Use of laboratory testing for genital chlamydial infection in Norway.
To assess the use of laboratory tests for genital chlamydial infection in Norway. Questionnaire survey of general practitioners' practice in chlamydial testing, retrospective survey of laboratory records, 1986-91, and prospective study of testing in one laboratory during four weeks. All 18 microbiological laboratories in Norway (4.2 million population), including one serving all doctors in Vestfold county (0.2 million population). 302 general practitioners. GPs' routine practice, methods used for testing, 1986-91, and sex specific and age group specific testing in 1991. 201(69%) GPs replied to the questionnaire: 101(51%) would test all women younger than 25 years at routine pelvic examination, 107(54%) all girls at first pelvic examination, 131(66%) all pregnant women, and 106(54%) all men whose female partner had urogenital complaints. Nationwide in 1986, 122,000 tests were performed (2.9 per 100 population); 10% were positive and 51% were cell culture tests. In 1991, 341,000 tests were performed (8.0 per 100 population); 4.5% were positive and 15% were cell culture tests. 13,184 tests were performed in Vestfold in 1991 (6.6 per 100 population). The age group specific rates (per 100 population) among women were: age 15-19 years, 22.0(95% confidence interval 18.2 to 25.8); 20-24 years, 47.2(42.1 to 52.3); 25-29 years, 42.3(37.1 to 47.5); 30-34 years, 29.8(25.4 to 34.2); and 35-39 years, 12.5(9.5 to 15.5). GPs use liberal indications for testing. The dramatic increase in testing, especially by enzyme immunoassays, in populations with a low prevalence of infection results in low cost effectiveness and low predictive value of positive tests, which in women over 29 years is estimated as 17-36%. Doctors should be educated about the limitations of enzyme immunoassays in screening low prevalence populations, and laboratories should apply a confirmatory test to specimens testing positive with such assays.


[Nitrogen input altered testate amoebae community in peatland of Sanjiang Plain, Northeast China].
In the present study, an in situ control experiment was carried out to explore the response of testate amoebae to exogenous nitrogen addition in peatland of Sanjiang Plain. The results showed that nitrogen addition increased the biomass of testate amoebae at lower levels (6 g N · m(-2)), while decreased it at higher levels (> 12 g N · m(-2)). At genus level, nitrogen addition significantly increased the biomass of Arcella and Phryganella, decreased the biomass of Euglypha. Only lower nitrogen addition significantly increased the biomass of Centropyxis. At species level, nitrogen addition significantly decreased the biomass of Euglypha rotunda, while the biomass of either Centropyxis cassis or Phryganella acropodia was increased by a lower nitrogen addition treatment. This study suggested that the response of peatland testate amoebae to nitrogen addition was species specific, which could potentially be used as an indicator for the environment of peatlands.


The experiences of spirituality among adults with mental health difficulties: a qualitative systematic review.
Despite an increasing awareness of the importance of spirituality in mental health contexts, a 'religiosity gap' exists in the difference in the value placed on spirituality and religion by professionals compared with service users. This may be due to a lack of understanding about the complex ways people connect with spirituality within contemporary society and mental health contexts, and can result in people's spiritual needs being neglected, dismissed or pathologised within clinical practice. The aim of this qualitative systematic review is to characterise the experiences of spirituality among adults with mental health difficulties in published qualitative research. An electronic search of seven databases was conducted along with forward and backward citation searching, expert consultation and hand-searching of journals. Thirty-eight studies were included from 4944 reviewed papers. The review protocol was pre-registered (PROSPERO:CRD42017080566). A thematic synthesis identified six key themes: Meaning-making (sub-themes: Multiple explanations; Developmental journey; Destiny v. autonomy), Identity, Service-provision, Talk about it, Interaction with symptoms (sub-themes: Interactive meaning-making; Spiritual disruption) and Coping (sub-themes: Spiritual practices; Spiritual relationship; Spiritual struggles; Preventing suicide), giving the acronym MISTIC. This qualitative systematic review provides evidence of the significant role spirituality plays in the lives of many people who experience mental health difficulties. It indicates the importance of mental health professionals being aware of and prepared to support the spiritual dimension of people using services. The production of a theory-based framework can inform efforts by health providers to understand and address people's spiritual needs as part of an integrated holistic approach towards care.


Collision-Induced Unfolding, Tandem MS, Bottom-up Proteomics, and Interactomics for Identification of Protein Complexes in Native Surface Mass Spectrometry.
Endogenously occurring salts and nonvolatile matrix components in untreated biological surfaces can suppress protein ionization and promote adduct formation, challenging protein identification. Characterization of labile proteins within biological specimens is particularly demanding because additional purification or sample treatment steps can be time-intensive and can disrupt noncovalent interactions. It is demonstrated that the combined use of collision-induced unfolding, tandem mass spectrometry, and bottom-up proteomics improves protein characterization in native surface mass spectrometry (NSMS). This multiprong analysis is achieved by acquiring NSMS, MS/MS, ion mobility (IM), and bottom-up proteomics data from a single surface extracted sample. The validity of this multiprong approach was confirmed by the successful characterization of nine surface-deposited proteins, with molecular weights ranging from 8 to 147 kDa, in two separate mixtures. Bottom-up proteomics provided a list of proteins to match against observed proteins in NSMS and their detected subunits in tandem MS. The method was applied to characterize endogenous proteins from untreated chicken liver samples. The subcapsular liver sampling for NSMS analysis allowed for the detection of endogenous proteins with molecular weights of up to ∼220 kDa. Moreover, using IM-MS, collision cross sections and collision-induced unfolding pathways of enzymatic proteins and protein complexes of up to 145 kDa were obtained.


[Participation of neurons of the midbrain reticular formation of the cat in conditioned reflex activity].
Spike discharges of mesencephalic reticular formation neurons were investigated during classical and instrumental conditional reflexes in chronic experiments on cats. Neurons were divided into several functional groups according to patterns of their responses. Two groups of neurons produced continuous tonic spike discharges. One of them was activated by positive conditional stimuli and did not respond to the same stimulus after extinction. Another group was involved in reaction only after extinction. Thus the neurons of these two groups developed additional tonic ascending action not only during fulfillment of conditional reflex but under its internal inhibition too. Neurons of the third group revealed double phasic responses: the first--to sound and the second--in connection with initiation of the conditioned movement. They decreased the level of the background and evoked activity during differentiation and extinction. Initial changes of reticular neuron responses were similar under conditioning and under pseudoconditioning. It is concluded that mesencephalic reticular formation takes an active and differential participation in elaboration, fulfillment and internal inhibition of classical and instrumental conditional reflexes.


ERBB2 S310F mutation independently activates PI3K/AKT and MAPK pathways through homodimers to contribute gallbladder carcinoma growth.
Genomic instability and mutability are a prominent character of tumor. The whole-exosome sequence reveals that ERBB2 mutations are the representative mutations of gallbladder carcinoma, which takes potential targets for gallbladder carcinoma therapy. However, the roles of ERBB2 mutations are unclear in gallbladder carcinoma. We identified S310F mutation is the hottest mutation of ERBB2 mutations from TCGA PanCancer Altas data with 10,967 samples and our previous study with 157 gallbladder carcinoma samples. S310F mutation located in ERBB2 extracellular domain, promoted ERBB2 homodimerization and consequent auto-phosphorylation to activate the downstream PI3K/AKT and MAPK pathways, which was independent on ERBB1, ERBB3, and ERBB4. ERBB2 S310F mutation up-regulated aerobic glycolysis and promoted gallbladder carcinoma growth. Our study reveals the roles of ERBB2 S310F mutation, which is beneficial to ERBB2 S310F mutant gallbladder carcinoma therapy.


Quantitative analysis of the high temperature-induced glycolytic flux increase in Saccharomyces cerevisiae reveals dominant metabolic regulation.
A major challenge in systems biology lies in the integration of processes occurring at different levels, such as transcription, translation, and metabolism, to understand the functioning of a living cell in its environment. We studied the high temperature-induced glycolytic flux increase in Saccharomyces cerevisiae and investigated the regulatory mechanisms underlying this increase. We used glucose-limited chemostat cultures to separate regulatory effects of temperature from effects on growth rate. Growth at increased temperature (38 degrees C versus 30 degrees C) resulted in a strongly increased glycolytic flux, accompanied by a switch from respiration to a partially fermentative metabolism. We observed an increased flux through all enzymes, ranging from 5- to 10-fold. We quantified the contributions of direct temperature effects on enzyme activities, the gene expression cascade and shifts in the metabolic network, to the increased flux through each enzyme. To do this we adapted flux regulation analysis. We show that the direct effect of temperature on enzyme kinetics can be included as a separate term. Together with hierarchical regulation and metabolic regulation, this term explains the total flux change between two steady states. Surprisingly, the effect of the cultivation temperature on enzyme catalytic capacity, both directly through the Arrhenius effect and indirectly through adapted gene expression, is only a moderate contribution to the increased glycolytic flux for most enzymes. The changes in flux are therefore largely caused by changes in the interaction of the enzymes with substrates, products, and effectors.


Violent firearm-related conflicts among high-risk youth: An event-level and daily calendar analysis.
Firearm homicide is the leading cause of violence-related youth mortality. To inform prevention efforts, we analyzed event-level data to identify unique precursors to firearm conflicts. Youth (ages:14-24) seeking Emergency Department (ED) treatment for assault or for other reasons and reporting past 6-month drug use were enrolled in a 2-year longitudinal study. Time-line follow-back substance use/aggression modules were administered at baseline and each 6-month follow-up. Violent non-partner conflicts were combined across time-points. Regression analyzed: a)antecedents of firearm-related conflicts (i.e., threats/use) as compared to non-firearm conflicts; and b)substance use on conflict (vs. non-conflict) days for those engaged in firearm conflict. During the 24-months, we found that 421-youth reported involvement in violent non-partner conflict (n=829-conflicts;197-firearm/632-non-firearm). Among firearm conflicts, 24.9% involved aggression and 92.9% involved victimization. Retaliation was the most common motivation for firearm-aggression (51.0%), while "shot for no reason" (29.5%) and conflicts motivated by arguments over "personal belongings" (24.0%) were most common for firearm-victimization. Male sex (AOR=5.14), Black race (AOR=2.75), a ED visit for assault (AOR=3.46), marijuana use before the conflict (AOR=2.02), and conflicts motivated by retaliation (AOR=4.57) or personal belongings (AOR=2.28) increased the odds that a conflict involved firearms. Alcohol (AOR=2.80), marijuana (AOR=1.63), and prescription drugs (AOR=4.06) had a higher association with conflict (vs. non-conflict) days among youth reporting firearm conflict. Overall, we found that firearm conflicts are differentially associated with substance use and violence motivations. Addressing substance use, interrupting the cycle of retaliatory violence, and developing conflict resolution strategies that address escalation over infringement on personal belongings may aid in decreasing and preventing adolescent firearm violence.


