Improved multi-shot diffusion imaging using GRAPPA with a compact kernel.
In multi-shot diffusion imaging, motion induced phase variations are traditionally seen as a source of artifacts and corrected in the image domain using SENSE-based methods. This correction usually requires image echo and navigator echo to be geometrically matched. Recently, a k-space based method, realigned GRAPPA, has been proposed. It realigns data from different shots into the same k-space locations, and then synthesizes the missing data using GRAPPA algorithm. In this study, we refined the theory for GRAPPA-based method. In the revised theory, phase variations are treated as a kind of encoding, similar to coil sensitivity encoding. Based on this, the missing data can be synthesized using k-space correlations among different shots and channels. Then a compact kernel is used which only includes acquired data with significant contribution for the data synthesis, and can generate accurate weights without strict navigator size requirements. Simulation studies as well as brain and cervical spine experiments demonstrate that the proposed reconstruction method can effectively suppress artifacts caused by phase variations, and provide diffusion images with high resolution and low distortion. Compared with SENSE-based methods, the proposed method is less sensitive to mismatch between image echo and navigator echo.


[Discharge against medical advice in Veneto Region].
Discharge against medical advice (DAMA) may put patients at risk of adverse health outcomes and often generate hospital readmission. A retrospective case-control study (2000-2004) of all DAMA in Veneto Region hospitals was carried out to determine the baseline characteristics of patients who leaves hospital. During the 5-years study period, the overall DAMA rates were 0.8 from ordinary hospitalization and 0.2 from daily. Prediction of patients at risk of DAMA may be possible with several defined variables and this analysis represent an instrument that should facilitate the development of successful strategies to reduce DAMA for high-risk patients.


Economic optimization of a global strategy to address the pandemic threat.
Emerging pandemics threaten global health and economies and are increasing in frequency. Globally coordinated strategies to combat pandemics, similar to current strategies that address climate change, are largely adaptive, in that they attempt to reduce the impact of a pathogen after it has emerged. However, like climate change, mitigation strategies have been developed that include programs to reduce the underlying drivers of pandemics, particularly animal-to-human disease transmission. Here, we use real options economic modeling of current globally coordinated adaptation strategies for pandemic prevention. We show that they would be optimally implemented within 27 y to reduce the annual rise of emerging infectious disease events by 50% at an estimated one-time cost of approximately $343.7 billion. We then analyze World Bank data on multilateral "One Health" pandemic mitigation programs. We find that, because most pandemics have animal origins, mitigation is a more cost-effective policy than business-as-usual adaptation programs, saving between $344.0.7 billion and $360.3 billion over the next 100 y if implemented today. We conclude that globally coordinated pandemic prevention policies need to be enacted urgently to be optimally effective and that strategies to mitigate pandemics by reducing the impact of their underlying drivers are likely to be more effective than business as usual.


Strength Training for Women as a Vehicle for Health Promotion at Work.
Women, on average, have less muscle strength than men. This anthropometric-physiological trait may make them more vulnerable to ex - cessive physical strain, injury, and inability to work. Strength training is used for preventive health maintenance and to lessen musculoskeletal symptoms. In this context, we studied whether the degree of muscle strength has any effect on women's health in everyday working life, and also the effects of strength training for women on their health in the workplace. We systematically searched the PubMed/MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and SPOLIT databases for pertinent publications, in accordance with the PRISMA criteria for literature searches. We analyzed all of the retrieved randomized controlled trials conducted on women aged 18 to 65 to determine the effects of training on muscle strength, physical performance ability, and health-related parameters including body composition, musculo - skeletal pain, and subjective well-being. We did not find any studies that provided answers to the first question. As for the second question, the selection criteria were met by 12 of the 4969 retrieved studies, which dealt with the effect of strength training on health in the occupational environment and involved a total of 1365 female subjects. These studies were carried out in heterogeneous subject groups, with a variety of overlapping interventions consisting of both strength and endurance training. Significantly increased strength was found in all studies, as was a reduction of pain in all of the studies where this question was asked. Inconsistent results were obtained with respect to body weight, body composition, and subjective well-being. The interventions that were conducted in these studies succeeded in increasing strength and reducing pain, even when the training was brief and of low intensity. This was true not only for women working in occupations requiring unusual physical strength, but also for those in sedentary occupations. The small number of studies performed on this subject to date is surprising in view of the high prevalence of musculoskeletal symptoms in women.


Influence of Helicobacter pylori Infection on Endoscopic Findings of Gastric Adenocarcinoma of the Fundic Gland Type.
Gastric adenocarcinoma of the fundic gland type (chief cell predominant type) (GA-FG-CCP) was first reported as a rare adenocarcinoma found in the normal fundic mucosa. Recent studies have proposed the possibility that GA-FG-CCPs were also generated in the atrophic mucosa after Helicobacter pylori (HP) eradication therapy. However, little is known on the endoscopic findings of GA-FG-CCP generated in the atrophic mucosa due to its extreme rarity. A total of 8 patients who underwent endoscopic submucosal resection and were diagnosed with GA-FG-CCP generated in the HP-uninfected mucosa (4 cases, HP-uninfected group) or HP-eradicated atrophic mucosa (4 cases, HP-eradicated group) were retrospectively analyzed, and their endoscopic findings, including magnifying endoscopy with narrow band imaging (M-NBI), and pathological features were compared. While GA-FG-CCPs in the 2 groups displayed similar macroscopic appearance, M-NBI demonstrated that characteristic microvessels (tapered microvessels like withered branches) were specifically identified in the HP-eradicated group. Pathological investigation revealed that a decreasing number of fundic glands and thinned foveolar epithelium covering tumor ducts were thought to lower the thickness of the covering layer over tumor ducts in the HP-eradicated group. Moreover, dilation of vessels just under the surface of the lesions contributed to the visualization of microvessels by M-NBI. The change in background mucosa due to HP infection influenced the thickness of the covering layer over the tumor ducts and M-NBI finding of GA-FG-CCP.


Markers of calcium and phosphate metabolism and osteopenic syndrome in patients with coronary artery disease.
The aim of the present study is to assess the level of specific markers of calcium and phosphate metabolism in the development of coronary atherosclerosis in patients with stable coronary artery disease, depending on the severity of osteopenic syndrome. METHODSː In the study 112 male patients aged from 49 to 73 years with verified coronary artery disease were included in the study. Calcium Score was measured using the Agatston Score. Besides, all of them were tested on the serum level of parathyroid hormone, calcitonin, osteocalcin, bone-specific alkaline phosphatase, osteoprotegerin, osteopontin, cathepsin K, estradiol and testosterone. RESULTSː The distribution of patients according to the severity of coronary atherosclerosis using the Syntax Score suggested that the levels of the studied markers did not differ significantly among the patients, despite significant differences in the severity of coronary artery disease. The levels of osteoprotegerin in patients with mild, moderate and severe calcification were significantly lower compared to patients with a zero calcium score. There were no clinical manifestations of osteopenic syndrome in all patients. However, they underwent osteodensitometry with measurement of bone mineral density at the lumbar spine and femoral neck to determine pre-clinical symptoms of bone destruction. Significant increase (P=0.03) in serum levels of osteocalcin was found in patients with radiological evidence of osteoporosis while the other markers did no differ significantly. CONCLUSIONSː We suppose that there is a reciprocal interaction of regulatory vectors with increased calcium deposition in the arterial wall and resorption of bone tissue.


Pancreas After Islet Transplantation: A First Report of the International Pancreas Transplant Registry.
Pancreas after islet (PAI) transplantation is a treatment option for patients seeking insulin independence through a whole-organ transplant after a failed cellular transplant. This report from the International Pancreas Transplant Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI transplant outcomes over a 10-year time period. Forty recipients of a failed alloislet transplant subsequently underwent pancreas transplant alone (50%), pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and kidney (SPK) transplant (27.5%). Graft and patient survival rates were not statistically significantly different compared with matched primary pancreas transplants. Regardless of the recipient category, overall 1- and 5-year PAI patient survival rates for all 40 cases were 97% and 83%, respectively; graft survival rates were 84% and 65%, respectively. A failed previous islet transplant had no negative impact on kidney graft survival in the SPK category: It was the same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI transplant is a safe procedure with low recipient mortality, high graft-function rates in both the short and long term and excellent kidney graft outcomes. Patients with a failed islet transplant should know about this alternative in their quest for insulin independence through transplantation.


Acidic amorphous silica prepared from iron oxide of bacterial origin.
Microporous and mesoporous silica derived from biogenous iron oxide is an attractive catalyst for various organic reactions. Biogenous iron oxide contains structural silicon, and amorphous silica remains after iron oxide is dissolved in concentrated hydrochloric acid. The amorphous silica containing slight amounts of iron (Si/Fe = ∼150) is composed of ∼6-nm-diameter granular particles. The amorphous silica has a large surface area of 540 m(2)/g with micropores (1.4 nm) and mesopores (<3 nm). By using pyridine vapor as a probe molecule to evaluate the active sites in the amorphous silica, it was found that this material has strong Brønsted and Lewis acid sites. When the catalytic performance of this material was evaluated for reactions including the ring opening of epoxides and Friedel-Crafts-type alkylations, which are known to be catalyzed by acid catalysts, this material showed yields higher than those obtained with common silica materials.


[Measurement of attitudes toward interprofessional collaboration in an operating theatre - a cross-sectional study].
Measurement of attitudes toward interprofessional collaboration in an operating theatre - a cross-sectional study Abstract.Background: Interprofessional cooperation (IC) between healthcare professionals is essential for good treatment outcomes. Surgical departments place special demands on interprofessional cooperation (situational team formation, alterning work environment, coordinative overcrowding of work) within a health organisation. In order to achieve common goals in a team, it is important that those involved have a comparable understanding of and attitude towards interprofessional cooperation, regardless of their profession. Research Question: What is the internal consistency of the German version of the Jefferson Scale of Attitudes Toward Interprofessional Collaboration (JeffSATIC) when applied to personnel in an operating theatre? What is the attitude towards interprofessional cooperation between the various occupational groups in a surgical department of an acute care hospital functioning as a centre and a training establishment? Are there differences between the individual occupational groups and the sexes? Method: The validated JeffSATIC questionnaire was translated back into German and sent to 283 people in a surgical department with eleven operating theatres. The internal consistency of the questionnaire and differences in attitude towards interprofessional cooperation were examined. Findings: The German version of the JeffSATIC questionnaire is a reliable instrument for measuring the attitude of individuals towards interprofessional cooperation. It was used for the first time in the context of a surgical department. In the institution examined, there are no statistically significant differences between the different occupational groups and sexes in relation to the attitude to IC in the dimensions 'work relationship' and 'responsibility' determined by the questionnaire. The medical service anaesthesia shows the greatest divergence in attitude towards interprofessional cooperation within a professional group. Conclusions: In the institution examined, the prerequisites for successful interprofessional cooperation exist. In general, it should be further examined which factors influence the divergence in attitude per occupational group and whether these divergences in attitude are also associated with the quality of the actual cooperation.


