Laypersons' expectation of the sequelae of whiplash injury: a cross-cultural comparative study between Canada and Greece.
The objective of the present study is to compare the frequency and nature of expected 'whiplash' symptoms in Greece [a country where the chronic whiplash syndrome is rare or unknown] with that in Canada. A symptom checklist was administered to 2 subject groups selected from local companies in Patras Greece, and Edmonton, Canada, respectively. Subjects were asked to imagine having suffered a neck sprain [whiplash injury] with no loss of consciousness in a motor vehicle collision, and to check which, of a variety of symptoms, they would expect might arise from the injury. For symptoms they anticipated, they were asked to select the period of time they expected those symptoms to persist. In both the Greek and Edmontonian groups, the pattern of symptoms anticipated closely resembled the acute symptoms commonly reported by accident victims with acute neck sprain, but while up to 50% of Edmontonians also anticipated symptoms to last months or years, very few Greek subjects selected any symptoms as likely to persist. In Greece, despite the documented occurrence of neck sprain symptoms in individuals following motor vehicle collisions, there is a very low rate of expectation of any sequelae from this injury. What current or previous aspects of society that underlie this remain uncertain. This lack of expectation of chronicity in Greece may, in part, determine the low prevalence of the chronic whiplash syndrome there. Further studies of symptom expectation as an etiologic factor in the chronic whiplash syndrome are needed.


Recommendations on modern contact investigation methods for enhancing tuberculosis control.
Effective contact investigations are paramount to the success of tuberculosis (TB) control in high-risk communities in low TB prevalence countries. National and international guidelines on TB contact investigations are available and vary widely on recommendations. Because of the limitations of traditional contact tracing, new approaches are under investigation, and in some cases in use, to ensure effective TB control in those persons and communities at greatest risk. These non-traditional approaches include the use of social network analysis, geographic information systems and genomics, in addition to the widespread use of genotyping, to better understand TB transmission. Detailed guidelines for the use of these methods during TB outbreaks and in routine follow-up of TB contact investigations do not currently exist despite evidence that they may improve TB control efforts. It remains unclear as to when it is most appropriate and effective to use a network-informed approach alone, or in combination with other methodologies as well as the extent of data collection required to inform practice. TB controllers should consider developing the capacity to facilitate the systematic collection, analysis, and interpretation of contact investigation data using such novel methodologies, particularly in high-risk communities. Further investigation should focus on questionnaire development and adaptation, electronic data management and infrastructure, development of local capability and consultant expertise, and the use of coordinated approaches, including deployment strategies and evaluation.


Urinary mRNA Signatures as Predictors of Renal Function Decline in Patients With Biopsy-Proven Diabetic Kidney Disease.
The clinical manifestations of diabetic kidney disease (DKD) are more heterogeneous than those previously reported, and these observations mandate the need for the recruitment of patients with biopsy-proven DKD in biomarker research. In this study, using the public gene expression omnibus (GEO) repository, we aimed to identify urinary mRNA biomarkers that can predict histological severity and disease progression in patients with DKD in whom the diagnosis and histologic grade has been confirmed by kidney biopsy. We identified 30 DKD-specific mRNA candidates based on the analysis of the GEO datasets. Among these, there were significant alterations in the urinary levels of 17 mRNAs in patients with DKD, compared with healthy controls. Four urinary mRNAs-LYZ, C3, FKBP5, and G6PC-reflected tubulointerstitial inflammation and fibrosis in kidney biopsy and could predict rapid progression to end-stage kidney disease independently of the baseline eGFR (tertile 1 vs. tertile 3; adjusted hazard ratio of 9.68 and 95% confidence interval of 2.85-32.87, p < 0.001). In conclusion, we demonstrated that urinary mRNA signatures have a potential to indicate the pathologic status and predict adverse renal outcomes in patients with DKD.


Prognostic indicators in bulimia nervosa treated with cognitive-behavioral group therapy.
Prognostic indicators of short-term outcome were identified in 69 women with the DSM-III-R diagnosis of bulimia nervosa who participated in a weekly 10-session structured cognitive-behavioral outpatient group program. Prior to treatment, all subjects completed the computerized Diagnostic Interview Schedule (DIS), the Moos Family Environment Scale (FES), the Diagnostic Survey for Eating Disorders (DSED), the Beck Depression Inventory (BDI), the Hopkins Symptom Checklist, Revised (SCL-90-R), the Bulimic Cognitive Distortions Scale (BCDS), the Eating Disorders Inventory (EDI), and the Bulimic Symptoms Checklist (BSCL). The latter three scales were readministered on completion of the 10-week group. Symptom improvement was assessed by examining percentage reduction in binge frequency, purge frequency, and summed scores for the EDI subscales Bulimia, Drive for Thinness, and Body Dissatisfaction. The only significant predictor of improvement in binge frequency and bulimic cognitions was family environment. Conflicted, controlling, and over-organized family environments appear to impede both reductions in binge frequency and changes in bulimic cognitions. Reduction in vomit frequency was associated with weight history and with laxative or diuretic use. The implications for planning psychotherapeutic interventions in bulimia nervosa are discussed.


Evaluation and treatment of accidental autoinjection of epinephrine.
A case of accidental autoinjection of epinephrine is described. A 47-year-old man arrived at the emergency department after accidental injection of epinephrine with an autoinjector into his left thumb. His vital signs were stable at admission. The patient was allergic to nuts and thought he may have eaten something containing a pine nut. The patient reported feeling itching in his throat but had no shortness of breath or swollen tongue. He tried to self-administer an epinephrine injection, but it did not inject. While he was checking the device, it accidently injected into his left thumb pad. A review of systems revealed throat discomfort, a tingling sensation of the tongue, and a left-thumb puncture with pain. Physical examination of the left thumb pad revealed a pale, cool thumb with diminished capillary refill and punctuate black discoloration at the site of injection. Topical nitroglycerin paste was applied but had no effect, so terbutaline was ordered. The terbutaline injection was prepared as a 1:1 preparation of terbutaline sulfate 1 mg/mL and 0.9% sodium chloride injection. The immediate effects were the return of color from pale white to red and observable perfusion to the area within seconds. After 20 minutes, the red color remained, with observable perfusion and warmth, in addition to complete neurosensory function. Sixty minutes after terbutaline administration, the patient was discharged home. A 47-year-old man who accidentally injected himself in the thumb with an epinephrine autoinjector was successfully treated with subcutaneous terbutaline. The treatment had an immediate effect, including revascularization and resolution of pain.


[Intramuscular hemangioma of the posterior wall of the pharynx. Diagnosis and differential diagnosis].
We report on the case of a seven-year old boy who developed an enlarged swelling of the oropharynx. Clinical examination revealed a well demarcated cystic tumour. Histopathologically the diagnosis of an intramuscular haemangioma could be made because of the multitude of vascular spaces filled with erythrocytes lying between bundles of smooth muscles. Such a lesion coming from the posterior wall of the oropharynx is not described in literature. In differential diagnosis the angiosarcoma and the arteriovenous aneurysm must have been involved since there were multiple arteries and veins lying close together in couples. Moreover the adenotomia carried out one and a half year earlier prompted us to think about the possibility of a traumatic arteriovenous fistula.


High complexity of aquatic irradiance may have driven the evolution of four-dimensional colour vision in shallow-water fish.
Humans use three cone photoreceptor classes for colour vision, yet many birds, reptiles and shallow-water fish are tetrachromatic and use four cone classes. Screening pigments, which narrow the spectrum of photoreceptors in birds and diurnal reptiles, render visual systems with four cone classes more efficient. To date, however, the question of tetrachromacy in shallow-water fish that, like humans, lack screening pigments, is still unsolved. We raise the possibility that tetrachromacy in fish has evolved in response to higher spectral complexity of underwater light. We compared the dimensionality of colour vision in humans and fish by examining the spectral complexity of the colour signal reflected from objects into their eyes. We show that fish require four to six cone classes to reconstruct the colour signal of aquatic objects at the accuracy level achieved by humans viewing terrestrial objects. This is because environmental light, which alters the colour signals, is more complex and contains more spectral fluctuations underwater than on land. We further show that fish cones are better suited than human cones to detect these spectral fluctuations, suggesting that the capability of fish cones to detect high-frequency fluctuations in the colour signal confers an advantage. Taken together, we propose that tetrachromacy in fish has evolved to enhance the reconstruction of complex colour signals in shallow aquatic environments. Of course, shallow-water fish might possess fewer than four cone classes; however, this would come with the inevitable loss in accuracy of signal reconstruction.


[Changes in the stimulation of mitochondrial respiration by adrenaline depending upon the dose].
Effects of low and high 25 and 100 micrograms per 100 g of body weight doses of adrenaline on respiration and oxidative phosphorylation in rat liver mitochondria are compared. The high dose of adrenaline is shown to decrease activation of respiration and phosphorylation typical of the low doses. This decrease is caused by inhibition of succinate dehydrogenase and is accompanied by uncoupling of respiration and phosphorylation in mitochondria.


Gel permeation chromatography process for highly oriented Cs3Cu2I5 nanocrystal film.
The emergence of green materials has attracted considerable attention in the field of optoelectronics. Copper-based lead-free metal halide (with a near-unity quantum yield) obtained from Cs3Cu2I5 nanocrystals (NCs) can exhibit blue emission with a wavelength of 440 nm and provide outstanding stability for various applications. However, in practical applications, colloidal dispersion purity and film quality are inadequate toward a high-performance device. In this study, antisolvent-free gel permeation chromatography is used to purify Cs3Cu2I5 NCs. The purified Cs3Cu2I5 NCs exhibit a high photoluminescent quantum yield and provide a highly oriented single-crystal film. Density functional theory calculation results indicate that the iodide-rich surface in the NCs makes them highly stable. In addition, it has been demonstrated for the first time that the mixture of polymethyl methacrylate (PMMA) and Cs3Cu2I5 NCs has waterproofing capabilities. The composite film consisting of Cs3Cu2I5 NCs and PMMA can survive in water for several days. This result opens up more possibilities for the application of these green material.