Diurnal variation of DNA synthesis in premalignant hamster cheek pouch.
The right cheek pouch of hamsters was painted twice a week with DMBA for 4 and 7 weeks in different groups. It was found that there were diurnal rhythms and non-random distributions of DNA synthesis and mitotic events in DMBA-treated hamster-cheek-pouch epithelium. The degree of these changes was markedly greater than the changes in non-treated control pouches. The finding of cluster formation was described as 'symphokinesis', the non-random grouping of basal cells with synchronous DNA cycles during tissue growth.


Varicella-zoster virus glycoprotein gE: endocytosis and trafficking of the Fc receptor.
Varicella-zoster virus (VZV) encodes a functional cell membrane Fc receptor called glycoprotein gE. VZV gE resembles other mammalian cell membrane receptors, such as the mammalian Fc receptor. In further analyses by transient transfection, the cellular trafficking of VZV gE was compared to other cell surface receptors. VZV gE was shown to undergo endocytosis from the cell membrane when visualized by laser scanning confocal microscopy. The endocytosis and trafficking pathway of VZV gE followed closely the pathway defined for the human transferrin receptor. Receptor-mediated endocytosis of VZV gE was dependent on a YAGL motif in its cytoplasmic tail. In addition, VZV gE underwent receptor-mediated endocytosis when it bound the Fc portion of immunoglobulin. Thus, this detailed study of VZV gE cellular trafficking has revealed potential roles for gE during viral infection.


Ferroelastic domain switching dynamics under electrical and mechanical excitations.
In thin film ferroelectric devices, switching of ferroelastic domains can significantly enhance electromechanical response. Previous studies have shown disagreement regarding the mobility or immobility of ferroelastic domain walls, indicating that switching behaviour strongly depends on specific microstructures in ferroelectric systems. Here we study the switching dynamics of individual ferroelastic domains in thin Pb(Zr0.2,Ti0.8)O3 films under electrical and mechanical excitations by using in situ transmission electron microscopy and phase-field modelling. We find that ferroelastic domains can be effectively and permanently stabilized by dislocations at the substrate interface while similar domains at free surfaces without pinning dislocations can be removed by either electric or stress fields. For both electrical and mechanical switching, ferroelastic switching is found to occur most readily at the highly active needle points in ferroelastic domains. Our results provide new insights into the understanding of polarization switching dynamics as well as the engineering of ferroelectric devices.


Comparison of Bipolar and Monopolar Electrode Configurations for FES on Biceps Brachii.
Function electrical stimulation (FES) is recommended as one of the effective methods for rehabilitation of motor function after stroke. There are two forms to deliver electrical stimulation to induce muscle contraction: Bipolar electrode configuration with two electrodes of the same size, and monopolar electrode configuration with a bigger electrode as an indifferent electrode and a smaller one as an active electrode. The purpose of this study is to compare the two kinds of configuration on biceps brachii in terms of induced muscle contraction force and muscle fatigue. In the experiment, electrical stimulation was applied on biceps brachii muscles of the right arm. Isometric contraction was induced by fixing the elbow joint during the stimulation. The experimental results showed that the induced contraction force was bigger using monopolar electrode configuration with the indifferent electrode on the antagonist muscle, and there was no significant difference in muscle fatigue between the configurations. Monopolar electrode configuration with the indifferent electrode on the antagonist muscle was suggested as the most effective method for FES on biceps brachii.Clinical Relevance- This study establishes an effective electrode configuration for FES on biceps brachii.


Racial and ethnic differences in reproductive potential across the life cycle.
To review variations in specific reproductive health outcomes by race and ethnicity. A growing number of reports have explored potential gaps in the quality of reproductive health and healthcare across racial and ethnic groups. Diverse results from numerous investigations have made it challenging for practitioners to confirm the significance of these disparities. Three specific areas of the reproductive life cycle were examined: pubertal onset, outcomes from treatment with assisted reproductive technologies (ART), and the menopausal transition. These areas were selected as they encompass a continuum of events across the reproductive life span of women. Outcomes were compared in black, white, Asian, and Hispanic women. Medline searches querying on keywords puberty, IVF, ART, menopause, menopausal symptoms, racial disparity, race, Asian, Japanese, Chinese, African American, black, Hispanic, and Latino were performed to isolate relevant publications for review. Differences across race and ethnicity were noted in each clinical endpoint. The most notable findings included earlier puberty in blacks and Hispanics compared with whites, significantly lower live birth rates after ART in all racial and ethnic groups compared with whites, and differences in perimenopausal symptomatology and possibly timing in various racial/ethnic groups compared with whites. Additional research is needed to completely unravel the full significance and basic underpinnings of these disparities. Some of the limitations of the current state of the literature in drawing conclusions about the independent effect of race/ethnicity on reproductive disparities include small samples sizes in some studies, inconsistencies in the characterization of racial/ethnic groups, and incomplete control of potential confounding. Race and ethnicity appear to be important correlates of outcomes from the initiation of reproduction functioning through to its conclusion. The ultimate goal of identifying racial disparities in reproduction is to isolate the basic determinants of disparities and formulate strategies to improve outcomes for women at risk. The differences demonstrated in this review of the literature could represent environmental, sociocultural, and/or genetic correlates of race that influence these important milestones.


Protection against oxidative damage to CNS by alpha-phenyl-tert-butyl nitrone (PBN) and other spin-trapping agents: a novel series of nonlipid free radical scavengers.
Brain is extremely susceptible to oxidative damage. Utilizing a series of novel approaches, we have demonstrated that oxidative damage occurs during an ischemia/reperfusion insult (IRI) to brain. Thus, we have demonstrated that an IRI to Mongolian gerbil brain results in: (1) an enhanced rate of salicylate hydroxylation, implicating an increased flux of hydroxyl free radicals; (2) an enhanced flux of free radicals as determined by spin-trapping; (3) an enhanced level of endogenous protein oxidation; (4) a decrease in glutamine synthetase (GS) activity, an enzyme very sensitive to oxidative damage; and (5) demonstration of protection from an IRI by administering the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN). The novel observation that PBN offers protection from the lethality brought on by a brain IRI appears to be clearly linked to the ability of the administered spin-trap to inhibit oxidative damage as evidenced by the decreased amount of brain protein oxidation and the prevention of an IRI-mediated loss of GS activity in treated animals. Aged gerbils are more sensitive to the lethal action of a brain IRI than younger animals, but they are protected by PBN administration as are the younger animals. Older gerbils have a significantly higher level of oxidized protein in the brain. Older gerbils have decreased activities of GS and neutral protease, the enzyme that removes oxidized protein, than younger animals. Chronic twice daily administration of PBN (32 mg/kg) for 14 days to older animals significantly lowered brain oxidized protein levels and raised GS and neutral protease activity to those observed in younger animals. Cessation of PBN administration resulted in a time-dependent restoration of protein oxidation levels and enzyme activities back to those observed prior to spin-trap administration. Older gerbils exhibit significantly higher errors in a radial arm maze than younger animals, but older gerbils that had received chronic daily treatments of PBN (32 mg/kg) for 14 days committed significantly less errors than untreated controls. The errors committed in PBN-treated animals was decreased down to the level of those observed in younger animals. Clearly the spin-trapping agent, PBN, appears to have promise in: (1) elucidation of the role of oxidative damage in normal brain function during aging, (2) understanding the development of pathological conditions, and (3) development of treatment regimens for prevention of damage that occurs during the development of pathological conditions and in aging.


NADPH oxidase activation by hyperglycaemia in cardiomyocytes is independent of glucose metabolism but requires SGLT1.
Exposure to high glucose (HG) stimulates reactive oxygen species (ROS) production by NADPH oxidase in cardiomyocytes, but the underlying mechanism remains elusive. In this study, we have dissected the link between glucose transport and metabolism and NADPH oxidase activation under hyperglycaemic conditions. Primary cultures of adult rat cardiomyocytes were exposed to HG concentration (HG, 21 mM) and compared with the normal glucose level (LG, 5 mM). HG exposure activated Rac1GTP and induced p47phox translocation to the plasma membrane, resulting in NADPH oxidase (NOX2) activation, increased ROS production, insulin resistance, and eventually cell death. Comparison of the level of O-linked N-acetylglucosamine (O-GlcNAc) residues in LG- and HG-treated cells did not reveal any significant difference. Inhibition of the pentose phosphate pathway (PPP) by 6-aminonicotinamide counteracted ROS production in response to HG but did not prevent Rac-1 upregulation and p47phox translocation leading to NOX2 activation. Modulation of glucose uptake barely affected oxidative stress and toxicity induced by HG. More interestingly, non-metabolizable glucose analogues (i.e. 3-O-methyl-D-glucopyranoside and α-methyl-D-glucopyranoside) reproduced the toxic effect of HG. Inhibition of the sodium/glucose cotransporter SGLT1 by phlorizin counteracted HG-induced NOX2 activation and ROS production. Increased glucose metabolism by itself does not trigger NADPH oxidase activation, although PPP is required to provide NOX2 with NADPH and to produce ROS. NOX2 activation results from glucose transport through SGLT1, suggesting that an extracellular metabolic signal transduces into an intracellular ionic signal.


