Development and validation of the first performance assessment scale for interdisciplinary chest tube insertion: a prospective multicenter study.
Chest tube insertion requires interdisciplinary teamwork including an emergency surgeon or physician in conjunction with a nurse. The purpose of the study was to validate an interdisciplinary performance assessment scale for chest tube insertion developed from literature analysis. This prospective study took place in the simulation center of the University of Paris. The participants included untrained emergency/intensivist residents and trained novice emergency/intensivist physicians with less than 2 years of clinical experience and 6 months following training in thoracostomy, and nursing students. Each interdisciplinary pair participated in a high-fidelity simulation session. Two independent observers (O1 and O2) evaluated 61 items. Internal coherence using the Cronbach's α coefficient, intraclass correlation coefficient (ICC), and correlation of scores by regression analysis (R2) were analyzed. Comparison between O1 and O2 mean scores used a t test and F test for SDs. p Value < 0.05 was significant. From an initial selection of 11,277 articles, 19 were selected to create the initial scale. The final scale comprises 61 items scored out of 80, including 24 items for nursing items, 24 items for medical competence, and 13 mixed items for the competence of both. 40 simulations including 80 participants were evaluated. Cronbach's α = 0.76, ICC = 0.92, R2 = 0.88. There was no difference between the observers' assessments of means (p = 0.82) and SDs (p = 0.92). Score was 51.6 ± 5.9 in the group of untrained residents and nursing student, and 57.2 ± 2.8 in the trained group of novice physicians and nursing students (p = 0.0003). This first performance assessment scale for interdisciplinary chest tube insertion is valid and reliable.


Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson's Disease: A Multicenter Study.
Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease.


Gabaergic neurons of the hippocampus: development in homotopic grafts and in dissociated cell cultures.
The hippocampus taken from E18-E19 rat embryos was dissociated into a cell suspension and was either grafted into the hippocampus of adult rats or cultured. The growth of GABAergic neurons was examined using a GABA directed antiserum. The implanted tissue was capable of survival and growth without exhibiting a laminar organization. Most of the various morphological neuronal types could be observed, establishing different types of synapses; however, granule neurons were rarely encountered. A substantial proportion of GABA-positive neurons was detected within the graft with profuse labelling of the neuropil. In cultures issued from the same cell suspension, GABA-immunoreactive neurons were numerous and had different morphologies. Altogether these data suggest that GABA neurons express a high potential for growth and sprouting in vitro and in vivo.


Early Detection of Subclinical Uremic Cardiomyopathy Using Two-Dimensional Speckle Tracking Echocardiography.
Overhydration has a deleterious effect on cardio myocytes. This study was designated to evaluate left ventricular (LV) systolic and diastolic dysfunction in patients with various stages of chronic kidney disease (CKD) using conventional, tissue Doppler and two-dimensional speckle tracking echocardiography (2DSTE). Forty controls and 90 CKD patients, aged 49.3 ± 14 years old, were enrolled in the study. Patients were divided into 3 groups depending on their glomerular filtration rate. Group 1 (≥60 mL/min per 1.73 m(2) ), group 2 (≤60 mL/min per 1.73 m(2) ), and group 3 (≤60 mL/min per 1.73 m(2) and on regular dialysis for at least 12 months). Pulsed-Doppler and tissue Doppler studies were used to estimate LV filling pressure E/E'. Using 2DSTE, circumferential, radial, and longitudinal functions of the LV have been measured. LV longitudinal systolic strain, early, and late diastolic strain rates were significantly reduced in CKD patients (-16.9 ± 3.8%, 1.6 ± 0.5%, and 1.3 ± 0.4% in CKD vs. -22.5 ± 0.6%, 2.3 ± 0.2%, and 1.9 ± 0.1% in controls, P < 0.001 for all), and no difference was observed in terms of the circumferential LV functions (-22.4 ± 1.7 vs. -22.5 ± 1.4, P = 0.567). Severity of the kidney dysfunction appears to parallel with the rise of E/E' significantly (P < 0.001). In CKD, although the longitudinal and radial systolic functions were reduced, LV ejection fraction may remain within normal limits due to the preservation of the circumferential functions. Early detection of uremic cardiomyopathy might provide useful information for the risk stratification and decide the proper dialysis therapy in these patients.


Once-Weekly Injection of Low-Dose Teriparatide (28.2 μg) Reduced the Risk of Vertebral Fracture in Patients with Primary Osteoporosis.
We conducted a randomized, double-blind trial to assess the effect of 28.2 μg teriparatide versus placebo (1.4 μg teriparatide) on reduction of the incidence of vertebral fractures. Individuals enrolled in this study included patients with primary osteoporosis with one to five vertebral fractures and capable of self-supported walking. Attention was focused on incident vertebral fractures, change in bone mineral density (BMD) of the lumbar spine, and safety. A total of 316 subjects participated in the study, which lasted up to 131 weeks. Incident vertebral fractures occurred in 3.3% of subjects in the 28.2 μg teriparatide-treated group and 12.6% of subjects in the placebo group during the 78-weeks study period. Kaplan-Meier estimates of risk after 78 weeks were 7.5 and 22.2 % in the teriparatide and placebo groups, respectively, with a relative risk reduction of 66.4% by teriparatide (P = 0.008). Lumbar BMD in the 28.2 μg teriparatide group increased significantly by 4.4 ± 4.7 % at 78 weeks, which was significantly higher than the corresponding data in the placebo group (P = 0.001). Adverse events were observed in 86.7% of individuals in the teriparatide group and 86.1% of those in the placebo group. In conclusion, weekly injection of a low-dose of teriparatide (28.2 μg) reduced the risk of incident vertebral fractures and increased lumbar BMD.


Harlequin colour in the Great Dane dog.
Breeding data from Eire and Great Britain confirm the hypothesis of Sponenberg (1985) that the harlequin colour of the Great Dane breed of dog is due the combined action of a dominant gene H with the merle gene M in the genotype H+M+. The typical bluish coloration induced by M is modified to white by the action of H. The H gene is a prenatal lethal when homozygous HH and this study offers clear indication that the heterozygous H+ interacts with M to reduce the viability of white merle homozygotes H+MM.


Bipolar disorder and medical comorbidities: A Portuguese population-based observational retrospective study (2008-2015).
This study aimed to use the Charlson Comorbidity Index (CCI) to assess the prevalence of medical comorbidities among hospitalization episodes with a primary Bipolar Disorder (BD) diagnosis, and to analyze its association with hospitalization outcomes. A population-based observational retrospective study was conducted using a Portuguese administrative database containing all mainland public hospitalizations. From 2008-2015, hospitalization episodes with a primary diagnosis of BD were analysed. Outcomes included: length of stay (LoS), in-hospital mortality and discharge destination. Overall, 20807 hospitalization episodes were analysed. Mean±standard deviation age at admission was 47.9±14.3 years, and these episodes mostly refer to women's admissions (66.6%). Median (1st quartile; 3rd quartile) LoS was 16.0 (9.0; 25.0) days. A total of 2145 (10.3%) episodes had ≥1 CCI comorbidities registered, being diabetes the most prevalent. LoS was significantly higher for episodes with secondary diagnoses of congestive heart failure, cerebrovascular disease, dementia, diabetes, renal disease and malignancy (all p<0.05). Episodes with a registry of myocardial infarction, peripheral vascular disease, malignancy and renal disease diagnoses had higher in-hospital mortality. Limitations include the use of data registered for administrative reasons rather than research purposes, and the analysis of hospitalization episodes, instead of patients. In this Portuguese nationwide study, greater comorbidity had a measurable impact on BD hospitalization outcomes. During the study period the prevalence of CCI comorbidities rose from 8.1% to 17.4%, which may reflect the overall increasing quality of hospital-coded data in Portugal throughout the years. The detection and timely management of medical comorbid conditions will likely prevent the high BD medical burden.


Finding a City Name in a Traffic Sign: Effects of Word Case and Visual Motion.
To investigate the word recognition effects of the use of all-uppercase (e.g., VALENCIA) or titled-case (e.g., Valencia) for city names in traffic signs, controlling for word size, and comparing stationary and dynamic viewing situations. Prior studies provide mixed evidence regarding the effects of word case on the recognition of city names in traffic signs. Moreover, the evidence on the potential impact of visual motion on these effects is scarce. We carried out an experimental study using simulated traffic signs. The task was to indicate, for each sign, whether it contained a given city name or not (word search task, 50% positive trials). Visual motion of signs was manipulated as a between-participants factor: stationary (the sign was still) versus dynamic (the sign expanded as if the participant was approaching to it). Word case was manipulated as a within-participants factor: all-uppercase versus two titled-case conditions varying in font size: width-matched titled-case and point size-matched titled-case. In both the stationary and dynamic conditions, all-uppercase resulted in more incorrect responses and slower latencies than width-matched titled-case. When compared to point size-matched titled-case, all-uppercase produced slower correct responses in the stationary condition, whereas faster in the dynamic condition. Other factors being equal, all-uppercase city names will be recognized worse than their titled-case versions in traffic signs, both in stationary and dynamic situations. Results in the current experimental study would be of interest in the design of traffic signs and other circumstances in which text is presented in motion.


Energy solvency. A new concept to prevent energy poverty in Spain.
The new concept of energy solvency is defined as the ability of a person buying or renting a dwelling to meet the energy costs necessary to keep the dwelling comfortable, without falling into energy poverty. The energy efficiency certificate information is used to calculate the economic expenditure that is theoretically necessary to maintain the property comfortable. This is a more robust value for calculating the energy poverty indicator 2 M than the available data on real expenditure. Dwellings' maximum surface may be determined in order to guarantee the energy solvency, depending on the climate zone, the energy class, the energy sources used, and the household's net income. The results indicate that in 15% of situations, it is not possible to have a dwelling that exceeds the minimum surface area stipulated by law without incurring an energy risk situation. It is also observed that in 86% of the cases, energy solvency is achieved for dwellings with energy classes A, B, C, and D, up to 120 m2. It is concluded that, by knowing the energy solvency before renting or buying a home, it is possible to prevent energy poverty by avoiding those operations in which it is known that this will happen.


Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer.
Oral abiraterone acetate (Zytiga®), a selective cytochrome P450 17A1 enzyme inhibitor, is used in combination with prednisone or prednisolone to treat patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel-containing chemotherapy. In a clinical trial in patients with CRPC, abiraterone acetate plus prednisone significantly prolonged overall survival, the time to prostate-specific antigen progression and progression-free survival compared with placebo plus prednisone.


