Sustained impact of UK FAST-test public education on response to stroke: a population-based time-series study.
Urgent assessment is essential after stroke. Several countries have had public education campaigns, based on the FAST (Face-Arm-Speech-Time) test to reduce delays in seeking attention. However, the impact of these campaigns on patient behavior is uncertain. We prospectively determined patient behavior after incident major stroke (NIHSS > 3) in a UK population based study (Oxford Vascular Study) before (2002-2008) and after (2009-2013) introduction of the FAST TV-campaign and assessed any sustained impact of campaign continuation. Among 668 consecutive patients with major stroke, medical attention was sought by a bystander in 553 (89·6%). Patients were more likely to present directly to emergency services (OR = 2·18, 95%CI:1·54-3·09, P < 0·0001) after the campaign and to arrive at hospital within 3 h (OR = 2·18, 1·55-3·06, P < 0·0001). Median [IQR] time to seeking attention fell from 53 [15-265] to 31 [7-120] minutes (P = 0·005) and median time to hospital arrival from 185 [88-885] to 119 [78-256] minutes (P < 0·0001). On time-series analysis improvements in hospital arrival within 3 h and use of emergency medical services were significantly associated to initiation of the campaign (aOR = 3·11, 1·53-6·29, P = 0·002; and 2·22, 1·05-4·67, P = 0·036, respectively), independent of trend, age, sex, ethnicity, educational level, social class, prior stroke and stroke severity, and have been sustained to 2013. Delays to seeking and receiving medical attention after major stroke in the UK. fell strikingly in 2009, coinciding with the start of the FAST TV campaign. That medical attention was sought by a bystander in nearly 90% of cases illustrates the importance of mass-media public education rather than focused programs in high-risk groups for major stroke.


Effect of peroral glycerol administration on inner ear fluid electrolytes of guinea pigs.
After the oral administration of 50% glycerol (12 mL/kg), serum, CSF and inner ear fluids from scala tympani perilymph, scala vestibuli perilymph, and scala media endolymph were collected from normal guinea pigs under sodium pentobarbital anesthesia (25-35 mg/kg). The sodium and potassium concentrations were determined by microflame photometry. Increases in sodium concentrations were found in CSF, scala tympani perilymph, scala vestibuli perilymph, and cochlear endolymph. No significant change was observed in the serum. These sodium increases were considered to be due to the dehydration caused by the osmotic action of glycerol. Potassium concentration was increased only in scala tympani perilymph. Oral administration of glycerol was found to be more gradual and effective in dehydration compared to intravenous injection.


Axotomy of single fluorescent nerve fibers in developing mammalian spinal cord by photoconversion of diaminobenzidine.
A technique has been developed for cutting single nerve fibers in mammalian spinal cord. In the presence of diaminobenzidine (DAB), a laser microbeam was applied to carbocyanine (Dil) stained sensory fibers in cultured spinal cords of the newly born opossum Monodelphis domestica. Digital images of fluorescent fibers were acquired with an intensified video CCD-camera coupled to an image processor. Laser illumination of two spots on a fiber in the presence of 3 mg/ml DAB cut it, so that following DAB wash out, Dil fluorescence did not return after the intermediate segment was bleached. In contrast, when a similar procedure was carried out without DAB, fluorescence of the bleached segment was recovered within minutes in darkness, by dye diffusion from adjacent regions of the uncut fiber. After exposure to DAB, through-conduction of compound action potentials continued in undamaged fibers. The DAB reaction product remained as a dark precipitate, helping to localize the lesion sites. By illuminating a continuous series of spots it was possible to cut whole nerve roots. Fluorescent fibers extended across the cut segment 24 h later. With minor modifications, the procedure described here allows a precise lesioning of single fibers within an intact nervous system.


What is the best animal model for acs?
Current treatment of the abdominal compartment syndrome (ACS) is based on consensus definitions but several questions regarding fluid regime or critical level of intra-abdominal hypertension (IAH)) remain unsolved. It is questionable whether these issues can be addressed in prospective randomized trials in the near future. This review aimed to summarize current animal models and to outline requirements for the best model. PubMed® data base was searched for articles describing animal models of ACS. 25 articles were found. ACS in animals has not been defined yet. Investigations varied considerably regarding the experimental design. Animals were rats, rabbits, dogs and pigs with a bodyweight from 200g to 70 kg. IAP increase varied from 20 to 50 mmHg. The time period of IAH ranged between 30 min and 24h. The time between the IAH insult and organ dysfunction varied between 15 min and 18h. Investigations demonstrated that IAH is able to induce loss of intravascular volume, organ hypoperfusion, ischemic organ damage and multiple organ failure within 4 to 6h. In contrast to IAH or pneumoperitoneum for surgical exposure, ACS in an animal may be stated if an artificially increased IAP leads to circulatory, respiratory and renal insufficiency. A next step in animal research would be the development of a "pathological" model in which haemorrhage or systemic inflammation together with resuscitation lead to abdominal fluid accumulation and increased intra-abdominal pressure.