Adenovirus-associated health risks for recreational activities in a multi-use coastal watershed based on site-specific quantitative microbial risk assessment.
We used site-specific quantitative microbial risk assessment (QMRA) to assess the probability of adenovirus illness for three groups of swimmers: adults with primary contact, children with primary contact, and secondary contact regardless of age. Human enteroviruses and adenoviruses were monitored by qPCR in a multi-use watershed and Adenovirus type 40/41 was detected in 11% of 73 samples, ranging from 147 to 4117 genomes per liter. Enterovirus was detected only once (32 genomes per liter). Seven of eight virus detections occurred when E. coli concentrations were below the single sample maximum water quality criterion for contact recreation, and five of eight virus detections occurred when fecal coliforms were below the corresponding criterion. We employed dose-harmonization to convert viral genome measurements to TCID50 values needed for dose-response curves. The three scenarios considered different amounts of water ingestion and Monte Carlo simulation was used to account for the variability associated with the doses. The mean illness risk in children based on adenovirus measurements obtained over 11 months was estimated to be 3.5%, which is below the 3.6% risk considered tolerable by the current United States EPA recreational criteria for gastrointestinal illnesses (GI). The mean risks of GI illness for adults and secondary contact were 1.9% and 1.0%, respectively. These risks changed appreciably when different distributions were fitted to the data as determined by Monte Carlo simulations. In general, risk was at a maximum for the log-logistic distribution and lowest for the hockey stick distribution in all three selected scenarios. Also, under default assumptions, the risk was lowered considerably when assuming that only a small proportion of Adenovirus 40/41 (3%) was as infectious as Adenovirus type 4, compared to the assumption that all genomes were Adenovirus 4. In conclusion, site-specific QMRA on water-borne adenoviruses in this watershed provided a similar level of protection against public health risks as would be obtained by enumeration of fecal indicator bacteria under the new U.S. EPA guidelines.


Proteome analysis for the identification of tumor-associated biomarkers in gastrointestinal cancer.
Gastrointestinal cancers are usually diagnosed at advanced stages, making a curative treatment difficult. Biomarkers can help to overcome this problem by allowing earlier diagnosis, and thus better therapy. Proteomics tools are novel technologies to identify such biomarkers. This review summarizes advances in biomarker detection using two-dimensional gel electrophoresis (2D-PAGE), chromatography and mass spectrometry technologies. 2D-PAGE combined with mass spectrometry has led to the identification of several differentially expressed proteins in cancer tissue. However, for serum analysis, 2D-PAGE has severe limitations. For serum-based cancer diagnosis, surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry is a promising new technology. The potential of proteins identified with this technology as novel cancer biomarkers still needs to be confirmed in clinical trials.


Dorsal and ventral distribution of excitable and synaptic properties of neurons of the bed nucleus of the stria terminalis.
The bed nucleus of the stria terminalis (BNST) is a structure uniquely positioned to integrate stress information and regulate both stress and reward systems. Consistent with this arrangement, evidence suggests that the BNST, and in particular the noradrenergic input to this structure, is a key component of affective responses to drugs of abuse. We have utilized an in vitro slice preparation from adult mice to determine synaptic and membrane properties of these cells, focusing on the dorsal and ventral subdivisions of the anterolateral BNST (dBNST and vBNST) because of the differential noradrenergic input to these two regions. We find that while resting membrane potential and input resistance are comparable between these subdivisions, excitable properties, including a low-threshold spike (LTS) likely mediated by T-type calcium channels and an Ih-dependent potential, are differentially distributed. Inhibitory and excitatory postsynaptic potentials (IPSPs and EPSPs, respectively) are readily evoked in both dBNST and vBNST. The fast IPSP is predominantly GABAA-receptor mediated and is partially blocked by the AMPA/kainate-receptor antagonist CNQX. In the presence of the GABAA-receptor antagonist picrotoxin, cells in dBNST but not vBNST are more depolarized and have a higher input resistance, suggesting tonic GABAergic inhibition of these cells. The EPSPs elicited in BNST are monosynaptic, exhibit paired pulse facilitation, and contain both an AMPA- and an N-methyl-d-aspartate (NMDA) receptor-mediated component. These data support the hypothesis that neurons of the dorsal and ventral BNST differentially integrate synaptic input, which is likely of behavioral significance. The data also suggest mechanisms by which information may flow through stress and reward circuits.


Transdiagnostic factors and pathways to multifinality: The error-related negativity predicts whether preschool irritability is associated with internalizing versus externalizing symptoms at age 9.
There is increasing interest among developmental psychopathologists in broad transdiagnostic factors that give rise to a wide array of clinical presentations (multifinality), but little is known about how these processes lead to particular psychopathological manifestations over the course of development. We examined whether individual differences in the error-related negativity (ΔERN), a neural indicator of error monitoring, predicts whether early persistent irritability, a prototypical transdiagnostic construct, is associated with later internalizing versus externalizing outcomes. When children were 3 years old, mothers were interviewed about children's persistent irritability and completed questionnaires about their children's psychopathology. Three years later, EEG was recorded while children performed a go/no-go task to measure the ΔERN. When children were approximately 9 years old, mothers again completed questionnaires about their children's psychopathology. The results indicated that among children who were persistently irritable at age 3, an enhanced or more negative ΔERN at age 6 predicted the development of internalizing symptoms at age 9, whereas a blunted or smaller ΔERN at age 6 predicted the development of externalizing symptoms. Our results suggest that variation in error monitoring predicts, and may even shape, the expression of persistent irritability and differentiates developmental trajectories from preschool persistent irritability to internalizing versus externalizing outcomes in middle to late childhood.


Autologous stem cell transplantation in advanced follicular lymphoma. A single center experience.
The use of intensive therapy supported by autologous stem cell transplantation (ASCT) is being investigated as treatment for poor-prognosis follicular lymphomas (FL). A single-center experience is herein reported. From September 1990 to October 1997, 30 consecutive patients (pts) with advanced FL received transplants, 8 of bone marrow and 22 of peripheral blood. Thirteen harvests were purged by an immunomagnetic method using anti-B antibodies. Twenty-seven patients received salvage chemotherapy (CT) before ASCT with the objective of reaching this procedure in the best possible response. The disease status at ASCT was: 1(st) CR in 7 pts, > or =2(nd) CR in 6 pts, PR in 10 pts, untreated relapse in 2 pts and chemoresistant disease in 5 pts. There was only one transplant-related death (one month after ASTC). With a median follow-up of 19 (1-89) months, 27 pts are alive, 8 pts have relapsed/progressed at a median time of 11 (6-22) months after ASCT. The estimated 2-year PFS and OS are 57% (95% CI, 34-81%) and 83% (95% CI, 64-100%). When comparing the progression-free interval (PFI) before salvage CT and ASCT and the PFI after ASCT, of 17 evaluable pts, 10 had a PFI after ASCT longer than the previous interval, and 5 additional pts remain in CR/PR with a follow-up that has not yet reached the duration of pre-transplant response. By contrast, 2 pts had a short post-transplant response. High-dose therapy followed by ASCT obtains a high rate of responses, frequently longer than any previous PFI. Additional follow-up is necessary to determine whether there is any "plateau" in response duration and to define what proportion of pts may be cured with ASCT in this setting.


AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study.
Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation. Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial. The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings. ISRCTN 7250 9687; Pre-results.


Arabidopsis thaliana genes encoding defense signaling and recognition proteins exhibit contrasting evolutionary dynamics.
The interplay between pathogen effectors, their host targets, and cognate recognition proteins provides various opportunities for antagonistic cycles of selection acting on plant and pathogen to achieve or abrogate resistance, respectively. Selection has previously been shown to maintain diversity in plant proteins involved in pathogen recognition and some of their cognate pathogen effectors. We analyzed the signatures of selection on 10 Arabidopsis thaliana genes encoding defense signal transduction proteins in plants, which are potential targets of pathogen effectors. There was insufficient evidence to reject neutral evolution for 6 genes encoding signaling components consistent with these proteins not being targets of effectors and/or indicative of constraints on their ability to coevolve with pathogen effectors. Functional constraints on effector targets may have provided the driving selective force for the evolution of guard proteins. PBS1, a known target of an effector, showed little variation but is known to be monitored by a variable guard protein. Evidence of selection maintaining diversity was present at NPR1, PAD4, and EDS1. Differences in the signatures of selection observed may reflect the numbers of effectors that target a particular protein, the presence or absence of a cognate guard protein, as well as functional constraints imposed by biochemical activities or interactions with plant proteins.


N6-Methyladenosine Role in Acute Myeloid Leukaemia.
We are currently assisting in the explosion of epitranscriptomics, which studies the functional role of chemical modifications into RNA molecules. Among more than 100 RNA modifications, the N6-methyladenosine (m⁶A), in particular, has attracted the interest of researchers all around the world. m⁶A is the most abundant internal chemical modification in mRNA, and it can control any aspect of mRNA post-transcriptional regulation. m⁶A is installed by "writers", removed by "erasers", and recognized by "readers"; thus, it can be compared to the reversible and dynamic epigenetic modifications in histones and DNA. Given its fundamental role in determining the way mRNAs are expressed, it comes as no surprise that alterations to m⁶A modifications have a deep impact in cell differentiation, normal development and human diseases. Here, we review the proteins involved in m⁶A modification in mammals, m⁶A role in gene expression and its contribution to cancer development. In particular, we will focus on acute myeloid leukaemia (AML), which provides an initial indication of how alteration in m⁶A modification can disrupt normal cellular differentiation and lead to cancer.


Wide-field calcium imaging of cortical activation and functional connectivity in externally- and internally-driven locomotion.
The neural dynamics underlying self-initiated versus sensory driven movements is central to understanding volitional action. Upstream motor cortices are associated with the generation of internally-driven movements over externally-driven. Here we directly compare cortical dynamics during internally- versus externally-driven locomotion using wide-field Ca2+ imaging. We find that secondary motor cortex (M2) plays a larger role in internally-driven spontaneous locomotion transitions, with increased M2 functional connectivity during starting and stopping than in the externally-driven, motorized treadmill locomotion. This is not the case in steady-state walk. In addition, motorized treadmill and spontaneous locomotion are characterized by markedly different patterns of cortical activation and functional connectivity at the different behavior periods. Furthermore, the patterns of fluorescence activation and connectivity are uncorrelated. These experiments reveal widespread and striking differences in the cortical control of internally- and externally-driven locomotion, with M2 playing a major role in the preparation and execution of the self-initiated state.


