Succinic acid production by Actinobacillus succinogenes from batch fermentation of mixed sugars.
Succinic acid production from the monosaccharides xylose, arabinose, glucose, mannose and galactose was studied using the bacterium Actinobacillus succinogenes. In Duran bottle cultures, containing 10 g/L of each of sugar, succinic acid was produced from all sugars except for galactose. The highest succinate yield, 0.56 g/g, was obtained with glucose, whereas the succinate yield was 0.42, 0.38 and 0.44 g/g for xylose, mannose and arabinose, respectively. The specific succinate productivity was 0.7 g/g h for glucose, but below 0.2 g/g h for the other sugars. Batch bioreactor fermentations were carried out using a sugar mixture of the five sugars giving a total concentration of 50 g/L, mimicking the distribution of sugars in spent sulfite liquor (SSL) from Eucalyptus which is rich in xylose. In this mixture, an almost complete conversion of all sugars (except galactose) was achieved resulting in a final succinate concentration of 21.8-26.8 g/L and a total yield of 0.59-0.68 g/g. There was evidence of co-consumption of glucose and xylose, whereas mannose was consumed after glucose. The main by-products were acetate 0.14-0.20 g/g and formate 0.08-0.13 g/g. NADH balance calculations suggested that NADH required for succinate production was not met solely from formate and acetate production, but other means of NADH production was necessary. Results from mixed sugar fermentations were verified using SSL as substrate resulting in a succinate yield of 0.60 g/g. In addition, it was found that CO2 sparging could replace carbonate supply in the form of MgCO3 without affecting the succinate yield.


Effects of timothy Cladosporium eyespot on photosynthesis and biomass.
Timothy is a forage mainly grown in Min County, Gansu Province, China. In 2021, a leaf spot disease outbreak on timothy grass occurred in Min County, adversely affecting its growth and productivity. Therefore, this study investigated the leaf spot disease incidence in Min County, morphologically and molecularly characterized the disease-causing pathogen, and assessed its effects on the growth, photosynthesis, and biomass of timothy seedlings re-inoculated with the isolated pathogen. In the field, the disease incidence on plants and leaves was 100 and 85%, respectively. Morphologically, young lesions were ellipsoidal-fusiform with dark purple margins and an off-white center, while the mature lesions were eye-shaped spots with a light brown center and dark purple edges. Molecular characterization identified the pathogen as Cladosporium phlei causing Cladosporium eyespot disease. The net photosynthetic rate, transpiration rate, fresh shoot weight, and dry shoot weight of timothy seedlings 14 days after inoculation with the pathogen were decreased by 29.77, 56, 45.45, and 46.42%, respectively, implying that Cladosporium eyespot disease is an important timothy grass disease in Min County. Therefore, developing an integrated control strategy is urgent to lessen the economic loss.


Exploration of the candidate beneficial bacteria for Penaeus vannamei culture by core microbiome analysis using amplicon sequencing.
Globally, Penaeus vannamei is the vital species in aquaculture production. Beneficial bacterial exploration of gut, sediment, and water were investigated in P. vannamei culture using Illumina Miseq sequencing of 16S RNA V3-V4 hypervariable regions. Predominant phyla identified were Proteobacteria, Tenericutes, Bacteroidetes in gut; Proteobacteria, Bacteroidetes, Planctomycetes in sediment and Cyanobacteria, Proteobacteria, and Planctomycetes in water. In total, 46 phyla, 509 families and 902 genera; 70 phyla, 735 families and 1255 genera; 55 phyla, 580 families and 996 genera were observed in gut, sediment and water, respectively. Diversity of microbial communities in respect of observed Operational Taxonomic Units, diversity indices (Shannon and Simpson), richness index (Chao1) were significantly high P (<0.05) in 60 DoC in gut and 30 DoC in sediment. Beta diversity indicated separate clusters for bacterial communities in gut, sediment and water samples and formation of distinct community profiles. Core microbiome in P. vannamei rearing ponds over a time consisted of 9, 21, and 20 OTUs in gut, rearing water and sediment, respectively. This study helps to intervene with suitable beneficial microbes to establish an aquaculture system thereby contributes to enhance the productivity, improve water quality and pond bottom condition, and control the pathogenic agents at each stage of the culture.


The association study of chemical compositions and their pharmacological effects of Cyperi Rhizoma (Xiangfu), a potential traditional Chinese medicine for treating depression.
Cyperi Rhizoma (CR) derives from the rhizome or tuber of Cyperus rotundus L. of Cyperaceae. It is an herbal medicine which has been widely used in different healthcare systems like in China, India, Iran, and Japan. In Chinese medicine, CR could promote the flow of Qi in the Liver and Sanjiao channels, regulate menstruation and alleviate pain. Clinically, CR is used for depression, flatulence, hypochondriac pain, and dysmenorrhea. Thus, it has a long history and significant curative effect for the treatment of various Qi stagnation symptoms. This review focuses on explaining the major antidepressant mechanisms of CR, and assessing the shortcomings of existing work. Besides, clinical applications, pharmacological effects and their corresponding chemical compositions and quality control of CR have been researched. The search terms "Cyperus rotundus L." was used to obtain the literatures from electronic databases such as Web of Science, ScienceDirect, PubMed, and China National Knowledge Infrastructure (CNKI). The information provided in this review to illustrate material basis of CR were only limited to papers which reported on the chemical compositions and pharmacological effects simultaneously. The study showed that CR has significant application in Qi stagnation, like depressed liver, stomach, and bowel disorders, etc. in different countries or districts. Aqueous extract, EtOH extract, essential oil, total oligomeric flavonoids and five other extracts were effective constituents displaying pharmacological activities such as antibacterial, antioxidant, neuroprotective, antihemolytic, and anti-inflammatory effect. 41 kinds of specific components like α-cyperone, nootkatone exhibited corresponding pharmacological activities mentioned above. Different concentrations of ethanol extract, essential oil, decoction of CR and monomer composition like α-cyperone, rotunduside G had anti-depressant effects. In the present study, we have provided scientific information and research developments on traditional uses, phytochemical compositions and corresponding pharmacological activities, and quality control status on CR. The antidepression effect and its corresponding chemical compositions were generalized separately. The pharmacological activities studies should be more focused on the reflection of traditional clinical values. CR could be a significant potential herbal medicine to develop antidepressant drugs with lower side effects.


A ligation and restriction enzyme independent cloning technique: an alternative to conventional methods for cloning hard-to-clone gene segments in the influenza reverse genetics system.
Reverse genetics is used in many laboratories around the world and enables the creation of tailor-made influenza viruses with a desired genotype or phenotype. However, the process is not flawless, and difficulties remain during cloning of influenza gene segments into reverse genetics vectors (pHW2000, pHH21, pCAGGS). Reverse genetics begins with making cDNA copies of influenza gene segments and cloning them into bi-directional (pHW2000) or uni-directional plasmids (pHH21, pCAGGS) followed by transfection of the recombinant plasmid(s) to HEK-293 T or any other suitable cells which are permissive to transfection. However, the presence of internal restriction sites in the gene segments of many field isolates of avian influenza viruses makes the cloning process difficult, if employing conventional methods. Further, the genetic instability of influenza gene-containing plasmids in bacteria (especially Polymerase Basic 2 and Polymerase Basic 1 genes; PB2 and PB1) also leads to erroneous incorporation of bacterial genomic sequences into the influenza gene of interest. Herein, we report an easy and efficient ligation and restriction enzyme independent (LREI) cloning method for cloning influenza gene segments into pHW2000 vector. The method involves amplification of megaprimers followed by PCR amplification of megaprimers using a bait plasmid, DpnI digestion and transformation. Hard-to-clone genes: PB2 of A/chicken/Bangladesh/23527/2014 (H9N2) and PB1 of A/chicken/Bangladesh/23527/2014 (H9N2), A/chicken/Jiangxi/02.05YGYXG023-P/2015 (H5N6) and A/Chicken/Vietnam/H7F-14-BN4-315/2014 (H9N2) were cloned into pHW2000 using our LREI method and recombinant viruses were subsequently rescued. The LREI cloning procedure represents an alternative strategy for cloning influenza gene segments which have internal restriction sites for the enzymes used in reverse genetics. Further, the problem of genetic instability in bacteria can be alleviated by growing recombinant bacterial cultures at a lower temperature. This technique can be applied to clone any influenza gene segment using universal primers, which would help in rapid generation of influenza viruses and facilitate influenza research and vaccine development.


Psychobiology and the athlete with anterior cruciate ligament (ACL) injury.
Over the past decade, research has increasingly highlighted the need for psychological aspects associated with sporting injury to be considered in treatment programmes. However, contemporary practice continues to focus on the treatment of the physical injury. The purpose of this article is to summarise research and contemporary thoughts on the psychological aspects associated with sporting injury. The potential for incorporating both physical and psychological aspects into the treatment of injury is discussed with special reference to the anterior cruciate ligament (ACL) injury. Specifically, the potential importance of athlete involvement throughout the treatment programme is discussed. Additionally, the physical and psychological measures that are available to the sports medicine team to measure rehabilitation outcome are critically evaluated. The limitations of psychological measures of the athlete's perception of outcome are outlined. Evidence for the utility of the performance profile technique is critically evaluated. The technique provides valid and reliable measures of the idiosyncratic responses of athletes to injury to provide a framework for effective treatment for optimised outcome.


Exaggerated exercise blood pressure response in middle-aged men as a predictor of future blood pressure: a 10-year follow-up.
The prognostic value of an exaggerated exercise systolic blood pressure response (EESBPR) remains controversial. This study was designed to assess whether an EESBPR is associated with the predictor of future blood pressure. From an initial population of 1,534 male-subjects with normal BP or no medication who underwent ergometric exercise, 733 subjects (mean age: 41 years old) at baseline to follow-up BP after an average of 10 years were selected. A 12-min exercise tolerance test with three phases of estimated load from predictive maximum oxygen intake was performed at baseline, and exercise BP was measured. Exercise BP response was classified by three group: Low group (G) (exercise SBP < 180 mmHg), Middle G (exercise BP:180-199 mmHg), High G (exercise BP:200 mmHg ≦). BP after 10 years in Low G was 123 ± 12/79 ± 7 mmHg, in Middle G:127 ± 13/81 ± 8 mmHg, in High G :134 ± 15/84 ± 10 mmHg. Compared with in Low G, BP after 10 years in High G significantly increased (p < 0.05). Multiple regression analysis was carried out to clarify the relationship of exercise SBP at baseline to BP after 10 years. In multivariate-adjusted models, the relationship of SBP at follow-up was stronger to exercise SBP (β = 0.271, P < 0.001) than to resting SBP (β = 0.148, P < 0.001). Maximum oxygen intake (β = -0.193, P = 0.003) and resting SBP correlated with SBP after 10 years. In middle-aged men, exercise SBP would be a stronger predictor of future SBP, DBP rather than BP at rest. In optimal of classification of BP (SBP < 120 mmHg), exercise BP response was clearly associated with BP after 10 years.