Robustness of a rhythmic circuit to short- and long-term temperature changes.
Recent computational and experimental work has shown that similar network performance can result from variable sets of synaptic and intrinsic properties. Because temperature is a global perturbation that differentially influences every biological process within the nervous system, one might therefore expect that individual animals would respond differently to temperature. Nonetheless, the phase relationships of the pyloric rhythm of the stomatogastric ganglion (STG) of the crab, Cancer borealis, are remarkably invariant between 7 and 23°C (Tang et al., 2010). Here, we report that, when isolated STG preparations were exposed to more extreme temperature ranges, their networks became nonrhythmic, or "crashed", in a reversible fashion. Animals were acclimated for at least 3 weeks at 7, 11, or 19°C. When networks from the acclimated animals were perturbed by acute physiologically relevant temperature ramps (11-23°C), the network frequency and phase relationships were independent of the acclimation group. At high acute temperatures (>23°C), circuits from the cold-acclimated animals produced less-regular pyloric rhythms than those from warm-acclimated animals. At high acute temperatures, phase relationships between pyloric neurons were more variable from animal to animal than at moderate acute temperatures, suggesting that individual differences across animals in intrinsic circuit parameters are revealed at high temperatures. This shows that individual and variable neuronal circuits can behave similarly in normal conditions, but their behavior may diverge when confronted with extreme external perturbations.


Suppression of intestinal neoplasia by deletion of Dnmt3b.
Aberrant gene silencing accompanied by DNA methylation is associated with neoplastic progression in many tumors that also show global loss of DNA methylation. Using conditional inactivation of de novo methyltransferase Dnmt3b in Apc(Min/+) mice, we demonstrate that the loss of Dnmt3b has no impact on microadenoma formation, which is considered the earliest stage of intestinal tumor formation. Nevertheless, we observed a significant decrease in the formation of macroscopic colonic adenomas. Interestingly, many large adenomas showed regions with Dnmt3b inactivation, indicating that Dnmt3b is required for initial outgrowth of macroscopic adenomas but is not required for their maintenance. These results support a role for Dnmt3b in the transition stage between microadenoma formation and macroscopic colonic tumor growth and further suggest that Dnmt3b, and by extension de novo methylation, is not required for maintaining tumor growth after this transition stage has occurred.


A QALY loss is a QALY loss is a QALY loss: a note on independence of loss aversion from health states.
Evidence has accumulated documenting loss aversion for monetary and, recently, for health outcomes-meaning that, generally, losses carry more weight than equally sized gains. In the conventional Quality-Adjusted Life Year (QALY) models, which comprise utility for quality and length of life, loss aversion is not taken into account. When measuring elements of the QALY model, commonly, the (implicit) assumption is that utility for length and quality of life are independent. First attempts to quantify loss aversion for QALYs typically measured loss aversion in the context of life duration, keeping quality of life constant (or vice versa). However, given that QALYs are multi-attribute utilities, it may be possible that the degree of loss aversion is dependent on, or inseparable from, quality of life and non-constant. We test this assumption using non-parametric methodology to quantify loss aversion, under different levels of quality of life. We measure utility of life duration for four health states within subjects, and present the results of a robustness test of loss aversion within the QALY model. We find loss aversion coefficients to be stable at the aggregate level, albeit with considerable heterogeneity at the individual level. Implications for applied work on prospect theory within health economics are discussed.


Multichannel terahertz time-domain spectroscopy system at 1030 nm excitation wavelength.
We present Terahertz (THz) imaging with a 1D multichannel time-domain spectroscopy (TDS) system which operates with a photoconductive array of 15 detection channels excited by a 1030 nm femtosecond fiber laser. The emitter and detector are photoconductive antennas based on InGaAs/InAlAs multi-layer heterostructures (MLHS). We characterized the THz optics and the resolution of the system. The performance is demonstrated by the multichannel imaging of two samples. A simultaneous measurement of 15 THz pulses with a pixel pitch of 1 mm increases the measurement speed of the TDS system by factor 15.