Antitumor activity of a novel bis-aziridinylnaphthoquinone (AZ4) mediating cell cycle arrest and apoptosis in non-small cell lung cancer cell line NCI-H460.
The cytotoxic activities of a series of bis-aziridinylnaphthoquinone, AZ1 to AZ4, on human lung carcinoma cell lines, H460, and normal lung cells fibroblast cell line, MRC-5, and the mechanisms of H460 cells induced by AZ4 were investigated. The MTT assay was used to determine the cell proliferation. Cell cycle was analysed by FACS. The activity of caspase 3, 8 and 9 was determined by cell-permeable fluorogenic detection system. Western blot assay was used to evaluate the regulation of cyclin B, Cdc-2, p53, p21, and the Bcl-2 protein. AZ1 to AZ4 displayed various cytotoxicity activities against H460 and MRC-5 cells. Compared to those compounds, AZ4 was with the most effective agent among the 5 tested analogues at reducing H460 cell viability with an IC(50) value of 1.23 micromol/L; it also exhibited weak cytotoxicity against MRC-5 cells with an IC(50) value of 12.7 micromol/L. The results show that growth arrest on the G2-M phase of H460 cells induced by AZ4 for 24 h was discovered, and this might be altered with the reduced Cdc-2 protein expression of 47% at 2.0 micromol/L AZ4, but not with cyclin B protein expression. The AZ4 treated cells were then led to apoptosis after 48 h. This was associated with the activation of apoptotic enzyme caspase 3 and mediated by caspase 8, but not caspase 9 at various concentrations of AZ4 after being cultured for 48 h and 30 h, respectively. The anti-apoptotic protein (Bcl-2) expression in H460 cells altered by 39% with downregulation, and the p53 protein by 25% with upregulation after being cultured with 2.0 micromol/L AZ4 for 48 h. In a time-dependent manner, the expression of the p53 and p21 proteins were increased to the maximum at 24 h, and then decreased at 48. AZ4 represents a novel antitumor aziridinylnaphthoquinone with therapeutic potential against the non-small cell lung cancer cells.


Toxicology in the fast lane: application of high-throughput bioassays to detect modulation of key enzymes and receptors.
Legislation at state, federal, and international levels is requiring rapid evaluation of the toxicity of numerous chemicals. Whole-animal toxicologic studies cannot yield the necessary throughput in a cost-effective fashion, leading to a critical need for a faster and more cost-effective toxicologic evaluation of xenobiotics. We tested whether mechanistically based screening assays can rapidly provide information on the potential for compounds to affect key enzymes and receptor targets, thus identifying those compounds requiring further in-depth analysis. A library of 176 synthetic chemicals was prepared and examined in a high-throughput screening (HTS) manner using nine enzyme-based and five receptor-based bioassays. All the assays have high Z' values, indicating good discrimination among compounds in a reliable fashion, and thus are suitable for HTS assays. On average, three positive hits were obtained per assay. Although we identified compounds that were previously shown to inhibit a particular enzyme class or receptor, we surprisingly discovered that triclosan, a microbiocide present in personal care products, inhibits carboxylesterases and that dichlone, a fungicide, strongly inhibits the ryanodine receptors. Considering the need to rapidly screen tens of thousands of anthropogenic compounds, our study shows the feasibility of using combined HTS assays as a novel approach toward obtaining toxicologic data on numerous biological end points. The HTS assay approach is very useful to quickly identify potentially hazardous compounds and to prioritize them for further in-depth studies.


Measurement of ultraviolet exposure in epidemiological studies of skin and skin cancers.
As our understanding of the role of UV in causing skin cancer continues to expand, researchers and clinicians must continue to remain up to date on the various means by which UV exposure can be quantified. The purpose of this article was to review the current methods used to measure lifetime exposure to UV and to summarize the strengths and weaknesses of each of these approaches. Thus we include here a review of research articles that deal with questionnaire reliability and physical examination. We also review more technologically advanced techniques used to measure chronic UV exposure; these include microtopography, histology, gene studies and spectroscopy. Both the utility of using a specific measurement technique and the accuracy of particular techniques are explored. Finally, we touch upon the results of articles that link UV exposure to skin cancer and what this means for the future of UV-induced skin cancer research.


Capacitive hyperthermia as an alternative to brachytherapy in DNA damages of human prostate cancer cell line (DU-145).
The aim of this study was the evaluation of induced DNA damages of human prostate cancer cells, DU-145, treated with a combination of radiofrequency capacitive hyperthermia (HT) and teletherapy (EBRT) compared to a combination of teletherapy with high-dose rate brachytherapy (BR). DU-145 cells were cultured as spheroids in 300 micron diameter. Then the following treatments were conducted: (a) EBRT at doses of either 2 Gy or 4 Gy of photon 15 MV, (b) HT for 0, 30, 60, and 90 minutes duration at 43 °C from a 13.56 MHz radiofrequency capacitive heating device (Celsius TCS), (c) BR with Ir-192 seed at doses of either 2 Gy or 5.5 Gy, (d) The mentioned HT followed by EBRT (HT + EBRT) and (e) EBRT followed by BR (EBRT + BR). Alkaline comet assay was performed to measure tail moment. The induced DNA damages of DU-145 cells treated by adding HT to EBRT compared with EBRT alone, showed a significant enhancement; 3.28 and 5.14 times respectively for 30 and 60 minutes HT. By plotting dose-response curves, we could find a range of doses, which create radiobiological iso-effect in HT + EBRT and EBRT + BR treatments. This study suggests that about DNA damages of DU-145 cells, HT + EBRT could partly be considered as an alternative to EBRT + BR.


Usefulness of aspirin therapy in high-risk pregnant women with abnormal uterine artery Doppler ultrasound at 14-16 weeks pregnancy: randomized controlled clinical trial.
To assess the effectiveness of low-dose aspirin in the prevention of preeclampsia and intrauterine growth restriction (IUGR) in high-risk pregnant women with abnormal findings at uterine artery Doppler velocimetry performed at 14-16 weeks. Randomized controlled clinical trial. Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Egypt. The trial enrolled 139 women at risk of preeclampsia or IUGR, with abnormal uterine artery Doppler findings that included the presence of unilateral or bilateral diastolic notch, high resistance index (RI), or high pulsatility index (PI) at 14-16 weeks of gestation. The women were randomly allocated into two groups, one receiving aspirin since admission to hospital (n=74) and the other serving as control (n=65). All women were followed up until delivery to assess maternal and perinatal outcomes. T-test was used for comparison of quantitative variables, and categorical variables were compared by chi2 test. OUTCOME CRITERIA: Development of mild or severe preeclampsia, time of onset of preeclampsia, preterm delivery, and the development of IUGR. Preeclampsia developed in 35% of women receiving aspirin and 62% of women in the control group (P=0.003), with severe preeclampsia developing in 8% and 23% of women (P=0.215), respectively. Preeclampsia before 37 weeks of gestation was recorded in only 4% of women receiving aspirin as opposed to 83% of controls (P<0.001). In the group of women receiving aspirin, 19% of newborns suffered from IUGR as opposed to 32%of newborns in the control group (P=0.106). There was no significant difference between the two groups in the rate of preterm delivery (P=0.080), mode of delivery (P=0.971), Apgar score <5 after one minute (P=0.273) and after 5 minutes (P=0.941), maternal or neonatal bleeding (P=0.948), and neonatal birth weight (P=0.399). Low-dose aspirin administered as early as 14-16 weeks of gestation to pregnant women at high risk of preeclampsia with abnormal uterine Doppler findings may reduce or modify the course of severe preeclampsia. Its effects on the prevention of IUGR need further evaluation.


The role of platelets in infections. I. Observations in human and murine malaria.
The interaction between platelets and microorganisms may be underestimated. Our in vivo studies support a direct role of thrombocytes in malarial infections. We have found intrathrombocytic parasites of Plasmodium vivax (in 10% of men naturally infected) and P berghei (in 53% of mice experimentally infected); these were both merozoites and trophozoites. Neither the mechanism of parasitization (whether by active penetration or by phagocytosis) nor the outcome of this phenomenon is known. However, structures suggestive of partially digested parasitic material were seen in platelets of almost 50% of the men and 75% of the mice. These findings suggest that other microoganisms (fungi, bacteria, and viruses) may also enter thrombocytes in vivo. If so, platelets could play important roles, either favorable or deleterious, in infections.


Arterial-ventricular coupling: mechanistic insights into cardiovascular performance at rest and during exercise.
Understanding the performance of the left ventricle (LV) requires not only examining the properties of the LV itself, but also investigating the modulating effects of the arterial system on left ventricular performance. The interaction of the LV with the arterial system, termed arterial-ventricular coupling (E(A)/E(LV)), is a central determinant of cardiovascular performance and cardiac energetics. E(A)/E(LV) can be indexed by the ratio of effective arterial elastance (E(A); a measure of the net arterial load exerted on the left ventricle) to left ventricular end-systolic elastance (E(LV); a load-independent measure of left ventricular chamber performance). At rest, in healthy individuals, E(A)/E(LV) is maintained within a narrow range, which allows the cardiovascular system to optimize energetic efficiency at the expense of mechanical efficacy. During exercise, an acute mismatch between the arterial and ventricular systems occurs, due to a disproportionate increase in E(LV) (from an average of 4.3 to 13.2, and 4.7 to 15.5 mmHg.ml(-1).m(-2) in men and women, respectively) vs. E(A) (from an average of 2.3 to 3.2, and 2.3 to 2.9 mmHg.ml(-1).m(-2) in men and women, respectively), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. As a result E(A)/E(LV) decreases from an average of 0.58 to 0.34, and 0.52 to 0.27 in men and women, respectively. In this review, we provide an overview of the concept of E(A)/E(LV), and examine the effects of age, hypertension, and heart failure on E(A)/E(LV) and its components (E(A) and E(LV)) in men and women. We discuss these effects both at rest and during exercise and highlight the mechanistic insights that can be derived from studying E(A)/E(LV).


