Effect of physical activity on the life quality of coronary artery bypass graft patients.
The quality of life depends on physical, psychological and social factors that are evidently influenced by the individual's actions, prospect, attitude and behavior. Heart disease is one of the most imperative health problems in the world. Studies showed that exercise-based rehabilitation for patients with coronary artery disease effectively lowers the rate of cardiac death. The intent of this study was to determine the effects of physical activity on the life quality of cardiovascular patients after coronary artery bypass graft. This randomized clinical trial was performed on two groups of coronary artery patients of Yazd Afshar hospital. All the 70 participants were post surgery coronary artery patients who were divided into two groups. Data was collected by two questionnaires: A personal information questionnaire and a quality of life questionnaire (SF=36). Data of both groups was collected in the first and fourth month after the discharge from surgery and sessions were analyzed by SPSS 16 and by using T-test and Chi-square. Results displayed that after the intervention, all the categories of the components of the quality of life were increased except for general health. There was no significant differentiation between these statuses in the control group and the premier grades about the components of the social function (88.98 out of 100). The comparison of total scores of the quality of life before the intervention showed the quality of life of both groups one month after surgery was not significant (p=75%), but in four months after surgery, the distinction between the mean grade scores of the intervention, the group was considerable (p=0.0001). The comparison of the total scores of the quality of life indicated an increase in the scores of the quality of life in the intervention group after the exercise.


The Pursuit of Enzyme Activation: A Snapshot of the Gold Rush.
A range of enzymes drive human physiology, and their activities are tightly regulated through numerous signaling pathways. Depending on the context, these pathways may activate or inhibit an enzyme as a way to ensure proper execution of cellular functions. From a drug discovery and development perspective, pharmacological inhibition of enzymes has been a focus of interest, as many diseases are associated with the upregulation of enzyme function. On the other hand, however, pharmacological activation of enzymes such as kinases and phosphatases has been of increasing interest. In this review, we discuss seven case studies that highlight pharmacological activation strategy, describe the binding modes and pharmacology of the activators, and comment on how this on-demand activation strategy complements the commonly pursued inhibition strategy, thus jointly enabling bidirectional modulation of specific target of interest. Going forward, we expect activators to play important roles as chemical probes and drug leads.


Molecular mechanism of thioflavin-T binding to the surface of beta-rich peptide self-assemblies.
A number of small organic molecules have been developed that bind to amyloid fibrils, a subset of which also inhibit fibrillization. Among these, the benzothiol dye Thioflavin-T (ThT) has been used for decades in the diagnosis of protein-misfolding diseases and in kinetic studies of self-assembly (fibrillization). Despite its importance, efforts to characterize the ThT-binding mechanism at the atomic level have been hampered by the inherent insolubility and heterogeneity of peptide self-assemblies. To overcome these challenges, we have developed a minimalist approach to designing a ThT-binding site in a "peptide self-assembly mimic" (PSAM) scaffold. PSAMs are engineered water-soluble proteins that mimic a segment of beta-rich peptide self-assembly, and they are amenable to standard biophysical techniques and systematic mutagenesis. The PSAM beta-sheet contains rows of repetitive amino acid patterns running perpendicular to the strands (cross-strand ladders) that represent a ubiquitous structural feature of fibril-like surfaces. We successfully designed a ThT-binding site that recapitulates the hallmarks of ThT-fibril interactions by constructing a cross-strand ladder consisting of contiguous tyrosines. The X-ray crystal structures suggest that ThT interacts with the beta-sheet by docking onto surfaces formed by a single tyrosine ladder, rather than in the space between adjacent ladders. Systematic mutagenesis further demonstrated that tyrosine surfaces across four or more beta-strands formed the minimal binding site for ThT. Our work thus provides structural insights into how this widely used dye recognizes a prominent subset of peptide self-assemblies, and proposes a strategy to elucidate the mechanisms of fibril-ligand interactions.


Reduction of enteric microbes in flushed swine wastewater treated by a biological aerated filter and UV irradiation.
An aerobic biofilter system was studied to assess its effectiveness for reducing enteric microbial indicators in flushed swine wastewater under different seasonal conditions. A laboratory-scale, low-pressure UV collimated beam apparatus was used to investigate the effectiveness of UV irradiation for inactivating enteric bacteria, coliphages, and bacterial spores in treated and untreated swine wastewater having unfiltered absorbances of 5 to 11 cm(-1) and total suspended solids concentrations of 500 to 1200 mg/L. Fecal coliforms, Escherichia coli, enterococci, somatic coliphages, and male-specific coliphages were reduced by 97 to 99% in the biofilter system when reactor water temperatures were between 23 and 32 degrees C. Salmonella were reduced by 95 to 97% when water temperatures were 17 to 32 degrees C. Of the six microbial indicators studied. Clostridium perfringens spores were typically reduced the least by the biofilter system. At an average absorbed UV irradiation dose of 13 mJ/cm2, maximum reductions of fecal coliforms, E. coli, enterococci, C. perfringens spores, and somatic coliphages in biofilter system effluent were 2.2, 2.1, 1.3, 0.2, and 2.3 log10, respectively. The results of this study show that the aerobic biofilter system can be an effective alternative for treatment of flushed swine waste. Ultraviolet irradiation can be effective for further reducing enteric microbe concentrations in biologically-treated swine waste, as well as in lower quality wastewaters, indicating its general potential for pathogen reductions in low-quality wastewaters intended for beneficial reuse.


Using ST2 in cardiovascular patients: a review.
Biomarkers have emerged as indispensable tools for diagnosis and prognostication in a variety of cardiovascular diseases, and several are now standard of care. New markers are constantly being developed, but few are able to significantly improve upon already established markers. ST2 is a marker of cardiomyocyte stress and fibrosis, which provides incremental value to natriuretic peptides for risk stratification of patients across a wide spectrum of cardiovascular diseases. Based upon the totality of data, measurement of ST2 is now recommended for additive risk stratification in patients with acute or ambulatory heart failure in the 2013 American College of Cardiology Foundation and American Heart Association joint guidelines. Looking forward, ST2 levels may be useful for tailoring medical therapy in those with or at risk for developing heart failure. This paper provides an up-to-date overview of the clinical studies that led to the endorsement of ST2 as a cardiovascular prognostic marker, and provides insight into the application of ST2 now and in the future.


Rose: generating sequence families.
We present a new probabilistic model of the evolution of RNA-, DNA-, or protein-like sequences and a software tool, Rose, that implements this model. Guided by an evolutionary tree, a family of related sequences is created from a common ancestor sequence by insertion, deletion and substitution of characters. During this artificial evolutionary process, the 'true' history is logged and the 'correct' multiple sequence alignment is created simultaneously. The model also allows for varying rates of mutation within the sequences, making it possible to establish so-called sequence motifs. The data created by Rose are suitable for the evaluation of methods in multiple sequence alignment computation and the prediction of phylogenetic relationships. It can also be useful when teaching courses in or developing models of sequence evolution and in the study of evolutionary processes. Rose is available on the Bielefeld Bioinformatics WebServer under the following URL: http://bibiserv.TechFak.Uni-Bielefeld.DE/rose/ The source code is available upon request. firstname.lastname@example.com


[The under-five mortality rate and the causes of death in Zhejiang Province between 2000 and 2009].
To study the under-five mortality rate and the causes of death in Zhejiang Province between 2000 and 2009 in order to provide a basis for reducing the mortality rate in the region. By stratified random cluster sampling, all the children under 5 years old from 30 sampling areas of Zhejiang Province between 2000 and 2009 were enrolled. The under-five mortality rate and the leading causes of death were investigated by descriptive analysis and Chi-square test. The under-five mortality rate demonstrated a decreased trend in Zhejiang Province between 2000 and 2009, with the under-five mortality rate of 14.83‰ in 2000 compared to 9.49‰ in 2009. In 2009, the under-five mortality rate in rural regions was significantly higher than that in urban regions (9.14‰ vs 6.50‰; P<0.01). Compared with the resident population, there were an increased under-five mortality rate in floating population (12.12‰ vs 6.42‰; P<0.01). Preterm delivery/low birth weight was the top death cause in children under 5 years old. The top three causes of death in infants less than 1 year old were preterm delivery/low birth weight, congenital heart disease and birth asphyxia compared to drowning, traffic accident and falling in children aged 1-4 years. There are differences in the under-five mortality rate between rural and urban children as well as between the floating and resident population in 2009. The leading causes of death in different age groups are different. It is essential to reduce the mortality rate by preventing preterm delivery, low birth weight and congenital malformations to infants and preventing accidental injuries to children aged 1-4 years.


Random walk in two-dimensional self-affine random potentials: strong-disorder renormalization approach.
We consider the continuous-time random walk of a particle in a two-dimensional self-affine quenched random potential of Hurst exponent H>0 . The corresponding master equation is studied via the strong disorder renormalization procedure introduced in Monthus and Garel [J. Phys. A: Math. Theor. 41, 255002 (2008)]. We present numerical results on the statistics of the equilibrium time t(eq) over the disordered samples of a given size L x L for 10 < or = L< or = 80. We find an "infinite disorder fixed point," where the equilibrium barrier Gamma(eq) identical with t(eq) scales as Gamma(eq)=L(H)u where u is a random variable of order O(1). This corresponds to a logarithmically slow diffusion |r(t)-r(0)| approximately (ln t)(1/H) for the position r(t) of the particle.


Predictors of intention to use condoms among Chinese college students.
China is experiencing one of the fastest growing human immunodeficiency virus (HIV) epidemics in the world. Condom use is consistently low among Chinese college students. The purpose of this study was to identify the predictors that determine the intention to use condoms among Chinese college students applying the theory of planned behavior (TPB). A non-probability convenience sample of 433 participants was drawn from three universities in Central, Eastern, and Southwestern China, respectively. An anonymous written questionnaire was self-administered. Data were collected and analyzed descriptively and statistically using Predictive Analytical Software 19.0. Multiple linear regression was performed to identify the predictors among 402 participants with non-missing data. Eighteen percent (78/433) of the participants reported being sexually active in the past 6 months. The percentage of times these individuals reported using condoms during intercourse was 38.19%. Intention to use condoms was statistically significantly (R(2) = 50.4%) predicted by attitudes (β = 0.213), subjective norms (β = 0.259), and perceived behavior control (PBC) (β = 0.332). All predictors were statistically significant at the 0.001 level (p < 0.001). PBC was the strongest predictor of intention to use condoms. The study findings indicated that the TPB could be used as a framework to determine the predictors of intention to use condoms among the Chinese college students. It is recommended that the HIV education programs should increase the intention to use condoms through promoting positive attitudes, subjective norms and PBC of condom use in Chinese college students.