Effects of flooding on Eucalyptus camaldulensis and Eucalyptus globulus seedlings.
Flooding for up to 40 days induced morphological changes and reduced growth of 6-week-old Eucalyptus camaldulensis and Eucalyptus globulus seedlings. However, the specific responses to flooding varied markedly between these species and with duration of flooding. Both species produced abundant adventitious roots that originated near the tap root and original lateral roots, but only E. camaldulensis produced adventitious roots on submerged portions of the stem. Flooding induced leaf epinasty and reduced total dry weight increment of seedling of both species but growth of E. globulus was reduced more. In both species dry weight increment of shoots was reduced more than dry weight increment of roots, reflecting compensatory growth of adventitious roots. Adaptation to flooding appeared to be greater in E. camaldulensis than in E. globulus. the importance of formation of adventitious roots in flooding tolerance is emphasized.


Adding the implantable cardioverter-defibrillator to cardiac resynchronization therapy is associated with improved long-term survival in ischaemic, but not in non-ischaemic cardiomyopathy.
Cardiac resynchronization therapy (CRT) improves symptoms, left ventricular function, and survival in patients with heart failure (HF) and wide QRS. The benefit of adding implantable cardioverter-defibrillator (ICD) backup is debated. We analysed the long-term outcome of patients with HF due to ischaemic cardiomyopathy (ICM) or non-ischaemic cardiomyopathy (NICM) treated with a CRT device with or without defibrillator backup. In this observational study, consecutive patients with an ejection fraction ≤35% and QRS width ≥120 ms receiving a CRT device at Aarhus University Hospital, Denmark from 2000 to 2010 were included. Baseline characteristics were retrieved from patient files and survival data were obtained from the Danish Civil Registration System. The primary outcome was all-cause mortality. The effect of ICD backup was estimated using Cox proportional hazards model, and the multivariate analyses were adjusted for a priori selected variables. We included 917 HF patients, 427 with NICM, and 490 with ICM. Median follow-up was 4.0 years. Adjusted hazard ratio (aHR) for all-cause mortality was 0.76 [95% confidence interval (95% CI), 0.60-0.97; P = 0.03] in all patients; 0.96 (95% CI, 0.60-1.51; P = 0.85) in patients with NICM, and 0.74 (95% CI, 0.56-0.97; P = 0.03) in patients with ICM. In patients with NICM, ICD backup seemed to be associated with improved survival among non-responders to CRT (P = 0.08), but not among responders (P = 0.61). Adding an ICD backup is associated with better survival in CRT recipients. This effect was evident among patients with ICM, but not in patients with NICM.


Phytobricks: Manual and Automated Assembly of Constructs for Engineering Plants.
Phytobricks are standardized DNA parts for plants that can be assembled hierarchically into transcriptional units and, subsequently, into multigene constructs. Phytobricks each contain the sequences of one or more functional elements that comprise eukaryotic transcription units, with sequence features that enable them to be used interchangeably in one-step cloning reactions to facilitate combinatorial assembly. The simplicity and efficiency of this one-step reaction has enabled Phytobrick assembly to be miniaturized and automated on liquid handing platforms. In this method, we describe how to design and construct new Phytobricks as well as how to assemble them in both manual and nanoscale automated one-step reactions. Finally, we describe a high-throughput method for sequence verification of assembled plasmids.


Postnatal exposure to DINP was associated with greater alterations of lipidomic markers for hepatic steatosis than DEHP in postweaning mice.
The toxicity of the endocrine disruptor di(2-ethylhexyl) phthalate (DEHP) has been extensively studied for its hormonal dysregulation, obesogenic effect and associated metabolic diseases. DEHP's primary substitute di-isononyl phthalate (DINP), however, although increased in annual production globally, requires better understanding of its health effect. Our previous work reported disruptions in plasma lipid profiles, but the metabolic responses following phthalate exposure in the liver, particularly the entire hepatic lipidome, have been lacking. A targeted lipidomic technique was applied to accurately quantify a total of 363 lipid species in the liver of neonatal mice after exposure to a daily dose of 4.8 mg/kg body weight/day from birth throughout lactation. Distinct patterns of disruption for each sum of lipid classes or sub-classes between the genders were the most noticeable. Following DINP administration, female pups were subject to greater changes in phosphatidylethanolamines, bis(monoacylglycero)phosphate and ceramides. In contrast, the males exhibited less changes in the phosphoglycerol backbone-based molecules, whereas glycerol and cholesterol esters were more disrupted by DINP. DEHP, however, induced less changes overall compared to DINP. These findings highlighted the predominant lipidomic disruption of DINP on glycerol (diacylglycerides and triacylglycerides) and/or cholesterol (in ester or free form) molecules in neonatal mice across genders, suggesting the genesis of hepatic steatosis occurring at as early as post weaning. Collectively, these findings question the suitability of DINP as a safe DEHP substitute and warrant further investigation on longer-term exposure to elucidate its effect on chronic liver diseases.


Analysis of high intensity focused ultrasound in treatment of uterine fibroids on ovarian function and pregnancy outcome.
To investigate the ovarian function and pregnancy outcome of patients with uterine fibroids and the influencing factors after high intensity focused ultrasound (HIFU) ablation treatment. A total of 80 patients were recruited. All patients were divided into the pregnancy group (64 cases) and the non-pregnancy group (16 cases). The pregnancy group was categorized into the good pregnancy outcome (GOP) group (46 cases) and adverse pregnancy outcome (APO) group (18 cases). The general data of all study subjects were collected. The changes of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B (INHB), and antral follicle count (AFC) before HIFU and 3, 6, and 12 months after HIFU were compared. The related factors affecting pregnancy and pregnancy outcomes were analyzed. There were no significant differences in AMH, FSH, INHB levels, and AFC at 6 and 12 months after HIFU compared with those before HIFU in pregnancy and non-pregnancy groups (p > 0.05). This study demonstrated that patients with prior history of pregnancy, younger age, lower body mass index (BMI), and smaller fibroids volume had a higher pregnancy rate (p < 0.05). Besides, younger age and smaller fibroids volume were associated with better pregnancy outcomes (p < 0.05). HIFU in the treatment of uterine fibroids has little effect on ovarian function and does not increase the risk of infertility and adverse pregnancy. The prior history of pregnancy, age, BMI, and fibroids volume are essential factors affecting the postoperative pregnancy.


Desired assistance versus care received for postpartum depression: access to care differences by race.
One in seven women who have a baby will experience postpartum depression. Although there are many treatments for postpartum depression, many women do not receive assistance. When left untreated, this condition can have a deleterious affect on the woman's health/mental health, the child's cognitive, psychological, emotional and social development, the marital relationship and ability to contribute to society. This study examined 45 women's self-reported desire for PPD care and ability to obtain to these services in Erie County, New York. Results showed differences in desired care by race, differences in access to care by race and revealed the lack of PPD care in general.


CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signaling to promote expansion of cortical progenitors.
The primary cilium is a central signaling component during embryonic development. Here we focus on CROCCP2, a hominid-specific gene duplicate from ciliary rootlet coiled coil (CROCC), also known as rootletin, that encodes the major component of the ciliary rootlet. We find that CROCCP2 is highly expressed in the human fetal brain and not in other primate species. CROCCP2 gain of function in the mouse embryonic cortex and human cortical cells and organoids results in decreased ciliogenesis and increased cortical progenitor amplification, particularly basal progenitors. CROCCP2 decreases ciliary dynamics by inhibition of the IFT20 ciliary trafficking protein, which then impacts neurogenesis through increased mTOR signaling. Loss of function of CROCCP2 in human cortical cells and organoids leads to increased ciliogenesis, decreased mTOR signaling, and impaired basal progenitor amplification. These data identify CROCCP2 as a human-specific modifier of cortical neurogenesis that acts through modulation of ciliary dynamics and mTOR signaling.


Developmental exposure to valproate and ethanol alters locomotor activity and retino-tectal projection area in zebrafish embryos.
Given the minimal developmental neurotoxicity data available for the large number of new and existing chemicals, there is a critical need for alternative methods to identify and prioritize chemicals for further testing. We outline a developmental neurotoxicity screening approach using zebrafish embryos. Embryos were exposed to nominal concentrations of either valproate or ethanol then examined for lethality, malformation, nervous system structure and locomotor activity. Developmental valproate exposure caused locomotor activity changes at concentrations that did not result in malformations and showed a concentration-dependent decrease in retino-tectal projection area in the optic tectum. Developmental ethanol exposure also affected retino-tectal projection area at concentrations below those concentrations causing malformations. As both valproate and ethanol are known human developmental neurotoxicants, these results add to the growing body of evidence showing the potential utility of zebrafish in screening compounds for mammalian developmental neurotoxicity.


Native tissue sacrospinous hysteropexy from an anterior approach.
The goal of urogynecologic surgeons is to pair patients with the most appropriate and effective surgery. Sacrospinous hysteropexy has become an increasingly utilized surgical option for uterovaginal prolapse repair. The primary aim of this video is to highlight the role that sacrospinous hysteropexy can have in prolapse repair and to demonstrate an anterior approach for this procedure. We performed a literature review to provide general information on the efficacy, risks, and comparative benefits of sacrospinous hysteropexy. Our video demonstrates the key steps in performing a sacrospinous hysteropexy procedure from an anterior approach including method of dissection, suture fixation to the sacrospinous ligament, and cervical suspension. Sacrospinous hysteropexy has generally been found to be an effective option for uterovaginal prolapse repair in properly selected patients. The demonstrated approach integrates sacrospinous ligament fixation with an anterior colporrhaphy. Data and experience to date on sacrospinous hysteropexy are largely based on a posterior approach for access to the sacrospinous ligament. This surgical video demonstrates an anterior approach to sacrospinous hysteropexy that is not well characterized in the literature.


