Combining pedicle screw stimulation with spinal navigation, a protocol to maximize the safety of neural elements and minimize radiation exposure in thoracolumbar spine instrumentation.
The O-arm-based navigation increases the accuracy of pedicle screw positioning and offers the possibility of performing a 3D scan before wound closure. However, repeating the 3D scan exposes the patient to additional radiation. We combined O-arm navigation with pedicle screw (PS) stimulation followed by a 3D scan to evaluate their accuracy and aimed for the creation of a protocol that maximizes the safety and minimizes radiation. Patients had pedicle screws insertion using O-arm spinal navigation, then had PS triggered electromyography (EMG), and finally a 3D scan to evaluate the accuracy of screw position. 447 screws were inserted in 71 patients. In 10 patients, 11 screws needed repositioning. Comparing results of PS triggered EMG responses to the 3D scan, we found: (a) negative stimulation response with negative 3D scan findings, corresponding to 432 acceptable screw position (96.6 %) in 58 patients (81.7 %). In these cases, the redo 3D scan could be avoided. (b) Positive stimulation response with positive 3D scan findings, corresponding to 7 unacceptable screw position (1.5 %) in 6 patients (8.4 %). In these cases, PS stimulation detected malpositioned screws that would be missed without a redo 3D scan. We propose a protocol of routinely performing PS stimulation after screw insertion using spinal navigation. In case of positive stimulation, a 3D scan must be performed to rule out a probable screw mal position (6 patients 8.4 %). However, in case of negative stimulation, redo 3D scan can be avoided in 81.7 % of patients.


Influence of biotic and abiotic factors on home range size and shape of invasive wild pigs (Sus scrofa).
Determining factors influencing animal movements at a temporal scale that is similar to that at which management actions are conducted (e.g. weekly) is crucial for identifying efficient methods of wildlife conservation and management. Using global positioning system (GPS) data from 49 wild pigs in the southeast United States, we constructed weekly 50% and 95% utilization distributions to quantify the effects of biotic and abiotic factors on weekly core area and home range size, as well as home range shape. We found vegetative composition (i.e. proportion of bottomland hardwoods), season (based on forage availability), meteorological conditions (i.e. temperature and pressure), and sex influenced wild pig weekly home range and core area size, while vegetative composition (i.e. proportion of upland pines) and landscape features (i.e. distance to streams) also were important factors influencing home range shape. At close distances to streams, wild pigs had more elongate home ranges when their home ranges comprised less upland pine habitat; however, farther from streams, there was no change in home range shape across fluctuating proportions of upland pines. These results demonstrate that fine-scale wild pig home ranges and movements are pliable from week to week and influenced by several habitat, landscape, and meteorological attributes that can easily be quantified from available land use and meteorological databases. These findings are important for designing monitoring studies, identifying high risk zones for disease transmission, planning response to disease emergence events, and allowing more effective and efficient short-term management planning.


Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression, and comparison with the human liver and muscle isozymes.
We have cloned the cDNA encoding a new isozyme of glycogen phosphorylase (1,4-D-glucan:orthosphosphate D-glucosyltransferase, EC 126.96.36.199) from a cDNA library prepared from a human brain astrocytoma cell line. Blot-hybridization analysis reveals that this message is preferentially expressed in human brain, but is also found at a low level in human fetal liver and adult liver and muscle tissues. Although previous studies have suggested that the major isozyme of phosphorylase found in all fetal tissues is the brain type, our data show that the predominant mRNA in fetal liver (24-week gestation) is the adult liver form. The protein sequence deduced from the nucleotide sequence of the brain phosphorylase cDNA is 862 amino acids long compared with 846 and 841 amino acids for the liver and muscle isozymes, respectively; the greater length of brain phosphorylase is entirely due to an extension at the far C-terminal portion of the protein. The muscle and brain isozymes share greater identity with regard to nucleotide and deduced amino acid sequences, codon usage, and nucleotide composition than either do with the liver sequence, suggesting a closer evolutionary relationship between them. Spot blot hybridization of the brain phosphorylase cDNA to laser-sorted human chromosome fractions, and Southern blot analysis of hamster/human hybrid cell line DNA reveals that the exact homolog of the newly cloned cDNA maps to chromosome 20, but that a slightly less homologous gene is found on chromosome 10 as well. The liver and muscle genes have previously been localized to chromosomes 14 and 11, respectively. This suggests that the phosphorylase genes evolved by duplication and translocation of a common ancestral gene, leading to divergence of elements controlling gene expression and of structural features of the phosphorylase proteins that confer tissue-specific functional properties.


Aortic valve repair using geometric ring annuloplasty in pediatric and congenital heart disease patients.
Existing replacement options for the aortic valve have significant drawbacks, especially in children. A geometric annuloplasty ring can help to achieve consistently successful aortic valve repair, but only limited experience with use of this device has been reported in pediatric and congenital heart disease patients. All pediatric and adult congenital patients at our institution who underwent aortic valve repair with placement of a geometric annuloplasty ring were reviewed. The study period spanned from July 2018 to April 2022. Hemodynamic outcomes were evaluated using transthoracic echocardiography. The study included 36 subjects. The median age was 17.4 years (range, 8-30 years). Twenty-one subjects were younger than age 18 years. The most common primary diagnoses were neoaortic valve insufficiency or neoaortic root dilation, and congenital aortic stenosis with bicuspid or functionally unicuspid aortic valve. Of the 34 subjects with procedural success, 31 (91%) had use of additional valve repair techniques and 26 (76%) had an additional concomitant procedure performed. Operative mortality was 0% (0/33), and major complication rate was 6% (2/33). The median follow-up time was 1.9 years (maximum, 3.8 years). The mean grade of aortic insufficiency was signific antly reduced after repair, with no change in mean gradients. Freedom from reoperation over the follow-up period was 97% (33/34), and freedom from ≥3+ recurrent aortic insufficiency was 94% (32/34). A geometric annuloplasty ring can be used to help achieve consistently successful aortic valve repair with excellent perioperative and follow-up outcomes, even in pediatric and complex congenital heart disease patients.


Temporal effects of nicotine nasal spray and gum on nicotine withdrawal symptoms.
Nicotine nasal spray and nicotine gum have been found to be effective in relieving nicotine withdrawal symptoms. In this randomized single-blind study, 91 cigarette smokers were randomly assigned to a single 1 mg dose of active nicotine nasal spray (n=29), active 4 mg nicotine gum (n=31), saline placebo nasal spray (n=16) or placebo gum (n=15). Following overnight abstinence, subjects repeatedly completed visual analog scales for assessing nicotine withdrawal symptoms over 30 min preceding (time -30 min to time 0) and 120 min following a single dose of study medication. This sequence was performed 3 times during the day. Nicotine withdrawal symptoms were assessed on a 41-point visual analog scale (1=no withdrawal, 41=extreme withdrawal). At the initial session only, blood samples for serum nicotine levels were taken at baseline, then at 5, 10, 30 and 120 min following study drug administration. The mean (+/-SD) age of the subjects was 38.6 (+/-10.1) years, 48% were females, smoking rate was 24.5 (+/-7.8) cigarettes per day, and years of smoking was 19.9 (+/-10.0). A single 1 mg dose of nicotine nasal spray provided more immediate relief for craving for a cigarette compared to a single 4 mg dose of nicotine gum. Serum venous nicotine levels for the active nicotine nasal spray and nicotine gum were comparable at 5 and 10 min while the levels were higher for nicotine gum at 30 and 120 min. Changes in withdrawal symptoms were not found to be related to serum venous nicotine levels. Our findings provide a rationale for the as needed use of nicotine nasal spray to control withdrawal symptoms, possibly in combination with other medications with longer acting effects.


Phytochemical and antimicrobial investigations of stilbenoids and flavonoids isolated from three species of Combretaceae.
The antimicrobial activity and chemistry of the African Combretaceae has been well studied in recent years. The present study aimed to investigate the phytochemistry and antimicrobial activity of lesser known members of this family viz. C. hereroense, C. apiculatum and C. collinum. Pulverized leaves of C. collinum and C. apiculatum, and the fruit of C. hereroense were extracted with organic solvents and subjected to preparative chromatography. Seventeen phenolic constituents including four phenanthrenes from the fruit of C. hereroense and two known bibenzyls (including a combretastatin) from the leaves of C. collinum were isolated. The compounds were then subsequently tested for their antimicrobial activity against Candida albicans, Mycobacterium fortuitum, Staphylococcus aureus, Escherichia coli and Proteus vulgaris. Pinocembrin showed excellent activity against C. albicans (MIC - 6.25 μg/ml), superior to that of the positive control, fluconazole and against S. aureus (MIC - 12.5 mg/ml). The phenanthrenes (compounds 1, 2, 3 and 5) showed some activity against M. fortuitum and S. aureus with a uniform MIC of 25 μg/ml. From this study it was evident that most stilbenoids and flavonoids from the selected Combretaceae have little or no antimicrobial activity.


Sodium-coupled neutral amino acid transporter 4 functions as a regulator of protein synthesis during liver development.
The molecular mechanisms by which hepatocyte nuclear factor (HNF)4α regulates fetal liver development have not been fully elucidated. We screened the downstream molecules of HNF4α during liver development and identified sodium-coupled neutral amino acid transporter (SNAT)4. The aim of this study is to investigate the regulation of SNAT4 by HNF4α and to clarify its roles in differentiating hepatocytes. HNF4α was overexpressed in cultured liver buds using adenovirus, and suppression subtractive hybridization screening was performed. Temporal and spatial expression of SNAT4 during liver development was investigated. Regulation of SNAT4 by HNF4α was examined by promoter analyses and electrophoretic mobility shift assays (EMSA). Metabolic labeling and western blotting were carried out using primary hepatoblasts with SNAT4 overexpression. The expression of Slc38a4 encoding SNAT4 showed a marked perinatal increase, and was predominant among system A amino acid transporters. It was first detected in embryonic day 18.5 liver, and found in most hepatocytes after birth. Three alternative first exons were found in the SNAT4 gene. Promoter analyses using approximately 3-kb fragments corresponding to each first exon (AP1, AP2, AP3) revealed that AP1 and AP2 exhibited strong promoter activity in mouse hepatoblasts with endogenous HNF4α. Transactivation of AP2 was upregulated by HNF4α in HeLa cells without endogenous HNF4α. EMSA has demonstrated that HNF4α directly binds to cis-elements in AP2. Overexpression of SNAT4 facilitated amino acid uptake and de novo protein synthesis in primary hepatoblasts. SNAT4 functions downstream of HNF4α and plays significant roles in liver development through mechanisms of amino acid uptake and protein synthesis.