A case of parathyroid carcinoma concurred with hyperplasia: an electron microscopic study.
A case of parathyroid carcinoma is reported. The histology of the parathyroid glands disclosed carcinoma in 1 gland and chief cell hyperplasia in another. Therefore, we recommend careful exploration of all parathyroid glands. An electron microscopic feature of parathyroid carcinoma is presented.


Hemodialysis patient preference for type of vascular access: variation and predictors across countries in the DOPPS.
Catheters are associated with worse clinical outcomes than fistulas and grafts in hemodialysis (HD) patients. One potential modifier of patient vascular access (VA) use is patient preference for a particular VA type. The purpose of this study is to identify predictors of patient VA preference that could be used to improve patient care. This study uses a cross-sectional sample of data from the Dialysis Outcomes and Practice Patterns Study (DOPPS 3, 2005-09), that includes 3815 HD patients from 224 facilities in 12 countries. Using multivariable models we measured associations between patient demographic and clinical characteristics, previous catheter use and patient preference for a catheter. Patient preference for a catheter varied across countries, ranging from 1% of HD patients in Japan and 18% in the United States, to 42% to 44% in Belgium and Canada. Preference for a catheter was positively associated with age (adjusted odds ratio per 10 years=1.14; 95% CI=1.02-1.26), female sex (OR 1.49; 95% CI=1.15-1.93), and former (OR=2.61; 95% CI=1.66-4.12) or current catheter use (OR=60.3; 95% CI=36.5-99.8); catheter preference was inversely associated with time on dialysis (OR per three years=0.90; 95% CI=0.82-0.97). Considerable variation in patient VA preference was observed across countries, suggesting that patient VA preference may be influenced by sociocultural factors and thus could be modifiable. Catheter preference was greatest among current and former catheter users, suggesting that one way to influence patient VA preference may be to avoid catheter use whenever possible.


Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions.
Most Gram-positive bacteria incorporate membrane- or peptidoglycan-attached carbohydrate-based polymers into their cell envelopes. Such cell-wall glycopolymers (CWGs) often have highly variable structures and have crucial roles in protecting, connecting and controlling the major envelope constituents. Further important roles of CWGs in host-cell adhesion, inflammation and immune activation have also been described in recent years. Identifying and harnessing highly conserved or species-specific structural features of CWGs offers excellent opportunities for developing new antibiotics, vaccines and diagnostics for use in the fight against severe infectious diseases, such as sepsis, pneumonia, anthrax and tuberculosis.


Apaf1 mediates apoptosis and mitochondrial damage induced by mutant human SOD1s typical of familial amyotrophic lateral sclerosis.
Several studies have indicated that apoptotic pathways are responsible for the loss of motor neurons that constitute the hallmark of amyotrophic lateral sclerosis (ALS). In this study, we demonstrate that apoptosis induced by the expression of several mutant Cu,Zn superoxide dismutases (SOD1) typical of familial ALS is mediated by Apaf1, a scaffold protein involved in neural development. Using different cell lines of neuronal origin and modulating the expression of both mutant SOD1s and Apaf1, we show that the removal of Apaf1 prevents cells death. Interestingly, intercepting activation of the caspases cascade is also effective in preventing both the mitochondrial damage and the increase in the production of reactive oxygen species induced by fALS-SOD1, even in the presence of cytochrome c release. This death pathway may be crucial also for the pathogenesis of the sporadic form of the disease, where markers of increased oxidative stress and mitochondria damage have been found.


[Migraine and hypothalamus].
Migraine is a complex brain disease. The "generator" of the migrainous attacks remains a subject of debate, but the hypothalamus, with its multiple connections with the other parts of the central nervous system and its controls on the pituitary gland and the autonomic nervous system, is a very serious candidate. Many of the premonitory symptoms of migraine attacks find their origin in the hypothalamus. The hormonal changes which occur during feminine genital life and which impact on the life of the migrainous women have their origin in the hypothalamus. The hypothalamus exerts control over the balance between the parasympathetic and orthosympathetic systems. Orexine, hormones originating in the hypothalamic, are involved in sleep regulation, thermoregulation and neuroendocrine and nociceptive functions. They could play a crucial role in the origin of the migrainous attack and might explain the influence of sleep, eating habits and excessive weight in the occurrence of attacks. Hypothalamic cerebral activation via H2 15OPET activity, suspected by clinical and experimental arguments as a possible trigger for migraine, has been demonstrated during spontaneous attacks. However, no conclusion can be made however as to whether this activation is the cause or the consequence of the migrainous pain.


Novel suicide ligands of tubulin arrest cancer cells in S-phase.
It is presently accepted that the mechanism of action for all anti-tumor tubulin ligands involves the perturbation of microtubule dynamics during the G2/M phase of cell division and subsequent entry into apoptosis [1]. In this report, we challenge the established dogma by describing a unique mechanism of action caused by a novel series of tubulin ligands, halogenated derivatives of acetamido benzoyl ethyl ester. We have developed a suicide ligand for tubulin, which covalently attaches to the target and shows potent cancericidal activity in tissue culture assays and in animal tumor models. These compounds target early S-phase at the G1/S transition rather than the G2/M phase and mitotic arrest. Bcl-2 phosphorylation, a marker of mitotic microtubule inhibition by other tubulin ligands was dramatically altered, phosphorylation was rapid and biphasic rather than a slow linear event. The halogenated ethyl ester series of derivatives thus constitute a unique set of tubulin ligands which induce a novel mechanism of apoptosis.


Nucleolar organizer regions and glycoprotein-hormone alpha-chain reaction as markers of malignancy in endocrine tumours of the pancreas.
The value of silver staining of nucleolar organizer regions (AgNORs) and human chorionic gonadotropin alpha-chain reaction (HCG-alpha) as markers of malignancy was investigated in 60 primary pancreatic endocrine tumours, 37 of which had metastasized at the time of surgery, and in one of which metastases developed 4 years after surgery. Assessment of AgNORs by digital image analysis revealed few but large AgNORs (mean number 2.5 +/- 1.1; mean area 0.32 +/- 0.1 microns 2) in the 22 benign tumours and many but small AgNORs (mean number 5.1 +/- 1.9, P < 0.05; mean area 0.18 +/- 0.09 microns 2, P < 0.01) in the malignant tumours. Quantification of the number of AgNORs per tumour cell nucleolus (AgNOR distribution score) showed that 96% (26/27) of tumours exhibiting at least 5% of cells with more than six AgNORs per nucleolus showed metastases either at the time of diagnosis or up to 4 years after surgery. HCG-alpha immunoreactive cells were present in 25/38 (66%) malignant tumours and in 4/22 (18%) benign tumours. Combined evaluation of AgNOR distribution and HCG-alpha scores showed a high positive predictive value of 96% in cases with a raised AgNOR distribution score irrespective of the HCG-alpha status. A good negative predictive value (81%) was, however, only obtained if both parameters, AgNOR distribution and HCG-alpha scores, were negative. Thus, investigation of AgNORs and HCG-alpha is helpful in predicting malignancy in a high percentage of pancreatic endocrine tumours.


Exposure to armed conflict as a factor associated with very low birth weight: Case-control population study.
To determine the association between armed conflict and very low birth wright (VLBW), which is a multifactorial etiology public health problem that includes aspects of poverty and violence. Case-control population study matched by year of delivery conducted in Cauca, Colombia, between 2010 and 2016. Cases of VLBW, with weights between 500 and 1499 g and controls weighing between 2500 and 3999 g. Cases and controls were identified through the vital statistics registry, and exposure was determined using a multidimensional index designed by the Colombian State. Multiple gestations were excluded. Conditional logistic regression for matched data was used, adjusting for confounding variables. Overall, 7068 matched participants (1767 cases and 5301 controls) were included. Cases and controls had similar baseline characteristics. Participants were predominantly women in the second and third decades of life, 3222 (46%) were exposed to armed conflict, and 1902 (27%) were of African-Colombian or indigenous ethnicity. Maternal exposure to armed conflict significantly increased the odds of VLBW among women with rural birth (adjusted odds ratio [aOR] 3.86, 95% confidence interval [CI] 2.74-5.45) and inadequate prenatal care (aOR 10.38, 95% CI 8.20-13.12). Exposure to armed conflict increases the odds of VLBW neonates. This factor needs to be considered in prenatal care.


Effectiveness and safety of secondary prevention of non-vitamin K oral anticoagulants use by drug type in Asian patients.
Although widely used in clinical fields, real-world data on the role of warfarin and non-vitamin K oral anticoagulants (NOACs) for the secondary prevention of thromboembolic complications in ischemic stroke patients with nonvalvular atrial fibrillation (NVAF) are scarce. This retrospective cohort study compared the effectiveness and safety of secondary prevention of NOAC and warfarin in ischemic stroke patients with NVAF. From the Korean National Health Insurance Service Database, we included 16,762 oral anticoagulants-naive acute ischemic stroke patients with NVAF between July 2016 and June 2019. The main outcomes included ischemic stroke, systemic embolism, major bleeding, and all-cause of death. In total, 1717 warfarin and 15,025 NOAC users were included in the analysis. After 1:8 propensity score matching, during the observation period, all types of NOACs had a significantly lower risk of ischemic stroke and systemic embolism than warfarin (edoxaban: adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.68-0.93, rivaroxaban: aHR, 0.82; 95% CI, 0.70-0.96, apixaban: aHR, 0.79; 95% CI, 0.69-0.91, and dabigatran: aHR, 0.82; 95% CI, 0.69-0.97). Edoxaban (aHR, 0.77; 95% CI, 0.62-0.96), apixaban (aHR, 0.73; 95% CI, 0.60-0.90), and dabigatran (aHR, 0.66; 95% CI, 0.51-0.86) had lower risks of major bleeding and all-cause of death. All NOACs were more effective than warfarin in the secondary prevention of thromboembolic complications in ischemic stroke patients with NVAF. Except for rivaroxaban, most NOACs demonstrated a lower risk of major bleeding and all-cause of death than warfarin.