β-Lapachone and Paclitaxel Combination Micelles with Improved Drug Encapsulation and Therapeutic Synergy as Novel Nanotherapeutics for NQO1-Targeted Cancer Therapy.
β-Lapachone (LPC) is a novel cytotoxic agent that is bioactivated by NADP(H): quinone oxidoreductase 1 (NQO1), an enzyme elevated in a variety of tumors, such as non-small cell lung cancer (NSCLC), pancreatic cancer, liver cancer, and breast cancer. Despite its unique mechanism of action, its clinical evaluation has been largely hindered by low water solubility, short blood half-life, and narrow therapeutic window. Although encapsulation into poly(ethylene glycol)-b-poly(D,L-lactic acid) (PEG-PLA) micelles could modestly improve its solubility and prolong its half-life, the extremely fast intrinsic crystallization tendency of LPC prevents drug loading higher than ∼2 wt %. The physical stability of the LPC-loaded micelles is also far from satisfactory for further development. In this study, we demonstrate that paclitaxel (PTX), a front-line drug for many cancers, can provide two functions when coencapsulated together with LPC in the PEG-PLA micelles; first, as a strong crystallization inhibitor for LPC, thus to significantly increase the LPC encapsulation efficiency in the micelle from 11.7 ± 2.4% to 100.7 ± 2.2%. The total drug loading efficiency of both PTX and LPC in the combination polymeric micelle reached 100.3 ± 3.0%, and the drug loading density reached 33.2 ± 1.0%. Second, the combination of LPC/PTX demonstrates strong synergistic cytotoxicity effect against the NQO1 overexpressing cancer cells, including A549 NSCLC cells, and several pancreatic cancer cells (combination index <1). In vitro drug release study showed that LPC was released faster than PTX either in phosphate-buffered saline (PH = 7.4) or in 1 M sodium salicylate, which agrees with the desired dosing sequence of the two drugs to exert synergistic pharmacologic effect at different cell checkpoints. The PEG-PLA micelles coloaded with LPC and PTX offer a novel nanotherapeutic, with high drug loading, sufficient physical stability, and biological synergy to increase drug delivery efficiency and optimize the therapeutic window for NOQ1-targeted therapy of cancer.


Wild animal and zoonotic disease risk management and regulation in China: Examining gaps and One Health opportunities in scope, mandates, and monitoring systems.
Emerging diseases of zoonotic origin such as COVID-19 are a continuing public health threat in China that lead to a significant socioeconomic burden. This study reviewed the current laws and regulations, government reports and policy documents, and existing literature on zoonotic disease preparedness and prevention across the forestry, agriculture, and public health authorities in China, to articulate the current landscape of potential risks, existing mandates, and gaps. A total of 55 known zoonotic diseases (59 pathogens) are routinely monitored under a multi-sectoral system among humans and domestic and wild animals in China. These diseases have been detected in wild mammals, birds, reptiles, amphibians, and fish or other aquatic animals, the majority of which are transmitted between humans and animals via direct or indirect contact and vectors. However, this current monitoring system covers a limited scope of disease threats and animal host species, warranting expanded review for sources of disease and pathogen with zoonotic potential. In addition, the governance of wild animal protection and utilization and limited knowledge about wild animal trade value chains present challenges for zoonotic disease risk assessment and monitoring, and affect the completeness of mandates and enforcement. A coordinated and collaborative mechanism among different departments is required for the effective monitoring and management of disease emergence and transmission risks in the animal value chains. Moreover, pathogen surveillance among wild animal hosts and human populations outside of the routine monitoring system will fill the data gaps and improve our understanding of future emerging zoonotic threats to achieve disease prevention. The findings and recommendations will advance One Health collaboration across government and non-government stakeholders to optimize monitoring and surveillance, risk management, and emergency responses to known and novel zoonotic threats, and support COVID-19 recovery efforts.


Comparison of intraoperative completion flowmeter versus duplex ultrasonography and contrast arteriography for carotid endarterectomy.
Intraoperative completion studies of the internal carotid artery following carotid endarterectomy are recommended to ensure technical perfection of the repair. Transit time ultrasound flowmeter does not require trained technicians, requires less time than other completion studies such as duplex ultrasonography and contrast arteriography, and is noninvasive. Flowmetry was compared with duplex ultrasonography and contrast arteriography to determine if the relatively simpler flowmetry could replace these two more widely accepted completion studies in the intraoperative assessment of carotid endarterectomy. Comparative intraoperative assessment was performed in 116 carotid endarterectomies using all three techniques between December 1, 2000 and November 30, 2003. Eversion endarterectomy was performed in 51 cases and standard endarterectomy with prosthetic patching in 65 cases. Patients underwent completion flowmetry, duplex ultrasonography, and contrast arteriography studies of the exposed arteries, which were performed by vascular fellows or senior surgical residents under direct supervision of board-certified vascular surgeons. Duplex ultrasonography surveillance was performed 1 and 6 months postoperatively and annually thereafter. Mean follow-up was 18 months (range, 6-42 months). The combined ipsilateral stroke and death rate was 0%. The mean internal carotid artery flow using flowmetry was 249 mL/min (range, 60-750 mL/min). Five (4.3%) patients had flow < 100 mL/min as measured with flowmetry, but completion contrast arteriography and duplex ultrasonography were normal and none of the arteries were re-explored. One carotid endarterectomy was re-explored based on completion duplex ultrasonography that showed markedly elevated internal carotid artery peak systolic velocity (> 500 cm/sec); however, exploration was normal and completion flowmetry and contrast arteriography were normal. Duplex ultrasonography studies revealed internal carotid artery peak systolic velocities > 150 cm/sec in 15 patients, but flowmetry and contrast arteriography were normal in all 15 cases and none of the arteries were re-explored. There was no correlation between flow rates measured using flowmetry and peak systolic velocities measured using duplex ultrasonography. One abnormal contrast arteriogram showed an intimal flap that was revised, but duplex ultrasonography and flowmetry were normal. Severe recurrent internal carotid artery stenosis developed in 2 patients at 6 and 9 months, but all 3 completion intraoperative studies at the time of the original operation were normal. Based on these results, wide variability in flowmetry values limits its potential usefulness to detect non-flow-limiting lesions and replace contrast arteriography or duplex ultrasonography as an intraoperative carotid endarterectomy completion study. Duplex ultrasonography was also of limited to no value, whereas contrast arteriography rarely documented a lesion that required repair.


Evolution of the cAMP-dependent protein kinase (PKA) catalytic subunit isoforms.
The 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase, or protein kinase A (PKA), pathway is one of the most versatile and best studied signaling pathways in eukaryotic cells. The two paralogous PKA catalytic subunits Cα and Cβ, encoded by the genes PRKACA and PRKACB, respectively, are among the best understood model kinases in signal transduction research. In this work, we explore and elucidate the evolution of the alternative 5' exons and the splicing pattern giving rise to the numerous PKA catalytic subunit isoforms. In addition to the universally conserved Cα1/Cβ1 isoforms, we find kinase variants with short N-termini in all main vertebrate classes, including the sperm-specific Cα2 isoform found to be conserved in all mammals. We also describe, for the first time, a PKA Cα isoform with a long N-terminus, paralogous to the PKA Cβ2 N-terminus. An analysis of isoform-specific variation highlights residues and motifs that are likely to be of functional importance.


The reentry process of adolescents.
The authors have been able to follow up on a number of residents over the years. Most of them have frequently referred to the helpfulness of the seminars during their reentry phase. Some have sought out private counseling once they felt problems cropping up. While there is no abundance of jobs awaiting the adolescent graduate, they must be prepared to the best of their, and the TC's, ability to confront the world. TCs need to provide them with the ability and skills to cope with the many realities they will be called on to face. A serious review of the adolescent TC process is called for, with greater emphasis on teaching, training and role modeling. TCs need to evolve more skill-training seminars in conjunction with community agencies and resources. Further training of TC staff is needed to strengthen their vulnerabilities and understand their own relationships with adolescent clients. Too many have lost touch with what it was like to be a frightened young adult. Unless more serious attention is paid to adolescent reentry candidates, TCs will find themselves being criticized for turning out incomplete graduates: graduates whose lifestyles have been behaviorally modified, but whose impoverished value systems have not been attended to. One without the other is programming clients for eventual recidivism and TCs for failure.


[Local anesthetic properties of a polymeric compound of trimecaine].
Original techniques were used in experiments on rabbits and rats to explore the activity and duration of a local anesthetic action of a new trimecaine polymer as compared with trimecaine hydrochloride. The polymer effect was found to be 1.5-2 times longer as compared to that of its low-molecular analog, which was discovered in experimental terminal, conduction and infiltration anesthesia in particular. According to the data obtained, the prolongation of the effect of the new drug is determined by slow separation of trimecain from the polymer.


