therefore evaluated the effect of P2Y12 inhibition on clinical outcomes in patients with S. aureus bacteremia across a large national cohort. Our retrospective cohort (2010 to 2018) included patients admitted to Veterans Affairs (VA) hospitals with blood cultures positive for S. aureus and treated with standard-of-care antibiotics. Employing propensity score-matched Cox proportional hazards regression models, we compared clinical outcomes in patients treated with clopidogrel for at least the 30 days prior to admission and continuing for at least 5 days after admission to patients without any P2Y12 inhibitor use in the year preceding admission. Mortality was significantly lower among clopidogrel users than P2Y12 inhibitor nonusers (n = 147 propensity score-matched pairs): the inpatient mortality hazard ratio (HR) was 0.11 (95% confidence interval [CI], 0.01 to 0.86), and 30-day mortality HR was 0.43 (95% CI, 0.19 to 0.98). There were no differences in 30-day readmission, 30-day S. aureus reinfection, microbiological clearance, or thrombocytopenia. Clopidogrel use at the time of infection reduced in-hospital mortality by 89% and 30-day mortality by 57% among a cohort of patients with S. aureus bacteremia. These results support the need to further study the use of P2Y12 inhibitors as adjunctive therapy in S. aureus bloodstream infections.


Improving the Prediction of Suicidal Behavior in Youth.
Suicidal behaviors increase dramatically during adolescence. In order to effectively intervene and ultimately prevent suicide in youth, the field needs to be able to identify and predict which adolescents are at greatest suicide risk. However, present knowledge of risk factors for suicide and techniques for identifying at-risk youth are insufficient. The purpose of the current manuscript is to highlight some of the key, yet unanswered, questions about the prediction of suicidal behavior in youth, and to suggest the types of research advances needed to move the field forward.


Power and sample size calculation for paired recurrent events data based on robust nonparametric tests.
The purpose of this paper is to develop a formula for calculating the required sample size for paired recurrent events data. The developed formula is based on robust non-parametric tests for comparing the marginal mean function of events between paired samples. This calculation can accommodate the associations among a sequence of paired recurrent event times with a specification of correlated gamma frailty variables for a proportional intensity model. We evaluate the performance of the proposed method with comprehensive simulations including the impacts of paired correlations, homogeneous or nonhomogeneous processes, marginal hazard rates, censoring rate, accrual and follow-up times, as well as the sensitivity analysis for the assumption of the frailty distribution. The use of the formula is also demonstrated using a premature infant study from the neonatal intensive care unit of a tertiary center in southern Taiwan. Copyright © 2017 John Wiley & Sons, Ltd.


Anthelmintic profile of methyl 5(6)-(4-methylpiperidin-1-yl) carbonylbenzimidazole-2-carbamate in experimental helminthiases.
Biological evaluation of methyl 5(6)-(4-methylpiperidin-1-yl) carbonylbenzimidazole-2-carbamate against Ancylostoma ceylanicum, Nippostrongylus brasiliensis, Syphacia obvelata, Hymenolepis nana, H. diminuta and Cysticercus fasciolaris in experimental animals is reported. The compound (mg/kg) causes 100% elimination of A. ceylanicum (25 x 1), N. brasiliensis (100 x 1), S. obvelata (50 x 1), H. nana (250 x 3) and C. fasciolaris (50 x 10). It was also effective against the developing larvae (L3, L4 and L5) of A. ceylanicum at a single oral dose of 100 mg/kg. Another study indicated that the compound elicits 100% response within 32 hr of drug administration. The drug is well tolerated and LD50 is greater than 4500 mg/kg.


Effects of hypothyroidism and undernourishment on nuclear-cytoplasmic transport "in vitro" of cerebral RNA.
Neonatal thyroidectomy impairs, at 10 days of age, the "in vivo" specific activity of brain "rapidly-labeled" RNA, both in nuclei and microsomes. The labeling of ribosomal RNA, whose nuclear synthesis is not affected by hypothyroidism, appears diminished at the microsomal level, indicating an impairment of transport across the nuclear membranes. "Rapidly-labeled" RNA values did not change under the same conditions. Underfeeding causes the same changes as thyroidectomy on the labeling and transport of cerebral RNA, with the only exception of the nuclear mRNA release, which is diminished by undernourishment. The alterations of cytosolic factors cause the impairment of cerebral ribosomal RNA release in hypothyroid rats, while changes in unknown intranuclear mechanisms are responsible for the decreased transport of ribosomal RNA in undernourished rats.


ST11 Carbapenem-Resistant Klebsiella pneumoniae Clone Harboring blaNDM Replaced a blaKPC Clone in a Tertiary Hospital in China.
The nosocomial spread of carbapenem-resistant Enterobacterales (CRE) is extremely common, resulting in severe burdens on healthcare systems. In particular, the high-risk Klebsiella pneumoniae ST11 strain has a wide endemic area in China. The current study describes the results of continuous monitoring of CRE genotypes and phenotypes in a tertiary hospital in North China from 2012 to 2020. A total of 160 isolates were collected, including 109 Klebsiella. pneumoniae (68.13%), 29 Escherichia coli (26.60%), 12 Enterobacter cloacae (7.50%), and 10 other strains (6.25%). A total of 149 carbapenemase genes were detected, of which blaKPC-2 (51.0%) was the most common, followed by blaNDM-1 (22.82%), and blaNDM-5 (23.49%). Based on multi-locus sequence typing, the ST11 strain (66.1%) dominates K. pneumoniae, followed by ST15 (13.8%). Interestingly, the proportion of blaNDM (22.2%, 16/72) in ST11 K. pneumoniae was significantly increased in 2018−2019. Hence, whole-genome sequencing was performed on ST11 K. pneumoniae. Growth curves and in vitro competition experiments showed that K. pneumoniae carrying blaNDM exhibited a stronger growth rate (p < 0.001) and competition index (p < 0.001) than K. pneumoniae carrying blaKPC. Moreover, K. pneumoniae carrying blaNDM had a stronger biofilm-forming ability than K. pneumoniae carrying blaKPC (t = 6.578; p < 0.001). K. pneumoniae carrying blaKPC exhibited increased defense against bactericidal activity than K. pneumoniae carrying blaNDM. Thus, ST11 K. pneumoniae carrying blaNDM has strong adaptability and can locally replace K. pneumoniae carrying blaKPC to become an epidemic strain. Based on these findings, infection control and preventive measures should focus on the high-risk ST11-K. pneumoniae strain.


A Novel Indolizine Derivative Induces Apoptosis Through the Mitochondria p53 Pathway in HepG2 Cells.
Indolizine derivatives are a class of compounds with excellent biological activity. In this study, a series of indolizine derivatives, compound 1 (C1), compound 2 (C2), compound 3 (C3), and compound 4 (C4), were synthesized. 3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) assay was used to evaluate their cytotoxicity against HepG2 (p53-wild), A549, and HeLa cell lines. HepG2 cells apoptosis induced by C3 was determined using Hoechst staining and acridine orange/ethidium bromide staining. Cells' apoptotic ratio was measured by Annexin V-FITC/PI double staining. Changes in mitochondrial membrane potential and intracellular reactive oxygen species (ROS) in HepG2 cells after C3 treatment were determined. Immunofluorescence staining and Western blot analysis were carried out to detect p53 levels and analyze the apoptosis-associated proteins, respectively. Moreover, the cytotoxic activity of C3 was examined in two other hepatocellular carcinoma (HCC) cell lines with different p53 status including Huh-7 cells (p53-mutant) and Hep3B cells (p53-null). The results indicated that C3 showed stronger inhibition towards HepG2 cells than other cell lines. Fluorescent staining and flow cytometry analysis confirmed that C3 induced apoptosis of HepG2 cells. C3 could also increase intracellular ROS and cause a decrease in the mitochondrial membrane potential. C3 promoted p53 activation and increased p53 accumulation in nuclei. The expression of p53 and Bax was increased with the down-regulation of Bcl-2, which promoted the release of cytochrome c and caspase-3 activation. Collectively, the study demonstrated that C3 caused HepG2 cell apoptosis via the mitochondria p53 pathway. These results inspired us to further develop indolizine derivatives as potential potent inhibitors against liver cancer.