Hedgehog Signaling Links Chronic Inflammation to Gastric Cancer Precursor Lesions.
Since its initial discovery in Drosophila, Hedgehog (HH) signaling has long been associated with foregut development. The mammalian genome expresses 3 HH ligands, with sonic hedgehog (SHH) levels highest in the mucosa of the embryonic foregut. More recently, interest in the pathway has shifted to improving our understanding of its role in gastrointestinal cancers. The use of reporter mice proved instrumental in our ability to probe the expression pattern of SHH ligand and the cell types responding to canonical HH signaling during homeostasis, inflammation, and neoplastic transformation. SHH is highly expressed in parietal cells and is required for these cells to produce gastric acid. Furthermore, myofibroblasts are the predominant cell type responding to HH ligand in the uninfected stomach. Chronic infection caused by Helicobacter pylori and associated inflammation induces parietal cell atrophy and the expansion of metaplastic cell types, a precursor to gastric cancer in human subjects. During Helicobacter infection in mice, canonical HH signaling is required for inflammatory cells to be recruited from the bone marrow to the stomach and for metaplastic development. Specifically, polarization of the invading myeloid cells to myeloid-derived suppressor cells requires the HH-regulated transcription factor GLI1, thereby creating a microenvironment favoring wound healing and neoplastic transformation. In mice, GLI1 mediates the phenotypic shift to gastric myeloid-derived suppressor cells by directly inducing Schlafen 4 (slfn4). However, the human homologs of SLFN4, designated SLFN5 and SLFN12L, also correlate with intestinal metaplasia and could be used as biomarkers to predict the subset of individuals who might progress to gastric cancer and benefit from treatment with HH antagonists.


Cryotolerance of porcine blastocysts is improved by treating in vitro matured oocytes with L-carnitine prior to fertilization.
Sufficient generation of adenosine triphosphate (ATP) by oocytes is critical for fertilization and embryo development. The objective of this study was to determine the effects of supplementing media with L-carnitine, a co-factor required for the metabolism of fatty acids, during the peri-fertilization period on embryo development and energy generation. Firstly, in vitro matured (IVM) porcine oocytes were co-incubated with sperm in IVF medium supplemented with 0‒24 mM L-carnitine. The blastocyst formation rate of the control group was greater than those of the L-carnitine groups (P < 0.05), except for the 3 mM L-carnitine group. Subsequently, oocytes and/or sperm were treated without or with 3 mM L-carnitine for either the 1 h pre-IVF oocyte incubation; the pre-IVF sperm preparation; the first 30 min of IVF; or the entire 5.5 h of IVF. Despite similar fertilization rates among the groups, the cleavage rate of the pre-IVF oocyte group was significantly greater than those of the other groups, except for the pre-IVF sperm group. Additionally, the oocyte ATP content and the cryotolerance of the resulting blastocysts were examined following the pre-IVF oocyte treatment. Oocyte ATP content was also similar among the groups (P > 0.05). Following vitrification, the post-warming survival rate of blastocysts derived from L-carnitine-treated oocytes was greater than that of blastocysts derived from untreated oocytes (42.4% vs. 24.9%; P < 0.05). In conclusion, a 1 h oocyte exposure to 3 mM L-carnitine immediately prior to insemination enhanced cleavage and improved the cryotolerance of resulting blastocysts. While the findings are suggestive of a lipolytic action, further studies are required to clarify the contributions of lipid metabolism and oxidative mechanisms to the observed effects of the L-carnitine treatment.


The use of Teflon as wrapping material in aneurysm surgery.
Even if clipping is the ideal and only complete treatment of the intracranial aneurysm, wrapping is a well-known alternative technique when aneurysm clipping is not feasible, or is not completely satisfactory. We present a technique of wrapping using fibres of Teflon material shaped in strings or in pledgets, arranged on or around the area to be treated and fixed by fibrin glue. This Teflon technique was used during the years 1990 to 1992, in 44 treated aneurysms (33% or all aneurysms treated during the same period), and in 3 situations: 1) to reinforce a residual or additional ectasia next to the clipped aneurysm, usually proximal to the clip (25 cases, i.e., 57%), 2) to treat an arterial ectasia, so called preaneurysmal ectasia, which proved not clippable at surgery (10 cases, 23%) and 3) to protect a nervous or vascular neighbouring structure which was compressed by the clip grip (9 cases, 20%). No complication was noted in relation to this technique. Up to now, no other know wrapping material has received worldwide approval for being completely innocuous and effective. The Teflon material has been widely used in neurosurgical microvascular decompression and in cardiovascular surgery. In these fields, its reliability, safety, and lack of harmful effects have been widely recognized and should also apply in aneurysm surgery. A very long follow-up will be necessary to assess the outcome for this new wrapping technique.


The utility of contrast echocardiographic techniques in the care of critically ill infants with cardiac and pulmonary disease.
In order to assess the utility of contrast M-mode echocardiography in an intensive care nursery population of critically ill newborns with cardiac and pulmonary disease and to validate contrast echo methods, we performed 200 serial contrast echoes on 40 infants via umbilical arterial or venous catheters which had been placed into these infants for clinical indications. The resulting contrast echoes recorded from the precordium or the suprasternal notch allowed the delineation of intra- and extracardiac right-to-left and left-to-right shunting patterns. Patterns identified and validated by cardiac catheterization (in cardiac patients) were: right-to-left atrial shunts, right-to-left ventricular shunts, and left-to-right patent ductus arteriosus shunts. The studies were without complication. Serial application of these echocardiographic techniques was extremely important in assessing changing physiology in these neonates. Contrast echocardiography adds physiologic flow information to the anatomical information available from M-mode echoes and is quite important in the diagnosis and sometimes in the management of critically ill newborns.


Janus Particles Templated by Janus Emulsions and Application as a Pickering Emulsifier.
One-step vibrational mixing has afforded the batch-scale preparation of a Janus emulsion. The fabrication of Janus particles (JPs) templated by Janus emulsions was motivated by the topology and composition of the Janus droplets being highly tunable and controllable. Two immiscible polymerizable monomers were introduced as inner phases of the Janus emulsion. The advanced geometry of the resultant JPs was easily and precisely controlled from "snowman" to "dumbbell" by adjusting the mass ratio of two oils in the initial emulsion. The surface coverage of one lobe to the other was tuned by adjusting the mass ratio of mixed surfactants. Moreover, the size of JPs was able to be extended continuously from hundreds of micrometers to a few hundred nanometers while their morphologies remained within this wide size range. The proposed strategy is a universal technique in the synthesis of a family of composite polymeric JPs with both chemical and shape anisotropy. In addition, the as-generated chemically biphasic JPs were applied as emulsifiers to stabilize Pickering emulsions, and more attractively, emulsion inversion was readily achieved by choosing JPs with different morphologies.


Plasma phosphatidylcholine hydroperoxide-reducing activity in pregnant women.
Plasma glutathione peroxidase (PGPx) and apolipoproteins A-I, A-II, and B-100 reduce phosphatidylcholine hydroperoxide (PC-OOH) to its hydroxide (PC-OH). To elucidate the relative importance of the reduction pathways we developed a simple assay for measuring total PC-OOH-reducing activity. Human plasma was incubated with 1-palmitoyl-2-linoleoyl-phosphatidylcholine hydroperoxide and the time-dependent reduction was confirmed by its hydroxide formation, measured by reversed-phase high performance liquid chromatography. We determined the PC-OOH reducing activity in blood plasma of healthy men and women as 119 +/- 7 (n = 13, aged 27 to 45) and 101 +/- 4 microM/h (n = 5, aged 24 to 30), respectively. In addition, we also measured PC-OOH-reducing activity in the plasma of 53 pregnant women since they usually show hyperlipidemia or hyper-apolipoproteinemia. The average rate of PC-OOH reduction was 101 +/- 34 microM/hr. The PC-OOH-reducing activity was not affected by the addition of iodoacetamide, an inhibitor of PGPx, suggesting that the activity is due to apolipoproteins. A significant correlation between plasma reducing activity with apolipoprotein B-100 was observed (r = 0.290), but not with apolipoprotein A-I (r = 0.118). In pre-eclamptic patients, about an 8% decrease in plasma PC-OOH-reducing activity was observed as compared to the normal pregnancy group, although the decrease was not statistically significant.


Effects of dihydropyridines and their combination with aspirin on blood pressure and circadian platelet activity in patients with essential hypertension.
The objective of this double-blind study was: 1) to evaluate and compare the effects of treatment with two dihydropyridines--isradipine and nitrendipine--on basal and circadian blood pressure and on 24-h platelet activity; and 2) to investigate the influence of low-dose aspirin on the antihypertensive, antiplatelet (antiaggregatory) efficacy of dihydropyridines. After a 4-week placebo period, 39 patients with mild-to-moderate essential hypertension were treated for 8 weeks, according to a double-blind design, with either isradipine at 2.5 mg/day (n = 20) or nitrendipine at 10 mg/day (n = 19). After this treatment period, aspirin at 100 mg/day was added to both treatments for a further 8 weeks. At week 0 (after placebo), week 8 (after dihydropyridines), and week 16 (after dihydropyridines + aspirin), blood pressure, plasma levels of beta-thromboglobulin (beta-TG) and platelet aggregation induced by serotonin (5-HT) were measured six times a day (at 5:30 AM, 9:00 AM, noon, 3:30 PM, 7:00 PM, and 11:30 PM). Both isradipine and nitrendipine significantly lowered basal and circadian blood pressure with no differences in antihypertensive efficacy between them. Low doses of aspirin did not interfere with the antihypertensive efficacy of either agent. All patients exhibited increased platelet activity after the placebo period in the form of increased beta-TG levels with circadian changes. The steepest increase in beta-TG was observed during the morning hours until midday. Treatment with the dihydropyridines inhibited platelet aggregability, shifting the beta-TG curve toward lower values. Addition of aspirin to nitrendipine produced a significant decrease and flattening of the beta-TG curve, whereas the combination of aspirin and isradipine was accompanied by a partial increase in plasma beta-TG levels. In conclusion, treatment with dihydropyridines alone or in combination with low-dose aspirin can prevent circadian increases in platelet activity in patients with essential hypertension.