The hemodynamics effects of ACE inhibitors in the treatment of congestive heart failure.
To determine the safety and efficacy of single oral doses of quinapril in the treatment of congestive heart failure (CHF), an open-label, hemodynamic trial was conducted in 11 patients with severe CHF [New York Heart Association (NYHA) class III or IV] in whom previous or current therapy with diuretics and digitalis had been inadequate. After participating in this single-dose trial (acute phase), all 11 patients were entered into a 16-week, multiple-dose investigation (chronic phase). In the acute phase of the study, single oral doses of quinapril (2.5, 5, and 10 mg/day) achieved beneficial hemodynamic changes within 1 h after the onset of therapy. Maximal improvements in key hemodynamic variables (i.e., pulmonary capillary wedge pressure, mean arterial blood pressure, cardiac output, and total systemic vascular resistance) were observed within 4 h after dosing. The hemodynamic changes after 16 weeks of chronic quinapril therapy (5, 10, 15, and 30 mg/day) were equivalent or superior to those observed after acute therapy, indicating that quinapril produces a sustained hemodynamic benefit after chronic oral dosing. Quinapril was shown to be safe and effective in the treatment of patients with severe CHF.


Toward a culturally inclusive understanding of wisdom: historical roots in the East and West.
To establish a clearer definition of wisdom as a psychological concept, Western and Eastern historical literatures were reviewed and assessed within a general analytical/synthetic framework. In the West, either in an ancient Egyptian, biblical, or philosophical sense, wisdom had been often identified as a form of analytical ability such as an increase in the knowledge database or an increase in information processing efficiency. By contrast, the Eastern understanding of wisdom, primarily derived from the ancient Vedic text, had been more inclusive, with both analytical and synthetic domains regarded as necessary moments to the whole of wisdom. The inclusive account was also discussed with respect to two important Eastern themes of wisdom: "void" and "codependence."


Applying generalizability theory to examine the antecedents of perceived coach support.
Although social support is integral to the coaching process, there is only a limited understanding of the antecedents of perceived coach support. We applied generalizability theory to examine perceived coach support and its antecedents at perceiver, provider, and relational levels of analysis. Two studies were conducted in which athletes rated the degree to which they identified with a selection of coaches, and the personality, competency, and supportiveness of those coaches. Univariate analyses demonstrated that the relational component accounted for a significant amount of variance in perceived coach support in both studies. Multivariate analyses demonstrated that when athletes perceive specific coaches to be highly agreeable, competent, and individuals with whom they share a common identity, they also perceive these same coaches to be particularly supportive in comparison with other coaches.


The design of the run Clever randomized trial: running volume, -intensity and running-related injuries.
Injury incidence and prevalence in running populations have been investigated and documented in several studies. However, knowledge about injury etiology and prevention is needed. Training errors in running are modifiable risk factors and people engaged in recreational running need evidence-based running schedules to minimize the risk of injury. The existing literature on running volume and running intensity and the development of injuries show conflicting results. This may be related to previously applied study designs, methods used to quantify the performed running and the statistical analysis of the collected data. The aim of the Run Clever trial is to investigate if a focus on running intensity compared with a focus on running volume in a running schedule influences the overall injury risk differently. The Run Clever trial is a randomized trial with a 24-week follow-up. Healthy recreational runners between 18 and 65 years and with an average of 1-3 running sessions per week the past 6 months are included. Participants are randomized into two intervention groups: Running schedule-I and Schedule-V. Schedule-I emphasizes a progression in running intensity by increasing the weekly volume of running at a hard pace, while Schedule-V emphasizes a progression in running volume, by increasing the weekly overall volume. Data on the running performed is collected by GPS. Participants who sustain running-related injuries are diagnosed by a diagnostic team of physiotherapists using standardized diagnostic criteria. The members of the diagnostic team are blinded. The study design, procedures and informed consent were approved by the Ethics Committee Northern Denmark Region (N-20140069). The Run Clever trial will provide insight into possible differences in injury risk between running schedules emphasizing either running intensity or running volume. The risk of sustaining volume- and intensity-related injuries will be compared in the two intervention groups using a competing risks approach. The trial will hopefully result in a better understanding of the relationship between the running performed and possible differences in running-related injury risk and the injuries developed. Clinical Trials NCT02349373 - January 23, 2015.