Metabolic activation of mutagenic tryptophan pyrolysis products by rat liver microsomes.
In an attempt to determine whether cytochrome P-450 metabolizes tryptophan pyrolysis products, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) to active forms, studies were done using microsomes and the 9000 x g supernatant (S-9) from polychlorinated biphenyl mixture-treated rat livers together with Salmonella typhimurium TA 98 as a tester strain. The number of revertants increased with increments in the amount of S-9 fraction added. The highest mutation was seen with an amount of S-9 that is equivalent to 2.5 mg of liver tissue; however, further increase in the S-9 fraction resulted in a sharp decline in the number of revertants. There was a similar biphasic response when a relatively large amount of S-9 fraction was incubated for an increasing length of time. Microsomes showed parallel biphasic responses, and, in addition, the 105,000 x g supernatant fraction was ineffective in increasing the number of revertants. These results suggested that most if not all of the ability of the S-9 fraction to convert Trp-1 and Trp-P-2 to active forms resided in the microsomes. The involvement of microsomal cytochrome P-450 in this process was further confirmed by the following evidence. The treatment of rats with polychlorinated biphenyl mixture and 3-methylcholanthrene resulted in a marked increase in the ability of microsomes to activate Trp-P-1 and Trp-P-2, and the activation reaction required reduced nicotinamide adenine dinucleotide phosphate as a cofactor and was inhibited by carbon monoxide, 7,8-benzoflavone, n-octylamine, and 2-diethylaminoethyl-2,2-diphenylvalerate. The mutagenic metabolite formed as a result of microsomal metabolism of Trp-P-2 was fairly stable and survived heating at 90 degrees for 7 min. With a high-performance liquid chromatography, an active metabolite of Trp-P-2 was purified. A preliminary analysis showed this molecule to be an N-hydroxylated derivative of Trp-P-2.


On the nature of Mycobacterium tuberculosis-latent bacilli.
Mycobacterium tuberculosis-latent bacilli are microorganisms that adapt to stressful conditions generated by the infected host against them. By slowing metabolism or becoming dormant, they may counterbalance these conditions and appear as silent to the immune system. Moreover, the dynamic turnover of the infected cells provokes a constant reactivation of the latent bacilli when the environmental conditions are favourable, or an activation after being dormant in necrotic and fibrotic lesions for a long period of time. Since there is no in vivo nor in vitro evidence for quick resuscitation of dormant bacilli, the current authors strongly favour the possibility that latent tuberculosis infection can be maintained for no longer than approximately 10 yrs, which is, nowadays, a time period very close to that considered for "primary" tuberculosis. This concept may also be helpful for newer epidemiological considerations regarding the real impact of reinfection in tuberculosis.


New frontier, new power: the retail environment in Australia's dark market.
To investigate the role of the retail environment in cigarette marketing in Australia, one of the "darkest" markets in the world. Analysis of 172 tobacco industry documents; and articles and advertisements found by hand searching Australia's three leading retail trade journals. As Australian cigarette marketing was increasingly restricted, the retail environment became the primary communication vehicle for building cigarette brands. When retail marketing was restricted, the industry conceded only incrementally and under duress, and at times continues to break the law. The tobacco industry targets retailers via trade promotional expenditure, financial and practical assistance with point of sale marketing, alliance building, brand advertising, and distribution. Cigarette brand advertising in retail magazines are designed to build brand identities. Philip Morris and British American Tobacco are now competing to control distribution of all products to retailers, placing themselves at the heart of retail business. Cigarette companies prize retail marketing in Australia's dark market. Stringent point of sale marketing restrictions should be included in any comprehensive tobacco control measures. Relationships between retailers and the industry will be more difficult to regulate. Retail press advertising and trade promotional expenditure could be banned. In-store marketing assistance, retail-tobacco industry alliance building, and new electronic retail distribution systems may be less amenable to regulation. Alliances between the health and retail sectors and financial support for a move away from retail dependence on tobacco may be necessary to effect cultural change.


[Case of mixed connective tissue disease complicated with sarcoidosis and central diabetes insipidus].
In 2003, a 64-year-old woman was diagnosed with mixed connective tissue disease and treated with oral prednisolone (30 mg/day). The prednisolone dose was gradually decreased, and a dose of 5 mg/day had been maintained since 2004. In 2009, she gradually developed vision loss, malaise, anorexia, and throat pain due to hydrodipsia. She was noted to have iritis and vitreous opacity by an ophthalmologist, and was referred for further evaluation. Fine rales were audible throughout the entire lung field, and chest CT showed diffuse small nodules that were more prominent on the upper and middle lobes, and swelling of the mediastinal and hilar lymph nodes. Transbronchial lung biopsy showed many epithelioid granulomas with multinuclear giant cells, compatible with sarcoidosis. Polyuria was identified as a cause of hydrodipsia and a diagnosis of partial central diabetes insipidus was made. High-dose prednisolone (40 mg/day) together with intranasal administration of desmopressin resulted in improvement of all of her clinical symptoms. MCTD followed by sarcoidosis is rare. Furthermore, this is the first reported case of MCTD complicated by sarcoidosis and central diabetes insipidus.


Measurement of temperature-dependent stability constants of Cu(I) and Cu(II) chloride complexes by voltammetry at a Pt ultramicroelectrode.
Cu(II)Cl complexes can undergo stepwise electrochemical reduction to Cu(I)Cl and then to Cu. In this paper, the Nernst equation is used to simultaneously calculate the temperature-dependent stability constants of both mononuclear Cu(II)Cl and Cu(I)Cl complexes for the first time. First, voltammograms were recorded at a Pt ultramicroelectrode (UME) with a variable of free chloride concentration at a given temperature. Using the equilibrium of Ag/AgCl redox couple, the free chloride activities were measured on an Ag electrode in different NaCl solutions, adjusting for the influence of ionic strength. This electrochemical technique was proved to be feasible at 25 and 90 °C. With increasing temperature, the Cu(II)Cl complex favored a lower coordination number and the CuCl2 complex prevailed, whereas the CuCl4(2-) was predicted to be unstable. The CuCl2(-) and CuCl3(2-) complexes were still the primary species for the Cu(I)Cl complex.


[Perfusion characteristics of normal pancreas and insulinoma on multi-slice spiral CT].
To investigate the perfusion characteristics of normal pancreas and insulinoma on multi-slice spiral CT (MSCT). Totally 21 subjects with suspected insulinoma were enrolled. Sixteen-slice spiral CT was used for perfusion scan following a standard contrast-enhanced scan. The surgical and pathological outcomes were collected for comparison. Perfusion characteristics, including blood flow (BF), patlak blood volume (pBV), time to peak (TTP), permeability, and peak enhancement (PE) of insulinomas and normal pancreas parenchyma were analyzed based on the MSCT data sets subsequently. Benign insulinoma was pathologically confirmed in 12 out of the 21 subjects, while the remaining 9 subjects were normal. Technical failures were experienced in 2 (9.5%) subjects. In both normal and tumor-suffered subjects (n = 19), perfusion parameters of normal pancreatic parachyma were measured as follows: BF (p) = 104. 9 +/- 28.9, pBV (p) = 166.4 +/- 41.8, TrP (p) = 133.3 +/- 24.4, Permeability (p) = 81.3 +/- 24.4, and peak enhancement (p) = 121.3 +/- 31.1. In subjects with insulinoma (n = 11), perfusion parameters of tumor tissue were measured as follows: F (i) = 206.5 +/- 42.2, BV (i) = 315.9 +/- 79.0, TFP (i) = 123.2 +/- 18.8, Permeability (i) = 102.5 +/- 54. 8, and peak enhancement (i) = 221.3 +/- 48.5. Results of F, BV, and peak enhancement in these two kinds of tissue showed significant differences (P < 0.01), while there were no significant difference (P > 0.05) in TTP and permeability between normal pancreatic parenchyma and insulinoma. Benign insulinoma has perfusion characteristics of increased blood flow and blood volume, but its TTP is consistent with normal pancreas and has normal permeability. MSCT allows further understanding of the blood flow of the normal pancreas and its benign tumor insulinoma.


