Surgical treatment of intracranial epidermoid tumors.
Intracranial epidermoid tumors are rare, potentially curable, benign lesions that are sometimes associated with perioperative complications, and tend to recur if not completely removed. Histologically benign epidermoid tumors may also develop into highly malignant tumors. This study evaluated on 28 cases of intracranial epidermoid tumor treated over a 13-year period by radical resection with microneurosurgical techniques. The majority of patients underwent computed tomography and/or magnetic resonance imaging within the first 24 hours postoperatively to confirm the results of surgery. Radical surgical resection was achieved in 21 of the 28 cases, and there was no operative mortality. The most common postoperative complication was transient paresis of various cranial nerves. During a mean follow up of 6 years, only one tumor became malignant. Radical surgical resection should be the goal in treating these benign lesions, but if not possible, every effort should be made to minimize the amount of tumor tissue that remains.


Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway.
Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood. The DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model. The fasting blood glucose level and ratio of kidney weight to body weight were measured after BBR treatment (50, 100, or 200 mg/kg) in STZ-induced DN rats. The renal injury parameters including 24-h urinary protein, blood urea nitrogen and serum creatinine were assessed. qRT-PCR was performed to detect the transcript amounts of inflammatory factors. The concentrations of inflammatory factors were evaluated by ELISA kits. Western blot analysis was conducted to measure the amounts of TLR4/NF-κB-related proteins. The apoptotic rate of podocytes was analyzed by flow cytometry using Annexin V/propidium iodide. Berberine reduced renal injury in STZ-induced DN rat model, as evidenced by the decrease in fasting blood glucose, ratio of kidney weight to body weight, 24-h urinary protein, serum creatinine, and blood urine nitrogen. BBR attenuated the systemic and renal cortex inflammatory response and inhibited TLR4/NF-κB pathway in STZ-induced DN rats and HG-induced podocytes. Also, HG-induced apoptosis of podocytes was lowered by BBR administration. Furthermore, blockade of TLR4/NF-κB pathway by resatorvid (TAK-242) or pyrrolidine dithiocarbamate aggravated the inhibitory effect of BBR on HG-induced inflammatory response and apoptosis in podocytes. Berberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway.


Angiosarcoma treated successfully with anti-PD-1 therapy - a case report.
Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative. Immunotherapy targeting either the PD-1 receptor or PD-L1 ligand has recently been shown to have activity in multiple cancers including melanoma, renal, and non-small lung cancer. Although these agents have been used in sarcoma therapy, their ability to treat angiosarcoma has not been reported. Here we describe the case of a 63-year-old man who presented initially with angiosarcoma of the nose and received surgery for the primary. Over 4 years he had recurrent disease in the face and liver and was treated with nab-paclitaxel, surgery, and radioembolization, but continued to have progressive disease. His tumor was found to express PD-L1 and he received off-label pembrolizumab 2 mg/kg every 21 days for 13 cycles with marked shrinkage of his liver disease and no new facial lesions. Secondary to this therapy he developed hepatitis and has been treated with decreasing doses of prednisone. During the 8 months off therapy he has developed no new or progressive lesions. Although occasional responses to immunotherapy have been reported for sarcomas, this case report demonstrates that angiosarcoma can express PD-L1 and have a sustained response to PD-1 directed therapy.


Mesenchymal stromal cells secretome restores bioenergetic and redox homeostasis in human proximal tubule cells after ischemic injury.
Ischemia/reperfusion injury is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal stromal cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy; however, their full potential in treating AKI remains unknown. In this study, we employed an in vitro model of chemically induced ischemia using antimycin A combined with 2-deoxy-D-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow, and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential), and overall cell metabolism by metabolomics. Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction, and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40-50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites. Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.


Crossover physics in the nonequilibrium dynamics of quenched quantum impurity systems.
A general framework is proposed to tackle analytically local quantum quenches in integrable impurity systems, combining a mapping onto a boundary problem with the form factor approach to boundary-condition-changing operators introduced by Lesage and Saleur [Phys. Rev. Lett. 80, 4370 (1998)]. We discuss how to compute exactly the following two central quantities of interest: the Loschmidt echo and the distribution of the work done during the quantum quench. Our results display an interesting crossover physics characterized by the energy scale T(b) of the impurity corresponding to the Kondo temperature. We discuss in detail the noninteracting case as a paradigm and benchmark for more complicated integrable impurity models and check our results using numerical methods.


Strain variation in hematological response of broilers to dietary aflatoxin.
The response of clinical blood values to graded levels of dietary aflatoxin was studied in three populations of chickens. Male chicks of two commercial broiler strains, one color-sexed and the other feather-sexed, and a randombred strain were fed dietary aflatoxin at levels of 0, 1.25, 2.50 or 5.0 microgram/g of diet from 1 to 21 days of age. At the conclusion of the 21-day treatment period, all remaining birds were bled by cardiac puncture and packed cell volume (PCV), erythrocyte counts (RBC), hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), total plasma protein, and total plasma cholesterol were determined. All strains of broilers were susceptible to aflatoxicosis as detected by total plasma protein and cholesterol. Anemia associated with aflatoxicosis was induced in the two commercial broiler lines, but not in the randombred line. The PCV, RBC, and Hb were diminished from control values in a dose-related fashion by graded levels of aflatoxin in the commercial broilers, but not in the randombred line. Decreases in MCV with no significant changes in MCHC were observed in all strains.


Effectiveness of short message services and voice call interventions for antiretroviral therapy adherence and other outcomes: A systematic review and meta-analysis.
The potential of using mobile phone technologies to improve antiretroviral therapy (ART) adherence has provided a new facet to human immunodeficiency virus (HIV) research. The quality of evidence and the strength of recommendations of existing reviews, however, do not adequately support large-scale adoption of the intervention. This review adopted broad selection criteria to include all mobile phone-based interventions designed to improve patient's adherence to ART. We performed a systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies. PUBMED, MEDLINE, EMBASE, PsychINFO, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, AMED and Web of Science were searched. Online abstracts archives of relevant conference proceedings and trial registries were also searched. Thirty-Five (35) full-text articles were assessed for eligibility. Included studies were conducted in high, low and middle-income countries and reported ART adherence interventions delivered by mobile phones (standard or smartphones) in the form of voice calls, interactive voice response calls (IVR), and short message service (SMS). Thirteen (13) studies met the inclusion criteria, and 11 were used in the meta-analysis. Intervention characteristics of included studies ranged from mobile phone functionalities to provision of study phones to participants. SMS and voice call contents were tailored to participants' specific adherence needs. Mobile SMS interventions improved adherence to ART compared with control conditions (OR, 95% CI = 1.59, 1.27-1.98). In subgroup analysis, only scheduled SMS was significant whereas triggered SMS had no effect on adherence to ART. Mobile voice calls did not significantly increase adherence to ART. The interventions were highly rated by > 90% of participants in the studies that reported on the experiences and satisfaction with the intervention. Scheduled mobile phone text-messaging have demonstrated significant improvement in adherence to ART. Mobile SMS adherence interventions that allow for two-way communication may, however, be more acceptable than standalone SMS reminders, which are seen to be intrusive, producing habituation and response fatigue. Voice calls and triggered SMS functionalities do not have a significant effect on adherence to ART although there is a higher preference for voice functionality over SMS especially in limited-resource and low-literacy settings. Further exploration of the mobile voice functionality and its possible combination with scheduled SMS functionality is recommended. Evidence provided in this study will guide the implementation of mobile phone intervention to improve adherence to ART, by addressing practical challenges that could militate against scalability especially in resource limited settings.


A key role for stimulus-specific updating of the sensory cortices in the learning of stimulus-reward associations.
Successful adaptive behavior requires the learning of associations between stimulus-specific choices and rewarding outcomes. Most research on the mechanisms underlying such processes has focused on subcortical reward-processing regions, in conjunction with frontal circuits. Given the extensive stimulus-specific coding in the sensory cortices, we hypothesized they would play a key role in the learning of stimulus-specific reward associations. We recorded electrical brain activity (using electroencephalogram) during a learning-based decision-making gambling task where, on each trial, participants chose between a face and a house and then received feedback (gain or loss). Within each 20-trial set, either faces or houses were more likely to predict a gain. Results showed that early feedback processing (~200-1200 ms) was independent of the choice made. In contrast, later feedback processing (~1400-1800 ms) was stimulus-specific, reflected by decreased alpha power (reflecting increased cortical activity) over face-selective regions, for winning-vs-losing after a face choice but not after a house choice. Finally, as the reward association was learned in a set, there was an increasingly stronger attentional bias towards the more likely winning stimulus, reflected by increasing attentional orienting-related brain activity and increasing likelihood of choosing that stimulus. These results delineate the processes underlying the updating of stimulus-reward associations during feedback-guided learning, which then guide future attentional allocation and decision-making.