Knowledge of HIV/AIDS and sexual practices among adolescents in Benin City, Nigeria.
A cross sectional study to determine the knowledge of HIV/AIDS and sexual practices of adolescents was undertaken in Benin City, Nigeria. Benin City the capital of Edo State, Nigeria, has 40 government owned secondary schools comprising 6 boys, 10 girls, and 24 mixed. Out of these 3 schools were randomly selected for survey viz; Adolor (boys only), Iyoba (girls only), Army Day (mixed). The sample size for the survey was 920 while the total population for selected schools was 1692 giving a sampling ratio of 1:2. Using the systematic sampling method and class register as sampling frame every other child was selected for the study. However, only 852 students consented to participate giving a response rate of 92.6%. An overwhelming majority of the adolescents were aware of HIV/AIDS but only 16.2% knew the cause of the disease. The submission that kissing, living with infected persons and sharing their utensils could lead to infection was an indication of ignorance. Sexual intercourse was the predominant route of transmission mentioned by 60.0% while multiple sexual partners was prevalent among age group 13-15 years. Playing with sharps, frequent clean head shave with unsterilised instruments in the barbing saloon and promiscuity were some of the activities that adolescents were involved in that could lead to HIV/AIDS infection. In conclusion, the knowledge of the study population was poor and correlates with their reckless sexual practices. Prevention is the best option to the disease. Better informed youths on HIV/AIDS will enhance the principle of prevention.


Beyond compliance: A randomized trial of DEI statements and subsequent signals for job seekers with disabilities.
Companies are increasingly attending to their Diversity, Equity, and Inclusion (DEI) statements in their public-facing documents, including job advertisements. Little is known about how various decisions about language type or placement within a job ad are received by marginalized populations, including those living with disabilities. This study aims to explore various options for DEI statements within job ads, to assess whether these choices have a measurable impact on potential job seekers living with disabilities. An experiment with a 2 × 2 × 2 design was used which varied the DEI language (legal/traditional or heartfelt), the placement at the top or the bottom of the job advertisement, and whether the company offered the opportunity to indicate a need for accommodations even before the interview. Quantitative and qualitative items measured general reactions to the statement, intent to apply to this company, willingness to disclose a need for accommodations, how supportive the company seemed, and impressions of the company's level of trustworthiness. Statistical tests include t-tests, z-tests for proportions, and regression-based tests for mediation. Heartfelt statements and upfront placement inspired more positive reactions from participants, with trust mediating these positive relationships. However, participants also expressed skepticism that, regardless of language, bias would still exist in the reality of the job. These results suggest that job candidates with disabilities are not indifferent to a company's DEI framing and prefer heartfelt language and earlier placement, though statements without direct evidence can raise suspicion about whether the actions would stay true to the words.


[Effect of bamboo leaf biochar addition on soil CO2 efflux and labile organic carbon pool in a Chinese chestnut plantation].
Effect of biochar addition on soil CO2 efflux in a typical Chinese chestnut (Castanea mollissima) plantation in Lin'an, Zhejiang Province, China was investigated from July 2012 to July 2013 by the static closed chamber-GC technique. Soil temperature, soil moisture, WSOC and MBC concentrations were determined as well. Results showed that soil CO2 efflux exhibited a strong sea- sonal pattern. Compared with the control (without biochar application), the biochar treatment increased the soil CO2 efflux only in the first month since application, and then the effect diminished thereafter. There were no significant differences in the annual cumulative value of soil CO2 efflux between the biochar and control treatments. The annual mean value in soil MBC concentration (362 mg · kg(-1)) in the biochar treatment was higher than that (322 mg · kg(-1)) in the control. However, no significant difference in the soil WSOC concentration was found between the biochar and control treatments. Strong exponential relationships between soil temperature and soil CO2 efflux were observed regardless of the treatment and soil layer. The apparent temperature sensitivity (Q10) of soil CO2 efflux in the biochar treatment was higher than that in the control. Soil CO2 efflux was related to soil WSOC concentration but not with soil MBC or moisture content. To conclude, the application of bamboo leaf biochar did not affect the annual cumulative CO2 emission in the Chinese chestnut plantation but increased the Q10, and the CO2 efflux was predominantly controlled by the soil temperature and soil WSOC level.


Hepatitis C virus core protein enhances hepatocellular carcinoma cells to be susceptible to oncolytic vesicular stomatitis virus through down-regulation of HDAC4.
Since hepatitis C virus (HCV) core protein is known to possess potential oncogenic activity, we explored whether oncolytic vesicular stomatitis virus (VSV) could efficiently induce cytolysis in hepatocellular carcinoma cells stably expressing HCV core protein (Hep3B-Core). We found that Hep3B-Core cells were more susceptible to VSV as compared to control (Hep3B-Vec) cells owing to core-mediated inactivation of STAT1 and STAT2 proteins. Core expression induced lower phosphorylation levels of type I IFN signaling proteins such as Tyk2 and Jak1, and a reduced response to exogenous IFN-α, which resulted in susceptibility to VSV. Furthermore, as STAT1 acetylation by switching phosphorylation regulated its activity, the role of STAT1 acetylation in susceptibility of Hep3B-Core cells to VSV was investigated. Treatment with trichostatin A, an inhibitor of histone deacetylase (HDAC), increased STAT1 acetylation but blocked IFN-α-induced phosphorylation of STAT1, leading to increase of susceptibility to VSV. Interestingly, the core protein decreased HDCA4 transcript levels, leading to down-regulation of HDAC4 protein. However, ectopic expression of HDAC4 conversely enforced phosphorylation of STAT1 and hindered VSV replication, indicating that core-mediated reduction of HDAC4 provides a suitable intracellular circumstance for VSV replication. Collectively, we suggest that VSV treatment will be a useful therapeutic strategy for HCV-infected hepatocellular carcinoma cells because HCV core protein suppresses the anti-viral threshold by down-regulation of the STAT1-HDAC4 signaling axis.


Beta-cell CaV channel regulation in physiology and pathophysiology.
The beta-cell is equipped with at least six voltage-gated Ca2+ (CaV) channel alpha1-subunits designated CaV1.2, CaV1.3, CaV2.1, CaV2.2, CaV2.3, and CaV3.1. These principal subunits, together with certain auxiliary subunits, assemble into different types of CaV channels conducting L-, P/Q-, N-, R-, and T-type Ca2+ currents, respectively. The beta-cell shares customary mechanisms of CaV channel regulation with other excitable cells, such as protein phosphorylation, Ca2+-dependent inactivation, and G protein modulation. However, the beta-cell displays some characteristic features to bring these mechanisms into play. In islet beta-cells, CaV channels can be highly phosphorylated under basal conditions and thus marginally respond to further phosphorylation. In beta-cell lines, CaV channels can be surrounded by tonically activated protein phosphatases dominating over protein kinases; thus their activity is dramatically enhanced by inhibition of protein phosphatases. During the last 10 years, we have revealed some novel mechanisms of beta-cell CaV channel regulation under physiological and pathophysiological conditions, including the involvement of exocytotic proteins, inositol hexakisphosphate, and type 1 diabetic serum. This minireview highlights characteristic features of customary mechanisms of CaV channel regulation in beta-cells and also reviews our studies on newly identified mechanisms of beta-cell CaV channel regulation.


2-Deoxy-D-glucose activates autophagy via endoplasmic reticulum stress rather than ATP depletion.
The glucose analog and glycolytic inhibitor 2-deoxy-D-glucose (2-DG), which is currently under clinical evaluation for targeting cancer cells, not only blocks glycolysis thereby reducing cellular ATP, but also interferes with N-linked glycosylation, which leads to endoplasmic reticulum (ER) stress and an unfolded protein response (UPR). Both bioenergetic challenge and ER stress have been shown to activate autophagy, a bulk cellular degradation process that plays either a pro- or anti-death role. Here, we investigate which pathway 2-DG interferes with that activates autophagy and the role of this process in modulating 2-DG-induced toxicity. Pancreatic cancer cell line 1420, melanoma cell line MDA-MB-435 and breast cancer cell line SKBR3 were used to investigate the relationship between induction by 2-DG treatment of ER stress/UPR, ATP reduction and activation of autophagy. ER stress/UPR (Grp78 and CHOP) and autophagy (LC3B II) markers were assayed by immunoblotting, while ATP levels were measured using the CellTiter-Glo Luminescent Cell Viability Assay. Autophagy was also measured by immunofluorescence utilizing LC3B antibody. Cell death was detected with a Vi-Cell cell viability analyzer using trypan blue exclusion. In the three different cancer cell lines described earlier, we find that 2-DG upregulates autophagy, increases ER stress and lowers ATP levels. Addition of exogenous mannose reverses 2-DG-induced autophagy and ER stress but does not recover the lowered levels of ATP. Moreover, under anaerobic conditions where 2-DG severely depletes ATP, autophagy is diminished rather than activated, which correlates with lowered levels of the ER stress marker Grp78. Additionally, when autophagy is blocked by siRNA, cell sensitivity to 2-DG is increased corresponding with upregulation of ER stress-mediated apoptosis. Similar increased toxicity is observed with 3-methyladenine, a known autophagy inhibitor. In contrast, rapamycin which enhances autophagy reduces 2-DG-induced toxicity. Overall, these results indicate that the major mechanism by which 2-DG stimulates autophagy is through ER stress/UPR and not by lowering ATP levels. Furthermore, autophagy plays a protective role against 2-DG-elicited cell death apparently by relieving ER stress. These data suggest that combining autophagy inhibitors with 2-DG may be useful clinically.


COVID-19 and contamination: impact on exposures to alcohol-based hand sanitizers reported to Texas Poison Control Centers, 2020.
The COVID-19 pandemic has increased use of alcohol-based hand sanitizers (ABHS), creating shortages leading to additional production by new, non-traditional manufacturers. In June 2020, the Food and Drug Administration (FDA) issued warnings about methanol or 1-propanol contaminated brands of hand sanitizer. Exposure to methanol, including dermally, can cause kidney damage, blindness and death. Exposure to 1-propanol can cause severe acidosis and death. Chronic exposure may be more likely due to increased hand sanitizer use in 2020. We used generic codes for ABHS to characterize exposures reported to the Texas Poison Control Network in 2019 and 2020. For 2020 cases, we also used case narratives to identify cases considered COVID-19 -related and cases where the caller reported exposure to unknown ABHS with safety concerns, specifically identified brands on the FDA warning list or before that warning was made in June 2020. Reported exposures to ABHS increased 72.5% between 2019 and 2020. In 2020, 10% of the cases were COVID-19 -related. COVID-19 -related cases in 2020 were likely to be older, to have a lower portion of young children exposed and to report chronic use of hand sanitizer. Similar trends were reported among cases who reported possible exposures to potentially unsafe ABHS products, including products on the FDA list. Most exposures were not referred for medical attention, and no deaths were reported among the Texas cases. Callers reporting exposures to ABHS related to use prompted by the novel severe acute respiratory syndrome coronavirus 2 (COVID-19) and specific exposure to unsafe products differ from the traditional callers in being older, reporting chronic use and in healthcare facility (HCF) referral. The 72.5% increase in 2020 calls compared to 2019 cases differ from typical exposures, which often involve young children. Changes in manufacturing processes by additional manufacturers have produced potential exposure to toxic alcohol-containing products and others in Texas.