Curbing an outbreak of circulating vaccine derived poliovirus type 2 in Dollo Zone, Somali Region, Ethiopia: response to outbreak.
although the oral polio vaccine prevents virus transmission from person to person, it is crucial for poliovirus eradication. The continued use of live attenuated poliovirus poses an ongoing risk of circulating Vaccine Derived Poliovirus-2 (cVDPV2) outbreaks. This study assesses the response to the cVDPV2 outbreak in Dollo Zone, Somali Region, Ethiopia. after examining and verifying the occurrence of the outbreak, a team was established and prepared by resource mobilization, advocacy, and social mobilization. The group endorsed a four-step vaccination strategy, first the rapid response within 14-days by vaccinating a monovalent oral poliovirus-2 (mOPV2) to all under 5-year children in the Zone. The team further enhanced Supplementary Immunization Activities (SIA) for all under-five children with repeated doses of vaccines. At the same time, the team initiated community-based surveillance of Acute Flaccid Paralysis (AFP). in the rapid-response immunization, an average of 91.4% of 0-11 months old and 90.2% of 12-59 months children were vaccinated. In SIA-1, the team vaccinated an average of 88% and 97%, and in SIA-2, 94.8% and 97.6% of children 0-11 months old and 12-59 months old, respectively. The active community-based surveillance of AFP revealed the existence of the disease in a sporadic form, of which two cases were found in Bokh district. the response to curb the outbreak of cVDPV2 has shown a flow of actions to combat the outbreak. Strengthening and formation of response teams at different levels, resource mobilization, advocacy, and social mobilization are all essential components in maximizing the response to the outbreak.


[Epidemiologic study of conjunctivochalasis in populations equal or over 60 years old in Caoyangxincun community of Shanghai, China].
To investigate the prevalence and relative factors of conjunctivochalasis among people over 60 years old in Caoyangxincun community of Shanghai. A cross-sectional study based on local residents in this community was carried out from September 2008 to October 2008. Cluster sampling was used in randomly selecting individuals aged > or = 60 years. Slit-lamp ophthalmoscope was used for eye examination and diagnosis. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. A database was set using SPSS 10.0 software, Chi-square test was used for data analysis. 2110 residents took part in this study, with the response rate 94.85%. 930 cases (1762 eyes) were confirmed as conjunctivochalasis, so the prevalence rate is 44.08%. The prevalence of conjunctivochalasis was increasing with age (chi(2) = 10.44, P < 0.01). 556 cases (943 eyes) were confirmed as degree I, 246 cases (647 eyes) as degree II, 120 cases (162 eyes) as degree III and the rest 8 cases (10 eyes) as degree IV. Several symptoms, such as blurred vision, asthenopia and eye pain were more frequent in patient group than in the normal ones (chi(2) value was 15.44, 20.54 and 19.74, respectively, P < 0.01). In the disease eyes, the conjunctiva usually piled up on the nasal and temporal side (944 eyes, 53.58%), the location of inferior lid margin was usually above corneal limbus (2589 eyes, 61.35%) and inferior lid margin entropion and introversion were always found (7.04% and 6.63%). Abnormal lacrimal river was found in 87.23% of the diseased eyes, more than the non-conjunctivochalasis eyes (chi(2) = 1615.81, P < 0.01). Conjunctivochalasis is a common eye disease in aged population, with obvious signs and symptoms of ocular surface and lacrimal river impairment. In the local residents, most patients were classified as minimal or moderate degree. The location of inferior lid margin and the tension of inferior lid may be related factor of conjunctivochalasis.


Field-Effect Transistors Based on van-der-Waals-Grown and Dry-Transferred All-Inorganic Perovskite Ultrathin Platelets.
Nowadays, the research on perovskite transistors is still in its infancy, despite the fact that perovskite-based solar cells and light-emitting diodes have been widely investigated. Two major hurdles exist before obtaining reliable perovskite-based transistors: the processing difficulty for their sensitivity to polar solvents and unsatisfactory perovskite quality on the transistor platform. Here, for the first time, we report on high-performance all-inorganic perovskite FETs profiting from both van der Waals epitaxial boundary-free ultrathin single crystals and completely dry-processed transfer technique without chemical contaminant. These two crucial factors ensure the unprecedented high-quality perovskite channels. The achieved FET hole mobility and on-off ratio reach 0.32 cm2 V-1 s-1 and 6.7 × 103, respectively. Moreover, at the low temperature, the mobility and on-off ratio can be enhanced to be 1.04 cm2 V-1 s-1 and 1.3 × 104. This work could open the door for the FET applications based on perovskite single crystals.


Evaluation of two carrier protein-angiotensin I conjugate vaccines to assess their future potential to control high blood pressure (hypertension) in man.
We aim to modulate the renin-angiotensin system (RAS) by active immunization against angiotensin I hormone (AI), potentially providing a novel conjugate vaccine treatment for hypertension in man. Immunization studies in rat and human subjects compare the effectiveness of tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH) vaccines for immunotherapy following conjugation with an AI peptide analogue (AI). Cardiovascular responses were assessed in immunized rats and human subjects (two-dose trial only), following increasing i.v. infusions of either AI or angiotensin II hormone (AII). The AI-TT and AI-KLH conjugate vaccines induced an equivalent immune response, and inhibition of the pressor effects to exogenous AI in rats. Single-dose clinical trials with both conjugate vaccines only resulted in an immune response to the KLH carrier protein. A two-dose clinical trial of AI-KLH conjugate vaccine resulted in a significant immune response to AI. A shift in diastolic blood pressure (DBP) dose-response was demonstrated following challenge with AI and AII for the study volunteer showing the largest anti-AI IgG induction. KLH was shown to be a suitable alternative to TT as a carrier protein for AI, thus supporting continued evaluation of our AI-KLH conjugate vaccine for treatment of hypertension in man.


A Head-to-Head Comparison of 18F-Fluorocholine PET/CT and Conventional MRI as Predictors of Outcome in IDH Wild-Type High-Grade Gliomas.
(1) Aim: To study the associations between imaging parameters derived from contrast-enhanced MRI (CE-MRI) and 18F-fluorocholine PET/CT and their performance as prognostic predictors in isocitrate dehydrogenase wild-type (IDH-wt) high-grade gliomas. (2) Methods: A prospective, multicenter study (FuMeGA: Functional and Metabolic Glioma Analysis) including patients with baseline CE-MRI and 18F-fluorocholine PET/CT and IDH wild-type high-grade gliomas. Clinical variables such as performance status, extent of surgery and adjuvant treatments (Stupp protocol vs others) were obtained and used to discriminate overall survival (OS) and progression-free survival (PFS) as end points. Multilesionality was assessed on the visual analysis of PET/CT and CE-MRI images. After tumor segmentation, standardized uptake value (SUV)-based variables for PET/CT and volume-based and geometrical variables for PET/CT and CE-MRI were calculated. The relationships among imaging techniques variables and their association with prognosis were evaluated using Pearson's chi-square test and the t-test. Receiver operator characteristic, Kaplan−Meier and Cox regression were used for the survival analysis. (3) Results: 54 patients were assessed. The median PFS and OS were 5 and 11 months, respectively. Significant strong relationships between volume-dependent variables obtained from PET/CT and CE-MRI were found (r > 0.750, p < 0.05). For OS, significant associations were found with SUVmax, SUVpeak, SUVmean and sphericity (HR: 1.17, p = 0.035; HR: 1.24, p = 0.042; HR: 1.62, p = 0.040 and HR: 0.8, p = 0.022, respectively). Among clinical variables, only Stupp protocol and age showed significant associations with OS and PFS. No CE-MRI derived variables showed significant association with prognosis. In multivariate analysis, age (HR: 1.04, p = 0.002), Stupp protocol (HR: 2.81, p = 0.001), multilesionality (HR: 2.20, p = 0.013) and sphericity (HR: 0.79, p = 0.027) derived from PET/CT showed independent associations with OS. For PFS, only age (HR: 1.03, p = 0.021) and treatment protocol (HR: 2.20, p = 0.008) were significant predictors. (4) Conclusions: 18F-fluorocholine PET/CT metabolic and radiomic variables were robust prognostic predictors in patients with IDH-wt high-grade gliomas, outperforming CE-MRI derived variables.


Fate of Worn-Out Functional Teeth in the Upper Jaw Dentition of Sicyopterus japonicus (Gobioidei: Sicydiinae) During Tooth Replacement.
Mochizuki and Fukui (Jpn J Ichthyol 30 () 27-36) studied the development and replacement of the upper jaw teeth in a Japanese fish species, Sicyopterus japonicus (Gobioidei: Sicydiinae), and they reported that worn-out functional teeth in the upper jaw were not shed outside the skin but were taken into the soft tissue of the upper jaw and completely resorbed there. To date, however, this phenomenon appears poorly documented. Furthermore, the mechanism for the resorption of these teeth remains to be determined. In this study, we examined this phenomenon by using 3D microcomputed tomography (m-CT), scanning electron microscopy (SEM), and various techniques of light (LM) and electron (EM) microcopy. This study demonstrated that the upper jaw dentition of this fish was more or less simultaneously replaced with the replacement occurring during short time periods and that the lingual movement of the replacement teeth to the functional tooth position advanced simultaneously in a given row. Furthermore, our study also revealed that many worn-out functional teeth were engulfed by the oral epithelium, invaginated into the lingual shallow ditch of the premaxilla, and were resorbed/degraded completely by numerous foreign body giant cells rather than by odontoclasts during periods of at least three intervals of tooth replacement. The complete resorption/degradation of worn-out functional teeth in the soft tissue of the upper jaw suggests the possibility of the reuse of their components (minerals such as Ca and P, including Fe) for rapid and successional production of new replacement teeth in the upper jaw of adult S. japonicus. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:111-124, 2018. © 2017 Wiley Periodicals, Inc.