Surgical treatment of tricuspid atresia.
From April 1984 to July 1989, 6 consecutive patients underwent an orthoterminal repair for classical tricuspid atresia (TA). Their ages ranged from 6 to 14 years with a mean of 8.3 years. Four patients had ventriculoarterial concordance (VA-con) and 2 had ventriculoarterial discordance (VA-dis). One patient with VA-dis underwent a total cavopulmonary connection. The other five patients had modified Fontan operation. All 6 patients survived the operation. At a mean follow-up of 28 months, all patients were in the New York Heart Association Functional Class I. A follow-up color Doppler echocardiogram showed that the forward pulmonary flow was mainly during the ventricular diastolic phase except in one case. In this case, a tripartite right ventricle (RV) could be identified by angiocardiogram 4.5 years after the atrioventricular (A-V) connection without obliteration of the trabecular portion. A big "V" wave was demonstrated in the RV and pulmonary trunk. The pulmonary valve was closed in the ventricular diastolic phase. In the other case with an A-V connection and obliteration of the trabecular portion, revealed a fixed-open pulmonary valve with a forward flow more in the atrial systolic phase than in the ventricular systolic phase. The graded exercise test in these 2 patients with an A-V connection revealed a normal functional capacity. The mean maximal oxygen uptake was 8.4 +/- 0.1 METS. In the other 3 children without an A-V connection the mean maximal oxygen uptake was 6.6 +/- 0.5 METS. We concluded that the Fontan-like repair was the procedure of choice for TA, and that excellent surgical results could be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of Indole-3-Butyric Acid (IBA) and rooting media on rooting and survival of air layered wax apple (Syzygium samarangense) CV Jambu Madu.
The wax apple or jambu madu, is a non-climacteric tropical fruit from Myrtaceae family and widely cultivated in South East Asia. The limited availability of good quality seedlings of wax apple is the main problem to development of flourish it's market share in the current fruit industry. Therefore, in order to produce good quality planting materials, a study aimed at optimizing propagation and adventitious rooting technique and survivability of wax apple air layer was conducted. In this study, four different levels of Indole-3-Butyric Acid (IBA) concentration (0, 1000, 1500 and 2000 mg L-1) and three rooting media (sphagnum moss, vermicompost and garden soil) were applied after removal of bark (phloem) on the shoot to determine the effect on rooting and survivability of the wax apple air layer under field conditions. The results showed that the wax apple shoots treated with 2000 mg L-1 IBA produced the significantly higher number of roots, increased length of root, diameter of branch, length of branch, number of leaf and leaf area of air layers. In addition, the highest chlorophyll content and stomatal aperture were recorded in 2000 mg L-1 IBA treatment compared to other treatments including control. Vermicompost medium was better than garden soil and sphagnum moss in respect of rooting and survivability of air layers. The results showed that the combination of 2000 mg L-1 IBA and vermicompost as rooting media give the best combination to root initiation, root number, root length and survival rate (100%) of wax apple air layers. From this study, it can be concluded that 2000 mg L-1 IBA and vermicompost treatment enhance the root initiation, early establishment and survivability of wax apple air layered under field conditions.


Spatially and temporally regulated expression of the MADS-box gene AGL2 in wild-type and mutant arabidopsis flowers.
AGL2 is one of several Arabidopsis floral MADS-box genes that were isolated based on sequence similarity to the homeotic gene AGAMOUS. To investigate its possible role in flower development, we have characterized in detail the expression pattern of AGL2 in both wild-type and mutant flowers using RNA in situ hybridization. We find that AGL2 is floral-specific; it is not expressed in the inflorescence meristem. Within the floral meristem, AGL2 is first expressed very early in development, after the floral meristem has emerged from the inflorescence meristem but before any of the organ primordia emerge. The AGL2 transcript is very abundant and uniform throughout the floral meristem and in the primordia of all four floral organs: sepals, petals, stamens and carpels. Thus, AGL2 represents a new class of MADS-box genes which is expressed in all four whorls of the flower. The AGL2 transcript remains abundant in each organ during morphological differentiation, but diminishes as each organ undergoes the final maturation phase of development. AGL2 expression is high in developing ovules and, after fertilization, in developing embryos and seed coats, abating as seeds mature. In the floral organ identity mutants ag-1, ap3-3 and ap2-2, the AGL2 expression pattern is organ- and stage-dependent. These results indicate that AGL2 may play a fundamental role in the development of all floral organs, and of seeds and embryos, and that AGL2 ultimately depends upon the organ identity genes for proper expression.


Dexamethasone alleviates allergic asthma immature rat through Toll like receptor 4.
The allergic asthma model induced by ovalbumin (OVA) was established in the immature rat. Dexamethasone (DXM) was adopted for intervention to analyze the treatment effect and to explore the relationship with toll-like receptor 4 (TLR4). Immature SD rat was treated by OVA to construct allergic asthma model and intervened by DXM. The rats were randomly divided into model group, experimental group, and control group. The changes in lung tissue were observed by light microscope. The EOS infiltration and reactivity of airway wall were compared. The expressions of TLR2 and TLR4 protein and mRNA in the lung tissue were tested by Western blot and RT-PCR. The lung tissue in the model group was infiltrated by a lot of inflammatory cells, and mucous membrane edema was observed, compared with that in the control group. There were only a few inflammatory cells in the interstitial tissue and pulmonary alveoli in the experimental group compared with that in the model group. EOS count of airway wall and airway reactivity decreased in the experimental group. The levels of TLR2 and TLR4 were significantly elevated in the third week compared with the first week (p<0.05). The treatment of DXM can alleviate the pathological changes of the lung tissue in SD immature rat with allergic asthma, reduce EOS infiltration in the airway wall, decrease airway reactivity, and elevate expressions of TLR2 and TLR4.


A femtosecond time-resolved investigation of dual fluorescence from N6,N6-dimethyladenine.
The excited electronic state dynamics of N(6),N(6)-dimethyladenine (DMAde), a molecule known to emit dual fluorescence, has been studied in aqueous solution using femtosecond fluorescence up-conversion spectroscopy. Time profiles of the fluorescence of DMAde excited at lambda= 258 nm were measured at a series of wavelengths in the range 320 nm <or=lambda(fl)<or= 650 nm. At wavelengths in the near UV (lambda(fl)<or= 420 nm), the time profiles were dominated by a very short-lived decay component with a lifetime between 0.2 ps <or=tau(1)<or= 0.6 ps, depending on the detection wavelength. Two other components with lifetimes of tau(2) approximately 3.5 ps and tau(3) approximately 60 ps gave minor contributions. In the emission observed at longer wavelengths (lambda(fl)>or= 500 nm), which appeared slightly delayed compared to the UV fluorescence, the long-lived fluorescence component (tau(3)) dominated, the second component (tau(2)) disappeared. The results are consistent with the assumption that DMAde is primarily excited to a short-lived local excited (LE) electronic state that fluoresces mostly in the UV and decays rapidly, on a approximately 0.5 ps timescale, to an intramolecular charge transfer (ICT) state that emits only at longer wavelengths in the visible spectrum. The fluorescence-time profiles and transient fluorescence spectra reconstructed from the time profiles provided further information on secondary relaxation processes within and between the excited states and their non-radiative relaxation to the electronic ground state.


Relationships between body weight, fasting blood glucose concentration, sex and age in tree shrews (Tupaia belangeri chinensis).
The tree shrew (Tupaia belangeri chinensis) is a squirrel-like lower primate or a close relative of primates, commonly used as an animal model in biomedical research. Despite more than three decades of usage in research, the clear relationships between body weight, fasting blood glucose concentration, sex and age among tree shrews remain unclear. Based on an investigation of 992 tree shrews (454 males and 538 females) aged between 4 months and 4 years old, we found that male tree shrews have significantly higher body weight and fasting blood glucose concentration than female tree shrews (p < 0.001). The concentration of fasting blood glucose slightly increased with body weight in males (r = 0.152, p < 0.001). Meanwhile, in females, the body weight, concentration of fasting blood glucose and waist circumference positively increased with age (p < 0.001). Additionally, 17 tree shrews with Lee index [body weight (g)*0.33*1000/body length (cm)] above 290 had significantly higher body weight, waist circumference and glycated haemoglobin A1c (HbA1c) than non-obese tree shrews with a Lee index score below 290 (p < 0.001). Interestingly, 6 of 992 tree shrews (three males and three females, 2-4 years old) displayed impaired plasma triglycerides, HbA1c, low-density lipoprotein and oral glucose tolerance test, suggestive of the early symptoms of metabolic syndrome. This study provides the first clear relationships between body weight, fasting blood glucose concentration, sex and age in tree shrews, further improving our understanding of this relationship in metabolic syndrome (MetS). Given the similarity of tree shrews to humans and non-human primates, this finding supports their potential use as an animal model in the research of MetS.


Surgical orthodontics.
The article reviews some commonly used orthodontic treatments as well as new strategies to assist in the correction of malocclusion. Many techniques are used in conjunction with surgical intervention and are a necessary compliment to orthognathic surgery. Basic knowledge of these practices will aid in the surgeon's ability to adequately treat the patient. Many orthodontists and surgeons are eliminating presurgical orthodontics to adopt a strategy of 'surgery first' orthodontics in orthognathic surgery. This has the benefit of immediate improvement in facial aesthetics and shorter treatment times. The advent of virtual surgical planning has helped facilitate the development of this new paradigm by making surgical planning faster and easier. Furthermore, using intraoperative surgical navigation is improving overall precision and outcomes. A variety of surgical and nonsurgical treatments may be employed in the treatment of malocclusion. It is important to be familiar with all options available and tailor the patient's treatment plan accordingly. Surgery-first orthodontics, intraoperative surgical navigation, virtual surgical planning, and 3D printing are evolving new techniques that are producing shorter treatment times and subsequently improving patient satisfaction without sacrificing long-term stability.


Partial Body Mass Recovery After Caloric Restriction Abolishes Improved Glucose Tolerance in Obese, Insulin Resistant Rats.
Caloric restriction, among other behavioral interventions, has demonstrated benefits on improving glycemic control in obesity-associated diabetic subjects. However, an acute and severe intervention without proper maintenance could reverse the initial benefits, with additional metabolic derangements. To assess the effects of an acute caloric restriction in a metabolic syndrome model, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without a 10-day body mass (BM) recovery period, along with their respective ad libitum controls. An oral glucose tolerance test (oGTT) was performed after CR and BM recovery. Both strains had higher rates of mass gain during recovery vs. ad lib controls; however, the regain was partial (ca. 50% of ad lib controls) over the measurement period. Retroperitoneal and epididymal adipose masses decreased 30% (8.8 g, P < 0.001) in OLETF; however, this loss only accounted for 11.5% of the total BM loss. CR decreased blood glucose AUC 16% in LETO and 19% in OLETF, without significant decreases in insulin. Following CR, hepatic expression of the gluconeogenic enzyme, PEPCK, was reduced 55% in OLETF compared to LETO, and plasma triglycerides (TG) decreased 86%. Acute CR induced improvements in glucose tolerance and TG suggestive of improvements in metabolism; however, partial recovery of BM following CR abolished the improvement in glucose tolerance. The present study highlights the importance of proper maintenance of BM after CR as only partial recovery of the lost BM reversed benefits of the initial mass loss.