The importance of fuel dissociation and propargyl + allyl association for the formation of benzene in a fuel-rich 1-hexene flame.
Fuel decomposition and benzene formation processes in a premixed, laminar, low-pressure, fuel-rich flame of 1-hexene (C(6)H(12), CH(2)=CH-CH(2)-CH(2)-CH(2)-CH(3)) are investigated by comparing quantitative mole fraction profiles of flame species with kinetic modeling results. The premixed flame, which is stabilized on a flat-flame burner under a reduced pressure of 30 Torr (= 40 mbar), is analyzed by flame-sampling molecular-beam time-of-flight mass spectrometry which uses photoionization by tunable vacuum-ultraviolet synchrotron radiation. The temperature profile of the flame is measured by OH laser-induced fluorescence. The model calculations include the latest rate coefficients for 1-hexene decomposition (J. H. Kiefer et al., J. Phys. Chem. A, 2009, 113, 13570) and for the propargyl (C(3)H(3)) + allyl (a-C(3)H(5)) reaction (J. A. Miller et al., J. Phys. Chem. A, 2010, 114, 4881). The predicted mole fractions as a function of distance from the burner are acceptable and often even in very good agreement with the experimentally observed profiles, thus allowing an assessment of the importance of various fuel decomposition reactions and benzene formation routes. The results clearly indicate that in contrast to the normal reactions of fuel destruction by radical attack, 1-hexene is destroyed mainly by decomposition via unimolecular dissociation forming allyl (a-C(3)H(5)) and n-propyl (n-C(3)H(7)). Minor fuel-consumption pathways include H-abstraction reactions producing various isomeric C(6)H(11) radicals with subsequent β-scissions into C(2), C(3), and C(4) intermediates. The reaction path analysis also highlights a significant contribution through the propargyl (C(3)H(3)) + allyl (a-C(3)H(5)) reaction to the formation of benzene. In this flame, benzene is dominantly formed through H-assisted isomerization of fulvene, which itself is almost exclusively produced by the C(3)H(3) + a-C(3)H(5) reaction.


Development and validation of an iodine-specific FFQ to estimate iodine intake in Australian pregnant women.
Adequate iodine is important during pregnancy to ensure optimal growth and development of the offspring. We validated an iodine-specific FFQ (I-FFQ) for use in Australian pregnant women. A forty-four-item I-FFQ was developed to assess iodine intake from food and was administered to 122 pregnant women at 28 weeks gestation. Iodine supplement use was captured separately at 28 weeks gestation. Correlation between iodine intake from food estimated using the I-FFQ and a 4 d weighed food record as well as correlation between total iodine intake and 24 h urinary iodine excretion (UIE), 24 h urinary iodine concentration (UIC), spot UIC and thyroid function were assessed at 28 weeks gestation. A moderate correlation between the two dietary methods was shown (r 0·349, P< 0·001), and it was strengthened with the addition of iodine supplements (r 0·876, P<0·001). There was a fair agreement (k= 0·28, P<0·001) between the two dietary measures in the classification of women as receiving adequate (≥160 μg/d) or inadequate (<160 μg/d) iodine intake from food, but the limits of agreement from the Bland-Altman plot were large. Total iodine intake was associated with 24 h UIE (β = 0·488, P<0·001) but not with spot UIC. Iodine intake from food using the I-FFQ was assessed at study entry (<20 weeks gestation) in addition to 28 weeks gestation, and there was a strong correlation in iodine intake at the two time points (r 0·622, P<0·001), which indicated good reproducibility. In conclusion, the I-FFQ provides a valid tool for estimating iodine intake in pregnant women and can be used to screen women who are at risk of inadequate intake.


The Veterans Administration and Department of Defense clinical practice guidelines for the diagnosis and management of sleep disorders: what does this mean for the practice of sleep medicine?
In 2017 the Veterans Administration (VA) and Department of Defense (DOD) launched development of clinical practice guidelines (CPGs) for the diagnosis and treatment of sleep disorders, with the goal of informing and improving patient care. The guideline development process followed GRADE methodology, considering studies and systematic reviews published over the 10-year period prior to guideline development. A total of 41 recommendations were made,18 related to the diagnosis and treatment of obstructive sleep apnea (OSA) and 23 regarding chronic insomnia disorder. In contrast to other published guidelines, the VA DoD CPGs provide a comprehensive approach to diagnosis and management of the two most common sleep disorders, including a discussion of the sequencing of diagnostic approaches and treatment options. Regarding OSA, strong recommendations were made for follow-up evaluation after non-diagnostic home sleep apnea tests, positive airway pressure therapy as first-line treatment, and the incorporation of supportive, educational and behavioral interventions for patients at high risk for PAP therapy non-adherence due to comorbid conditions. Strong recommendations were also made for the use of cognitive-behavioral therapy for insomnia and against the use of kava (an herbal supplement) in the treatment of chronic insomnia disorder. These guidelines, while intended to directly inform care within VA and DOD, are broadly relevant to the practice of sleep medicine. The majority of scientific evidence was based on studies of non-military, non-veteran populations. The CPG is a major milestone for the VA and DOD in recognizing the importance of evidence-based treatments for sleep disorders in military personnel and veterans.


Radiographic study of the fifth metatarsal for optimal intramedullary screw fixation of Jones fracture.
Jones fractures occur in the relatively avascular metadiaphyseal junction of the fifth metatarsal (MT), which predisposes these fractures to delayed union and nonunion. Operative treatment with intramedullary (IM) screw fixation is recommended in certain cases. Incorrect screw selection can lead to refractures, nonunion, and cortical blowout fractures. A better understanding of the anatomy of the fifth MT could aid in preoperative planning, guide screw size selection, and minimize complications. We retrospectively identified foot computed tomographic (CT) scans of 119 patients that met inclusion criteria. Using interactive 3-dimensional (3-D) models, the following measurements were calculated: MT length, "straight segment length" (distance from the base of the MT to the shaft curvature), and canal diameter. The diaphysis had a lateroplantar curvature where the medullary canal began to taper. The average straight segment length was 52 mm, and corresponded to 68% of the overall length of the MT from its proximal end. The medullary canal cross-section was elliptical rather than circular, with widest width in the sagittal plane and narrowest in coronal plane. The average coronal canal diameter at the isthmus was 5.0 mm. A coronal diameter greater than 4.5 mm at the isthmus was present in 81% of males and 74% of females. To our knowledge, this is the first anatomic description of the fifth metatarsal based on 3-D imaging. Excessive screw length could be avoided by keeping screw length less than 68% of the length of the fifth metatarsal. A greater than 4.5 mm diameter screw might be needed to provide adequate fixation for most study patients since the isthmus of the medullary canal for most were greater than 4.5 mm. Our results provide an improved understanding of the fifth metatarsal anatomy to guide screw diameter and length selection to maximize screw fixation and minimize complications.


The association between depression, lung function, and health-related quality of life among adults with cystic fibrosis.
More than 40% of people born with cystic fibrosis (CF) now reach adulthood. Greater attention is being focused on improving their health-related quality of life (HRQoL). While markers of disease severity such as lung function are only modestly associated with HRQoL, in other chronic illnesses depression is an important correlate. The objective of this study was to evaluate the relationships among lung function (ie, FEV(1) percent predicted), depressive symptoms, and HRQoL among adults with CF. Seventy-six adults with CF completed a mail-based survey. The Beck Depression Inventory and the Cystic Fibrosis Questionnaire were used to assess depressive symptoms and HRQoL, respectively. Values for FEV(1) percent predicted were abstracted from the medical record. Thirty percent of participants screened positive for depressive symptoms. Depressive symptoms and lung function were inversely correlated (rho = -0.25; p < .05). Correlations between depressive symptoms and HRQoL were maintained after stratifying by lung function. In the absence of depressive symptoms, those patients with good lung function (ie, FEV(1), > 70% predicted) reported better physical HRQoL than those with poor lung function. Participants with both depressive symptoms and poor lung function reported significantly worse HRQoL on all domains than participants without depressive symptoms regardless of lung function status. Depressive symptoms are prevalent among adults with CF and are associated with poorer HRQoL even after controlling for lung function. These results suggest that screening for and treating depression is important and may potentially improve HRQoL among patients with CF.


Large Multidirectional Spin-to-Charge Conversion in Low-Symmetry Semimetal MoTe2 at Room Temperature.
Efficient and versatile spin-to-charge current conversion is crucial for the development of spintronic applications, which strongly rely on the ability to electrically generate and detect spin currents. In this context, the spin Hall effect has been widely studied in heavy metals with strong spin-orbit coupling. While the high crystal symmetry in these materials limits the conversion to the orthogonal configuration, unusual configurations are expected in low-symmetry transition-metal dichalcogenide semimetals, which could add flexibility to the electrical injection and detection of pure spin currents. Here, we report the observation of spin-to-charge conversion in MoTe2 flakes, which are stacked in graphene lateral spin valves. We detect two distinct contributions arising from the conversion of two different spin orientations. In addition to the conventional conversion where the spin polarization is orthogonal to the charge current, we also detect a conversion where the spin polarization and the charge current are parallel. Both contributions, which could arise either from bulk spin Hall effect or surface Edelstein effect, show large efficiencies comparable to the best spin Hall metals and topological insulators. Our finding enables the simultaneous conversion of spin currents with any in-plane spin polarization in one single experimental configuration.