Gain control of NMDA-receptor currents by intracellular sodium.
The influx of Na+ is fundamental to electrical signalling in the nervous system and is essential for such basic signals as action potentials and excitatory postsynaptic potentials. During periods of bursting or high levels of discharge activity, large increases in intracellular Na+ concentration ([Na+]i) are produced in neuronal soma and dendrites. However, the intracellular signalling function of raised postsynaptic [Na+]i is unknown. Here we show that [Na+]i regulates the function of NMDA (N-methyl-D-aspartate) receptors, a principal subtype of glutamate receptor. NMDA-receptor-mediated whole-cell currents and NMDA-receptor single-channel activity were increased by raising [Na+]i and channel activity decreased upon lowering [Na+]i; therefore, the activity of NMDA channels tracks changes in [Na+]i. We found that the sensitivity of the channel to Na+ was set by a Src kinase that is associated with the channel. Raising [Na+]i selectively increased synaptic responses mediated by NMDA receptors, but not by non-NMDA receptors. Thus, the change in postsynaptic [Na+]i that occurs during neuronal activity is a signal for controlling the gain of excitatory synaptic transmission. This mechanism may be important for NMDA-receptor-dependent plasticity and toxicity in the central nervous system.


Onchocerca volvulus heat shock protein 70 is a major immunogen in amicrofilaremic individuals from a filariasis-endemic area.
Infestation with organisms causing lymphatic filariasis (i.e. Wuchereria bancrofti and Brugia malayi) results in a variety of clinical presentations. It is possible that some of the variation is due to differences in host response to parasite. To determine whether individuals who live in an endemic area but differ in their clinical manifestations respond to different filarial antigens, we screened Onchocerca volvulus expression libraries with sera from a number of individuals belonging to different clinical groups. The results of the study demonstrate that there are indeed differences in the recognition of three cloned filarial antigens and that this differential recognition is related to clinical symptomatology. The most striking finding is that an Onchocerca volvulus protein homologous to the 70 kDa Xenopus laevis heat shock protein is primarily recognized by individuals who are amicrofilaremic. Further analysis is required to determine whether these antigens play any role in the pathogenesis of filarial infection or have any potential value in protective immunity.


Role of oral corticosteroids in orbital cellulitis.
To evaluate the role of oral corticosteroids as an anti-inflammatory adjunct in the treatment of orbital cellulitis. Prospective, comparative, single-masked, interventional clinical study. setting: Tertiary eye care center (All India Institute of Medical Sciences). study population: Patients with acute onset (within 14 days) of orbital cellulitis with or without abscess. intervention: Patients were randomized into 2 groups in the ratio of 1:2. Both groups received initial intravenous antibiotics. In Group 2, oral steroids were added after an initial response to intravenous antibiotics. main outcome measures: Resolution of signs and symptoms, duration of intravenous antibiotics, length of hospital stay, and sequelae of disease (ptosis, proptosis, and movement restriction) were evaluated and compared between the 2 groups. A total of 21 patients (age range, 11-59 years) with orbital cellulitis were studied. There were 7 patients in Group 1, who received standard intravenous antibiotics, and 14 in Group 2, who received adjuvant steroids. Patients in Group 2 showed an earlier resolution of inflammation in terms of periorbital edema (P = .002 at day 7), conjunctival chemosis (P < .001 at day 10), and pain (P = .012 at day 7). They also attained vision of 0.02 on logMAR earlier than Group 1 patients. Decrease in proptosis and improvement in extraocular movements were also significantly better with the use of steroids (P = .027 at day 10, P = .003 at day 14, respectively). While a significant number of patients in Group 1 had mild residual ptosis, proptosis, and movement restriction at 12 weeks, none of the patients treated with steroids had any residual changes (P = .023, P = .001, and P = .001, respectively). The durations of intravenous antibiotics and hospital stay were significantly less in Group 2. Use of oral steroids as an adjunct to intravenous antibiotic therapy for orbital cellulitis may hasten resolution of inflammation with a low risk of exacerbating infection.


The impact of oxytocin on the hemodynamic features of the milk vein in dairy cows: a Color Doppler investigation.
This manuscript investigates, by Color Doppler ultrasonography, the basal hemodynamic features of the left cranial epigastric vein (milk vein) of 210 Holstein-Friesian cows, throughout lactation. Blood velocity, diameter, blood flow of the milk vein (before and after milking) and milk production detected in cows administered oxytocin were compared with the same parameters found in untreated cows. Blood velocity tended to decrease throughout lactation as did milk production, whereas both diameters and blood flows tended to increase towards the end of the study. All the four parameters showed higher values in the treated cows than in the untreated ones. This study provides a detailed picture of the hemodynamic features of the milk vein of the dairy cows throughout lactation and suggest that oxytocin may exert a vasodilatory effect, in vivo, at least on the cranial epigastric vein of the dairy cow.


Effect of double bond geometry in sphingosine base on the antioxidant function of sphingomyelin.
We previously showed that sphingomyelin (SM) inhibits peroxidation of phosphatidylcholine (PC) and cholesterol. Since SM uniquely has a trans unsaturation in its sphingosine base, we investigated whether this feature is important for its antioxidant function. Substitution of the natural trans Delta(4)-double bond with a cis double bond (cis-SM), however, increased SM's ability to inhibit Cu(2+)-mediated 16:0-18:2 PC oxidation by up to eightfold. Dihydro-SM, which lacks the double bond, was equally effective as trans-SM. In contrast to its effect in the sphingosine base, the presence of a cis double bond in the N-acyl group of trans-SM was not protective. cis-SM also inhibited the oxidation of cholesterol by FeSO_(4)/ascorbate more efficiently than the trans isomer. The enhanced protective effect of cis-SM is selective for metal ion-promoted oxidation, and appears to arise from a decrease in the effective concentration of metal ions. These studies show that the trans double bond of SM is not essential for its antioxidant effects.


AKT1 Is Required for a Complete Palbociclib-Induced Senescence Phenotype in BRAF-V600E-Driven Human Melanoma.
Cellular senescence is a carefully regulated process of proliferative arrest accompanied by functional and morphologic changes. Senescence allows damaged cells to avoid neoplastic proliferation; however, the induction of the senescence-associated secretory phenotype (SASP) can promote tumor growth. The complexity of senescence may limit the efficacy of anti-neoplastic agents, such as CDK4/6 inhibitors (Cdk4/6i), that induce a senescence-like state in tumor cells. The AKT kinase family, which contains three isoforms that play both unique and redundant roles in cancer progression, is commonly hyperactive in many cancers including melanoma and has been implicated in the regulation of senescence. To interrogate the role of AKT isoforms in Cdk4/6i-induced cellular senescence, we generated isoform-specific AKT knockout human melanoma cell lines. We found that the CDK4/6i Palbociclib induced a form of senescence in these cells that was dependent on AKT1. We then evaluated the activity of the cGAS-STING pathway, recently implicated in cellular senescence, finding that cGAS-STING function was dependent on AKT1, and pharmacologic inhibition of cGAS had little effect on senescence. However, we found SASP factors to require NF-κB function, in part dependent on a stimulatory phosphorylation of IKKα by AKT1. In summary, we provide the first evidence of a novel, isoform-specific role for AKT1 in therapy-induced senescence in human melanoma cells acting through NF-κB but independent of cGAS.


Portfolio Analysis of Research Grants in Data Science Funded by the National Heart, Lung, and Blood Institute.
Leveraging emerging opportunities in data science to open new frontiers in heart, lung, blood, and sleep research is one of the major strategic objectives of the National Heart, Lung, and Blood Institute (NHLBI), one of the 27 Institutes/Centers within the National Institutes of Health (NIH). To assess NHLBI's recent funding of research grants in data science and to identify its relative areas of focus within data science, a portfolio analysis from fiscal year 2008 to fiscal year 2017 was performed. In this portfolio analysis, an efficient and reliable methodology was used to identify data science research grants by utilizing several NIH databases and search technologies (iSearch, Query View Reporting system, and IN-SPIRE [Pacific Northwest National Laboratory, Richland, WA]). Six hundred thirty data science-focused extramural research grants supported by NHLBI were identified using keyword searches based primarily on NIH's working definitions of bioinformatics and computational biology. Further analysis characterized the distribution of these grants among the heart, lung, blood, and sleep disease areas as well as the subtypes of data science projects funded by NHLBI. Information was also collected for data science research grants funded by other NIH institutes/centers using the same search and analysis methodology. The funding comparison among different NIH institutes/centers highlighted relative data science areas of emphasis and further identified opportunities for potential data science areas in which NHLBI could foster research advances.


Hospital-at-home care for immunodeficient patients with COVID-19: Approach to persistent COVID-19 infection.
Patients with COVID-19 who have undergone B-cell depletion therapy could have prolonged SARS-CoV-2 infection; therefore, even in the hospital-at-home setting, primary care physicians should carefully consider the treatment regimen and the timing of ending isolations in such cases, and should not hesitate to consult with infectious disease specialists if necessary. We presented the first reported case of hospital-at-home care for a patient with persistent COVID-19 who had undergone B-cell depletion therapy. He received hospital-at-home care, including two courses of remdesivir; however, he ultimately failed to recover and was transferred to the hospital.


Suitability evaluation of potential arable land in the Mediterranean region.
The existing cultivated land in the Mediterranean region faces great pressure from various sources. A suitability evaluation of potential arable land is urgent for helping adaptation measures to mitigate the impacts of climate change and human pressure on agricultural production in the Mediterranean region. We integrated 15 biophysical and socio-economic factors from GIS and remote sensing data to perform a suitability evaluation of potential arable land in the Mediterranean region using analytical hierarchy process and radial basis function artificial neural network methods. Moreover, we analyzed the gap between potential arable land and existing cultivated land and compared the evaluation results between the analytical hierarchy process and artificial neural network methods. The results show that the suitability index of potential arable land based on artificial neural network with 6 neurons has the best correlation with average yield and average harvested area. The land area with a suitability grade over medium level accounts for 62.95% of the potential arable land area, of which 45.71% is uncultivated land. Cyprus, France, Greece, Italy, Lebanon, Portugal, Spain and Turkey have great opportunities for agricultural development. Radial basis function artificial neural network outperforms analytical hierarchy process, has better verification results, and requires less input. This study provides an initial insight into the agricultural land suitability of 16 countries around the Mediterranean Sea and introduces a research idea for agricultural land suitability evaluation.


β-Catenin and Associated Proteins Regulate Lineage Differentiation in Ground State Mouse Embryonic Stem Cells.
Mouse embryonic stem cells (ESCs) cultured in defined medium resemble the pre-implantation epiblast in the ground state, with full developmental capacity including the germline. β-Catenin is required to maintain ground state pluripotency in mouse ESCs, but its exact role is controversial. Here, we reveal a Tcf3-independent role of β-catenin in restraining germline and somatic lineage differentiation genes. We show that β-catenin binds target genes with E2F6 and forms a complex with E2F6 and HMGA2 or E2F6 and HP1γ. Our data indicate that these complexes help β-catenin restrain and fine-tune germ cell and neural developmental potential. Overall, our data reveal a previously unappreciated role of β-catenin in preserving lineage differentiation integrity in ground state ESCs.