Pairwise learning problems with regularization networks and Nyström subsampling approach.
Pairwise learning usually refers to the learning problem that works with pairs of training samples, such as ranking, similarity and metric learning, and AUC maximization. To overcome the challenge of pairwise learning in the large scale computation, this paper introduces Nyström sampling approach to the coefficient-based regularized pairwise algorithm in the context of kernel networks. Our theorems establish that the obtained Nyström estimator achieves the minimax error over all estimators using the whole data provided that the subsampling level is not too small. We derive the function relation between the subsampling level and regularization parameter that guarantees computation cost reduction and asymptotic behaviors' optimality simultaneously. The Nyström coefficient-based pairwise learning method does not require the kernel to be symmetric or positive semi-definite, which provides more flexibility and adaptivity in the learning process. We apply the method to the bipartite ranking problem, which improves the state-of-the-art theoretical results in previous works. By developing probability inequalities for U-statistics on Hilbert-Schmidt operators, we provide new mathematical tools for handling pairs of examples involved in pairwise learning.


Determination of dosulepin and its metabolite: application of high-performance liquid chromatography with electrochemical detection.
Dosulepin, 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenzo [b,e]thiepin hydrochloride, is a thio analogue of amitriptyline and is used for the treatment of anxiety and affective disorders. The present study developed a simple and sensitive procedure for the determination of this compound and its metabolite, northiaden, by a combination of high-performance liquid chromatography with electrochemical detection. Hydrodynamic voltammograms demonstrated an optimal applied potential at 1300 mV for both dosulepin and northiaden. A mobile phase consisting of 0.1 M acetate buffer-acetonitrile-perchloric acid-trichloroacetic acid (50:50:2:1.5) provided the best separation of the drugs. The extraction procedure, which used a heptane-isoamyl alcohol (99:1) mixture, was successfully applied with a recovery of over 90%. A preliminary pharmacokinetic study was performed by the proposed method.


Complexity, rate, and scale in sliding friction dynamics between a finger and textured surface.
Sliding friction between the skin and a touched surface is highly complex, but lies at the heart of our ability to discriminate surface texture through touch. Prior research has elucidated neural mechanisms of tactile texture perception, but our understanding of the nonlinear dynamics of frictional sliding between the finger and textured surfaces, with which the neural signals that encode texture originate, is incomplete. To address this, we compared measurements from human fingertips sliding against textured counter surfaces with predictions of numerical simulations of a model finger that resembled a real finger, with similar geometry, tissue heterogeneity, hyperelasticity, and interfacial adhesion. Modeled and measured forces exhibited similar complex, nonlinear sliding friction dynamics, force fluctuations, and prominent regularities related to the surface geometry. We comparatively analysed measured and simulated forces patterns in matched conditions using linear and nonlinear methods, including recurrence analysis. The model had greatest predictive power for faster sliding and for surface textures with length scales greater than about one millimeter. This could be attributed to the the tendency of sliding at slower speeds, or on finer surfaces, to complexly engage fine features of skin or surface, such as fingerprints or surface asperities. The results elucidate the dynamical forces felt during tactile exploration and highlight the challenges involved in the biological perception of surface texture via touch.


Greek college students and psychopathology: new insights.
College students' mental health problems include depression, anxiety, panic disorders, phobias and obsessive compulsive thoughts. To investigate Greek college students' psychopathology. During the initial evaluation, 638 college students were assessed through the following psychometric questionnaires: (a) Eysenck Personality Questionnaire (EPQ); (b) The Symptom Checklist-90 (SCL-90); (c) The Beck Depression Inventory (BDI); (d) State-Trait Anxiety Inventory (STAI). State anxiety and trait anxiety were correlated, to a statistically significant degree, with the family status of the students (p = 0.024) and the past visits to the psychiatrist (p = 0.039) respectively. The subscale of psychoticism is significantly related with the students' origin, school, family status and semester. The subscale of neuroticism is significantly related with the students' school. The subscale of extraversion is significantly related with the students' family psychiatric history. Students, whose place of origin is Attica, have on average higher scores in somatization, phobic anxiety and paranoid ideation than the other students. Students from abroad have, on average, higher scores in interpersonal sensitivity and psychoticism than students who hail from other parts of Greece. The majority of the students (79.7%) do not suffer from depression, according to the Beck's depression inventory scale. Anxiety, somatization, personality traits and depression are related with the students' college life.


Cycles of transient high-dose cyclophosphamide administration and intratumoral oncolytic adenovirus vector injection for long-term tumor suppression in Syrian hamsters.
Immune responses against oncolytic adenovirus (Ad) vectors are thought to limit vector anti-tumor efficacy. With Syrian hamsters, which are immunocompetent and whose tumors and normal tissues are permissive for replication of Ad5-based oncolytic Ad vectors, treating with high-dose cyclophosphamide (CP) to suppress the immune system and exert chemotherapeutic effects enhances Ad vector anti-tumor efficacy. However, long-term CP treatment and immunosuppression can lead to anemia and vector spread to normal tissues. Here, we employed three cycles of transient high-dose CP administration plus intratumoral injection of the oncolytic Ad vector VRX-007 followed by withdrawal of CP. Each cycle lasted 4-6 weeks. This protocol allowed the hamsters to remain healthy so the study could be continued for ~100 days. The tumors were very well suppressed throughout the study. With immunocompetent hamsters, the vector retarded tumor growth initially, but after 3-4 weeks the tumors resumed rapid growth and further injections of vector were ineffective. Preimmunization of the hamsters with Ad5 prevented vector spillover from the tumor to the liver yet still allowed for effective long-term anti-tumor efficacy. Our results suggest that a clinical protocol might be developed with cycles of transient chemotherapy plus intratumoral vector injection to achieve significant anti-tumor efficacy while minimizing the side effects of cytostatic treatment.


Genetics of idiopathic nephrotic syndrome.
Nephrotic syndrome (NS) is a pathological entity characterized by massive proteinuria and has diverse etiology. Although it is one of the most common renal diseases in children, the etiological factors responsible for idiopathic NS/FSGS remain largely unknown. Previous studies had implicated a variety of factors including genetic factors, although NS is generally regarded as a sporadic disease. Familial cases of NS have however been reported periodically, and both autosomal dominant and recessive forms have been identified. Studies of familial NS/FSGS have led to the discovery of several genes that are expressed in podocytes and are associated with proteinuria. These discoveries have shifted the focus from glomerular basement membrane (GBM) to recognition of the central role of podocytes in maintaining glomerular perm selectivity and pathogenesis of NS/FSGS. Associations with various genes (NPHS1, ACTN4, NPHS2, WT-1) and linkage to several chromosomal regions (such as 19q13, 11q21, 11q24) have been reported in patients with familial NS/FSGS.


[Increase in the number of reported cases of child abuse following adoption of a structured approach in the VU Medical Centre, Amsterdam, in the period 2001-2004].
Description of the characteristics of (suspected) child abuse after the establishment of a Child Abuse Team and the introduction of guidelines on how to deal with child abuse and a standardised registration form for suspicions of child abuse. Retrospective. An inventory and analysis of the available data on the reporting of, approach to and care provided in case of(suspected) child abuse from I January 2oo0 to 30 April 2004 in the VU Medical Centre in Amsterdam, the Netherlands. The Child Abuse Team received 220 reports of suspected child abuse and the number of suspected and confirmed cases of child abuse increased each year. In 58 suspected cases, the suspicions were confirmed on the basis of additional information from the general practitioners or other attending physicians, or conversations with the parents and the child. There were 29 girls and 29 boys; 22 of them were from families with multiple problems. Of these 58 confirmed cases, 31 were reported to the national Advisory Centre for Registration of Child Abuse. In 120 of the 220 suspected cases of child abuse, this suspicion was refuted, while in 42 cases the suspicion could neither be refuted nor confirmed. An increased number of suspected cases of child abuse were reported and confirmed each year following the introduction of a standardised registration form and subsequent analysis by a multidisciplinary team. Broader application of this approach may contribute to improved insight into the prevalence and causes of child abuse.


Reference intervals for plasma pro-gastrin releasing peptide (ProGRP) levels in healthy adults of Chinese Han ethnicity.
To determine the upper limits of the 95th percentile reference intervals (RIs) for the detection of the pro-gastrin releasing peptide (ProGRP) in plasma according to the Clinical and Laboratory Standards Institute (CLSI) C28-A3 guideline in a population of adult Chinese of Han ethnicity. Plasma samples were collected from 578 healthy adults. Plasma ProGRP values were measured by chemiluminescent microparticle immunoassay (CMIA) on Abbot ARCHITECT i2000 system analyzers. Plasma ProGRP values did not conform to a Gaussian distribution, and thus non-parametric statistical methods were used to calculate RIs. Plasma ProGRP levels significantly increased with age, thus age-dependent RIs were determined. The upper limit of the 95th percentile RIs for plasma ProGRP was ≤57.26 pg/mL for young adults (18-50 years) and ≤81.42 pg/mL for old adults (>50 years). By CMIA, we established distinct age-dependent RIs for plasma ProGRP in healthy adults of Chinese Han ethnicity, thus generating a valuable reference for future clinical and laboratory studies.


Outcome of coronary endarterectomy with coronary artery bypass grafting in patients with diffuse coronary artery disease in Bangladesh: A retrospective cohort study.
In this study, we aimed to review the consequences of coronary endarterectomy with coronary artery bypass grafting, and assess outcomes of this combined surgical technique for patients with diffuse coronary artery disease in a single surgeon's practice. We retrospectively reviewed outcome of 1198 endarterectomized coronary artery in 1000 patients with diffuse coronary artery disease, who have had experienced coronary endarterectomy with off pump coronary artery bypass grafting in between 2009 and 2016. The mean age was 61.5 ± 5.5 years. Coronary endarterectomy was performed on 74.7% in the left coronary territory (43.2% left anterior descending, 26.6% diagonal, 4.9% Obtuse Marginal), and 25.3% in the right coronary territory. Post-operative intensive care unit mortality rate was 1.9%, and there were 11 (1.1%) late deaths. Mean intensive care unit stay was 36.6 ± 6.7 hours. Patients were extubated following a mean of 9.8 ± 1.25 hours. The mean duration of hospital stay was 10 ± 1 days. One-year survival rate was 97.8% and 89.5% survival rate was at 5 years follow up. However, 91.8% of patients were angina free at median follow-up of 2.5 years. Coronary endarterectomy with off pump coronary artery bypass grafting is attainable and accomplishes surgical revascularization in coronary artery disease patients when there is no other alternative for sufficient revascularization.