Proteome-pI 2.0: proteome isoelectric point database update.
Proteome-pI 2.0 is an update of an online database containing predicted isoelectric points and pKa dissociation constants of proteins and peptides. The isoelectric point-the pH at which a particular molecule carries no net electrical charge-is an important parameter for many analytical biochemistry and proteomics techniques. Additionally, it can be obtained directly from the pKa values of individual charged residues of the protein. The Proteome-pI 2.0 database includes data for over 61 million protein sequences from 20 115 proteomes (three to four times more than the previous release). The isoelectric point for proteins is predicted by 21 methods, whereas pKa values are inferred by one method. To facilitate bottom-up proteomics analysis, individual proteomes were digested in silico with the five most commonly used proteases (trypsin, chymotrypsin, trypsin + LysC, LysN, ArgC), and the peptides' isoelectric point and molecular weights were calculated. The database enables the retrieval of virtual 2D-PAGE plots and customized fractions of a proteome based on the isoelectric point and molecular weight. In addition, isoelectric points for proteins in NCBI non-redundant (nr), UniProt, SwissProt, and Protein Data Bank are available in both CSV and FASTA formats. The database can be accessed at http://isoelectricpointdb2.org.


Immune infertility and new approaches to treatment.
A number of patients who have involuntary infertility show sperm antibodies in the blood serum, as detected by two quite different methods of spermagglutination. These techniques are the Kibrick method (gelatin agglutination test) and the F-D method (tube-slide agglutination test). By the former technique, the sera of 18% of women and 9% of men from infertile couples were found to be positive; by the latter technique, the sera of 15% of women and 5% of men were positive. Such cases are termed "immunologic infertility." In an effort to develop new methods for the treatment of infertility, two procedures were explored. One is a sperm washing insemination method in which fresh semen from a man with the antibody is centrifuged, resuspended in an albumin solution, and then used for insemination. The second is an immunosuppression method, using methylprednisolone at a dose of 96 mg/day for 7 days. A striking decrease in antibody level was seen in some cases, with ensuing pregnancy. The success rates for these methods have been of the order of 14% to 22%.


Ozone attributed to Madrid and Barcelona on-road transport emissions: Characterization of plume dynamics over the Iberian Peninsula.
Despite the ~30% emission decrease of the main tropospheric ozone (O3) precursors in Spain in the 2001-2012 period, the O3 concentration in summer still exceeds the target value for the protection of the human health of the Air Quality Directive (2008/50/EC). On-road transport is the main anthropogenic contributor to O3 precursor's emissions in Madrid and Barcelona metropolitan areas (65%/59% of NOx, 40%/33% of NMVOC, and 67%/85% of CO emissions) but this contribution to O3 formation is not well understood. The present work aims at increasing the understanding on the role of on-road transport emissions from main Spanish urban areas in O3 dynamics over Spain under typical circulation types. For that purpose, the Integrated Source Apportionment Method is used within the CALIOPE modelling system (WRF/CMAQ/HERMES/BSC-DREAM8b). The results indicate that the daily maximum O3 concentration attributed to the on-road transport emissions from Madrid (O3T-MAD) and Barcelona metropolitan areas (O3T-BCN) contribute up to 24% and 8% to total O3 concentration, respectively, within an area of influence of 200 km. The contribution of O3T-MAD and O3T-BCN is particularly significant (up to 80-100 μg m(-3) in an hour) to the O3 concentration peak during the central hours of the day in the high O3 concentration season (April-September). The maximum O3T-MAD concentration is calculated within the metropolitan area of Madrid but the plume, channelled by the Tajo and the Henares valleys, affects large areas of the Iberian Peninsula. The O3T-BCN plume is more driven by sea-land and mountain-valley breezes than by the synoptic advection and its maximum concentration is usually registered over the Mediterranean Sea. The O3 concentration transported long-range to the Iberian Peninsula is significant in the area of influence of Madrid and Barcelona, being maxima under cold (70-96%) and minima in warm circulation types (35-70%).


The twisting force of aged consumers when opening a jar.
Many people experience difficulty when opening a vacuum-sealed jar. Yet solutions to the problem continue to be tool-based rather than exploring the possibility of innovative changes in product packaging. Improvement depends on gaining knowledge of the capabilities of users, and of using that knowledge as a base for product innovation. To establish such a base we took a sample of 750 subjects and asked them two questions about how they opened jars at home. We then carried out torque measurements using a force transducer shaped like a jam jar. We reached the conclusion that if opening torque was reduced to 2 N m then 97.6% of users between 50 and 94 years of age and 100% of 20-30 year old users would have no difficulty opening a jar.


Contributions of Parasympathetic Arousal-Related Activity to Cognitive Performance in Patients With First-Episode Psychosis and Control Subjects.
Cognitive impairment is integral to the pathophysiology of psychosis. Recent findings implicate autonomic arousal-related activity in both momentary fluctuations and individual differences in cognitive performance. Although altered autonomic arousal is common in patients with first-episode psychosis (FEP), its contribution to cognitive performance is unknown. A total of 24 patients with FEP (46% male, age = 24.31 [SD 4.27] years) and 24 control subjects (42% male, age = 27.06 [3.44] years) performed the Multi-Source Interference Task in-scanner with simultaneous pulse oximetry. First-level models included the cardiac-blood oxygen level-dependent regressor, in addition to task (congruent, interference, and error) and nuisance (motion and CompCor physiology) regressors. The cardiac-blood oxygen level-dependent regressor reflected parasympathetic arousal-related activity and was created by convolving the interbeat interval at each heartbeat with the hemodynamic response function. Group models examined the effect of group or cognitive performance (reaction times × error rate) on arousal-related and task activity, while controlling for sex, age, and framewise displacement. Parasympathetic arousal-related activity was robust in both groups but localized to different regions for patients with FEP and healthy control subjects. Within both groups, arousal-related activity was significantly associated with cognitive performance across occipital and temporal cortical regions. Greater arousal-related activity in the bilateral prefrontal cortex (Brodmann area 9) was related to better performance in healthy control subjects but not patients with FEP. Autonomic arousal circuits contribute to cognitive performance and the pathophysiology of FEP. Arousal-related functional activity is a novel indicator of cognitive ability and should be incorporated into neurobiological models of cognition in psychosis.


Inhibition of ribosome biogenesis by actinomycin D affects Arabidopsis root development.
Actinomycin D has been reported to selectively inhibit rRNA synthesis and ribosome biogenesis, induce G2 checkpoint of cell cycle arrest in HeLa cells. In Arabidopsis, actinomycin D was also used as agent to preferentially inhibit the ribosome biosynthesis and ribosomal function. However, the function of actinomycin D on Arabidopsis root development remains to be elucidated. In this study, we exposed Arabidopsis seedlings to actinomycin D with the aim of evaluating the effects of ribosome biogenesis on root development. The results demonstrated that actinomycin D inhibited Arabidopsis root growth by reduced meristematic activity in a dose dependent manner. Exposure to actinomycin D decreased the expression of WOX5 and key stem cell niche-defining transcription factors SHR and PLT1, thus the loss function of QC identity and stem cell niche maintenance. In addition, dead cells were observed after actinomycin D treatment in root stele initials and DNA damage response was constitutively activated. Collectively, we propose that ribosome biogenesis plays key role in primary root growth through maintenance of root stem cell niche and DNA damage response in Arabidopsis.


Uterine artery Doppler and placental volume in the first trimester in the prediction of pregnancy complications.
To evaluate placental volume and uterine artery Doppler in the first trimester in the prediction of pregnancies that subsequently develop pre-eclampsia, pregnancy-induced hypertension, preterm placental abruption or fetal growth restriction. In 380 singleton pregnancies attending our center for nuchal translucency screening at 11-14 weeks of gestation, Doppler assessment of both uterine arteries was carried out for measurement of the pulsatility index and the mean pulsatility index of the two vessels was calculated. In addition, three-dimensional ultrasound was used to obtain images for subsequent measurement of placental volume. The 90th centile of the uterine artery mean pulsatility index and the 10th centile of the placental volume for crown-rump length (placental quotient) were calculated. These cut-offs were used for the prediction of pregnancy complications. Complications occurred in 36 (9.5%) of the 380 pregnancies, including 31 cases of fetal growth restriction, two of pregnancy-induced hypertension and abruption, two of pregnancy-induced hypertension, and one of abruption. The uterine artery mean pulsatility index was > or =90th centile in 38 (10%) pregnancies and this group contained nine (25%) of those that developed complications. The placental quotient was < or =10th centile in 39 (10%) pregnancies and this group contained eight (22%) of those that developed complications. In eight (2%) pregnancies the uterine artery mean pulsatility index was > or =90th centile and the placental quotient was < or =10th centile and this group contained six (17%) of those that developed complications. The combination of placental volume measurement and uterine artery Doppler in the first trimester may identify women at risk for subsequent development of pregnancy complications.


Hand functions in systemic sclerosis and rheumatoid arthritis and influence on clinical variables.
Hand joints are the main target in rheumatoid arthritis (RA) and hand involvement in terms of thickening of the skin and contractures are also well known in systemic sclerosis (SSc). Assessment of hand function in SSc is generally an overlooked entity with respect to RA. Therefore the aim of this study was to compare hand functions and potential influence of functional loss on patients' overall physical functions, health-related quality of life (HRQoL) and psychological status in RA and SSc. Age- and gender-matched adult patients with SSc and RA were consecutively recruited. Patients' hand functions were evaluated by using the Duruöz Hand Index (DHI), and hand span and hand grip strength were measured. Patients were evaluated for disease-specific and generic outcome measures including disease activity parameters and HRQoL measures. Fifty patients (44 female, six male) with SSc and 51 (45 female, six male) with RA were included. Despite similar functioning and HRQoL, patients with RA had higher visual analog scale-pain and body mass index. In both groups DHI revealed similar functional loss and correlated with various measurements related to HRQoL. In SSc, hand span, grip strength and modified Rodnan skin score had major influences on hand functions. Assessment of hand function is an important component in the clinical evaluation of patients with RA and SSc. Loss of hand functions is an important feature contributing negatively to the overall physical status and HRQoL in patients with SSc and may be more frequent and important than expected.