Effectiveness of a Text Messaging-Based Intervention Targeting Alcohol Consumption Among University Students: Randomized Controlled Trial.
Excessive drinking among university students is a global challenge, leading to significant health risks. However, heavy drinking among students is widely accepted and socially normalized. Mobile phone interventions have attempted to reach students who engage in excessive drinking. A growing number of studies suggest that text message-based interventions could potentially reach many students and, if effective, such an intervention might help reduce heavy drinking in the student community. The objective of this study was to test the effectiveness of a behavior change theory-based 6-week text message intervention among university students. This study was a two-arm, randomized controlled trial with an intervention group receiving a 6-week text message intervention and a control group that was referred to treatment as usual at the local student health care center. Outcome measures were collected at baseline and at 3 months after the initial invitation to participate in the intervention. The primary outcome was total weekly alcohol consumption. Secondary outcomes were frequency of heavy episodic drinking, highest estimated blood alcohol concentration, and number of negative consequences attributable to excessive drinking. A total of 896 students were randomized to either the intervention or control group. The primary outcome analysis included 92.0% of the participants in the intervention group and 90.1% of the control group. At follow-up, total weekly alcohol consumption decreased in both groups, but no significant between-group difference was seen. Data on the secondary outcomes included 49.1% of the participants in the intervention group and 41.3% of the control group. No significant between-group difference was seen for any of the secondary outcomes. The present study was under-powered, which could partly explain the lack of significance. However, the intervention, although theory-based, needs to be re-assessed and refined to better support the target group. Apart from establishing which content forms an effective intervention, the optimal length of an alcohol intervention targeting students also needs to be addressed in future studies. International Standard Randomised Controlled Trial Number ISRCTN95054707; http://www.isrctn.com/ISRCTN95054707 (Archived by WebCite at http://www.webcitation.org/70Ax4vXhd).


Should diagnosis codes from emergency department data be used for case selection for emergency department key performance indicators?
The aim of the present study was to assess the suitability of emergency department (ED) discharge diagnosis for identifying patient cohorts included in the definitions of key performance indicators (KPIs) that are used to evaluate ED performance. Hospital inpatient episodes of care with a principal diagnosis that corresponded to an ED-defined KPI were extracted from the Queensland Hospital Admitted Patient Data Collection (QHAPDC) for the year 2010-2011. The data were then linked to the corresponding ED patient record and the diagnoses applied in the two settings were compared. The asthma and injury cohorts produced favourable results with respect to matching the QHAPDC principal diagnosis with the ED discharge diagnosis. The results were generally modest when the QHAPDC principal diagnosis was upper respiratory tract infection, poisoning and toxic effects or a mental health diagnosis, and were quite poor for influenza. There is substantial variation in the capture of patient cohorts using discharge diagnosis as recorded on Queensland Hospital Emergency Department data. WHAT IS KNOWN ABOUT THE TOPIC? There are several existing KPIs that are defined according to the diagnosis recorded on ED data collections. However, there have been concerns over the quality of ED diagnosis in Queensland and other jurisdictions, and the value of these data in identifying patient cohorts for the purpose of assessing ED performance remains uncertain. WHAT DOES THIS PAPER ADD? This paper identifies diagnosis codes that are suitable for use in capturing the patient cohorts that are used to evaluate ED performance, as well as those codes that may be of limited value. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? The limitations of diagnosis codes within ED data should be understood by those seeking to use these data items for healthcare planning and management or for research into healthcare quality and outcomes.


[Results of intraocular lens implantation on top of the anterior capsule in cases of phaco complications].
Posterior capsule rupture during cataract extraction requires that the intraocular lens (IOL) implanted on top of the capsular bag was stable and well-centered. The objective of this study was to evaluate the results of Rayner C-flex aspheric and M-flex aspheric (United Kingdom) IOLs implantation on top of the capsular bag and their stability in patients with phaco complications. A total of 2556 phacoemulsification cases were analyzed. Posterior capsule rupture as a complication occurred in 7 cases, that is 0.27%. In all patients Rayner C-flex (5) and M-flex (6) IOLs were implanted on top of the capsular bag according to the initial calculations and with no modifications in the procedure. The 2nd-year follow-up included measurement of the corneal compensated intraocular pressure (IOP) and B-mode and 3D grey-scale ultrasound in order to assess the structures of the anterior segment and to check the position of the IOL. All surgeries yielded positive clinical results. In 2 years after the intervention uncorrected visual acuity averaged 0.7-0.13, corrected-- 0.91+0.07; clinical refraction: sphera-- +0.46 +/- 0.26 diopters, cylinder-- 0.71 +/- 0.29 diopters. The shape and other parameters of Rayner IOLs contribute to their long-term stability. Postoperative lOP in the treated eye was higher than in the fellow nonoperated eye (13.9 +/- 0.76 and 11.8 +/- 0.59 mmHg correspondingly) but the difference lied within the range of normal asymmetry. The 3D ultrasound technology is an informative mean of monitoring the position of the IOL in case of its extracapsular implantation; a comparatively higher IOP in the operated eye does not exceed the range of normal asymmetry between the two eyes; Rayner C-flex and M-flex IOLs remain stable and well-centered after being implanted on top of the capsular bag.


Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity.
Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including β-cell function, interact to affect reward discounting in humans.


Associations of Autism Spectrum Disorder with PM2.5 Components: A Comparative Study Using Two Different Exposure Models.
This retrospective cohort study examined associations of autism spectrum disorder (ASD) with prenatal exposure to major fine particulate matter (PM2.5) components estimated using two independent exposure models. The cohort included 318 750 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California hospitals from 2001 to 2014 and followed until age five. ASD cases during follow-up (N = 4559) were identified by ICD codes. Prenatal exposures to PM2.5, elemental (EC) and black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-) were constructed using (i) a source-oriented chemical transport model and (ii) a hybrid model. Exposures were assigned to each maternal address during the entire pregnancy, first, second, and third trimester. In single-pollutant models, ASD was associated with pregnancy-average PM2.5, EC/BC, OM, and SO42- exposures from both exposure models, after adjustment for covariates. The direction of effect estimates was consistent for EC/BC and OM and least consistent for NO3-. EC/BC, OM, and SO42- were generally robust to adjustment for other components and for PM2.5. EC/BC and OM effect estimates were generally larger and more consistent in the first and second trimester and SO42- in the third trimester. Future PM2.5 composition health effect studies might consider using multiple exposure models and a weight of evidence approach when interpreting effect estimates.


Risk factors for early colonoscopic perforation include non-gastroenterologist endoscopists: a multivariable analysis.
Bowel perforation is a rare but serious complication of colonoscopy. Its prevalence is increasing with the rapidly growing volume of procedures performed. Although colonoscopies have been performed for decades, the risk factors for perforation are not completely understood. We investigated risk factors for perforation during colonoscopy by assessing variables that included sedation type and endoscopist specialty and level of training. We performed a retrospective multivariate analysis of risk factors for early perforation (occurring at any point during the colonoscopy but recognized during or immediately after the procedure) in adult patients by using the Clinical Outcomes Research Initiative National Endoscopic Database. Risk factors were determined from published articles. Additional variables assessed included endoscopist specialty and years of experience, trainee involvement, and sedation with propofol. We identified 192 perforation events during 1,144,900 colonoscopies from 85 centers entered into the database from January 2000-March 2011. On multivariate analysis, increasing age, American Society of Anesthesia class, female sex, hospital setting, any therapy, and polyps >10 mm were significantly associated with increased risk of early perforation. Colonoscopies performed by surgeons and endoscopists of unknown specialty had higher rates of perforation than those performed by gastroenterologists (odds ratio, 2.00; 95% confidence interval, 1.30-3.08). Propofol sedation did not significantly affect risk for perforation. In addition to previously established risk factors, non-gastroenterologist specialty was found to affect risk for perforations detected during or immediately after colonoscopy. This finding could result from differences in volume and style of endoscopy training. Further investigation into these observed associations is warranted.


Emergency ultrasound of the chest.
Thoracic ultrasound is a noninvasive and portable diagnostic tool which is highly indicated for an initial workup of thoracic emergencies. The suspicion of a pneumothorax, pneumonia, pulmonary embolism or a lung contusion after trauma can be quickly assessed using ultrasound. Main advantages are its good availability and the steep learning curve. Another advantage of thoracic sonography is that this rapid, symptom-based examination has a high sensitivity and specificity. However, a disadvantage is that only pleura-affecting lesions or lesions visible through a sound window, e.g. an effusion or a subpleural consolidation, can be reached.


Effect of pre- and postoperative bleaching on marginal leakage of amalgam and composite restorations.
The aim of this study was to investigate the effect of pre- and postoperative bleaching with 10% carbamide peroxide on marginal leakage of amalgam and resin composite restorations. Three groups were made using 30 extracted, caries-free third molars (n = 10). In the preoperative group, bleaching was performed with 10% carbamide peroxide, followed by the placement of resin composite and amalgam restorations on Class V cavity preparations. In the postoperative group, bleaching was performed after the resin composite and amalgam restorations were fabricated. The third group served as a control in which no bleaching was performed. Dye penetration was used for evaluation of marginal leakage. Chi-square test showed that marginal leakage of resin composite restorations increased in both pre- and postoperatively bleached groups, but marginal leakage of amalgam restorations showed no alterations. Bleaching with carbamide peroxide may alter the marginal leakage of resin composite restorations, but amalgam restorations are not affected adversely in vitro.


Renal Oxygenation (rSO 2 ) Population Parameter Estimates in Premature Infants Routinely Monitored With Near-Infrared Spectroscopy.
Currently, reference ranges for renal oxygenation measured by near-infrared spectroscopy (NIRS) in preterm infants beyond the first days of life are lacking, especially those born prior to 29 weeks' gestation. Population estimates of renal oxygenation (rSO 2 ) levels among preterm infants over time have yet to be established, leading to reluctance in clinical application. To characterize the distribution and estimate population parameters for renal oxygenation measured by NIRS during the first 14 days of life among preterm infants. We prospectively observed rSO 2 trends of 37 infants before 34 weeks' gestation and 1800-g or less birth weight for the first 14 days of life. Analyses included distribution fit tests, ordinary least squares (OLS) regression, and t tests. Average daily rSO 2 variation steadily increased with 42% difference through the first 14 days of life. For all infants, renal rSO 2 means peaked during the first 3 days of life and plateaued around 7 days. Daily rSO 2 slopes were significantly lower among males and infants 29 weeks' or less gestation. Renal rSO 2 during the first 14 days of life reflects normal extrauterine transition reaching stabilization around 7 days of life. Gestational age, birth weight, and gender may predict the early trajectory of rSO 2 patterns. Population estimates provide parameters for renal rSO 2 that may indicate early-onset tissue hypoxia when acute or significant drops from baseline occur. We present a framework to guide future research using renal NIRS technology in preterm infants to determine deviations from expected trends that may precede renal injury.