'I don't want to cause any trouble': the attitudes of hospital patients towards patient empowerment strategies to reduce healthcare-acquired infections.
Patients have, traditionally, been assumed to be the passive party in the healthcare-associated infections equation, with relatively little research focused on the patients' perspective. This study aimed to explore the attitudes of hospital patients towards patient empowerment as one of the key components of patient engagement. Semi-structured interviews were undertaken with surgical patients from a major public hospital in Sydney, Australia. While participants acknowledged that patients could play a role in preventing infections while in hospital, that role was largely associated with maintaining their own personal hygiene. No reference was made to patients interacting with staff members. Some participants said that they would feel comfortable and happy to engage with staff, while others voiced concerns. Some about not wanting to 'cause trouble or start fires' and therefore would not tell staff members to perform hand hygiene. Some participants articulated a fear that their care may be negatively affected if they directly engaged or confronted clinicians about their behaviours. We found that patient engagement remains an underused method of preventing healthcare-associated infections, and the deep-seated public fears about individual vulnerabilities still need to be addressed.


Superficial granulomatous pyoderma: a localized vegetative form of pyoderma gangrenosum.
Twenty-five patients had superficial ulcerative and vegetative pyoderma with granulomatous histologic findings. Healing occurred without systemic corticosteroid therapy in all but three patients. All patients had clinical pyoderma gangrenosum. In five patients the lesion occurred after surgery of the skin. Histopathologic study of 40 biopsy specimens showed focal neutrophilic abscesses of the papillary dermis, often with peripheral palisading histiocytes and foreign-body giant cells. Pseudoepitheliomatous, vegetative hyperplasia and sinus tract formation were observed frequently. All patient had massive areas of plasmacytosis, and 13 had eosinophils. Granulation tissue, hemorrhage, and fibrosis were additional features in some areas. Foreign material in the lesions was considered unimportant, except in one patient with a starch granuloma. Therapy with local corticosteroids, minocycline, tetracycline, or sulfa drugs resulted in healing in 15 patients. We believe that we have identified a localized, limited form of chronic superficial pyoderma gangrenosum with verrucous and ulcerative lesions and a granulomatous histologic appearance that represents a unique pattern of this disease in some patients.


Antimicrobial properties of the essential oil of Schinus areira (Aguaribay) against planktonic cells and biofilms of S. aureus.
The essential oil (EO) of Schinus areira L. (Anacardiaceae) leaves has shown antibacterial activity against Staphylococcus aureus. In this study, we aimed to unravel the mechanisms of its antibacterial action by using bacterial cells and model membranes. First, the integrity of the S. aureus membrane was evaluated by fluorescence microscopy. It was observed that there was an increase in the permeability of cells that was dependent on the EO concentration as well as the incubation time. For a deep comprension of the action of the EO on the lipids, its effect on the membrane fluidity was evaluated on DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine): DMPG (1,2-dimyristoyl-sn-glycero-3-phospho-1'-rac-glycerol) (5:1) liposomes by dynamic light scattering and by using Laurdan doped liposomes. The results indicate that EO produces changes in lipid membrane packing, increasing the fluidity, reducing the cooperative cohesive interaction between phospholipids and increasing access of water or the insertion of some components of the EO to the interior of the membrane. In addition, the potential effect of EO on intracellular targets, such as the increase of cytosolic reactive oxygen species (ROS) and DNA damage, were analyzed. The EO was capable of increasing the production of ROS as well as inducing a partial DNA degradation. Finally, the effect of EO on S. aureus biofilm was tested. These assays showed that EO was able to inhibit the biofilm formation, and also eradicate preformed biofilms. The results show, that the EO seems to have several bacterial targets involved in its antibacterial activity, from the bacterial membrane to DNA. Furthermore, the antibacterial action affects not only planktonic cells but also biofilms; reinforcing the potential application of this EO.


A Pedagogy of Preparation: Helping Underprepared Students Succeed in College-Level Coursework in Community Colleges.
This paper presents an overall educational philosophy of working with students underprepared for college-level work, which we term "a pedagogy of preparation." We consider how instructors scaffolded instruction to foster college readiness in students who were now able to enroll in college-level work regardless of academic preparation after state-level legislation (SB 1720) that dramatically altered the delivery of developmental education in the Florida College System (FCS). We also consider how collaboration increased among campus personnel after the legislation to foster college readiness in students underprepared for college-level work.


[Pathogenesis of RA: more than just immune cells].
Rheumatoid arthritis (RA) is a chronic inflammatory disorder that primarily affects the joints and results in their progressive destruction. Research during past years has shown that in addition to inflammatory cells and their mediators, resident fibroblasts of the synovial membrane play an important role in the pathogenesis of the disease. These cells exhibit features of stable cellular activation that is maintained in the absence of continuous inflammatory stimuli. In contrast to normal synovial fibroblasts or fibroblasts from patients with osteoarthritis, RA synovial fibroblasts show an upregulation of proto-oncogenes and transcription factors, which in a self-perpetuating manner mediate the expression of adhesion molecules and matrix degrading enzymes, and result in alterations in apoptosis. As a consequence, these activated fibroblasts attach to cartilage and bone and progressively destroy articular structures. A better understanding of the molecular mechanisms that lead to the stable activation of synovial fibroblasts in RA is, therefore, of utmost importance for elucidating the pathogenesis of RA as well as for the development of novel therapeutic strategies aimed at inhibiting joint destruction.


Effect of temperature and pH on 31P nuclear magnetic resonances of phospholipids in cholate micelles.
Accurate and precise determination of phospholipid composition by 31P NMR spectroscopy requires correct assignments and adequate spectral resolution. Because temperature and pH may affect chemical shifts (delta), our first aim was to establish the temperature coefficient (Deltadelta/DeltaT) of common phospholipid classes when using sodium cholate as detergent. This parameter can then be used to aid in resonance assignments. The second goal was to investigate the pH dependence of delta so that, in addition to temperature, pH control can be used to minimize spectral overlap. For phosphatidylcholine, sphingomyelin, dihydrosphingomyelin and phosphatidylglycerol, delta values were invariant with pH and temperature. Whereas the Deltadelta/DeltaT for phosphatidylinositol was 4 x 10(-3)ppm/ degrees C, regardless of pH, these coefficients were highly pH-dependent for phosphatidic acid, phosphatidylethanolamine and phosphatidylserine, exhibiting maximal variations with the deprotonation of the headgroup, particularly for phosphatidic acid. These trends indicate the importance of H-bonding on delta and Deltadelta/DeltaT for phospholipid resonances.


Mental health and the poor: have the gaps between the poor and the "nonpoor" narrowed in the last decade?
Because of the difficulty of measuring mental health status and the lack of systematic and longitudinal data reflecting economic status and mental health, and arbitrary definition is used for this paper: changes in the accessibility to and utilization of psychiatric services by the poor compared with that of the nonpoor will be interpreted as changes in mental health status. Patterns of utilization of mental health facilities in the United States and in Monroe County, New York, by economic variables and/or by race, for periods spanning the Great Society programs, are descirbed. In addition, the location and availability of services provided by community mental health centers since their development are examined. Although these data indicate increased accessibility to facilities by the poor, there continue to be differences in the ways different economic groups use psychiatric facilities. In addition to a discussion of the implications of the findings for service delivery, definitional limitations are cited and additional information needed for making any judgements totward planning future mental health programs are explored.


Methylprednisolone potentiates tetrandrine pharmacodynamics against human T lymphoblastoid leukemia MOLT-4 cells via regulation of NF-κB activation and cell cycle transition.
Low response to glucocorticoid (GC) predicts therapeutic failure in acute T lymphoblastic leukemia (T-ALL). The efficient and safe strategies are still required for the treatment of relapsed T-ALL. Our previous study revealed that tetrandrine induces apoptosis in human T lymphoblastoid leukemia cells possibly via activation of NF-κB. GCs are recognized as typical NF-κB inhibitors and are used for the treatment of T-ALL patients. In the present study, we examined whether methylprednisolone (MP) potentiates the cytotoxic effect of tetrandrine (TET) via NF-κB regulation by using human T lymphoblastoid leukemia MOLT-4 cells. WST-8 assay data showed that nM grade of MP increased cytotoxicity of TET against MOLT-4 cells in vitro. This effect seemed to be related to the potentiation of TET action by MP to induce apoptosis. Meanwhile, the combination also impeded the transition of cell cycle from G0/G1 phase to S phase. However, the regulation effect of this combination on cell cycle had no relationship with cyclin signaling pathway, since the drug-combination did not influence on the expression of cyclin A2/B1/D1 in MOLT-4 cells. On the other hand, the combination significantly inhibited the phosphorylation of NF-κB (p < 0.01). These results suggest that nM grade of MP potentiates the cytotoxic effect of TET possibly via regulation of NF-κB activation and "G0/G1 to S" phase transition in human T lymphoblastoid leukemia MOLT-4 cells. Combination of TET and MP may provide a new therapeutic strategy for relapsed T-ALL.


The (gt)n(ga)m containing intron 2 of HLA-DRB alleles binds a zinc-dependent protein and forms non B-DNA structures.
We studied protein binding and structural features of perfect and imperfect composite (gt)n(ga)m blocks from different HLA-DRB1 alleles in their original genomic and artificial environments. The major retarded protein/DNA complex of the genomic (gt)n(ga)m fragments comprises a zinc-dependent protein present in nuclear extracts from different cell types. The protein binding is characterized by moderate affinities independent of the polymorphic form of the physiological microsatellite allele. The binding affinity depends on the 5' and 3' adjacent single copy parts. DNase I footprinting of genome-derived fragments revealed that the 5' adjacent sequence and the (gt)n repeat are preferentially protected on the (gt)n(ga)m strand. Comparing three alleles, a regular pattern of footprints was not detectable in the (gt)n part, indicating that the zinc-dependent protein recognizes structural rather than sequence-specific features in this region. Chemical probing resulted in a pattern characteristic for Z-DNA in the (gt)n tract of the fragments. However, EMSA experiments using the Z-DNA specific monoclonal antibody mABZ-22 did not prove the presence of Z-DNA. As demonstrated by chemical modifications of the different (ga)m targets, only one of three (gt)n(ga)m fragments formed intramolecular triplexes of the type H-y3 and H-y5. DNase I footprinting revealed only weak protection, if any, in the homopurine tract. Rather, the (tc)m strands are hypersensitive for DNase I. This is probably due to structural conversions into intramolecular *H-triplexes after binding of HIZP.