Total Hip Arthroplasty in Young Patients in The Netherlands: Trend Analysis of >19,000 Primary Hip Replacements in the Dutch Arthroplasty Register.
Total hip arthroplasty (THA) is one of the most successful interventions in medical care. Because of shifting trends in THA and failure rates being higher in younger patients, we aimed to assess trends in implant fixation, bearing type, head diameter, and surgical approach in patients younger than 55 years in the Netherlands using data from the Dutch Arthroplasty Register. Trends in the method of implant fixation, bearing type, head diameter, and surgical approach were analyzed over year of surgery (2007-2016) and over age groups (<25, 25-29, 30-34, 35-39, 40-44, 45-49, and 50-54 years). Between 2007 and 2016, a total of 19,915 primary THAs were performed in patients <55 years. Osteoarthritis was the most prevalent diagnosis (66.1%). Uncemented fixation was used in 79.5% of all performed THAs. The use of 32-mm head diameters increased (from 32.6% in 2007 to 50.1% in 2016), where an increasing trend toward the use of ceramic-on-polyethylene as most frequently used bearing type was present (from 37.5% in 2007 to 53.8% in 2016). The posterolateral surgical approach was the most frequently used approach; however, the anterior approach is used increasingly (0.1% in 2007 to 21.1% in 2016). Ceramic-on-polyethylene bearing surfaces, 32-mm head diameters, and the anterior approach were most commonly used in patients between 50 and 54 years. There was a clear preference for uncemented fixation in young patients. In head diameter, bearing type, and surgical approach, clear trends were visible. Characteristics of THA in young patients were subject to changing perspectives.


Cervical cancer heterogeneity: a constant battle against viruses and drugs.
Cervical cancer is the first identified human papillomavirus (HPV) associated cancer and the most promising malignancy to be eliminated. However, the ever-changing virus subtypes and acquired multiple drug resistance continue to induce failure of tumor prevention and treatment. The exploration of cervical cancer heterogeneity is the crucial way to achieve effective prevention and precise treatment. Tumor heterogeneity exists in various aspects including the immune clearance of viruses, tumorigenesis, neoplasm recurrence, metastasis and drug resistance. Tumor development and drug resistance are often driven by potential gene amplification and deletion, not only somatic genomic alterations, but also copy number amplifications, histone modification and DNA methylation. Genomic rearrangements may occur by selection effects from chemotherapy or radiotherapy which exhibits genetic intra-tumor heterogeneity in advanced cervical cancers. The combined application of cervical cancer therapeutic vaccine and immune checkpoint inhibitors has become an effective strategy to address the heterogeneity of treatment. In this review, we will integrate classic and recently updated epidemiological data on vaccination rates, screening rates, incidence and mortality of cervical cancer patients worldwide aiming to understand the current situation of disease prevention and control and identify the direction of urgent efforts. Additionally, we will focus on the tumor environment to summarize the conditions of immune clearance and gene integration after different HPV infections and to explore the genomic factors of tumor heterogeneity. Finally, we will make a thorough inquiry into completed and ongoing phase III clinical trials in cervical cancer and summarize molecular mechanisms of drug resistance among chemotherapy, radiotherapy, biotherapy, and immunotherapy.


Cervical antibodies to herpes simplex virus proteins in pregnancy and puerperium: a pilot study.
This study was undertaken to evaluate the changes in total and anti-herpes simplex virus (HSV)-specific cervical IgA and IgG antibody profiles during and after pregnancy. Serum and cervical secretions were obtained from pregnant patients before 20 weeks gestation, at 34-36 weeks gestation, and at 6 weeks postpartum and tested for total IgA and IgG antibody and for IgA and IgG to HSV proteins by Western blot. Seven women were HSV seronegative, 14 HSV-1 seropositive, and 14 HSV-2 +/- HSV-1 seropositive. Minimal changes in the serum anti-HSV profiles were seen over the 3 visits. The total cervical IgA, IgG, and protein levels did not change between the 2 pregnancy visits but tended to increase at the postpartum visit. No consistent change in cervical HSV-specific IgA and IgG was seen during pregnancy, but the levels increased markedly at the postpartum visit. Lower cervical anti-HSV antibody levels may be related to the previously reported increased frequency of a reactivation of HSV during late pregnancy. Further evaluation is necessary to confirm and quantify the changes in genital immunity during pregnancy and to evaluate whether the increased levels at the postpartum visit are sustained.


Loudness dependence of auditory evoked potentials as indicator of central serotonergic neurotransmission: simultaneous electrophysiological recordings and in vivo microdialysis in the rat primary auditory cortex.
Serotonin released in synapsis is one of the key neurotransmitters in psychiatry and psychopharmacology. The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a marker for central serotonergic neurotransmission. Several findings in animals and humans support this hypothesis. However, the in vivo measurement of cortical extracellular serotonin levels has never been performed simultaneously with the recording of auditory evoked potentials. The interrelationship between low cortical serotonergic activity and strong LDAEP is yet to be proven. The auditory evoked potentials were recorded in the epidura above the primary auditory cortex of male Wistar rats whereas extracellular serotonin levels in the primary auditory cortex were measured by in vivo microdialysis before and after i.p. application of the selective serotonin reuptake inhibitor citalopram. At baseline, the correlation of coefficients between the LDAEP, especially of the N1 component, and extracellular serotonin levels in the primary auditory cortex was negative. The increase of serotonin levels after citalopram application was significantly related to a decrease of LDAEP of the N1 component (r=-0.86, p=0.003). These data support the view that the LDAEP is closely modulated by cortical serotonergic activity. Thus, the LDAEP might serve as an inversely related marker of synaptically released serotonin in the CNS.


Diabetes and the heart: could the diabetic myocardium be protected by preconditioning?
Both type 1 and type 2 diabetes (insulin-dependent and non-insulin dependent diabetes, respectively) are associated with increased risk for microvascular and macrovascular complications including retinopathy, neuropathy, nephropathy and atherosclerosis. Type 2 diabetes markedly increases the risk for cardiovascular morbidity and mortality, which has major public health implications. In this review, molecular mechanisms pertaining to diabetes-induced heart pathology are addressed.


Serum lipid levels and suicide attempts.
To determine whether a correlation exists between lower serum lipid concentrations and increased suicide risk. Serum lipid profiles were pair-matched for 60 patients who had recently experienced failed attempts at suicide and equal numbers of non-suicidal psychiatric patients, and normal controls. Suicide attempt severity was scored using Weisman and Worden's risk-rescue rating scale. (a). Total serum cholesterol and low density lipoprotein levels were found to be lower in the parasuicidal population at statistically significant levels (P < 0.01 and <0.05, respectively); (b). triglyceride concentrations were lower in suicide attempters with major depression compared with non-suicidal depressed patients; and (c). risk-rescue rating scores were negatively correlated with total serum cholesterol levels (r = -0.347, P = 0.007). Low lipid metabolism may be a potential biological marker in the assessment of suicide risk. Further investigations are necessary to elucidate the biological mechanisms of these findings.


Evaluation of quality and hydrogeochemistry of rock aquifers in Jurong Formation at Southern Johor Bahru, Malaysia.
Jurong Formation underlies part of Southern Johor Bahru which comprises well cemented and consolidated volcanic-sedimentary rocks. The study aims to assess quality and hydrogeochemistry of rock aquifer in Jurong Formation at Southern Johor Bahru which is mainly overlain by rhyolitic tuff. It also evaluates the differences in quality and hydrogeochemistry of rhyolitic tuff aquifer found in source and floodplain zones of South-West Johor Rivers Basin. In this study, a total of nine samples from four wells, namely TW1-TW4, were collected at foothills of Gunung Pulai (TW1) and Iskandar Puteri (TW2-TW4) in Southern Johor Bahru. The samples were examined for physiochemical parameters. The groundwater in the study area is fresh and non-saline with hardness of soft to hard. The pH of groundwater in source zone is significantly higher than in floodplain zone. Meanwhile, the hardness of groundwater in source zone is significantly lower than in other deep wells in floodplain zone as more calcite mineral is present. The concentration of manganese, iron and zinc is lower at source zone than floodplain zone. Three facies of water types were encountered during the study such as CaNaHCO3 in TW2, CaHCO3 in TW1 and TW3 and CaCl2 in TW4. The deep wells in floodplain zone are susceptible to saline intrusion. Finally, the groundwater quality in the study area is found to control by rock weathering especially silicates and carbonates, rainfall and proximity to seawater. This suggests the major control on groundwater chemistry is due to leaching of volcanic rocks and dissolution on calcite infillings. In conclusion, the groundwater is clean and safe in general although pH value is slightly acidic closer to straits and magnesium's presence in higher concentration at TW2.


The fractured genome of HeLa cells.
Whole-genome sequencing of the widely used HeLa cell line provides a nucleotide-resolution view of a greatly mutated and in some places shattered genome.


Roles for structural and temporal shelter-changing by fern-feeding lepidopteran larvae.
Larvae of the pyralid moth, Herpetogramma aeglealis, construct feeding shelters upon the Christmas fern (Polystichum acrostichoides). Field and laboratory study involving 532 shelters showed that as the larvae mature, they sequentially inhabit approximately 5 shelters of 3 distinct types, constructed at night on different fronds of the same plant. The bundle shelter, simple and ephemeral, is first to be inhabited and constructed. The fiddlehead shelter which houses slightly older larvae strongly resembles contemporaneously emerging frond fiddleheads. The final shelter form, the globe, is a silk-bound ball of leaflets at the frond tip. An individual larva usually constructs 3 globe shelters on different fronds of the same plant before completing its development. As shelter sites, sterile Polystichum fronds are chosen preferentially over fertile fronds. The bundle and fiddlehead shelter forms, less abundant, appear cryptic to humans and perhaps to other vertebrates. The final globe shelter form is larger and quite conspicuous. However, the persistence of empty globe shelters left on the plant as the larva moves to a new one may serve to make searching for larvae less profitable for potential predators and parasites. We suggest that the energetic costs of constructing and occupying multiple shelters may be offset by circumvention of reduced frond palatability and reduced exposure to predators and parasites.