Effects of cagA+ and cagA- strains of Helicobacter pylori on the human gastric mucus layer thickness.
Infection with cytotoxin-associated gene A (cagA) Helicobacter pylori is associated with severe gastric diseases, with contradictory views being expressed concerning the effect of H. pylori on the gastric mucus thickness. The aim of the present study was to differentiate between the effect of cagA+ and cagA- strains on gastric mucus thickness. Ninety-nine patients without peptic ulcers who were not on medication were randomly recruited from consecutive endoscopy clinics: six biopsies (five antral, one body) were obtained from each patient. Cryostat sections (18 microm) were cut and stained using the modified periodic acid-Schiff/Alcian blue technique. Mucus thickness was measured using computer-assisted light microscopy. The H. pylori status was assessed by histology, Campylobacter-like organism (CLO)test and culture, and cagA+ status determined by polymerase chain reaction (PCR). There was no significant difference (P = 0.784) in mean mucus thickness between cagA+ (52.7 +/- 1.2 microm, n = 10), cagA- (46.6 +/- 1.1 microm, n = 18) or H. pylori-negative patients (51.3 +/- 1.1 microm, n = 30). In cagA- patients, mucus thickness was significantly reduced with increased H. pylori colonization density, Spearman (r(s)) = -0.805, P < 0.0001. In contrast, in cagA+ patients there was a weak positive, but not significant, association between mucus thickness and H. pylori colonization density, r(s) = 0.333, P = 0.381. The human gastric mucus thickness is not affected by infection with cagA+ or cagA- strains of H. pylori compared with uninfected. Although a trend of increased mucus thickness with cagA+ infection was observed.


Combining the ASA Physical Classification System and Continuous Intraoperative Surgical Apgar Score Measurement in Predicting Postoperative Risk.
The surgical Apgar score predicts major 30-day postoperative complications using data assessed at the end of surgery. We hypothesized that evaluating the surgical Apgar score continuously during surgery may identify patients at high risk for postoperative complications. We retrospectively identified general, vascular, and general oncology patients at Vanderbilt University Medical Center. Logistic regression methods were used to construct a series of predictive models in order to continuously estimate the risk of major postoperative complications, and to alert care providers during surgery should the risk exceed a given threshold. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the discriminative ability of a model utilizing a continuously measured surgical Apgar score relative to models that use only preoperative clinical factors or continuously monitored individual constituents of the surgical Apgar score (i.e. heart rate, blood pressure, and blood loss). AUROC estimates were validated internally using a bootstrap method. 4,728 patients were included. Combining the ASA PS classification with continuously measured surgical Apgar score demonstrated improved discriminative ability (AUROC 0.80) in the pooled cohort compared to ASA (0.73) and the surgical Apgar score alone (0.74). To optimize the tradeoff between inadequate and excessive alerting with future real-time notifications, we recommend a threshold probability of 0.24. Continuous assessment of the surgical Apgar score is predictive for major postoperative complications. In the future, real-time notifications might allow for detection and mitigation of changes in a patient's accumulating risk of complications during a surgical procedure.


The discovery of equipotent PPARalpha/gamma dual activators.
We report the design and synthesis of equipotent PPARalpha/gamma dual agonists starting from selective PPAR alpha agonist 1. In vivo data for 7 in the Zucker fa/fa rat are presented.


4'-(4-Fluoro-phen-yl)-1'-methyl-dispiro-[indane-2,2'-pyrrolidine-3',2''-indane]-1,3,1''-trione methanol hemisolvate.
The asymmetric unit of the title compound, C29H24FNO5·0.5CH3OH, contains two independent mol-ecules and a one methanol solvent mol-ecule. The methanol mol-ecule is O-H⋯O hydrogen bonded to one of the independent mol-ecules. The pyrrolidine rings in both mol-ecules adopt half-chair conformations, while the cyclo-pentane rings within the indane groups are in flattened envelope conformations, with the spiro C atoms forming the flaps. The benzene rings of the indane ring systems form a dihedral angle of 35.06 (7)° in one independent mol-ecule and 31.16 (8)° in the other. The fluoro-substituted benzene ring forms dihedral angles of 65.35 (6) and 85.87 (7)° with the indane group benzene rings in one mol-ecule, and 72.78 (8) and 77.27 (8)° in the other. In each mol-ecule, a weak intra-molecular C-H⋯O hydrogen bond forms an S(6) ring motif. In the crystal, weak C-H⋯O, C-H⋯N and C-H⋯F hydrogen bonds link the mol-ecules into a three-dimensional network.


[The biochemical marker dynamics of the maternal serum in different chromosomal disorders of the fetus].
The reasons for false-positive results of Down syndrome screening have been analysed. It has been found that the family pericentric inversions of chromosome 9 in fetus are accompanied by AFP and HCG changes equal to Down syndrome pregnancies. The average marker's levels in cases of per inv (9) were: AFp-0.51 MoM, HCG-3.71 MoM. The dynamics of markers in amniotic fluid has been studied. Clinical significance of per inv (9) in medicogenetic consultation were discussed.


Long-term follow-up of 2529 patients with gastric and duodenal ulcer: survival rate and causes of death.
We investigated 2529 patients with peptic ulcer diagnosed from 1963 to 1975 to determine the prognosis relative to life span and causes of death. During the follow-up period of 9-23 yr, 486 patients (19.2%) died, 2025 (80.1%) were alive, and the fate of 18 (0.7%) was unknown. No significant differences were found between these numbers and the numbers expected from the sex- and age-matched general population at 1-20 yr after the initial diagnosis for patients with gastric ulcer, duodenal ulcer, or both gastric and duodenal ulcer, or for all ulcer groups combined. The survival rate for the surgically treated patients did not differ from the expected survival rate. The number of deaths from peptic ulcer (observed/expected = 18/5.47) was statistically high and the number from cerebrovascular disease was significantly low. Our results show that for patients with a peptic ulcer, the prognosis relative to life span is as good as that of the general population and surgery has little influence on the prognosis.


Lack of bioequivalence of a generic mefloquine tablet with the standard product.
To assess the bioequivalence between a generic tablet of mefloquine (Mephaquin = M1) with the reference tablet (Lariam = M2) in healthy volunteers. This open label, randomized two-way crossover study was performed in a single centre. Following an overnight fast, eighteen healthy volunteers received a single oral dose of 750 mg mefloquine either in the form of three M1 lactabs or three M2 tablets. Serial blood samples were collected up to 8 weeks after drug administration. Plasma samples were analysed for mefloquine and its carboxylic acid metabolite using liquid chromatography and subsequent tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of mefloquine and its metabolite were estimated by non-compartmental methods. The pharmacokinetics of mefloquine after administration of M1 and M2 tablets were significantly different as reflected by the respective mean values of maximum plasma concentration (Cmax 656 vs 1018 ng x ml(-1)), time to reach maximum concentration (tmax 46 vs 13 h) and area under the plasma concentration-time curve (AUC0-->infinity 338 vs 432 microg x h x ml(-1)). No significant differences existed between the elimination half-lives of the two formulations (394 vs 396 h). The relative bioavailability (M1 vs M2) was 0.78 and ranged from 0.38 to 1.37. Bioequivalence could not be demonstrated for log-transformed data of AUC0-->infinity or AUC0-->last within a predefined range of 80-125% and for Cmax within a range of 70-143%. The observed differences in Cmax, tmax and AUC are consistent with a slower rate and lower extent of mefloquine absorption after administration of M1. Statistical evaluation of these kinetic data showed that the M1 tablet is not bioequivalent to the M2 tablet. Clinical consequences of this finding cannot be excluded.


Sol-gel derived terbium-containing mesoporous bioactive glasses nanospheres: In vitro hydroxyapatite formation and drug delivery.
Terbium (Tb) doped mesoporous bioactive glasses (Tb/MBG) nanospheres were successfully synthesized by a facile sol-gel method using cetyl trimethyl ammonium bromide (CTAB) as the template. Results indicated that Tb/MBG had spherical morphology (100-200nm), higher specific surface area (250-350m2/g) and narrow mesopore size distribution (2-3nm). In order to investigate the effects of Tb on the in vitro bioactivity, prepared Tb/MBG nanospheres were soaking in simulated body fluid (SBF) for 3 days, and results indicated incorporation Tb ions in the MBG nanospheres could improve the hydroxyapatite formation ability. In addition, Tb/MBG nanospheres showed controlled release property of anti-cancer drugs (DOX) and distinct degradation in PBS with different pH values. Their release mechanism can be explained by Fickian diffusion according the Higuchi model, and the delivery of DOX from Tb/MBG nanospheres can be dominated by changing the doping concentration of Tb and the values of pH. In addition, the cytotoxicity of Tb/MBG nanospheres was assessed using a cell counting kit-8 (CCK-8), and results showed that the synthesized Tb/MBG nanospheres at low concentration had no significant cytotoxicity in MC3T3 cells. These all note that this material is a promising candidate for the therapy of bone tissue regeneration.


Measuring tracheal airway pressures during transtracheal jet ventilation: an observational study.
Tracheal airway pressures were measured via a transduced fibrescope during transtracheal jet ventilation in 10 patients. Ravussin transtracheal jet ventilation catheters were inserted under local anaesthesia. Following induction of general anaesthesia, tracheal airway pressures were measured at three anatomical levels during fibreoptic intubation. Overall pressure changes during transtracheal jet ventilation were small with the maximal pressure increase (13 mmHg) measured at the carina.


Effects of Tigecycline combined with Cefoperazone on bacterial clearance and serum biochemical indexes in patients with pulmonary infections in ICU.
To investigate the effects of tigecycline combined with Cefoperazone on bacterial clearance and the expression of serum biochemical indexes [C-reactive protein (CRP), leukocyte count (WBC) and procalcitonin (PCT)] in patients with infection in an intensive care unit (ICU). The clinical data of 79 patients with pulmonary infections within the ICU of Chenzhou first people's Hospital from October 2019 to September 2021 were retrospectively analyzed. From the total, 38 patients received intravenous drip of Cefoperazone (control group), and 41 patients received intravenous drip of Cefoperazone and tigecycline (observation group). The treatment effect, bacterial clearance effect, serum biochemical index level and adverse reactions of the two groups were counted before and after treatment. The total efficacy in the observation group (95.12%) was higher than that of the control group (78.95%) (P<0.05). After treatment, the bacterial clearance rate in the observation group (87.04%) was higher than that in the control group (66.67%) (P<0.05). After treatment, the levels of CRP, WBC and PCT in the two groups were lower than those before treatment (P<0.05), and the levels in the observation group were lower than those in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the observation group (9.76%) and the control group (5.26%) (P>0.05). The combination of Cefoperazone and tigecycline in the treatment of ICU infection can effectively improve the treatment effect of the disease, have a significant bacterial clearance effect, and can reduce the serum levels of CRP, WBC and PCT.