Mobilization of arsenic and other naturally occurring contaminants in groundwater of the Main Ethiopian Rift aquifers.
This study investigates the mechanisms of arsenic (As) and other naturally occurring contaminants (F(-), U, V, B, and Mo) mobilization from Quaternary sedimentary aquifers of the Main Ethiopian Rift (MER) and their enrichment in the local groundwater. The study is based on systematic measurements of major and trace elements as well as stable oxygen and hydrogen isotopes in groundwater, coupled with geochemical and mineralogical analyses of the aquifer rocks. The Rift Valley aquifer is composed of rhyolitic volcanics and Quaternary lacustrine sediments. X-ray fluorescence (XRF) results revealed that MER rhyolites (ash, tuff, pumice and ignimbrite) and sediments contain on average 72 wt. % and 65 wt. % SiO2, respectively. Petrographic studies of the rhyolites indicate predominance of volcanic glass, sanidine, pyroxene, Fe-oxides and plagioclase. The As content in the lacustrine sediments (mean = 6.6 mg/kg) was higher than that of the rhyolites (mean: 2.5 mg/kg). The lacustrine aquifers of the Ziway-Shala basin in the northern part of MER were identified as high As risk zones, where mean As concentration in groundwater was 22.4 ± 33.5 (range of 0.60-190 μg/L) and 54% of samples had As above the WHO drinking water guideline value of 10 μg/L. Field As speciation measurements showed that most of the groundwater samples contain predominantly (~80%) arsenate-As(V) over arsenite-As(III) species. The As speciation together with field data of redox potential (mean Eh = +73 ± 65 mV) and dissolved-O2 (6.6 ± 2.2 mg/L) suggest that the aquifer is predominantly oxidative. Water-rock interactions, including the dissolution of volcanic glass produces groundwater with near-neutral to alkaline pH (range 6.9-8.9), predominance of Na-HCO3 ions, and high concentration of SiO2 (mean: 85.8 ± 11.3 mg/L). The groundwater data show high positive correlation of As with Na, HCO3, U, B, V, and Mo (R(2) > 0.5; p < 0.001). Chemical modeling of the groundwater indicates that Fe-oxides and oxyhydroxides minerals were saturated in the groundwater, suggesting that the As reactivity is controlled by adsorption/desorption processes with these minerals. The data show that As and other oxyanion-forming elements such as U, B, Mo, and V had typically higher concentrations at pH > ~8, reflecting the pH-dependence of their mobilization. Based on the geochemical and stable isotope variations we have established a conceptual model for the occurrence of naturally occurring contaminants in MER groundwater: 1) regional groundwater recharge from the Highland, along the Rift margins, followed by lateral flow and water-rock interactions with the aquifer rocks resulted in a gradual increase of the salinity and naturally occurring contaminants towards the center of the valley; and (2) local δ(18)O-rich lake water recharge into adjacent shallow aquifers, followed by additional mobilization of As and other oxyanion-forming elements from the aquifer rocks. We posit that the combined physical-chemical conditions of the aquifers such as oxidizing state, Na-HCO3 composition, and pH>~8 lead to enhanced mobilization of oxyanion-forming elements from Fe-oxides and consequently contamination of local groundwater. These geochemical conditions characterize groundwater resources along the Eastern African Rift and thus constitute a potential threat to the quality of groundwater in larger areas of Eastern Africa.


Testing ChatGPT ability to answer laypeople questions about cardiac arrest and cardiopulmonary resuscitation.
Cardiac arrest leaves witnesses, survivors, and their relatives with a multitude of questions. When a young or a public figure is affected, interest around cardiac arrest and cardiopulmonary resuscitation (CPR) increases. ChatGPT allows everyone to obtain human-like responses on any topic. Due to the risks of accessing incorrect information, we assessed ChatGPT accuracy in answering laypeople questions about cardiac arrest and CPR. We co-produced a list of 40 questions with members of Sudden Cardiac Arrest UK covering all aspects of cardiac arrest and CPR. Answers provided by ChatGPT to each question were evaluated by professionals for their accuracy, by professionals and laypeople for their relevance, clarity, comprehensiveness, and overall value on a scale from 1 (poor) to 5 (excellent), and for readability. ChatGPT answers received an overall positive evaluation (4.3±0.7) by 14 professionals and 16 laypeople. Also, clarity (4.4±0.6), relevance (4.3±0.6), accuracy (4.0±0.6), and comprehensiveness (4.2±0.7) of answers was rated high. Professionals, however, rated overall value (4.0±0.5 vs 4.6±0.7; p=0.02) and comprehensiveness (3.9±0.6 vs 4.5±0.7; p=0.02) lower compared to laypeople. CPR-related answers consistently received a lower score across all parameters by professionals and laypeople. Readability was 'difficult' (median Flesch reading ease score of 34 [IQR 26-42]). ChatGPT provided largely accurate, relevant, and comprehensive answers to questions about cardiac arrest commonly asked by survivors, their relatives, and lay rescuers, except CPR-related answers that received the lowest scores. Large language model will play a significant role in the future and healthcare-related content generated should be monitored.


Metabolic response of soy pinitol on lipid-lowering, antioxidant and hepatoprotective action in hamsters fed-high fat and high cholesterol diet.
This study was performed to investigate the lipid-lowering, antioxidant, and hepato-protective effects of pinitol in dose-dependent manners in hamsters fed-high fat and high cholesterol (HFHC) diet. Pinitol supplementation (0.05%, P-I and 0.1% pinitol, P-II) with an HFHC diet (10% coconut oil plus 0.2% cholesterol) for 10 wks significantly lowered the white adipose tissue weights, hepatic lipid droplets, plasma glucose, total-cholesterol, nonHDL-cholesterol, total-cholesterol/HDL-cholesterol ratio, and hepatic lipid levels. Whereas it significantly increased the brown adipose tissue weight, plasma HDL-cholesterol, apolipoprotein A-I (apo A-I) concentrations, paraoxonase (PON) activity, and/or mRNA expression, compared to the HFHC control group. Plasma insulin and adiponectin levels were significantly lower and higher, respectively, in both P-I and P-II groups than the HFHC control group. Dietary pinitol significantly inhibited hepatic HMG-CoA reductase, acyl-CoA:cholesterol acyltransferase (ACAT), and cytochrome P4502E1 (CYP2E1) activities without altering their mRNA expressions compared to the control group. Pinitol significantly elevated the hepatic antioxidant enzyme activities, whereas it also significantly reduced the hepatic lipid peroxide and H2O2 production. Accordingly, these results indicate that both 0.05 and 0.1% pinitol supplementation may improve the lipid and antioxidant metabolism in HFHC diet-fed hamsters. In particular, pinitol supplementation was very effective on the elevation of antiatherogenic factors, including plasma HDL-cholesterol, apo A-I, adiponectin, and PON.


Epileptic seizures associated with syncope: Ictal bradycardia and ictal asystole.
Heart rate decrease during epileptic seizures is rare and should be considered in patients with unusual or refractory episodes of syncope or in patients with a history suggestive of both epilepsy and syncope. We systematically reviewed the literature to better understand the clinical signs and risk factors of ictal heart rate decreases. We performed a literature-search on "ictal bradycardia" and "ictal asystole" in Pubmed and added papers from the references and personal archives. Articles relating to animal studies, seizures without ictal decrease of heart rate, cases without simultaneous electroencephalography (EEG) and electrocardiography (ECG), convulsive syncopes, or cases with bradycardia before seizure onset and articles written in other languages than English, Dutch, German, French, or Spanish were excluded. Full texts of the remaining articles were screened for cases of ictal bradycardia or ictal asystole. Cases were selected on the basis of a self-designed quality score. The relationship of RR wave interval of at least 5 s, signs of syncope, and EEG signs of ischemia were analyzed with chi-square test and identifying 95% confidence intervals. Ictal bradycardia and ictal asystole predominantly occurred during focal seizures with loss of awareness (proportion in the combined group of bradycardia and asystole (p1 + 2) = 0.85) in people with mainly left lateralized (p1 + 2 = 0.64; p = 0.001) temporal lobe seizures (p1 + 2 = 0.91). Seizures with ictal asystole typically started with a heart rate decrease. During ictal asystole in the majority of cases, not only the clinical signs of syncope occurred (change of proportion (Δp) = 0.67; 95% CI: 0.48-0.86; p < 0.0001), i.e., interrupting the seizure semiology, but also the characteristic EEG signs of ischemia (Δp = 0.50; 95% CI: 0.26-0.74; p < 0.001). We found a statistically significant relation between signs of syncope and EEG signs of ischemia (Δp = -0.37; 95% CI: (-0.64)-(-0.10); p < 0.01) but not between duration of asystole (5 s) and either signs of syncope (Δp = -0.36; 95% CI: (-0.77)-0.05; p = 0.03) or EEG signs of ischemia (Δp = -0.37; 95% CI: (-1.07)-0.33; p = 0.16). In the ictal bradycardia syndrome, signs of syncope disrupt the semiology of ongoing seizures and are associated with EEG signs of brain ischemia and the duration of the cardiac arrhythmia.


αVβ3-integrin expression through ERK activation mediates cell attachment and is necessary for production of tumor necrosis factor alpha in monocytic THP-1 cells stimulated by phorbol myristate acetate.
Macrophages play a key role in inflammation. Activated macrophages express adhesion molecules and produce tumor necrosis factor alpha (TNFα). Integrins are the main adhesion molecules that mediate binding to the extracellular matrix and they are involved in intracellular pathways. In the present study, human monocytic THP-1 cell adhesion to uncoated plastic plate was examined to investigate the regulatory mechanism of TNFα secretion. Addition of phorbol myristate acetate (PMA) for THP-1 cell activation induced cell adhesion in parallel with TNFα production. Among the mitogen-activated protein kinase pathways, the protein kinase C (PKC)-extracellular signal-regulated kinase (ERK) pathway was involved in αVβ3-integrin expression and PMA-induced cell adhesion. Flow cytometry and reverse transcription - quantitative polymerase chain reaction analysis revealed increased expression of matrix-binding integrins including integrin-αVβ3. Blockade of αVβ3-integrin by a specific antibody suppressed cell adhesion and TNFα production. These findings indicate that TNFα production from THP-1 cells is PKC-ERK, αVβ3-integrin and adhesion-dependent and its related pathway could be a target for TNFα-related diseases.