Surgical treatment of malignant esophagotracheal fistulas.
Malignant esophagotracheal fistulas represent the fatal evolution of esophageal cancer. Since October 1974, 18 patients were seen who had confirmed esophagotracheal fistula, and in half of these patients, the fistula was the revealing symptom. Upper gastrointestinal studies (using hydrosoluble dye) and bronchoscopic examination confirmed the diagnosis, which was already strongly suspected in 16 of the patients due to the specific nature of the cough triggered by swallowing. The average age of the patients was 57 years, (range, 32 to 78 years). In 12 patients, the nutritional repercussions were moderate, and in only 6 patients, were the bronchopulmonary consequences serious. Therapeutically, we adopted a palliative surgical attitude since the physical and psychological condition of these patients was considered fatal the month after discovery of the fistula. In addition, the results of intubation were uncertain and transitory. Our surgical methods evolved in three stages: first, we performed bipolar exclusion of the esophagus coupled with gastrostomy (four patients), second, we performed retrosternal coloplasty (five patients), and third retrosternal gastroplasty with drainage of the inferior portion of the esophagus by Roux-Y jejunal anastomosis (six patients). The latter technique was inspired from that described by Kirschner in 1920. It is moderately aggressive and has the advantage of dealing with several objectives: exclusion of the fistula, reestablishment of normal alimentation, drainage of the inferior portion of the esophagus, and permitting postoperative radiotherapy. In our series, when only the patients who underwent coloplasty or gastroplasty were considered, 3 of 11 died, and the longest postoperative survival times were 16 and 23 months. Regarding gastroplasty alone, our results were in agreement with those in the literature. In the 19 patients who underwent gastroplasty, the operative mortality was 31.5 percent and the average length of survival was 9 months. Six patients survived from 8 to 26 months. Therefore, this "last resort" surgery seems legitimate in light of the fact that the results are sometimes superior to those of radical curative surgery for extirpative esophageal cancer.


The elongation of fatty acids by microsomes and mitochondria from normal and pyridoxine-deficient rat brains.
The developmental profile of fatty acid elongation enzymes of rat brain microsomes and mitochondria and the consequences of pyridoxine deficiency have been investigated. The results suggest that a single enzyme system is responsible for elongation of the various fatty acids by mitochondria whereas the microsomal elongation system is diverse.


[Systematic errors and control measures during epidemiological surveys of myopia among schoolchildren and adolescents].
Systematic errors and bias are common problems that affect the validity and reliability of epidemiological surveys of myopia among schoolchildren and adolescents worldwide. To provide guidance for standardization of such surveys, the perniciousness, causes and control measures of errors in surveying respondents and bias during the examination and diagnosis are discussed in this article. It is emphasized that controlling systematic errors and bias is the key to ensuring the quality of an epidemiological survey of pediatric and adolescent myopia.


[The value of needle biopsy of the liver in the differential diagnosis of cholestatic jaundice. A clinico-pathologic study of 101 cases (author's transl)].
The examination of needle biopsy of the liver has permitted the identification of the aetiology of cholestatic jaundice in eighty five cases out of a series of one hundred-and-one patients, leaving eight without definite diagnosis and eight false diagnosis. The characteristic histopathologic lesions of lobular hepatitis and of obstructive jaundice are reviewed. The problems of identification of particular microscopic forms (obstructive jaundice with minimal portal tracts alterations, residual stage of hepatitis, cholangiolitic and hypercholestatic forms of hepatitis) are discussed.


Sympathetic nerve hyperactivity of essential hypertension is lower in postmenopausal women than men.
Sympathetic activation has been associated with the development and complications of hypertension. While the prevalence of hypertension and its cardiovascular risks in women are found to be less than in men and tend to become similar to men after the menopause, there have been no data on the level of sympathetic activation in postmenopausal women relative to men. Therefore, we planned to find out whether muscle sympathetic nerve hyperactivity of essential hypertension (EHT) in postmenopausal women is different from that in matched men. We quantified muscle sympathetic nerve activity (MSNA) as mean frequency of single units (s-MSNA) and multiunit bursts (b-MSNA) in 21 postmenopausal women with EHT (W-EHT) relative to 21 matched men with EHT (M-EHT), in comparison to two control groups of 21 normal women (W-NC) and 21 men (M-NC), respectively. The EHT groups had greater MSNA indices than NC groups. W-EHT had lower (P<0.05) s-MSNA (63+/-22.7 impulses per 100 cardiac beats) than M-EHT (78+/-11.2 impulses per 100 cardiac beats). W-NC had lower (P<0.05) s-MSNA (53+/-12.4 impulses per 100 cardiac beats) than M-NC (65+/-16.3 impulses per 100 cardiac beats). Similar results were obtained for b-MSNA. Postmenopausal women with EHT had lower level of central sympathetic hyperactivity than men. Similarly, normal postmenopausal women had lower MSNA than men. These findings suggest that postmenopausal women continue to have a lower sympathetic nerve activity than men even after the development of EHT, and that this could have implications for gender-specific management of hypertension.


New translocation in acute myeloid leukemia M4 eos.
The most common childhood malignancy is acute leukemia. Approximately 15- 20% of it, is Acute myeloid leukemia (AML). The general symptoms of this malignancy include fatigue, weakness, fever, paleness and bleeding disorders. There are two methods of classifying for AML: The French-American-British (FAB) and the World Health Organization (WHO) classification.The M4 eos subtype, also called myelomonocytic leukemia, is one subtype of AML with eosinophilia. The most common cytogenetic variations in this leukemia include inv (16) (p13q22) or the variant t (16; 16) (p13; q22). In this report, we present the first AML-M4 eos case with a new translocation that has not yet been reported.


The proline-, glycine-, glutamic acid-rich pink-violet staining proteins in human parotid saliva are phosphoproteins.
The major proteins in human parotid saliva, isolated in Fractions II-V following chromatography on Sephacryl S-200, DEAE-Sephadex A-50, or CM cellulose, contain 6 moles of phosphate per mole of protein, the phosphate probably bound to the protein via an ester linkage. This phosphate represents greater than 90% of the protein-bound phosphate in human parotid saliva. Neither purified gustin nor amylase, the two other major proteins in human parotid saliva, contain phosphate.


The lacrimal glands of the rat and the guinea pig are innervated by nerve fibers containing immunoreactivities for substance P and vasoactive intestinal polypeptide.
Two neuropeptides, substance P and vasoactive intestinal polypeptide, have been shown to increase secretion of exocrine glands. We have studied immunohistochemically the intra- and exorbital lacrimal glands of the rat and the guinea pig for the presence of substance P-like and vasoactive intestinal polypeptide-like immunoreactive (SPLI and VIPLI, respectively) nerve fibers. Both SPLI and VIPLI nerve fibers were found surrounding glandular acini, secretory ducts and blood vessels. Their distribution, however, was uneven. The SPLI fibers predominated around the ducts whereas VIPLI fibers predominated around acini. The results suggest that the two neuropeptides may both regulate the lacrimal secretion, but they may have two different sites of actions because they prevail in different locations.


Complete mesocolic excision in colon cancer surgery: a comparison between open and laparoscopic approach.
Complete mesocolic excision (CME) with central vessel ligation (CVL) as performed in Erlangen offers the best long-term outcome for colon cancer. The aim of this study was to assess specimens after laparoscopic vs open CME-CVL macroscopically and morphometrically in patients with left and right colon cancers. All specimens were freshly photographed. Precise tumour morphometry and grading of the surgical plane were performed as described by pathologists in Leeds, UK. Thirty-four specimens from right-sided cancers were divided into 18 transverse colon cancers (nine laparoscopic vs nine open) and 16 caecum-ascending colon cancers (seven laparoscopic vs nine open) and 56 specimens from left-sided cancers (33 laparoscopic vs 23 open). There was no difference between laparoscopically and open acquired left- and right-sided specimens. Specimens of transverse colon displayed differences in length of central ligation to tumour (open 11.67 cm vs laparoscopic 8.72 cm, P = 0.049), length of central ligation to bowel wall (open 9.11 cm vs laparoscopic 6.5 cm, P = 0.015) and lymph node clearance (open 46.33 vs laparoscopic 39.33, P = 0.033). Laparoscopy seems to offer specimens of similar quality after CME-CVL surgery for colon cancer to the open approach. Issues of completeness of excision from laparoscopy are raised for tumours located in the transverse colon.


Differences in Child Passenger Safety Counseling Frequency and Attitudes by Health Care Provider Specialty.
Many children are not being properly restrained in motor vehicles, resulting in unnecessary injury and fatalities. Health care provider (HCP) education is effective at increasing proper child restraint within vehicles. However, differences exist by HCP specialty in regards to frequency of child passenger safety (CPS) counseling. This study of a sample of 255 HCPs examined differences in CPS counseling by HCP specialty (pediatric vs. non-pediatric). HCPs from several upper Midwest states were surveyed about how frequently they provide CPS counseling in their practice by patient age and their attitudes toward CPS-related issues. Pediatric HCPs were twice as likely as non-pediatric HCPs to always provide CPS counseling to parents/guardians of children aged 5 or older. Non-pediatric HCPs were more likely than pediatric HCPs to feel that counseling is ineffective at increasing child seat/booster (p = 0.001) or seat belt use (p = 0.006). Non-pediatric HCPs were more likely than pediatric HCPs to feel there is inadequate time to provide CPS counseling in their practice setting (p = 0.001), and were less likely to know where to refer patients if they have questions regarding CPS issues (0.0291). The differences in HCP attitudes toward CPS counseling provision and the resulting differences in counseling frequency by patient age may contribute to disparities for patients who have limited or no access to pediatric HCPs. Additional research is needed to investigate the rationale for counseling differences seen by HCP specialty and patient age, and the potential effect on child motor vehicle injuries and fatalities.