Synthesis of creatinine-imprinted poly(beta-cyclodextrin) for the specific binding of creatinine.
An artificial receptor for creatinine was synthesized by the method of molecularly imprinted polymer (MIP). beta-Cyclodextrin was used as a monomer cross-linked with epichlorohydrin in the presence of creatinine, which was a template for the imprinting. Different molar ratios of monomer to template were used to synthesize the polymers so that better specific adsorption ability towards creatinine could be achieved. The results showed that to carry out the polymerization with a molar ratio of monomer to template of 3:2 and monomer to cross-linking agent of 1:10 was proper. N-hydroxysuccinimide and 2-pyrrolinidone were used as the analogues of creatinine in the adsorption experiments of multi-component solutions to reveal the specific recognition ability of the molecularly imprinted poly(beta-cyclodextrin) (poly(beta-CD)) for the template molecule, creatinine. One such detection interference of creatinine was creatine, which also co-exists in serum. Hence, adsorption experiments of creatinine/creatine binary mixture were also carried out to investigate and confirm the specific binding of the creatinine-imprinted poly(beta-cyclodextrin) towards creatinine. The hydroxyl groups of the imprinted poly(beta-CD) was further capped by chlorotrimethylsilane (CTMS) to investigate the interaction between creatinine and the imprinted poly(beta-CD). The adsorption resulting from the mixture solution by MIPs suggested that the creatinine-imprinted poly(beta-CD) demonstrated superior binding effect for the target molecule, creatinine, rather than creatine, N-hydroxysuccinimide and 2-pyrrolinidone.


Downregulation of Renal MRPs Transporters in Acute Lymphoblastic Leukemia Mediated by the IL-6/STAT3/PXR Signaling Pathway.
Considering prior investigations on reductions of renal multidrug resistance-associated protein (MRP) 2 and 4 transporters in mice with acute lymphoblastic leukemia (ALL), we sought to characterize the underlying mechanisms responsible for IL-6/STAT3/PXR-mediated changes in the expression of MRP2 and MRP4 in ALL. ALL xenograft models were established and intravenously injected with methotrexate (MTX) of MRPs substrate in NOD/SCID mice. Protein expression of MRPs and associated mechanisms were detected by Western blotting and immunocytochemistry. Plasma concentrations of MTX were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Plasma IL-6 levels in patients with newly diagnosed ALL were increased compared to children with pneumonia. Similarly, plasma IL-6 levels in ALL, ALL-tocilizumab (TCZ, an IL-6 receptor inhibitor) and ALL-S3I-201 (a selective inhibitor of STAT3) mice were increased compared to the control group. The MRP2, MRP4, and PXR expression in HK-2 cells treated with IL-6 were decreased, whereas the p-STAT3 expression was significantly increased compared to the control group results. These results are consistent with clearance of MRPs-mediated MTX in the ALL group. These effects were attenuated by blocking IL-6/STAT3/PXR signaling pathway. Inflammation-mediated changes in pharmacokinetics are thought to be executed through pathways IL-6-activated pathways, which can facilitate a better understanding of the potential for the use of IL-6 to predict the severity of adverse outcomes and the major implications on potential ALL treatments.


[Treatment of pancreatic adenocarcinoma].
Better results of resections for pancreatic adenocarcinoma are reported in published data from 1990: 1. the lower mortality rate is probably not the only reason why these results are better; 2. the palliative resections rate seem to be lower (as the rates of exploratory laparotomies and by-pass procedures); 3. the impact of resection's quality on the results is difficult to demonstrate and the benefit of extended lymphadenectomy remains unclear; 4. moreover, in recent published series, many patients had adjuvant or neoadjuvant therapy, but often in uncontrolled studies. Multimodality treatment is probably useful for better local control and better disease free survival; this therapeutic approach is widely used today but the results remain to be confirmed by clinical trials. Unfortunately, 90% of the patients had locally advanced or metastatic disease at the time of diagnosis; in these patients clinical research is a challenge in order to change the prognosis; actually, epidemiological studies are still showing that quite all the patients die.


Signaling Network Response to α-Particle-Targeted Therapy with the 225Ac-Labeled Minigastrin Analog 225Ac-PP-F11N Reveals the Radiosensitizing Potential of Histone Deacetylase Inhibitors.
α-particle emitters have recently been explored as valuable therapeutic radionuclides. Yet, toxicity to healthy organs and cancer radioresistance limit the efficacy of targeted α-particle therapy (TAT). Identification of the radiation-activated mechanisms that drive cancer cell survival provides opportunities to develop new points for therapeutic interference to improve the efficacy and safety of TAT. Methods: Quantitative phosphoproteomics and matching proteomics followed by the bioinformatics analysis were used to identify alterations in the signaling networks in response to TAT with the 225Ac-labeled minigastrin analog 225Ac-PP-F11N (DOTA-(dGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe) in A431 cells, which overexpress cholecystokinin B receptor (CCKBR). Western blot analysis and microscopy verified the activation of the selected signaling pathways. Small-molecule inhibitors were used to validate the potential of the radiosensitizing combinatory treatments both in vitro and in A431/CCKBR tumor-bearing nude mice. Results: TAT-induced alterations were involved in DNA damage response, cell cycle regulation, and signal transduction, as well as RNA transcription and processing, cell morphology, and transport. Western blot analysis and microscopy confirmed increased phosphorylations of the key proteins involved in DNA damage response and carcinogenesis, including p53, p53 binding protein 1 (p53BP1), histone deacetylases (HDACs), and H2AX. Inhibition of HDAC class II, ataxia-telangiectasia mutated (ATM), and p38 kinases by TMP269, AZD1390, and SB202190, respectively, sensitized A431/CCKBR cells to 225Ac-PP-F11N. As compared with the control and monotherapies, the combination of 225Ac-PP-F11N with the HDAC inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) significantly reduced the viability and increased the DNA damage of A431/CCKBR cells, led to the most pronounced tumor growth inhibition, and extended the mean survival of A431/CCKBR xenografted nude mice. Conclusion: Our study revealed the cellular responses to TAT and demonstrated the radiosensitizing potential of HDAC inhibitors to 225Ac-PP-F11N in CCKBR-positive tumors. This proof-of-concept study recommends development of novel radiosensitizing strategies by targeting TAT-activated and survival-promoting signaling pathways.


Induction of drought tolerance in tomato upon the application of ACC deaminase producing plant growth promoting rhizobacterium Bacillus subtilis Rhizo SF 48.
A total of ten 1-aminocyclopropane-1-carboxylate (ACC) deaminase producing PGPR isolates were selected and evaluated for the induction of drought stress tolerance in tomato. Among the selected PGPR, maximum seed (laboratory) and plant growth promotion (greenhouse) was observed in tomato seeds bacterized with Bacillus subtilis Rhizo SF 48. The genomic study confirmed the presence of ACC deaminase gene in Rhizo SF 48 and the obtained sequence was deposited to the NCBI database with the Accession No. MK652706. The tomato plants grown upon treatment with Rhizo SF 48 significantly enhanced plant growth even after exposing to different levels of drought stress as compared to stress induced control plants. About 7.5% and 38% increase in RWC were observed in Rhizo SF 48 treated tomato plants grown under well-watered and stress conditions (S4) compared to their control plants, respectively. An increase of 0.76, 0.23 and 0.78 fold in proline, SOD and APX activity and a decrease of 0.3 fold in MDA and H2O2 contents were observed in Rhizo SF 48 treated plants compared to control plants grown under S4 conditions. The histo-chemical studies showed lower accumulations of H2O2 and superoxide anion in the leaves of Rhizo SF 48 treated plants under drought stress, which was in confirmation with the quantification results of H2O2 and SOD. The qRT-PCR studies on drought (Le25) and ethylene responsive factor (SlERF84) marker genes showed that a significant decrease of 0.75 and 0.81 folds, respectively in Le25 and SlERF84 accumulation was observed in Rhizo SF 48 treated plants compared to untreated plants grown under S4 conditions. From the results, it can be attributed that ACC deaminase producing Rhizo SF 48 was able to protect tomato plants against oxidative damage caused due to drought stress and enhanced plant growth promotion. It can be concluded that ACC deaminase producing Rhizo SF 48 can serve as a useful bio-inoculant for sustainable tomato production in arid and semi-arid regions with water deficit.