Biodistribution and excretion of colloidal gold nanoparticles after intravenous injection: Effects of particle size.
Inorganic gold nanoparticles (NPs) have a huge potential in targeted drug delivery. Simple preparation and surface modification procedure with their special physicochemical properties of gold NPs attract their use such as tumor targeting and the detection of cancerous cell. Various studies were reported, however, details of biodistribution profile of gold NPs were not enough evaluated. We have studied biodistribution profile of gold NPs having various particle sizes (20, 50 and 100 nm). Gold concentrations in brain, heart, lungs, liver, stomach, pancreas, spleen, kidneys, blood, urine, and feces were measured at 5 minutes, 0.25, 0.5, 1, 2, 3, 6, 12, 18 and 24 hours after administration of gold NPs using inductively coupled plasma atomic emission spectrometry. In lungs and brain, especially 20-nm gold NPs were accumulated after 2-3 hours of dose administration, and they were kept for 24 hours, whereas they showed relatively low accumulation in heart, stomach and pancreas. After 12 hours, 3.3-14.4% of the injected gold were observed in fecal matter and urine. From this study, the application of gold NPs for targeted delivery to lungs and brain and the excretion route of the gold NPs from the body were suggested.


Acute optic neuritis: combined immunological markers and magnetic resonance imaging predict subsequent development of multiple sclerosis. The Optic Neuritis Study Group.
The diagnostic significance of intrathecally synthesized IgG and virus-specific antibodies to measles, rubella and varicella-zoster (MRZ) in cerebrospinal fluid (CSF) remains controversial in cases of acute optic neuritis (AON). This study evaluates the prognostic value of baseline CSF and serum markers in AON, and correlates them with magnetic resonance imaging (MRI) and progression to multiple sclerosis (MS). Paired CSF and serum samples from 36 AON patients, 26 MS patients and 22 controls were analyzed for albumin, IgG, oligoclonal IgG (OI), MRZ antibodies, and blood-CSF barrier function; baseline MRI scanning of the head was also performed. The most sensitive parameter for detection of intrathecal inflammation in AON was OI (75%). Baseline MRI scans revealed abnormalities in 46% of the 28 patients with AON. Fifty percent of AON patients developed MS over the following 4 years. Ninety four percent of patients progressing to MS were positive for either OI, MRI or both. Of the AON patients initially positive for MRI and intrathecally-produced MRZ antibodies, 86% developed MS after 4 years. Only 17% of AON patients with negative results for OI and MRI developed MS. Six patients with abnormal OI but normal MRI progressed to MS. CSF and serum analyses, together with MRI, are the methods of choice for prognostic evaluation of patients with AON.


Biochar production from cellulose under reductant atmosphere: influence of the total pyrolysis time.
Today's rising energy costs, coupled with increasing energy demand, make it necessary to search for more efficient energy processes. In recent years, there have been increasing efforts to develop efficient catalysts based on waste-derived char, by a single step where the carbon precursor and the metallic active phase one undergo a single common thermal process under a reductant atmosphere at high temperature. The use of a reductant atmosphere drives the formation of carbonaceous materials with different characteristics than those obtained under the standard nitrogen-inert one. Our work evaluates the influence of the residence time and the heating rate on the physicochemical properties of the biochar obtained. Relatively long residence times and slow heating rates, improve the yield to the resulting biochar, without increasing production cost, making the subsequent char-based metallic catalyst synthesis more efficient. The heating rate was shown to be key in improving the properties of the char in a smoother and more controlled way, unlocking a new working pathway for the efficient design and production of char-based catalysts in a one-pot synthesis.


Multi-Racial Normative Data for Lobar and Subcortical Brain Volumes in Old Age: Korean and Caucasian Norms May Be Incompatible With Each Other†.
Brain aging is becoming an increasingly important topic, and the norms of brain structures are essential for diagnosing neurodegenerative diseases. However, previous studies of the aging brain have mostly focused on Caucasians, not East Asians. The aim of this paper was to examine ethnic differences in the aging process of brain structures or to determine to what extent ethnicity affects the normative values of lobar and subcortical volumes in clinically normal elderly and the diagnosis in multi-racial patients with Alzheimer's disease (AD). Lobar and subcortical volumes were measured using FreeSurfer from MRI data of 1,686 normal Koreans (age range 59-89) and 851 Caucasian, non-Hispanic subjects in the ADNI and OASIS datasets. The regression models were designed to predict brain volumes, including ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and MRI scanner manufacturers as independent variables. Ethnicity had a significant effect for all lobar (|β| > 0.20, p < 0.001) and subcortical regions (|β| > 0.08, p < 0.001) except left pallidus and bilateral ventricles. To demonstrate the validity of the z-score for AD diagnosis, 420 patients and 420 normal controls were selected evenly from the Korean and Caucasian datasets. The four validation groups divided by race and diagnosis were matched on age and sex using a propensity score matching. We analyzed whether and to what extent the ethnicity adjustment improved the diagnostic power of the logistic regression model that was built using the only z-scores of six regions: bilateral temporal cortices, hippocampi, and amygdalae. The performance of the classifier after ethnicity adjustment was significantly improved compared with the classifier before ethnicity adjustment (ΔAUC = 0.10, D = 7.80, p < 0.001; AUC comparison test using bootstrap). Korean AD dementia patients may not be classified by Caucasian norms of brain volumes because the brain regions vulnerable to AD dementia are bigger in normal Korean elderly peoples. Therefore, ethnicity is an essential factor in establishing normative data for regional volumes in brain aging and applying it to the diagnosis of neurodegenerative diseases.


[The pharmacokinetics of propofol used in cesarean section; a preliminary study in the newborn infant].
A prospective study was carried out: 1) To compare the pharmacokinetics of propofol in two groups of patients: group 1 (eight pregnant women undergoing a prophylactic caesarean section at term), group 2 (control group: eight non pregnant women anaesthetized for short gynaecological procedures). 2) To study the kinetics of this agent in five newborns. Both groups were similar for weight, age, ASA I, oral premedication, anaesthetic method and duration. Dosages were performed using HPLC and results were statistically compared by Student's t-test. The haemodynamic parameters did not show large variations during induction. Propofol plasma levels were high (4,600 +/- 2,200 ng/ml-1) at intubation time; however, at extraction time (group 1) or 25 minutes after induction (group 2), plasma levels were close to anaesthetic threshold. The decreasing slopes were similar in the two groups. The quality of recovery in both groups was satisfactory. The first measured level in umbilical cord blood after birth was low, close to half of the maternal level, without any constant correlation. During the first hour of life, the drug catabolism is lesser in the newborn than in its mother, then plasmatic concentrations decrease similarly. Apgar scores were excellent in four of the five studied newborns; one child had a mean score notwithstanding a low propofol level (171 ng/ml-1), but recovery was perfect after a short oxygenation. There was no significant difference between pregnant women and control group with the propofol dose of 4 mg/kg-1 used for anaesthesia. Thus propofol appears to be convenient for prophylactic caesarean section without damage for the newborn.


Has growth mixture modeling improved our understanding of how early change predicts psychotherapy outcome?
Early change in psychotherapy predicts outcome. Seven studies have used growth mixture modeling [GMM; Muthén, B. (2001). Second-generation structural equation modeling with a combination of categorical and continuous latent variables: New opportunities for latent class-latent growth modeling. In L. M. Collins & A. G. Sawyers (Eds.), New methods for the analysis of change (pp. 291-322). Washington, DC: American Psychological Association] to identify patient classes based on early change but have yielded conflicting results. Here, we review the earlier studies and apply GMM to a new data set. In a university-based training clinic, 251 patients were administered the Outcome Questionnaire-45 [Lambert, M. J., Hansen, N. B., Umphress, V., Lunnen, K., Okiishi, J., Burlingame, G., … Reisinger, C. W. (1996). Administration and scoring manual for the Outcome Questionnaire (OQ 45.2). Wilmington, DE: American Professional Credentialing Services] at each psychotherapy session. We used GMM to identify class structure based on change in the first six sessions and examined trajectories as predictors of outcome. The sample was best described as a single class. There was no evidence of autoregressive trends in the data. We achieved better fit to the data by permitting latent variables some degree of kurtosis, rather than to assume multivariate normality. Treatment outcome was predicted by the amount of early improvement, regardless of initial level of distress. The presence of sudden early gains or losses did not further improve outcome prediction. Early improvement is an easily computed, powerful predictor of psychotherapy outcome. The use of GMM to investigate the relationship between change and outcome is technically complex and computationally intensive. To date, it has not been particularly informative.