Circulating miRNAs in extracellular vesicles related to treatment response in patients with idiopathic membranous nephropathy.
Extracellular vesicle (EV)-microRNAs (miRNAs) are potential biomarkers for various renal diseases. This study attempted to identify the circulating EV-miRNA signature not only for discriminating idiopathic membranous nephropathy (IMN) from idiopathic nephrotic syndrome (INS), but also to predict the treatment response of patients with IMN. We prospectively enrolled 60 participants, including those with IMN (n = 19) and INS (n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum EV-miRNA profiles of all participants. To identify the EV-miRNAs predictive of treatment response in IMN, we also analyzed EV-miRNAs among patients with IMN with and without clinical remission. The expression levels of 3 miRNAs differed between IMN patients, INS patients and HVs. In addition, compared to HVs, RNA sequencing revealed differential expression of 77 and 44 EV-miRNAs in patients with IMN without and with remission, respectively. We also identified statistically significant (|fold change ≥ 2, p < 0.05) differences in the expression levels of 23 miRNAs in IMN without remission. Biological pathway analysis of miRNAs in IMN without remission indicated that they are likely involved in various pathways, including renal fibrosis. Our study identified EV-miRNAs associated with IMN as well as those associations with therapeutic response. Therefore, these circulating EV-miRNAs may be used as potential markers for the diagnosis and prediction of treatment response in patients with IMN.


The molecules of social recognition memory: implications for social cognition, extended mind, and neuroethics.
Social cognition, cognitive neuroscience, and neuroethics have reached a synthesis of late, but some troubling features are present. The neuroscience that currently dominates the study of social cognition is exclusively cognitive neuroscience, as contrasted with the cellular and increasingly molecular emphasis that has gripped mainstream neuroscience over the past three decades. Furthermore, the recent field of molecular and cellular cognition has begun to unravel some molecular mechanisms involved in social cognition, especially pertaining to the consolidation of memories of particular conspecific organisms. Some new experimental techniques for positive interventions into these hypothesized mechanisms offer opportunities for establishing direct causal linkages between intra-neuronal molecular events and the behaviors used to measure social cognitive phenomena. Predicted results from an experiment described below also cast doubt on the application of the "extended mind" approach from recent cognitive science to ground the neuroscience of social cognition. Since neuroethics relies heavily on our best neuroscience of social cognition, that field may soon need to extend its attention beyond cognitive neuroscience, and into neuroscience's cellular and molecular mainstream.


Results of the prospective evaluation of radial keratotomy (PERK) study one year after surgery.
The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center, self-controlled clinical trial of a standardized technique of radial keratotomy in 435 patients who had physiologic myopia with a preoperative refraction between -2.00 and -8.00 diopters. The surgical technique consisted of eight incisions using a diamond micrometer knife with blade length determined by intraoperative ultrasonic pachymetry and the diameter of central clear zone determined by preoperative refraction. At one year after surgery, myopia was reduced in all eyes; 60% were within +/- 1.00 diopter of emmetropia; 30% were undercorrected and 10% were overcorrected by more than 1.00 diopter (range of refraction, -4.25 to +3.38 D). Uncorrected visual acuity was 20/40 or better in 78% of eyes. The operation was most effective in eyes with a refraction between -2.00 and -4.25 diopters. Thirteen percent of patients lost one or two Snellen lines of best corrected visual acuity. However, all but three eyes could be corrected to 20/20. Ten percent of patients increased astigmatism more than 1.00 diopter. Disabling glare was not detected with a clinical glare tester, but three patients reduced their driving at night because of glare. Between six months and one year, the refraction changed by greater than 0.50 diopters in 19% of eyes.


Stimulatory effect of antidepressants on the production of IL-6.
A body of evidence indicates that the therapeutic activity of antidepressants is connected with their modulatory effect on the inflammatory response system and cell-mediated immunity. The present study was carried out to examine the effects of antidepressant agents, such as imipramne, venlafaxine, l-5-hydroxytryptophan, fluoxetine and a combination of l-5-hydroxytryptophan and fluoxetine, on the production of the pleotrophic cytokines TNF-alpha and IL-6. Diluted whole blood from fluoxetine-treated patients with treatment-resistant depression (TRD) (mean age: 50.6+/-3.9 years), age-matched healthy controls (mean age: 51.6+/-1.7 years) and younger healthy volunteers (mean age: 35.4+/-1.7 years) was stimulated with phytohemagglutinin (PHA) and lipopolysaccharide (LPS) for 48 h with or without incubation with the antidepressants at 10(-6) and 10(-5) M. The major findings of this study are: (1). imipramine and venlafaxine (at the higher concentration), 5-HTP (at lower and higher concentrations) and a combination of 5-HTP and fluoxetine (both at the lower concentration) increased the production of IL-6; (2). all drugs used did not affect TNF-alpha production. IL-6 production was significantly higher in depressed patients than in age-matched volunteers, whereas TNF-alpha production was significantly higher in older volunteers than in younger ones. We speculate that the therapeutic activity of these antidepressants is at least partly connected with their effect on the cytokine network and IL-6 production.


Assessment of immediate pain relief with laser treatment in recurrent aphthous stomatitis.
To compare immediate pain relief, healing time between minor recurrent aphthous ulcers treated with a single session of carbon dioxide (CO2) laser and a placebo. A prospective clinical study was performed on 25 patients with minor recurrent aphthous stomatitis. Pretreatment pain levels were recorded using a numerical rating scale. Ulcers were randomized to either receive treatment or placebo. Pain levels were assessed immediately after treatment and after 24 h. Healing was assessed on days 3 and 4, and once every 2 days thereafter for 2 weeks. Mean pain scores in the laser group were significantly reduced immediately after treatment (0.68 ± 0.6) compared with pretreatment (8.48 ± 0.71; P < .001). In contrast, the placebo group showed little difference in pain scores between pretreatment (8.08 ± 0.70) and immediately after treatment (7.96 ± 0.84). In the laser group, significant improvements in healing times were observed (4.08 ± 0.81 vs. 7.84 ± 0.90 days; P < .001). CO2 laser therapy in recurrent aphthous stomatitis (RAS) provides immediate pain relief sustained over 24 h, along with accelerated healing time.


3,4-methylenedioxymethamphetamine induces gene expression changes in rats related to serotonergic and dopaminergic systems, but not to neurotoxicity.
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is an amphetamine derivative widely abused by young adults. Although many studies have reported that relatively high doses of MDMA deplete serotonin (5-HT) content and decrease the availability of serotonin transporters (5-HTT), limited evidence is available as to the adaptive mechanisms taking place in gene expression levels in the brain following a dosing regimen of MDMA comparable to human consumption. In order to further clarify this issue, we used quantitative PCR to study the long-term changes induced by acute administration of MDMA (5 mg/kg × 3) in the expression of genes related to serotonergic and dopaminergic systems, as well as those related to cellular toxicity in the cortex, hippocampus, striatum, and brain stem of rats. Seven days after MDMA administration, we found a significantly lower expression of the 5-HTT (Slc6a4) and the vesicular monoamine transporter (Slc18a2) genes in the brain stem area. In the hippocampus, monoamine oxidase B (Maob) and tryptophan hydroxylase 2 (Tph2) gene expressions were increased. In the striatum, tyrosine hydroxylase (Th) expression was decreased, and a lower expression of α-synuclein (Snca) was observed in the cortex. In contrast, no significant changes were observed in the genes considered to be biomarkers of toxicity including the glial fibrillary acidic protein (Gfap) and the heat-shock 70 kD protein 1A (Hspa1a) in any of the structures assayed. These results suggest that MDMA promotes adaptive changes in genes related to serotonergic and dopaminergic functionality, but not in genes related to neurotoxicity.


Studies on lymphocytotoxicity in acute and chronic liver disease.
The cytotoxicity of lymphocytes from patients with chronic active hepatitis, chronic persistent hepatitis, acute hepatitis B and rheumatoid arthritis as well as from normal controls was studied in a microcytotoxicity assay according to COHEN et al. using 125I-iododeoxyuridine labeled embryonal liver cells and Chang cells as target cells. Unfractionated lymphocytes of the peripheral blood from patients with chronic active hepatitis and rheumatoid arthritis showed a high frequency of cytotoxic activity. The lymphocytotoxicity in chronic active hepatitis was significantly increased in comparison to normal controls at the EC/TC of 10:1 and 100:1. Specificity of the cytotoxic reaction to target cells could not be demonstrated. Addition of autologous serum to the cytotoxic assay blocked the lymphocytotoxicity in patients with chronic active hepatitis. A weak potentiating effect on lymphocytotoxicity was observed in patients with hepatitis B after addition of autologous serum. It is discussed that this reaction is due to the presence of HB-antigen in the serum since addition of HB-antigen from other sources increased also the lymphocytotoxicity in hepatitis B patients. This effect was observed neither in HB-antigen positive nor in HB-antigen negative patients with chronic active hepatitis or chronic persistent hepatisis.


Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Childhood Inflammatory Disorders: Diagnosis and Management.
Macrophage activation syndrome (MAS), a form of secondary hemophagocytic lymphohistiocytosis, is a frequently fatal complication of a variety of pediatric inflammatory disorders. MAS has been most commonly associated with systemic juvenile idiopathic arthritis (sJIA), as approximately 10% of children with sJIA develop fulminant MAS, with another 30-40% exhibiting a more subclinical form of the disease. Children with other rheumatologic conditions such as systemic lupus erythematosus and Kawasaki disease are also at risk for MAS. Moreover, MAS also complicates various genetic autoinflammatory disorders such as gain of function mutations in the cytosolic inflammasome NLRC4, pediatric hematologic malignancies (e.g., T-cell lymphoma), and primary immunodeficiencies characterized by immune dysregulation. Disease-specific and broadly inclusive diagnostic criteria have been developed to facilitate the diagnosis of MAS. Recently, simple screening tools such as the serum ferritin to erythrocyte sedimentation rate ratio have been proposed. Early diagnosis and rapid initiation of immunosuppression are essential for the effective management of MAS. With a better understanding of the pathophysiology of MAS and the advent of novel therapeutics, a broad immunosuppressive approach to treatment is giving way to targeted anti-cytokine therapies. These treatments include agents that block interleukin-1 (IL-1), IL-6, IL-18, interferon-γ, as well as inhibitors of downstream targets of cytokine signaling (e.g., Janus kinases). Increased early recognition of MAS among pediatric inflammatory disorders combined with the use of effective and less toxic cytokine-targeted therapies should lower the mortality of this frequently fatal disorder.