A case of idiopathic hypertrophic pachymeningitis presenting with chronic headache and multiple cranial nerve palsies: A case report.
Idiopathic hypertrophic pachymeningitis (IHP) is a rare condition, characterized by a chronic fibrosing inflammatory process usually involving either the intracranial or spinal dura mater, but rarely both. Here, we report a rare case of IHP affecting both the intracranial and spinal dura mater. We also discussed the diagnosis, management, and outcome of IHP. We reviewed the case of a 60-year-old woman presenting with chronic headache, multiple cranial nerve palsies and gait disturbance. Magnetic resonance imaging (MRI) of her head revealed thickened and contrast-enhanced dura in the craniocervical region as well as obstructive hydrocephalus and cerebellar tonsillar herniation. The patient had a suboccipital craniectomy and posterior decompression through C1 plus a total laminectomy. The dura was partially resected to the extent of the bony decompression, and a duroplasty was performed. Microscopic examination of the surgically resected sample showed chronic inflammatory changes, lymphoplasmacytic cell infiltration, fibrous tissue hyperplasia, and hyaline degeneration. Blood tests to evaluate the secondary causes of hypertrophic pachymeningitis (HP) were unremarkable. Steroid was used to treat suspected IHP. Postoperatively, the patient showed gradual improvement in her headache, glossolalia, and bucking. Prior to discharge, a follow-up MRI showed improvement of the dura mater thickening. IHP is a chronic inflammatory disorder of the dura mater that usually causes neurological deficits. Clinical manifestations of IHP, MRI findings, and laboratory abnormalities are the essential components for making an accurate diagnosis. When the radiological or laboratory evaluation is uncertain, but neurological deficits are present, a prompt surgical approach should be considered. Postoperative steroid therapy and close observation for recurrence are necessary to ensure a good long-term outcome.


Application of hidden Markov random field approach for quantification of perfusion/diffusion mismatch in acute ischemic stroke.
The perfusion/diffusion 'mismatch model' in acute ischemic stroke provides the potential to more accurately understand the consequences of thrombolytic therapy on an individual patient basis. Few methods exist to quantify mismatch extent (ischemic penumbra) and none have shown a robust ability to predict infarcted tissue outcome. Hidden Markov random field (HMRF) approaches have been used successfully in many other applications. The aim of the study was to develop a method for rapid and reliable identification and quantification of perfusion/diffusion mismatch using an HMRF approach. An HMRF model was used in combination with automated contralateral identification to segment normal tissue from non-infarcted tissue with perfusion abnormality. The infarct was used as a seed point to initialize segmentation, along with the contralateral mirror tissue. The two seeds were then allowed to compete for ownership of all unclassified tissue. In addition, a novel method was presented for quantifying tissue salvageability by weighting the volume with the degree of hypoperfusion, allowing the penumbra voxels to contribute unequal potential damage estimates. Simulated and in vivo datasets were processed and compared with results from a conventional thresholding approach. Both simulated and in vivo experiments demonstrated a dramatic improvement in accuracy with the proposed technique. For the simulated dataset, the mean absolute error decreased from 171.9% with conventional thresholding to 2.9% for the delay-weighted HMRF approach. For the in vivo dataset, the mean absolute error decreased from 564.6% for thresholding to 34.2% for the delay-weighted HMRF approach. The described method represents a significant improvement over thresholding techniques.


Creation of a Geospatially Explicit, Agent-based Model of a Regional Healthcare Network with Application to Clostridioides difficile Infection.
Agent-based models (ABMs) describe and simulate complex systems comprising unique agents, or individuals, while accounting for geospatial and temporal variability among dynamic processes. ABMs are increasingly used to study healthcare-associated infections (ie, infections acquired during admission to a healthcare facility), including Clostridioides difficile infection, currently the most common healthcare-associated infection in the United States. The overall burden and transmission dynamics of healthcare-associated infections, including C difficile infection, may be influenced by community sources and movement of people among healthcare facilities and communities. These complex dynamics warrant geospatially explicit ABMs that extend beyond single healthcare facilities to include entire systems (eg, hospitals, nursing homes and extended care facilities, the community). The agents in ABMs can be built on a synthetic population, a model-generated representation of the actual population with associated spatial (eg, home residence), temporal (eg, change in location over time), and nonspatial (eg, sociodemographic features) attributes. We describe our methods to create a geospatially explicit ABM of a major regional healthcare network using a synthetic population as microdata input. We illustrate agent movement in the healthcare network and the community, informed by patient-level medical records, aggregate hospital discharge data, healthcare facility licensing data, and published literature. We apply the ABM output to visualize agent movement in the healthcare network and the community served by the network. We provide an application example of the ABM to C difficile infection using a natural history submodel. We discuss the ABM's potential to detect network areas where disease risk is high; simulate and evaluate interventions to protect public health; adapt to other geographic locations and healthcare-associated infections, including emerging pathogens; and meaningfully translate results to public health practitioners, healthcare providers, and policymakers.


Elevation of creatine kinase is associated with acute kidney injury in hospitalized patients infected with seasonal influenza virus.
Although acute kidney injury (AKI) is known as a potential complication of influenza infections, there is limited information concerning the association between influenza and AKI. The aim of this study is to evaluate the incidence, the mortality, and risk factors of AKI in hospitalized patients by seasonal influenza viral infections. We performed a single center, retrospective observational study. 123 patients admitted to Iwata City Hospital due to influenza for 3 seasons were included. We examined the association between the incidence of AKI and clinical parameters using Spearman's correlation analyses, receiver-operating characteristic (ROC) curves, and multivariate logistic regression analyses. Of 123 patients, AKI developed in 46 patients (37.4%). Patients with AKI showed higher serum creatine kinase (CK, P < 0.001), higher creatinine (Cr, P < 0.001), and higher C-reactive protein (CRP) levels (P < 0.001) at admission and higher mortality rate (P < 0.05) compared with patients without AKI. The severity of kidney injuries was well correlated with serum CK levels (P < 0.001). By ROC curve analysis, 186 U/L was the most predictive value of CK levels for AKI (sensitivity, 0.674; specificity, 0.688; and area under the curve [AUC], 0.714). Multivariate logistic regression analyses revealed that elevated CK levels (> 186 U/L) were significantly associated with AKI (P < 0.01). The incidence of AKI and the mortality were high in hospitalized patients infected with seasonal influenza. The slight elevation of CK levels (> 186 U/L) at admission was associated with the development of AKI.


Gross, Background, and Net Anthropogenic Soil Nitrous Oxide Emissions from Soybean, Corn, and Wheat Croplands.
Agricultural soils are the largest single source of NO emissions globally. However, soils left uncultivated would still release NO. Distinguishing anthropogenic from natural emissions (i.e., background emissions) in crops is important if we want to assess the net effect of human activity. This study aimed to characterize NO emissions from croplands and unmanaged grasslands to estimate the net anthropogenic emissions and to gain a better insight into their main drivers. We established a replicated manipulative field experiment in the Pampas Region of Argentina to quantify soil NO emissions from corn ( L.), wheat ( L.), and soybean [ (L.) Merr.] crops, and from adjacent unmanaged grassland plots for 1 yr. We also analyzed the main controls of NO emissions and the correlation between the normalized difference vegetation index (NDVI) and NO fluxes. Background emissions represented between 21 and 32% of total emissions from croplands, depending on crop type. No differences were detected in NO emissions between total and background during winter and peak crop growing season. NDVI showed a significant correlation with NO fluxes which was positive in grasslands and negative in growing season of soybean crops. Our results showed that NO emissions from croplands were higher than background emissions, but also that background represented an important fraction of cropland emissions. Higher emissions in croplands occurred during pre-seeding, after harvest, and after N fertilization in fertilized crops. In addition, our study informs about NO emissions from crops and unmanaged systems in South America where field data are very scarce.


Papilionoid inflorescences revisited (Leguminosae-Papilionoideae).
The inflorescence structure determines the spatiotemporal arrangement of the flowers during anthesis and is therefore vital for reproductive success. The Leguminosae are among the largest angiosperm plant families and they include some important crop plants. In papilionoid legumes, the raceme is the most common type of inflorescence. However, a range of other inflorescence types have evolved via various developmental processes. A (re-)investigation of inflorescences in Swainsona formosa, Cicer arietinum, Abrus precatorius, Hardenbergia violacea and Kennedia nigricans leads to new insights into reduction mechanisms and to a new hypothesis on the evolution of the papilionoid pseudoraceme. Inflorescence morphology and ontogeny were studied using scanning electron microscopy (SEM). The inflorescence in S. formosa is an umbel with a rare type of pendulum symmetry which may be triggered by the subtending leaf. Inflorescences in C. arietinum are reduced to a single flower. An early formed adaxial bulge is the sterile apex of the inflorescence (i.e. the inflorescence is open and not terminated by a flower). In partial inflorescences of A. precatorius, the axis is reduced and its meristem is relocated towards the main inflorescence. Flower initiation follows a peculiar pendulum pattern. Partial inflorescences in H. violacea and in K. nigricans show reduction tendencies. In both taxa, initiated but early reduced bracteoles are present. Pendulum symmetry in S. formosa is probably associated with distichous phyllotaxis. In C. arietinum, strong reduction tendencies are revealed. Based on studies of A. precatorius, the papilionoid pseudoraceme is reinterpreted as a compound raceme with condensed lateral axes. From an Abrus-like inflorescence, other types can be derived via reduction of flower number and synchronization of flower development. A plea is made for uniform usage of inflorescence terminology.


DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation.
DNA methylation, histone modifications, and nucleosomal occupancy collaborate to cause silencing of tumor-related genes in cancer. The development of drugs that target these processes is therefore important for cancer therapy. Inhibitors of DNA methylation and histone deacetylation have been approved by the Food and Drug Administration for treatment of hematologic malignancies. However, drugs that target other mechanisms still need to be developed. Recently, 3-deazaneplanocin A (DZNep) was reported to selectively inhibit trimethylation of lysine 27 on histone H3 (H3K27me3) and lysine 20 on histone H4 (H4K20me3) as well as reactivate silenced genes in cancer cells. This finding opens the door to the pharmacologic inhibition of histone methylation. We therefore wanted to further study the mechanism of action of DZNep in cancer cells. Western blot analysis shows that DZNep globally inhibits histone methylation and is not selective. Two other drugs, sinefungin and adenosine dialdehyde, have similar effects as DZNep on H3K27me3. Intriguingly, chromatin immunoprecipitation of various histone modifications and microarray analysis show that DZNep acts through a different pathway than 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor. These observations give us interesting insight into how chromatin structure affects gene expression. We also determined the kinetics of gene activation to understand if the induced changes were somatically heritable. We found that upon removal of DZNep, gene expression is reduced to its original state. This suggests that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors.