ZFC3H1 and U1-70K promote the nuclear retention of mRNAs with 5' splice site motifs within nuclear speckles.
Quality control of mRNA represents an important regulatory mechanism for gene expression in eukaryotes. One component of this quality control is the nuclear retention and decay of misprocessed RNAs. Previously, we demonstrated that mature mRNAs containing a 5' splice site (5'SS) motif, which is typically found in misprocessed RNAs such as intronic polyadenylated (IPA) transcripts, are nuclear retained and degraded. Using high-throughput sequencing of cellular fractions, we now demonstrate that IPA transcripts require the zinc finger protein ZFC3H1 for their nuclear retention and degradation. Using reporter mRNAs, we demonstrate that ZFC3H1 promotes the nuclear retention of mRNAs with intact 5'SS motifs by sequestering them into nuclear speckles. Furthermore, we find that U1-70K, a component of the spliceosomal U1 snRNP, is also required for the nuclear retention of these reporter mRNAs and likely functions in the same pathway as ZFC3H1. Finally, we show that the disassembly of nuclear speckles impairs the nuclear retention of reporter mRNAs with 5'SS motifs. Our results highlight a splicing independent role of U1 snRNP and indicate that it works in conjunction with ZFC3H1 in preventing the nuclear export of misprocessed mRNAs by sequestering them into nuclear speckles.


COVID-19 pandemic in Economic Community of West African States (ECOWAS) region: implication for capacity strengthening at Point of Entry.
Free movement between countries without a visa is allowed within the 15-country Economic Community of West African States (ECOWAS) region. However, little information is available across the region on the International Health Regulation (IHR 2005) capacities at points of entry (PoE) to detect and respond appropriately to public health emergencies such as Coronavirus Disease 2019 (COVID-19). ECOWAS and the member states can better tailor border health measures across the region by understanding public health strengths and priorities for improvement at PoEs. A comprehensive literature review was combined with a self-assessment of capacities at PoEs across the fifteen member states from February to July 2020. For the assessment, the member states completed an adapted World Health Organization (WHO) self-assessment checklist by classifying capacity for seven domains as fully, partially, or not implemented. The team implemented three focus group discussion (FGD) sessions and 13 key informant interviews (KII) with national-level border health stakeholders. Univariate analysis was used to summarize the assessment data and detailed content analysis was applied to evaluate FGD and KII results. Of the 15 member states, 3 (20%) are landlocked; 3 (20%) have more than one seaport. Eleven (73%) countries have 1 designated airport, 3 (20%) have two airports, and only one country (6.7%) has three airports. Two hundred and seventy-eight designated ground crossings were identified in 12 countries (80%). Strengths across the PoE were existence of decrees and ministerial acts in some ECOWAS countries and establishment of national taskforces for the COVID-19 response at PoE in ECOWAS. Major challenges were porous borders, poor intersectoral coordination, lack of harmonized traveler screening measures, shortage of staff, and inadequate financial resources. Despite all these challenges, there are opportunities such as leveraging the regional cross-border poliomyelitis coordination and control mechanism, and existence of networks of infection prevention and control specialists and field epidemiologists. However, political instabilities in some countries pose a threat to government commitments to PoE activities. The capacity to respond to public health emergencies at PoE in the ECOWAS region is still below IHR standard. Public health capacities at a majority of IHR-designated PoE in the 15-country region do not meet required core capacities standards.


[Idiopathic hypercalciuria. Diagnosis and treatment].
Most patients with idiopathic hypercalciuria and calcium nephrolithiasis have a family history of the disease. Idiopathic hypercalciuria is a metabolic abnormality with various causes and developmental pathways. The systematic review describes specific mutations associated with idiopathic hypercalciuria and nephrolithiasis. Detection of these mutations may provide a better understanding of the pathogenesis of this heterogeneous disease and personalize patient management depending on the detected polymorphisms. A promising treatment option for a mutation in the vitamin D receptor gene is thiazide diuretics in combination with bisphosphonates. Among bisphosphonates, the drug of choice which has been most strongly supported by research evidence is alendronate.


Evaluation of Oversized Drilling on Implant Survival and Stability Versus Traditional Drilling Technique: A Randomized Clinical Trial.
This study aimed to investigate the influence of oversized drilling on the stability of the implant and the bone response during osseointegration. The trial was designed as a prospective, parallel-group randomized controlled clinical trial with 20 implants placed in the posterior region of the maxilla. The sample size was divided into two groups, 10 each, with implants being placed with manufacturer-recommended implant osteotomy preparation according to the manufacturer guidelines in one group (MR group) vs oversized osteotomy preparation (3 to 5 mm) in the other group (oversized drilling [OD] group). The implant stability was monitored for 3 months by means of resonance frequency analysis, while the crestal bone levels were recorded using parallel technique periapical radiography for 6 months. Patient-reported outcomes including pain, swelling, satisfaction, and implant survival were all monitored throughout the study. In the MR group, a mean decrease in implant stability quotient (ISQ) values was detected during the first 4 weeks, after which a gradual increase in values was recorded. In comparison, the OD group showed a rapid increase in ISQ value over the entire follow-up period from baseline and up to week 12. Regarding crestal bone level, follow-up showed a significant difference when comparing baseline and 6-month radiographs (P = .00) between the OD group, 0.908 mm ± 0.343, and the MR group, 1.3 ± 0.23 mm. Within the limitations of this study, the results suggest that the oversized osteotomy technique may lead to earlier implant stability and postsurgical recovery compared with the manufacturer-recommended technique for osteotomy preparation. However, further studies are needed to confirm these findings.


Red blood cell metallothionein as an indicator of zinc status during pregnancy.
We describe the levels and patterns of change in red blood cell (RBC) metallothionein (MT) during pregnancy and the neonate and relate RBCMT to other indicators of zinc and iron status. As part of a double-masked controlled trial of prenatal zinc supplementation among 242 Peruvian pregnant women, we determined RBCMT at enrollment (10-16 wk), at 28 and 36 wk of gestation, and in the cord blood at delivery in 158 women (86 who received daily supplements containing 60 mg of iron and 250 microg of folic acid and 72 whose supplements also contained 25 mg of zinc). In addition, we measured plasma and urinary zinc concentrations, hemoglobin and serum ferritin, and, on a limited sample, RBC zinc and placental MT. RBCMT increased during pregnancy, and levels in the cord blood approximated maternal values at 36 wk. Only RBC zinc at 36 wk differed by supplement type (P < 0.05). Increases in RBCMT over pregnancy were, however, related to early pregnancy RBC zinc and inversely with the decline in plasma zinc from baseline to 36 wk of gestation. Changes in RBCMT throughout pregnancy were consistent with the hypothesized role of MT in regulating zinc homeostasis. RBCMT appears to not be responsive during pregnancy to changes in zinc status achieved with supplements.


Expression, Purification, Crystallization and Preliminary X-ray Diffraction Analysis of the Mutant Pro(229)Ser of Thermostable Catechol 2,3-dioxygenase.
The mutant Pro(229)Ser of thermostable catechol 2,3-dioxygenase (TC23O) was expressed and purified. Enzymatic analysis revealed that its thermostability was decreased, the temperature corresponding to 50% enzyme activity being about 10.2 degrees lower than that of the wild type TC23O. Its kinetic parameter k(cat)/K(m) value (4.89x 10(6) mol(-1).s(-1)) was lower than that of the wild type TC23O(6.97x10(6) mol(-1).s(-1)). By the hanging-drop vapor-diffusion method using polyethylene glycol 400 as a precipitant, the mutant Pro(229)Ser of TC23O crystallizedat 4 degrees. X-ray diffraction analysis revealed that the crystals belong to the orthorhombic space group I(222) with unit-cell parameters a 7.059 nm, b 7.415 nm, c 13.311 nm, and they diffracted to at least 0.24 nm resolution. Assuming the presence of 2 molecules of the mutant Pro(229)Ser in the asymmetric unit, the Matthews parameter (Vm) was calculated to be 2.49x10( 3) nm(3).D(-1), and the solventcontent was about 51%. The crystal structure determination is now in progress.


[The Rehberg-Tareev test in assessing the glomerular filtration rate].
The history of glomerular filtration rate assessment is presented, an important step of which was the glomerular filtration rate evaluation by the endogenous creatinine clearance (known as the RehbergTareev test). The article highlights the diagnostic value of the RehbergTareev test and its place among modern methods for assessing glomerular filtration rate.


Sphere-shaped hierarchical cathode with enhanced growth of nanocrystal planes for high-rate and cycling-stable li-ion batteries.
High-energy and high-power Li-ion batteries have been intensively pursued as power sources in electronic vehicles and renewable energy storage systems in smart grids. With this purpose, developing high-performance cathode materials is urgently needed. Here we report an easy and versatile strategy to fabricate high-rate and cycling-stable hierarchical sphered cathode Li(1.2)Ni(0.13)Mn(0.54)Co(0.13)O2, by using an ionic interfusion method. The sphere-shaped hierarchical cathode is assembled with primary nanoplates with enhanced growth of nanocrystal planes in favor of Li(+) intercalation/deintercalation, such as (010), (100), and (110) planes. This material with such unique structural features exhibits outstanding rate capability, cyclability, and high discharge capacities, achieving around 70% (175 mAh g(-1)) of the capacity at 0.1 C rate within about 2.1 min of ultrafast charging. Such cathode is feasible to construct high-energy and high-power Li-ion batteries.


Speckled lentiginous naevus: which of the two disorders do you mean?
Speckled lentiginous naevus (synonym: naevus spilus) no longer represents one clinical entity, but rather, two different disorders can be distinguished. Naevus spilus maculosus is consistently found in phacomatosis spilorosea, whereas naevus spilus papulosus represents a hallmark of phacomatosis pigmentokeratotica. The macular type is characterized by dark speckles that are completely flat and rather evenly distributed on a light brown background, resembling a polka-dot pattern. In contrast, naevus spilus papulosus is defined by dark papules that are of different sizes and rather unevenly distributed, reminiscent of a star map. Histopathologically, the dark spots of naevus spilus maculosus show a 'jentigo' pattern and several nests of melanocytes involving the dermoepidermal junction at the tips of the papillae, whereas most of the dark speckles of naevus spilus papulosus are found to be dermal or compound melanocytic naevi. The propensity to develop Spitz naevi appears to be the same in both types of speckled lentiginous naevus, whereas development of malignant melanoma has been reported far more commonly in naevus spilus maculosus.