Heat Shock Improves Random Spore Analysis in Diverse Strains of Saccharomyces cerevisiae.
Random spore analysis (RSA) is a classic method in yeast genetics that allows high-throughput purification of recombinant haploid spores following specific crosses. RSA typically involves a number of steps to induce sporulation, purge vegetative cells that fail to sporulate, and disrupt the ascus walls of sporulated cells to release haploid spores. These steps generally require expensive chemicals and/or enzymes that kill diploid cells but have few effects on spores. In the fission yeast Schizosaccharomcyes pombe, heat shock has been reported as an effective addition to RSA protocols, but to our knowledge heat shock has not been used for this purpose in the budding yeast Saccharomyces cerevisiae. Here, we evaluate the effects of heat shock on vegetative and sporulated cultures of four diverse yeast strains: a European wine strain (DBVPG6765), a Japanese sake strain (Y12), a West African palm wine strain (DBVPG6044) and a North American strain isolated from the soil beneath an oak tree (YPS128). We characterize this phenotype under multiple combinations of temperature and incubation time, and find specific conditions that lead to the exclusion of vegetative cells and an enrichment in spores, which differ by strain. We also collected genome sequence data from a recombinant population that experienced multiple rounds of RSA, including one round with a heat shock treatment. These data suggest that when incorporated into an RSA protocol, heat shock leads to increased genetic diversity among the cells that survive and mate. Ultimately, our work provides evidence that short heat treatments can improve existing RSA protocols, though in a strain-specific manner. This result informs applications of high-throughput RSA protocols, such as QTL mapping and experimental evolution research.


Functional domains of the heavy metal-responsive transcription regulator MTF-1.
Metallothioneins (MTs) constitute a class of low molecular weight, cysteine-rich, metal binding proteins which are regulated at the level of gene transcription in response to heavy metals and other adverse treatments. We have previously cloned a zinc finger factor (MTF-1) that binds specifically to heavy metal-responsive DNA sequence elements in metallothionein promoters and shown that this factor is essential for basal and heavy metal-induced transcription. Here we report that the C-terminal part of MTF-1 downstream of the DNA binding zinc fingers harbours three different transactivation domains, namely an acidic domain, a proline-rich domain and a domain rich in serine and threonine. When fused to the heterologous DNA binding domain of the yeast factor GAL4 these activation domains function constitutively, i.e. transcription of a GAL4-driven reporter gene is not induced by heavy metals. In search of the region(s) responsible for metal induction, external and internal deletion mutations of mouse and human MTF-1 and chimeric variants thereof were tested with a reporter gene driven by a metal-responsive promoter. The N-terminal part of MTF-1 containing the zinc fingers, which are dependent on zinc for efficient DNA binding, can indeed confer a limited (3- to 4-fold) zinc-responsive transcription when fused to the heterologous activation domain of the viral VP16 protein. Another region containing the acidic and proline-rich activation domains also contributes to metal inducibility, but only in the context of intact MTF-1. This indicates that the activity of MTF-1 results from a complex interplay of different functional domains.


mTOR inhibition elicits a dramatic response in PI3K-dependent colon cancers.
The phosphatidylinositide-3-kinase (PI3K) signaling pathway is critical for multiple cellular functions including metabolism, proliferation, angiogenesis, and apoptosis, and is the most commonly altered pathway in human cancers. Recently, we developed a novel mouse model of colon cancer in which tumors are initiated by a dominant active PI3K (FC PIK3ca). The cancers in these mice are moderately differentiated invasive mucinous adenocarcinomas of the proximal colon that develop by 50 days of age. Interestingly, these cancers form without a benign intermediary or aberrant WNT signaling, indicating a non-canonical mechanism of tumorigenesis. Since these tumors are dependent upon the PI3K pathway, we investigated the potential for tumor response by the targeting of this pathway with rapamycin, an mTOR inhibitor. A cohort of FC PIK3ca mice were treated with rapamycin at a dose of 6 mg/kg/day or placebo for 14 days. FDG dual hybrid PET/CT imaging demonstrated a dramatic tumor response in the rapamycin arm and this was confirmed on necropsy. The tumor tissue remaining after treatment with rapamycin demonstrated increased pERK1/2 or persistent phosphorylated ribosomal protein S6 (pS6), indicating potential resistance mechanisms. This unique model will further our understanding of human disease and facilitate the development of therapeutics through pharmacologic screening and biomarker identification.


Autonomous underwater vehicle fault diagnosis dataset.
The dataset contains 1225 data samples for 5 fault types (labels). We divided the dataset into the training set and the test set through random stratified sampling. The test set accounted for 20 % of the total dataset. Our experimental subject is 'Haizhe', which is a small quadrotor AUV developed in the laboratory. For each fault type, 'Haizhe' was tested several times. For each time, 'Haizhe' ran the same program and sailed underwater for 10-20 s to ensure that state data was long enough. The state data recorded in each test were then used as a data sample, and the corresponding fault type was the true label of the data sample. The dataset was used to validate a model-free fault diagnosis method proposed in our paper [1] and the complete dynamic model of 'Haizhe' AUV was reported in [2].


The donation and transplantation of kidneys: should the law be changed?
It is now eighteen years on since the Human Tissue Act 1961, but this legislation is still unchanged in England, Scotland and Wales. Ian Kennedy, in this paper, lays before us the law as it is, the problems of its interpretation and his opinion of what government should be doing to help clarify the situation and remove some of the problems which exist daily for the doctors who face the dilemma of seeking consent for transplants at the moment of extreme grief for the surviving spouses or relatives of the patient who has been in his care only moments before. Ian Kennedy suggests that by doing nothing the Department of Health and the government are being both callous and less than honest.


Plasma urate and Parkinson's disease in the Atherosclerosis Risk in Communities (ARIC) study.
Higher plasma urate concentration has been linked to lower risk of Parkinson's disease in men, but data are lacking on women and African Americans. The authors examined plasma urate in relation to Parkinson's disease in the biracial, population-based Atherosclerosis Risk in Communities (ARIC) cohort. Between 1987 and 1989, 15,792 participants, aged 45-64 years, were recruited from 4 US communities and have since been followed with 3 triennial visits and annual surveillance. Plasma urate was measured at visits 1 and 2, and the concentrations were highly correlated. From visit 1 through 2004, 95 potential cases of Parkinson's disease were identified from multiple sources. Odds ratios and 95% confidence intervals were calculated from multivariate logistic regression models. Plasma urate concentration was inversely associated with Parkinson's disease occurrence. The odds ratios between extreme quartiles of plasma urate were 0.4 (95% confidence interval: 0.2, 0.8) in the overall analysis, 0.3 (95% confidence interval: 0.1, 0.7) for men, and 0.4 (95% confidence interval: 0.2, 1.0) for Caucasians. Such an association was also suggested among women and African Americans but was not statistically significant because of small sample sizes. These data support the previous finding that urate may be a protective factor against Parkinson's disease.


Health information, privacy, confidentiality and ethics.
Electronic patient records are becoming tologically reified entities that play the role of epistemic patient analogues in information space. The traditional property-model of patient records is therefore no longer appropriate. A shift in paradigm is required. This paper suggests a new paradigm, examines its ethical implications and explores ways in which these could be reflected in legal and regulatory mechanisms. Special attention is paid to privacy, security and access relative to the so-called 'fair information principles'.


Exercise and mental illness: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
Regular exercise is thought to be associated with low rates of mental illness, but this association has been inadequately studied. The purpose of this study was to test the hypotheses that the recommended amount of self-reported vigorous exercise would be cross-sectionally associated with reduced prevalence and incidence of various DSM-IV psychiatric disorders, as well as increased rates of remission. Data were collected from 2001 to 2005 as part of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a 2-wave face-to-face survey conducted by the National Institute on Alcohol Abuse and Alcoholism. For this study, the sample consisted of 23,505 nondisabled adults aged between 18 and 65 years. Individuals who engaged in vigorous exercise at Wave 2 were significantly more likely than were nonexercisers to be diagnosed with a current psychiatric disorder (adjusted odds ratio [AOR] = 1.22, 95% CI, 1.12-1.34 for the nationally recommended amount vs no exercise), significantly less likely to attain remission from a psychiatric disorder between waves (AOR = 0.77, 95% CI, 0.65-0.91), and significantly more likely to relapse or be newly diagnosed with a psychiatric disorder between waves (AOR = 1.15, 95% CI, 1.02-1.30). Alcohol dependence and bipolar II disorder were the disorders most strongly associated with exercise. This investigation suggests that the pursuit of vigorous exercise is associated with a vulnerability to mental illness. This surprising finding may be due to reward-related factors that influence both exercise engagement and the expression of certain psychiatric disorders. Prospective trials will be helpful in further clarifying the associations between exercise and mental illness, as the relationships between the 2 are more complex than previously believed.


Influence of Temperature-Guided SAM Growth on Wetting and Its Mass Transfer Models.
The formation and growth of self-assembled monolayers (SAMs) composed of amphiphiles have garnered significant attention due to their diverse technical applications. This article reports the findings of molecular dynamics simulations aimed at elucidating the intricate relationship between the wetting behavior of amphiphiles, specifically n-alkanols, and the growth of their SAMs on a mica surface under varying temperature conditions. The investigation quantifies the structural characteristics of the formed SAMs, including density profiles, in-plane radial distribution functions, order parameters, and end-to-end length distributions of n-alkanol molecules within the SAM. Thermodynamic properties, such as the second virial coefficient and excess entropy, are examined in relation to temperature and time. The growth of the SAM is assessed by analyzing characteristic time scales at different temperatures and in-plane diffusion of n-alkanol molecules and utilizing classical theories of mass transfer to quantify the growth rate as a function of temperature. These results are then correlated with changes in the contact angle and spreading coefficient of n-alkanol droplets on the mica surface over time, providing insights into the impact of SAM growth on the wetting behavior and the mass transfer model of such systems.