Carpal tunnel syndrome: matching minimally invasive surgical techniques. Technical note.
In the past few years, several different minimally invasive surgical techniques have been proposed to decompress the median nerve at the wrist. Use of these techniques has become widespread due to fewer local complications, faster functional recovery, and reduced surgical time. In this paper the authors compare 3 different minimally invasive surgical techniques used at their institution in the past 13 years. Between January 1994 and January 2007, 891 patients underwent 1272 surgeries at the authors' institution for carpal tunnel syndrome (CTS), for which a minimally invasive technique was used. In 473 cases (Group A), the transillumination technique with a single wrist incision and a "carpalotome" (a modified Paine retinaculotome) was used; in 216 cases (Group B), transillumination was abandoned and a single linear wrist incision for access with the carpalotome was performed; and in 583 cases (Group C), the techniques were further modified by making a second incision in the palm using the carpalotome. All 3 groups of patients were homogeneous for age, sex, and duration of the symptomatology. In 90% of the patients in Group A, in 88% of those in Group B, and 99.8% of patients in Group C, complete remission of symptoms was obtained. Due to persistence of symptoms, 44 patients in Group A, 24 in Group B, and only 1 in Group C underwent a repeated operation with the open technique. The only surgical complication requiring repeated operation of the 1272 operations was a lesion of the primitive median artery (1 patient in Group C). The technique of median nerve decompression at the wrist that was used for patients in Group C represents a valid alternative for treatment of CTS.


Dye-doped biodegradable nanoparticle SiO2 coating on zinc- and iron-oxide nanoparticles to improve biocompatibility and for in vivo imaging studies.
In vivo imaging and therapy represent one of the most promising areas in nanomedicine. Particularly, the identification and localization of nanomaterials within cells and tissues are key issues to understand their interaction with biological components, namely their cell internalization route, intracellular destination, therapeutic activity and possible cytotoxicity. Here, we show the development of multifunctional nanoparticles (NPs) by providing luminescent functionality to zinc and iron oxide NPs. We describe simple synthesis methods based on modified Stöber procedures to incorporate fluorescent molecules on the surface of oxide NPs. These procedures involve the successful coating of NPs with size-controlled amorphous silica (SiO2) shells incorporating standard chromophores like fluorescein, rhodamine B or rhodamine B isothiocyanate. Specifically, spherical Fe3O4 NPs with an average size of 10 nm and commercial ZnO NPs (ca. 130 nm), both coated with an amorphous SiO2 shell of ca. 15 and 24 nm thickness, respectively, are presented. The magnetic nanoparticles, with a major presence of magnetite, show negligible coercitivity. Hence, interactions (dipolar) are very weak and the cores are in the superparamagnetic regime. Spectroscopic measurements confirm the presence of fluorescent molecules within the SiO2 shell, making these hybrid NPs suitable for bioimaging. Thus, our coating procedures improve NP dispersibility in physiological media and allow the identification and localization of intracellular ZnO and Fe3O4 NPs using confocal microscopy imaging preserving the fluorescence of the NP. We demonstrate how both Fe3O4 and ZnO NPs coated with luminescent SiO2 are internalized and accumulated in the cell cytoplasm after 24 hours. Besides, the SiO2 shell provides a platform for further functionalization that enables the design of targeted therapeutic strategies. Finally, we studied the degradation of the shell in different physiological environments, pointing out that the SiO2 coating is stable enough to reach the target cells maintaining its original structure. Degradation took place only 24 hours after exposure to different media.


Counterion controlled photoisomerization of retinal chromophore models: a computational investigation.
CASPT2//CASSCF photoisomerization path computations have been used to unveil the effects of an acetate counterion on the photochemistry of two retinal protonated Schiff base (PSB) models: the 2-cis-penta-2,4-dieniminium and the all-trans-epta-2,4,6-trieniminium cations. Different positions/orientations of the counterion have been investigated and related to (i) the spectral tuning and relative stability of the S0, S1, and S2 singlet states; (ii) the selection of the photochemically relevant excited state; (iii) the control of the radiationless decay and photoisomerization rates; and, finally, (iv) the control of the photoisomerization stereospecificity. A rationale for the results is given on the basis of a simple (electrostatic) qualitative model. We show that the model readily explains the computational results providing a qualitative explanation for different aspects of the experimentally observed "environment" dependent PSB photochemistry. Electrostatic effects likely involved in controlling retinal photoisomerization stereoselectivity in the protein are also discussed under the light of these results, and clues for a stereocontrolled electrostatically driven photochemical process are presented. These computations provide a rational basis for the formulation of a mechanistic model for photoisomerization electrostatic catalysis.


Primary breast carcinoma in patients with malignant melanoma.
Malignant melanoma and primary breast cancer are tumours which have an association based on genetic and hormonal factors. It is not generally appreciated that there is an increased incidence of melanoma in patients with breast cancer and vice versa. We present two cases of patients who developed breast carcinoma following previous treatment for melanoma. We review previous reports of this association and examine the theoretical reasons why this should be so. Medical practitioners should be aware of this association in order to alter their index of suspicion appropriately.


The effects of metformin on the fibrinolytic system in diabetic and non-diabetic subjects.
Type II (non-insulin dependent) diabetes is associated with a high incidence of vascular disease that causes morbidity and mortality. The principal organs affected by this process are the heart, brain and lower limbs. For many years it has been proposed that depression of the fibrinolytic system, which acts to maintain patency of blood vessels, may contribute to the development of vascular disease. A number of pharmacological agents have been shown to enhance circulating fibrinolytic activity of which metformin is perhaps the most interesting because of its low incidence of serious side effects. Early studies with metformin demonstrated an increase in global fibrinolytic activity in patients with coronary artery disease, peripheral vascular disease and diabetes. Recent studies using assays specific for the components of the fibrinolytic system have shown that the effects of metformin are to cause a fall in plasma levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1). There is evidence to suggest that the relationship between depressed fibrinolysis and vascular disease is due to high levels of PAI-1, and reasons to believe that a lowering of PAI-1 may be beneficial in this respect. Further studies are warranted to evaluate the long term effects of metformin warranted to evaluate the long term effects of metformin on the incidence of vascular disease in diabetic patients.


Effect of arteriolar dilation on coronary artery diameter distal to coronary stenoses.
Previous studies have suggested that worsening hemodynamic severity of coronary stenoses in response to distal arteriolar dilation may be related to dilation of the normal epicardial artery adjacent to the stenosis resulting in increasing percent stenosis. To test this hypothesis we used sonomicrometry to continuously measure external circumflex coronary artery diameter distal to snare stenoses of varying severity in 19 open-chest dogs and 5 awake, chronically instrumented dogs. Arteriolar dilation produced by release of a transient coronary occlusion or by intracoronary injection of adenosine caused a decrease in circumflex coronary diameter distal to the stenosis. Regression analysis showed that circumflex diameter and pressure distal to the stenosis were directly related (mean r: transient occlusion, 0.86 +/- 0.04; adenosine, 0.97 +/- 0.01). The close relationship between pressure and diameter suggests that the decrease in diameter in response to arteriolar dilation was a passive effect. Passive coronary narrowing distal to a stenosis suggests that a similar effect may occur within a compliant stenosis, thus partly explaining the increase in severity of compliant stenoses in response to arteriolar dilation.


Contemporary cost analysis of single instillation of mitomycin after transurethral resection of bladder tumor in a universal health care system.
Although recommended management strategy for nonmuscle-invasive bladder cancer (NMIBC) involves a single postoperative intravesical therapy with mitomycin C (MMC), it is uncommonly used among urologists, in part because of potential increased costs. Our objective was to perform a 5-year cost analysis of this strategy within a single-provider health care environment. A decision-analytic model was used. Input estimates for 5-year recurrence rates (50%) and MMC efficacy (absolute risk reduction of 17% and 12%) were identified via a systematic literature search and data from 2 meta-analyses. Direct costs included physician fees, MMC drug and preparation costs, transurethral bladder tumor resection (TURBT), and cystoscopy, as well as institutional hospital fees. Indirect societal costs such as work absences and productivity loss were not considered. The model was limited to a 5-year follow-up period with the following assumptions: similar rates of progression, constant recurrence rates, and no cross-over between groups. Overall 5-year analysis reveals that TURBT plus MMC strategy is not associated with increased costs; it saves the Medicare system $148/patient compared with TURBT alone. Calculated differences took into account avoidance of cystoscopic surveillance, urinary cytology, and reoperative and follow-up costs associated with multiple recurrences. Analysis revealed dominance of MMC usage over TURBT alone as early as 4 years from surgery. Routine usage of MMC after TURBT is not associated with increased costs to the health care system. In fact, there is a significant cost savings. Nonquantified patient quality of life benefits and secondary societal advantages of gained wages and productivity owing to decreases in recurrence and surgery would further increase the cost savings.


Propofol Inhibits the Progression of Cervical Cancer by Regulating HOTAIR/miR-129-5p/RPL14 Axis.
Propofol has been proposed to function as a tumor suppressor in various human cancers. In this study, we aimed to investigate the anti-tumor effect of propofol on cervical cancer (CC). Cell Counting Kit-8 (CCK-8) assay, colony formation assay, flow cytometry analysis, transwell assay and wound healing assay were conducted for cell viability, colony formation, apoptosis, invasion and migration, respectively. Western blot assay was used for protein levels. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for HOX antisense intergenic RNA (HOTAIR), miR-129-5p and RPL14 levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were executed to verify the interaction between miR-129-5p and HOTAIR or RPL14. Murine xenograft model assay was used for the role of propofol in tumor progression in vivo. Propofol treatment suppressed CC cell viability, colony formation, invasion and migration and facilitated apoptosis. Propofol treatment led to a marked reduction in HOTAIR level in CC cells. HOTAIR overexpression promoted cell colony formation, invasion and migration and repressed apoptosis in CC cells and propofol-treated CC cells. For mechanism analysis, HOTAIR positively regulated RPL14 expression via acting as the sponge of miR-129-5p. MiR-129-5p overexpression reversed the impacts of HOTAIR on the malignant behaviors of propofol-treated CC cells. Furthermore, miR-129-5p inhibition accelerated the progression of CC cells, while RPL14 interference rescued the effect. In addition, propofol treatment restrained tumor growth of CC in vivo. Propofol inhibited CC development by modulation of HOTAIR/miR-129-5p/RPL14 axis.