ENHANCING THE RETRDEVABILITY OF POPULATION GENETIC SURVEY DATA? AN ASSESSMENT OF ANIMAL MITOCHONDRIAL DNA STUDIES.
Surveys of genetic variation in natural populations represent a valuable and often irreplaceable resource. It may be desirable to reanalyze data as new methods are developed for comparisons with other populations or for comparisons with the same populations at different times. We evaluated existing mechanisms of data preservation in a survey of 627 published surveys of mitochondrial DNA variation in animal and found that over half of the datasets (56%) contained insufficient information for reanalysis. In many cases, publication of complete data would not have added excessively to the length of the publication. Because at present, publications represent the main archive of population genetic data, we offer recommendations for how the essential data from mtDNA surveys can be presented in a form that is complete and concise.


Melanoma and melanocytic nevi in pediatric patients: a single institution experience.
Melanoma is an infrequent neoplasm in children and adolescents. The number of consultancies for melanocytic nevi control in the pediatric population is increased by the major anxiety of parents and pediatricians. A retrospective chart review was performed in order to evaluate the incidence rate of melanoma, Spitz nevi, congenital and acquired melanocytic nevi in patients aged 14 years or less and referred to our institution from April 2010 to September 2015. A total of 32,755 dermatologic pediatric consultancies were performed in the considered 66 months period, including 4260 patients referred for mole control (13%). During the same period, a total of 5193 excisions of melanocytic lesions were performed (adults and pediatric patients), 259 of which were performed in 250 patients aged 14 years or less (4.98%). Only 1 in situ melanoma of the nail matrix was detected in a 12-year-old female patient (0.38% of surgical excisions). The number needed to excise (NNE) in our pediatric population, calculated by comparing the total number of excised lesions and the number of melanomas found, was 259. Our data leads to 3 major observations: 1) the rarity of melanoma in patients with 14 years of age or less is confirmed; 2) the number of excisions performed in this pediatric population is extremely high; 3) neither the cases of melanoma and atypical Spitz neoplasm (ASN) nor the majority of Spitz nevi were referred to us for a generic mole control. Mole controls in the pediatric population should be properly addressed, incrementing the attention on specific suspicious cutaneous lesions.


Perfect Detection of Spikes in the Linear Sub-threshold Dynamics of Point Neurons.
Spiking neuronal networks are usually simulated with one of three main schemes: the classical time-driven and event-driven schemes, and the more recent hybrid scheme. All three schemes evolve the state of a neuron through a series of checkpoints: equally spaced in the first scheme and determined neuron-wise by spike events in the latter two. The time-driven and the hybrid scheme determine whether the membrane potential of a neuron crosses a threshold at the end of the time interval between consecutive checkpoints. Threshold crossing can, however, occur within the interval even if this test is negative. Spikes can therefore be missed. The present work offers an alternative geometric point of view on neuronal dynamics, and derives, implements, and benchmarks a method for perfect retrospective spike detection. This method can be applied to neuron models with affine or linear subthreshold dynamics. The idea behind the method is to propagate the threshold with a time-inverted dynamics, testing whether the threshold crosses the neuron state to be evolved, rather than vice versa. Algebraically this translates into a set of inequalities necessary and sufficient for threshold crossing. This test is slower than the imperfect one, but can be optimized in several ways. Comparison confirms earlier results that the imperfect tests rarely miss spikes (less than a fraction 1/108 of missed spikes) in biologically relevant settings.


Current status and future prospects of array-based comparative genomic hybridisation.
The majority of human cancers as well as many developmental abnormalities harbour chromosomal imbalances, many of which result in the gain and/or loss of genomic material. Conventional comparative genomic hybridisation (CGH) has been used extensively to map DNA copy number changes to chromosomal positions. The introduction of microarray CGH provided a powerful tool to precisely detect and quantify genomic aberrations and map these directly onto the sequence of the human genome. In the past several years, a number of different approaches towards array-based CGH have been undertaken. This paper reviews these approaches and presents some of the recently-developed applications of this new technology in both research and clinical settings.


[Candidiasis in the experimental model of ulcerative colitis].
In the present study on animal model of ulcerative colitis the influence of fungal colonization on the severity of inflammatory lesions in the colon and the course of their healing was evaluated. The results of our studies revealed, that significant fungal colonization (over 10(4) CFU/ml) delayed ulcer healing in the colon. It corresponded with the decrease of colonic blood flow (CBF) in the region of lesions and increase of interleukin (IL)-1beta, tumor necrosis factor(TNF)-alpha level in the serum. Introduction of antifungal therapy (fluconazole) or probiotic in rats inoculated with Candida accelerated the process of ulcer healing in the colon, expressed through the reduction of macro- and microscopic lesions in the colon and decrease of MPO, IL-beta TNF-alpha serum level.


Multiantennary group-specific polysaccharide of group B Streptococcus.
The group-specific antigen of group B Streptococcus is composed of four different oligosaccharide units of Mw 766 (III), 1277 (II), 1462 (IV), and 1788 (I). The major constituent sugars of the oligosaccharides are alpha-L-rhamnopyranose, alpha-D-galactopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranosyl, and D-glucitol except that III does not contain alpha-D-galactopyranosyl or 2-acetamido-2-deoxy-beta-D-glucopyranosyl residues and IV contains no D-glucitol but has one additional beta-L-rhamnopyranosyl residue. The structures of II and III have been previously elucidated [Michon, F., Katzenellenbogen, E., Kasper, D. L., & Jennings, H. J. (1987) Biochemistry 26, 476-486]. In the group B antigen all the oligosaccharides are linked by one type of phosphodiester bond from O6 of the D-glucitol residue of one oligosaccharide to O6 of the alpha-D-galactopyranosyl residue of the next to form a complex and highly branched multiantennary structure. However, despite the heterogeneous nature of its component oligosaccharides, some order has been identified in the biosynthesis of the group B antigen from chemical and enzymatic sequence studies. Because III lacks an alpha-D-galactopyranosyl residue but has a D-glucitol residue, it is situated at the reducing terminus of all the branches of the group B antigen where it is always adjacent to a II moiety. Conversely, IV has an alpha-D-galactopyranosyl residue but has no D-glucitol and is therefore located at the reducing terminus of the group B antigen where it probably functions as a linker molecule between the group B polysaccharide and the cell wall peptidoglycan of the group B streptococcal organisms. Oligosaccharide I contains two alpha-D-galactopyranosyl residues and one D-glucitol residue and thus constitutes the branch point in the group B antigen, whereas II contains one of each of the above residues and therefore is situated in linear interchain positions. The group B antigen is highly branched and probably has a unique multiantennary structure.


Hypoxically inducible barley lactate dehydrogenase: cDNA cloning and molecular analysis.
In the roots of barley and other cereals, hypoxia induces a set of five isozymes of L-lactate dehydrogenase [LDH; (S)-lactate:NADH oxidoreductase, EC 184.108.40.206]. Biochemical and genetic data indicate that the five LDH isozymes are tetramers that arise from random association of the products of two Ldh loci. To investigate this system, cDNA clones of LDH were isolated from a lambda gt11 cDNA library derived from hypoxically treated barley roots. The library was screened with antiserum raised against barley LDH purified approximately 3000-fold by an improved three-step procedure. Immunopositive clones were rescreened with a cDNA probe synthesized by the polymerase chain reaction using primers modeled from the amino acid sequences of two tryptic LDH peptides. Two types of LDH clones were found. Nucleotide sequence analysis of one representative insert of each type (respectively, 1305 and 1166 base pairs) revealed open reading frames encoding 10 peptide fragments of LDH. The 1305-base-pair insert included the entire coding region of a 356-residue LDH monomer. The nucleotide sequences of the two LDH cDNAs were 92% identical in the coding region, but highly divergent in the 3' noncoding region, and thus probably correspond to the two postulated Ldh loci. The deduced amino acid sequences of the two barley LDHs were 96% identical to each other and very similar to those from vertebrate and bacterial LDHs. RNA blot hybridization showed a single mRNA band of 1.5 kilobases whose level rose about 8-fold in roots during hypoxic induction, as did the level of translatable LDH message.


Portal and systemic haemodynamic response to acute and chronic administration of low and high dose isosorbide-5-mononitrate in patients with cirrhosis.
Oral isosorbide-5-mononitrate (Is-5-Mn) was given in doses of 10 and 40 mg acutely and chronically (twice daily for four weeks), allowing a nitrate free interval to 25 patients with cirrhosis. Both 10 mg and 40 mg Is-5-Mn reduced the hepatic venous pressure gradient acutely and chronically, without evidence of tolerance. This was achieved by a reduction in the wedged hepatic venous pressure. The effect on mean azygos blood flow was variable with no significant mean change seen acutely or after chronic use with either dose. The variability was dependent not on the dose used but on the initial azygos flow; the flow in patients with initially low values increased and those with high azygos flows decreased after nitrate challenge. The development of the porto-collateral flow seems an important parameter in predicting haemodynamic response to Is-5-Mn.


[Urachal transitional cell carcinoma invading the sigmoid colon].
We report a patient with urachal transitional cell carcinoma invading the sigmoid colon. The diagnostic and therapeutic aspects of this disease are discussed. The literature is also reviewed. This 42-year-old man was admitted with the chief complaint of micturition pain. Operation consisting of total cystourethrectomy, excision of the urachus together with the umbilicus, pelvic lymphadenectomy, ilial conduit plasty, sigmoidectomy, and colorectostomy was performed on June 3, 1986, after the diagnosis of urachal carcinoma invading the sigmoid colon. A tumor the size of a hen's egg was found at the dome of the bladder extending to the sigmoid colon. The urachus 8 cm in length and 2 cm in diameter extended from the site of the tumor to the umbilicus. Histologically the tumor was a transitional cell carcinoma Grade III. The urachus was composed of epithelioid and muscle layers, and its lower end was filled with necrotic inflammatory debris so that the canal was obliterated; tumor cells infiltrated the muscle layer. No metastasis was found in lymphnodes. Combination therapy of 5 fluorouracil, adriamycin and cis-platinum was given after operation. He has returned to work and is doing well without evidence of metastasis or recurrence now at 1 year after the operation.