Circular RNA Fibroblast Growth Factor Receptor 1 Promotes Pancreatic Cancer Progression by Targeting MicroRNA-532-3p/PIK3CB Axis.
The aim of the study is to explore the contribution and mechanism of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in pancreatic ductal adenocarcinoma (PDAC) progression. Expressions of circFGFR1, microRNA (miR)-532-3p, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) were assessed by quantitative real-time polymerase chain reaction or in situ hybridization. Fluorescence in situ hybridization determined the subcellular localization of circFGFR1. Immunohistochemistry was used to detect PIK3CB expression in PDAC tissues. Cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Wound healing, transwell, and flow cytometry assays examined the migration, invasion, and apoptosis. Dual-luciferase and RNA pull-down assay verified the interactions between circFGFR1/PIK3CB and miR-532-3p. In vivo xenograft tumor growth and lung metastasis were assessed in nude mice. Functionally, knockdown of circFGFR1 restrained in vitro PDAC cell growth, migration, invasion, and in vivo xenograft tumor growth and lung metastasis. In addition, circFGFR1 could sponge miR-532-3p to upregulate PIK3CB level. Rescue experiments revealed that the tumor-suppressive effects caused by miR-532-3p mimics could be reversed by circFGFR1 or PIK3CB overexpression. Our data revealed that circFGFR1 driven the malignant progression of PDAC by targeting miR-532-3p/PIK3CB axis, suggesting that inhibition of circFGFR1 might be considered as a therapeutic target for PDAC.


Thiamine pyrophosphate biosynthesis and transport in the nematode Caenorhabditis elegans.
Thiamine (vitamin B1) is required in the diet of animals, and thiamine deficiency leads to diseases such as beri-beri and the Wernicke-Korsakoff syndrome. Dietary thiamine (vitamin B1) consists mainly of thiamine pyrophosphate (TPP), which is transformed into thiamine by gastrointestinal phosphatases before absorption. It is believed that TPP itself cannot be transported across plasma membranes in significant amounts. We have identified a partial loss-of-function mutation in the Caenorhabditis elegans gene (tpk-1) that encodes thiamine pyrophosphokinase, which forms TPP from thiamine at the expense of ATP inside cells. The mutation slows physiological rhythms and the phenotype it produces can be rescued by TPP but not thiamine supplementation. tpk-1 functions cell nonautonomously, as the expression of wild-type tpk-1 in one tissue can rescue the function of other tissues that express only mutant tpk-1. These observations indicate that, in contrast to expectation from previous evidence, TPP can be transported across cell membranes. We also find that thiamine supplementation partially rescues the phenotype of partial loss-of-function mutants of the Na/K ATPase, providing genetic evidence that thiamine absorption, and/or redistribution from the absorbing cells, requires the full activity of this enzyme.


The different pathogeneses of sporadic adenoma and adenocarcinoma in non-ampullary lesions of the proximal and distal duodenum.
Non-ampullary duodenal adenoma with activation of Wnt/β-catenin signalling is common in familial adenomatous polyposis (FAP) patients, whereas sporadic non-ampullary adenoma is uncommon. The adenoma-carcinoma sequence similar to colon cancer is associated with duodenal tumors in FAP, but not always in sporadic tumors. We obtained 37 non-ampullary duodenal tumors, including 25 adenomas and 12 adenocarcinomas, were obtained from biopsies and endoscopic resections. We performed immunohistochemistry for β-catenin, the hallmark of Wnt activation, and aldehyde dehydrogenase 1 (ALDH1), a putative cancer stem cell marker. In non-ampullary lesions, abnormal nuclear localization of β-catenin was observed in 21 (84.0%) of 25 adenomas and 4 (33.3%) of 12 adenocarcinomas. In the proximal duodenum, nuclear β-catenin was less frequent in both adenomas and adenocarcinomas. Gastric duodenal metaplasia (GDM) was observed only in the proximal duodenum. All adenomas with GDM were the gastric foveolar and pyloric gland types, and showed only membranous β-catenin. The intestinal-type adenomas had nuclear β-catenin in the proximal and distal duodenum. ALDH1-positive cells were more frequent in adenocarcinomas than adenomas. Nuclear β-catenin accumulation frequently occurred in ALDH1-positive cells in adenoma, but not in adenocarcinoma. In the non-ampullary proximal duodenum, Wnt/β-catenin pathway activation was more closely associated with adenomas than adenocarcinomas, and while it might cooperate with ALDH1 in adenoma, it does not in adenocarcinoma. The pathogenesis thus may differ between sporadic adenoma and adenocarcinoma of non-ampullary duodenal lesions, especially in the proximal and distal duodenum.


Pioneer Axons Utilize a Dcc Signaling-Mediated Invasion Brake to Precisely Complete Their Pathfinding Odyssey.
Axons navigate through the embryo to construct a functional nervous system. A missing part of the axon navigation puzzle is how a single axon traverses distinct anatomic choice points through its navigation. The dorsal root ganglia (DRG) neurons experience such choice points. First, they navigate to the dorsal root entry zone (DREZ), then halt navigation in the peripheral nervous system to invade the spinal cord, and then reinitiate navigation inside the CNS. Here, we used time-lapse super-resolution imaging in zebrafish DRG pioneer neurons to investigate how embryonic axons control their cytoskeleton to navigate to and invade at the correct anatomic position. We found that invadopodia components form in the growth cone even during filopodia-based navigation, but only stabilize when the axon is at the spinal cord entry location. Further, we show that intermediate levels of DCC and cAMP, as well as Rac1 activation, subsequently engage an axon invasion brake. Our results indicate that actin-based invadopodia components form in the growth cone and disruption of the invasion brake causes axon entry defects and results in failed behavioral responses, thereby demonstrating the importance of regulating distinct actin populations during navigational challenges.SIGNIFICANCE STATEMENT Correct spatiotemporal navigation of neuronal growth cones is dependent on extracellular navigational cues and growth cone dynamics. Here, we link dcc-mediated signaling to actin-based invadopodia and filopodia dynamics during pathfinding and entry into the spinal cord using an in vivo model of dorsal root ganglia (DRG) sensory axons. We reveal a molecularly-controlled brake on invadopodia stabilization until the sensory neuron growth cone is present at the dorsal root entry zone (DREZ), which is ultimately essential for growth cone entry into the spinal cord and behavioral response.


The rate of handedness conversion and related factors in left-handed children.
The rate of handedness conversion was 2.7% to 11.8% in prior studies based on the total population including innately right-handed people. However, the conversion rate of innately left-handed people has not been reported. The purpose of this study was to investigate the percentage of handedness conversion in children who are innately left-handed. The data in the present study showed that 59.3% (121/211) of left-handed children had been forced to convert to right-handedness. Current handedness was also reported by 114 of the 121 informants, and the rates of right-, left-, and mixed-handedness were 56.1% (64/114), 26.3% (30/114), and 17.5% (20/114) respectively. More than half had successfully changed from left to right. Some variables, especially the educational level of the parents and the child's grade level, were related to this conversion intention. The children whose parents had less education were more likely to be forced to change handedness. Additionally, the rate of handedness conversion in younger children was lower than in older children. However, even for the children whose parents had higher education, or for the children who were younger, there was a high percentage (45.7% and 41.8% respectively) who had changed their handedness. Therefore, preventing the possible side effects for children who have undergone hand conversion should be emphasised in the future.


Effect of exercise training and isoflavones on hepatic steatosis in overweight postmenopausal women.
Postmenopausal women are particularly inclined to an increased risk of developing non-alcoholic hepatic steatosis. The purpose of this study was to investigate whether adding isoflavone supplementation to exercise training could reduce the risk. In a 6-month, double-blind, randomized, controlled trial, 54 healthy overweight-to-obese (body mass index 28-40 kg/m2) postmenopausal women were randomly assigned to one of the following groups: (1) exercise and isoflavones (Ex-Iso; n = 26), (2) exercise and placebo (Ex-Pla; n = 28). Exercise training consisted of three weekly sessions of mixed training. We examined the plasma level of specific hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and alkaline phosphatase) as a reflection of fatty liver along with the calculation of the fatty liver index. All measures were obtained at baseline and after the 6-month intervention. Following the intervention, a lower fatty liver index (p <0.01; 29% in Ex-Iso, 18% in Ex-Pla) and plasma γ-glutamyltransferase (p <0.01; 22% in Ex-Iso, 16% in Ex-Pla) were observed in both groups, with a higher reduction in the Ex-Iso group. On the other hand, for all other hepatic enzymes, there was no change. Our results show that exercise training appears to bring favorable changes in the plasma level of hepatic enzymes, possibly due to the lowering of liver fat content. While postmenopausal women can benefit from this intervention to decrease the risk of developing non-alcoholic hepatic steatosis, it seems that the addition of isoflavones to exercise training provides some additional effects to those provided by exercise alone.


Delayed intraventricular hemorrhage is common and worsens outcomes in intracerebral hemorrhage.
To evaluate the incidence, characteristics, and clinical consequences of delayed intraventricular hemorrhage (dIVH). Patients with primary intracerebral hemorrhage (ICH) were enrolled into a prospective registry between December 2006 and February 2012. Patients were managed, and serial neuroimaging obtained, per a structured protocol. Initial and delayed IVH were identified on imaging, along with ICH volumes, with outcomes blinded. Multivariate models were developed to test whether the occurrence of dIVH was a predictor of functional outcomes independent of known predictors, including the ICH score elements and ICH growth. A total of 216 patients were studied, and 104 (48%) had IVH on initial imaging. Of the 112 with no IVH, 23 (21%) subsequently developed IVH. Emergent surgical intervention, mostly ventriculostomy placement, was required after discovery of dIVH in 10 (43%) of these 23. In multivariate models adjusting for all elements of the ICH score and hematoma growth, dIVH was an independent predictor of death at 14 days (p = 0.015) and higher modified Rankin Scale scores at 3 months (all p = 0.037). The effect of dIVH remained significant in a secondary analysis that adjusted for all other variables significant in the univariate analysis. Similar to hematoma expansion dIVH is independently associated with death and poor outcomes. Because IVH is easily detected by serial neuroimaging and often requires emergent surgical intervention, monitoring for dIVH is recommended.