Direct cross-linking of snRNP proteins F and 70K to snRNAs by ultra-violet radiation in situ.
Protein-RNA interactions in small nuclear ribonucleoproteins (UsnRNPs) from HeLa cells were investigated by irradiation of purified nucleoplasmic snRNPs U1 to U6 with UV light at 254 nm. The cross-linked proteins were analyzed on one- and two-dimensional gel electrophoresis systems, and the existence of a stable cross-linkage was demonstrated by isolating protein-oligonucleotide complexes from snRNPs containing 32P-labelled snRNAs after exhaustive digestion with a mixture of RNases of different specificities. The primary target of the UV-light induced cross-linking reaction between protein and RNA was protein F. It was also found to be cross-linked to U1 snRNA in purified U1 snRNPs. Protein F is known to be one of the common snRNP proteins, which together with D, E and G protect a 15-25 nucleotide long stretch of snRNAs U1, U2, U4 and U5, the so-called domain A or Sm binding site against nuclease digestion (Liautard et al., 1982). It is therefore likely that the core-protein may bind directly and specifically to the common snRNA domain A, or else to a sub-region of this. The second protein which was demonstrated to be cross-linked to snRNA was the U1 specific protein 70K. Since it has been shown that binding of protein 70K to U1 RNP requires the presence of the 5' stem and loop of U1 RNA (Hamm et al., 1987) it is likely that the 70K protein directly interacts with a sub-region of the first stem loop structure.


['Charitable brothers' in charge of hospitals in early modern times: The hospital in Linz/Austria and its patients up to c. 1780].
The article deals with the history of the Hospital of the Brothers of St. John of God (in German: "Barmherzige Brüder"; official name "Ordo Hospitalarius Sancti Joannis a Deo") in the capital of Upper Austria, Linz, from its founding in 1757 to c. 1780. Primarily, the organisational development and the patients of the institute are discussed. The order's hospital already functioned as a medical hospital for the treatment of acute diseases: It was oriented towards the reestablishment of health of its inmates during short time and offered treatment by a staff of learned medical experts, among them academically trained physicians. The accommodation of the patients yet took place in a largely undifferentiated manner, as most of them were situated in a large common hall. This was obviously a consequence of the comparatively little capacity of the organisation, too, which sustained about 12 beds in the beginning, and about 20 around 1780. Nonetheless, the number of patients treated there summed up to nearly 1% of the entire male population of Upper Austria even during the first decade of its existence. In early modern time, only men were admitted to this hospital, the average age of them being only ca. 30 years. As far as social status is concerned, most of them (according to a representative sample out of the admissions of 1757-1767) were handicraftsmen (more than two thirds), labourers and servants. Thus, the organisation was obviously destined to broad social strata, but by no way displays itself as a poorhouse. Average annual mortality was 10 to 13%, which is comparable to that of other hospitals of the order in 18th century Austria. Most of the admitted persons suffered from "fever" or inner diseases and were dismissed as healed already after some weeks of stay.


Comparative toxicology of fatal heroin overdose cases and morphine positive homicide victims.
To compare the blood toxicology of heroin overdose cases and morphine positive homicide victims. Analysis of coronial cases. Sydney, Australia. Cases A total of 705 cases of death due to opioid toxicity and 28 morphine positive homicide cases (1 January 1998-31 December 2002). There was no significant difference between the median morphine concentrations of the overdose and homicide groups (0.50 versus 0.45 mg/l). The overdose group was more likely to have blood alcohol (OR 3.21) present, but less likely to have methadone (OR 0.26) and cannabis (OR 0.04). There was a significant negative correlation between blood morphine and alcohol concentrations among the overdose group (rho = -0.32), but not among the homicide group (rho = -0.03). Independent predictors of a higher blood morphine concentration were a lower alcohol concentration and a higher methadone concentration. Morphine concentrations per se are not diagnostic of overdose. The study confirms the salience of concomitant alcohol consumption in such events.


The representational bias of acquired memory processes.
The notion that some memory processes are acquired has been around for at least two thousand years. However, acquired memory processes have been made the object of scientific investigation in only the past two decades. Traditionally, psychologists have assumed that acquired memory processes are equally effective across the entire range of memory tasks. This article reviews research that has investigated whether these processes are equally effective across tasks or are more effective for just certain tasks. The review indicates that most, if not all, acquired memory processes are biased to deal effectively just certain kinds of mental representation. The article proposes that these processes are representationally biased because (1) they activate basic memory processes (e.g. imagery, rehearsal) which themselves are biased to process certain representational attributes and because (2) their use of basic processes follows a sequence required by particular memory tasks. Increased understanding of the representational bias of acquired processes may be seen to enable better control of memory performance and to foster more powerful investigations of memory phenomena.


Pseudoangiomatous stromal hyperplasia: An observation on its microscopic involvement in breast carcinoma and the presence of lymph node metastases.
The spaces of pseudoangiomatous stromal hyperplasia (PASH) are postulated to be important in the intramammary spread of breast carcinoma. The present study aimed to note the prevalence of inconspicuous, microscopic foci of PASH (identified as CD34+ve, CD31-ve and D2-40-ve spaces containing tumour emboli) involved in breast carcinoma and to establish the significance of its relationship to lymph node metastases. A total of 80 cases of breast carcinoma were examined for microscopic foci of PASH permeated by carcinoma and, of the four cases found to demonstrate such involvement, three had lymph node metastases.


Kveim test reactivity in Melkersson-Rosenthal syndrome (cheilitis granulomatosa).
The relation between the Melkersson-Rosenthal syndrome (MRS) and sarcoidosis is unclear. The Kveim test, a test for sarcoidosis, was performed in seven patients, two with complete and five with abortive forms of Melkersson-Rosenthal syndrome. All were found to be negative. Serum levels of angiotensin converting enzyme and calcium were normal. These facts make it unlikely that MRS is a type of sarcoidosis.


Clinical features associated with ADB-BUTINACA exposure in patients attending emergency departments in England.
Synthetic cannabinoid receptor agonists (SCRA) are commonly encountered new psychoactive substances. Here we report the recent detection of ADB-BUTINACA in samples from patients attending United Kingdom emergency departments with toxicity after suspected drug misuse and describe the associated clinical features. Consenting adults (≥16 y) presenting to participating hospitals with toxicity after suspected drug misuse have been included in the Identification Of Novel psychoActive substances (IONA) study since March 2015. Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. By December 2021, analytical data were available for 1279 IONA participants and ADB-BUTINACA was detected in at least one sample from 10 (9 males, age range 16-51 median 45 years), all presenting since February 2021. Smoking 'spice' was reported by four patients, two had ingested edible "cannabis" gums and four reported heroin use (2 intravenous, 1 smoked, 1 route not known). Co-use of pregabalin (oral) and crack cocaine (smoked) were also reported. In 3 cases ADB-BUTINACA was the only substance detected, while in seven other substances of misuse were also detected including other SCRA, opioids, benzodiazepines cocaine and pregabalin. Clinical features reported in these 2 groups respectively included reduced level of consciousness (3/3, 6/7), agitation (0/3, 4/7), tachycardia (0/3, 3/7), seizures (1/3, 1/7), hallucinations (1/3, 1/7), hypotension (1/3, 1/7). Metabolic acidosis (1/3, 0/7) and respiratory acidosis (1/3, 0/7), All 10 patients recovered with supportive care, including intubation and ventilation for one case. The median length of hospital stay was 19 h (range 2.6-131 h). ADB-BUTINACA has recently emerged as a drug of misuse in England. Clinical features of toxicity are consistent with those of other SCRA and include reduced level of consciousness, respiratory and/or metabolic acidosis, seizures, confusion and hallucinations.