The hidden Markov Topic model: a probabilistic model of semantic representation.
In this paper, we describe a model that learns semantic representations from the distributional statistics of language. This model, however, goes beyond the common bag-of-words paradigm, and infers semantic representations by taking into account the inherent sequential nature of linguistic data. The model we describe, which we refer to as a Hidden Markov Topics model, is a natural extension of the current state of the art in Bayesian bag-of-words models, that is, the Topics model of Griffiths, Steyvers, and Tenenbaum (2007), preserving its strengths while extending its scope to incorporate more fine-grained linguistic information.


Daytime sleep accelerates cardiovascular recovery after psychological stress.
Sleep restriction and poor sleep quality is linked with cardiovascular morbidity. The present study aimed to explore the influence of daytime sleep supplementation on cardiovascular reactivity. Participants (N = 85) were generally healthy young adults and were randomized to a 60-min polysomnographically-monitored sleep condition or to a no-sleep condition. Participants then completed a standard three-phase mental stress reactivity task. Significantly lower mean arterial pressure means were found in the recovery phase of the stress reactivity task among participants that accrued more than 45 min of daytime sleep. These findings suggest daytime sleep may offer cardiovascular benefit in the form of greater cardiovascular recovery from psychological stress. Further research should assess daytime sleep characteristics (time of day, length, and architecture) on cardiovascular response, in an effort to better understand its role as a possible recuperative agent against suboptimal nocturnal sleep patterns.


[Clinical efficiency of combined chemotherapy of patients with progressive forms of pulmonary tuberculosis].
Presented in the report are results of treatment of 217 patients with progressive forms of pulmonary tuberculosis. Results of treatment were found out to be dependent on the duration of progression of tuberculosis and degree of immunodepression, the ratio of exudative to caseous changes in the lungs. With more than 4-month duration of progression intensive chemotherapy is of no effect. Cure is only possible in those patients with freshly detected processes, with the duration of progression not exceeding 4 months, immunodepression not too profound.


Anxiety Symptoms, Depressive Symptoms, and Traditional Chinese Medicine Use in U.S. Chinese Older Adults.
This study examined the association between anxiety symptoms, depressive symptoms, and Traditional Chinese Medicine (TCM) use among U.S. Chinese older adults. Data was obtained from the Population Study of Chinese Elderly in Chicago (N = 3157; mean age = 72.8). Anxiety symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS-A). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ-9). TCM modalities included herbal products, acupuncture, massage therapy, Taichi, and other types of TCM. Although not significant, there was a trend indicating that higher levels of anxiety symptoms showed a higher rate of acupuncture use and massage therapy. Older Chinese Americans with depressive symptoms were more likely to use acupuncture and massage therapy; and they were less likely to use other TCM. Future research is needed to identify reasons for TCM use; and how these factors mediate or moderate the relationship between psychiatric symptoms and TCM use.


Effects of sample collection and handling on concentration of osteocalcin in equine serum.
A commercially available radioimmunoassay kit for measurement of human osteocalcin was validated for use in horses. For accurate measurement of equine serum osteocalcin, blood samples may be collected at a temperature between 20 and 25 C, then centrifuged within 90 minutes; serum may be stored at -20 C in plastic tubes for up to 26 weeks. Serum may be thawed and refrozen up to 5 times without significant change in measured equine serum osteocalcin concentration. Assay sensitivity was 0.16 ng/ml. Recovery of bovine osteocalcin standard added to equine serum was linear. Intra-assay coefficient of variation (x 100) for 2 equine serum pools was 6.9 (mean +/- SD, 13.9 +/- 1.0 ng/ml) and 7.5 (10.6 +/- 0.8 ng/ml) %. Interassay coefficient of variation for 3 equine serum pools measured in 12 assays was 12.5 (16.1 +/- 2.0 ng/ml), 12.7 (11.5 +/- 1.5 ng/ml), and 24.6 (3.0 +/- 0.7 ng/ml) %. Dilutional parallelism was documented by assaying pooled equine serum at 4 dilutions and correcting the mean result for dilution. Significant change was not observed in equine serum osteocalcin concentration for various time-of-day blood sample collections in horses housed under continuous lighting.