Perioperative and late clinical outcomes of percutaneous transluminal stentings of the celiac and superior mesenteric arteries over the past decade.
Several authorities have proposed stenting of the superior mesenteric artery (SMA)/celiac artery (CA) as the primary treatment for patients with chronic mesenteric ischemia. However, most of these reports had small samples and short follow-up periods. Eighty-three patients were treated over a 10-year period. Clinical follow-up and duplex ultrasound exams were done to evaluate long-term patency. We used our newly validated duplex criteria to detect ≥70% in-stent stenosis of the SMA and CA. A Kaplan-Meier life-table analysis was used to estimate freedom from in-stent stenosis and late symptom and survival rates. Fifty-four SMA and 51 CA stents were analyzed. The initial technical and clinical success rates were 97% and 96%, respectively, with 2% procedure morbidity and 2% mortality. The primary late clinical success rate was 59%, and the late ≥70% in-stent stenosis rate was 51% at a mean follow-up of 31 months (range, 1-124). Freedom from late recurrent symptoms at 1, 2, 3, 4, and 5 years was 83, 77, 70, 70, and 65%, respectively. Survival rates at the same intervals were 88%, 82%, 70%, 64%, and 51%. Primary patency rates for the whole series were 69%, 48%, 39%, 28%, and 19% at 1, 2, 3, 4, and 5 years, respectively. Assisted primary patency rates for the whole series were 80%, 61%, 54%, 43%, and 34% at 1, 2, 3, 4, and 5 years, respectively. Primary patency rates for the SMA at 1, 2, 3, 4, and 5 years were 71%, 47%, 37%, 28%, and 18%, respectively; and assisted primary rates were 82%, 64%, 57%, 45%, and 32%, respectively. Primary patency rates for the CA were 68%, 50%, 40%, 29%, and 21%; and assisted primary rates were 79%, 58%, 52%, 42%, and 36% for 1, 2, 3, 4, and 5 years, respectively. There were no significant differences in either primary or assisted primary patency between the SMA and CA (P = .7729 and .8169). A secondary intervention was carried out in 30% of the series. Freedom from ≥70% in-stent stenosis for the SMA was 82%, 65%, 56%, 42%, and 34%, and that for the CA was 73%, 59%, 48%, 34%, and 25%, at 1, 2, 3, 4, and 5 years, respectively. Stenting of SMA/CA stenosis has high technical/early clinical success rates with a satisfactory late clinical outcome; however, it is associated with high rates of late in-stent stenosis and intervention.


LncRNA-SNHG29 inhibits vascular smooth muscle cell calcification by downregulating miR-200b-3p to activate the α-Klotho/FGFR1/FGF23 axis.
Vascular calcification (VC) is characterized by mineral accumulation on the walls of arteries and veins, which is a pathological process commonly found in elderly individuals and patients with atherosclerosis, hypertension, and diabetes. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play an important role in VC. However, the role of SNHG29 is less clear. The expression of SNHG29, miR-200b-3p, α-Klotho, FGFR1 and FGF23 in vascular smooth muscle cells (VSMCs) was quantified by qRT-PCR and western blot assays. β-GP was used to construct an in vitro calcification model, followed by MTT assay to detect cell viability. Calcification was determined by alizarin red S staining and quantified by calcification assay. ALP activity was investigated by ALP staining. The interactions among SNHG29, miR-200b-3p and α-Klotho were verified by luciferase assay. In the in vitro calcification model, SNHG29 was downregulated, while miR-200b-3p was upregulated. SNHG29 overexpression and miR-200b-3p knockdown significantly suppressed osteoblast-related factors (RUNX2 and BMP2), accompanied by activation of the α-Klotho/FGFR1/FGF23 axis, further inhibiting the formation of calcified nodules. Moreover, miR-200b-3p overexpression and α-Klotho knockdown reversed the SNHG29 overexpression-induced inhibitory effects on calcified VSMCs. Our study is the first to demonstrate that SNHG29 could inhibit VSMC calcification by downregulating miR-200b-3p to activate the α-Klotho/FGFR1/FGF23 axis, suggesting SNHG29 as a novel therapeutic target for VC-associated diseases.


nor-Oleanene type triterpene glycosides from the leaves of Acanthopanax japonicus.
Three new (1-3) and two known (4-5) triterpene glycosides were isolated from the leaves of Acanthopanax japonicus (Araliaceae) and elucidated structurally by mass, 1D, and 2D NMR spectroscopy. All the compounds possessed a nor-oleanene triterpene skeleton as the aglycone. The structures of 1-5 were established as 28-O-alpha-L-rhamno-pyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester of 3beta-hydroxy- 30-nor-olean-12,20(29)-diene-23,28-dioic acid, designated as acanjaposide A, 3beta- hydroxy-23-oxo-30-nor-olean-12,20(29)-diene-28-oic acid, named acanjaposide B, 3beta,20alpha-dihydroxy-23-oxo-30-nor-olean-12-en-28-oic acid, named acanjaposide C, and nipponoside E, a known saponin, respectively.


Carcinoid tumour of the uterine corpus.
A carcinoid tumour occurred in the uterine fundus causing an enlargement (12-14 weeks size). The patient did not have the carcinoid syndrome, despite elevated urinary 5-hydroxyindole acetic acid levels. The tumour had a typical organoid pattern with argentaffin-positive cells. Whilst a metastasis from an occult primary lesion cannot be entirely excluded, it is felt that this is a primary tumour most likely arising from resident endocrine cells in the endometrium.


The major ribonucleoprotein-associated protein kinase of vesicular stomatitis virus is a host cell protein.
Ribonucleoprotein particles (RNPs) of vesicular stomatitis virus (VSV) were fractionated by column chromatography through Fractogel TSK HW-55F and by centrifugation through KCl sucrose. Analyses of fractions for protein content and for protein kinase activity indicated that the major peak of kinase activity did not correspond exactly with any of the VSV-specific proteins. Neither anti-NS nor anti-M IgG preparations inhibited protein kinase activity, and IgG did not act as an exogenous phosphate acceptor. Reconstitution of an RNP-enzyme complex did not result in a restoration of protein kinase activity. In vitro translation of VSV-specific poly(A)-containing RNA did not result in any detectable production of kinase activity. Thus, the major RNP-associated kinase is a host cell protein which is tightly bound to the RNP particle.


Effects of lamotrigine on mood in older adults with epilepsy and co-morbid depressive symptoms: an open-label, multicentre, prospective study.
Both epilepsy and depressive symptoms are more prevalent in older individuals than in any other age group. Furthermore, depressive symptoms are among the most common interictal psychiatric co-morbid disorders in people with epilepsy. For these reasons, pharmacological treatment of epilepsy that might also confer antidepressant effects may be particularly beneficial in older patients. In this respect, lamotrigine is of considerable interest amongst antiepileptic drugs (AEDs) because it has proven thymoleptic activity. These analyses, conducted on a data set drawn from a previously reported, open-label, multicentre, prospective study, examined the effect of lamotrigine on mood in adults aged>or=50 years with epilepsy and co-morbid depressive symptoms. All subjects were receiving background AED therapy at baseline. Of the 158 subjects enrolled in the initial study, 40 adults (24 women, 16 men) met the age criterion for these analyses. The study consisted of a screening/baseline phase and four treatment phases over 36 weeks: lamotrigine escalation phase (7 weeks); lamotrigine maintenance or adjunctive therapy phase (12 weeks); concomitant AED withdrawal phase (5 weeks); and lamotrigine monotherapy phase (12 weeks). Psychometric evaluation of mood utilized the Beck Depression Inventory (BDI-II), Center for Epidemiological Studies Depression Scale (CES-D), the Neurological Disorders Depression Inventory in Epilepsy (NDDI-E) and the Profile of Mood States (POMS). Scores at the end of the adjunctive and monotherapy phases were compared with baseline scores. Lower scores on these scales indicate less depressive symptomatology. Mean baseline scores for the BDI-II, CES-D, NDDI-E and POMS were 15.8, 24.3, 13.8 and 57.7, respectively. Change scores were statistically significant (p<0.01) compared with baseline at the end of the adjunctive and monotherapy phases for all four psychometric measures of mood, with the exceptions of BDI-II and NDDI-E at the end of the adjunctive phase. The older adults in these analyses presented with low to moderate levels of depressive symptoms. Addition of lamotrigine to background AED therapy demonstrated antidepressant activity similar to that for the whole sample in the initial study. Given that the onset and prevalence of epilepsy are higher in older adults than in any other age group, pharmacological treatment for epilepsy in older patients that might also confer antidepressant therapy may be particularly beneficial.


Expression of the estrogen receptor gene in developing and adult human breast.
Although studies of the estrogen receptor gene abound in rodent models and breast cancer cell lines, little is known about expression of this gene in normal human breast. Information regarding the physiology of this gene's expression is important if we are to elucidate abnormalities of the gene that may be involved in breast carcinogenesis. We evaluated levels of mRNA expression of the estrogen receptor (ER) gene and its protein product in a set of 89 breasts from clinically normal female infants, children, adolescents, and adult premenopausal and post-menopausal women. mRNA expression of the gene varied with the hormonal status. Relatively higher levels of gene transcripts were found in breasts of peri-menarchal girls, women in the luteal phase of the menstrual cycle, and in those with fibrocystic change. Higher levels were also occasionally found in breasts of infants and in most pre-adolescent children. Lower levels were seen in breasts of women in the follicular phase of the menstrual cycle, during pregnancy, and after menopause. Nuclear protein staining was common in breasts of normal children and peri-menarchal adolescents, and in post-menopausal atrophic breasts. Nuclear ER protein was infrequently detected in reproductive aged women's breasts, but was more often seen in follicular than in luteal menstrual phase or pregnant breast. ER protein was more frequently seen in post-menopausal than in pre-menopausal breasts with fibrocystic change. The results fit a model in which circulating levels of estrogen are inversely related to levels of mRNA transcribed from the estrogen receptor gene in normal physiologic states. Abnormally high levels of gene transcription may occur in some cases of fibrocystic change.


Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer.
A phase III, multicenter, randomized study compared conventional dosing of fluorouracil (FU) plus folinic acid with pharmacokinetically guided FU dose adjustment in terms of response, tolerability, and survival. Two hundred eight patients with measurable metastatic colorectal cancer were randomly assigned to one of two arms: arm A (104 patients; 96 assessable), in which the FU dose was calculated based on body-surface area; and arm B (104 patients; 90 assessable), in which the FU dose was individually determined using pharmacokinetically guided adjustments. The initial regimen was 1,500 mg/m(2) FU plus 200 mg/m(2) folinic acid infusion during a continuous 8-hour period administered once weekly. FU doses were adjusted weekly in arm B based on a single-point measurement of FU plasma concentrations at steady state until the therapeutic range (targeted area under the curve 20-25 mg x h x L(-1)) previously established in other studies was reached. An intent-to-treat analysis of the 208 patients showed the objective response rate was 18.3% in arm A and 33.7% in arm B (P = .004). Median overall survival was 16 months in arm A and 22 months in arm B (P = .08). The mean FU dose throughout treatment was 1,500 mg/m(2)/wk in arm A and 1,790 +/- 386 mg/m(2)/wk (range, 900 to 3,300 mg/m(2)/wk) in arm B. Toxic adverse effects were significantly more frequent and severe in arm A compared with arm B (P = .003). Individual FU dose adjustment based on pharmacokinetic monitoring resulted in significantly improved objective response rate, a trend to higher survival rate, and fewer grade 3/4 toxicities. These results support the value of pharmacokinetically guided management of FU dose in the treatment of metastatic colorectal patients.


A novel AMT gene mutation in a newborn with nonketotic hyperglycinemia and early myoclonic encephalopathy.
Early myoclonic encephalopathy (EME) presents in neonatal period with erratic or fragmentary myoclonus and a burst-suppression electroencephalography (EEG) pattern. Nonketotic hyperglycinemia (NKH) is the most common metabolic cause of EME and genetic testing confirms the diagnosis of NKH in around 75% of the patients with a clinical diagnosis of NKH. Three genes are known to cause NKH. Here we describe a case of EME caused by NKH in which a new mutation in aminomethyltransferase (AMT) gene has been detected.


Brain atrophy in the visual cortex and thalamus induced by severe stress in animal model.
Psychological stress induces many diseases including post-traumatic stress disorder (PTSD); however, the causal relationship between stress and brain atrophy has not been clarified. Applying single-prolonged stress (SPS) to explore the global effect of severe stress, we performed brain magnetic resonance imaging (MRI) acquisition and Voxel-based morphometry (VBM). Significant atrophy was detected in the bilateral thalamus and right visual cortex. Fluorescent immunohistochemistry for Iba-1 as the marker of activated microglia indicates regional microglial activation as stress-reaction in these atrophic areas. These data certify the impact of severe psychological stress on the atrophy of the visual cortex and the thalamus. Unexpectedly, these results are similar to chronic neuropathic pain rather than PTSD clinical research. We believe that some sensitisation mechanism from severe stress-induced atrophy in the visual cortex and thalamus, and the functional defect of the visual system may be a potential therapeutic target for stress-related diseases.


Mitogenic signaling by epidermal growth factor (EGF), but not platelet-derived growth factor, requires arachidonic acid metabolism in BALB/c 3T3 cells. Modulation of EGF-dependent c-myc expression by prostaglandins.
Previously, we have shown that prostaglandins are necessary, but not sufficient, for the stimulation of mitogenesis in BALB/c 3T3 fibroblasts by epidermal growth factor (EGF) (Nolan, R. D., Danilowicz, R. M., and Eling, T. E. (1988) Mol. Pharmacol. 33, 650-656). The purpose of this work was to extend these findings to another potent mitogen, platelet-derived growth factor (PDGF), and to determine if metabolism of arachidonic acid to prostaglandins is necessary for stimulation of expression of the protooncogene c-myc by EGF, which is an early event in the mitogenic cascade. In BALB/c 3T3 cells grown to about 70% confluence and deprived of serum for 16-24 h, PDGF stimulated [3H]thymidine uptake into DNA significantly in a concentration-dependent manner, but did not increase production of prostaglandin E2 (PGE2). The addition of indomethacin, a prostaglandin H synthase inhibitor, or nordihydroguaiaretic acid, a lipoxygenase inhibitor, did not affect PDGF-stimulated thymidine uptake into DNA. In addition, PGE2 enhanced EGF-dependent, but not PDGF-dependent, mitogenesis. Taken together, the data support the hypothesis that prostaglandins are not involved in PDGF-dependent mitogenesis. In contrast, indomethacin (10(-6) M) and nordihydroguaiaretic acid (10(-6) M) inhibited EGF-stimulated thymidine uptake and c-myc expression by approximately 50%. Addition of PGG2 (10(-7) to 10(-5) M) in the presence of indomethacin and EGF restored the ability of EGF to elevate c-myc RNA levels and DNA synthesis. When PGF2 alpha (10(-8) to 10(-5) M) was added in the presence of EGF, c-myc RNA levels and thymidine incorporation were elevated up to 5-6-fold above levels observed with EGF alone. These data support the hypothesis that metabolism of arachidonic acid to prostaglandins is necessary for stimulation of c-myc expression by EGF in BALB/c 3T3 cells.


Pancreatogastrostomy versus pancreatojejunostomy for RECOnstruction after partial PANCreatoduodenectomy (RECOPANC): study protocol of a randomized controlled trial UTN U1111-1117-9588.
Pancreatoduodenectomy is one of the most complex abdominal operations, usually performed for tumors of the periampullary region and chronic pancreatitis. Leakage of pancreatic juice from the pancreatoenteric anastomosis, called postoperative pancreatic fistula, is the most prominent postoperative complication. Retrospective studies show a significant reduction of fistula rates with pancreatogastrostomy as compared to pancreatojejunostomy, the most frequently employed method of pancreatoenterostomy. Most single-center prospective trials, however, have not validated this finding. A large multicenter trial is needed for clarification. RECOPANC is a prospective, randomized, controlled multicenter trial with two treatment arms, pancreatogastrostomy versus pancreatojejunostomy. The trial hypothesis is that postoperative pancreatic fistula rate is lower after pancreatogastrostomy when compared to pancreatojejunostomy. Fourteen academic centers for pancreatic surgery will participate to allocate 360 patients to the trial. The duration of the entire trial is four years including prearrangement and analyses. Postoperative pancreatic fistula is the main reason for clinically important postoperative morbidity after pancreatoduodenectomy. The primary goal of the chosen reconstruction technique for pancreatoenteric anastomosis is to minimize postoperative fistula rate. A randomized trial performed at multiple high-volume centers for pancreatic surgery is the best opportunity to investigate one of the most crucial issues in pancreatic surgery. German Clinical Trials Register DRKS00000767 (2011/03/23), FSI 2011/05/31. Universal Trial Number U1111-1117-9588.


Effect of acid etching time on bond strength of an etch-and-rinse adhesive to primary tooth dentine affected by amelogenesis imperfecta.
Dentine affected by amelogenesis imperfecta (AI) is histologically altered following loss of the hypoplastic enamel and becomes hypermineralized, which would make bonding less predictable. This study examined the effect of etching time on the microtensile bond strength (microTBS) to AI-affected primary dentine. Flat coronal dentine surface was obtained from extracted AI-affected and noncarious primary molars. Teeth were etched either for 15 or for 30 s using 34% phosphoric acid. Prime & Bond NT (Dentsply De Trey), an etch-and-rinse adhesive, was applied to dentine surfaces, air-dried and light-cured, followed by composite build-ups. The bonded teeth were sectioned into beams of 0.8 mm(2) and stressed to failure under tension. Representative fractured beams from each group were examined under scanning electron microscopy. The extended etching time had an adverse effect on the microTBS for the normal dentine, while no significant difference was found for AI-affected dentine. When the AI-affected dentine was etched for 30 s, the fracture occurred in the demineralized dentine at the base of the hybrid layer. Bonding to AI-affected dentine compromised the bonding of the etch-and-rinse adhesive. The bonding could not be improved by increasing etching time.


High frequency of allelic deletion on chromosome 17p in advanced colorectal cancer.
Colorectal cancers often show allelic loss of chromosomes 5q and 17p, regions where the tumor suppressor genes p53 and adenomatous polyposis coli are known to reside. Currently, the inactivation of tumor suppressor genes and the activation of oncogenes are considered major events involved in tumor development. According to a recent genetic model, ras gene mutations and allelic deletion of chromosome 5q are early changes, whereas chromosome 17p and 18q deletions are late changes in colorectal tumorigenesis. It has been shown that 17p and 18q deletions are associated with an increased tendency of disease dissemination in colorectal cancer. Most of the studies on allelic deletion in colorectal cancer were undertaken with Western population cohorts. The authors examined the association of chromosomes 5q and 17p deletions with clinical parameters, including metastasis in a predominantly Chinese population with a high incidence of colorectal cancer. Allelic deletion was studied with the restriction fragment length polymorphism technique in tumors from 102 and 100 sporadic colorectal cancer cases for chromosomes 5q and 17p, respectively. Probes pi 227 and ECB27 were used for chromosome 5q, and probe YNZ22.1 was used for chromosome 17p. 5q Deletion was found in 33% of informative cases, whereas 17p deletion was seen in 69% of informative cases. 17p Allelic loss showed significant association with Dukes' Stage D as well as the presence of distant metastasis, whereas 5q deletion showed no such association. Allelic loss on chromosome 17p may be a useful prognostic marker in cases of colorectal cancer.


Hemostatic Resuscitation in Children.
Trauma is a major source of morbidity and mortality for children worldwide; life-threatening hemorrhage is a primary cause of preventable death. Essential interventions in children with life-threatening hemorrhage include hemostatic resuscitation and mechanical control of bleeding. Herein we review pediatric hemostatic resuscitation, a strategy that addresses both hemorrhagic shock and the coagulopathic complications described in patients with major hemorrhage. Some components of hemostatic resuscitation may include: early and aggressive resuscitation with blood products, minimizing crystalloid and hemodilution, antifibrinolytic adjuncts such as tranexamic acid, and the novel use of low-titer group O whole-blood (LTOWB) transfusion in injured children. The following selection of important publications address the current state of hemostatic resuscitation strategies in pediatric trauma patients as well as the remaining knowledge gaps and areas for further research.