Radical-mediated carboxylation of alkyl iodides with [11C]carbon monoxide in solvent mixtures.
[reaction: see text] [carboxyl-(11)C]Carboxylic acids were prepared from alkyl iodides via photoinitiated radical reactions using 10(-)(8) mol of [(11)C]carbon monoxide in binary and ternary homogeneous solvent mixtures. Short- (isobutyric), medium-, and long-chain saturated fatty acids (heptadecanoic) were labeled with isolated decay-corrected radiochemical yields ranging from 55% to 70% in 5-7-min reactions. The conversion of [(11)C]carbon monoxide to products reached 80-90%. To obtain good yields in the reactions performed in water-acetonitrile and water-THF mixtures, the addition of tetrabutylammonium hydroxide or potassium hydroxide was essential. The carboxylation was efficient for primary and secondary alkyl iodides. The carboxylation of tertiary iodides was feasible for 1-iodoadamantane but not for tert-butyl iodide. The dependence of the radiochemical yields on reaction time, photoirradiation conditions, and organic and inorganic additives was studied. The method provides a one-step route to [carboxyl-(11)C]carboxylic acids; traditional methods, in contrast, would require several steps. For example, using the devised reaction conditions, 3.19 GBq of purified [1-(11)C]1,10-decanedicarboxylic acid (specific radioactivity 188 GBq/mumol) was obtained within 35 min of the end of 10 muAh bombardment. (1-(13)C)4-Phenylbutyric acid was synthesized using ((13)C)carbon monoxide for identifying the labeling position with (1)H and (13)C NMR.


Validation of oxidative stress assay for schizophrenia.
Accumulating evidence implicates oxidative stress in a range of diseases, yet no objective measurement has emerged that characterizes the global nature of oxidative stress. Previously, we reported a measurement that employs the moderately strong oxidant iridium (Ir) to probe the oxidative damage in a serum sample and reported that in a small study (N = 15) the Ir-reducing capacity assay could distinguish schizophrenia from healthy control groups based on their levels of oxidative stress. Here, we used a larger sample size to evaluate the Ir-reducing capacity assay to assess its ability to discriminate the schizophrenia (N = 73) and healthy control groups (N = 45). Each serum sample was measured (in triplicate) at three different times that were separated by several weeks. The Intraclass Correlation Coefficient (ICC = 0.69) for these repeated measurements indicates the assay detects stable components in the sample (i.e., it is not detecting transient reactive species or air-oxidizable serum components). Correlations between the Ir-reducing capacity assay and independently-measured total serum protein levels (r = +0.74, p < 2.2 × 10-16) suggest the assay is detecting information in the protein pool. For cross-validation of the discrimination ability, we used machine learning and receiver operating characteristic (ROC) analysis. After adjusting for potential confounders (age and smoking status), an area under the curve (AUC) of ROC curve was calculated to be 0.89 (p = 9.3 × 10-5). In conclusion, this validation indicates the Ir-reducing capacity assay provides a simple global measure of oxidative stress, and further supports the hypothesis that oxidative stress is linked with schizophrenia.


Cervical chordoma with intradural invasion. A case report.
An unusual case of cervical chordoma with intradural invasion is presented. Anterior resection of the vertebral body with Kiel (calf) bone grafting was performed. Computer tomographs taken on follow-up, four-and-a-half years later, showed the bone graft to be well incorporated and the residual tumor in arrest.


Teaching about the brain and reaching the community: undergraduates in the pipeline neuroscience program at the university of pennsylvania.
This article provides an overview of the University of Pennsylvania School of Medicine's Pipeline Neuroscience Program, a multi-tiered mentorship and education program for Philadelphia high school students in which University of Pennsylvania undergraduates are integrally involved. The Pipeline Neuroscience Program provides mentorship and education for students at all levels. High school students are taught by undergraduates, who learn from medical students who, in turn, are guided by neurology residents and fellows. Throughout a semester-long course, undergraduates receive instruction in neuroanatomy, neuroscience, and clinical neurology as part of the Pipeline's case-based curriculum. During weekly classes, undergraduates make the transition from students to community educators by integrating their new knowledge into lesson plans that they teach to small groups of medically and academically underrepresented Philadelphia high school students. The Pipeline program thus achieves the dual goals of educating undergraduates about neuroscience and providing them with an opportunity to perform community service.


Enhanced fibrinolysis in Nigerians--probable contributory factor to low prevalence of atherosclerosis in the Nigerian.
Results of more detailed study of the fibrinolytic enzyme system in Nigerians is reported. A relatively short euglobulin lysis time (ELT, range 75.87-196.08 units) in the males was observed, while a longer time (49.50-98.04 units) was observed in females aged 19-35 years. The mean concentrations of fibrinogen (0.41+/-14 g/100 ml) and plasminogen (2.45+/-1.03 Casein units) which are reported, the latter for the first time in this population are similar to values in other populations. Although plasminogen/plasmin inhibitors were not separately determined in this study, results of the ELT suggest that this was probably due to increased activator activity, and supports a previous suggestion that this increased activator activity may be a mechanism of the enhanced ELT in the males examined.


Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis.
A preestablished infection with the parasitic helminth, Schistosoma mansoni, significantly reduced the incidence and delayed the onset of experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice immunized with myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide. The altered disease progression was not solely due to the induction of a strong Th2 response, since intraperitoneal injection of schistosome eggs did not affect disease development. MOG-specific gamma interferon (IFN-gamma), nitric oxide, and tumor necrosis factor alpha production by splenocytes was significantly reduced in schistosome-infected mice compared to uninfected mice. However, similar levels of interleukin-10 (IL-10) were produced in an antigen-specific manner, suggesting that the induction of antigen-specific responses was not inhibited. Analysis of in vivo cytokine production by real-time PCR indicated that IL-12p40, but not IFN-gamma, transcript levels were dramatically reduced in the spinal cords of schistosome-infected, MOG-immunized mice. Furthermore, analysis of the cellular composition of the spinal cords and brains revealed that a preestablished infection with S. mansoni decreased central nervous system (CNS) inflammation, particularly of macrophages and CD4 T cells. These results suggest that schistosomiasis may negatively regulate the onset of EAE by downregulating the production of proinflammatory cytokines and altering CNS inflammation.


Survival analysis of total condylar-type prostheses.
Between 1975 and 1983, 280 patients received 422 posterior cruciate ligament-retaining total condylar knee arthroplasties. Fifty-nine were excluded for one of the following reasons: previous total knee replacement, follow-up less than 1 year, or infection at any time during the life of the prosthesis. The 363 remaining knees were observed from 1 to 13 years (mean, 6.86). Kaplan-Meier and "crude" survival estimates at 12 years were 94.7% and 96.6%, respectively. Results of various survival analyses by other authors yield similar successful results.


Mesoporous TiO2 single crystals: facile shape-, size-, and phase-controlled growth and efficient photocatalytic performance.
In this work, we have succeeded in preparing rutile and anatase TiO2 mesoporous single crystals with diverse morphologies in a controllable fashion by a simple silica-templated hydrothermal method. A simple in-template crystal growth process was put forward, which involved heterogeneous crystal nucleation and oriented growth within the template, a sheer spectator, and an excluded volume, i.e., crystal growth by faithful negative replication of the silica template. A series of mesoporous single-crystal structures, including rutile mesoporous TiO2 nanorods with tunable sizes and anatase mesoporous TiO2 nanosheets with dominant {001} facets, have been synthesized to demonstrate the versatility of the strategy. The morphology, size, and phase of the TiO2 mesoporous single crystals can be tuned easily by varying the external conditions such as the hydrohalic acid condition, seed density, and temperature rather than by the silica template, which merely serves for faithful negative replication but without interfering in the crystallization process. To demonstrate the application value of such TiO2 mesoporous single crystals, photocatalytic activity was tested. The resultant TiO2 mesoporous single crystals exhibited remarkable photocatalytic performance on hydrogen evolution and degradation of methyl orange due to their increased surface area, single-crystal nature, and the exposure of reactive crystal facets coupled with the three-dimensionally connected mesoporous architecture. It was found that {110} facets of rutile mesoporous single crystals can be considered essentially as reductive sites with a key role in the photoreduction, while {001} facets of anatase mesoporous single crystals provided oxidation sites in the oxidative process. Such shape- and size-controlled rutile and anatase mesoporous TiO2 single crystals hold great promise for building energy conversion devices, and the simple solution-based hydrothermal method is extendable to the synthesis of other mesoporous single crystals beyond TiO2.


Inhibition of ANP clearance receptors and endopeptidase 24.11 in maturing rats.
Systemic clearance of atrial natriuretic peptide (ANP) decreases during postnatal development. To determine the relative contribution of ANP clearance (C) receptors and neutral endopeptidase 24.11 (NEP; EC 22.214.171.124) in regulation of plasma ANP concentration ([ANP]) during maturation, 18- to 60-day-old male Sprague-Dawley rats were anesthetized and infused with rat ANP (35 ng.kg-1.min-1). Infusion of the NEP inhibitor phosphoramidon increased [ANP] and urine guanosine 3',5'-cyclic monophosphate (cGMP) excretion in both weanling and adult rats. Infusion of C-ANP, an analogue that binds C receptors selectively, resulted in a greater rise in [ANP] in preweaned than in adult rats, suggesting a maturational decrease in function of C receptors. Despite the increase in [ANP], however, urine flow, cGMP, and sodium excretion failed to increase in preweaned compared with adult rats. Combined infusion of phosphoramidon and C-ANP resulted in a marked increase in [ANP] and cGMP excretion in weanling and adult rats. These results indicate that both C receptors and NEP modulate plasma [ANP] in the physiological range and that each pathway compensates when the other is inhibited. Age-related differences in the renal response to ANP clearance inhibitors may have important physiological implications in the regulation of sodium balance during development.


[Study of the relationship between the function of the lymphocytes and monocytes and the level of various lipids and 11-hydroxycorticosteroids in diabetes mellitus].
On the example of diabetes mellitus there was shown a close interrelationship between the blood lymphocytes and monocytes function, on the one hand, and the disturbances of carbohydrate and lipid metabolism--on the other hand. Patients were examined both during the decompensated stage of diabetes and during the compensated one as a result of treatment. A reduction of lipid and 11-oxycorticosteroid level, a rise in T-lymphocyte percentage, an increase of the lymphocyte blasttransformation reaction, and of lysosomal and phagocytic activity of monocytes followed the treatment.


Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin.
The aim of this study was to investigate structural changes in the brain stem of adolescents with narcolepsy, a disorder characterized by excessive daytime sleepiness, fragmented night-time sleep, and cataplexy. For this purpose, we used quantitative magnetic resonance imaging to obtain R1 and R2 relaxation rates, proton density, and myelin maps in adolescents with narcolepsy (n = 14) and healthy controls (n = 14). We also acquired resting state functional magnetic resonance imaging (fMRI) for brainstem connectivity analysis. We found a significantly lower R2 in the rostral reticular formation near the superior cerebellar peduncle in narcolepsy patients, family wise error corrected p = .010. Narcolepsy patients had a mean R2 value of 1.17 s-1 whereas healthy controls had a mean R2 of 1.31 s-1, which was a large effect size with Cohen d = 4.14. We did not observe any significant differences in R1 relaxation, proton density, or myelin content. The sensitivity of R2 to metal ions in tissue and the transition metal ion chelating property of neuromelanin indicate that the R2 deviant area is one of the neuromelanin containing nuclei of the brain stem. The close proximity and its demonstrated involvement in sleep-maintenance, specifically through orexin projections from the hypothalamus regulating sleep stability, as well as the results from the connectivity analysis, suggest that the observed deviant area could be the locus coeruleus or other neuromelanin containing nuclei in the proximity of the superior cerebellar peduncle. Hypothetically, the R2 differences described in this paper could be due to lower levels of neuromelanin in this area of narcolepsy patients.


Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level.
Moloney murine leukemia virus (M-MuLV) and Moloney murine sarcoma virus (M-MSV) exert a regulatory effect on the class I genes of the murine major histocompatibility complex (MHC). We have previously shown that M-MuLV infection of mouse fibroblasts results in a substantial increase in cell surface expression of H-2K, H-2D, and H-2L proteins, whereas M-MSV, upon coinfection of the same cells, is apparently able to override the MuLV-induced increase in H-2 expression. As a result of this modulation, immune recognition of the infected cells is profoundly altered. Our efforts have been directed toward elucidating the molecular basis for this phenomenon. We report here that stimulation of interferon production as a result of infection with MuLV does not occur and, therefore, is not the cause of MuLV-induced enhancement of MHC expression. Control of H-2 class I and beta 2-microglobulin gene expression by M-MuLV, and probably by M-MSV, takes place at the transcriptional level as indicated by nuclear runoff studies and analysis of steady-state mRNA levels. Our demonstration that M-MuLV controls expression of widely separated endogenous cellular genes (those coding for H-2D, H-2K, H-2L, and beta 2-microglobulin), transfected class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to sequences encoding a procaryotic enzyme, chloramphenicol acetyltransferase, suggests that M-MuLV exerts its effect in trans and not by proviral integration in the vicinity of the H-2 gene complex. Finally, we show that the sequences of at least one MHC gene, which are responsive to trans regulation by M-MuLV, lie within 1.2 kilobases upstream of the initiation codon for that gene.


Sulfur Availability Impacts Accumulation of the 2-Thiouridine tRNA Modification in Bacillus subtilis.
Posttranscriptional modifications to tRNA are critical elements for the folding and functionality of these adaptor molecules. Sulfur modifications in tRNA are installed by specialized enzymes that act on cognate tRNA substrates at specific locations. Most studied organisms contain a general cysteine desulfurase to mobilize sulfur for the synthesis of S-tRNA and other thio-cofactors. Bacillus subtilis and other Gram-positive bacteria encode multiple cysteine desulfurases that partner with specific sulfur acceptors in the biosynthesis of thio-cofactors. This metabolic layout suggests an alternate mode of regulation in these biosynthetic pathways. In this study, tRNA modifications were exploited as a readout for the functionality of pathways involving cysteine desulfurases. These analyses showed that the relative abundance of 2-thiouridine-modified tRNA (s2U) responds to sulfur availability in the growth medium in a dose-dependent manner. This study found that low sulfur concentrations lead to decreased levels of the s2U cysteine desulfurase YrvO and thiouridylase MnmA, without altering the levels of other cysteine desulfurases, SufS, NifS, and NifZ. Analysis of pathway metabolites that depend on the activity of cysteine desulfurases indicates that sulfur nutrient availability specifically impacts s2U accumulation while having no effect on the levels of other S-modified tRNA or activity levels of Fe-S enzymes. Collectively, these results support a model in which s2U tRNA serves as a marker for sulfur availability in B. subtilis. IMPORTANCE The 2-thiouridine (s2U) tRNA modification is found ubiquitously across all domains of life. YrvO and MnmA, the enzymes involved in this modification, are essential in B. subtilis, confirming the well-established role of s2U in maintaining translational efficiency and, consequently, cellular viability. Herein, we show that in the model Gram-positive organism Bacillus subtilis, the levels of s2U are responsive to sulfur availability. Downregulation of the s2U biosynthetic components leads to lower s2U levels, which may serve as a signal for the slowing of the translational apparatus during cellular nutrient insufficiency. Our findings provide the basis for the identification of a potential bacterial mode of regulation during S-metabolite depletion that may use s2U as a marker of suboptimal metabolic status.


The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlations with insulin-like growth factor I.
To assess the effects of delta wave sleep interruption (DWSI) on pain thresholds and fibromyalgia-like symptoms. To examine the potential correlations between DWSI and serum insulin-like growth factor 1 (IGF-1). Thirteen healthy volunteers were subjected to 3 consecutive nights of DWSI (Group 1). Pain thresholds were measured by dolorimetry and symptoms by visual analog scale. Six subjects not undergoing DWSI served as dolorimetry and symptom controls (Group 2). Serum IGF-1 was measured by competitive binding radioimmunoassay before and after DWSI. No significant differences in pain thresholds as a function of condition (baseline, DWSI, recovery) or overnight change were detected between or within groups (p>0.05). Morning mean dolorimeter scores were lower than evening scores in both groups during all 3 conditions, and were lower in Group 1 than in Group 2 during DWSI. Group 1 subjects had higher composite symptom scores during DWSI (p< or =0.005), attributed largely to increases in fatigue. Serum levels of IGF-1 from Group 1 subjects showed no significant change after DWSI (p>0.05). In our study subjects, 3 nights of DWSI caused no significant lowering of pain thresholds compared with a control group. Subjects appeared to have lower pain thresholds in the mornings, and DWSI appeared to augment this effect. Symptoms were more apparent during DWSI, but were primarily related to fatigue. IGF-1 was not altered by 3 nights of DWSI. The low levels of IGF-1 seen in patients with fibromyalgia syndrome may result from chronic rather than acute DWSI, or may be dependent on factors other than disturbances of delta wave sleep.


Intercomparison of activity size distributions of thoron progeny by alpha- and gamma-counting methods.
It is difficult to calibrate sampling devices using radon or thoron progeny or particles measuring 1-4 nm; therefore, an interlaboratory comparison is important to verify the performance of graded diffusion batteries for the activity size distributions of the "unattached" progeny. This paper describes the results of an interlaboratory comparison of 220Rn progeny size distributions using graded diffusion batteries by alpha- and gamma-counting methods with different data inversion schemes. Graded diffusion batteries designed at the Inhalation Toxicology Research Institute and at the Environmental Measurement Laboratory were used in the study. Screens and backup filters from the Environmental Measurement Laboratory-graded diffusion batteries were counted simultaneously in alpha counters for total alpha activities, and those of the Inhalation Toxicology Research Institute-graded diffusion batteries were counted in a gamma detector for gamma activities from 212Pb. Because of the different counting methods and data analysis procedures used, this interlaboratory study of 220Rn progeny allows a more rigorous way of testing instrument performance. 212Pb particles generated in well-controlled environments of oxygen, nitrogen, or oxygen with 1 ppm of nitrogen oxide were measured. In general, good agreement in activity size distributions was obtained from these two methods. Some differences observed in individual size spectra were attributable to the data inversion programs used in each laboratory. When the data were analyzed by the same computer program, most differences disappeared.


[Posttraumatic deformity correction at the foot].
Posttraumatic foot deformities requiring correction result from overlooked or inadequately treated injuries and, on the other hand, from protracted courses because of avascular necrosis, non-union or infection after primary surgery. To achieve a maximum benefit, corrective surgery has to be carried out early before arthritic involvement of adjacent joint becomes evident. As salvage procedures, arthrodeses should be restricted to the affected joints. Especially talus malunion and non-union should be corrected with preservation of the joints whenever possible to achieve favourable functional outcomes. In case of calcaneal malunion with consequential lateral translation a reorientating subtalar arthrodesis should be supplemented by corrective osteotomy of the fracture line. Corrections at the level of Chopart's and Lisfranc's (mid-tarsal and tarsometatarsal) joints must restore the exact relationship between the medial and lateral foot columns. Malunions of the metatarsals and toes are corrected in cases of symptomatic malalignment. This paper reviews corrective procedures for posttraumatic deformities at the different foot regions. A therapy-based classification for mal-unions of the talus and calcaneus is proposed.


Proteomics for monitoring immune responses to cancer vaccines.
Standardized biomarkers for the detection of clinically significant immunological responses would be extremely valuable in immunotherapy trials. Most available assays measure either the frequency or function of antigen-specific T-cells, or the titers of antibodies or immune complexes. These assays have generally exhibited either inadequate sensitivity or too high a signal-to-noise ratio to reliably detect the low-frequency T-cell responses induced by cancer vaccines. In addition, such assays reflect only one aspect of the immune response rather than the complete picture. Proteomics, the study of proteins within a cell or biological sample, may offer a novel approach to immunological monitoring that complements existing immunological assays. By studying the protein content of T-cells responding to a vaccine or in the serum of vaccinated individuals, it may be possible to develop a metric for quantitating the magnitude of immunological responses. Proteomics could also provide a tool for establishing the quality of the immune response and for obtaining valuable information regarding the underlying regulatory mechanisms and pathways. Advances in miniaturization and automation may also permit characterization of the immune response more rapidly and from smaller amounts of biological material than is possible with existing assay systems.