Computational mechanisms for context-based behavioral interventions: A large-scale analysis.
Choice context influences decision processes and is one of the primary determinants of what people choose. This insight has been used by academics and practitioners to study decision biases and to design behavioral interventions to influence and improve choices. We analyzed the effects of context-based behavioral interventions on the computational mechanisms underlying decision-making. We collected data from two large laboratory studies involving 19 prominent behavioral interventions, and we modeled the influence of each intervention using a leading computational model of choice in psychology and neuroscience. This allowed us to parametrize the biases induced by each intervention, to interpret these biases in terms of underlying decision mechanisms and their properties, to quantify similarities between interventions, and to predict how different interventions alter key choice outcomes. In doing so, we offer researchers and practitioners a theoretically principled approach to understanding and manipulating choice context in decision-making.


A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy.
The objectives of the current study were to determine the maximum tolerated dose (MTD) of irinotecan and carboplatin in combination, to evaluate the efficacy and toxicity of the combination in patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy, and to examine the pharmacokinetics and pharmacodynamics of both drugs by using the Chatelut formula. Patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy were treated with a combination of irinotecan and carboplatin. Carboplatin was administered as a 60-minute intravenous infusion on Day 1 and was followed by irinotecan, which was administered as a 90-minute intravenous infusion on Days 1, 8, and 15. Six dose levels of irinotecan (in mg/m(2))/carboplatin (mg . mL/min) were planned: 50 mg/m(2)/4 mg . mL/minute, 60 mg/m(2)/4 mg . mL/minute, 50 mg/m(2)/5 mg . mL/minute, 60 mg/m(2)/5 mg . mL/minute, 50 mg/m(2)/6 mg . mL/minute, and 60 mg/m(2)/6 mg . mL/minute. The carboplatin dosage was calculated by using the Chatelut formula. Treatment was repeated at 28-day intervals. In total, 19 patients in cohorts of 3 to 5 patients received irinotecan and carboplatin at 5 dose levels. The dose-limiting toxicities were Grade 4 neutropenia and Grade 4 thrombocytopenia. The MTD of the irinotecan/carboplatin combination was 60 mg/m(2)/5 . mg mL/minute. Partial responses were observed at higher dose levels. Pharmacologic studies demonstrated that administration of the dosage estimated with the Chatelut formula instead of the Chatelut formula with adjustment for serum creatinine resulted in a slightly excessive dose of carboplatin. The recommended dose for the Phase II study was irinotecan 60 mg/m(2) on Days 1, 8, and 15 with carboplatin 5 mg/mL . minute on Day 1 repeated every 4 weeks.


Socioeconomic deprivation and the clinical management of self-harm: a small area analysis.
Socioeconomic deprivation is associated with increased rates of self-harm but its association with levels of clinical care has not previously been explored. The aim of the current study was to investigate socioeconomic differences in the clinical management of people who self-harm. Cross-sectional analysis of 3607 people presenting to a large inner-city hospital following self-harm. People living in the least deprived quintile were more likely to receive a psychosocial assessment (most vs. least deprived: 63.51 vs. 70.14%). This effect persisted in our fully adjusted model (OR 1.45, CI 1.15-1.82, p = 0.002). Mediation analysis suggested this association was in large part explained by higher rates of self-discharge in people presenting from areas of higher deprivation. Compared to those from more deprived areas, people from less deprived areas are more likely to receive a psychosocial assessment when presenting to hospital following self-harm. The occurrence of higher rates of self-discharge from emergency departments among those from more deprived areas may explain the association.


Morphological abnormalities in ticks (Acari: Ixodidae) collected from domestic animal species in Sudan.
Morphological abnormalities in ticks have rarely been reported in nature. The existing knowledge about anomalies in ticks collected in Africa is very sparse. In this paper, we describe abnormalities in Amblyomma, Hyalomma, and Rhipicephalus ticks collected from cattle, sheep, goats, camels, and horses in Kassala and North Kordofan states, Sudan, between January and August 2017. A number of 15 adult ticks displayed one or several local anomalies, such as ectromely, abnormalities of the ventral plates, and body deformities, besides newly described multiple cuticula scars. This study presents the first report of local anomalies in ticks belonging to three genera in Sudan and highlights the need to investigate the association between such morphological abnormalities and tick biology.


The removal of cranial springs used in the treatment of scaphocephaly: A minimal access approach.
The treatment of non-syndromic scaphocephaly with spring-activated cranioplasty offers acceptable outcomes with the potential for reduced surgical morbidity when compared with cranial vault remodelling procedures. A disadvantage of this technique is the need for a second operative intervention to remove the implanted devices. There are many descriptions of the surgical technique for performing spring-activated cranioplasty available in the literature; however, little is documented regarding the procedures used for device removal. The published accounts of spring removal demonstrate a wide range of approaches, from the reopening and dissection of the entire previous surgical field, to attempts to limit the incisions and dissection. In this study we describe our technique for the minimally invasive removal of cranial springs used in the treatment of scaphocephaly. Our technique focuses on minimal soft tissue disruption and uses a Kirschner wire cutter to divide the spring at its mid-point so as to relieve any residual internal forces acting on the footplates.


Acute effects of lidocaine on repolarization and conduction in patients with coronary artery disease.
Right ventricular repolarization and refractoriness were studied during continuous infusion of lidocaine in patients with coronary artery disease. Compared with baseline the duration of monophasic action potential was shortened (p less than 0.01) at constant and premature stimulation. Early premature action potentials were less shortened (p less than 0.05). Therefore the difference between the longest and shortest action potential duration elicited 2 to 150 msec after refractoriness decreased during lidocaine infusion (p less than 0.01). The right ventricular effective refractory period was shortened similarly to the action potential duration. Lidocaine did not change the conduction of constant paced beats, whereas the more rapid conduction of the midrange premature beats was inhibited (p less than 0.01). The inhibition of premature conduction 50 to 150 msec from the right ventricular effective refractory period may be attributed to the effect of lidocaine on the rate-dependent recovery from inactivation. The effect on the restitution curve indicates that lidocaine may influence the dispersion of premature action potentials in human beings.


Wolbachia endosymbionts of Onchocerca volvulus express a putative periplasmic HtrA-type serine protease.
Wolbachia are intracellular bacteria of many filarial nematodes. A mutualistic interaction between the endobacteria and the filarial host is likely, because the clearance of Wolbachia by tetracycline leads to the obstruction of embryogenesis and larval development. Databases were searched for exported molecules to identify candidates involved in this mutualism. Fragments of a Wolbachia serine protease from the human filarial parasite Onchocerca volvulus were obtained (Wol-Ov-HtrA) by the use of a PCR technique and primers based on the Rickettsia prowazekii genome. The deduced amino acid sequence exhibited 87% and 81% identity to the homologous Wolbachia proteases identified from Brugia malayi and Drosophila melanogaster, respectively. The full-length cDNA encodes 494 amino acids with a calculated mass of 54 kDa. Three characteristic features, (i) a catalytic triad of serine proteases, (ii) two PDZ domains and (iii) a putative signal peptide, classify the endobacterial protein as a member of the periplasmic HtrA family of proteases known to express chaperone and regulator activity of apoptosis. Using a rabbit antiserum raised against a recombinantly expressed 33-kDa fragment of Wol-Ov-HtrA, strong labelling of the antigen was found associated with endobacteria in hypodermis, oocytes, zygotes, all embryonic stages and microfilariae of O. volvulus. Staining of hypodermal cytoplasm surrounding the endobacteria indicated a possible release of the protein from the Wolbachia. The demonstration of Wol-Ov-HtrA-reactive IgG1 antibodies in sera of O. volvulus-infected persons indicated the exposure to the protein and its recognition by the human immune system. Wol-Ov-HtrA is a candidate for an exported Wolbachia protein that may interact with the filarial host metabolism.


Low energy reporting may increase in intervention participants enrolled in dietary intervention trials.
To examine differences in low energy intake reporting between intervention and control groups during a dietary intervention trial. Retrospective data analysis from a subcohort of participants in the Polyp Prevention Trial (PPT), a 4-year, multisite, randomized, controlled dietary intervention trial. Intervention consisted of educational material and counseling sessions supporting a low-fat, high-fiber diet. Baseline and annual demographics, behavioral characteristics, energy intake (EI) based on self-reported 4-day food records, and height and weight of participants were collected at baseline and annually. Basal metabolic rate (BMR) was estimated (using the Schofield equation) to calculate EI/BMR. Of the 443 participants (302 male, 141 female) at baseline, 195 (43.3%) were younger than 60 years, and 394 (91%) were white. At Year 4, 383 participants remained: 186 (122 men, 64 women) in the intervention group, and 197 (133 men, 64 women) in the control group. Using either paired t tests or analysis of variance, the differences between the means for EI, weight, and EI/BMR were compared at baseline, Year 1, and Year 4 for the participants who remained at Year 4. The Goldberg EI/BMR cutoff value of 1.06 (for plausible EI) identified participants who reported low EI. Linear regression was used to quantify the association of various risk factors to EI/BMR and for multivariate analyses within groups. chi(2) contingency table analysis quantified differences of low energy reporting within groups. At baseline, 46.8% of women and 11.6% of men reported lower than plausible EI. Only men had a significant increase in low energy reporting after randomization. At Year 1, 18.9% of intervention group men reported low EI compared with 9.8% of control group men (P<.05). At Year 4, 23.0% of intervention group men reported low EI compared with 12.8% of control group men (P<.05). Difference in low EI reporting between intervention and control groups could distort results from dietary intervention trials; interpretation of findings from dietary trials must include this potential bias. Intervention study design should include dietary intake data collection methods that are not subject to such bias (ie, biomarkers and performance criteria) to measure intervention compliance.


High sensitivity detection of bisphenol A using liposome chromatography.
An antibody column in tandem with a fluorescent dye entrapped liposome column was developed for highly sensitive detection of an endocrine disruptor, bisphenol A (BPA). Anti-BPA antibody was immobilized in a protein G column with orientation control. A derivative of BPA was conjugated to phospholipase A2 (PLA2). BPA sample solutions mixed with the BPA-PLA2 conjugates were injected on to the anti-BPA antibody column and competitive binding occurred in the antibody column. The amount of the free conjugate was proportional to the concentration of the BPA sample. The eluted conjugates were injected on to the second column gel on which calcein-entrapped liposomes were immobilized and the PLA2-catalyzed hydrolysis of liposomal phospholipids causing fluorescent dye leakage as a signal amplification. In this system, the mixture of BPA and BPA-PLA2 conjugate were incubated for 60 min in the anti-BPA column, and then the collected solution was applied to the liposome column. The BPA detection range of 0.02-140 ng mL(-1) was wider than 0.03-6.6 ng mL(-1) obtained by the method of competitive ELISA using the same antibody. Moreover, this system could be adapted to an HPLC system resulting in almost the same detection limit in online detection. The method could be applied to environmental samples, river water and soil extracts. The BPA concentration of 0.1 ng mL(-1) and 10 ng g(-1) was detectable in water and soil extract, respectively.