The iliac buttress. A computed tomographic study of sacral anatomy.
Fifty randomly selected computed tomographic (CT) scans of the lumbosacral spine (25 males and 25 females) were studied to determine: 1) if the lateral sacral masses could safely accept a 7 mm diameter rod (i.e., intrasacral rod insertion) and 2) what percentage of patients, both males and females, demonstrated coverage of the posterolateral sacrum by the ilia (i.e., iliac buttressing). In all patients the lateral masses (i.e., the lateral intrasacral mass measurements) appeared wide enough on CT to allow for safe insertion of a 7 mm diameter rod, or other similar size implant, down to at least the level of S2. The smallest distance measured for the width between the posteromedial margin of the sacroiliac joint and the lateral cortex of the S1 neuroforamen (i.e., the lateral intrasacral mass measurement) at its location approximately midway (anteroposterior) through the sacrum on CT cuts was 17 mm (mean 28 mm). This would appear to give adequate room for a 7 mm diameter rod to be inserted at this level in the lateral sacrum (i.e., intrasacral rod insertion). Forty-six patients (24 males, 96%; and 22 females, 88%) appeared to have sufficient CT coverage of the sacrum to conceptually provide for so called "sacroiliac buttressing" of rods, if rods or other implants were to be inserted distally into the lateral masses. After a review of the sacral anatomy by CT it appears that: 1) insertion of rods into the lateral sacral masses (i.e. intrasacral rod insertions), or intrasacral fixation with other similar size implants, would be possible and apparently safe; and 2) the ilia along with the sacroiliac interosseous ligaments sufficiently surround the back and sides of the posterolateral sacrum in most patients (92%), at least by CT assessment, to conceptually offer an indirect "buttress" for implants so inserted. Theoretically, this could biomechanically help resist the flexural loads across the lumbosacral level and possibly provide a method for improved sacral fixation with spinal instrumentation in certain patients.


The DNA-bending protein HMGB1 is a cellular cofactor of Sleeping Beauty transposition.
Sleeping Beauty (SB) is the most active Tc1/ mariner-type transposon in vertebrates. SB contains two transposase-binding sites (DRs) at the end of each terminal inverted repeat (IR), a feature termed the IR/DR structure. We investigated the involvement of cellular proteins in the regulation of SB transposition. Here, we establish that the DNA-bending, high-mobility group protein, HMGB1 is a host-encoded cofactor of SB transposition. Transposition was severely reduced in mouse cells deficient in HMGB1. This effect was rescued by transient over-expression of HMGB1, and was partially complemented by HMGB2, but not with the HMGA1 protein. Over-expression of HMGB1 in wild-type mouse cells enhanced transposition, indicating that HMGB1 can be a limiting factor of transposition. SB transposase was found to interact with HMGB1 in vivo, suggesting that the transposase may recruit HMGB1 to transposon DNA. HMGB1 stimulated preferential binding of the transposase to the DR further from the cleavage site, and promoted bending of DNA fragments containing the transposon IR. We propose that the role of HMGB1 is to ensure that transposase-transposon complexes are first formed at the internal DRs, and subsequently to promote juxtaposition of functional sites in transposon DNA, thereby assisting the formation of synaptic complexes.


Multiple extra-bone accumulations of technetium-99m-HMDP.
Bone scintigraphy was performed on a woman 2 y and 10 mo after surgery for rectal cancer. Intense extra-bone accumulations of 99mTc-HMDP were visible in an aortic atherosclerosis lesion and in a metastatic liver tumor. Uptake in the metastatic lesion was confirmed by x-ray CT. Uptake in the aortic lesion was shown as typical calcification by x-ray CT.


Development of a Biological Science Quantitative Reasoning Exam (BioSQuaRE).
Multiple reports highlight the increasingly quantitative nature of biological research and the need to innovate means to ensure that students acquire quantitative skills. We present a tool to support such innovation. The Biological Science Quantitative Reasoning Exam (BioSQuaRE) is an assessment instrument designed to measure the quantitative skills of undergraduate students within a biological context. The instrument was developed by an interdisciplinary team of educators and aligns with skills included in national reports such as BIO2010, Scientific Foundations for Future Physicians, and Vision and Change Undergraduate biology educators also confirmed the importance of items included in the instrument. The current version of the BioSQuaRE was developed through an iterative process using data from students at 12 postsecondary institutions. A psychometric analysis of these data provides multiple lines of evidence for the validity of inferences made using the instrument. Our results suggest that the BioSQuaRE will prove useful to faculty and departments interested in helping students acquire the quantitative competencies they need to successfully pursue biology, and useful to biology students by communicating the importance of quantitative skills. We invite educators to use the BioSQuaRE at their own institutions.


Compo: composite motif discovery using discrete models.
Computational discovery of motifs in biomolecular sequences is an established field, with applications both in the discovery of functional sites in proteins and regulatory sites in DNA. In recent years there has been increased attention towards the discovery of composite motifs, typically occurring in cis-regulatory regions of genes. This paper describes Compo: a discrete approach to composite motif discovery that supports richer modeling of composite motifs and a more realistic background model compared to previous methods. Furthermore, multiple parameter and threshold settings are tested automatically, and the most interesting motifs across settings are selected. This avoids reliance on single hard thresholds, which has been a weakness of previous discrete methods. Comparison of motifs across parameter settings is made possible by the use of p-values as a general significance measure. Compo can either return an ordered list of motifs, ranked according to the general significance measure, or a Pareto front corresponding to a multi-objective evaluation on sensitivity, specificity and spatial clustering. Compo performs very competitively compared to several existing methods on a collection of benchmark data sets. These benchmarks include a recently published, large benchmark suite where the use of support across sequences allows Compo to correctly identify binding sites even when the relevant PWMs are mixed with a large number of noise PWMs. Furthermore, the possibility of parameter-free running offers high usability, the support for multi-objective evaluation allows a rich view of potential regulators, and the discrete model allows flexibility in modeling and interpretation of motifs.


THEORY OF REGENERATION BASED ON MASS ACTION. II.
1. Quantitative proof is furnished that all the material available for shoot and root formation in an isolated leaf of Bryophyllum calycinum flows to those notches where through the influence of gravity or by a more abundant supply of water growth is accelerated. As soon as the acceleration of growth in these notches commences, the growth of shoots and roots in the other notches which may already have started ceases. 2. It had been shown in a preceding paper that the regeneration of an isolated piece of stem may be and frequently is in the beginning not markedly polar, but that after some time the growth of all the roots except those at the base and of all the shoots except those at the apex is suppressed. This analogy with the behavior of regeneration in a leaf in which the growth in one set of notches is accelerated, suggests that in an isolated stem a more rapid growth is favored at the extreme ends (probably by a block of the sap flow at the extreme ends) and that when this happens the total flow of ascending sap goes to the most apical buds and the total flow of the descending sap goes to the most basal roots. As soon as this occurs, the growth of the other roots and shoots is suppressed.


MoS2-Decorated Graphene@porous Carbon Nanofiber Anodes via Centrifugal Spinning.
Sodium-ion batteries (SIBs) are promising alternatives to lithium-ion batteries as green energy storage devices because of their similar working principles and the abundance of low-cost sodium resources. Nanostructured carbon materials are attracting great interest as high-performance anodes for SIBs. Herein, a simple and fast technique to prepare carbon nanofibers (CNFs) is presented, and the effects of carbonization conditions on the morphology and electrochemical properties of CNF anodes in Li- and Na-ion batteries are investigated. Porous CNFs containing graphene were fabricated via centrifugal spinning, and MoS2 were decorated on graphene-included porous CNFs via hydrothermal synthesis. The effect of MoS2 on the morphology and the electrode performance was examined in detail. The results showed that the combination of centrifugal spinning, hydrothermal synthesis, and heat treatment is an efficient way to fabricate high-performance electrodes for rechargeable batteries. Furthermore, CNFs fabricated at a carbonization temperature of 800 °C delivered the highest capacity, and the addition of MoS2 improved the reversible capacity up to 860 mAh/g and 455 mAh/g for Li- and Na-ion batteries, respectively. A specific capacity of over 380 mAh/g was observed even at a high current density of 1 A/g. Centrifugal spinning and hydrothermal synthesis allowed for the fabrication of high-performance electrodes for sodium ion batteries.


Surgical technique for idiopathic spinal cord herniation: the Hammock method. Technical note.
Idiopathic spinal cord herniation is a rare disease, and surgical treatment is recommended for patients with motor deficits or progressive neurological symptoms. Surgery is performed to release and reposition the tethered spinal cord. In terms of repositioning and prevention of reherniation, various procedures have been proposed; enlargement of the ventral dural defect, primary closure of the defect with sutures, and insertion of a ventral patch for duraplasty. We treated 3 patients with idiopathic spinal cord herniation, using a ventral patch for duraplasty with an expanded polytetrafluoroethylene pericardial membrane (the Hammock method), and all 3 cases had good clinical outcome. The specific important technical aspects are described and illustrated. If this procedure is performed meticulously under the microscope by following the specific techniques, the Hammock method is safer and more effective for prevention of reherniation than simple enlargement of the dural defect.


Enhanced Thermal Conductivity of Copper Nanofluids: The Effect of Filler Geometry.
Nanofluids are colloidal dispersions that exhibit enhanced thermal conductivity at low filler loadings and thus have been proposed for heat transfer applications. Here, we systematically investigate how particle shape determines the thermal conductivity of low-cost copper nanofluids using a range of distinct filler particle shapes: nanospheres, nanocubes, short nanowires, and long nanowires. To exclude the potential effects of surface capping ligands, all the filler particles are kept with uniform surface chemistry. We find that copper nanowires enhanced the thermal conductivity up to 40% at 0.25 vol % loadings; while the thermal conductivity was only 9.3% and 4.2% for the nanosphere- and nanocube-based nanofluids, respectively, at the same filler loading. This is consistent with a percolation mechanism in which a higher aspect ratio is beneficial for thermal conductivity enhancement. To overcome the surface oxidation of the copper nanomaterials and maintain the dispersion stability, we employed polyvinylpyrrolidone (PVP) as a dispersant and ascorbic acid as an antioxidant in the nanofluid formulations. The thermal performance of the optimized fluid formulations could be sustained for multiple heating-cooling cycles while retaining stability over 1000 h.