Construction of a general library for the rational design of nanomagnets and spin qubits based on mononuclear f-block complexes. The polyoxometalate case.
This paper belongs to a series of contributions aiming at establishing a general library that helps in the description of the crystal field (CF) effect of any ligand on the splitting of the J ground states of mononuclear f-element complexes. Here, the effective parameters associated with the oxo ligands (effective charges and metal-ligand distances) are extracted from the study of the magnetic properties of the first two families of single-ion magnets based on lanthanoid polyoxometalates (POMs), formulated as [Ln(W5O18)2](9-) and [Ln(β2-SiW11O39)2](13-) (Ln = Tb, Dy, Ho, Er, Tm, Yb). This effective CF approach provides a good description of the lowest-lying magnetic levels and the associated wave functions of the studied systems, which is fully consistent with the observed magnetic behavior. In order to demonstrate the predictive character of this model, we have extended our model in a first step to calculate the properties of the POM complexes of the early 4f-block metals. In doing so, [Nd(W5O18)2](9-) has been identified as a suitable candidate to exhibit SMM behavior. Magnetic experiments have confirmed such a prediction, demonstrating the usefulness of this strategy for the directed synthesis of new nanomagnets. Thus, with an effective barrier of 51.4 cm(-1) under an applied dc field of 1000 Oe, this is the second example of a Nd(3+)-based single-ion magnet.


Ligand-induced heterodimerization between the ligand binding domains of the Drosophila ecdysteroid receptor and ultraspiracle.
The insect ecdysteroid receptor consists of a heterodimer between EcR and the RXR-orthologue, USP. We addressed the question of whether this heterodimer, like all other RXR heterodimers, may be formed in the absence of ligand and whether ligand promotes dimerization. We found that C-terminal protein fragments that comprised the ligand binding, but not the DNA binding domain of EcR and USP and which were equipped with the activation or DNA binding region of GAL4, respectively, exhibit a weak ability to interact spontaneously with each other. Moreover, the heterodimer formation is greatly enhanced upon administration of active ecdysteroids in a dose-dependent manner. This was shown in vivo by a yeast two-hybrid system and in vitro by a modified electromobility shift assay. Furthermore, the EcR fragment expressed in yeast was functional and bound radioactively labelled ecdysteroid specifically. Ligand binding was greatly enhanced by the presence of a USP ligand binding domain. Therefore, ecdysteroids are capable of inducing heterodimer formation between EcR and USP, even when the binding of these receptor proteins to cognate DNA response elements does not occur. This capability may be a regulated aspect of ecdysteroid action during insect development.


Contamination and ecological risk assessment of Cr, As, Cd and Pb in water and sediment of the southeastern Bay of Bengal coast in a developing country.
Safe levels of heavy metals in the surface water and sediment of the eastern Bay of Bengal coast have not been universally established. Current study characterized heavy metals such as arsenic (As), chromium (Cr), cadmium (Cd) and lead (Pb) in surface water and sediments of the most important fishing resource at the eastern Bay of Bengal coast, Bangladesh. Both water and sediment samples were analyzed using inductively coupled plasma mass spectrometer. Considering both of the seasons, the mean concentrations of Cr, As, Cd, and Pb in water samples were 33.25, 8.14, 0.48, and 21.14 μg/L, respectively and in sediment were 30.47, 4.48, 0.20, and 19.98 mg/kg, respectively. Heavy metals concentration in water samples surpassed the acceptable limits of usable water quality, indicating that water from this water resource is not safe for drinking, cooking, bathing, and any other uses. Enrichment factors also directed minor enrichment of heavy metals in sediment of the coast. Other indexes for ecological risk assessment such as pollution load index (PLI), contamination factor (CF), geoaccumulation index (Igeo), modified contamination degree (mCd), and potential ecological risk index (PERI) also indicated that sediment of the coastal watershed was low contamination. In-depth inventorying of heavy metals in both water and sediment of the study area are required to determine ecosystem health for holistic risk assessment and management.


Characterization of human rotavirus recovered from children with acute diarrhea in Kinshasa, Democratic Republic Of Congo.
Between July and October of 2003, 2004, and 2005, outbreaks of acute gastroenteritis occurred among children <5 years of age in Kinshasa, Democratic Republic of the Congo. Stool specimens (67 in 2003, 108 in 2004, and 116 in 2005) were collected and screened for rotaviruses using either latex agglutination (Diarlex LAA; Orion Diagnostics) or enzyme immunoassay (IDEIA; DakoCytomation). The molecular characteristics of the rotavirus strains were then determined. Group A rotavirus was detected in 195 (76%) of 258 stool specimens. Polyacrylamide gel electrophoresis was used to observe the 11 rotavirus double-stranded RNA segments in 83% of the 195 rotavirus-positive specimens. Six rotavirus group A electropherotypic patterns were noted, predominantly within the short classic pattern (111 [69%]) and the long pattern (37 [23%]). Mixed patterns were noted in the 14 remaining specimens (9%). Of the 29 samples subjected to subgrouping VP6 enzyme immunoassay, subgroup I predominated. Some of the specimens collected in 2003 (n = 26), 2004 (n = 38), and 2005 (n = 52) were analyzed by reverse-transcription polymerase chain reaction, which showed that t G8P[6] and G8P[8] strains predominated in 2003, and G1P[6] strains with short electropherotypic patterns predominated in 2004 and 2005. The emergence in Kinshasa of G8 serotypes, unusually associated with the P[6] genotype, as well as uncommon G1 rotavirus strains showing a short RNA pattern, is significant in relation to the introduction of a rotavirus vaccine and underscores the need for continued rotavirus serotype surveillance in the Democratic Republic of the Congo.


Gamma and Beta Bursts Underlie Working Memory.
Working memory is thought to result from sustained neuron spiking. However, computational models suggest complex dynamics with discrete oscillatory bursts. We analyzed local field potential (LFP) and spiking from the prefrontal cortex (PFC) of monkeys performing a working memory task. There were brief bursts of narrow-band gamma oscillations (45-100 Hz), varied in time and frequency, accompanying encoding and re-activation of sensory information. They appeared at a minority of recording sites associated with spiking reflecting the to-be-remembered items. Beta oscillations (20-35 Hz) also occurred in brief, variable bursts but reflected a default state interrupted by encoding and decoding. Only activity of neurons reflecting encoding/decoding correlated with changes in gamma burst rate. Thus, gamma bursts could gate access to, and prevent sensory interference with, working memory. This supports the hypothesis that working memory is manifested by discrete oscillatory dynamics and spiking, not sustained activity.


[Electric potential of the erythrocyte membrane in essential hypertension and symptomatic hypertensions].
Electric potential was studied in erythrocytes of patients with essential (20) and renal (16) hypertension and in those with the Icenko-Cushing disease (9 patients) by means of fluorescent dye diS-D3-(5). A decrease of membrane potential was found in erythrocytes of essentially hypertensive patients as compared to the normotensive controls (27). No differences were demonstrated in the values of membrane potential between normotensive individuals and patients with secondary hypertension.


High protein intake promotes the growth of hepatic preneoplastic foci in Fischer #344 rats: evidence that early remodeled foci retain the potential for future growth.
The effects of successive administration, withdrawal and readministration of high protein diets (20% casein) on the promotional growth, remodeling and regrowth of aflatoxin B1-induced preneoplastic liver lesions (foci) were examined. Weanling male Fischer 344 rats were given 10 intragastric doses of aflatoxin B1 at a level of 250 micrograms/kg body weight over a 2-wk dosing period (initiation). The subsequent 12-wk period was subdivided into four feeding periods, each lasting 3 wk (promotion). Two groups of rats were fed either a 20 or 5% casein diet during all four periods; additional groups were alternately fed these diets in different sequences. Switching from the high protein diet to a low protein diet (5% casein) resulted in marked remodeling (regression) of the growing lesions to a response level similar to that in animals that did not receive the initial promotional stimulus of high protein feeding. However, refeeding the high protein diet caused significant reappearance of these lesions. The restimulated development of these remodeled lesions far exceeded lesion growth in animals receiving only the late promotional stimulus of high dietary protein. Thus, these data suggest that a second occurrence of high protein feeding promotes the growth of remodeled foci, thus demonstrating their potential for future promotional growth.