Comparison of Proteomic Expression Profiles after Radiation Exposure across Four Different Species.
There is a need to identify biomarkers of radiation exposure for use in development of circulating biodosimeters for radiation exposure and for clinical use as markers of radiation injury. Most research approaches for biomarker discovery rely on a single animal model. The current study sought to take advantage of a novel aptamer-based proteomic assay which has been validated for use in many species to characterize changes to the blood proteome after total-body irradiation (TBI) across four different mammalian species including humans. Plasma was collected from C57BL6 mice, Sinclair minipigs, and Rhesus non-human primates (NHPs) receiving a single dose of TBI at a range of 3.3 Gy to 4.22 Gy at 24 h postirradiation. NHP and minipig models were irradiated using a 60Co source at a dose rate of 0.6 Gy/min, the C57BL6 mouse model using an X-ray source at a dose rate of 2.28 Gy/min and clinical samples from a photon source at 10 cGy/min. Plasma was collected from human patients receiving a single dose of 2 Gy TBI collected 6 h postirradiation. Plasma was screened using the aptamer-based SomaLogic SomaScan® proteomic assay technology to evaluate changes in the expression of 1,310 protein analytes. Confirmatory analysis of protein expression of biomarker HIST1H1C, was completed using plasma from C57BL6 mice receiving a 2, 3.5 or 8 Gy TBI collected at days 1, 3, and 7 postirradiation by singleplex ELISA. Summary of key pathways with altered expression after radiation exposure across all four mammalian species was determined using Ingenuity Pathway Analysis (IPA). Detectable values were obtained for all 1,310 proteins in all samples included in the SomaScan assay. A subset panel of protein biomarkers which demonstrated significant (p < 0.05) changes in expression of at least 1.3-fold after radiation exposure were characterized for each species. IPA of significantly altered proteins yielded a variety of top disease and biofunction pathways across species with the organismal injury and abnormalities pathway held in common for all four species. The HIST1H1C protein was shown to be radiation responsive within the human, NHP and murine species within the SomaScan dataset and was shown to demonstrate dose dependent upregulation at 2, 3.5 and 8 Gy at 24 h postirradiation in a separate murine cohort by ELISA. The SomaScan proteomics platform is a useful screening tool to evaluate changes in biomarker expression across multiple mammalian species. In our study, we were able to identify a novel biomarker of radiation exposure, HIST1H1C, and characterize panels of radiation responsive proteins and functional proteomic pathways altered by radiation exposure across murine, minipig, NHP and human species. Our study demonstrates the efficacy of using a multispecies approach for biomarker discovery.


Overexpression of IL-7R alpha provides a competitive advantage during early T-cell development.
Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre-T-cell antigen receptor. Although alpha beta T-cell development is observed in IL-7- and IL-7R alpha-deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7R alpha that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7R alpha was revealed by surface staining, and increased IL-7R alpha mRNA was documented by using reverse transcriptase-polymerase chain reaction (RT-PCR). This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL(+) (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate [dUTP]-fluorescein nick end labeling) cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over healthy thymocytes. This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy.


PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68 Ga-PSMA-11 PET Using Cyclotron-Produced 68 Ga.
Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68 Ga-PSMA-11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68 Ga-PSMA-11 PET was prospectively performed in patients with treatment-naïve HCC on a digital PET scanner using cyclotron-produced 68 Ga. Uptake was graded qualitatively and semi-quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor-associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10-5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = -0.753; P = 1.58 × 10-6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68 Ga-PSMA-11 standardized uptake value: SUVmax (median [range] 9.2 [4.9-28.4]), SUVmean 4.7 (2.4-12.7), and tumor-to-liver background ratio 2 (1.1-11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68 Ga-PSMA-11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.