[Ligament injuries in tibial plateau fractures].
Fracture dislocations of the proximal tibia are associated with a markedly high incidence of ligament ruptures. Despite knowledge on the frequency of accompanying ligament injuries, even now neither adequate diagnostics nor targeted treatment of associated ligament injuries are the gold standard in the treatment algorithm for tibial plateau fractures. To be able to assess the risk and the type of accompanying ligament injuries in tibial plateau fractures, it is recommended to decidedly analyze the fracture morphology. For example, flexion varus fractures are very frequently associated with injuries to the anterior cruciate ligament, whereas valgus fractures are prone to ruptures of the medial collateral ligament and (hyper)extension fractures facilitate ruptures of the posterior cruciate ligament and the posterolateral corner. In order not to overlook high-grade instability, magnetic resonance imaging or intraoperative dynamic fluoroscopy can be carried out after completing osteosynthesis. Bony avulsions should either be addressed directly during osteosynthesis or indirectly retained via interfragmentary compression. In cases of direct visualization or relevant instability, intraligamentous tears should at least be intraoperatively reduced. If patients suffer from persistent instability a secondary ligament reconstruction with autologous tendons can be carried out following bony consolidation of the tibial plateau fracture.


Validity of the Best Practice Tariff in paediatric major trauma: A retrospective cohort study from a level 1 children's major trauma centre.
The Best Practice Tariff (BPT) in major trauma awards Major Trauma Centres (MTCs) a financial incentive when predefined standards of care are met. However, no tailored criteria exist with regards to the reimbursement policy in paediatric major trauma. In this study, we aim to examine the utility of the paediatric Major Trauma BPT and identify predictors of additional resource utilisation. This cohort study encompassed all paediatric major trauma calls (N = 682) presenting to a designated combined adult and paediatric MTC between July 2014 and June 2017. Patient demographics, admission pattern, injury parameters, length of stay (LOS) and the need for operative management were collected. Patients approved for the BPT uplift payment (BPT group) were compared with the cohort of children not qualifying (non-BPT group). Overall, less than a quarter (23.2%) of the trauma population qualified for the BPT. The proportion of patients requiring operative intervention and CT scanning in the BPT group was significantly higher (p<0.001). These children also attained a higher ISS (median, 13.5 vs. 0, p <0.001) and required longer hospitalisation. Following a Receiver Operator Characteristic (ROC) curve analysis, a cut off ISS score > 8 demonstrated an excellent predictive value in identifying children qualifying for BPT (true positive and false positive rates: 90% and 10.7%). However, a subgroup analysis including the more severely injured children (ISS >8) not qualifying for the uplift payment revealed that equally substantial resource went into their management - 42.9% needed surgical intervention and 57.1% a CT scan. This study demonstrated that BPT in paediatric major trauma is a valuable reimbursement; however, our findings also unveiled a cohort deemed ineligible for BPT despite the high costs accrued. Re-evaluation of the remuneration criteria of paediatric major trauma networks with an alternative, more inclusive reimbursement policy is needed.


Global proteomic profiling and enrichment maps of dilated cardiomyopathy.
Global expression profiling is a promising technique to help uncover perturbations associated with heart disease. With the large amount of expression data generated, we demonstrate how a list of differentially expressed proteins or genes can be translated into a list of perturbed pathways and functions using conventional overrepresentation analysis such as gene set enrichment analysis, DAVID, and BiNGO. As outputs from ORA can be daunting in themselves, we further demonstrate how to visualize enrichment results as Enrichment Maps for easy interpretation and analysis.


Cold-induced changes in amphibian oocytes.
Female Pleurodeles waltl newts (Amphibia, urodele), usually raised at 20 degrees C, were submitted to low temperatures; oocytes responded to this cold stress by drastic changes both in lampbrush chromosome structure and in protein pattern. Preexisting lateral loops of lampbrush chromosomes were reduced in size and number, while cold-induced loops which were tremendously developed, occurred on defined bivalents of the oocyte at constant, reproducible sites. A comparison of protein patterns in control and stressed oocytes showed two main differences: in stressed oocytes, overall protein synthesis was reduced, except for a set of polypeptides, the "cold-stress proteins"; second, there was a striking inversion of the relative amount of beta- and gamma-actin found in the oocyte nucleus before and after cold stress. Whereas beta-actin was the predominant form in control oocytes, gamma-actin became the major form in stressed oocytes.


Highly stable lanthanide macrocyclic complexes: in search of new contrast agents for NMR imaging.
This paper presents the views of a coordination chemist on the synthesis and the properties of new contrast agents containing gadolinium. Attention is drawn to various macrocyclic complexes such as the polyaza polycarboxylic chelates, the cryptates as well as compounds obtained by template synthesis. The structural factors influencing the kinetic and thermodynamic stability of the gadolinium complexes are discussed with special emphasis on the polyaza polycarboxylic derivatives. Some of the macrocyclic complexes under investigation are more stable than Gd-DTPA.


Successful grafting elite cocoa clones (Theobroma cacao L.) as a function of the age of rootstock.
Côte d'Ivoire, the world's largest cocoa producer, faces numerous challenges because the yield of orchards is low due to several factors including the non-use of improved plant materials. This work is part of ICRAF's Vision for Change (V4C) project, which aimed at contributing to the regeneration of cocoa farms by making effective plant materials available to small cocoa producers. It essentially consisted in evaluating the effect of the age of the rootstock on the success of grafting to obtain a satisfactory quantity of improved plants in the nursery. The study was carried out in Adiopodoumé at the National Agronomic Research Center (CNRA). Ten elite cocoa clones from the "Vision for Change" project were used as scions. Top grafting was performed on seedlings of 2, 3- and 4-months used as rootstocks. The experimental design was a randomized complete block design with 3 replications. Data collection was focused on the grafting success rate and morphological parameters. The results showed that the grafting success rate is proportional to the rootstock age. Two months after grafting, the success rate was low. This indicates that grafting should eventually start at 3 months. This period could therefore represent a good stage to successfully graft and replant cocoa seedlings.


Blood levels of cytokines in children with idiopathic partial and generalized epilepsy.
Antiepileptic drugs have been reported to reduce the levels of serum immunoglobulins and affect the production and levels of certain cytokines. We investigated the effects of valproic acid (VPA) and topiramate (TPM) on the blood levels of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and TNF-α in children with idiopathic generalized and partial epilepsy. Forty prepubertal children aged 6-12 (mean 8.3±1.7) years, 19/40 (47.5%) female and 21/40 (52.5%) male, with idiopathic generalized or partial epilepsy diagnosed in the child neurology outpatient clinic were included. The patients were divided into two treatment groups: 20 were treated with VPA and 20 with TPM. The plasma levels of IL-1α, IL-1β, IL-6, IL-10, TNF-α were measured using ELISA method before the initiation of treatment and at the 6th and 12th months of the treatment. The Chi-square test was used to compare qualitative data. To compare the periods, recurrence measurements were done using variance analysis and Freidman 2-sided variance analysis. p<0.05 was considered as statistically significant. In the VPA group, the levels of IL-1α significantly increased at 12 months while the levels of IL-10 decreased at 6 months of treatment compared to values before treatment (p<0.05). There was no significant difference in levels of IL-1β, IL-6, TNF-α (p>0.05). In the TPM group, lower levels of IL-10 were observed at 6th and 12th months compared to the onset of treatment (p<0.05). The results of this study demonstrated that VPA and TPM might lead to changes in the levels of cytokines in epileptic patients. The next step would be to investigate the relation of these findings to the outcome of epilepsy and response to treatment.


The Myhre syndrome: report of two cases.
Two unrelated patients, aged 19 and 6 years, were studied and diagnosed as having Myhre syndrome (MS). This review, together with three previous cases, permits further delineation of MS. The main features are: short stature, mental retardation, blepharophimosis, muscular hypertrophy, decreased joint mobility, thick calvarium, broad ribs, hypoplastic iliac wings and short tubular bones. Advanced paternal age at the propositi's birth suggests an autosomal dominant mutation as the cause of MS.


The Cell Protective Effect of Adenine on Hypoxia-Reoxygenation Injury through PPAR Delta Activation.
Ischemia followed by blood supply reperfusion in cardiomyocytes leads to an overproduction of free radicals and a rapid decrease of adenosine triphosphate concentration. The cardioprotective effect of a potential drug, adenine, was evaluated using H9c2 rat cardiomyoblasts. After hypoxia-reoxygenation (HR) treatment consisting of hypoxia for 21 h followed by reoxygenation for 6 h, it was revealed that pretreatment with 200 µM adenine for 2 h effectively prevented HR-induced cell death. Adenine also significantly decreased the production of reactive oxygen species and reduced cell apoptosis after HR injury. The antioxidant effect of adenine was also revealed in this study. Adenine pretreatment significantly reduced the expression of activating transcription factor 4 (ATF4) and glucose-regulated protein 78 (GRP78) proteins, and protein disulfide isomerase induced a protective effect on mitochondria after HR stimulation. Intracellular adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor delta (PPARδ), and perilipin levels were increased by adenine after HR stimulation. Adenine had a protective effect in HR-damaged H9c2 cells. It may be used in multiple preventive medicines in the future.


1,2- and 1,4-Cyclohexanediol: major urinary metabolites and biomarkers of exposure to cyclohexane, cyclohexanone, and cyclohexanol in humans.
The metabolism and toxicokinetics of cyclohexane (CH) and cyclohexanol (CH-ol), important solvents and chemical intermediates, were studied in volunteers after 8-h periods of inhalation exposure at concentrations of 1010 and 236 mg m(-3), respectively (occupational exposure limits: CH, 1050 mg m(-3); CH-ol, 200 mg m(-3)). Of the dose of absorbed parent compounds, the yields of urinary CH-ol and 1,2- and 1,4-cyclohexanediol (CH-diol) were 0.5%, 23.4%, and 11.3%, respectively, after exposure to CH and 1.1%, 19.1%, and 8.4%, respectively, after exposure to CH-ol as determined by a gas chromatography method involving hydrolysis of glucuronide conjugates. The metabolic patterns of CH and CH-ol were very similar to that of cyclohexanone (CH-one) studied in the laboratory previously. For all three compounds, peak excretion of CH-ol occurred at the end of the exposure period, after which it decayed rapidly. Excretion curves of 1,2- and 1,4-CH-diol reached maximal values within 0-6 h postexposure, with subsequent elimination half-lives being 14-18 h. The rate-limiting step in the elimination of CH compounds from the organism is renal clearance of CH-diols. Determination of CH-diols in end-of-shift urine samples is recommended as a useful new method of biomonitoring of CH, CH-ol, and CH-one at the workplace. However, due to accumulation of CH-diols in the body during repeated exposure, quantitative relationships between the exposure and the level of CH-diols have to be adjusted according to the day of sampling during the working week.