Phase II Study of S-1 plus Trastuzumab for HER2-positive Metastatic Breast Cancer (GBCCSG-01).
Treatment strategies for patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC) have significantly progressed. The use of trastuzumab, a monoclonal antibody targeting the HER2 (human epidermal growth factor 2) protein, in combination with chemotherapy improves survival in patients with HER2-positive breast cancer. S-1, an oral combination of fluorouracil derivatives, is widely used in Japan and is more convenient than intravenous drugs. However, little is known about the combination of S-1 and trastuzumab in patients with HER2-positive MBC. We conducted a single-arm, open-label, multicenter prospective phase II study to evaluate the efficacy of an S-1 plus trastuzumab regimen for HER2-positive MBC. S-1 was administered orally [80-120 mg, based on body surface area (BSA)] twice a day for 14 consecutive days in a 3-week cycle. Patients with BSA of <1.25 m2 received a total of 80 mg of S-1, those with BSA ≥1.5 m2 received 120 mg, and the remaining received 100 mg daily in two divided doses. Trastuzumab was administered intravenously at 8 mg/kg on day 1 of the first cycle and at 6 mg/kg on day 1 of subsequent cycles, i.e., every 3 weeks. Between December 2008 and March 2013, 10 patients were enrolled and received a median of 17 (range=3-76) cycles of treatment. Overall response and clinical benefit rates were 60.0% and 90.0%, respectively. Progression-free survival was 15.8 (95% confidence interval=9.4-29.6) months and overall survival was 45.5 (95% confidence interval=37.1-62.2) months. Grade 3/4 adverse events included were neutropenia and hyperglycemia in one patient each (10.0%). There was no clinically significant cardiotoxicity. The combination of S-1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this study. S-1 plus anti-HER2 therapy is a feasible treatment option for HER2-positive MBC.


[Relationship between grief support and burnout syndrome in professionals and technicians of pediatric health].
Detect the presence of Burnout and bereavement support of health professionals in oncology and pediatric intensive care units in Chilean public hospitals. Transversal design of descriptive correlational type. Auto-evaluation using the Maslach Burnout Inventory and Grief Support Health Care Scale instruments in 210 professionals and technicians. For the analysis of a means comparison, the t-student test was used and for the comparison between the variables, the correlations of Pearson and Spearman were used, considering a level of significance of 5%. 4% of the participants presented with Burnout and 71% were at risk of suffering it. 52% had a high level of perception of bereavement support, especially in women and oncology personnel. When correlating support in bereavement and Burnout, the data suggests that both the recognition of the bond, as well as the loss after death of a patient, helps decrease the depersonalization of the professional and improves their personal fulfillment. Professionals in areas of high pediatric complexity are at high risk of Burnout, due to greater emotional exhaustion and low personal accomplishment. However, a greater perception of recognition and support in their bereavement is a factor that can reduce that risk. Therefore, continuous intervention programs are required within these units, with concrete strategies for accompaniment, teamwork and mourning rituals.


Thinking Forward: Future-oriented Thinking among Patients with Tobacco-associated Thoracic Diseases and Their Surrogates.
The goal of shared decision making is to match patient preferences, including evaluation of potential future outcomes, with available management options. Yet, it is unknown how patients with smoking-related thoracic diseases or their surrogates display future-oriented thinking. To document prevalent themes in patients' and potential surrogate decision makers' future-oriented thinking when facing preference-sensitive choices. We conducted 44 scenario-based semistructured interviews among a diverse group of outpatients with smoking-associated thoracic diseases and potential surrogates for whom one of three preference-sensitive decisions would be medically relevant. Using content analysis, we documented prevalent themes to understand how these individuals display future-oriented thinking. Patients and potential surrogates generally expressed expectations for future outcomes but also acknowledged their limitations in doing so. When thinking about potential outcomes, decision makers relied on past experiences, including those only loosely related; perceived familiarity with treatment options; and spirituality. The content of these expectations included effects on family, emotional predictions, and prognostication. For surrogates, a tension existed between hope-based and fact-based expectations. Patients and surrogates may struggle to generate expectations, and these future-oriented thoughts may be based on loosely related past experiences or unrealistic optimism. These tendencies may lead to errors, preventing selection of treatments that promote true preferences. Clinicians should explore how decision makers engage in future-oriented thinking and what their expectations are as a component of the shared decision-making process. Future research should evaluate whether targeted guidance in future-oriented thinking may improve outcomes important to patients.


Exploring the Preferences of the Australian Public for Antibiotic Treatments: A Discrete Choice Experiment.
Identify Australian public preferences for antibiotic treatments in the context of antibiotic stewardship. A discrete choice experiment (DCE) was conducted in Australia to investigate the importance of seven attributes associated with antibiotic treatments and related stewardship practices: contribution to antimicrobial resistance (AMR), treatment duration, side effects, days needed to recover, days before taking antibiotics, treatment failure and out-of-pocket costs. The DCE data were analysed using conditional logit, mixed logit and latent class conditional logit models. The relative importance of each attribute was calculated. A total of 1882 respondents completed the survey; the main study sample consist of 1658 respondents (mean age 48 years) who passed quality checks. All seven attributes significantly influenced respondents' preferences for antibiotic treatments. Based on the designed attribute levels in the DCE, on average, out-of-pocket costs (32.8%) and contribution to antibiotic resistance (30.3%) were the most important attributes, followed by side effects (12.9%). Days before starting medication was least important (3.9%). Three latent classes were identified. Class 1 (including respondents who were more likely to be older and more health literate; 24.5%) gave contribution to antibiotic resistance greater importance in treatment preferences. Class 2 (including respondents more likely to report poorer health; 25.2%) gave out-of-pocket costs greater importance. The remaining (50.4%), who were generally healthier, perceived side effects as the most important attribute. Despite concerted public awareness raising campaigns, our results suggest that several factors may influence the preferences of Australians when considering antibiotic use. However, for those more likely to be aware of the need to preserve antibiotics, out-of-pocket costs and limiting the contribution to antibiotic resistance are the dominant influence. Delays in starting treatment were not important for any latent class, suggesting public tolerance for this measure. These results could help inform strategies to promote prudent antibiotic stewardship.


Ethical issues in psychotherapy with adolescents.
Treating adolescents in psychotherapy presents a number of unique ethical challenges. Because many adolescents who enter treatment have not yet attained the age of majority, reside in families that include other people with emotional difficulties, attend school, become involved with community agencies (e.g., the courts), and must generally take direction from adult authority figures, the role of the therapist becomes particularly complex. The unique dilemmas include developing specialized clinical competence, treatment contracting, choice of treatment modality, direction of the therapeutic process, and confidentiality. This article discusses the range of ethical concerns involved in treating adolescents and suggests strategies for optimal ethical care.


MSCs with ACE II gene affect apoptosis pathway of acute lung injury induced by bleomycin.
The aim of this study was to evaluate the effect and related mechanisms of Mesenchymal stem cells (MSCs) and Angiotensin converting enzyme II (ACE II) on acute lung injury (ALI). MSCs were separated from umbilical cord cells, and the changes of phenotype before and after ACE II silence were observed using Flow Cytometer. ALI model was induced by 10 mg/mL bleomycin in 60 Balb/c mice, and the rest 8 mice were regarded as the baseline group. The mice were randomly divided into four groups (n = 15): control, ACE II, stem, and stem + ACE II. The apoptotic index (AI) was calculated using TUNEL, and the detection of protein and mRNA of Bax, Bak and p53, Bcl-2, Grp78, CHOP and Caspase 12 were used by western-blot and RT-PCR, respectively. The umbilical cord cells differentiated into stable MSCs about 14 days, and ACE II transfection reached a peak at the 5th day after transfection. ACE II silence did not affect the phenotype of MSCs. All the proteins and mRNAs expression except Bcl-2 in the stem and stem + ACE II were significantly lower than those in control from 8 h (p < 0.05, p < 0.01), while Bcl-2 exhibited an opposite trend. Stem + ACE II performed a better effect than single stem in most indexes, including AI (p < 0.05, p < 0.01). The co-administration of MSCs and ACE II can significantly suppress apoptosis in ALI mice, and may be an effective clinical treatment for ALI.


Synchronous Acute Appendicitis and Acute Cholecystitis: A Case Report.
Acute cholecystitis (AC) and acute appendicitis (AA), independently, are among the most commonly diagnosed conditions in the emergency department (ED). However, their synchronous presentation is very rare. Here, we present a 31-year-old man with worsening right flank abdominal pain, nausea, and vomiting. Physical examination results were significant for moderate to severe right upper abdominal quadrant pain with a positive Murphy's sign and right lower quadrant pain with rebound. Workup in the ED revealed leukocytosis with a left shift, and the abdominal ultrasound and computerized tomography scan showed AA and AC. A literature review revealed a paucity of publications on concomitant AA and AC. Reporting new cases will contribute to improving our understanding of the biology, natural history, and management of this rare pathological combination.


Tough Bonding, On-Demand Debonding, and Facile Rebonding between Hydrogels and Diverse Metal Surfaces.
Hybrid systems of hydrogels and metals with tough bonding may find widespread applications. Here, a simple and universal method to obtain strong adhesion between hydrogels and diverse metal surfaces, such as titanium, steel, nickel, tantalum, argentum, and aluminum, with adhesion energy up to >1000 J m-2 is reported. To achieve such, the metal surfaces are instantly modified with a linker molecule via soaking, dip-coating, or drop-casting. The designed linker molecule has a carboxylic acid group to bind with a metal surface, and a methacrylic group to crosslink with a hydrogel, thus bridging the interface between them. In addition, by introducing a stimulus-responsive disulfide bond into the linker molecule, the on-demand debonding between toughly bonded hydrogel and metal surface, which is enabled by reductive cleavage of the disulfide chemical linkage, is also demonstrated. More interestingly, after the reductive debonding, the resulting metal surface with free thiol groups can be easily rebonded with a second hydrogel without any further surface modification. The strategy may provide unique opportunities in designing hybrid devices that are suitable for complex and dynamic environments.


Identification of pyroptosis-related lncRNA subtype and signature predicts the prognosis in bladder cancer.
Pyroptosis is a new type of programmed cell death involved in all stages of tumorigenesis. Herein, a comprehensive study was conducted to evaluate the prognostic significance of pyroptosis-related lncRNAs in bladder cancer. Consensus clustering analysis was performed to identify the subclusters of bladder cancer. The prognostic pyroptosis-related lncRNA signature was constructed using LASSO Cox regression analysis. Consensus clustering identified 2 clusters of bladder cancer. Interestingly, significant differences in the ESTIMAE score, immune cell infiltration and immune checkpoint expression were obtained between the 2 clusters. A signature consisting of 11 pyroptosis-related lncRNAs was established and it had a good performance in predicting the overall survival rate of bladder cancer, with an AUC of 0.713. Moreover, pyroptosis-related lncRNA signature acted as a risk factor in bladder cancer. Bladder cancer patients with high-risk score had a higher tumor grade and higher clinical stage. A significant correlation was obtained between the risk score and immune cell infiltration. The expression of most checkpoints was higher in bladder cancer patients with high-risk score. A novel pyroptosis-related lncRNA signature was identified with prognostic value for bladder cancer patients. Pyroptosis-related lncRNAs have a potential role in cancer immunology and may serve as prognostic or therapeutic targets in bladder cancer.