Fascin Activates β-Catenin Signaling and Promotes Breast Cancer Stem Cell Function Mainly Through Focal Adhesion Kinase (FAK): Relation With Disease Progression.
Cancer stem cells (CSCs), a rare population of tumor cells with high self-renewability potential, have gained increasing attention due to their contribution to chemoresistance and metastasis. We have previously demonstrated a critical role for the actin-bundling protein (fascin) in mediating breast cancer chemoresistance through activation of focal adhesion kinase (FAK). The latter is known to trigger the β-catenin signaling pathway. Whether fascin activation of FAK would ultimately trigger β-catenin signaling pathway has not been elucidated. Here, we assessed the effect of fascin manipulation in breast cancer cells on triggering β-catenin downstream targets and its dependence on FAK. Gain and loss of fascin expression showed its direct effect on the constitutive expression of β-catenin downstream targets and enhancement of self-renewability. In addition, fascin was essential for glycogen synthase kinase 3β inhibitor-mediated inducible expression and function of the β-catenin downstream targets. Importantly, fascin-mediated constitutive and inducible expression of β-catenin downstream targets, as well as its subsequent effect on CSC function, was at least partially FAK dependent. To assess the clinical relevance of the in vitro findings, we evaluated the consequence of fascin, FAK, and β-catenin downstream target coexpression on the outcome of breast cancer patient survival. Patients with coexpression of fascinhigh and FAKhigh or high β-catenin downstream targets showed the worst survival outcome, whereas in fascinlow, patient coexpression of FAKhigh or high β-catenin targets had less significant effect on the survival. Altogether, our data demonstrated the critical role of fascin-mediated β-catenin activation and its dependence on intact FAK signaling to promote breast CSC function. These findings suggest that targeting of fascin-FAK-β-catenin axis may provide a novel therapeutic approach for eradication of breast cancer from the root.


[Vogt-Koyanagi-Harada Disease: clinical features, therapy and long-term visual outcome in a Caucasian and African population].
Seventeen consecutive cases of Vogt-Koyanagi-Harada (VKH) disease were studied to determine their clinical profile. This was a retrospective study of 17 cases, in a white and African population. The sex ratio (female/male) was 1.6. Mean age was 37.65 +/- 10.2 years. Eight patients were Caucasian (47%), and seven were from North Africa (41%), and two were black Africans (12%). Eleven patients were referred during the acute stage, and six patients secondarily. All patients had bilateral ocular involvement. Panuveitis with retinal serous detachment was the most frequent presentation (88%). Extraocular signs were found in 87% of the cases. Initial visual acuity was 0.29 +/- 0.36, and final visual acuity was 0.78 +/- 0.3. Patients seen during the acute stage were treated with general corticotherapy. Immunosuppressive agents were given in 56% of the cases. Vogt-Koyanagi-Harada disease, in a Caucasian and African population, has a presentation close to that of the Japanese population. However, cutaneous signs are much rarer. Visual prognosis was generally favorable.


New approaches to progeria.
Progeria (Hutchinson-Gilford progeria syndrome) is a rare genetic disorder that offers considerable insight into the biology of premature aging. This review summarizes the clinical characteristics of this disease and the underlying mutation in the lamin A (LMNA) gene that results in this phenotype. Modifications in the processing of prelamin A through alterations in farnesylation are detailed, because this pathway offers a possible drug target. Finally, discussion of an ongoing clinical trial for these children, including possible parameters for evaluation, are discussed. In the span of less than a decade, this disease has progressed from an interesting phenotype to one in which the gene defect has been identified, animal models have been created and tested with drugs that target the primary disease pathway, and significant clinical baseline data for the support of a clinical trial have been obtained.


Sedimentation behavior of activated human granulocytes. Aggregation and volume effects.
Human peripheral blood granulocytes (PMNs) obtained from normal adults were studied by an analytical gravity sedimentation system. Exposure of PMNs to endotoxin-activated serum (EAS) in a Ficoll density gradient containing Hank's balanced salt solution with calcium and magnesium produced significantly different sedimentation patterns compared to those from granulocytes exposed to normal serum under the same conditions. Experiments were performed to determine whether changes in granulocyte density, volume, shape, or aggregation were responsible for the sedimentation pattern of granulocytes exposed to EAS. The altered gravity sedimentation behavior of endotoxin-activated granulocytes was abolished when calcium and magnesium were not present in the Ficoll density gradient. Granulocyte aggregation was inhibited by the absence of calcium and magnesium in the medium during granulocyte stimulation, whereas the changes in granulocyte shape and volume associated with granulocyte stimulation were not affected. The data indicate that the altered granulocyte sedimentation pattern in the presence of EAS and calcium and magnesium was produced by granulocyte aggregation and not by changes in granulocyte volume or shape.


Spinal epidural lipomatosis: two new idiopathic cases and a review of the literature.
Thoracic spinal epidural lipomatosis, a rare cause of myelopathy, is most commonly associated with exogenous corticosteroid use. The authors present the clinical, magnetic resonance imaging, computed tomography, and surgical findings for two patients with idiopathic epidural lipomatosis, successfully treated with decompressive laminectomy accompanied by fatty debulking, followed for > 3 postoperative years. They review the literature on idiopathic spinal epidural lipomatosis as well as cases associated with exogenous steroid use.


Important Factors Controlling Gibberellin Homeostasis in Plant Height Regulation.
Plant height is an important agronomic trait that is closely associated with crop yield and quality. Gibberellins (GAs), a class of highly efficient plant growth regulators, play key roles in regulating plant height. Increasing reports indicate that transcriptional regulation is a major point of regulation of the GA pathways. Although substantial knowledge has been gained regarding GA biosynthetic and signaling pathways, important factors contributing to the regulatory mechanisms homeostatically controlling GA levels remain to be elucidated. Here, we provide an overview of current knowledge regarding the regulatory network involving transcription factors, noncoding RNAs, and histone modifications involved in GA pathways. We also discuss the mechanisms of interaction between GAs and other hormones in plant height development. Finally, future directions for applying knowledge of the GA hormone in crop breeding are described.


Coacervation of resilin fusion proteins containing terminal functionalities.
Liquid-liquid phase transition known as coacervation of resilin-like-peptide fusion proteins containing different terminal domains were investigated. Two different modular proteins were designed and produced and their behavior were compared to a resilin-like-peptide without terminal domains. The size of the particle-like coacervates was modulated by the protein concentration, pH and temperature. The morphology and three-dimensional (3D) structural details of the coacervate particles were investigated by cryogenic transmission electron microscopy (cryo-TEM) and tomography (cryo-ET) reconstruction. Selective adhesion of the coacervates on cellulose and graphene surfaces was demonstrated.


Inflammation affects sufentanil consumption in ulcerative colitis.
Previous studies have demonstrated an increased perioperative opioid requirement during inflammatory disease. To evaluate the influence of the inflammatory process, we studied in the same patient the sufentanil requirement during procedures that occur during two distinct phases of ulcerative colitis with different inflammatory profiles: (1) left colectomy for major colitis unresponsive to medical treatment during acute inflammation and (2) coloprotectomy with ileoanal anastomosis, three months after recovery of the acute inflammatory episode. Sixteen patients with clinical and histological evidence of ulcerative colitis scheduled for colectomy with ileoanal anastomosis were included. For each surgical procedure, anaesthesia was induced with sufentanil 0.5 microg kg(-1) and propofol 2 mg kg(-1). Patients were ventilated with 50% nitrous oxide and oxygen, and tidal volume was adjusted to keep end-tidal CO2 at 30 mmHg. Anaesthesia was maintained with end-tidal isoflurane at 0.5%. Analgesia was achieved with continuous infusion of sufentanil at 0.3 microg kg(-1) h(-1). Additional boluses of sufentanil and increases in infusion rates were used when haemodynamic variables increased to more than 20% of preoperative values. Sufentanil consumption during surgery was analysed by Wilcoxon signed rank sum test. P < 0.05 was considered significant. Total intra-operative sufentanil requirement was significantly larger during colectomy performed for acute inflammatory colitis than during ileoanal anastomosis performed after the inflammatory process (1.24 +/- 0.48 microg kg(-1) h(-1) vs. 0.62 +/- 0.3 microg kg(-1) h(-1); P < 0.05). For the same patient, inflammatory status influences opioid requirements during surgery for ulcerative colitis.


Oligosaccharyltransferase structures provide novel insight into the mechanism of asparagine-linked glycosylation in prokaryotic and eukaryotic cells.
Asparagine-linked (N-linked) glycosylation is one of the most common protein modification reactions in eukaryotic cells, occurring upon the majority of proteins that enter the secretory pathway. X-ray crystal structures of the single subunit OSTs from eubacterial and archaebacterial organisms revealed the location of donor and acceptor substrate binding sites and provided the basis for a catalytic mechanism. Cryoelectron microscopy structures of the octameric yeast OST provided substantial insight into the organization and assembly of the multisubunit oligosaccharyltransferases. Furthermore, the cryoelectron microscopy structure of a complex consisting of a mammalian OST complex, the protein translocation channel and a translating ribosome revealed new insight into the mechanism of cotranslational glycosylation.


Invisible steps for a global endemy: molecular strategies adopted by Clostridioides difficile.
Clostridioides difficile infection (CDI) is on the rise worldwide and is associated with an increase in deaths and socio-health burden. C. difficile has become ubiquitous in anthropized environments because of the extreme resistance of its spores. Based on the epidemiological data and knowledge of molecular pathogenesis of C. difficile, it is possible to predict its progressive colonization of the human population for the following reasons: first, its global spread is unstoppable; second, the toxins (Tcds) produced by C. difficile, TcdA and TcdB, mainly cause cell death by apoptosis, but the surviving cells acquire a senescence state that favours persistence of C. difficile in the intestine; third, proinflammatory cytokines, tumour necrosis factor-α and interferon-γ, induced during CDI, enhance the cytotoxicity of Tcds and can increase the survival of senescent cells; fourth, Tcds block mobility and induce apoptosis in immune cells recruited at the infection site; and finally, after remission from primary infection or relapse, C. difficile causes functional abnormalities in the enteric glial cell (EGC) network that can result in irritable bowel syndrome, characterized by a latent inflammatory response that contributes to C. difficile survival and enhances the cytotoxic activity of low doses of TcdB, thus favouring further relapses. Since a 'global endemy' of C. difficile seems inevitable, it is necessary to develop an effective vaccine against Tcds for at-risk individuals, and to perform a prophylaxis/selective therapy with bacteriophages highly specific for C. difficile. We must be aware that CDI will become a global health problem in the forthcoming years, and we must be prepared to face this menace.