Prehospital Detection of Large Vessel Occlusion Stroke With Electroencephalography: Results of the ELECTRA-STROKE Study.
Endovascular thrombectomy (EVT) is standard treatment for anterior large vessel occlusion stroke (LVO-a stroke). Prehospital diagnosis of LVO-a stroke would reduce time-to-EVT by allowing direct transportation to an EVT-capable hospital. We aim to evaluate the diagnostic accuracy of dry electrode electroencephalography (EEG) for detection of LVO-a stroke in the prehospital setting. ELECTRA-STROKE was an investigator-initiated, prospective, multi-center, diagnostic study, performed in the prehospital setting. Adult patients were eligible if they had suspected stroke (as assessed by the attending paramedic), and symptom onset <24 hours. A single dry electrode EEG recording (8 electrodes) was performed by the paramedic. Primary endpoint was the diagnostic accuracy of the theta/alpha frequency ratio for LVO-a stroke (intracranial ICA, A1, M1 or proximal M2 occlusion) among patients with EEG data of sufficient quality, expressed as the area under the receiver operating characteristic curve (AUC). Secondary endpoints were diagnostic accuracies of other EEG features quantifying frequency band power and the pairwise derived Brain Symmetry Index. Neuroimaging was assessed by a neuroradiologist blinded to EEG results. Between August 2020 and September 2022, 311 patients were included. Median EEG duration time was 151 (IQR 151-152) seconds. For 212/311 (68%) patients, EEG data were of sufficient quality for analysis. Median age was 74 (IQR 66-81) years, 90/212 (42%) were women, and median baseline NIHSS was 1 (IQR 0-4). Six (3%) patients had an LVO-a stroke, 109/212 (51%) a non-LVO-a ischemic stroke, 32/212 (15%) a transient ischemic attack, 8/212 (4%) a hemorrhagic stroke, and 57/212 (27%) a stroke mimic. AUC for the theta/alpha ratio was 0.80 (95% CI 0.58-1.00). Of the secondary endpoints, the pairwise derived Brain Symmetry Index in the delta frequency band had highest diagnostic accuracy (AUC 0.91 [95% CI 0.73-1.00]; sensitivity 80% [95% CI 38%-96%]; specificity 93% [95% CI 88%-96%]; positive likelihood ratio 11.0 [95% CI 5.5-21.7]). The data from this study suggest that dry electrode EEG has potential to detect LVO-a stroke among patients with suspected stroke in the prehospital setting. Towards future implementation of EEG in prehospital stroke care, EEG data quality needs to be improved. ClinicalTrials.gov identifier: NCT03699397. This study provides Class II evidence that prehospital dry electrode scalp EEG accurately detects LVO-a stroke among patients with suspected acute stroke.


Saviour-sibling and the psychological, ethical and judicial issues that it creates: should English and French legislators close the Pandora's Box?
Since the advent of test-tube babies, advances in the biomedical field have risen steadily. In parallel, the scientific body has never since ceased to debate the ethical issues that they arise. This is particularly the case regarding saviour-sibling. Saviour-sibling refers to a child who is conceived to cure an older brother or sister suffering from a serious family genetic disease. Therefore, it is meant to give birth to a child who will provide stem-cells taken from the umbilical cord or bone marrow afterwards, to treat an elder sick sibling. In England, this practice has been explicitly allowed by the new Human Fertilisation and Embryology Act 2008 under some strict conditions. In France, this practice, authorized by the Bioethics Law of August 2004 and confirmed by its decree of implementation published in the Official Journal on 23 December 2006, is also strictly regulated. This technique opens up new perspectives and enormous hope. Its legalisation is certainly justified by the suffering of the parents and to avoid that they travel to other States where it is permitted. However, it raises serious psychological ethical and judicial issues. Following an analysis of the English and French laws on saviour siblings, its controversial side will be highlighted, before concluding whether or not this new Pandora's box which is saviour-sibling, should be closed and other alternative methods encouraged.


Reducing patient re-identification risk for laboratory results within research datasets.
To try to lower patient re-identification risks for biomedical research databases containing laboratory test results while also minimizing changes in clinical data interpretation. In our threat model, an attacker obtains 5-7 laboratory results from one patient and uses them as a search key to discover the corresponding record in a de-identified biomedical research database. To test our models, the existing Vanderbilt TIME database of 8.5 million Safe Harbor de-identified laboratory results from 61 280 patients was used. The uniqueness of unaltered laboratory results in the dataset was examined, and then two data perturbation models were applied-simple random offsets and an expert-derived clinical meaning-preserving model. A rank-based re-identification algorithm to mimic an attack was used. The re-identification risk and the retention of clinical meaning for each model's perturbed laboratory results were assessed. Differences in re-identification rates between the algorithms were small despite substantial divergence in altered clinical meaning. The expert algorithm maintained the clinical meaning of laboratory results better (affecting up to 4% of test results) than simple perturbation (affecting up to 26%). With growing impetus for sharing clinical data for research, and in view of healthcare-related federal privacy regulation, methods to mitigate risks of re-identification are important. A practical, expert-derived perturbation algorithm that demonstrated potential utility was developed. Similar approaches might enable administrators to select data protection scheme parameters that meet their preferences in the trade-off between the protection of privacy and the retention of clinical meaning of shared data.