An Expert-Supervised Registration Method for Multiparameter Description of the Knee Joint Using Serial Imaging.
As knee osteoarthritis is a disease of the entire joint, our pathophysiological understanding could be improved by the characterization of the relationships among the knee components. Diverse quantitative parameters can be characterized using magnetic resonance imaging (MRI) and computed tomography (CT). However, a lack of methods for the coordinated measurement of multiple parameters hinders global analyses. This study aimed to design an expert-supervised registration method to facilitate multiparameter description using complementary image sets obtained by serial imaging. The method is based on three-dimensional tissue models positioned in the image sets of interest using manually placed attraction points. Two datasets, with 10 knees CT-scanned twice and 10 knees imaged by CT and MRI were used to assess the method when registering the distal femur and proximal tibia. The median interoperator registration errors, quantified using the mean absolute distance and Dice index, were ≤0.45 mm and ≥0.96 unit, respectively. These values differed by less than 0.1 mm and 0.005 units compared to the errors obtained with gold standard methods. In conclusion, an expert-supervised registration method was introduced. Its capacity to register the distal femur and proximal tibia supports further developments for multiparameter description of healthy and osteoarthritic knee joints, among other applications.


Effects of house sparrow age and arbovirus infection on attraction of mosquitoes.
To test the hypothesis that arbovirus infection or advancing age increases the attractiveness of avian hosts to vector mosquitoes, we used an olfactometer that measures the response of mosquitoes to the passive, vertical diffusion of host-related cues. St. Louis encephalitis or western equine encephalomyelitis virus infection in house sparrows (Passer domesticus (L.], regardless of age, had no detectable effect on Culex quinquefasciatus Say or Cx. tarsalis Coquillett attraction, respectively, at close range. Sparrow age, however, was associated positively with increased Cx. quinquefasciatus attraction; i.e., nestlings were significantly less attractive than adults, and there was a trend for increased mosquito attraction as nestling age increased. When birds were examined in groups, attraction was not equal to the sum of the individual birds in the group. Nestlings, either alone or in a group, were less attractive than a single adult. One adult plus three older nestlings were more attractive than one adult with three young nestlings, but no more attractive than one adult alone. We speculate on the epidemiological significance of these laboratory results to arbovirus epizootic transmission.


Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10.
Matrix metalloproteinases (MMPs) may have pro and antifibrotic roles within the lungs, due to its ability to modulate collagen turnover and immune mediators. MMP-8 is a collagenase that also cleaves a number of cytokines and chemokines. To evaluate its relevance in lung fibrosis, wildtype and Mmp8(-/-) mice were treated with either intratracheal bleomycin or saline, and lungs were harvested at different time points. Fibrosis, collagen, collagenases, gelatinases, TGFβ and IL-10 were measured in lung tissue. Mmp8(-/-) mice developed less fibrosis than their wildtype counterparts. This was related to an increase in lung inflammatory cells, MMP-9 and IL-10 levels in these mutant animals. In vitro experiments showed that MMP-8 cleaves murine and human IL-10, and tissue from knockout animals showed decreased IL-10 processing. Additionally, lung fibroblasts from these mice were cultured in the presence of bleomycin and collagen, IL-10 and STAT3 activation (downstream signal in response to IL-10) measured by western blotting. In cell cultures, bleomycin increased collagen synthesis only in wildtype mice. Fibroblasts from knockout mice did not show increased collagen synthesis, but increased levels of unprocessed IL-10 and STAT3 phosphorylation. Blockade of IL-10 reverted this phenotype, increasing collagen in cultures. According to these results, we conclude that the absence of MMP-8 has an antifibrotic effect by increasing IL-10 and propose that this metalloprotease could be a relevant modulator of IL-10 metabolism in vivo.


Antioxidant activities of mamao luang (Antidesma thwaitesianum Müll. Arg.) fruit: Extraction and application in raw chicken patties.
Extraction of mamao luang (hereafter called mamao) with different solvents and varying solid to liquid (S:L) ratio was conducted to verify its antioxidant activities. Total phenolic content (TPC), total flavonoid content, total monomeric anthocyanin content, and antioxidant activities, namely, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and ferric reducing antioxidant power (FRAP) of the unrefined extracts, were analyzed. The extraction with 70% acetone and 70% methanol and the S:L ratio of 1:30 seemed to be more appropriate and gave significantly (P < 0.05) higher values of the previously mentioned properties. Whole ground fruits were then incorporated into the blended chicken patties to compare their antioxidant and antimicrobial properties with butylated hydroxyanisole (BHA). During refrigeration storage of 20 days, the highest level (1,000 mg TPC/kg meat) could retard lipid oxidation relatively comparable to the efficiency of BHA (200 ppm). However, when microbiological aspect was considered together, a limited storage of 12 days was consequently suggested. PRACTICAL APPLICATION: Mamao fruit is a splendid source of phenolic compounds. The antioxidant properties have been demonstrated using DPPH and FRAP assay. The suitable type of solvent and S:L ratio were provided for the extraction. Our findings have shown that addition of mamao, a source of natural antioxidants, especially at the highest level increased oxidative stability of chicken patties. The research outcomes identify the potential bioactive compound and provide beneficial information related to the feasibility of incorporation of mamao phenolics as antioxidant agents in suitable food matrices. However, further investigation is still required for successful application in meat and meat products.


BJ-48, a novel thrombin-like enzyme from the Bothrops jararacussu venom with high selectivity for Arg over Lys in P1: Role of N-glycosylation in thermostability and active site accessibility.
BJ-48, a serine protease from the venom of Bothrops jararacussu, was purified to homogeneity using affinity chromatography on p-aminobenzamidine-agarose followed by HPLC gel filtration. BJ-48 presented 52kDa by SDS-PAGE analysis and 48,036Da by electron spray mass spectrometry. The enzyme was shown to be highly glycosylated with 42% of N-linked carbohydrates composed of Fuc(1):GalN(4):GlcN(5):Gal(1):Man(2) and a high content of sialic acid residues (8-12%). BJ-48 had optimal esterase activity at pH 7.5 and displayed maximum catalytic rate at 50 degrees C. Its hydrolytic activity was strongly inhibited by aprotinin and dithiothreitol while N-tosyl-l-phenylalanine chloromethyl ketone, 6-aminocaproic acid, E-64 and soybean trypsin inhibitor (SBTI) were ineffective. The kinetics of BJ-48 with chromogenic substrates revealed an unprecedented selectivity (10(4)-fold) for Arg over Lys in P1. BJ-48 proved to be a thrombin-like enzyme (TLE) with a specific fibrinogen-clotting activity of 73.4NIH units/mg. The TLE rapidly digested human fibrinogen Bbeta chain, but the Aalpha chain was cleaved specifically to release fibrinopeptide A with k(cat)/K(m)=2.1 microM(-1)s(-1). The TLE showed no activity toward other thrombin substrates like protein C, protease-activated receptor-1 or inhibitors such as hirudin and antithrombin. A non-denaturing procedure using PNGase F and neuraminidase followed by hydrophobic interaction chromatography was employed to obtain active BJ-48 forms with variable carbohydrate content. Compared to the native enzyme, total or partially deglycosylated BJ-48 forms presented up to 2-fold reduction in their specific activities upon heating at 55/65 degrees C or treatment with SBTI. These results point out a role for BJ-48 glycosylation in thermostability and controlling the access of some canonical protein inhibitors to the active site.


The Concentric Square Field: a multivariate test arena for analysis of explorative strategies.
In this study, we describe the behavior of laboratory rats in a recently developed observation arena, the Concentric Square Field (CSF). The CSF contains a number of areas designed to provoke exploration and behaviors associated with risk assessment, risk taking and security seeking in an environment not previously experienced. The model includes sheltered, open and elevated areas, a hole board device, areas with different light conditions, and wall-enclosed corridors. The rationale behind the CSF is to meet the demand for multivariate test situations that are not predictive in the sense of previous definition of a specific purpose of measuring a certain mental state. We define multivariate as being a free choice of where to stay in areas of different qualities. In the present study, identification of risky as opposed to safe areas is based on the retrieval behavior in lactating females and hoarding of food pellets in food-deprived males. Furthermore, we describe the effects of pre-trial food deprivation, immobilization, social stress, strain differences (Sprague-Dawley, Wistar and Lister Hooded males), sex differences (Sprague-Dawley) and repeated testing. Besides the conventional statistics, a principal component analysis (PCA) helped to discriminate between the various categories tested. Our conclusion is that the multivariate and non-predictive test situation (CSF) and the use of PCA provide a good tool for ethoexperimental analysis.