Evaluating the Blood Supply of the Femoral Head During Different Stages of Necrosis Using Digital Subtraction Angiography.
The authors investigated changes in the blood supply of necrotic femoral heads using digital subtraction angiography (DSA). Digital subtraction angiography was used to evaluate the blood perfusion of osteonecrosis of the femoral head of 81 patients (81 hips). Necrotic hips were grouped according to the Association Research Circulation Osseous staging classification. Five parameters were assessed to evaluate the intraosseous blood supply of the necrotic femoral heads. The authors chose the most effective images retrospectively and measured the following parameters: the blood vessel diameter ratio between the medial circumflex femoral artery (MCFA) and the deep femoral artery (DFA) (MCFA/DFA); the blood vessel diameter ratio between the lateral circumflex femoral artery (LCFA) and the DFA (LCFA/DFA); the ratio between the MCFA extending length and the width of the femoral neck (A); the number of vessels that reach or exceed line I (a, horizontal line through the junction of the upper femoral head and neck); and the number of vessels that reach or exceed line II (b, the boundary between the femoral head and neck). Significantly negative correlation with Association Research Circulation Osseous stage II to IV necrosis was found for A, a, and b. These parameters were significant (P<.05). Compared with the length and distribution of the vessels, differences in width (MCFA/DFA and LCFA/DFA) were not statistically significant in patients with Association Research Circulation Osseous stage II to IV necrosis. The relative length of the MCFA and the number of vessels above line I and line II are related to the severity of osteonecrosis of the femoral head, as revealed by DSA. Evaluation of blood supply by DSA can be used as one element to predict the fate of precollapsed femoral head. [Orthopedics. 2019; 42(2):e210-e215.].


Activation of noncanonical NF-kappaB signaling by the oncoprotein Tio.
NF-kappaB transcription factors are key regulators of cellular proliferation and frequently contribute to oncogenesis. The herpesviral oncoprotein Tio, which promotes growth transformation of human T cells in a recombinant herpesvirus saimiri background, potently induces canonical NF-kappaB signaling through membrane recruitment of the ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6). Here, we show that, in addition to Tio-TRAF6 interaction, the Tio-induced canonical NF-kappaB signal requires the presence of the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, NF-kappaB essential modulator (NEMO), and the activity of its key kinase, IKKbeta, to up-regulate expression of endogenous cellular inhibitor of apoptosis 2 (cIAP2) and interleukin 8 (IL-8) proteins. Dependent on TRAF6 and NEMO, Tio enhances the expression of the noncanonical NF-kappaB proteins, p100 and RelB. Independent of TRAF6 and NEMO, Tio mediates stabilization of the noncanonical kinase, NF-kappaB-inducing kinase (NIK). Concomitantly, Tio induces efficient processing of the p100 precursor molecule to its active form, p52, as well as DNA binding of nuclear p52 and RelB. In human T cells transformed by infection with a Tio-recombinant virus, sustained expression of p100, RelB, and cIAP2 depends on IKKbeta activity, yet processing to p52 remains largely unaffected by IKKbeta inhibition. However, long term inhibition of IKKbeta disrupts the continuous growth of the transformed cells and induces cell death. Hence, the Tio oncoprotein triggers noncanonical NF-kappaB signaling through NEMO-dependent up-regulation of p100 precursor and RelB, as well as through NEMO-independent generation of p52 effector.


Hearing threshold levels and speech recognition in noise in 7-year-olds.
International standards define normal hearing threshold levels (HTLs) and many studies describe speech recognition in noise (SRN) for adults. Less has been published on these characteristics for children. This study aims to establish ranges of HTLs and SRN for otologically normal 7-year-olds. Air conduction HTLs were measured in 189 7-year-olds within an audiometric booth. Speech recognition was measured adaptively for BKB sentences in noise presented binaurally through headphones, determining the speech-to-noise ratio (SNR) required to score 71% correct. The mean HTLs of otologically normal 7-year-olds were significantly lower (better) than those published for young adults at 1 and 2 kHz. Speech recognition in noise was unrelated to HTLs and was higher (worse) for 7-year-olds (SNR = -4 dB) than has been found for young otologically normal adults (SNR = -6 dB). It is concluded that although the HTLs of 7-year-old children are generally better than those of young adults, their speech recognition in noise is worse. This confirms that their ability to recognise speech in noise is not fully developed at this age.


Separation of younger red cells with improved survival in vivo: an approach to chronic transfusion therapy.
Transfusion of donor blood containing predominantly younger red cells with prolonged survival in vivo could significantly reduce the iron overload of patients requiring chronic transfusion. Age-dependent separation of red cells can be obtained by buoyant density centrifugation on isotonic solutions of arabino-galactane. By this technique, rabbit red cells were separated on a single layer of arabino-galactane and the appropriate fraction, after being labeled with (51)Cr, was reinfused into the donor. The survival in vivo was calculated by a mathematical model which corrects for both (51)Cr elution and random loss. There was a significant difference in survival in vivo between the light young red cells and the heavy old red cells. The potential survival in vivo of the 50% lightest red cells was 56 days, compared to 28 days for the heaviest red cells. Arabino-galactane appeared to be devoid of acute toxicity and of strong antigenicity and it did not appear to adhere to the red cell stroma. These data extrapolated to humans indicate that it may be feasible and advantageous to use red cells fractionated by this technique for transfusion. The 50% lightest human red cells can be expected to have a mean survival of 88 days, compared with 60 days for unfractionated blood. Transfusion of young red cells could significantly reduce the iron overload for patients requiring chronic transfusion, by avoiding infusion of the oldest red cells, which contribute equally to iron overload yet offer only transient survival in vivo.


Angioimmunoblastic T-cell lymphoma with elevated serum IgA and infiltration of IgA-positive plasma cells into a skin lesion.
Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common types of peripheral T-cell lymphoma. Laboratory examination exhibits immunological abnormalities, such as polyclonal hypergammaglobulinemia and hemolytic anemia. Skin lesions are also observed in approximately half of AITL cases. However, the relationship of skin involvement with the clinical course and prognosis is unknown. Herein, we report the case of a patient with AITL with elevated serum immunoglobulin A (IgA) level, which was a predictive element of poor prognosis, and infiltration of IgA-positive plasma cells into the skin lesions. Based on this case, we believe that skin manifestations could be used to identify the characteristics of immune disorders and prognosis of AITL.


CA 125 in preoperative evaluation of pelvic masses.
Serum CA 125 levels were measured preoperatively in 126 women subjected to laparotomy due to palpable pelvic mass. Forty out of 42 patients with true malignant serous ovarian carcinoma had serum CA 125 levels higher than 35 U/ml. Among 62 patients with some types of gynecologic malignancy, 48 also met the cutoff value of 35 U/ml. Sensitivity, specificity, positive and negative predictive value of CA 125 as a tumor marker, proved to be satisfactory. These results suggest that CA 125 assay can be used as a diagnostic adjunct in the preoperative evaluation of patients with a pelvic mass.


Development of a local carbon dioxide emissions inventory based on energy demand and waste production.
This paper describes the study that led to the development of a carbon dioxide emissions matrix for the Oeiras municipality, one of the largest Portuguese municipalities, located in the metropolitan area of Lisbon. This matrix takes into account the greenhouse gas (GHG) emissions due to an increase of electricity demand in buildings as well as solid and liquid wastes treatment from the domestic and services sectors. Using emission factors that were calculated from the relationship between the electricity produced and amount of treated wastes, the GHC emissions in the Oeiras municipality were estimated for a time series of 6 yr (1998-2003). The obtained results showed that the electricity sector accounts for approximately 75% of the municipal emissions in 2003. This study was developed to obtain tools to base options and actions to be undertaken by local authorities such as energy planning and also public information.


Research misconduct: time for a re-think?
The incidence of research misconduct appears to be increasing, drawing attention in the general media and academic literature. Concerns have been expressed about probable under-reporting, harms arising, lack of an agreed international definition, welfare of whistleblowers and the adequacy of the investigation processes and any subsequent sanctions. A fully satisfactory approach to prevention, detection, investigation and adjudication has yet to emerge. While the definition of research misconduct contained in the Australian Code for the Responsible Conduct of Research is comprehensive, universities and other research institutions at times struggle in their task of investigating and adjudicating allegations of research misconduct. A more centralised, independent process of oversight and monitoring of this role played by the universities and institutions would help support those institutions and help maintain community confidence in the research endeavour.


Cowden disease.
Cowden disease represents an unusual, but unique syndrome which can be recognized most consistently by the development of characteristic verrucous, keratotic, papular, and nodular lesions about facial orifices, on the oral mucosa, and over the dorsal surfaces of the forearms and hands. The cause of these diverse hyperplastic changes is not known. Recognition of these lesions as signs of more extensive disease should alert the physician to examine the thyroid gland, breasts, female reproductive tract, GI tract, and skeleton for evidence of the associated changes we have enumerated. Because of the tendency for lesions of the thyroid, breast, and intestines to undergo malignant change, these patients require close observation and evaluation.


Monitoring and Follow-up of Chronic Heart Failure: a Literature Review of eHealth Applications and Systems.
In developed countries heart failure is one of the most important causes of death, followed closely by strokes and other cerebrovascular diseases. It is one of the major healthcare issues in terms of increasing number of patients, rate of hospitalizations and costs. The main aim of this paper is to present telemedicine applications for monitoring and follow-up of heart failure and to show how these systems can help reduce costs of administering heart failure. The search for e-health applications and systems in the field of telemonitoring of heart failure was pursued in IEEE Xplore, Science Direct, PubMed and Scopus systems between 2005 and the present time. This search was conducted between May and June 2015, and the articles deemed to be of most interest about treatment, prevention, self-empowerment and stabilization of patients were selected. Over 100 articles about telemonitoring of heart failure have been found in the literature reviewed since 2005, although the most interesting ones have been selected from the scientific standpoint. Many of them show that telemonitoring of patients with a high risk of heart failure is a measure that might help to reduce the risk of suffering from the disease. Following the review conducted, in can be stated that via the research articles analysed that telemonitoring systems can help to reduce the costs of administering heart failure and result in less re-hospitalization of patients.