Diabetes and risk of cancer.
Diabetes and cancer represent two complex, diverse, chronic, and potentially fatal diseases. Cancer is the second leading cause of death, while diabetes is the seventh leading cause of death with the latter still likely underreported. There is a growing body of evidence published in recent years that suggest substantial increase in cancer incidence in diabetic patients. The worldwide prevalence of diabetes was estimated to rise from 171 million in 2000 to 366 million in 2030. About 26.9% of all people over 65 have diabetes and 60% have cancer. Overall, 8-18% of cancer patients have diabetes. In the context of epidemiology, the burden of both diseases, small association between diabetes and cancer will be clinically relevant and should translate into significant consequences for future health care solutions. This paper summarizes most of the epidemiological association studies between diabetes and cancer including studies relating to the general all-site increase of malignancies in diabetes and elevated organ-specific cancer rate in diabetes as comorbidity. Additionally, we have discussed the possible pathophysiological mechanisms that likely may be involved in promoting carcinogenesis in diabetes and the potential of different antidiabetic therapies to influence cancer incidence.


A multilayer self-organizing model for convex-hull computation.
A self-organizing neural-network model is proposed for computation of the convex-hull of a given set of planar points. The network evolves in such a manner that it adapts itself to the hull-vertices of the convex-hull. The proposed network consists of three layers of processors. The bottom layer computes some angles which are passed to the middle layer. The middle layer is used for computation of the minimum angle (winner selection). These information are passed to the topmost layer as well as fed back to the bottom layer. The network in the topmost layer self-organizes by labeling the hull-processors in an orderly fashion so that the final convex-hull is obtained from the topmost layer. Time complexity of the proposed model is analyzed and is compared with existing models of similar nature.


An empirical comparison of the therapeutic benefits of physical exercise and cognitive training on the executive functions of older adults: a meta-analysis of controlled trials.
A robust body of aging-related research has established benefits of both physical exercise (PE) and cognitive training (CT) on executive functions related to the activities of daily living of older adults; however, no meta-analysis has compared these treatments. The current quantitative review involved a comparison of the overall effect sizes of PE and CT interventions on executive functions (Morris, 2008; pre-post-controlled effect size: d(ppc)), while also exploring contextual moderators of treatment outcomes. A systematic review identified 46 studies (23 PE, 21 CT, and 2 both) meeting inclusion criteria (i.e., controlled interventions, executive-related outcomes, mean ages 65+, information to calculate d(ppc)). The weighted mean dppc values came to 0.12 (p < .01) for PE and 0.24 (p < .01) for CT. Treatment effects differed based on executive constructs for CT, with problem solving presenting the highest d(ppc) (0.47, p < .01). Notably, PE produced similar effect sizes across distinct executive functions. Treatment characteristics (e.g., session length/frequency) did not predict effect sizes. CT had a significant benefit on healthy participants (0.26, p < .01), but cognitively impaired samples did not experience a significant effect. Both treatments improved executive functions, but CT presented a potential advantage at improving executive functions. Improvements in executive functions differed depending on construct for CT, whereas each construct produced similar, modest effect sizes for PE. Publication bias and study quality variability potentially bias these conclusions, as lower quality studies likely produced inflated effect sizes.


A checkerboard pattern manifested by the oviduct epithelium of the Japanese quail.
The oviduct epithelium of the Japanese quail is a monolayered epithelium consisting of two types of columnar cells, goblet type gland (G-) cells and ciliated (C-) cells. We found these cells to be arranged in a checkerboard pattern. Three types of cell boundaries formed between the two different types of cells were examined statistically at various levels of the columnar cells. There was a tendency on the part of the cells to form boundaries between G- and C- cells rather than between two C- cells or between two G- cells. We therefore propose that the pattern is constructed under a rule of maximizing the length of boundaries of two different types of cells owing to the fact that theirs is the greatest adhesion capacity. The role of microfilament bundles running along the apical cell boundaries is also discussed. It is suggested that they are in a tense state so as to shorten total length by contraction.


Using a Virtual Reality and Communication Intervention to Reduce Pain and Anxiety in Patients Undergoing Lipoma Excision With Local Anesthesia: A Randomized Controlled Trial.
In this randomized controlled trial, we assessed the effects of using a virtual reality (VR) and communication intervention on pain and anxiety in patients undergoing lipoma excision under local anesthesia. We conducted the study at a large hospital in Turkey between March 15 and September 15, 2019, with 100 participants. We used a pretest and posttest design to collect data with a personal information form, the Numeric Pain Rating Scale, and the State-Trait Anxiety Inventory. The intervention group participants watched a video using a VR headset during the procedure and communicated with an investigator; the control group participants only received routine surgical treatment. The intervention had a significant effect on pain during the procedure (P < .001) and a moderate effect on anxiety 60 minutes after the procedure (P = .01). Use of VR and active communication may help reduce pain and anxiety for patients undergoing procedures performed with local anesthesia.