[Hypertension due to liquorice and liquorice tea consumption].
--Compared to other countries, liquorice consumption in the Netherlands is very high; on average it is 2 kg per person annually. Also liquorice tea is growing in popularity. Both products contain glycyrrhizin. The pathophysiological mechanism of the effect ofglycyrrhizin was described earlier. --In a literature study, the quantitative effect of liquorice consumption on blood pressure was evaluated. An Internet search on PubMed and Embase revealed 7 publications, all ofwhich short-term studies. --These studies showed that a daily consumption of glycyrrhetinic acid of 95 mg or more caused an increase in blood pressure. --A practical guideline for an acceptable daily intake of glycyrrhetinic acid seems to be 9.5 mg a day. This means no more than 10-30 g liquorice and no more than half a cup of liquorice tea a day. --On diagnosing hypertension, the effects of liquorice and liquorice tea consumption on blood pressure should be kept in mind.


Probing protein ensemble rigidity and hydrogen-deuterium exchange.
Protein rigidity and flexibility can be analyzed accurately and efficiently using the program floppy inclusion and rigid substructure topography (FIRST). Previous studies using FIRST were designed to analyze the rigidity and flexibility of proteins using a single static (snapshot) structure. It is however well known that proteins can undergo spontaneous sub-molecular unfolding and refolding, or conformational dynamics, even under conditions that strongly favor a well-defined native structure. These (local) unfolding events result in a large number of conformers that differ from each other very slightly. In this context, proteins are better represented as a thermodynamic ensemble of 'native-like' structures, and not just as a single static low-energy structure. Working with this notion, we introduce a novel FIRST-based approach for predicting rigidity/flexibility of the protein ensemble by (i) averaging the hydrogen bonding strengths from the entire ensemble and (ii) by refining the mathematical model of hydrogen bonds. Furthermore, we combine our FIRST-ensemble rigidity predictions with the ensemble solvent accessibility data of the backbone amides and propose a novel computational method which uses both rigidity and solvent accessibility for predicting hydrogen-deuterium exchange (HDX). To validate our predictions, we report a novel site specific HDX experiment which characterizes the native structural ensemble of Acylphosphatase from hyperthermophile Sulfolobus solfataricus (Sso AcP). The sub-structural conformational dynamics that is observed by HDX data, is closely matched with the FIRST-ensemble rigidity predictions, which could not be attained using the traditional single 'snapshot' rigidity analysis. Moreover, the computational predictions of regions that are protected from HDX and those that undergo exchange are in very good agreement with the experimental HDX profile of Sso AcP.


Herpesvirus DNA detection in cerebral spinal fluid: differences in clinical presentation between alpha-, beta-, and gamma-herpesviruses.
To evaluate the role of 6 human herpesviruses (cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV)) in infections of the nervous system, cerebrospinal fluid (CSF) samples from 662 patients with suspected viral aetiology to neurological symptoms were investigated for presence of herpesviral DNA in a PCR-based study. Of the 69 patients (2 patients had 2 herpesvirus DNA detected in CSF) who had herpesvirus DNA detected in the CSF, 60 (87%) were non-immunocompromised (CMV 7; HHV-6 6; EBV 16; HSV-1 18; HSV-2 9 and VZV 6) and 9 (13%) were immunocompromised (CMV 3; HHV-6 0; EBV 5; HSV-1 0; HSV-2 1 and VZV 0). The study was performed in a retrospective/prospective manner. The HSV-1, HSV-2, VZV and CMV DNA-positive patients usually had typical clinical syndromes, such as encephalitis/myelitis and meningitis, but also other neurological conditions were associated with findings of these viruses. HHV-6 and EBV DNA were detected in patients presenting with a variety of neurological symptoms, and in some of the cases, concurrent with diagnosis of other infections of the central nervous system. Despite the overall variability of clinical conditions seen, a pattern associated with each investigated herpesvirus was discernable as regards clinical presentation.


Assessment of Bone Fracture Healing Using Micro-Computed Tomography.
Micro-computed tomography (µCT) is the most common imaging modality to characterize the three-dimensional (3D) morphology of bone and newly formed bone during fracture healing in translational science investigations. Studies of long bone fracture healing in rodents typically involve secondary healing and the formation of a mineralized callus. The shape of the callus formed and the density of the newly formed bone may vary substantially between timepoints and treatments. Whereas standard methodologies for quantifying parameters of intact cortical and trabecular bone are widely used and embedded in commercially available software, there is a lack of consensus on procedures for analyzing the healing callus. The purpose of this work is to describe a standardized protocol that quantitates bone volume fraction and callus mineral density in the healing callus. The protocol describes different parameters that should be considered during imaging and analysis, including sample alignment during imaging, the size of the volume of interest, and the number of slices that are contoured to define the callus.


A Method for Creating Artificial Thrombi In Vitro Using a Rotating Mechanical Surface.
Thromboembolism is a common concern in ventricular assist device (VAD) therapy. Precise VAD response to pass-through thromboembolism needs to be studied in a controlled in vitro setting where specific pump parameters (i.e., power consumption, flow rates, impeller RPM) can be monitored while various types of thrombi are introduced. In this article, we describe a method for creating standardized fibrin thrombi that could be introduced into a mock circulatory loop for testing VAD response to thromboembolism. Donor equine blood collected using a sodium citrate was allowed to clot by adding calcium chloride (CaCl2) while a rotating component applied shear forces to the blood. This rotating force was applied at various speeds and at various distances into the blood. Resulting clots showed similar microscopic features to thrombi taken from explanted clinical VADs. Higher RPM of the rotating component and smaller clearances between the rotating component and the blood created clots that closely resembled ante-explant clots found within VADs in vivo. This method is an effective way to create artificial fibrin clots for use in in vitro experiments to test thromboembolism in VADs.


Clinical heterogeneity and phenotype/genotype findings in 5 families with GYG1 deficiency.
To describe the variability of muscle symptoms in patients carrying mutations in the GYG1 gene, encoding glycogenin-1, an enzyme involved in the biosynthesis of glycogen, and to discuss genotype-phenotype relations. We describe 9 patients from 5 families in whom muscle biopsies showed vacuoles with an abnormal accumulation of glycogen in muscle fibers, partially α-amylase resistant suggesting polyglucosan bodies. The patients had either progressive early-onset limb-girdle weakness or late-onset distal or scapuloperoneal muscle affection as shown by muscle imaging. No clear definite cardiac disease was found. Histologic and protein analysis investigations were performed on muscle. Genetic analyses by direct or exome sequencing of the GYG1 gene revealed 6 different GYG1 mutations. Four of the mutations were novel. They were compound heterozygous in 3 families and homozygous in 2. Protein analysis revealed either the absence of glycogenin-1 or reduced glycogenin-1 expression with impaired glucosylation. Our report extends the genetic and clinical spectrum of glycogenin-1-related myopathies to include scapuloperoneal and distal affection with glycogen accumulation.


Balancing risk versus benefit: the elderly patient's perspective on warfarin therapy.
Warfarin therapy is underused in the target at-risk elderly population. Clinicians perceive that older patients are reluctant to use this therapy, however the perspective of patients or their carers has yet to be explored. To explore in-depth the perspectives of elderly patients and/or their carers regarding the use of warfarin therapy. A qualitative study, using semi-structured group interviews was undertaken. The audio-taped discussions were transcribed verbatim, then thematically analysed to identify emergent themes. Group discussions were conducted at a major Sydney teaching hospital, over a 2-month period. Individuals aged 65 years or older (and/or their carers) who were using long-term (6 months) warfarin therapy were recruited by voluntary response to study flyers. 17 patients and carers (mean age 77.2 SD=7.5 years) participated in one of two focus groups. Five core themes emerged regarding warfarin therapy: inadequate knowledge and understanding about it, patients/carers variable experience of information provision, cycle of reactions to being on it, issues in its practical management, and the spectrum of experiences with it. Overall, participants were very accepting of the therapy, describing a high level of compliance, despite initial fears and anxieties, and a relative lack of knowledge. Patients felt somewhat abandoned in their management of warfarin due to the lack of ongoing support services in the community, and inadequate information provision. Elderly patients and their carers appear to be quite accepting of warfarin therapy, in contrast to the perceptions of health care professionals. More effort is needed, however, in terms of information provision, particularly in the form of community-based services, to assist patients in the long-term management of warfarin.


Can the Student Outperform the Master? A Plan Comparison Between Pinnacle Auto-Planning and Eclipse knowledge-Based RapidPlan Following a Prostate-Bed Plan Competition.
Pinnacle Auto-Planning and Eclipse RapidPlan are 2 major commercial automated planning engines that are fundamentally different: Auto-Planning mimics real planners in the iterative optimization, while RapidPlan generates static dose objectives from estimations predicted based on a prior knowledge base. This study objectively compared their performances on intensity-modulated radiotherapy planning for prostate fossa and lymphatics adopting the plan quality metric used in the 2011 American Association of Medical Dosimetrists Plan Challenge. All plans used an identical intensity-modulated radiotherapy beam setup and a simultaneous integrated boost prescription (68 Gy/56 Gy to prostate fossa/lymphatics). Auto-Planning was used to retrospectively plan on 20 patients, which were subsequently employed as the library to build an RapidPlan model. To compare the 2 engines' performances, a test set including 10 patients and the Plan Challenge patient was planned by both Auto-Planning (master) and RapidPlan (student) without manual intervention except for a common dose normalization and evaluated using the plan quality metric that included 14 quantitative submetrics ranging over target coverage, spillage, and organ at risk doses. Plan quality metric scores were compared between the Auto-Planning and RapidPlan plans using the Mann-Whitney U test. There was no significant difference between the overall performance of the 2 engines on the 11 test cases ( P = .509). Among the 14 submetrics, Auto-Planning and RapidPlan showed no significant difference on most submetrics except for 2. On the Plan Challenge case, Auto-Planning scored 129.9 and RapidPlan scored 130.3 out of 150, as compared with the average score of 116.9 ± 16.4 (range: 58.2-142.5) among the 125 Plan Challenge participants. Using an innovative study design, an objective comparison has been conducted between 2 major commercial automated inverse planning engines. The 2 engines performed comparably with each other and both yielded plans at par with average human planners. Using a constant-performing planner (Auto-Planning) to train and to compare, RapidPlan was found to yield plans no better than but as good as its library plans.