Nephrotic syndrome in Nigerian children with homozygous sickle cell disease.
Two hundred and seventy two children with the nephrotic syndrome were seen and followed up at the Paediatric Renal Unit of the University of Nigeria Teaching Hospital, Enugu over 12 1/2 year period, between June 1983 and December 1995. Of these, there were nine (3.3%) children with homozygous sickle cell disease (SS). This latter group had a mean age of 9.6 +/- 3.2 years, male to female ratio of 1:2 and serum cholesterol of 3.13 +/- 1.48 mmol/l at the time of diagnosis. The mortality rate was 55.6% in these sicklers, death occurring within one and a half to five years of diagnosis. Causes of death were attributable to sickle cell disease in 60%, renal diseases in 20%, and other causes in 20%. Renal biopsy in two of the sicklers showed membrano-proliferative glomerulonephritis (MPGN) and focal glomerulosclerosis (FGS) respectively. Homozygous sickle cell disease does seem to predispose to the development of the nephrotic syndrome and those that do develop nephrotic syndrome exhibit some special characteristics, when compared to non-sicklers with nephrotic syndrome. These include older age of onset of the nephrotic syndrome, reverse sex ratios, lower serum cholesterol, higher mortality rate and sickle cell complications rather than chronic renal failure as the major cause of death.


Selective salpingography and fallopian tube recanalisation: experience from a district general hospital.
The Royal College of Obstetricians and Gynaecologists has included selective salpingography and tubal catheterisation (SS-TC) in its evidence-based clinical guideline for the management of infertility in secondary care. In spite of being a cost-effective and minimally invasive treatment option for proximal tubal blockage, SS-TC has been slow to become adopted across the UK. We here describe our initial experience with setting up of tubal recanalisation service in a district general hospital (DGH) in the UK, along with our preliminary results. Tubal patency was achieved in 11 patients out of 14 who underwent SS-TC (78%). Four women achieved spontaneous pregnancy (success rate 28.57%) within 1 year of treatment. The procedure should become a universally accepted, taught and practiced approach in the diagnosis and treatment of the fallopian tube. Especially in infertility units located in a DGH it can be used selectively in the patients with good prognosis and other cases referred to tertiary center for more rapid in-vitro fertilisation (IVF).


Regional impairments of cortical folding in premature infants.
This study was undertaken to evaluate the influence of preterm birth and other factors on cerebral cortical maturation. We have evaluated the effects of preterm birth on cortical folding by applying cortical cartography methods to a cohort of 52 preterm infants (<31 weeks gestation, mild or no injury on conventional magnetic resonance imaging) and 12 term-born control infants. All infants were evaluated at term-equivalent postmenstrual age. Preterm infants had lower values for the global measures of gyrification index (GI; 2.06 ± 0.07 vs 1.80 ± 0.12, p < 0.001; control vs preterm) and cortical surface area (CSA; 316 ± 24 cm(2) vs 257 ± 40 cm(2) , p < 0.001). Regional analysis of sulcal depth and cortical shape showed the greatest impact of preterm birth on the insula, superior temporal sulcus, and ventral portions of the pre- and postcentral sulci in both hemispheres. Although CSA and GI are related, CSA was more sensitive to antenatal and postnatal factors than GI. Both measures were lower in preterm infants of lower birth weight standard deviation scores and smaller occipitofrontal circumference at time of scan, whereas CSA alone was lower in association with smaller occipitofrontal circumference at birth. CSA was also lower in infants with higher critical illness in the first 24 hours of life, exposure to postnatal steroids, and prolonged endotracheal intubation. Preterm birth disrupts cortical development in a regionally specific fashion with abnormalities evident by term-equivalent postmenstrual age. This disruption is influenced by both antenatal growth and postnatal course.


Antioxidant capacity and phenolic content of two Algerian Mentha species M. rotundifolia (L.) Huds, M. pulegium L., extracted with different solvents.
Background It is important to consider the optimum conditions and processing factors (like solvent type) influencing activity of plant antioxidants for utilization in food and biological systems. Methods The antioxidant capacity and phenolic content of two Mentha species, namely, Mentha pulegium L. (MP) and Mentha rotundifolia (L.) Huds (MR), were studied and six solvent systems were used. The total antioxidant capacity of the mint species extracts was evaluated using phosphomolybdenum method and the free radical-scavenging capacity by 2,2-diphenyl-1-picrylhydrazyl radical-scavenging assay. Results The efficiency of the used solvents to extract phenols from the two species varied considerably. The highest total phenolic content was obtained from methanol extract of MP (25.3±1.3 mg GAE/gdw) and total flavonoid content from methanol extract of MR (10.1±0.1 mg QE/gdw). High phenol content was significantly correlated with high antioxidant capacity. The methanol extracts showed the highest radical scavenging activity. All the extracts showed variable antioxidant capacity by the formation of phosphomolybdenum complex. Acetone extract of MP and methanol extract of MR exhibited marked reducing power in this method. Conclusions Our findings identified the appropriate solvent for extracting MP and MR phenolics which might provide a rich source of natural antioxidants.


Extended darkness induces internal turnover of glucosinolates in Arabidopsis thaliana leaves.
Prolonged darkness leads to carbohydrate starvation, and as a consequence plants degrade proteins and lipids to oxidize amino acids and fatty acids as alternative substrates for mitochondrial ATP production. We investigated, whether the internal breakdown of glucosinolates, a major class of sulfur-containing secondary metabolites, might be an additional component of the carbohydrate starvation response in Arabidopsis thaliana (A. thaliana). The glucosinolate content of A. thaliana leaves was strongly reduced after seven days of darkness. We also detected a significant increase in the activity of myrosinase, the enzyme catalyzing the initial step in glucosinolate breakdown, coinciding with a strong induction of the main leaf myrosinase isoforms TGG1 and TGG2. In addition, nitrilase activity was increased suggesting a turnover via nitriles and carboxylic acids. Internal degradation of glucosinolates might also be involved in diurnal or developmental adaptations of the glucosinolate profile. We observed a diurnal rhythm for myrosinase activity in two-week-old plants. Furthermore, leaf myrosinase activity and protein abundance of TGG2 varied during plant development, whereas leaf protein abundance of TGG1 remained stable indicating regulation at the transcriptional as well as post-translational level.


Targeting HSP90-HDAC6 Regulating Network Implicates Precision Treatment of Breast Cancer.
Breast cancer is the leading cause of women death. Heat shock protein 90 (HSP90) and Histone deacetylase 6 (HDAC6) are promising anti-cancer drug targets. However, it's still unclear the applicability of anti-HSP90 and anti-HDAC6 strategies in precision treatment of breast cancer. In current study, we found that triple negative breast cancer (TNBC) cells, compared to T47D, an ERα+ breast cancer cell line, exhibited 7~40 times lower IC50 values, stronger cell cycle perturbation, increased cell apoptosis and stronger inhibition of cell migration upon 17-DMAG treatment, while T47D, compared to TNBC cells, expressed higher HDAC6 and showed stronger anti-cancer response upon treatment of Tubacin. Mechanically, 17-DMAG treatment inhibited a complex network consists at least ERK, AKT, and Hippo pathway in TNBC cells, and higher expression of HDAC6 inhibited HSP90 activity via deacetylating HSP90. Furthermore, we found higher HDAC6 expression level in tamoxifen-resistance T47D than that in T47D, and Tubacin treatment suppressed the growth of tamoxifen-resistant cells in vivo. Our data suggested that anti-HSP90 and anti-HDAC6 are promising strategies to treat TNBC and ERα+ breast cancers respectively, and anti-HDAC6 can be considered during treatment of tamoxifen-resistance breast cancers.


The effect of glucocorticoids on fat and lean tissue masses in giant cell arteritis.
The aim of the present prospective study over a follow-up period of two years was to assess the influence of various doses of glucocorticosteroids on the total body fat and lean tissue masses and their regional distribution, using DXA technique, in twenty-four patients with giant cell arteritis (GCA). Treatment with glucocorticoids for two years, using high doses of prednisolone the first six months and lower doses thereafter, resulted in a significant increase in total body fat as well as in trunk fat expressed either as absolute values or as a proportion of body weight. The abnormal accumulation of fat mass remained also after switching to a low dose glucocorticoid schedule. There was no redistribution of fat from peripheral areas to central parts of the body and there was no depletion of lean tissue at peripheral sites.


Lexical Competition between Spoken and Literary Arabic: A New Look into the Neural Basis of Diglossia Using fMRI.
Diglossia in the Arabic language refers to the socio-linguistic situation in which Spoken Arabic (SA), which is the first to be acquired, is used for everyday communications, while Literary Arabic (LA), acquired at school for reading and writing, is also used for formal functions. Although some authors consider SA and LA as a first and second language, the question of how these are managed in the brain has not yet been understood. Using functional magnetic resonance brain imaging (fMRI) analysis, this study aimed at exploring the neural basis of diglossia during picture naming in two contexts. In the first, healthy young participants were instructed to name each image either in SA or LA on the basis of cue word appearing after the stimulus. In the second, they were instructed to name images either in SA or in Hebrew. Behavioral analysis showed that naming in SA was slightly easier than LA and considerably easier than Hebrew. fMRI analysis showed no difference between SA and LA. Hebrew compared to SA revealed activation differences explainable in terms of engagement of language control modules and second- to first-language effects. These findings, discussed in the light of previous findings in bilingual literature, support the view that dominance in diglossia is modality-dependent.


[Intraoperative facial nerve monitoring in parotid gland surgery].
To re-evaluate the value and the methods of intraoperative facial nerve monitoring in parotid gland surgery. Sixty-five cases received intraoperative facial nerve monitoring in parotidectomy (test group) since 2000 - 2008. The facial nerve was identified through central trunk method (n = 18), branch method (n = 35) and mixed method (n = 12). Most patients accepted general anesthesia by incubation. The operating duration and minimum electronic stimulation threshold values of EMG in evoked facial muscle were recorded. Facial nerve was identified though branch method (n = 44) and no intraoperative facial nerve monitoring was performed in parotidectomy (control group). There were four cases (6.1%) of mild temporary paralysis and no permanent post-operative paralysis of facial nerve in the test group. The average operating duration was 1.8 hour. The minimum reactive electronic stimulation threshold of EMG in evoked facial muscle was 0.08 mA. The range of suitable electronic stimulation threshold of EMG was from 0.2 mA to 1.0 mA. While there were nine cases (20.5%) of mild temporary paralysis and two cases (4.5%) of permanent post-operative paralysis of facial nerve in the control group and the average operating duration was 3.0 hours. Intraoperative facial nerve monitoring (IFNM) in parotidectomy can assist a surgeon to confirm and identify the facial nerve and exercise precautions so as to shorten operating duration and prevent potential surgical complications.