Loureirin B protects against cerebral ischemia/reperfusion injury through modulating M1/M2 microglial polarization via STAT6 / NF-kappaB signaling pathway.
The latest research indicates that modulating microglial polarization from M1 to M2 phenotype may be a coping therapy for ischemic stroke. The present study thereby evaluated the effects of loureirin B (LB), a monomer compound extracted from Sanguis Draconis flavones (SDF), on cerebral ischemic injury and the potential mechanisms. The middle cerebral artery occlusion (MCAO) model was established in male Sprague-Dawley rats to induce cerebral ischemia/reperfusion (I/R) injury in vivo, and BV2 cells were exposed to oxygen-glucose deprivation and reintroduction (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that LB significantly reduced infarct volume, neurological deficits and neurobehavioral deficits, apparently improved histopathological changes and neuronal loss in cortex and hippocampus of MCAO/R rats, markedly decreased the proportion of M1 microglia cells and the level of pro-inflammatory cytokines, and increased the proportion of M2 microglia and the level of anti-inflammatory cytokines both in vivo and in vitro. In addition, LB evidently improved the p-STAT6 expression and reduced the NF-κB (p-p65) expression after cerebral I/R injury in vivo and in vitro. IL-4 (a STAT6 agonist) exhibited a similar impact to that of LB, while AS1517499 (a STAT6 inhibitor) significantly reversed the effect of LB on BV-2 cells after OGD/R. These findings point to the protection of LB against cerebral I/R injury by modulating M1/M2 polarization of microglia via the STAT6/NF-κB signaling pathway, hence LB may be a viable treatment option for ischemic stroke.


Fluorescence origin and chirality mechanism of graphene quantum Dots: Twist or Non-Twist?
In this paper, we theoretically investigate the fluorescence origin and chirality mechanism of graphene quantum dots with non-twist and twist geometries, respectively. It is revealed that twist is not necessary for fluorescence; but twist is must for the chirality, which can significantly enhance the intensity of chirality, demonstrated by ECD spectra. Our results provide deeper understanding on the physical mechanism of fluorescence and chirality of graphene quantum dot influenced by geometric twist.


Beta 1 integrin-dependent binding of Jurkat cells to fibronectin is regulated by a serine-threonine phosphatase.
We investigated the effects of signaling molecule inhibitors on the expression and function of beta1 integrins in Jurkat cells. Jurkat cells expressed alpha4beta1 and alpha5beta1, with significant levels of constitutively activated beta1 integrins as assessed by labeling with mAb 15/7 that distinguishes between activation states. Adhesion to fibronectin (Fn) was mediated equally through alpha4 and alpha5 subunits, and was potentiated by the beta1 integrin activating mAb 8A2. Fn adhesion was decreased by okadaic acid through effects on both alpha4beta1, and alpha5beta1. Tyrphostin A23 also decreased adhesion but was less potent. Neither inhibitor had any effect on the surface expression of total or activated beta1 integrins. The effect of tyrphostin was completely reversed by 8A2; the effect of okadaic acid was only partially reversed. Using Calyculin A, we determined that Jurkat adhesion to Fn was regulated via protein phosphatase 1, independent of the levels of integrins or integrin activation epitopes. Activation of Jurkat cells with a CD3-stimulating mAb enhanced adhesion to Fn and was partially blocked by okadaic acid. These data demonstrate different regulatory pathways for constitutive versus activation-dependent adhesion via beta1 integrins, and implicate both tyrosine kinases and serine-threonine phosphatases in integrin function.


Three new triterpenoid saponins from the seeds of Aesculus turbinata.
Three new triterpenoid saponins, named isoescins VIIa (1), VIa (2), and VIIIa (3), were isolated from the seeds of Aesculus turbinata and identified by spectroscopic analysis and chemical hydrolysis. Their structures were established as 21beta-O-tigloyl-28-O-acetylprotoaescigenin 3beta-O-[beta-d-galactopyranosyl(1 --> 2)][beta-d-glucopyranosyl(1 --> 4)]-beta-d-glucopyranosiduronic acid (Isoescin VIIa, 1), 21beta-O-(2-methylbutyryl)-28-O-acetylprotoaescigenin 3beta-O-[beta-d-glucopyranosyl(1 --> 2)] [beta-d-glucopyranosyl(1 --> 4)]-beta-d-glucopyranosiduronic acid (Isoescin VIa, 2), and 21beta-O-angeloyl-28-O-acetylbarringtogenol C 3beta-O-[beta-d-glucopyranosyl(1 --> 2)] [beta-d-glucopyranosyl(1 --> 4)]-beta-d-glucopyranosiduronic acid (Isoescin VIIIa, 3).


Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro.
1. 45-Ca uptake by pinched-off nerve terminals (synaptosomes) of rat brain incubated in standard physiological saline (including 132 mM-Na + 5mM-K + 1-2 mM-Ca) at 30 degrees C averages about 0-5 mumole Ca per g protein per minute. This may be equivalent to a Ca influx of about 0-03 p-mole/cm-2 sec. 2. The rate of 45-Ca uptake is increased when the concentration of K in the medium is increased above 15-20 mM, K replacing Na isosmotically. Maximum stimulation, a three- to six-fold increase in the rate of Ca uptake, occurs when [K]o is about 60 mM. The effect of increased [K]o is reversible. 3. The K-stimulated Ca uptake is associated primarily with the nerve terminal fraction of brain homogenates. The entering Ca is not accompanied by extracellular markers such as mannitol or inulin. Replacement of external chloride by methylsulphate or sulphate does not prevent the stimulation by K. 4. The effects of external K are quantitatively mimicked by Rb. Caesium also stimulates Ca uptake, but is only about one fifth as effective as K or Rb; Li is ineffective. 5. Two other depolarizing agents also stimulate Ca uptake by synaptosomes: veratridine (7-5 times 10- minus 6 to 7-5 times 10- minus 5 M) and scorpion (Leirus quinquestriatus) venom (6-7 times 10- minus 7 to 6-7 times 10- minus g/ml.). The stimulatory effects of veratridine and scorpion venom, but not of increased [K] are blocked by 2 times 10- minus 7 M tetrodotoxin. 6. Internal K also influences the rate of 45-Ca uptake by synaptosomes: lowering [K]i reduces the stimulatory effect of external K and veratridine. 7. Replacement of external Na by choline markedly inhibits the response to veratridine, but has a much smaller effect on the response to increased [K]o. 8. The Ca uptake mechanism has an apparent dissociation constant for Ca (KCa) of about 0-8 mM. Increasing [K]o increases the maximal rate of Ca uptake, but has no effect on KCa. The K-induced 45-Ca uptake is competitively inhibited by Mg-2+, Mn-2+ and La-3+. 9. The release of acetylcholine and noradrenaline was also studied. Increasing [K]o stimulates external Ca-dependent acetylcholine release. Scorpion venom stimulates noradrenaline release from synaptosomes; this effect could be prevented by adding tetrodotoxin or removing external Ca. 10. These results indicate that synaptosomes may increase their permeability to Ca, accumulate Ca and release neural transmitter substances, when stimulated by depolarizing agents under appropriate physiological conditions.


Physical and chemical control of the phytoplankton of Ahe lagoon, French Polynesia.
The environmental characteristics of Ahe deep lagoon (Tuamotu Archipelago, French Polynesia) were studied over 3 years with the aim of explaining the spatial and temporal variability of the natural food available for pearl oysters with a special focus on phytoplankton biomass and global photosynthesis/respiration ratio of the lagoon. Chlorophyll averaged 0.34±0.01 μg L(-1) and our findings did not confirm increased phytoplankton biomass in deep lagoonal waters. Phytoplankton production appears to be limited firstly by nitrogen and respiratory processes overpass photosynthetic processes at least in the north-eastern edge of the atoll. Grazing by pearl oysters in culture seems to decrease the POC concentration but not the phytoplankton biomass. Oysters graze mainly on non chlorophyllian particles.


A second example of hemolysis due to IgA autoantibody with anti-e specificity.
A case of warm autoimmune hemolytic anemia due to IgA antibody is described. The patient had clinical and hematologic signs of hyperhemolysis, but all specific tests were negative. The direct antiglobulin test was positive only when it was performed with anti-IgA monospecific antiserum. The autoantibody eluted from the patient's red cells showed anti-e specificity. The sensitivity of broad-spectrum antiglobulin serum and the possible hemolytic mechanisms of IgA-coated red cells are discussed.


Ghost Cell Odontogenic Carcinoma Arising in a Previous Calcifying Odontogenic Cyst: A Case Report and Review of Literature.
Ghost cell odontogenic carcinoma (GCOC) is a rare malignant tumor of odontogenic origin, with only about 50 cases reported in the English literature so far. Histologically, it is characterized by ghost cells, dentinoid deposits, high grade malignant cellular features, and areas of necrosis and invasion. Having common histological features with other odontogenic ghost cell lesions (OGCL) like calcifying odontogenic cyst (COC) and dentinogenic ghost cell tumors, it is crucial to recognize GCOC malignant features, as it can be destructive and invasive, sometimes showing distant metastases and high recurrence rate. For this reason, it may entail more aggressive surgical approach and multimodal therapeutic regimen. Here we present a case report of GCOC arising in a previous COC, treated with surgical excision that showed persistence and recurrence after two years. The clinical and histological features of this rare occurrence are presented, in addition to the surgical approach, and a summary of literature review of OGCL.


Increased incidence of shoulder dystocia but a declining incidence of obstetric brachial plexus palsy in vaginally delivered infants.
Obstetric brachial plexus palsy (OBPP) is a serious form of neonatal morbidity. The primary aim of this population-based registry study was to examine temporal trends, 1997-2019, of OBPP in infants delivered vaginally in a cephalic presentation. The secondary aim was to examine temporal changes in the incidence of associated risk factors. This was a population-based registry study including singleton, cephalic, vaginally delivered infants, 1997-2019, in Sweden. To compare changes in the incidence rates of OBPP and associated risk factors over time, univariate logistic regression was used and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The incidence of OBPP in infants delivered vaginally in a cephalic presentation decreased from 3.1 per 1000 births in 1997 to 1.0 per 1000 births in 2019 (OR 0.31, 95% CI 0.24-0.40). Conversely, the incidence of shoulder dystocia increased from 2.0 per 1000 in 1997 to 3.3 per 1000 in 2019 (OR 1.64, 95% CI 1.34-2.01). Over time, the proportion of women with body mass index of 30 kg/m2 or greater increased (14.5% in 2019 compared with 8.0% in year 1997, OR 1.96, 95% CI 1.89-2.03), more women had induction of labor (20.5% in 2019 compared with 8.6% in 1997, OR 2.74, 95% CI 2.66-2.83) and epidural analgesia (41.2% in 2019 compared with 29.0% in 1997, OR 1.72, 95% CI 1.68-1.75). In contrast, there was a decrease in the rate of operative vaginal delivery (6.0% in 2019, compared with 8.1% in 1997, OR 0.72, 95% CI 0.69, 0.75) and in the proportion of infants with a birthweight greater than 4500 g (2.7% in 2019 compared with 3.8% in 1997, OR 0.70, 95% CI 0.66-0.74). The decline in the incidence of these two risk factors explained only a small fraction of the overall decrease in OBPP between 1997-2002 and 2015-219. The incidence of OBPP in vaginally delivered infants in a cephalic presentation at birth decreased during the period 1997-2019 despite an increase in important risk factors including shoulder dystocia.