Performance of Automated Software in the Assessment of Segmental Left Ventricular Function in Cardiac CT: Comparison with Cardiac Magnetic Resonance.
To evaluate the accuracy, reliability and time saving potential of a novel cardiac CT (CCT)-based, automated software for the assessment of segmental left ventricular function compared to visual and manual quantitative assessment of CCT and cardiac magnetic resonance (CMR). Forty-seven patients with suspected or known coronary artery disease (CAD) were enrolled in the study. Wall thickening was calculated. Segmental LV wall motion was automatically calculated and shown as a colour-coded polar map. Processing time for each method was recorded. Mean wall thickness in both systolic and diastolic phases on polar map, CCT, and CMR was 9.2 ± 0.1 mm and 14.9 ± 0.2 mm, 8.9 ± 0.1 mm and 14.5 ± 0.1 mm, 8.3 ± 0.1 mm and 13.6 ± 0.1 mm, respectively. Mean wall thickening was 68.4 ± 1.5 %, 64.8 ± 1.4 % and 67.1 ± 1.4 %, respectively. Agreement for the assessment of LV wall motion between CCT, CMR and polar maps was good. Bland-Altman plots and ICC indicated good agreement between CCT, CMR and automated polar maps of the diastolic and systolic segmental wall thickness and thickening. The processing time using polar map was significantly decreased compared with CCT and CMR. Automated evaluation of segmental LV function with polar maps provides similar measurements to manual CCT and CMR evaluation, albeit with substantially reduced analysis time. • Cardiac computed tomography (CCT) can accurately assess segmental left ventricular wall function. • A novel automated software permits accurate and fast evaluation of wall function. • The software may improve the clinical implementation of segmental functional analysis.


Neuronal nicotinic acetylcholine receptors in rat trigeminal ganglia.
The application of nicotine to the various epithelia served by the trigeminal nerve produces irritation and/or pain by activating neuronal nicotinic acetylcholine receptors (NnAChRS) in sensory neurons. In this study the NnAChRs were identified in rat trigeminal ganglia (TG) using RT-PCR and immunocytochemistry. With RT-PCR the subunits of NnAChRs in rat TG were determined, and with immunocytochemistry the localization of three prominent subunits (alpha 7, alpha 4 and beta 2) were localized in intact TG neurons. The relative abundance of the alpha and beta subunits were: alpha 7 approximately alpha 3 > alpha 6 > alpha 4 approximately alpha 5 > alpha 9 > or = alpha 2, and beta 2 approximately beta 3 > beta 4. This is the first report of the alpha 9 subunit in TG. Immunohistochemical studies revealed that almost all TG neurons contained alpha 7-LI and alpha 4-LI, and that 85% had beta 2-LI. For these three subunits much of the label was internalized. Immunocytochemical studies using antibodies raised against chick alpha 8 subunits did not specifically label rat TG. These data reveal that rat TG neurons contain the entire spectrum of mammalian NnAChR subunits.


Mammographic and ultrasonographic features after autogenous myocutaneous flap reconstruction mammoplasty.
To present mammographic and ultrasonographic findings in various types of reconstruction using an autogenous myocutaneous flap after mastectomy or breast-conserving surgery. Mammography and ultrasonography performed in patients who had undergone reconstruction mammoplasty using the autogenous myocutaneous flap procedure were reviewed to facilitate recognition of both normal and abnormal postoperative appearances of the various types of reconstruction using the autogenous myocutaneous flap after mastectomy or breast-conserving surgery. Normal mammographic and ultrasonographic findings include predominance of a fatty appearance, surgical clips, and surgical scars. Abnormal mammographic and ultrasonographic findings include fat necrosis, calcifications, and locally recurrent carcinoma. Ultrasonographic findings of fat necrosis were cystic, complex, and solid-appearing masses with circumscribed or poorly defined margins in peripheral portions of the flap. Ultrasonographic findings of locally recurrent carcinoma were poorly defined heterogeneous hypoechoic lesions in reconstructed breast, similar to those of primary breast cancer. Breast reconstruction using the autogenous myocutaneous flap has increased in popularity with various methods. Mammography and ultrasonography facilitated excellent visualization of normal and abnormal findings of various reconstructed breasts with the autogenous myocutaneous flap.


Calcium ionophore-induced apoptosis of human B cells is preceded by the induced expression of early response genes.
We have investigated the effects of calcium ionophore on apoptosis of Ramos human B cells. Our results show that the calcium ionophore A23187 at defined concentrations leads to apoptosis of Ramos cells. The majority of cells (> 90%) undergo apoptosis in response to ionophore. The response is rapid and nuclear condensation and DNA degradation can be detected within 2 h after addition of ionophore. In attempts to define the changes in gene expression preceding apoptosis, we investigated the expression of a panel of early response genes in these cells after ionophore addition. We show that calcium ionophore-induced apoptosis of Ramos cells is preceded by the induced expression of a number of early response genes. These results are consistent with calcium ionophore initiating changes in gene expression which may be important in signaling these cells to undergo apoptosis.


Interaction of cocaine and bunaphtide on the 3H-norepinephrine uptake mechanism on isolated left atrium of guinea-pig.
Bunaphtide induces a blockade in the 3H-norepinephrine uptake and retention in the isolated guinea-pig left atrium. However, this blockade does not seem to be related with the cardiodepressant effect of the drug.


Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer.
The ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab. The subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis. Sixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0-1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46-1.34], p = 0.373, adjusted HR: 0.87 [0.41-1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38-1.12], p = 0.125, adjusted HR 0.53 [0.27-1.07], p = 0.078). In mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.


Clinical Significance of Increased FDG Uptake in the Waldeyer Ring and the Nasopharynx Region Identified by PET-CT in Postchemotherapy Follow-up in Patients With Lymphoma: When Should We Perform Biopsy?
To identify whether fluorodeoxyglucose (FDG) uptake in the Waldeyer ring (WR)/nasopharyngeal (NP) region by positron emission tomography-computed tomography (PET-CT) was physiologic or pathologic in the follow-up of lymphoma patients receiving postchemotherapy treatment. We retrospectively examined FDG uptake in the WR/NP region in 534 patients with lymphoma as assessed by PET-CT used for both diagnosis and follow-up. Forty-nine patients had FDG uptake in the WR/NP region by PET-CT performed after completion of a chemotherapy regimen. Biopsy was performed for 11 of these patients in whom the uptake was considered to be pathologic, and results indicated the presence of reactive follicular hyperplasia. It was considered to be physiologic in 38 patients. PET-CT was repeated after 1 year, and no significant difference was identified between the standardized maximum uptake values (SUVmax; P = .107). The initial diagnosis of 20 patients was made via biopsy performed in the WR/NP region. The SUVmax for the FDG uptake in these patients, asymmetry, SUVmax of the coexisting lymphadenopathies in the neck, and FDG uptake with a counterpart finding by CT were significantly higher than other groups (P = .047, .001, and .005). When deciding whether to resample after treatment completion, it should be taken into account that, in addition to the SUVmax of the lesion, asymmetry, and the SUVmax of the coexisting lymphadenopathy in the neck, a crucial criterion is whether the FDG uptake has a counterpart finding by CT.


Kinematics and power requirements of ascending and descending flight in the pigeon (Columba livia).
Ascending or descending locomotion involves a change in potential energy (PE) and a corresponding change in power requirement. We sought to test whether the mechanical power required for steady ascending or descending flight is a simple sum of the power required for level flight and the power necessary for potential energy change. Pigeons (Columba livia) were trained to fly at varying angles of ascent and descent (60 degrees , 30 degrees , 0 degrees , -30 degrees , -60 degrees ), and were recorded using high-speed video. Detailed three-dimensional kinematics were obtained from the recordings, allowing analysis of wing movement. Aerodynamic forces and power requirements were then estimated from kinematic data. As expected, ;PE flight power' increased significantly with angle of flight (0.234 W deg.(-1)), though there appeared to be a limit on the amount of PE that the birds could gain or dissipate per wingbeat. We found that the total power output for flight at various angles was not different from the sum of power required for level flight and the PE rate of change for a given angle, except for the steep -60 degrees descent. The total power for steep descent was higher than this sum because of a higher induced power due to the bird's deceleration and slower flight velocity. Aerodynamic force estimates during mid-downstroke did not differ significantly in magnitude or orientation among flight angles. Pigeons flew fastest during -30 degrees flights (4.9+/-0.1 m s(-1)) and slowest at 60 degrees (2.9+/-0.1 m s(-1)). Although wingbeat frequency ranged from 6.1 to 9.6 Hz across trials, the variation was not significant across flight angles. Stroke plane angle was more horizontal, and the wing more protracted, for both +60 degrees and -60 degrees flights, compared with other flight path angles.


Age-Related Features of the Viscosity of Plasma and Mitochondrial Membranes of Hepatocytes in Liver Cirrhosis.
The viscosity of plasma and mitochondrial membranes of hepatocytes was studied in young (3-month-old) and old (9-month-old) male Wistar rats. It was shown that viscosity of hepatocyte plasma and mitochondrial membranes in young rats under optimal vital functions in the area of protein-lipid membrane contacts was significantly lower than in old rats. No age-related differences in the viscosity of lipid-lipid membrane contacts and in the polarity of protein-lipid contacts and lipid layers were found. Liver cirrhosis induced by carbon tetrachloride and ethanol administration was associated with increased fluidity of the plasma and mitochondrial membranes of hepatocytes in rats of both age groups. The decrease in membrane viscosity in young rats occurred due to a decrease of the viscosity in the area of protein-lipid and lipid-lipid contacts, while in old rats in the area of protein-lipid contacts. Carbon tetrachloride and ethanol did not affect the polarity of lipid contacts and lipid layers.