Neural Basis of Increased Cognitive Control of Impulsivity During the Mid-Luteal Phase Relative to the Late Follicular Phase of the Menstrual Cycle.
Hormonal changes across the menstrual cycle have been shown to influence reward-related motivation and impulsive behaviors. Here, with the aim of examining the neural mechanisms underlying cognitive control of impulsivity, we compared event-related monetary delay discounting task behavior and concurrent functional magnetic resonance imaging (fMRI) revealed brain activity as well as resting state (rs)-fMRI activity, between women in the mid-luteal phase (LP) and women in the late follicular phase (FP). The behavioral data were analyzed and related to neural activation data. In the delay discounting task, women in the late FP were more responsive to short-term rewards (i.e., showed a greater discount rate) than women in the mid-LP, while also showing greater activity in the dorsal striatum (DS). Discount rate (transformed k) correlated with functional connectivity between the DS and dorsal lateral prefrontal cortex (dlPFC), consistent with previous findings indicating that DS-dlPFC circuitry may regulate impulsivity. Our rs-fMRI data further showed that the right dlPFC was significantly more active in the mid-LP than in late FP, and this effect was sensitive to absolute and relative estradiol levels during the mid-LP. DS-dlPFC functional connectivity magnitude correlated negatively with psychometric impulsivity scores during the late FP, consistent with our behavioral data and further indicating that relative estradiol levels may play an important role in augmenting cognitive control. These findings provide new insight into the treatment of conditions characterized by hyper-impulsivity, such as obsessive compulsive disorder, Parkinson disease, and attention deficit hyperactivity disorder. In conclusion, our results suggest that cyclical gonadal hormones affect cognitive control of impulsive behavior in a periodic manner, possibility via DS-dlPFC circuitry.


The 7H11 Agar Medium Supplemented with Calf Bovine Serum for Susceptibility Testing of Mycobacterium tuberculosis Isolates Against Pyrazinamide.
Despite its importance, pyrazinamide (PZA) is a blind spot in drug susceptibility testing in tuberculosis laboratories. The aim of this study was to set up a reliable agar-based proportion method for detection of PZA-resistant phenotypes using Middlebrook 7H11 agar supplemented with calf bovine serum (CBS) compared with albumin/dextrose/catalase (ADC) enrichment and pncA/rpsA sequencing results. The 7H11 agar medium supplemented with 10% ADC or 10% CBS (pH 6.2) and 100 μg/mL PZA was used to detect PZA resistance among 64 Mycobacterium tuberculosis isolates. Sanger sequencing and whole-genome sequencing were performed to track mutations in the pncA, rpsA, and their upstream regions. A total of 43 rifampicin/multidrug-resistant, 20 drug-susceptible, and 1 isoniazid mono-resistant M. tuberculosis isolates were investigated. The 7H11+ADC and 7H11+CBS could detect 22 and 23 PZA-resistant strains, respectively. With the same specificity, the sensitivity and accuracy of 7H11+CBS was found to be a little greater than 7H11+ADC in PZA resistance detection compared with sequencing results. Twenty-four mutant strains were found to have different mutations in pncA-upstream, pncA and rpsA genes, in which Gly97Asp was the most dominant mutation. The results obtained from 7H11+CBS were comparable to the results of 7H11+ADC. Therefore, the 7H11 agar proportion method would be a less-expensive test using CBS and produces reliable results.


A role for fascin in preventing filopodia breakage in Drosophila tracheal cells.
Filopodia are long and thin finger-like protrusions essential for cell migration. They are formed by parallel actin bundles tightly packed by cell type and context dependent actin-bundling proteins. Our recent work analyzing the role of Fascin during tracheal development in Drosophila has shown that Singed (the Drosophila Fascin homolog) acts as a molecular link between the Branchless (FGF)/Breathless (FGFR) pathway and the actin cytoskeleton. We have reported that the lack of Singed (Sn) leads to wavy and flaccid filopodia due to the disorganization of the tracheal actin cytoskeleton. Here we describe for the first time filopodia breakage in Drosophila, and show that Fascin plays a role in this event. We propose that actin filaments in sn mutant filopodia buckle under membrane pressure due to lower bending stiffness, eventually undergoing breakage. Both Filopodia buckling and breakage would impair correct cell navigation and migration.


[Detection and genotype analysis of sapovirus associated with sporadic diarrhea in Shenzhen in 2009].
To conduct an epidemiological and genotype analysis of sapovirus (SaV) associated with sporadic diarrhea in Shenzhen in the year 2009. A total of 852 fecal samples were collected from sporadic cases of diarrhea in Shenzhen in 2009 and detected by reverse-transcription polymerase chain reaction (RT-PCR) using the primers of SLV5317/5749. The PCR products were analyzed with 1.5% agarose gel electrophoresis and sequenced to construct the phylogenetic tree. Sixteen samples were found positive for SaV, with a positivity rate of 1.88%. Sequence analysis identified 8 isolates as SaV GI genotype (including 3 SaV GI.1 and 5 SaV GI.2), 7 as SaV GIV genotype, and 1 as GII genotype. SaV infection is present in Shenzhen with GI as the predominant genotype. This is the first report of SaV GIV strains in China, which differs from the strains of Anhui-A141 and Beijing-CHN99/BJ360, suggesting the genotypic variety of SaV infection in China.


Follow-up study of chronic gastric erosions.
Chronic gastric erosions were detected with a frequency of 4.4% in 8,468 patients over the six year period from 1971 to 1977. The lesions were usually multiple, chain-like or clustered, along the greater curvature. The age group most often afflicted was the 50-60 year olds, and male predominance were three to one. In one-third of the cases, chronic erosions were found in combination with gastric or duodenal ulceration. Longterm observation of 64 patients over a period of four and a half years revealed no change in the condition in 50%, increase, decrease or complete disappearance of the lesions were found in the remaining 50%. In 10% chain-like multiple erosions developed into a persisting fold in the gastric mucosa. No evidence suggesting that erosive lesions lead to chronic ulceration or development of either polyps or malignancy within 4 1/2 years was recorded, nor was there any association with gastric protein loss.


The Role of Neck Musculature in Traumatic Brain Injuries in Older Adults: Implications From Sports Medicine.
Traumatic brain injuries (TBIs) are common and serious injuries to older adults. The majority of TBIs in older adults are sustained when the head impacts the ground or other surface during a fall. While several non-modifiable risk factors have been identified for fall-related TBIs in older adults, there still remains a dearth of knowledge surrounding modifiable risk factors. Thus, this significant knowledge gap warrants an investigation into research across disciplines. The sports medicine literature has examined several modifiable risk factors to prevent a mild form of TBI known as concussion. While this research has identified several risk factors, one particular risk factor may have potential implications to fall-related TBIs in older adults. The sports medicine literature has shown that decreased neck strength and slower neck muscle activation are significant predictors for sports-related concussion. Similarly, older adults experience age-related declines to neck muscle strength and muscle activation. Consequently, these age-related declines to the neck musculature may result in the inability of older adults to control their head during a fall, which results in greater impact forces being transmitted to the brain and increases the risk of TBI. This perspective article assesses the sports medicine literature related to the implications of neck strength and muscle activation in sports-related concussion, discusses age-related declines to neck strength and muscle activation, and highlights the potential impact of the neck musculature on fall-related TBIs in older adults.


[Research of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits].
To investigate the curative effect and mechanism of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits. The rabbits were all transplanted with VX2 carcinoma on kidney. Fifty-five rabbits were randomly divided into 11 groups. Rabbits in these groups were administered interventional treatment of normal saline, iodinated oil, mitomycin, 5-fluorouracil, beta-elemene, cisplatin, carboplatin, adriamycin, thiotepa, cyclophopsphamide, and vincristine, respectively. After corresponding intervention, the tumor volume in each group was measured by ultrasonography and spiral computed tomography, and the tumor growth rate (TGR) was calculated. Nenal and hepatic functions of the rabbits in each group were compared 1 day, 7 and 14 days after the interventional treatment. Morphologic change of the tumor was observed by a light microscopy and a transmission electron microscopy 14 days after interventional treatment. The expressions of Bax and Bcl-2 were measured by immunohistochemical straining. There was statistical significance in the effects of different medicines intervened on VX2 kidney transplanted carcinoma. The VX2 carcinoma of rabbits had high-sensitivity to iodized oil embolism, mitomycin, cisplatin and carboplatin, which showed serious damage to the kidney function, medium-sensitivity to beta-elemene, adriamycin and 5-fluorouracil, in which beta-elemene showed slight damage to the kidney function, and resistance to thiotepa, cyclohosphamide and vincristine. Most tumor cells displayed apoptosis in the beta-elemene interventional treatment group under light microscopy and transmission electron microscopy, and only few tumor cells displayed necrosis. The Bax expression was up-regulated (P<0.05) and the Bcl-2 expression had no significant difference (P>0.05) in the beta-elemene interventional treatment group. Intervention treatment of beta-elemene has significant effect on VX2 kidney transplanted carcinoma and little side effect on the kidney function. Its mechanism is related to enhancing the apoptosis of tumor cells, and Bax gene participates in this action.