Systematic studies of light scattering. 1: Particle shape.
The light scattering properties of twenty-eight particles, spanning four sizes (near the resonance region) and seven related shapes (a 4:1 cylinder, 4:1 and 2:1 prolate spheroids, a sphere, 2:1 and 4:1 oblate spheroids, and a 4:1 disk), are presented for a common index of refraction, m = 1.61-i0.004, representing silicates. Microwave analog and theoretical methods were used to derive the scattered intensity and degree of polarization as a function of the scattering angle along with the extinction. All results refer to an ensemble or a cloud of identical particles because averages have been taken over random particle orientations. The degree of polarization, backscatter, and the radiation-pressure cross section are most sensitive to particle shape, implying that the use of Mie theory may be inappropriate for many applications.


The respiratory chain provides salt stress tolerance by maintaining a low NADH/NAD+ ratio in Zymomonas mobilis.
The respiratory chain of ethanol-producing Zymomonas mobilis shows an unusual physiological property in that it is not involved in energy conservation, even though this organism has a complete electron transport system. We reported previously that respiratory-deficient mutants (RDMs) of Z. mobilis exhibit higher growth rates and enhanced ethanol productivity under aerobic and high-temperature conditions. Here, we demonstrated that the salt tolerance of RDM strains was drastically decreased compared with the wild-type strain. We found that the NADH/NAD+ ratio was maintained at low levels in both the wild-type and the RDM strains under non-stress conditions. However, the ratio substantially increased in the RDM strains in response to salt stress. Complementation of the deficient respiratory-chain genes in the RDM strains resulted in a decrease in the NADH/NAD+ ratio and an increase in the growth rate. In contrast, expression of malate dehydrogenase, activity of which increases the supply of NADH, in the RDM strains led to an increased NADH/NAD+ ratio and resulted in poor growth. Taken together, these results suggest that the respiratory chain of Z. mobilis functions to maintain a low NADH/NAD+ ratio when the cells are exposed to environmental stresses, such as salinity.


Human development x: Explanation of macroevolution--top-down evolution materializes consciousness. The origin of metamorphosis.
In this paper, we first give a short discussion of the macroevolution viewing life as information-directed, complex, dynamic systems. On this basis, we give our explanation of the origin of life and discuss the top-down evolution of molecules, proteins, and macroevolution. We discuss these subjects according to our new holistic biological paradigm. In view of this, we discuss the macroevolution of the organism, the species, the biosphere, and human society. After this, we discuss the shift in evolution from natural selection to a new proposed process of nature called the "metamorphous top-down" evolution. We discuss the capability of the evolutionary shift to govern some of the processes that lead to the formation of new species. We discuss the mechanisms we think are behind this proposed shift in evolution and conclude that this event is able to explain the huge biological diversity of nature in combination with evolutionary natural selection. We also discuss this event of nature as an isolated, but integrated, part of the universe. We propose the most important genetic and biochemical process that we think is behind the evolutionary shift as a complicated symbiosis of mechanisms leading to metamorphosis in all biological individuals, from bacteria to humans. The energetic superorbital that manifests the consciousness governs all these processes through quantum chemical activity. This is the key to evolutionary shift through the consciousness, and we propose to call this process "adult human metamorphosis".


Serum lipemia: an overlooked cause of tissue hypoxia.
This article discusses an overlooked subject, namely that serum lipemia affects the transfer of oxygen from the blood to the tissues. It discusses several mechanisms whereby lipemia limits oxygen diffusion. Observations of improved tissue oxygenation in atherosclerotic patients coincident with the clearing of lipemia by heparin are described. Conversely, the adverse effects of increased lipemia after fat meals upon tissue oxygen are noted. The contribution of hypoxia of the arterial wall to atherogenesis is outlined, and its adverse effects in the ischemic heart are listed.


[Pseudoaneurysm - a rare complication after insertion of a distal locking bolt of an intramedullary femur nail].
A pseudoaneurysm is caused by an extravasal hematoma after vessel injury. Persistent blood supply via the afferent artery can lead to aneurysm growth with potential rupture of the lesion. We present a case of a 27-year-old man who developed three independent pseudoaneurysms after insertion of percutaneous distal locking bolts for static locking of an intramedullary femur nail. Color-coded Doppler sonography and intraarterial subtraction angiography were used to detect the lesion. Successful treatment consisted of endovascular embolization (coiling) with injection of a platinum coil into the aneurysm's supplying vessel. Pseudoaneurysm after fracture or fracture fixation represents a rare complication, but the risk of acute bleeding by pseudoaneurysm rupture should not be neglected.


Impact of Social Desirability and Common Method Variance on Two Measures of Entitlement.
Entitlement is the predisposition toward expecting or demanding more rewards than someone else regardless of one's own contribution, effort, or performance. This study examines the impact of social desirability and common method variance on the discriminant validity of the two most popular measures of entitlement: The Psychological Entitlement Scale and the Entitlement subscale of the Narcissistic Personality Inventory. Data were gathered using three independent samples. In all three studies, forcing items to load on their intended and separate constructs measuring entitlement fit the data well thus providing some evidence of discriminant validity. The correlation between the two entitlement constructs was larger than in previous studies but short of that which is necessary for collinearity providing further evidence of discriminant validity in each study. In each study the amount of shared variance between the two latent entitlement constructs was more than the variance explained in either construct thus failing to provide evidence of discriminant validity. These two measures are similarly affected by socially desirable responding but not likely contaminated by common method variance. Because of their consistently and moderately strong correlation, the PES and the entitlement subscale of the NPI likely measure different but strongly related constructs.


Decrease of 4-vinylguaiacol during beer aging and formation of apocynol and vanillin in beer.
In this study the decrease of 4-vinylguaiacol (4VG) during beer aging was investigated and the products that arise from it were identified. Two compounds, vanillin and apocynol, were identified in beer model solutions after forced aging and in naturally aged beers by GC-MS and HPLC-ECD analyses. Both account for up to 85% of the decrease of 4VG. Only in the presence of substantial amounts of oxygen in the bottle headspace was vanillin detected. Apocynol [4-(1-hydroxyethyl)-2-methoxyphenol] was found to be the main degradation product, and its formation was shown to be highly dependent on the beer pH. Because both apocynol and vanillin have a clear vanilla-like aroma, the decrease of 4-vinylguaiacol during beer aging might impart a shift from a clove-like aroma in fresh specialty beers (such as wheat beers and other top-fermented blond or dark ales) to a sweeter, more vanilla-like flavor impression of aged specialty beers.


Studies of multiple sclerosis in communities concerned about environmental exposures.
Multiple sclerosis (MS) is an autoimmune disease that differentially affects women, people 30-60 years old, and Caucasians. Evidence indicates that it is a complex disease determined by both environmental factors and genetic susceptibility. People across the United States have expressed concern about perceived clusters of MS in their communities and the role of environmental exposures in the development of the disease. The Agency for Toxic Substances and Disease Registry (ATSDR) has funded several studies to address this issue, including a cluster investigation, several prevalence studies, and a case-control study. The cluster investigation illustrated that there are few data regarding the number of individuals with MS in the United States. Prevalence studies were conducted in Ohio, Missouri, and Texas to address this deficiency. The results support a regional difference in MS prevalence, although the reason for this difference is unclear. The results also underscore the need for additional epidemiological information about the distribution of MS in other areas of the United States and information on the underlying etiology of the disease. A case-control study is currently being conducted to examine potential risk factors for MS, including the role of environmental exposures and genetic susceptibility. Future research on MS should focus on large-scale studies and include collaboration among researchers with varied fields of expertise, such as epidemiology, neurology, and genetics.


[Level of completion of the prehospital care and transfer record as a quality indicator in an emergency medical service].
BASICS: A Prehospital Care and Transfer Recording (PCTR) is an out-of-hospital medical recording. This paper was made to assess and compare the level of fulfillment of the basic parameters of the PCTR developed by the Life Support Units with nurses (Life Support Units with Nurse, LSUwN and without nurses (Basic Life Support Units, BLSU) from SAMUR Bilbao in 2010. A descriptive, retrospective and comparative study was performed by analysing a randomized sample of 660 PCTR (precision 3%), aiming to check the fulfillment of the basic data. 98.33% of total recordings were readable. In overall, fulfillment rate was 90.31% (CI 89.24- 97.3 71%) of all basic parameters for LSUwN PCTR and 84.81% (CI 83.56 to 86%) for BLSU. 34.1% of PCTR were completely and correctly fulfilled. The LSUwN scored significantly better (p < 0.000). There were recording failures in "date and time", "address" and "physical examination". There were differences between the recording of clinical and administrative information (88.64% vs 86.72%, p = 0.02). In order to consider a parameter has optimal, it has to reach 100% of fulfillment. If it doesn't, and its score reaches no more than 80%, it should be reviewed. In this case, the results would be considered acceptable, but the administrative items of BLSU records, and allergies in both units should be strengthened. LSUwN has obtained better scores. The need of recording clinical information must be instilled as evidence of quality care.