Effect of inclusion complexation on the photophysical behavior of diphenylamine in β-cyclodextrin medium: a study by electronic spectra.
Spectral characteristics of diphenylamine (DPA) have been investigated in β-cyclodextrin (β-CDx) solution. The formation of the complex was revealed by UV, steady state and time-resolved fluorescence spectroscopy. The stoichiometry of DPA:β-CDx complex, determined using Benesi-Hildebrand equation and Job's continuous variation method is 1:1. The binding constants calculated from various methods are reported. This inclusion complex formation from DPA and β-CDx was also confirmed by the FT-IR spectral study and SEM image analysis of solid complex prepared by co-precipitation method.


Isolation and characterization of acetylated histones H3 and H4 and their assembly into nucleosomes.
Nucleosome and chromatin structure/function relationships of histone acetylations are not understood. To address these questions we have developed chromatographic procedures that separate subtypes of H3 and the acetylated states of histone H3 and H4 in exceptionally pure forms. The sites of acetylation of the intermediately acetylated states of H3 have been determined and show a specific pattern of acetylation. An unexpected finding was the identification of a fifth site of acetylation in H3 at lysine 27. Nucleosome particles with fully acetylated H3 and H4 have been assembled on the Lytechinus variegatus 5 S rRNA DNA phasing sequence and characterized. These defined acetylated H3 and H4 particles migrate more slowly in polyacrylamide nucleoprotein particle gels than the control particles indicating a subtle effect of acetylation in nucleosome structure. However, DNA footprinting of these particles using DNase I show only small changes when compared to control particles over the core particle DNA length. It is shown further that H3 cysteines in the particle containing fully acetylated H3 and H4 were not accessible to iodoacetamide indicating that protein factors additional to H3 and H4 acetylation are required to make H3 cysteines accessible to the label. These findings are consistent with the proposal that histones H3, H4 acetylations exert their major effects outside of the core particle 146-base pair DNA, either on the DNA segment entering and leaving the nucleosome or possibly on the internucleosome interactions that involve the amino-terminal domains of the core histones in organization and stability of higher order chromatin structures.


Orcokinins contribute to the regulation of vitellogenin transcription in the cockroach Blattella germanica.
Orcokinins (OKs) are neuropeptides that were first identified in crustacean through their myotropic activity. In insects, the OK gene gives rise to two mRNAs coding for two different families of conserved mature neuropeptides: OKA and OKB. Although OKs are conserved in many insect species, its physiological role in this animal class is not fully understood. Until now prothoracicotropic, regulatory of light entrainment to the circadian clock and "awakening" activities have been reported for these peptides in different insect species. Here we report the identification of OKA and OKB precursors in the cockroach Blattella germanica. OKA mRNA was detected in brain, whereas OKB mRNA was detected both in brain and midgut. In vivo silencing of OK precursors suggests the involvement of OK gene products in the regulation of vitellogenin expression in the fat body, an action that appears to be independent of juvenile hormone. This is the first time that a function of this kind has been reported for OKs.


Training Load, Injury Burden, and Team Success in Professional Rugby Union: Risk Versus Reward.
Individual and team injury burden and performance are 2 key considerations facing practitioners in the daily prescription of an athlete's training load. Whereas a considerable number of researchers have examined univariate relationships between training load and performance, training load and injury, or injury and performance, few investigators have examined all 3 concurrently. To assess the association among training load, injury burden, and performance in professional rugby union. Descriptive epidemiology study. The English Premiership competition. Individual injury and training load data, as well as team performance data, were captured during the 2015-2016 (n = 433 players) and 2016-2017 (n = 569 players) seasons. Data were aggregated into team average scores for each week, including weekly (acute) load, smoothed chronic load, changes in load, injury burden, and weekly performance. Linear mixed modelling techniques were used to assess the association among measures. Injury burden was negatively associated with performance, with a high weekly burden associated with a likely harmful (P = .01) decrease in performance. Training load measures displayed only trivial associations with performance. Only the acute:chronic workload ratio measure was clearly associated with injury burden, with a possibly harmful effect (P = .02). Both squad size and player availability were associated with only trivial changes in performance. Whereas no association between average training load and performance existed, associations between training load and injury burden and between injury burden and performance were clear. Further investigation using more sensitive and individualized measures of load, performance, and injury may elicit a clearer relationship and should be considered for future work.


The effect of topiramate on GABA(B) receptor, vesicular GABA transporter and paired-pulse inhibition in the gerbil hippocampus.
To extend our understanding of the properties of topiramate (TPM), we investigated the effect of TPM on GABAergic transmission in the dentate gyrus of gerbil. TPM treatment (> or = 40 mg/kg) dramatically decreased GABA(B)R2, not GABA(B)R1, immunoreactivity in hilar interneurons. In contrast, TPM treatment increased vesicular GABA transporter immunoreactivity and the paired-pulse inhibition in the dentate gyrus of seizure prone gerbils. Furthermore, TPM effectively prevented the reduction of paired-pulse inhibition induced by baclofen treatment. These findings suggest that TPM may enhance GABA release in the dentate gyrus of gerbils by down-regulation of GABA(B) autoreceptor expression. Therefore, these properties of TPM may be another possible antiepileptic effect, which plays an important role in preventing the spread of seizure activity without proconvulsive effects.


Rare male mating advantage for inversion karyotype in Drosophila ananassae.
These experiments were conducted to study frequency-dependent sexual selection on the alpha inversion in the left arm of the second chromosome (2L) in Drosophila ananassae. Two different strains, ST/ST-standard gene arrangement and AL/AL-alpha inversion in 2L were used. Female-choice experiments were carried out in five different male ratios. Two different methods of observation have been employed, one in which copulating pairs are aspirated out and the other, in which pairs are not removed. Results were analyzed by chi(2) tests, and log odds plus regression analyses. Regression analyses revealed the presence of one-sided rare male mating advantages for AL/AL males. Preferential mating is present within the strain having AL/AL karyotype. The minority male advantage and preferential mating found in the AL/AL strain are different components of mating success. ANOVA fails to show any significant difference between the outcomes of rare-male experiments using these two different methods.


Oligonucleotide-based therapy for neurodegenerative diseases.
Molecular genetics insight into the pathogenesis of several neurodegenerative diseases, such as Alzheimer׳s disease, Parkinson׳s disease, Huntington׳s disease and amyotrophic lateral sclerosis, encourages direct interference with the activity of neurotoxic genes or the molecular activation of neuroprotective pathways. Oligonucleotide-based therapies are recently emerging as an efficient strategy for drug development and these can be employed as new treatments of neurodegenerative states. Here we review advances in this field in recent years which suggest an encouraging assessment that oligonucleotide technologies for targeting of RNAs will enable the development of new therapies and will contribute to preservation of brain integrity.


Drivers of foliar 15 N trends in southern China over the last century.
Foliar stable nitrogen (N) isotopes (δ15 N) generally reflect N availability to plants and have been used to infer about changes thereof. However, previous studies of temporal trends in foliar δ15 N have ignored the influence of confounding factors, leading to uncertainties on its indication to N availability. In this study, we measured foliar δ15 N of 1811 herbarium specimens from 12 plant species collected in southern China forests from 1920 to 2010. We explored how changes in atmospheric CO2 , N deposition and global warming have affected foliar δ15 N and N concentrations ([N]) and identified whether N availability decreased in southern China. Across all species, foliar δ15 N significantly decreased by 0.82‰ over the study period. However, foliar [N] did not decrease significantly, implying N homeostasis in forest trees in the region. The spatiotemporal patterns of foliar δ15 N were explained by mean annual temperature (MAT), atmospheric CO2 ( P CO 2 ), atmospheric N deposition, and foliar [N]. The spatiotemporal trends of foliar [N] were explained by MAT, temperature seasonality, P CO 2 , and N deposition. N deposition within the rates from 5.3 to 12.6 kg N ha-1 year-1 substantially contributed to the temporal decline in foliar δ15 N. The decline in foliar δ15 N was not accompanied by changes in foliar [N] and therefore does not necessarily reflect a decline in N availability. This is important to understand changes in N availability, which is essential to validate and parameterize biogeochemical cycles of N.


Climate change decouples dominant tree species in African savannas.
To understand how two dominant African savanna trees will continue to respond to climate changes, we examined their regeneration niche and adult tree distributions. Specifically, we wanted to (1) determine if distributional patterns were shifting, (2) predict future distributions under different climate change scenarios and (3) evaluate the realism of predicted future distributions. We randomly placed 40 grids into 6 strata across a climate gradient in the kingdom of Eswatini. Within these grids, we sampled adult and seedling marula (Scelerocarya birrea) and knobthorn (Senegalia nigrecens) trees and used the data to model their abundance. Next, we quantified shifts in distributional patterns (e.g., expansion or contraction) by measuring the current and projected areas of overlap between seedling and adult trees. Finally, we predicted future distributions of abundance based on predicted climate conditions. We found knobthorn seedlings within a small portion of the adult distribution, suggesting it was unlikely to track climate changes. Alternatively, finding marula seedlings on and beyond one edge of the adult distribution, suggested its range would shift toward cooler climates. Predicted future distributions suggest suitable climate for both species would transition out of savannas and into grasslands. Future projections (2041-2070) appeared consistent with observed distributions of marula, but knobthorn predictions were unrealistic given the lack of evidence for regeneration outside of its current range. The idiosyncratic responses of these species to climate change are likely to decouple these keystone structures in the coming decades and are likely to have considerable cascading effects including the potential rearrangement of faunal communities.