[Investigation and application of Dendrobium resources in Qinba Mountains with a discussion on industrial poverty alleviation model].
The Dendrobium species are rare and endangered medicinal plants, and it is difficult to investigate their wild resources with conventional methods because of typical epiphytic herbaceous. We explored Dendrobium resources(include culture resource) of Qinba Mountains and the boundary Mountain area in Hubei, Chongqing using the methods of literatures and field investigation, and found that the cultural base of Dendrobium were profound in Qinba Mountains region. Furthermore, its germplasm resources of Dendrobium were established for the first time in Wanzhou Luotian town. In case the advantages of local rock resources and poverty alleviation demand, we have actively carried out the cultivating mode of Dendrobium which grow on rock, and the poverty alleviation model of local characteristic Dendrobium industry were established preliminarily. Our application case can provide reference for the mining and transformation of traditional Chinese medicine resources census results.


[Antiepileptic effects of globulin-N as an intact human immunoglobulin and its tissue-distribution in kindled cats].
The antiepileptic effects of Globulin-N as an intact human immunoglobulin were examined using the amygdaloid kindled animals, which was prepared by the method of Goddard et al (1969) and Wada et al (1974). In the non-treated kindled cats, generalized convulsion (GC) and after-discharge (AD) in amygdala, hippocampus and neocortex was caused synchronously by electrical stimulation with generalized seizure-triggering threshold (GST) at constant intervals of 24 hours. By contrast, in kindled cats treated intravenously with 200 mg/kg Globulin-N, the GC and AD due to the GST-stimulation disappeared entirely for the period 4 to 8 days after medication in 8 out of 10 cases. Further, kindled cats treated with anticonvulsant, phenobarbital or phenytoin inhibited GC and AD to GST-stimulation until 24-48 hours after medication. On the other hand, the plasma half-life of Globulin-N was determined as about 10 days in the kindled cats, and Globulin-N was distributed immunohistochemically not only in the visceral organ-tissues but also in the tissues of the brain and spinal cord. The administered Globulin-N or 14C-human immunoglobulin pass through the blood-brain barrier easily in kindled cats with GST induced-epileptic seizure, and was apparently taken up by the nerve cells and glial cells in the cerebral cortex and other extensive deep structure involved in the central nervous system. These results seem to support the clinical usefulness of Globulin-N in patients with epilepsy (Ariizumi et al, 1982) and also epileptic psychosis.


Hierarchical Structure of Silk Materials Versus Mechanical Performance and Mesoscopic Engineering Principles.
A comprehensive review on the five levels of hierarchical structures of silk materials and the correlation with macroscopic properties/performance of the silk materials, that is, the toughness, strain-stiffening, etc., is presented. It follows that the crystalline binding force turns out to be very important in the stabilization of silk materials, while the β-crystallite networks or nanofibrils and the interactions among helical nanofibrils are two of the most essential structural elements, which to a large extent determine the macroscopic performance of various forms of silk materials. In this context, the characteristic structural factors such as the orientation, size, and density of β-crystallites are very crucial. It is revealed that the formation of these structural elements is mainly controlled by the intermolecular nucleation of β-crystallites. Consequently, the rational design and reconstruction of silk materials can be implemented by controlling the molecular nucleation via applying sheering force and seeding (i.e., with carbon nanotubes). In general, the knowledge of the correlation between hierarchical structures and performance provides an understanding of the structural reasons behind the fascinating behaviors of silk materials.


Genetic interventions for vein bypass graft disease: a review.
The failure of vein bypass grafting in the coronary or lower extremity circulation is a common clinical occurrence that incurs significant morbidity, mortality, and cost. Vein grafts are uniquely amenable to intraoperative genetic modification because of the ability to manipulate the tissue ex vivo with controlled conditions. Although the pathophysiology of vein graft failure is incompletely understood, numerous relevant molecular targets have been elucidated. Interventions designed to influence cell proliferation, thrombosis, inflammation, and matrix remodeling at the genetic level have been described, and many have been tested in animal models. Both gene delivery and gene blockade strategies have been investigated, with the latter now reaching the stage of advanced clinical trials. This review describes the basic and translational science of genetic interventions for vein graft disease and the current state of application in the clinic.


[Clinical question for psychosis.].
The analysis treatment of a psychotic individual presupposes a global problem focus on the causes of psychosis, its structure, its outbreak, and the stages in its development. Here, psychosis is viewed in its specifically psychic dimension, where Lacanian theory, to which the author adheres, places the cause of the sickness: (the "forclusion" of the names of the father). This formula indicates the absence of the paternal function. This lack originates in the fact that a dysfunction of the symbolic order in the family structure presides over the birth of a subject. The locating of the elements (the signifiers) of such symbolic dysfunction is essential because the delusion attempts to repair this defect in the representational order. Against this defect the subject first constructed imaginary assemblings which allow him a provisional articulation, satisfying for him, to others and to social reality. The outbreak of the psychosis results in the collapse of such imaginary scaffoldings. Then after a period of bewilderment and psychic retreat, all the effort of the psychotic is directed at the reconstitution of a new representational order. The work of the analysis consistants of attempting, on the basis of the signifiers put forward by the delusion, to assist the psychotic in his reconstitution of symbolic order. The delusion is the access road to this work in psychosis just as the dream is the royal road to the unconscious in the neurosis. The effort of this article is directed at situating these stages in the treatment of psychosis in their theorical and clinical foundations.


Aspergillus section Flavi community structure in Zambia influences aflatoxin contamination of maize and groundnut.
Aflatoxins are cancer-causing, immuno-suppressive mycotoxins that frequently contaminate important staples in Zambia including maize and groundnut. Several species within Aspergillus section Flavi have been implicated as causal agents of aflatoxin contamination in Africa. However, Aspergillus populations associated with aflatoxin contamination in Zambia have not been adequately detailed. Most of Zambia's arable land is non-cultivated and Aspergillus communities in crops may originate in non-cultivated soil. However, relationships between Aspergillus populations on crops and those resident in non-cultivated soils have not been explored. Because characterization of similar fungal populations outside of Zambia have resulted in strategies to prevent aflatoxins, the current study sought to improve understanding of fungal communities in cultivated and non-cultivated soils and in crops. Crops (n=412) and soils from cultivated (n=160) and non-cultivated land (n=60) were assayed for Aspergillus section Flavi from 2012 to 2016. The L-strain morphotype of Aspergillus flavus and A. parasiticus were dominant on maize and groundnut (60% and 42% of Aspergillus section Flavi, respectively). Incidences of A. flavus L-morphotype were negatively correlated with aflatoxin in groundnut (log y=2.4990935-0.09966x, R2=0.79, P=0.001) but not in maize. Incidences of A. parasiticus partially explained groundnut aflatoxin concentrations in all agroecologies and maize aflatoxin in agroecology III (log y=0.1956034+0.510379x, R2=0.57, P<0.001) supporting A. parasiticus as the dominant etiologic agent of aflatoxin contamination in Zambia. Communities in both non-cultivated and cultivated soils were dominated by A. parasiticus (69% and 58%, respectively). Aspergillus parasiticus from cultivated and non-cultivated land produced statistically similar concentrations of aflatoxins. Aflatoxin-producers causing contamination of crops in Zambia may be native and, originate from non-cultivated areas, and not be introduced with non-native crops such as maize and groundnut. Non-cultivated land may be an important reservoir from which aflatoxin-producers are repeatedly introduced to cultivated areas. The potential of atoxigenic members of the A. flavus-L morphotype for management of aflatoxin in Zambia is also suggested. Characterization of the causal agents of aflatoxin contamination in agroecologies across Zambia gives support for modifying fungal community structure to reduce the aflatoxin-producing potential.


Future of infertility treatment.
The development of techniques to prolong the window of fertility for women has the ability to meet the needs of future populations and their delay in childbearing. With current techniques of cryopreservation of embryos, oocytes, or ovarian tissue, prolongation of fertility with varying success is feasible. In the future, rejuvenation of aging oocytes will offer the opportunity for the aging women to achieve pregnancy with their own genetic offspring. Production of germ cells from embryonic stem cells is another alternative for patient with poor or depleted germ cells. Better understanding of the cause of infertility can be achieved with new techniques to evaluate the oocytes, spermatozoa, and embryos on molecular and genetic levels. With improved understanding of the etiology of infertility, treatment will be more effective. With the advance of new drugs and surgical equipment, treatment of infertility will become more convenient and effective.