Conversation therapy for agrammatism: exploring the therapeutic process of engagement and learning by a person with aphasia.
A recent systematic review of conversation training for communication partners of people with aphasia has shown that it is effective, and improves participation in conversation for people with chronic aphasia. Other research suggests that people with aphasia are better able to learn communication strategies in an environment which closely mirrors that of expected use, and that cognitive flexibility may be a better predictor of response to therapy than severity of language impairment. This study reports results for a single case, one of a case series evaluation of a programme of conversation training for agrammatism that directly involves a person with aphasia (PWA) as well as their communication partner. It explores how a PWA is able to engage with and learn from the therapy, and whether this leads to qualitative change in post-therapy conversation behaviours. A 55-year-old man with chronic agrammatism and his wife took part in eight weekly sessions of conversation therapy, adapted from Supporting Partners of People With Aphasia in Relationships and Conversation (SPPARC). Language and conversation were assessed before and after therapy, and the couple's views on conversation and disability were elicited. Conversation analysis was used to analyse: (1) pre-therapy conversation patterns, (2) how the PWA engaged and learned during therapy and the forms of facilitation that aided this process, and (3) qualitative change in post-therapy conversation behaviour. After therapy, the PWA showed increased insight and acceptance of the use of strategies such as writing and drawing in the face of conversational difficulty. However, use was prompted by his wife and was rarely spontaneous. This single case study suggests that conversation training based around an experiential learning process is able to engage a PWA directly in learning about the effects of aphasia on conversation. Key facilitators were self-study via video and experience of practising conversation whilst receiving online feedback from a speech and language therapist. However, increased insight did not automatically change conversation behaviour. Although he better understood the effects of his aphasia on conversations with his wife, learning stopped short of the ultimate goal of the conversation training programme; the spontaneous use of strategies worked on in therapy when faced with conversation breakdown. One explanation may be that limited cognitive flexibility lead to problems with switching from one strategy to another.


Determinants of mechanical properties in the developing ovine thoracic aorta.
We previously reported changes in mechanical properties and collagen cross-linking of the ovine thoracic aorta during perinatal development and postnatal maturation, and we now report changes in biochemical composition (elastin, collagen, and DNA contents per mg wet wt) over the same developmental intervals. A comparison of results from the present and previous studies has yielded novel and important observations concerning the relationship between aortic mechanics and composition during maturation. Developmental changes in aortic incremental elastic modulus at low tensile stress (E(low)) closely followed changes in relative elastin content (i.e., per mg wet wt). An 89% increase in E(low) during the perinatal period was associated with a 69% increase in relative elastin content, whereas neither variable changed during postnatal life. Incremental elastic modulus at high tensile stress (E(high)) did not change during the perinatal period but increased 88% during postnatal life. This pattern closely paralleled changes in collagen cross-linking index, which did not change perinatally but almost doubled postnatally. In contrast, relative collagen content (per mg wet wt) increased only slightly from fetal to adult life, a trend that was unrelated to aortic mechanics. Substantial, progressive decreases in measures of wall viscosity (pressure wave attenuation coefficient and viscoelastic phase angle) from fetal to adult life followed the pattern observed for relative DNA (smooth muscle cell) content (per mg wet wt). Our findings suggest that accumulation of elastin per milligram wet weight contributes most to developmental changes in E(low), change in collagen cross-linking is the primary determinant of developmental changes in E(high), and cell accumulation contributes most to developmental changes in wall viscosity.


Identification and characterization of a novel botulinum neurotoxin.
Botulinum neurotoxins are known to have seven serotypes (BoNT/A-G). Here we report a new BoNT serotype, tentatively named BoNT/X, which has the lowest sequence identity with other BoNTs and is not recognized by antisera against known BoNTs. Similar to BoNT/B/D/F/G, BoNT/X cleaves vesicle-associated membrane proteins (VAMP) 1, 2 and 3, but at a novel site (Arg66-Ala67 in VAMP2). Remarkably, BoNT/X is the only toxin that also cleaves non-canonical substrates VAMP4, VAMP5 and Ykt6. To validate its activity, a small amount of full-length BoNT/X was assembled by linking two non-toxic fragments using a transpeptidase (sortase). Assembled BoNT/X cleaves VAMP2 and VAMP4 in cultured neurons and causes flaccid paralysis in mice. Thus, BoNT/X is a novel BoNT with a unique substrate profile. Its discovery posts a challenge to develop effective countermeasures, provides a novel tool for studying intracellular membrane trafficking, and presents a new potential therapeutic toxin for modulating secretions in cells.


Human postprandial gastric emptying of indigestible solids can occur unrelated to antral phase III.
According to animal experiments, postprandial gastric emptying of indigestible solids is mainly related to the antral phase III activity of the migrating motor complex. Gastric emptying of indigestible solids in humans has not been directly correlated to pressure recordings. The aim of the present study was to investigate the postprandial emptying pattern of indigestible solids in humans and its relation to fed and fasted antral motility. Ten healthy volunteers participated. After an overnight fast they had a standard breakfast. Two sizes of radiopaque markers (ROMs) were given with the test meal; ten cubes each of side measurement 1.5 mm and 3 mm, respectively. Emptying of the ROMs from the stomach was followed by fluoroscopy with simultaneous antral manometry. In six of the subjects, fasting antral manometry was performed on one day and on another day, the emptying of 7 mm cylindrical particles together with 3 mm cubes, in the absence of a gastric tube was recorded. All ROMs were emptied within 5 h (range 1.5-4.5 h). In all subjects, the smaller particles (1.5 mm) showed a slight, insignificant tendency to move from the stomach more rapidly than the larger (3 mm) particles. None of the subjects had an antral phase III before all ROMs were emptied from the stomach. Instead, the typical irregular postprandial pressure activity was present in all subjects until the emptying was completed. Furthermore, the highest postprandial motility index during the emptying study was far below the motility index during phase III, but comparable to the motility index during late phase II. Emptying of the 7 mm particles occurred significantly more slowly at 1.5-2.5 h, but otherwise was similar to the emptying of the smaller particles. There was no difference between emptying of the 3 mm cubes with or without the presence of the tube. Contrary to common opinion, gastric emptying of indigestible solids after a meal can occur unrelated to the antral phase III, at least up to a particle size of 3 mm and perhaps even 7 mm. These findings are of great importance for the evaluation of gastric emptying of indigestible solids, including the pharmacodynamics of orally administered drugs.


Our Healthy Clarence: A Community-Driven Wellbeing Initiative.
In 2015-2016, the Clarence Valley in Northern New South Wales, Australia, experienced an unexpectedly high number of deaths by suicide, and the resulting distress was exacerbated by unhelpful press coverage. The local response was to adopt a community-wide positive mental health and wellbeing initiative. This paper describes the process and achievements of the initiative called 'Our Healthy Clarence'. Key stakeholders were interviewed at year two and relevant documents reviewed. Data were analysed using document and thematic analysis. Our Healthy Clarence was established following community consultation, including forums, interviews, surveys and workshops. It adopted a strengths-based approach to suicide prevention, encompassing positive health promotion, primary and secondary prevention activities, advocacy, and cross-sectoral collaboration. A stakeholder group formed to develop and enact a community mental health and wellbeing plan. Factors contributing to its successful implementation included a collective commitment to mental health and wellbeing, clarity of purpose, leadership support from key local partners, a paid independent coordinator, and inclusive and transparent governance. Stakeholders reported increased community agency, collaboration, optimism and willingness to discuss mental health, suicide and help-seeking. Our Healthy Clarence draws ideas from mental health care, community development and public health. This initiative could serve as a model for other communities to address suicide, self-harm and improve wellbeing on a whole-of-community scale.


Levels of short (1-15 ms) electrical shocks from a 50 Hz supply inducing ventricular fibrillation in hyperbaric helium and oxygen.
An investigation was undertaken to determine the ventricular fibrillation (VF) threshold of anaesthetised dogs subjected to external application of electric shocks between a foreleg and a hindleg. The shocks were 2-15 ms sections of 50 Hz sine waveform starting at peak current and were applied at a known time in the heart cycle. The object of the experiment was to determine if there was an increase in cardiac susceptibility to electrically induced VF at 31 atmospheres absolute (atm abs) in a helium and oxygen environment. The duration and position of that part of the cardiac cycle most vulnerable to induction of VF by electrocution was found (seven animals) using 4 ms shocks and then the minimum fibrillating current for shocks of 2-15 ms (min FC2-15) delivered at the most vulnerable point of the cycle (five animals). Body resistance was calculated from the data so gathered. Fibrillation thresholds were not changed by compression and there were no significant changes in the vulnerable period of the cardiac cycle. Min FC2 was significantly higher than for other durations under both control (3.21 A, SD 1.08) and test conditions (3.26 A, SD 0.39), p = 0.001. There was no difference in body resistance at 31 atm abs (395.5, SD 12.9) from control values at 1 atm abs (396.7, SD 10.9). From these data it was concluded that the heart is no more susceptible to the induction of VF at 31 atm abs in a helium oxygen environment and additional safety factors are unnecessary from this point of view.


Evaluation of a clinic education program for patients with rheumatoid arthritis.
A group education program was developed for clinic patients with rheumatoid arthritis. Teaching methods used included the Arthritis Foundation's handbook, Rheumatoid Arthritis, and a lecture by a rheumatologist. The 20 patients in the study were given a multiple choice test before and after the teaching program to determine their knowledge of arthritis. Results showed group education to be an effective teaching device. It was demonstrated that patients learned from reading the handbook alone, but the combination of reading and lecture was found to be a more effective method. Correlation studies showed that prior to group education, patients had a significant knowledge of their disease which was related to native intelligence, formal education, and socio-economic status, but not to duration of disease or length of clinic attendance. This suggests that future patient education experiments should include a pre-instruction test to document prior knowledge.