Evaluation of the Western immunoblot as a detection method for Brucella abortus exposure in elk.
Brucella abortus has been an important wildlife disease issue for most of the last century, especially because wildlife species are considered to be important disease reservoirs for cattle. Diagnostic uncertainty, caused in part by cross-reactions of antibodies to environmental pathogens such as Yersinia enterocolitica O:9 on standard Brucella serology, has exacerbated the challenges of managing the disease and has highlighted the need for test validation in wildlife species. The western immunoblot was evaluated for use in detecting B. abortus exposure in elk (Cervus elaphus) and for ruling out exposure to cross-reacting bacteria. Samples collected from 2003 to 2006, including 54 female and immature elk from four different elk herds, were tested using standard Brucella serologic methods (card, rapid automated presumptive [RAP], and rivanol tests), as well as the western immunoblot. Samples (n=28) from animals known to be naturally infected with B. abortus biovar 1 served as positive controls. For presumed negative samples, sera (n=26) were collected from two elk herds in which negative serologic tests, and the absence of clinical signs of disease such as abortions, supported Brucella-negative classification. In addition to these study samples, serologic data from 12 tule elk (Cervus elaphus nannodes) were provided from the California Department of Fish and Game in order to illustrate a field application of the western blot. The western immunoblot had the highest sensitivity (1.0; % 0.899-1.0) and specificity (1.0; 0.891-1.0) among all tests used in the study. The Kappa statistic for agreement between the western blot and the card, rivanol, and RAP tests were 0.701, 0.808, and 0.921, respectively, showing good to excellent agreement with the standard diagnostic tests currently in use. Although the western immunoblot is more expensive and time intensive than other tests, in this limited study, it was shown to be reliable for establishing and confirming B. abortus disease status in elk. In addition to this study, subsequent applications of the western blot assay have been successful in detecting Yersinia sp. exposure in elk after their antibodies cross-reacted on standard Brucella serology.


Identification of a gene cluster for antibacterial polyketide-derived antibiotic biosynthesis in the nystatin producer Streptomyces noursei ATCC 11455.
Streptomyces noursei ATCC 11455 produces the antifungal polyene antibiotic nystatin containing the deoxysugar moiety mycosamine. Part of the deoxythymidyl diphosphate (TDP)-glucose dehydratase gene (gdhA) known to be involved in deoxysugar biosynthesis was amplified by PCR from genomic DNA of S. noursei ATCC 11455. A gene library for S. noursei was made and screened with the gdhA probe. Several overlapping phage clones covering about 30 kb of the S. noursei genome were physically mapped. A partial DNA sequencing analysis of this region resulted in the identification of several putative genes typical of macrolide antibiotic biosynthetic gene clusters. A gene-transfer system for 5. noursei has been established, and gene deletion or disruption experiments within the putative biosynthetic gene cluster were performed. All of the knock-out mutants retained the ability to produce nystatin, suggesting that the identified gene cluster is not involved in biosynthesis of this antibiotic. Culture extracts from the wild-type strain and three knock-out mutants were analysed by TLC followed by a bioassay against Micrococcus luteus. Two antibacterial compounds were found to be synthesized by the wild-type strain while only one was produced by the mutants. This provided evidence for the involvement of the identified gene cluster in the biosynthesis of a presumably novel antibacterial macrolide antibiotic in S. noursei.


ADP-Glucose pyrophosphorylase from potato tubers. Site-directed mutagenesis studies of the regulatory sites.
Several lysines (Lys) were determined to be involved in the regulation of the ADP-glucose (Glc) pyrophosphorylase from spinach leaf and the cyanobacterium Anabaena sp. PCC 7120 (K. Ball, J. Preiss [1994] J Biol Chem 269: 24706-24711; Y. Charng, A.A. Iglesias, J. Preiss [1994] J Biol Chem 269: 24107-24113). Site-directed mutagenesis was used to investigate the relative roles of the conserved Lys in the heterotetrameric enzyme from potato (Solanum tuberosum L.) tubers. Mutations to alanine of Lys-404 and Lys-441 on the small subunit decreased the apparent affinity for the activator, 3-phosphoglycerate, by 3090- and 54-fold, respectively. The apparent affinity for the inhibitor, phosphate, decreased greater than 400-fold. Mutation of Lys-441 to glutamic acid showed even larger effects. When Lys-417 and Lys-455 on the large subunit were mutated to alanine, the phosphate inhibition was not altered and the apparent affinity for the activator decreased only 9- and 3-fold, respectively. Mutations of these residues to glutamic acid only decreased the affinity for the activator 12- and 5-fold, respectively. No significant changes were observed on other kinetic constants for the substrates ADP-Glc, pyrophosphate, and Mg2+. These data indicate that Lys-404 and Lys-441 on the small subunit are more important for the regulation of the ADP-Glc pyrophosphorylase than their homologous residues in the large subunit.


Boosting Interfacial Charge-Transfer Kinetics for Efficient Overall CO2 Photoreduction via Rational Design of Coordination Spheres on Metal-Organic Frameworks.
The recombination of electron-hole pairs severely detracts from the efficiency of photocatalysts. This issue could be addressed in metal-organic frameworks (MOFs) through optimization of the charge-transfer kinetics via rational design of structures at atomic level. Herein, a pyrazolyl porphyrinic Ni-MOF (PCN-601), integrating light harvesters, active catalytic sites, and high surface areas, has been demonstrated as a superior and durable photocatalyst for visible-light-driven overall CO2 reduction with H2O vapor at room temperature. Kinetic studies reveal that the robust coordination spheres of pyrazolyl groups and Ni-oxo clusters endow PCN-601 with proper energy band alignment and ultrafast ligand-to-node electron transfer. Consequently, the CO2-to-CH4 production rate of PCN-601 far exceeds those of the analogous MOFs based on carboxylate porphyrin and the classic Pt/CdS photocatalyst by more than 3- and 20-fold, respectively. The reaction avoids the use of hole scavengers and proceeds in a gaseous phase which can take full advantage of the high gas uptake of MOFs. This work demonstrates that the rational design of coordination spheres in MOF structures not only reconciles the contradiction between reactivity and stability but also greatly promotes the interfacial charge transfer to achieve optimized kinetics, providing guidance for the design of highly efficient MOF photocatalysts.


Measurement of Whole-Brain and Gray Matter Atrophy in Multiple Sclerosis: Assessment with MR Imaging.
Purpose To compare available methods for whole-brain and gray matter (GM) atrophy estimation in multiple sclerosis (MS) in terms of repeatability (same magnetic resonance [MR] imaging unit) and reproducibility (different system/field strength) for their potential clinical applications. Materials and Methods The softwares ANTs-v1.9, CIVET-v2.1, FSL-SIENAX/SIENA-5.0.1, Icometrix-MSmetrix-1.7, and SPM-v12 were compared. This retrospective study, performed between March 2015 and March 2017, collected data from (a) eight simulated MR images and longitudinal data (2 weeks) from 10 healthy control subjects to assess the cross-sectional and longitudinal accuracy of atrophy measures, (b) test-retest MR images in 29 patients with MS acquired within the same day at different imaging unit field strengths/manufacturers to evaluate precision, and (c) longitudinal data (1 year) in 24 patients with MS for the agreement between methods. Tissue segmentation, image registration, and white matter (WM) lesion filling were also evaluated. Multiple paired t tests were used for comparisons. Results High values of accuracy (0.87-0.97) for whole-brain and GM volumes were found, with the lowest values for MSmetrix. ANTs showed the lowest mean error (0.02%) for whole-brain atrophy in healthy control subjects, with a coefficient of variation of 0.5%. SPM showed the smallest mean error (0.07%) and coefficient of variation (0.08%) for GM atrophy. Globally, good repeatability (P > .05) but poor reproducibility (P < .05) were found for all methods. WM lesion filling technique mainly affected ANTs, MSmetrix, and SPM results (P < .05). Conclusion From this comparison, it would be possible to select a software for atrophy measurement, depending on the requirements of the application (research center, clinical trial) and its goal (accuracy and repeatability or reproducibility). An improved reproducibility is required for clinical application. © RSNA, 2018 Online supplemental material is available for this article.


Tracheobronchial Involvement of Rosai-Dorfman Disease: Case Report and Review of the Literature.
Rosai-Dorfman Disease (RDD) is a rare non-neoplastic entity, also known as sinus histiocytosis with massive lymphadenopathy (SHML), characterized by a benign proliferation of histiocytes in lymph nodes. Localized forms of RDD involving the tracheobronchial tree are very rare. There is no consensus regarding the management of central airway forms and recurrence is frequent. We report the case of an 81-year-old Caucasian woman admitted in 2014 for chronic cough. Her main medical past history included a diagnosis of sinonasal RDD in 1996 with recurrent obstructive rhinosinusitis requiring repeated sinonasal surgery, and a diagnosis of tracheal RDD in 2010 with 2 asymptomatic smooth lesions (5 and 7 mm) on the anterior tracheal wall. Physical examination was normal in 2014. Pulmonary function tests showed an obstructive pattern. Computed tomographic scan revealed a mass arising from the anterior wall of the trachea that projects into the tracheal lumen. Fiberoptic bronchoscopy showed a hypervascular multilobular lesion (2 cm) arising from the anterior tracheal wall and causing 50% obstruction of the tracheal lumen. Mechanical resection with electrocoagulation of the tracheal mass was performed by rigid bronchoscopy with no complication. Histological examination demonstrated tracheal RDD. One year after endotracheal resection, the patient presented no recurrence of cough and the obstructive pattern had resolved. Reports on tracheobronchial involvement are scarce. Symptomatic tracheobronchial obstruction requires mechanical resection by rigid bronchoscopy or surgery. Recurrence is frequent, justifying long-term follow-up.