Online Contingent Attention Training (OCAT): transfer effects to cognitive biases, rumination, and anxiety symptoms from two proof-of-principle studies.
The aim of the present research was to develop and test the efficacy of a novel online contingent attention training (i.e., OCAT) to modify attention and interpretation biases, improve emotion regulation, and reduce emotional symptom levels in the face of major stressors. Two proof-of-principle studies were carried out. In study 1, 64 undergraduates who were about to start a major stressful period (i.e., final exams) were randomized to undergo 10 days of active OCAT or a sham-control training. Emotion regulation (habitual use of rumination and reappraisal) and symptom levels (depression and anxiety) were assessed before and after the intervention. In study 2, the same 2 × 2 mixed design was used with 58 individuals from the general population undergoing a major stressful situation (the lockdown period at the beginning of the COVID-19 pandemic in 2020). In both studies, the OCAT group showed significant improvements on attention towards negative information and interpretation biases in comparison to the sham-control group. Additionally, changes in cognitive biases transferred to reductions of participants' use of rumination and anxiety symptom levels. These results show preliminary evidence regarding the efficacy of the OCAT to target attention and interpretation biases as well as to improve emotion regulation processes and to buffer against the effects of major stressors.


Comparison of metrizamide CT cisternography with radionuclide cisternography in abnormal cerebrospinal fluid dynamics.
Metrizamide CT cisternograms were performed on 39 patients with a clinical diagnosis of CSF abnormalities; 20 of these patients underwent radionuclide cisternography as well. Comparison of metrizamide CT and RN cisternography revealed good correlation in the degree, extent, and time sequence of ventricular reflux as well as the extent of cortical staining and cisternal filling. Metrizamide cisternography had the advantage of excellent anatomic detail and lower exposure dose, although minor complications were more frequent with this technique. Metrizamide CT cisternography has a potential to become the preferred method of evaluating patients with abnormal CSF dynamics.


A critical review of advancement in scientific research on food animal welfare-related air pollution.
Air pollution generates hazardous pollutants that have resulted in safety, health, and other welfare issues of food animals. This paper reviewed scientific research advancement in food animal welfare-related air pollution based on 219 first-hand research publications in refereed journals (referred to as "RPs") over the past nine decades. Scientific studies in this area began in the 1930s. The number of RPs has increased significantly with each decade from the 1960s to the 1980s, then decreased until the 2010s. Twenty-six countries have contributed to this multidisciplinary research. About 52% of the studies were conducted in the U.S. and U.K. Research activities have surged in China since the 2010s. On-farm discoveries in air toxicity that resulted in animal death or injury were all from observational studies. About 75% of the studies were experimental and conducted primarily under laboratory conditions. Ammonia (NH3) was the main pollutant in 59% of the RPs, followed by dust, hydrogen sulfide (H2S), bacteria and endotoxins, carbon dioxide (CO2), carbon monoxide (CO), silo gas, sulfur dioxide (SO2), and odor. Approximately 23% of RPs reported multiple pollutants in the same study. The most intensively studied animal species were poultry (broilers, hens, turkeys, ducks, and eggs and embryos in 44% of the RPs) and pigs (also 44%), followed by cattle, and sheep and goats. Scientific investigations in this area were driven by the research focuses in the areas of animal agriculture and industrial air pollution. Some major research teams played important roles in advancing scientific research. However, research in this area is still relatively limited. There is a great need to overcome some technical challenges and reverse the trend of decreasing research activities in North America and Europe.


Failure of prostaglandins, prostaglandin metabolites and arachidonic acid to elicit chemotaxis of human polymorphonuclear leukocytes.
This paper reports chemotactic studies on human polymorphonuclear leukocytes using prostaglandins, prostaglandin precursors and prostaglandin metabolites in vitro. Chemotaxis could not be demonstrated when arachidonic acid, prostaglandins D2, E1, E2, F2alpha, and the prostaglandin metabolites 15 keto E2, 15 keto F2alpha were incubated with polymorphonuclear leukocytes using the Boyden millipore technique.


Experiences in the determination of activity in thorium contaminated materials in working areas, using gamma spectrometer measurements, from the viewpoint of practical radiation protection.
In industrial processes, classification and clearance of thorium contaminated material is often a time problem. Short-term decisions have to be made about acceptance limits, industrial safety as the workers are in contact with the contaminated material. and the environmental aspect regarding the disposal of the wastes. The use of gamma ray spectrometry measurements is an easy method to estimate the level of activity in materials. Under the precondition of equilibrium of activity within the thorium decay chain, which can be assumed only with knowledge of the materials' history, adequate results can be produced in a reasonable time. The advantages of gamma ray spectrometry are the low investment and operational costs, simple sample preparation, and a system that is relatively quick and easy to operate.


Associations between Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers in People with Mild Cognitive Impairment.
Neuropsychiatric symptoms (NPS) are associated with faster decline in mild cognitive impairment (MCI). This study aimed to investigate the association between NPS severity and Alzheimer's disease (AD) biomarkers, i.e., amyloid-β (Aβ), phosphorylated tau protein (p-tau) and hippocampal volume ratio (HR), to characterise in more detail MCI patients with a poor prognosis. A total of 506 individuals with MCI and 99 cognitively unimpaired older adults were selected from the ADNI dataset. The patients were divided into three different groups based on their NPI-Q total scores: no NPS (n = 198), mild NPS (n = 160) and severe NPS (n = 148). Regression models were used to assess the association between the severity of NPS and each biomarker level and positivity status. Cerebrospinal fluid Aβ levels were positively associated with older age and lower MMSE scores, while higher p-tau levels were associated with female sex and lower MMSE scores. Only patients with severe NPS had a lower HR (β = -0.18, p = 0.050), i.e., more pronounced medio-temporal atrophy, than those without NPS. Only HR was associated with the presence of NPS, partially in line with previous evidence showing that severe NPS may be explained primarily by greater grey matter loss. Future longitudinal studies will be needed to ascertain the relevance of this finding.


Characterization of warfarin unusual peak profiles on oligoproline chiral high performance liquid chromatography columns.
Unusual peak profiles of warfarin were characterized on two oligoproline chiral stationary phases (CSPs). The pattern of 1st peak (S(-)) broadening and the 2nd peak (R(+)) compression was observed under mobile phase of hexane (0.1% TFA)/2-propanol (IPA) on a triproline CSP 1, and with other alcohol modifier such as ethanol, 1-propanol, 1-butanol, 2-butanol, and tert-butanol as well. Through analyzing system peak of additives, the unusual peak profile was interpreted by perturbation of TFA additive system peak. The unusual peak profile was also found in enantioseparation of coumachlor and on a covalently bonded doubly tethered diproline CSP 2. The pattern of 1st peak (S(-)) broadening and the 2nd peak (R(+)) compression can change to pattern of 1st peak compression and the 2nd peak broadening from 15 to 50°C. Chiral separation of warfarin created nonlinear van't Hoff plots on CSP. No peak broadening/compression were observed with methyl tertiary butyl ether or ethyl acetate as the modifier. The peak shapes of the two warfarin enantiomers can thus be tuned by varying alcohol concentration and column temperature. High separation factor and resolution may be carried out to tune the peak profiles into Langmuir/anti-Langmuir band-shape composition. Using none hydrogen donor modifier may avoid interference of the TFA system peak.


Number of random test cells for antibody detection.
The sensitivity of antibody screening carried out by reacting a serum with random test cells depends on the probability of a given antigen being present in the cell panel. This probability (p) is defined by the formula p = 1-(1-f)n where f is the antigen phenotype frequency and n the number of reacted random cells.


Assessment of Fluoride Content in Water and Its Impact on the Intelligence Quotient of School Children Aged 12-13 Years.
The preliminary study was undertaken with the aim to assess the effect of fluoride content in water on the Intelligence Quotient (IQ) of school children aged 12-13 years residing in areas that differ with respect to fluoride levels. The IQ was measured using Raven's Colored Progressive Matrices in 90 children, who were life-long residents in three villages (30 children each) of similar population size but differing in the level of fluoride in drinking water. Urinary fluoride concentration was measured using the selective ion electrode technique. One-way ANOVA was used for the statistical analysis of the data. Results: Children who lived in locations with fluoride levels of 1.60, 6.70, or 2.80 parts per million in their drinking water had urinary fluoride concentrations of 1.60, 6.82, or 2.69 parts per million, and IQ scores of 16.77 + 8.24, 19.36 + 9.98, or 21.87 + 7.47, respectively. The results indicated that there was a positive correlation between excess fluoride in drinking water and IQ.


Plasma concentrations of fibrinopeptide A, fibrinogen fragment B beta 1-42 and beta-thromboglobulin following total hip replacement.
Plasma concentrations of thrombin sensitive peptide fibrinopeptide A (FpA), plasmin sensitive fibrinogen fragment B beta 1-42 and the platelet release product beta-thromboglobulin (beta TG) have been measured in 36 patients before and after total hip replacement. Statistically significant elevations of all three activation products were observed in the days following operation. There were small differences in plasma concentrations of FpA, B beta 1-42 and beta TG in patients who did (n = 13) and did not (n = 23) develop post operative deep vein thrombosis, as assessed by ascending venography on post operative day 10, but these differences were not statistically significant. It is concluded that coagulation and fibrinolytic systems and also blood platelets are activated following total hip replacement operations. However, the formation of post operative deep vein thrombosis can not be effectively monitored by measurement of the activation products.


Thioredoxin-(dithiol-)linked inactivation of elastase.
Following inactivation by the alpha-1-antitrypsin (AAT) inhibitor, the protease elastase was reduced by thioredoxin, itself reduced by NADPH and NADP-thioredoxin reductase (NTR). Under these conditions, reduction of enzyme disulfide groups was accompanied by loss of more than 60% of the activity measured following dissociation of the enzyme-inhibitor complex with NaCl. The inhibitor was required (1) to prevent proteolysis of both reduced thioredoxin and NTR and (2) to assess the progress of the reduction reaction. At elevated temperature, elastase was also reduced by dithiols (dithiothreitol and lipoic acid) but not by monothiols (reduced glutathione, beta-mercaptoethanol). When reduced by dithiols under these conditions, the enzyme digested itself. Self-digestion was independent of the antitrypsin inhibitor and was proportional to temperature in the 37-50 degree C range. These findings open the door to a new mode of regulation of elastase and to possible new therapies for treating diseases associated with the enzyme.