Development of two radioimmunoassays to detect paclitaxel in sera and in cerebrospinal, ascitic, and pleural fluids.
Paclitaxel is an antimitotic agent isolated from the Pacific yew tree. It has demonstrated antitumor activity in several cancers and is the first of a new class of antineoplastic agents containing a taxane ring system. Its levels in serum and urine have been measured previously by high performance liquid chromatography (HPLC). In this study, the authors developed two competitive radioimmunoassay methods to determine whether they could reliably be used to measure levels of paclitaxel in sera and in cerebrospinal, ascitic, and pleural fluids. A monoclonal antibody prepared against paclitaxel was employed in an immunoradiometric assay (IRMA), in which 125I-labeled antibody was used, and in a more conventional tritiated radioimmunoassay (RIA),in which 3H-paclitaxel was used. Both radioimmunoassays detected levels of paclitaxel in sera that were comparable to those observed with HPLC. However, the IRMA was the most sensitive. Only the IRMA was able to detect low levels of paclitaxel in cerebrospinal fluid after paclitaxel infusion and in sera 3 weeks after infusion. Both the IRMA and RIA methods were able to detect paclitaxel in ascitic and pleural fluids. Monitoring paclitaxel levels reliably in sera and other bodily fluids is possible with these radioimmunoassays and may be of value in predicting and preventing toxicity and optimizing paclitaxel treatments.


Rat homolog of mouse interleukin-1 receptor accessory protein: cloning, localization and modulation studies.
A protein which facilitates the binding between interleukin-1 (IL-1) and the type I IL-1 receptor (designated as interleukin-1 receptor accessory protein, IL-1RAcP) has recently been cloned in mouse cells. In the present study, a rat homolog of the mouse IL-1RAcP was isolated from a rat superior cervical ganglion library. The deduced 570 amino acid sequences between rat and mouse IL-1RAcP have > 95% sequence identity to each other with similar predicted signal peptide sequence (20 amino acids), extracellular domain (339 amino acids), a single transmembrane domain (24 amino acids) and a long intracellular domain (187 amino acids). The rat IL-1RAcP has approximately 25% sequence identity to the rat type I IL-1 receptor and a predicted extracellular domain with three immunoglobulin-like loops. RNase protection assays demonstrated that rat IL-1RAcP is expressed in both brain and peripheral tissues with the highest densities present in liver and brain areas such as hypothalamus, cerebral cortex, hippocampus and cerebellum; significantly lower densities were present in lung and in immune tissues such as thymus and spleen. The presence of IL-1RAcP in brain was confirmed by in situ hybridization histochemical studies with a discrete localization present in the dentate gyrus of the hippocampus. The IL-1RAcp was down-regulated in parallel with the type I IL-1 receptor in the liver following endotoxin treatment in rats. These data demonstrating the presence and modulation of a rat homolog of a mouse IL-1RAcP, which is highly expressed in brain and peripheral tissues containing type I rat IL-1 receptor, further suggest the importance of the interaction between the two proteins in rat in modulating the actions of IL-1. On the other hand, the presence of the IL-1RAcP in brain areas which show an absence of type I IL-1 receptors suggests additional functions for this protein in the rat.


Uncovering of Key Pathways and miRNAs for Intracranial Aneurysm Based on Weighted Gene Co-Expression Network Analysis.
Intracranial aneurysm (IA) is a serious cerebrovascular disease. The identification of key regulatory genes can provide research directions for early diagnosis and treatment of IA. Initially, the miRNA and mRNA data were downloaded from the Gene Expression Omnibus database. Subsequently, the limma package in R was used to screen for differentially expressed genes. In order to investigate the function of the differentially expressed genes, a functional enrichment analysis was performed. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to identify the hub module and hub miRNAs. The correlations between miRNAs and mRNAs were assessed by constructing miRNA-mRNA regulatory networks. In addition, in vitro validation was performed. Finally, diagnostic analysis and electronic expression verification were performed on the GSE122897 dataset. In the present study, 955 differentially expressed mRNAs (DEmRNAs, 480 with increased and 475 with decreased expression) and 46 differentially expressed miRNAs (DEmiRNAs, 36 with increased and 10 with decreased expression) were identified. WGCNA demonstrated that the yellow module was the hub module. Moreover, 16 hub miRNAs were identified. A total of 1,124 negatively regulated miRNA-mRNA relationship pairs were identified. Functional analysis demonstrated that DEmRNAs in the targeted network were enriched in vascular smooth muscle contraction and focal adhesion pathways. In addition, the area under the curve of 16 hub miRNAs was >0.8. It is implied that 16 hub miRNAs may be used as potential diagnostic biomarkers of IA. Hub miRNAs and key signaling pathways were identified by bioinformatics analysis. This evidence lays the foundation for understanding the underlying molecular mechanisms of IA and provided potential therapeutic targets for the treatment of this disease.


Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line.
Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse hypothalamic cell line as a model for GnRH secretion, because these cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1-7 cells by transient expression of the dominant-negative Clock-Delta19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.


Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon.
Inflammatory bowel diseases (IBDs), primarily ulcerative colitis and Crohn's disease, are inflammatory disorders caused by multiple factors. Research on IBD has often used the dextran sodium sulfate (DSS)-induced colitis mouse model. DSS induces in vivo but not in vitro intestinal inflammation. In addition, no DSS-associated molecule (free glucose, sodium sulfate solution, free dextran) induces in vitro or in vivo intestinal inflammation. We find that DSS but not dextran associated molecules established linkages with medium-chain-length fatty acids (MCFAs), such as dodecanoate, that are present in the colonic lumen. DSS complexed to MCFAs forms nanometer-sized vesicles ~200 nm in diameter that can fuse with colonocyte membranes. The arrival of nanometer-sized DSS/MCFA vesicles in the cytoplasm may activate intestinal inflammatory signaling pathways. We also show that the inflammatory activity of DSS is mediated by the dextran moieties. The deleterious effect of DSS is localized principally in the distal colon, therefore it will be important to chemically modify DSS to develop materials beneficial to the colon without affecting colon-targeting specificity.


Pseudophakia retards axial elongation in neonatal monkey eyes.
To evaluate the affect of removing the crystalline lens and implanting an intraocular lens on the axial elongation of a neonatal eye. Monocular lensectomy coupled with the implantation of a monofocal or multifocal intraocular lens was performed on 21 neonatal rhesus monkeys. Fellow eyes were randomized to part-time occlusion therapy or no treatment. Longitudinal axial elongation of the pseudophakic eyes was then compared to that of the fellow eyes, to the eyes of 19 monkeys made monocularly aphakic as neonates, and to the eyes of 39 normal monkeys. At 5 weeks of age, aphakic and pseudophakic eyes were significantly shorter than their fellow eyes (P < 0.01). After 1 year of follow-up, the mean axial lengths of the pseudophakic and aphakic eyes were 2.0 +/- 0.2 mm and 2.3 +/- 0.2 mm, respectively, shorter than their fellow eyes. This axial length difference persisted through a second year of follow-up. The difference between the mean axial lengths of the aphakic and pseudophakic eyes was not significant (P > 0.10). Part-time occlusion of the fellow eyes did not affect axial elongation. Removing the crystalline lens and implanting an intraocular lens in a neonatal monkey eye retards its axial elongation.


Measurement of a superconducting qubit with a microwave photon counter.
Fast, high-fidelity measurement is a key ingredient for quantum error correction. Conventional approaches to the measurement of superconducting qubits, involving linear amplification of a microwave probe tone followed by heterodyne detection at room temperature, do not scale well to large system sizes. We introduce an approach to measurement based on a microwave photon counter demonstrating raw single-shot measurement fidelity of 92%. Moreover, the intrinsic damping of the photon counter is used to extract the energy released by the measurement process, allowing repeated high-fidelity quantum nondemolition measurements. Our scheme provides access to the classical outcome of projective quantum measurement at the millikelvin stage and could form the basis for a scalable quantum-to-classical interface.


Two-dimensional 67Zn HYSCORE spectroscopy reveals that a Zn-bacteriochlorophyll aP' dimer is the primary donor (P840) in the type-1 reaction centers of Chloracidobacterium thermophilum.
Chloracidobacterium (C.) thermophilum is a microaerophilic, chlorophototrophic species in the phylum Acidobacteria that uses homodimeric type-1 reaction centers (RC) to convert light energy into chemical energy using (bacterio)chlorophyll ((B)Chl) cofactors. Pigment analyses show that these RCs contain BChl aP, Chl aPD, and Zn2+-BChl aP' in the approximate ratio 7.1 : 5.4 : 1. However, the functional roles of these three different Chl species are not yet fully understood. It was recently demonstrated that Chl aPD is the primary electron acceptor. Because Zn2+-(B)Chl aP' is present at low abundance, it was suggested that the primary electron donor might be a dimer of Zn2+-BChl aP' molecules. In this study, we utilize isotopic enrichment and high-resolution two-dimensional (2D) 14N and 67Zn hyperfine sublevel correlation (HYSCORE) spectroscopy to demonstrate that the primary donor cation, P840+, in the C. thermophilum RC is indeed a Zn2+-BChl aP' dimer. Density functional theory (DFT) calculations and the measured electron-nuclear hyperfine parameters of P840+ indicate that the electron spin density on P840+ is distributed nearly symmetrically over two Zn2+-(B)Chl aP' molecules as expected in a homodimeric RC. To our knowledge this is the only example of a photochemical RC in which the Chl molecules of the primary donor are metallated differently than those of the antenna.