Optimal dose and type of physical activity to improve functional capacity and minimise adverse events in acutely hospitalised older adults: a systematic review with dose-response network meta-analysis of randomised controlled trials.
To identify the optimal dose and type of physical activity to improve functional capacity and reduce adverse events in acutely hospitalised older adults. Systematic review and Bayesian model-based network meta-analysis. Four databases were searched from inception to 20 June 2022. Randomised controlled trials that assessed the effectiveness of a physical activity-based intervention on at least one functional outcome in people aged ≥50 years hospitalised due to an acute medical condition were included. Pooled effect estimates (ie, standardised mean differences for functional capacity and the ratio of means for adverse events) were calculated using random treatment effects network meta-analysis models. Nineteen studies (3842 participants) met the inclusion criteria. Approximately 100 Metabolic Equivalents of Task per day (METs-min/day) (~40 min/day of light effort or ~25 min/day of moderate effort activities) was the minimal dose to improve the functional capacity of acute hospitalised older adults (standardised mean difference (SMD)=0.28, 95% credible interval (CrI) 0.01 to 0.55). The optimal dose was estimated at 159 METs-min/day (~70 min/day of light effort or ~40 min/day of moderate effort activities; SMD=0.41, 95% CrI 0.08 to 0.72). Ambulation was deemed the most efficient intervention, and the optimal dose was reached at 143 METs-min/day (~50 min/day of slow-paced walking; SMD=0.76, 95% CrI 0.35 to 1.16), showing a high evidential power (87.68%). The minimal effective ambulation dose was estimated at 74 METs-min/day (~25 min/day of slow-paced walking; SMD=0.25, 95% CrI 0.01 to 0.41). Physical activity interventions resulted in a decrease in the rate of adverse events compared with usual care at discharge (ratio of means=0.96, 95% CrI 0.95 to 0.97; median time 7 days). This meta-analysis yielded low to moderate evidence supporting the use of in-hospital supervised physical activity programmes in acutely hospitalised older adults. As little as ~25 min/day of slow-paced walking is sufficient to improve functional capacity and minimise adverse events in this population. PROSPERO CRD42021271999.


Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum beta-lactamase-producing organisms.
The pharmacodynamics of piperacillin/tazobactam and cefepime were evaluated against extended-spectrum beta-lactamase (ESBL)-producing organisms. Ten thousand patients were simulated based on ESBL minimum inhibitory concentrations (MICs) from our laboratory (N=39) and on pharmacokinetic data from peer-reviewed literature. The desired proportion of the dosing interval that the concentration remains above the MIC (%T>MIC) for the intermittent bolus regimens was >/=40% for piperacillin/tazobactam and >/=60% for cefepime. The desired C(ss)/MIC ratio (where C(ss) is the concentration at steady state) was >/=2 for all continuous infusion (CI) regimens. MIC(50), MIC(90) and %S were, respectively, 64/4mug/mL, 1024/4mug/mL and 33% for piperacillin/tazobactam and 8mug/mL, 16mug/mL and 0% for cefepime. For piperacillin/tazobactam, 3.375g every 4h (q4h) achieved the highest probability of target attainment (43%), followed by 13.5g CI (31%), 3.375g q6h (27%), 4.5g q8h (17%) and 6.75g CI (10%). However, for cefepime, 4g CI had the highest probability of target attainment (77%), followed by 1g q8h (65%), 2g q12h (58%), 3g CI (46%) and 1g q12h (27%). Although the probabilities of target attainment for cefepime were higher than for piperacillin/tazobactam, neither agent achieved a high probability of target attainment and should not be used routinely for the treatment of ESBL infections.


The mystery of persistent, asymptomatic Plasmodium falciparum infections.
Plasmodium falciparum causes millions of malaria infections and hundreds of thousands of deaths annually. These parasites avoid the adaptive immune response by systematically cycling through a limited repertoire of variant surface antigens after which the number of circulating parasites drops to extremely low levels, coinciding with a loss of symptoms and eventual clearance of the infection. However, in regions with extended dry seasons or in individuals who no longer reside in endemic areas, asymptomatic infections have been observed to persist for many months or years, potentially serving as reservoirs for transmission. Recent work suggests the possibility that parasites can assume a state in which no variant surface antigens are expressed, thus rendering them virtually invisible to the immune system and enabling them to persist at low levels indefinitely.


B cell subsets in adult-onset Still's disease: potential candidates for disease pathogenesis and immunophenotyping.
Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder of unknown etiology. B cells are critical participants in different rheumatic diseases, and their roles in AOSD are rarely investigated. This study aimed to unveil the B cell subset features in AOSD and provide evidence for B cell-based diagnosis and targeted therapies of AOSD. B cell subsets in the peripheral blood of AOSD patients and healthy controls (HCs) were detected by flow cytometry. Firstly, the frequencies of B cell subsets were compared. Then, the correlation analysis was performed to explore the correlation between B cell subsets and clinical manifestations in AOSD. Finally, unbiased hierarchical clustering was performed to divide AOSD patients into three groups with different B cell subset features, and the clinical characteristics of the three groups were compared. The frequencies of B cell subsets were altered in AOSD patients. Disease-promoting subsets (such as naïve B cells, double negative B cells (DN B cells), and plasmablasts) increased, and potential regulatory subsets (such as unswitched memory B cells (UM B cells) and CD24hiCD27+ B cells (B10 cells)) decreased in the peripheral blood of AOSD patients. In addition, the altered B cell subsets in AOSD correlated with the clinical and immunological features, such as immune cells, coagulation features, and liver enzymes. Intriguingly, AOSD patients could be divided into three groups with distinct B cell immunophenotyping: group 1 (naïve B cells-dominant), group 2 (CD27+ memory B cells-dominant), and group 3 (precursors of autoantibody-producing plasma cells-dominant). Moreover, these three group patients demonstrated differential manifestations, including immune cells, liver or myocardial enzymes, coagulation features, and systemic score. B cell subsets are significantly altered in AOSD patients, potentially contributing to the disease pathogenesis. These findings would inspire B cell-based diagnosis and targeted therapies for this refractory disease.


Influence of bile flow obstruction vs bile diversion on pancreatic secretion in the conscious rat.
Changes in pancreatic exocrine functions were compared between conscious rats with bile duct ligation and bile diversion from the duodenum on the first, third, fifth, and seventh postoperative days. Body weight was significantly decreased with time in both groups. Basal secretions of fluid, bicarbonate, and protein remained unchanged throughout the experimental period in bile duct ligated rats, whereas in bile diverted rats, the basal bicarbonate secretion with returning of pancreatic juice to the duodenum increased on the third postoperative day, and the basal protein output significantly increased with time. Basal secretions with returning of pancreatic juice to the duodenum in both groups were higher than that in control (bile and pancreatic juice returned to the intestine) rats. Stepwise increases in fluid and bicarbonate outputs responding to the graded doses of secretin were observed in bile duct ligated rats on the first and third postoperative days, as has been observed in bile diverted rats. However, on the fifth and seventh postoperative days, stepwise responses to graded doses of secretin were no longer observed in bile duct ligated rats. The pancreatic response to cerulein was greater in bile diverted rats than in bile duct ligated rats. Plasma CCK concentration in 7-d bile duct ligated rats (4.7 pM) was significantly higher than that in 7-d bile diverted rats (1.6 pM), although the pancreatic wet weight, protein concentration, and total content were comparable for the two groups. It was suggested that the presence of bile in the duodenum is required to maintain normal pancreatic secretion, and that the removal of bile from the intestine has quite different effects, depending on whether the bile flow is obstructed or diverted.


High Frequency Deep Brain Stimulation and Neural Rhythms in Parkinson's Disease.
High frequency (HF) deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease (PD). It effectively treats the cardinal motor signs of PD, including tremor, bradykinesia, and rigidity. The most common neural target is the subthalamic nucleus, located within the basal ganglia, the region most acutely affected by PD pathology. Using chronically-implanted DBS electrodes, researchers have been able to record underlying neural rhythms from several nodes in the PD network as well as perturb it using DBS to measure the ensuing neural and behavioral effects, both acutely and over time. In this review, we provide an overview of the PD neural network, focusing on the pathophysiological signals that have been recorded from PD patients as well as the mechanisms underlying the therapeutic benefits of HF DBS. We then discuss evidence for the relationship between specific neural oscillations and symptoms of PD, including the aberrant relationships potentially underlying functional connectivity in PD as well as the use of different frequencies of stimulation to more specifically target certain symptoms. Finally, we briefly describe several current areas of investigation and how the ability to record neural data in ecologically-valid settings may allow researchers to explore the relationship between brain and behavior in an unprecedented manner, culminating in the future automation of neurostimulation therapy for the treatment of a variety of neuropsychiatric diseases.