Genome-wide identification, characterization analysis and expression profiling of auxin-responsive GH3 family genes in wheat (Triticum aestivum L.).
Auxin affects many aspects of plant growth and development by regulating the expression of auxin-responsive genes. As one of the three major auxin-responsive families the Gretchen Hagen3 (GH3) gene family maintains hormonal homeostasis by conjugating excess indole-3-acetic acid (IAA), salicylic acid (SA), and jasmonic acid (JA) to amino acids during hormone and stress-related signaling. Although some work has been carried out the functions of wheat GH3 (TaGH3) family genes in response to abiotic stresses (including salt stress and osmotic stress) are largely unknown. Access to the complete wheat genome sequence permits genome-wide studies on TaGH3s. We performed a systematic identification of the TaGH3 gene family at the genome level and detected 36 members on 14 wheat chromosomes. Many of the genes were segmentally duplicated and Ka/Ks and inter-species synthetic analyses indicated that polyploidization was the contributor to the increased number of TaGH3 members. Phylogenetic analyses revealed that TaGH3 proteins could divided into three major categories (TaGH3-I, TaGH3-II, and TaGH3-III). Diversified cis-elements in the promoters of TaGH3 genes were predicted as essential players in regulating TaGH3 expression patterns. Gene structure and motif analyses indicated that most TaGH3 genes have relatively conserved exon/intron arrangements and motif compositions. Analysis of multiple transcriptome data sets indicated that many TaGH3 genes are responsive to biological and abiotic stresses and possibly have important functions in stress response. qRT-PCR analysis revealed that TaGH3s were induced by salt and osmotic stresses. Customized annotation results revealed that TaGH3s were widely involved in phytohormone response, defense, growth and development, and metabolism. Overall, our work provides a comprehensive insight into the TaGH3 family members, and a basis for the further study of their biological functions in wheat.


Further biochemical characterization of an Na+ pump inhibitor purified from human urine.
An increase in endogenous Na+,K+-ATPase inhibitor(s) with digitalis-like properties has been reported in chronic renal insufficiency, in Na+-dependent experimental hypertension and in some essential hypertensive patients. The present study specifies some properties and some biochemical characteristics of a semipurified compound from human urine having digitalis-like properties. The urine-derived inhibitor (endalin) inhibits Na+,K+-ATPase activity and [3H]-ouabain binding, and cross-reacts with anti-digoxin antibodies. The inhibitory effect on ATPases of endalin is higher on Na+,K+-ATPase than on Mg2+-ATPase and Ca2+-ATPase. The mechanism of endalin action on highly purified Na+,K+-ATPase was compared to that of ouabain and was similar in that it reversibly inhibited Na+,K+-ATPase activity; it inhibited Na+,K+-ATPase non-competitively with ATP; its inhibitory effect was facilitated by Na+; K+ decreased its inhibitory effect on Na+,K+-ATPase; it competitively inhibited ouabain binding to the enzyme; its binding was maximal in the presence of Mg2+ and Pi; it decreased the Na+ pump activity in human erythrocytes; it reduced serotonin uptake by human platelets; and it was diuretic and natriuretic in rat bioassay. The endalin differed from ouabain in only three aspects: its inhibitory effect was not really specific for Na+,K+-ATPase; its binding to the enzyme was undetectable in the presence of Mg2+ and ATP; it was not kaliuretic in rat bioassay. Endalin is a reversible and partial specific inhibitor of Na+,K+-ATPase, its Na+,K+-ATPase inhibition closely resembles that of ouabain and it could be considered as one of the natriuretic hormones.


Antibody production in vitro. II. Effects of actinomycin D and puromycin on the secondary response to sheep erythrocytes.
The effects of actinomycin D and puromycin on spleen cell suspensions from rabbits immunized to SRC's were studied. These inhibitors, in high concentration, suppressed PFC's when added initially to recently isolated cells. When such cells were incubated for several days in the presence of both antigen and inhibitor, both actinomycin D and puromycin produced an increase in PFC's after the initial suppression. This recovery effect was best seen with cells from rabbits killed 3 days after boosting with SRC's, and was usually absent when cells were taken from rabbits killed 2 days after boosting. When actinomycin D or puromycin was added after several days in culture in the presence of SRC's, surviving PFC's were found to be not only resistant to these inhibitors, but there was also an increased number of PFC's compared to similar cultures incubated without these agents. Radioautographic studies showed that PFC's stimulated by the presence of actinomycin D or puromycin were not incorporating precursors for RNA or protein synthesis. In view of the known mode of action of these inhibitors, it was postulated that they were stimulating antibody production by PFC's in vitro either by interfering with represser mechanisms or stimulating the completion of antibody molecules, perhaps by causing the release of preformed antibody chains from ribosomes. Since the presence of specific antigens in vitro were necessary for these observed stimulatory effects on PFC's, and since antigens were producing an effect on antibody production on cells which were being suppressed by these inhibitors, added initially, it was further suggested that one role of antigen in the immune response was concerned with the completion of antibody synthesis on the ribosomes, perhaps by acting as an inducer as has been suggested previously (1).


SEROLOGY OF THE SOLUBLE ANTIGENS OF THE PATHOGENIC CLOSTRIDIA.
Ellner, Paul D. (University of Vermont, Burlington), and Stanley S. Green. Serology of the soluble antigens of the pathogenic clostridia. J. Bacteriol. 86:1084-1097. 1963.-Soluble antigens of 42 strains, representing nine species of clostridia commonly occurring in human infections, were prepared by growing the organisms in a nonantigenic medium. Serological studies demonstrated the occurrence of considerable strain variation within each species. Interactions among the nine species, as well as with the previously characterized Clostridium perfringens, were also investigated. Extreme heterogeneity was observed among the species studied, with many cross-reactions due to common antigens, although species-specific antigens were also found in some cases. Occasional weak reactions were also demonstrated between certain clostridial antisera and the soluble antigens of three of the four species of Bacillus studied.


Understanding the basis of space closure in Orthodontics for a more efficient orthodontic treatment.
Space closure is one of the most challenging processes in Orthodontics and requires a solid comprehension of biomechanics in order to avoid undesirable side effects. Understanding the biomechanical basis of space closure better enables clinicians to determine anchorage and treatment options. In spite of the variety of appliance designs, space closure can be performed by means of friction or frictionless mechanics, and each technique has its advantages and disadvantages. Friction mechanics or sliding mechanics is attractive because of its simplicity; the space site is closed by means of elastics or coil springs to provide force, and the brackets slide on the orthodontic archwire. On the other hand, frictionless mechanics uses loop bends to generate force to close the space site, allowing differential moments in the active and reactive units, leading to a less or more anchorage control, depending on the situation. This article will discuss various theoretical aspects and methods of space closure based on biomechanical concepts.


Roles of Low-Dimensional Nanomaterials in Pursuing Human-Machine-Thing Natural Interaction.
A wide variety of low-dimensional nanomaterials with excellent properties can meet almost all the requirements of functional materials for information sensing, processing, and feedback devices. Low-dimensional nanomaterials are becoming the star of hope on the road to pursuing human-machine-thing natural interactions, benefiting from the breakthroughs in precise preparation, performance regulation, structural design, and device construction in recent years. This review summarizes several types of low-dimensional nanomaterials commonly used in human-machine-thing natural interactions and outlines the differences in properties and application areas of different materials. According to the sequence of information flow in the human-machine-thing interaction process, the representative research progress of low-dimensional nanomaterials-based information sensing, processing, and feedback devices is reviewed and the key roles played by low-dimensional nanomaterials are discussed. Finally, the development trends and existing challenges of low-dimensional nanomaterials in the field of human-machine-thing natural interaction technology are discussed.


Markers of cadmium exposure in workers in a cadmium pigment factory after changes in the exposure conditions.
The objective of this study was to assess changes in concentrations of cadmium in the blood (Cd-B), cadmium in the urine (Cd-U), beta2-microglobulin in the serum (beta2-mG-S) and beta2-microglobulin in the urine (beta2-mG-U) of workers at a cadmium (Cd) pigment factory in Japan in which exposure conditions improved. We evaluated reversibility of these markers in continuously employed workers in relation to changes in exposure levels resulting from improvements in the workplace and the reduced production of Cd. Our study involved both environmental and biological monitoring. Data were collected for four years. We measured the Cd concentration in the air of each work area, using the time-weighted average (TWA). Cd-B and Cd-U were measured in workers as direct indices of Cd exposure. beta2-mG-S and beta2-mG-U were measured as markers of renal tubular function. Exposure levels were high in all work areas, according to the criteria set by the American Conference of Governmental Industrial Hygienists (ACGIH). Workers' Cd-B and Cd-U concentrations reflected high levels of exposure. Correlation was found between these direct indices and beta2-mG-S concentrations. Since the second year, ambient Cd concentrations decreased and reacted markers have been improved. Our results suggest that Cd-B, Cd-U, beta2-mG-S and beta2-mG-U are appropriate markers for monitoring both the level of Cd exposure and the tubular function of workers. Reversibility of urinary low molecular weight protein was observed in the workers over the four years.


A new species of Muscicapa flycatcher from Sulawesi, Indonesia.
The Indonesian island of Sulawesi, a globally important hotspot of avian endemism, has been relatively poorly studied ornithologically, to the extent that several new bird species from the region have been described to science only recently, and others have been observed and photographed, but never before collected or named to science. One of these is a new species of Muscicapa flycatcher that has been observed on several occasions since 1997. We collected two specimens in Central Sulawesi in 2012, and based on a combination of morphological, vocal and genetic characters, we describe the new species herein, more than 15 years after the first observations. The new species is superficially similar to the highly migratory, boreal-breeding Gray-streaked Flycatcher Muscicapa griseisticta, which winters in Sulawesi; however, the new species differs strongly from M. griseisticta in several morphological characters, song, and mtDNA. Based on mtDNA, the new species is only distantly related to M. griseisticta, instead being a member of the M. dauurica clade. The new species is evidently widely distributed in lowland and submontane forest throughout Sulawesi. This wide distribution coupled with the species' apparent tolerance of disturbed habitats suggests it is not currently threatened with extinction.


The role of specific side groups and pH in magnetization transfer in polymers.
The nature of water-macromolecule interactions in aqueous model polymers has been investigated using quantitative measurements of magnetization transfer. Cross-linked polymer gels composed of 94% water, 3% N,N'-methylene-bis-acrylamide, and 3% functional monomer (acrylamide, methacrylamide, acrylic acid, methacrylic acid, 2-hydroxyethyl-acrylate, or 2-hydroxyethyl-methacrylate) were studied. Water-macromolecule interactions were modified by varying the pH and specific functional group on the monomer. The magnitudes of the interactions were quantified by measuring the rate of proton nuclear spin magnetization exchange between the polymer matrix and the water. This rate was highly sensitive to the presence of carboxyl side groups on the macromolecule. However, the dependence of the rate on pH was not consistent with simple acid/base-catalyzed chemical exchange, and instead, the data suggest that multiequilibria proton exchange, a wide distribution in surface group pK values, and/or a macromolecular structural dependence on pH may play a significant role in magnetization transfer in polymer systems. These model polymer gels afford useful insights into the relevance of chemical composition and chemical dynamics on relaxation in tissues.


Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe.
To improve visualization of upper tract urothelial carcinomas. Previous studies using the novel pH low insertion peptide (pHLIP) variant 3 (Var3) conjugated to indocyanine green (ICG) have demonstrated high sensitivity and specificity for imaging of bladder urothelial carcinoma. Here, we describe a novel approach for the imaging of upper tract urothelial carcinomas using ICG-Var3 pHLIP. Twelve ex-vivo upper urinary tract specimens were irrigated with ICG-Var 3 pHLIP for 15 minutes and then examined using a white light laparoscopic camera followed by near infrared fluorescent (NIRF) imaging using a Stryker 1588 AIM imaging system. Standard histopathologic evaluation was performed and findings were correlated with white light and ICG-Var3 NIRF imaging. One patient who underwent radical nephrectomy for renal cell carcinoma was used as a negative control. Nineteen lesions were identified on histopathologic evaluation in 10 patients, including 82% high-grade urothelial carcinoma and 18% low-grade urothelial carcinoma. Nineteen (100%) malignant lesions were identified using NIRF imaging, while 15 (78.9%) lesions were identified using conventional white light examination. The sensitivity of ICG-Var3 pHLIP NIRF imaging was 100% compared to 78.9% white light examination. Both modalities are 100% specific. Benign collecting systems and ureters did not show uptake of the pHLIP construct. In this feasibility study, the ICG-Var3 pHLIP imaging agent demonstrated superior diagnostic performance compared to conventional white light examination. While additional studies are required for validation and in-vivo translation, pHLIP-based imaging represents a promising tool to improve the evaluation and management of upper tract urothelial carcinoma.


Nuclear remodeling assay in Xenopus egg extract.
Xenopus egg extract is an ideal material to identify nuclear remodeling activities important for nuclear cloning. Since the protocol for egg extract preparation was established more than 20 yr ago, egg extract has been widely used as a source for the purification of factors associated with a number of physiological activities. The eggs are large, easily obtained in large quantities, and are abundant in a variety of bioactive proteins. Many aspects of somatic nuclear remodeling observed in nuclear cloning are recapitulated in somatic nuclei incubated in egg extract. Our in vitro nuclear remodeling assay has proven effective for the purification of two novel nuclear remodeling activities, ISWI, a key player in the dissociation of TATA binding protein from chromatin, and FRGY2a and FRGY2b, two proteins capable of nucleolar disassembly. Here we outline our protocol of egg extract preparation and in vitro nuclear remodeling assay, as well as the purification method for FRGY2a and FRGY2b. Our in vitro nuclear remodeling assay in combination with egg extract will serve as a powerful tool with which to biochemically uncover molecular events involved in nuclear cloning.


Vaccination With Live Attenuated Vaccines in Four Children With Chronic Myeloid Leukemia While on Imatinib Treatment.
Chronic myeloid leukemia (CML) in childhood and adolescence is a rare malignancy that can successfully be treated with the tyrosine kinase inhibitor (TKI) imatinib. According to the current experience, treatment is necessary for years and, in the majority of cases, a lifelong approach is required to control the malignant disease. To what extent imatinib causes immunosuppression in different age cohorts is a controversial discussion. According to general medical recommendations, live vaccines are contraindicated in individuals treated with imatinib. However, a recent increase in the number of globally reported cases of measles has been observed and continues to rise. Due to the high contagiousness of the virus, near-perfect vaccination coverage (herd immunity of 93 to 95%) is required to effectively protect against measles resurgence-a scenario that is not realistic in many countries. When four teenagers with CML (median age 13 years, range 12-15) who were enrolled into pediatric trial CML-paed II while on imatinib treatment (median treatment duration 36 months, range 11-84) were identified without protective measles and/or varicella titers, we carefully balanced the risks of a live vaccination under immunosuppressive TKI medication against the benefit of being protected. The patients underwent live vaccination with the live attenuated vaccines M-M-RVAX Pro® and Varivax® simultaneously (Patient #1), Priorix® and Varilix® consecutively (Patient #2), and Priorix® (Patients #3 and #4). While the first three patients were vaccinated while receiving TKI therapy, treatment with imatinib was interrupted in patient #4 for 1 week prior and 2 weeks after vaccination. Patients #1 and #3 reacted with stable long-term seroconversion. In Patient #2, serum titer conversion against measles and varicella could not be demonstrated and thus revaccination with Priorix® and Varilix® was performed 3 years later. However, protective titers did not develop or were lost again. Patient #4 also lost protective titers against measles when assessed 10 months after vaccination, but revaccination resulted in stable seroprotective titers over 12 months after the last vaccination during ongoing imatinib treatment. We conclude that in all patients, the safety of live vaccines could be documented, as no acute or late adverse events were observed. However, in line with observations that memory B-cells are lost under exposure to imatinib, revaccination may become necessary (two out of four patients in this small series lost their seroprotection). Considering that the number of cases is very small, we also suggest some criteria for decision-making regarding live vaccinations of CML patients treated with imatinib.


Isolated tubercular hypoglossal nerve paralysis.
Hypoglossal nerve palsy is not an uncommon neurological finding but primary nasopharyngeal tuberculosis (TB) presenting as hypoglossal nerve palsy is very rare. A 31-year-old woman presented with headache and progressive tongue deviation towards the right side. Diagnostic nasal endoscopy revealed soft tissue mass lesion on the posterior wall of nasopharynx while MRI revealed isointense tumour in nasopharynx with normal hypoglossal nerve and brain. Histopathological examination found TB. We discuss the clinical challenges and possible pathogenesis of this rare clinical entity.


Understanding the interplay of weak forces in [3,3]-sigmatropic rearrangement for stereospecific synthesis of diamines.
Chiral diamines are important building blocks for constructing stereoselective catalysts, including transition metal based catalysts and organocatalysts that facilitate oxidation, reduction, hydrolysis, and C-C bond forming reactions. These molecules are also critical components in the synthesis of drugs, including antiviral agents such as Tamiflu and Relenza and anticancer agents such as oxaliplatin and nutlin-3. The diaza-Cope rearrangement reaction provides one of the most versatile methods for rapidly generating a wide variety of chiral diamines stereospecifically and under mild conditions. Weak forces such as hydrogen bonding, electronic, steric, oxyanionic, and conjugation effects can drive this equilibrium process to completion. In this Account, we examine the effect of these individual weak forces on the value of the equilibrium constant for the diaza-Cope rearrangement reaction using both computational and experimental methods. The availability of a wide variety of aldehydes and diamines allows for the facile synthesis of the diimines needed to study the weak forces. Furthermore, because the reaction generally takes place cleanly at ambient temperature, we can easily measure equilibrium constants for rearrangement of the diimines. We use the Hammett equation to further examine the electronic and oxyanionic effects. In addition, computations and experiments provide us with new insights into the origin and extent of stereospecificity for this rearrangement reaction. The diaza-Cope rearrangement, with its unusual interplay between weak forces and the equilibrium constant of the reaction, provides a rare opportunity to study the effects of the fundamental weak forces on a chemical reaction. Among these many weak forces that affect the diaza-Cope rearrangement, the anion effect is the strongest (10.9 kcal/mol) followed by the resonance-assisted hydrogen-bond effect (7.1 kcal/mol), the steric effect (5.7 kcal/mol), the conjugation effect (5.5 kcal/mol), and the electronic effect (3.2 kcal/mol). Based on both computation and experimental data, the effects of these weak forces are additive. Understanding the interplay of the weak forces in the [3,3]-sigmatropic reaction is interesting in its own right and also provides valuable insights for the synthesis of chiral diamine based drugs and catalysts in excellent yield and enantiopurity.


Clinical laboratory hematology reference values among infants aged 1month to 17 months in Kombewa Sub-County, Kisumu: A cross sectional study of rural population in Western Kenya.
There is an urgent need for reliable region-specific hematological reference values for clinical monitoring. Laboratory reference ranges are important for assessing study participant eligibility, toxicity grading and management of adverse events in clinical trials and clinical diagnosis. Most clinical laboratories in Kenya rely on hematological reference values provided by instrument manufacturers and/or textbooks, which are based on population from Europe or North America. The use of such values in medical practice could result in improper patient management, selection bias in selection of appropriate participants for clinical trials and flawed classification of the clinical adverse events when applied to African populations. The aim of this study was to establish local laboratory hematological reference values in infants aged 1 month to 17 months from Kombewa Sub-county that could be true representative of the existing rural population. The study participants in the current study were those who had previously been recruited from GSK-sponsored study. This study was a phase III, Double Blind, Randomized, GSK-sponsored, Malaria Vaccine Clinical Trial that was conducted in infants aged 1month to 17months. 1,509 participants were included in the study analysis. Data were partitioned into 3 different age groups (1-6 months[m], 6-12 m and 12-17 m) and differences between gender were compared within each group. Data were analyzed using Graphpad prism V5 to generate 95% reference ranges (2.5th-97.5th percentile). There was evidence of gender differences in hemoglobin values (p = 0.0189) and platelet counts (p = 0.0005) in the 1 to 6m group. For the 12-17m group, there were differences in MCV (p<0.0001) and MCH (p = 0.0003). Comparing gender differences for all age groups, differences were noted in percent lymphocytes (p = 0.0396), percent monocytes (p = 0.0479), percent granulocytes (p = 0.0044), hemoglobin (p = 0.0204), hematocrit (p = 0.0448), MCV (p = 0.0092), MCH (p = 0.0089), MCHC (p = 0.0336) and absolute granulocytes (p = 0.0237). In 1 to 6m age group and all age groups assessed, for WBCs, hemoglobin, hematocrit, MCV and lymphocytes absolute counts, both 2.5th and 97.5th percentiles for Kisumu infants were higher than those from Kilifi. Platelet ranges for Kisumu children were narrower compared to Kilifi ranges. Kisumu hematology reference ranges were observed to be higher than the ranges of Tanzanian children for the WBCs, absolute lymphocyte and monocyte counts, hemoglobin, hematocrit and MCV. Higher ranges of WBCs, absolute lymphocyte and monocyte counts were observed compared to the values in US/Europe. Wider ranges were observed in hemoglobin, hematocrit, and MCV. Wider ranges were observed in platelet counts in Kisumu infants compared to the US/Europe ranges. Compared to Harriet Lane Handbook reference values that are used in the area, higher counts were observed in WBC counts, both absolute and percent lymphocyte counts, as well as monocyte counts for current study. Wider ranges were observed in RBC, platelets and RDW, while lower ranges noted in the current study for hemoglobin, hematocrit and granulocyte counts. This study underscores the importance of using locally established hematology reference ranges of different age groups in support of proper patient management and for clinical trials.