Carbamazepine for schizophrenia.
Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to promote additional response. The antiepileptic carbamazepine is one such drug. To evaluate the effects of carbamazepine and its derivatives for the treatment of schizophrenia and related psychoses. For the original version we searched Biological Abstracts (1980-2001), The Cochrane Library (Issue 3, 2001), The Cochrane Schizophrenia Group's Register of Trials (December 2001), EMBASE (1980-2001), MEDLINE (1966-2001), PsycLIT (1886-2001) and PSYNDEX (1974-2001). For the current update we searched the Cochrane Schizophrenia Group's Register of Trials in March 2005 and in December 2006. We also inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors for additional data. We included all randomised controlled trials comparing carbamazepine or compounds of the carbamazepine family to placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). The update search did not reveal any further studies that met our inclusion criteria. The number of included studies therefore remains at ten with the number of participants randomised still 258. One study comparing carbamazepine with placebo as the sole treatment for schizophrenia was abandoned early due to high relapse rate with 26 out of 31 participants relapsing by three months. No effect of carbamazepine was evident with no difference in relapse between the two groups (1 RCT n=31, RR 4.1 CI 0.8 to 1.5). Another study compared carbamazepine with antipsychotics as the sole treatment for schizophrenia. No differences in terms of mental state were found when comparing 50% reduction in BPRS scores (1 RCT n=38, RR 1.2 CI 0.8 to 1.9). A favourable effect for carbamazepine was found when more people who received the antipsychotic (perphenazine) had parkinsonism (1 RCT n=38, RR 0.03 CI 0.00 to 0.04, NNH 1 CI 0.9 to 1.4). Eight studies compared adjunctive carbamazepine versus adjunctive placebo. Adding carbamazepine to antipsychotic treatment was as acceptable as adding placebo with no difference between the numbers leaving the study early from each group (8 RCTs n=182, RR 0.5 CI 0.2 to 1.4). Carbamazepine augmentation was superior compared with antipsychotics alone in terms of overall global improvement, but participant numbers were low (2RCTs n=38, RR 0.6 CI 0.4 to 0.9, NNT 2 CI 1 to 5). There were no differences for the mental state outcome of 50% reduction in BPRS scores (6 RCTs n=147, RR 0.9 CI 0.7 to 1.1). Less people in the carbamazepine augmentation group had movement disorders than those taking haloperidol alone (1 RCT n=20, RR 0.4 CI 0.1 to 1.0). No data were available for the effects of carbamazepine on subgroups of people with schizophrenia and aggressive behaviour, negative symptoms or EEG abnormalities or with schizoaffective disorder. Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified especially if focusing on those with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities.


Characteristics of electrode impedance and stimulation efficacy of a chronic cortical implant using novel annulus electrodes in rat motor cortex.
Cortical neural prostheses with implanted electrode arrays have been used to restore compromised brain functions but concerns remain regarding their long-term stability and functional performance. Here we report changes in electrode impedance and stimulation thresholds for a custom-designed electrode array implanted in rat motor cortex for up to three months. The array comprises four 2000 µm long electrodes with a large annular stimulating surface (7860-15700 µm(2)) displaced from the penetrating insulated tip. Compared to pre-implantation in vitro values there were three phases of impedance change: (1) an immediate large increase of impedance by an average of two-fold on implantation; (2) a period of continued impedance increase, albeit with considerable variability, which reached a peak at approximately four weeks post-implantation and remained high over the next two weeks; (3) finally, a period of 5-6 weeks when impedance stabilized at levels close to those seen immediately post-implantation. Impedance could often be temporarily decreased by applying brief trains of current stimulation, used to evoke motor output. The stimulation threshold to induce observable motor behaviour was generally between 75-100 µA, with charge density varying from 48-128 µC cm(-2), consistent with the lower current density generated by electrodes with larger stimulating surface area. No systematic change in thresholds occurred over time, suggesting that device functionality was not compromised by the factors that caused changes in electrode impedance. The present results provide support for the use of annulus electrodes in future applications in cortical neural prostheses.


Evolution of galanin receptor genes: insights from the deuterostome genomes.
Galanin exerts its biological activities through three different G protein-coupled receptors, Galr1, Galr2 and Galr3. To obtain insights into the evolution of Galrs, we searched the genomes of the deuterostomes by extensive BLAST survey and phylogenetic analyses. The Galr2 and Galr3 share similar genomic structures, and most of them are composed of 2 exons and 1 intron. However, most of Galr1 are composed of 3 extrons and 2 introns. We did not detect the typical Galr genes in the genomic databases of invertebrate deutserotomes, but three Galr1/Alstr homologs and two Galr1/Gpr151 homologs in amphioxus, two Galr1/Gpr151 homologs in sea squirt and one Galr1/Gpr151 homologs in sea urchin were identified. It is highly possible that the Galr genes in vertebrates may evolve from the homologous genes of Galr1/Alstr/Gpr151 in invertebrate deuterostomes. We also proposed that Galr3 genes were the products of Galr2 duplication during evolution, while Galr2 genes may evolve from Galr1.


Expression of tartrate-resistant acid phosphatase and cathepsin K during osteoclast differentiation in developing mouse mandibles.
The present study was designed to test the hypothesis that osteoclasts appear after or at the same time as the initiation of bone mineralization in developing intramembranous bones. We examined mineral deposition via Von Kossa staining to determine when bone mineralization begins, tartrate-resistant acid phosphatase (TRAP) activity and cathepsin K immunoreactivity to identify the presence of osteoclasts, and their mRNA expression levels to assess osteoclastic differentiation in the embryonic mouse mandible. Cathepsin K-immunopositive cells were detected around the same time as the onset of bone mineralization, whereas TRAP-positive cells appeared prior to bone mineralization. Cathepsin K protein was expressed only in multinucleated osteoclasts, whereas TRAP activity was identified in both mono- and multinucleated cells. During bone development, TRAP-positive cells altered their morphology, which was related to the number of their nuclei. The elevated mRNA levels of TRAP and cathepsin K were consistent with the increased percentage of multinucleated osteoclasts and the progression of bone development. Our study revealed that TRAP-positive cells appear prior to bone mineralization, and TRAP- and cathepsin K-positive multinucleated osteoclasts appear at the same time as the initiation of bone mineralization in embryonic mouse mandibles, suggesting that osteoclasts contribute to bone matrix maturation during intramembranous ossification.


Characterizing Fluorescence Emissions of Hairpin DNA-Templated Silver Nanoclusters by cDNA Hybridization.
Stem-loop hairpin DNA probes have high hybridization specificity and unique selectivity to target molecules such as DNA and small molecules. DNA-templated silver nanoclusters (DNA-AgNCs) has been widely used to detect biomolecules of interest due to the photostable, bright, and efficient methods. In this study, we measured fluorescence emission of hairpin DNA upon hybridization with cDNA and mutant cDNA (cDNA-1) or mutant cDNA containing mismatched bases in the stem region (cDNA-2). Fluorescence intensity of hairpin DNA-AgNCs in the presence of cDNA was 1.80 times higher than that of hairpin DNA-AgNCs alone, but decreased to 66% in the presence of cDNA-1 containing mismatched base corresponding to the hairpin stem region. This study demonstrated that fluorescence intensities of hairpin DNA-AgNCs were dependent on hybridization with either wild-type and mutant cDNAs.


Coimmunoprecipitation with MYR1 Identifies Three Additional Proteins within the Toxoplasma gondii Parasitophorous Vacuole Required for Translocation of Dense Granule Effectors into Host Cells.
Toxoplasma gondii is a ubiquitous, intracellular protozoan that extensively modifies infected host cells through secreted effector proteins. Many such effectors must be translocated across the parasitophorous vacuole (PV), in which the parasites replicate, ultimately ending up in the host cytosol or nucleus. This translocation has previously been shown to be dependent on five parasite proteins: MYR1, MYR2, MYR3, ROP17, and ASP5. We report here the identification of several MYR1-interacting and novel PV-localized proteins via affinity purification of MYR1, including TGGT1_211460 (dubbed MYR4), TGGT1_204340 (dubbed GRA54), and TGGT1_270320 (PPM3C). Further, we show that three of the MYR1-interacting proteins, GRA44, GRA45, and MYR4, are essential for the translocation of the Toxoplasma effector protein GRA16 and for the upregulation of human c-Myc and cyclin E1 in infected cells. GRA44 and GRA45 contain ASP5 processing motifs, but like MYR1, processing at these sites appears to be nonessential for their role in protein translocation. These results expand our understanding of the mechanism of effector translocation in Toxoplasma and indicate that the process is highly complex and dependent on at least eight discrete proteins.IMPORTANCEToxoplasma is an extremely successful intracellular parasite and important human pathogen. Upon infection of a new cell, Toxoplasma establishes a replicative vacuole and translocates parasite effectors across this vacuole to function from the host cytosol and nucleus. These effectors play a key role in parasite virulence. The work reported here newly identifies three parasite proteins that are necessary for protein translocation into the host cell. These results significantly increase our knowledge of the molecular players involved in protein translocation in Toxoplasma-infected cells and provide additional potential drug targets.