A novel approach for quantitative analysis of intracoronary optical coherence tomography: high inter-observer agreement with computer-assisted contour detection.
This study aims to examine observer-related variability of quantitative optical coherence tomography (OCT) derived measurements from both in vitro and in vivo pullback data. Intravascular OCT is a new imaging modality using infrared light and offering 10 times higher image resolution (15 microm) compared to intravascular ultrasound. The quantitative analysis of in vivo intracoronary OCT imaging is complicated by the presence of blood, motion artifacts and the large quantity of information that has to be processed. We developed a standardized, automated quantification process for intracoronary OCT pullback data with inter-observer variability assessed both in vitro by using postmortem human coronary arteries and in vivo by studying simple and complex coronary pathology and outcomes following stent implantation. The consensus between measurements by two observers was analyzed using the intraclass and interclass correlation coefficient and the reliability coefficients. Bland-Altman plots were generated to assess the relationship between variability and absolute measurements. In vitro OCT assessment was performed in nine postmortem coronary arteries. The time needed for semiautomated contour detection of a 15-mm long coronary segment was approximately 40 min. The absolute and relative difference between lumen area measurements derived from two observers was low [0.02 +/- 0.10 mm(2); (0.3 +/- 0.5)% respectively] with excellent correlation confirmed by linear regression analysis (R(2) = 0.99; P < 0.001). Similarly, in vivo measurements demonstrated a high correlation with the main source of inter-observer variation occurring as a result of coronary dissection and motion artifact. The absolute and relative difference between measurements were 0.11 +/- 0.33 mm(2) (1.57 +/- 0.05)% for lumen area (R(2) = 0.98; P < 0.001), 0.17 +/- 0.68 mm(2) (1.44 +/- 0.08)% for stent area (R(2) = 0.94; P < 0.001), and 0.26 +/- 0.72 mm(2) (14.08 +/- 0.37)% for neointimal area (R(2) = 0.78; P < 0.001). Highly accurate computer-assisted quantitative analysis ofintracoronary OCT pullbacks is feasible with low inter-observer variability. The presented approach allows for observer independent analysis of detailed vessel structures, and may be a valuable tool for future longitudinal studies incorporating OCT.


[A rare diagnosis of an intrascrotal tumor: polyorchidism].
The authors report a new case of polyorchidism and review the literature. They discuss the different anatomo-clinical forms and the therapy of this rare anomaly.


Male-female differences in the setting and construction of violence among people with severe mental illness.
Data from a sample of severely and persistently mentally ill involuntary patients indicated that differences in violence between males and females in the 4 months prior to hospital admission depended on the measure. In the bivariate analysis, males had a greater prevalence of violence on the two indicators which separated more serious violence from lesser and no violence; but there was no gender difference on the more inclusive measure which incorporated threats and fights not involving weapons or injuries. In multivariate analysis when other relevant predictors were controlled, gender was significant in predicting only the most inclusive indicator of violence and only in interaction with substance abuse problems.


Radiograph ordering: agreement between the triage nurse and the physician in a pediatric emergency department.
We hypothesized that the triage nurse in a busy pediatric emergency department (ED) could accurately order radiographs, ultimately reducing patient waiting time. Protocols utilized to reduce patient waiting time are of importance in busy emergency departments. All patients registering at the ED of the Children's Hospital in a one-week period were entered into the study. The triage nurse documented whether they would send the patient for a radiograph, if allowed to, and were asked to designate a specific radiograph. The radiographs that were actually ordered by the physicians were subsequently obtained from radiology records. Data were analyzed for agreement beyond chance (kappa), positive (PPV) and negative predictive values. The results showed excellent agreement for extremity radiographs and poor agreement for nonextremity radiographs.


Framing heuristics in inclusive education: The case of Uganda's preservice teacher education programme.
Recent education-related research has raised concerns about the persistent exclusion of vulnerable learners in Uganda. The Revised Primary Teacher Education Curriculum of 2013 marked an ambitious yet inconclusive attempt to advance the implementation of inclusive education but has encountered deeply entrenched sociocultural exclusionary practices among education experts. This study aimed to explicate education practitioners' interpretations of Uganda's flagship inclusive education programme in preservice primary teacher education. Drawing on the conceptual vocabulary of frame analysis and the qualitative analysis of individual and group interviews and classroom observations, the interpretations of inclusive education implementation in preservice primary teacher education in Uganda were examined. The participants included policy design experts, curriculum design experts and classroom practitioners. Three main findings emerged. Firstly, interpretations of inclusive education displayed a narrow framing heuristic of inclusive education as a perfunctory, daily practice rather than a pathway for reflective, inclusive pedagogical engagement. Secondly, the heuristic encouraged the treatment of inclusive pedagogy as a 'label' under a specific rubric referring to sensory impairments or disabilities - a historical device for sociocultural exclusion. Thirdly, inclusive education was a praxis but was misframed from its original intentions, causing tension and resentment among practitioners. These findings contribute to the debates on the sustainability of inclusive education beyond preservice teacher education. Uganda's flagship inclusive education programme in preservice primary teacher education was fraught with tensions, ambiguities and an overt, urgent need for change.


Regulation of the heme A biosynthetic pathway in Saccharomyces cerevisiae.
Biosynthesis of heme A, a prosthetic group of cytochrome oxidase (COX), involves an initial farnesylation of heme B. The heme O product formed in this reaction is modified by hydroxylation of the methyl group at carbon C-8 of the porphyrin ring. This reaction was proposed to be catalyzed by Cox15p, ferredoxin, and ferredoxin reductase. Oxidation of the alcohol to the corresponding aldehyde yields heme A. In the present study we have assayed heme A and heme O in yeast COX mutants. The steady state concentrations of the two hemes in the different strains studied indicate that hydroxylation of heme O, catalyzed by Cox15p, is regulated either by a subunit or assembly intermediate of COX. The heme profiles of the mutants also suggest positive regulation of heme B farnesylation by the hydroxylated intermediate formed at the subsequent step or by Cox15p itself.


Single-molecule studies of riboswitch folding.
The folding dynamics of riboswitches are central to their ability to modulate gene expression in response to environmental cues. In most cases, a structural competition between the formation of a ligand-binding aptamer and an expression platform (or some other competing off-state) determines the regulatory outcome. Here, we review single-molecule studies of riboswitch folding and function, predominantly carried out using single-molecule FRET or optical trapping approaches. Recent results have supplied new insights into riboswitch folding energy landscapes, the mechanisms of ligand binding, the roles played by divalent ions, the applicability of hierarchical folding models, and kinetic vs. thermodynamic control schemes. We anticipate that future work, based on improved data sets and potentially combining multiple experimental techniques, will enable the development of more complete models for complex RNA folding processes. This article is part of a Special Issue entitled: Riboswitches.


Quality of Life in Food Allergy Patients and Their Families.
Pediatric food allergy is a growing health problem in the United States that has been found to adversely impact the quality of life of both affected children and their caregivers. This article provides a review of how food allergy affects the quality of life of patients and their families within the domains of school, social activities, relationships, and daily life. Efforts to improve food allergy-related quality of life among caregivers are also discussed.


Cytogenetic study of a group of workers exposed to thinner.
The frequency of sister-chromatid exchanges (SCE) was evaluated in a group of 24 workers exposed to thinner in a luminous advertisements factory and in three workshops for painting sheet metal in Mexico City. 50 metaphases for each exposed individual and each control were analysed; air samples of the working places were also studied; it was observed that among all the components of thinner, only benzene exceeded advisable limits. The cytogenetic data were subject to one-way analyses of variance indicating that no significant differences existed between both groups; also, there are no significant differences among workers with a long exposure time and those with fewer than 5 years of exposure. Nevertheless, use of tobacco increased significantly the SCE frequencies among the exposed group, but did not increase SCE in the control group.


Molecular genetic detection of female carriers of protan defects.
Females heterozygous for congenital colour vision defects are of interest because they are believed to have cone photoreceptor ratios and cone photopigments that differ from normal. We describe a molecular genetic method to identify protan carriers that involves characterizing the genes that occur in the most upstream position in each of the X-chromosome photopigment gene arrays.


Strategy for screening cognitive impairment in Chinese patients with amyotrophic lateral sclerosis.
It is an economical strategy to design a screening method to decide which patients with amyotrophic lateral sclerosis/ motor neuron disease (ALS/MND) should enter into the stage for further comprehensive neuropsychological investigation. 59 patients (including 8 with frank dementia) were recruited. They underwent the extensive neuropsychological evaluation and short screening batteries, namely the Mini-Mental State Examination (MMSE), the Peking Union Medical College Hospital version of Montreal Cognitive Assessment (MoCA-P) and the Frontal Assessment Battery (FAB). Results of the extensive neuropsychological evaluation were set as the gold standard to diagnose cognitive impairment, and the effectiveness of screening tests were measured against them. By comparing the sensitivity and specificity, we found that the combination of FAB plus both or either of the other 2 short batteries provided a satisfactorily high sensitivity, but none of these screening batteries was significantly associated with quantitative behavioral measurements among non-demented subjects, the Frontal Behavioral Inventory-ALS version (FBI-ALS). The combination of the FBI-ALS, the FAB, and the MMSE or the MoCA-P or both could effectively screen comorbid dementia, cognitive and behavioral impairment in ALS but this implicates a limited specificity. And the FAB needed to be validated in large Chinese sample.


Peroxisome Proliferator-Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats.
Early brain injury is proposed to be the primary cause of the poor outcome after subarachnoid hemorrhage (SAH), which is closely related to the neural apoptosis. To date, the relationship between peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and nuclear factor-κB/matrix metalloproteinase-9 (NF-κB/MMP-9) pathway, both of which are closely related to apoptotic effects, has been poorly studied in SAH. The present study was undertaken to evaluate the effects of PPARβ/δ on early brain injury and NF-κB/MMP-9 pathway after SAH in rats. SAH model was established by injecting nonheparinized autologous arterial blood into the prechiasmatic cistern in male Sprague-Dawley rats. Adenoviruses or small interfering RNAs were injected into the right lateral cerebral ventricle to, respectively, up- or downregulate PPARβ/δ expression before SAH. All animals were assessed with a neurological score and then killed at 24 hours after SAH surgery. The indexes of brain water content, blood-brain barrier permeability, and apoptosis were used to detect brain injury. The expression of PPARβ/δ, NF-κB, and MMP-9 were measured by immunohistochemistry, gelatin zymography, and Western Blot methods, respectively. In addition, GW0742, a specific agonist of PPARβ/δ, was used to treat SAH in rats, the effects of which were evaluated by neurological scoring and Evans blue extravasation. Overexpression of PPARβ/δ by adenoviruses treatment significantly ameliorated brain injury with improvement in neurological deficits, brain edema, blood-brain barrier impairment, and neural cell apoptosis at 24 hours after SAH in rats, whereas downregulation of PPARβ/δ by small interfering RNAs administration resulted in the reverse effects of the above. The expression levels of NF-κB and MMP-9 were markedly downregulated when PPARβ/δ increased after PPARβ/δ adenovirus transfection and upregulated when PPARβ/δ decreased by PPARβ/δ small interfering RNAs treatment. Moreover, GW0742 improved neurological deficits and reduced Evans blue extravasation at 24 hours after SAH. PPARβ/δ's overexpression may attenuate early brain injury after rats' SAH administration, which reduces neural apoptosis possibly through blocking NF-κB/MMP-9 pathway.