[The prediction of the minimum incidence of AIDS in Spain for the period 1992-1995].
In order to estimate minimum AIDS incidence in Spain between 1992 and 1995, annual AIDS incidence up to 1991 has been obtained from the June 1992 update of the National Register. Correction was made for reporting delays in cases diagnosed since July 1989, in order to run a subsequent back calculation on all cases and for each separate mode of transmission. It was assumed that no new HIV infections would appear after 1991. Since 1981 to 1995, more than 38,000 AIDS cases will have been diagnosed. Minimum AIDS incidence as forecast exhibits a rise between 1992 and 1995 for the total number of cases and for all categories of transmission, except for recipients of blood and blood products, and children of mothers at risk. Real incidence will probably prove higher than estimated owing to the effect of new infections which may arise, and to the underreporting of cases.


Minimally invasive (99m)Tc-sestamibi radioguided surgery of parathyroid adenomas.
In the last 10 to 15 years surgery of primary hyperparathyroidism (PHPT) moved from the wide bilateral neck exploration to various types of limited neck exploration ranging from unilateral neck surgery to minimally invasive approaches as the minimally invasive radioguided parathyroidectomy. In contrast with the bilateral neck exploration, an accurate preoperative localizing imaging, which is mainly based on (99m)TC-sestamibi scintigraphy, is mandatory when planning a concise parathyroidectomy. Following imaging criteria, only a fraction of PHPT patients accounting for approximately 60% to 70% of all PHPT patients can be eligible for a minimally invasive parathyroidectomy. Only PHPT patients with a high probability to be affected by a solitary parathyroid adenoma showing a high (99m)TC-sestamibi uptake and with a normal thyroid gland should be offer a minimally invasive radioguided parathyroidectomy. The (99m)TC-sestamibi SPECT technique and the double-tracer 123-iodine or (99m)TC-pertecnetate/(99m)TC-sestamibi scintigraphic technique are the most sensitive and accurate preoperative imaging modalities and their utilization is recommended when considering a minimally invasive radioguided parathyroidectomy. Two main intraoperative procedures for the minimally invasive radioguided surgery have been described: the single-day protocol and the different-day protocol. In the single-day protocol a 740 MBq dose of (99m)TC-sestamibi is injected to the patient, scintigraphic imaging is obtained by dual-phase technique and then the patient is operated on within approximately 3 hours from radio-tracer injection. In the different-day protocol, a double-tracer parathyroid scintigraphy is obtained some days before surgery with the aim of better planning the type and extension of intervention. The day of intervention, for the purpose of radioguided surgery only, a low 37 MBq dose of (99m)TC-sestamibi is injected to the patient in the operating theatre a few minutes before the start of intervention. The main advantages of minimally invasive radioguided parathyroidectomy over the traditional wide bilateral neck exploration can be resumed as follows: a shortening in the operating and recovery time, possibility of local anesthesia, possibility of ambulatory surgery or same-day discharge, less postsurgical hypocalcemia, less postsurgical pain, favourable cosmetic results, benefits from a cost-analysis point of view.


Dandelion root extract suppressed gastric cancer cells proliferation and migration through targeting lncRNA-CCAT1.
Gastric cancer (GC) is one of the most common tumors worldwide. Standard treatment after early detection involves surgical excision (recurrence is possible), and metastatic gastric cancer is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively suppresses proliferation and migration in human gastric cells without inducing toxicity in noncancerous cells. Long noncoding RNAs (lncRNAs) are known to promote tumorigenesis in many cancer types. Here, we showed that the lncRNA colon cancer-associated transcript-1 (CCAT1) was down-regulated in dandelion-treated GC cells. Furthermore, downregulation of CCAT1 inhibited proliferation and migration of gastric cells. We also found that DRE exerted its function in GC cells partially through targeting CCAT1. This data will provide a basis on which further research in cancer treatment through DRE can be executed.


The decomposition of benzodiazepines during analysis by capillary gas chromatography/mass spectrometry.
A capillary gas chromatography column directly interfaced to a mass spectrometer was used for the analysis of sixteen benzodiazepines. The thermal stability of the drugs was found to be related to their chemical structure. Nine of the benzodiazepines were thermally unstable indicating that care should be taken in the interpretation of gas chromatographic data from this class of drugs. The unstable benzodiazepines were: ketazolam which decomposes to diazepam; N-4 oxides (chlordiazepoxide and demoxepam) which lose an oxygen radical; aromatic 7-nitro compounds (nitrazepam and clonazepam) which are partially reduced to the corresponding amine; alpha-hydroxy ketones (lorazepam and oxazepam) which decompose with the loss of water and N-methyl-alpha-hydroxy ketones (lormetazepam and temazepam) which partially decompose with the loss of a hydrogen molecule to produce the corresponding alpha, beta-diketones. Few problems were encountered in distinguishing the drugs by their mass spectra, the exceptions being ketazolam which decomposes to diazepam and demoxepam which decomposes to desmethyldiazepam. In general, good spectra were obtained from 20-50 ng of drug injected. However, for those compounds where the decompositions were not quantitative (nitrazepam, clonazepam, lormetazepam, temazepam) detection limits were poor.


Synthesis and biological evaluation of diaryl ether linked DC-81 conjugates as potential antitumor agents.
A series of new diaryl ether linked pyrrolobenzodiazepine (PBD) conjugates (4a-i, 5a-i and 6a-f) was synthesized and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. These conjugates exhibited significant anticancer activity with GI50 values in the range of 0.1-3.88 μM. Some of the potent conjugates (4b, 4h, 5h, 6b, 6c and 6e) were further investigated on cell cycle distribution. FACS analysis showed the accumulation of cells in G0 phase indicating the apoptosis inducing nature of these conjugates. Moreover, compound 6b caused a decrease in the mitochondrial membrane potential, which indicates the apoptotic nature of the compound through mitochondrial mediated pathway. Further conjugates 4b, 4h and 6b induce the activation of caspase and PARP proteins, followed by apoptotic cell death in MCF7 cell line.


The multifunctionality of expression systems in Bacillus subtilis: Emerging devices for the production of recombinant proteins.
Bacillus subtilis is a successful host for producing recombinant proteins. Its GRAS (generally recognized as safe) status and its remarkable innate ability to absorb and incorporate exogenous DNA into its genome make this organism an ideal platform for the heterologous expression of bioactive substances. The factors that corroborate its value can be attributed to the scientific knowledge obtained from decades of study regarding its biology that has fostered the development of several genetic engineering strategies, such as the use of different plasmids, engineering of constitutive or double promoters, chemical inducers, systems of self-inducing expression with or without a secretion system that uses a signal peptide, and so on. Tools that enrich the technological arsenal of this expression platform improve the efficiency and reduce the costs of production of proteins of biotechnological importance. Therefore, this review aims to highlight the major advances involving recombinant expression systems developed in B. subtilis, thus sustaining the generation of knowledge and its application in future research. It was verified that this bacterium is a model in constant demand and studies of the expression of recombinant proteins on a large scale are increasing in number. As such, it represents a powerful bacterial host for academic research and industrial purposes.


Specialist paediatric palliative care for children and young people with cancer: A mixed-methods systematic review.
Specialist paediatric palliative care services are promoted as an important component of palliative care provision, but there is uncertainty about their role for children with cancer. To examine the impact of specialist paediatric palliative care for children and young people with cancer and explore factors affecting access. A mixed-methods systematic review and narrative synthesis (PROSPERO Registration No. CRD42017064874). Database (CINAHL, Cochrane Database of Systematic Reviews, Embase, MEDLINE, PsycINFO) searches (2000-2019) identified primary studies of any design exploring the impact of and/or factors affecting access to specialist paediatric palliative care. Study quality was assessed using The Mixed Methods Appraisal Tool. An evidence base of mainly low- and moderate-quality studies (n = 42) shows that accessing specialist paediatric palliative care is associated with less intensive care at the end of life, more advance care planning and fewer in-hospital deaths. Current evidence cannot tell us whether these services improve children's symptom burden or quality of life. Nine studies reporting provider or family views identified uncertainties about what specialist paediatric palliative care offers, concerns about involving a new team, association of palliative care with end of life and indecision about when to introduce palliative care as important barriers to access. There was evidence that children with haematological malignancies are less likely to access these services. Current evidence suggests that children and young people with cancer receiving specialist palliative care are cared for differently. However, little is understood about children's views, and research is needed to determine whether specialist input improves quality of life.


Age-period-cohort effect on female breast cancer mortality in Southern Spain.
Breast cancer is the most common cancer in women worldwide. The analysis of breast cancer mortality is needed to plan healthcare systems. This study aims to evaluate the age-period-cohort effects on breast cancer mortality in Andalusia (Southern Spain) as a whole and in each of its eight provinces during the period 1981-2008. A population-based ecological study was conducted. In all, 19,707 deaths from breast cancer were analysed for individuals between the ages of 40 and 84 years who died in Andalusia in the period of study. A nonlinear regression model was estimated for each gender group and geographical area. The effects of age, year of death and birth cohort were parameterised using B-spline smoothing functions. There is an upward trend in mortality by age until around the age of 75 years, from which point the trend turned downwards. The analysis of the cohort effect reveals a steady fall in breast cancer mortality risk for female generations born after 1940. Death rates increased until 1995 and then declined until the end of the period. There is an age-period-cohort effect on breast cancer mortality similar in all the provinces of Andalusia and for Andalusia as a whole. If the current trends continue, it can be expected that these effects will continue to reduce female mortality.