Nanoparticle formulated alpha-galactosylceramide activates NKT cells without inducing anergy.
Activation of innate immunity is critical for vaccine development and immunotherapy, through triggering antigen specific immune responses. Natural killer T (NKT) cells are a unique type of innate immune cells which exert potent anti-viral and anti-metastasis function, through producing interferon-gamma and activating dendritic cells to present tumor antigens to CD8 T cells. alpha-Galactosylceramide, a synthetic antigen for NKT cells, is an adjuvant for protein antigens which can induce protective immunity against cancer and viral diseases, and has been proven to be safe and immune stimulatory in human cancer and hepatitis patients. Current existing problem for alpha-galactosylceramide is its induction of anergy of NKT cells, due to the non-selective presentation of alpha-galactosylceramide antigen by B cells. We hypothesized that nanoparticle formulated alpha-galactosylceramide may be selectively presented by dendritic cells and macrophages, but not B cells, thus avoiding anergy induction in NKT cells. We have prepared poly-lactic acid based nanoparticles conjugated with alpha-galactosylceramide, examined their stimulation of NKT cells in vitro and in vivo in mice, and showed that nanoparticle formulated alpha-galactosylceramide stimulates NKT cells. In contrast to soluble alpha-galactosylceramide, which caused NKT anergy after single stimulation, nanoparticle formulated alpha-galactosylceramide repeatedly stimulates NKT cells without inducing anergy. Mechanistic studies showed that nanoparticle formulated alpha-galactosylceramide is efficiently presented by mouse CD11c+population containing dendritic cells, and CD11b+population containing macrophages, but very poorly by B220+population containing B cells. Hence, nanoparticle formulated alpha-galactosylceramide is an attractive immunomodulator for immunotherapy and vaccine development. Future studies will be focused on its application as adjuvant for protein and/or peptide antigens.


Quality of life for Thai women with diabetes.
Based on the data obtained from a larger exploratory descriptive study, life quality of 57 Thai women with diabetes was explored. Eighteen women from 57 original participants were interviewed regarding life characteristics that are important to their life quality. Thai women with diabetes perceived moderate satisfaction with their life at present. The age at onset of diabetes significantly correlated (r = -.30, p < .05) with life satisfaction scores of women. Life characteristics that were important to their life quality included five categories: family, living conditions, success in life, health, and personal faith. The findings add to the knowledge base about life quality of women with diabetes in Thailand and to the understanding of the cultural specificity of human experiences and the quality of life concept in general.


Time-Varying Effects of Marital Status on Gastric Cancer: A Population-Based Study.
Although prior studies have shown that marital status affects the prognosis of patients with gastric cancer, its time-varying effects are not well understood. We aimed to investigate the changes in marital status' impact over a 10-year follow-up time among patients with gastric cancer (GC) in the United States. All patients with gastric cancer diagnosed between 2004 and 2008 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. Married patients and unmarried patients (single, separated, divorced or widowed) with complete survival time were selected for comparisons. A total of 14,545 patients who had clinical data and follow-up information available were enrolled. We used Kaplan-Meier analyses and time-dependent flexible parametric models to estimate time-varying hazard ratios (HRs). Unmarried GC patients had worse overall and cancer-specific survival compared with married patients (log-rank test: P < 0.001 and P < 0.001, respectively). The time-varying analysis found that unmarried patients had a significantly higher risk of overall mortality during the 10-year follow-up time, with the lowest adjusted hazard ratio (HR) at 12 months after diagnosis (HR at 12 months, 1.08; 95% CI, 1.03-1.15). For cancer-specific mortality, the time-varying adjusted HR of unmarried patients was significantly higher initially (HR at 12 months, 1.08; 95% CI, 1.02-1.14) but decreased to null after 20 months (HR at 24 months = 1.04; 95% CI = 0.99-1.11). Unmarried patients had a higher risk of cancer-specific mortality during the 20 months after gastric cancer diagnosis, which may be an appropriate time frame for intervention.


Effects of ethanol ingestion on thirst and fluid consumption in humans.
To investigate the effects of ethanol on thirst, fluid intake was measured in 24 normal subjects for 3 h after consumption of 1.0 g/kg ethanol, with or without administration of a vasopressin analogue (DDAVP) before ethanol ingestion. Fluid consumption was reduced in subjects receiving DDAVP, suggesting that thirst after ethanol is largely secondary to dehydration due to inhibition of vasopressin release. Further, the effects of ethanol on salt-load-elicited thirst and fluid consumption in normal subjects were studied using intravenous hypertonic saline infusions. Subjects acted as their own controls and received 0.5 or 1.0 ml/kg ethanol 30 min before infusions on one day and an equal volume of fluid on another day. During infusions after ethanol, subjects experienced thirst later and at higher osmolalities. They also drank less immediately after infusions with prior ethanol ingestion. The relationship between thirst score and plasma osmolality was shifted to higher osmolalities by ethanol. Thus, although ethanol progressively causes thirst secondary to dehydration, it has a direct inhibitory effect on the thirst response to osmotic stimulation.


Gastric and autonomic responses to stress in functional dyspepsia.
It has been suggested that functional dyspepsia might arise from the effect of stress on upper gut motility in susceptible individuals. The aim of this study was to evaluate posticibal antral motility in the presence and absence of sustained experimental stress by means of a transcutaneous electrical nerve stimulator. Two groups of patients could be recognized from these studies: first, those with postcibal antral hypomotility that was not changed during stress; and second, patients with normal postcibal motility which was normally suppressed by stress. Experimental stress significantly increased skin conductance and plasma beta-endorphin levels. However, in these two groups, there were no differences in clinical presentation and personality traits or in autonomic and humoral variables either before or during stress. Stepwise discriminant analysis of the autonomic or humoral responses to stress was unable to predict the different postcibal antral motor responses among the subsets of patients with functional dyspepsia. These data suggest that there are two subtypes of antral motility in functional dyspepsia: disordered gastric function under basal conditions resulting in antral hypomotility, and normal basal antral motility and autonomic and gastric motor responses to stress. In the latter subgroup, the cause of symptoms is unclear, but it appears not to be a motility disorder.


[Maintenance of 2S retinol receptor in the retina of rats in injuries induced by visible light].
Male Wistar rats (140-150 g) were subjected to constant fluorescent light exposure (400 ft-cd) of 24 hrs-21 day; contents of rhodopsin, total soluble proteins, 2 S cytosolic receptor as well as the morphological (light microscopy) characteristics were studied in retina. After 24 hrs exposure content of rhodopsin was decreased by 82%, after 48 hrs--by 37% as compared with control level, and decreased down to zero value within the 20 day. The content of total cytosol proteins decreased more slowly and within 3 weeks constituted 68-72% as compared with the control level. There were progressive dystrophic changes of rods and cones within the third day, culminating in their destruction. 2 S receptor was determined by incubation of the cytosol with 2.0-6.0. 10(-8) M of 3H-retinol followed by sucrose gradient fractionation. During all the periods studied the 2 S receptor peak was observed. The data obtained suggest the maintenance of molecular mechanisms of vitamin A functioning in damaged retina.


PET imaging of high-affinity α4β2 nicotinic acetylcholine receptors in humans with 18F-AZAN, a radioligand with optimal brain kinetics.
We evaluated (-)-2-(6-[(18)F]fluoro-2,3'-bipyridin-5'-yl)-7-methyl-7-aza-bicyclo[2.2.1]heptane ((18)F-AZAN), a novel radiotracer that binds to α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) and shows high specific binding and rapid and reversible kinetics in the baboon and human brain. We tested safety tolerability and test-retest reliability (n = 5) and proposed initial quantification of (18)F-AZAN receptors in 3 healthy human subjects who had nicotine exposure and 9 who did not. We also present a receptor blocking study in a nicotine subject dosed with the α4β2-nAChR-selective partial agonist varenicline. Radiation dosimetry PET/CT experiments indicated that most human organs received doses between 0.008 and 0.015 mSv/MBq, with an effective dose of approximately 0.014 mSv/MBq. The tracer rapidly entered the brain, and the peak was reached before 20 min, even for thalamus. Ninety-minute scans were sufficient for (18)F-AZAN to obtain the ratio at equilibrium of specifically bound radioligand to nondisplaceable radioligand in tissue (BPND) using plasma reference graphical analysis, which showed excellent reproducibility of BPND (test-retest variability < 10%) in the nAChR-rich brain regions. Regional plasma reference graphical analysis BP(ND) values exceeded 2 in the midbrain tegmental nuclei, lateral geniculate body, and thalamus for nonsmokers (n = 9) but were less than 1 in the nAChR-poor brain regions. There was a dramatic reduction of (18)F-AZAN brain uptake in smokers and varenicline-treated subjects. (18)F-AZAN is a highly specific, safe, and effective PET radioligand for human subjects that requires only 90 min of PET scanning to estimate high-affinity α4β2-nAChR in the living human brain.


Stage-specific expression of a selectable marker in Toxoplasma gondii permits selective inhibition of either tachyzoites or bradyzoites.
The establishment of culture conditions suitable for inducing differentiation of Toxoplasma gondii tachyzoites into parasites resembling the latent bradyzoite form has opened this important developmental transition to experimental analysis. In order to develop a genetic marker suitable for positive and negative selection during parasite differentiation. the T. gondii HXGPRT gene was placed under control of 5' flanking sequences derived from two bradyzoite-specific genes: BAG1 and LDH2. Random transgene integration at undefined genomic loci resulted in modest regulation (approximately 5-6-fold induction) above relatively high background levels (approximately 4% of wild-type controls). Integration of transgenes at a defined genomic position was achieved by targeting the uracil phosphoribosyl transferase (UPRT) locus using flanking homologous sequences and fluorouracil selection. This strategy was found to provide the added advantage of enhancing bradyzoite induction frequencies under conditions of pyrimidine starvation (low CO2). Constructs integrated in the direction of normal UPRT transcription exhibited moderate levels of inducibility, but transgenes integrated in the opposite direction were dramatically induced under differentiation conditions: 50-100-fold above the very low levels observed in tachyzoites (< 1% control). Positive selection (using mycophenolic acid) was shown to inhibit tachyzoites but not bradyzoites, while negative selection (using 8-azahypoxanthine) inhibited bradyzoites only. Stage-specific regulation of the HXGPRT selectable marker should permit genetic selections for the identification of mutants in the bradyzoite differentiation process.