Predictive processing: Is the future just a memory?
Predictive processing seems like a radical departure from traditional theories of information processing in the brain, but a broader view of predictions highlights many similarities with standard frameworks. Predictive processing is memory and competitive bias in a new outlook-and we should use this correspondence to advance research on both fronts.


Implementing intimate partner violence (IPV) screening within emergency departments - Barriers, challenges and enablers experienced by intimate partner violence practice change champions.
To identify the barriers, challenges, and enablers that clinical champions experience whilst implementing Intimate Partner Violence (IPV) screening within Emergency Departments (EDs). Champions support the introduction of IPV screening within EDs. This paper shares new knowledge about IPV practice change champions: barriers, challenges and enablers they experienced in their efforts. Between 2017-2019, semi structured qualitative interviews were conducted with 23 individuals who identified as champions, working to introduce routine IPV in two rural tertiary hospital Emergency Departments. An interpretive framework and process of constant comparison was used to thematically analyse data from transcribed interviews. Champions identified barriers, challenges, and enablers that they experienced. Enablers included: support for the work of champions; champion leadership and collegiality; and training for the champion role. Challenges and Barriers included: resistance to a change in the focus of practice; and workflow and workload. Nurse champions can effectively support IPV practice change but face certain barriers, challenges and enablers. Nurse managers can use this information to support champions to undertake their role effectively in order to better meet the needs of individuals experiencing IPV.


Value of placental volume and vascular flow indices as predictors of intrauterine growth retardation.
To evaluate the utility of first-trimester placental volume and vascular flow indices to predict intrauterine growth retardation (IUGR). In 1004 singleton pregnancies attending routine care we recorded maternal characteristics, biophysical and biochemical factors included in the first trimester screening for aneuploidy (FTSA) and uterine artery pulsatility index (PI). Placental volume, Vascularization Index, Flow Index and Vascularization Flow Index were obtained. Customized curves were used to define IUGR. We compared pregnancies with and without IUGR. The performance of different predictive models was described by the areas under the receiver operator characteristic (AUROC) curve. Predictive models of IUGR were compared using a two by two approach and subset analysis was performed. Placental volume and all vascular indices were significantly lower (p<0.001, p≤0.01), and uterine artery PI higher (p<0.001), in pregnancies with IUGR, with and without associated pre-eclampsia. obtained in the analysis of homogeneous subsets showed that the effectiveness of combined predictive models for IUGR improved significantly after adding vascular indices or placental volume to maternal characteristics, FTSA variables and uterine artery PI (AUROC curve value 0.703 (95% CI 0.663-0.744) versus 0.720 (95% CI 0.681-0.759) and 0.735 (95% CI 0.696-0.733), respectively). The most effective model at first trimester was that which included only maternal characteristics, uterine a-PI and placental volume, similar to that of the most complex model built with all the factors analyzed in this study AUROC curve value 0.735 (95% CI 0.696-0.773). Placental volume and vascular indices were predictors factors of IUGR at first trimester. The effectiveness of combined predictive models for IUGR increased significantly after adding these factors, but the sensitivity of these models was too low for them to be considered useful in clinical practice.


Comparative biochemical responses and antioxidant activities of the rabbit urinary bladder to whole grapes versus resveratrol.
The objective of this study is to compare the antioxidant activity of a whole-grape suspension with the antioxidant activity or pure resveratrol on the effect of hydrogen peroxide (H2O2) on malondialdehyde (MDA) generation, choline acetyltransferase (ChAT) activity, calcium ATPase activity, and sarcoendoplasmic reticular ATPase (SERCA) of the male rabbit urinary bladder. MDA was used as a model for the effect of H2O2 on lipid peroxidation. ChAT, SERCA, and calcium ATPase were evaluated based on their importance in urinary bladder physiology and pathology. Four male rabbit bladders were used. Each bladder was separated into muscle and mucosa, frozen under liquid nitrogen and stored at -80 °C for biochemical evaluation. The effect of H2O2 on the enzymes listed above was determined in the presence and absence of either resveratrol or a whole-grape suspension. (1) Resveratrol was significantly more effective than the grape suspension at protecting the bladder muscle and mucosa against peroxidation as quantitated by MDA formation. (2) The grape suspension was significantly more effective at protecting ChAT activity against oxidative stress of the muscle than resveratrol. (3) Neither the grape suspension nor resveratrol were particularly effective at protecting the bladder muscle or mucosa calcium ATPase or SERCA against oxidative stress. (4) ChAT was significantly more sensitive to oxidative stress than either calcium ATPase or SERCA. These data support the idea that the grape suspension protects the mitochondria and nerve terminals to a significantly greater degree than resveratrol which suggests that the activities of the grape suspension are due to the combination of active components found in the grape suspension and not just resveratrol alone.


Mapping quantitative trait loci for yield-related traits and predicting candidate genes for grain weight in maize.
Quantitative trait loci (QTLs) mapped in different genetic populations are of great significance for marker-assisted breeding. In this study, an F2:3 population were developed from the crossing of two maize inbred lines SG-5 and SG-7 and applied to QTL mapping for seven yield-related traits. The seven traits included 100-kernel weight, ear length, ear diameter, cob diameter, kernel row number, ear weight, and grain weight per plant. Based on an ultra-high density linkage map, a total of thirty-three QTLs were detected for the seven studied traits with composite interval mapping (CIM) method, and fifty-four QTLs were indentified with genome-wide composite interval mapping (GCIM) methods. For these QTLs, Fourteen were both detected by CIM and GCIM methods. Besides, eight of the thirty QTLs detected by CIM were identical to those previously mapped using a F2 population (generating from the same cross as the mapping population in this study), and fifteen were identical to the reported QTLs in other recent studies. For the fifty-four QTLs detected by GCIM, five of them were consistent with the QTLs mapped in the F2 population of SG-5 × SG-7, and twenty one had been reported in other recent studies. The stable QTLs associated with grain weight were located on maize chromosomes 2, 5, 7, and 9. In addition, differentially expressed genes (DEGs) between SG-5 and SG-7 were obtained from the transcriptomic profiling of grain at different developmental stages and overlaid onto the stable QTLs intervals to predict candidate genes for grain weight in maize. In the physical intervals of confirmed QTLs qKW-7, qEW-9, qEW-10, qGWP-6, qGWP-8, qGWP-10, qGWP-11 and qGWP-12, there were 213 DEGs in total. Finally, eight genes were predicted as candidate genes for grain size/weight. In summary, the stable QTLs would be reliable and the candidate genes predicted would be benefit for maker assisted breeding or cloning.


Anticholinergic Medications and Parent-Reported Anticholinergic Symptoms in Neurologically Impaired Children.
Children with severe neurological impairment and polypharmacy are exposed to anticholinergic (AC) medications that may have anticholinergic side effects, but this is understudied. Anticholinergic Cognitive Burden (ACB) scores measure total anticholinergic burden for a medication regimen, and scores ≥3 have been associated with increased morbidity and mortality in adults. We assessed the relationship between ACB scores and parent-reported anticholinergic symptoms in children. Cross-sectional study of patients one to 18 years-old with ICD-defined severe neurological impairment and polypharmacy. At routine clinical visits, total ACB scores were computed for all medications. Parent-reported AC symptoms (constipation, drowsiness, difficulty concentrating, dry mouth, or urinary problems) were assessed. Multivariable logistic regression was used to test the association between total ACB scores ≥3 for scheduled medications and the presence of AC symptoms, adjusted for age and recent acute healthcare utilization. Among 123 unique patients, 87% were prescribed AC medications. Common AC medication classes included: systemic antihistamines (64%), anxiolytics (53%), antidepressants (30%), H2 blockers (22%), and muscle relaxants (20%). Total ACB scores ≥3 were observed in 44% for scheduled medications and in 63% of patients for scheduled plus PRN medications. Total ACB scores ≥3 were significantly associated with an increased odds of ≥1 anticholinergic symptoms for scheduled medications (OR: 3.1; 95% CI: 1.4, 6.7) and for scheduled plus PRN medications (OR: 2.9; 95% CI: 1.3, 6.4). If replicated in larger populations, the association between elevated total ACB scores and anticholinergic side effects in children should prompt clinicians to consider deprescribing potentially unneeded anticholinergic medications.


Carnitine prevention of adriamycin toxicity in mice.
Carnitine, a naturally occurring nontoxic compound which aids the myocardial cell in efficiently meeting energy requirements, has been evaluated as a possible protective agent against acute and chronic adriamycin induced mouse toxicity. We have shown that carnitine treatment significantly decreases both acute high dose and chronic, intermittent, low dose adriamycin associated lethality in normal mice. These protective effects are accomplished without decreasing adriamycin anti-tumor activity or increasing bone marrow toxicity.


Oculomotor apraxia: the presenting sign of Gaucher disease.
Oculomotor apraxia may be idiopathic or a symptom of a variety of diseases. In Gaucher disease, oculomotor deficit is characterized by a failure of volitional horizontal gaze with preservation of vertical movements. We present 2 sisters, 6 1/2 and 5 1/2 years of age, in whom the presenting sign was oculomotor apraxia. Oculomotor apraxia has not been previously reported as the presenting manifestation of Gaucher disease.


Regulation of human ornithine decarboxylase expression by the c-Myc.Max protein complex.
The presence of a CACGTG element within a region of the human ornithine decarboxylase (ODC) promoter located at -491 to -474 base pairs 5' to the start site of transcription suggested that the c-Myc.Max protein complex may play a role in the regulation of ODC expression during growth. Electrophoretic mobility shift assays and methylation interference analysis showed that the nuclei of WI-38 cells expressing ODC contained proteins that bound to this region of the ODC gene in a manner that correlated with growth-associated ODC expression. Also, use of antibodies against c-Myc and Max and purified recombinant c-Myc and Max protein in the electrophoretic mobility shift assay confirmed that these proteins can specifically bind this portion of the human ODC promoter. Transient transfection studies showed that increase in the level of c-Myc and/or Max led to a significant enhancement of expression of a human ODC promoter-CAT reporter construct. Moreover, treatment of actively growing WI-38 cells with an antisense oligomer to c-Myc reduced the amount of endogenous protein complex formed and the amount of endogenous ODC mRNA expressed. These studies show that the c-Myc.Max protein complex plays a role in the transcriptional regulation of human ODC in vivo.