Post-translational regulation of PTEN catalytic function and protein stability in the hibernating 13-lined ground squirrel.
The insulin signaling pathway functions as a major regulator of many metabolic and cellular functions, and has been shown to be reversibly suppressed in many species during hibernation. This study characterized the regulation of PTEN phosphatase, a negative regulator of the insulin receptor network, over the torpor-arousal cycle of hibernation in the skeletal muscle of Ictidomys tridecemlineatus. Western blotting and RT-PCR were used to analyze post-translational and transcriptional regulations of PTEN respectively. Enzymatic activities were determined by the malachite green assay, while protein stability was assessed the using pulse-proteolysis method. During torpor, the ratio of non-phosphorylated PTEN (S380/T382/T383) was significantly elevated by 1.4-fold during late torpor compared with euthermic controls; this was coupled with an increase in substrate affinity for PIP3 (by 56%) in late torpor. Two proteolytic cleavage PEST motifs were identified in the C-terminus that overlapped with the phosphorylation sites of PTEN; pulse-proteolysis analysis of PTEN protein showed a decrease in protein stability during late torpor (Cm of urea decreased by 21%). Furthermore, the increase in PTEN activity observed was correlated with a decrease in PDK-1 phosphorylation by 32%, suggesting a downstream effect of PTEN activation during torpor. Transcriptional analysis showed that mRNA expression of pten and pdk-1 remain unchanged during hibernation, suggesting post-translation modification as the primary regulatory mechanism of PTEN function. Phosphorylation plays an important role in the regulation of PTEN enzymatic activity and protein stability. Activation of PTEN during torpor can regulate insulin signaling during periods of low energy state.


Variations of 3-methylhistidine in blood of dairy cows.
Blood plasma 3-methylhistidine, in comparison with other blood variables, has been measured in high-yielding dairy cows with relation to energy and protein supply. Circulating 3-methylhistidine markedly increased to 1 wk after calving, then continuously decreased to 5 wk postpartum to lower than during the last 2 wk of pregnancy. In experiments 36 d after calving, circulating 3-methylhistidine did not change during 24 h despite marked variations of food intake. Peak 3-methylhistidine immediately after parturition coincided with relatively low insulin, thyroxine, triiodothyronine, glucose, protein, and urea with elevated concentrations of nonesterified fatty acids and with greatest estimated energy and protein deficiencies. However, during the ensuing period to 12 wk of lactation, circulating 3-methylhistidine was not closely related to these measures nor to creatinine, beta-hydroxybutyrate, and milk production, but relationships to milk protein yield were close. The postparturient increase of 3-methylhistidine may have been a consequence of enhanced breakdown of skeletal muscle and uterine smooth muscle or another pool with a transiently enhanced turnover rate. Variations of plasma 3-methylhistidine were associated only in part with estimated negative energy and protein balances and corresponding endocrine and metabolic adaptations.


Specific uptake of an amyloid-β protofibril-binding antibody-tracer in AβPP transgenic mouse brain.
Evidence suggests that amyloid-β (Aβ) protofibrils/oligomers are pathogenic agents in Alzheimer's disease (AD). Unfortunately, techniques enabling quantitative estimates of these species in patients or patient samples are still rather limited. Here we describe the in vitro and ex vivo characteristics of a new antibody-based radioactive ligand, [125I]mAb158, which binds to Aβ protofibrils with high affinity. [125I]mAb158 was specifically taken up in brain of transgenic mice expressing amyloid-β protein precursor (AβPP) as shown ex vivo. This was in contrast to [125I]mAb-Ly128 which does not bind to Aβ. The uptake of intraperitoneally-administered [125I]mAb158 into the brain was age- and time-dependent, and saturable in AβPP transgenic mice with modest Aβ deposition. Brain uptake was also found in young AβPP transgenic mice that were devoid of Aβ deposits, suggesting that [125I]mAb158 targets soluble Aβ protofibrils. The radioligand was diffusely located in the parenchyma, sometimes around senile plaques and only occasionally colocalized with cerebral amyloid angiopathy. A refined iodine-124-labeled version of mAb158 with much improved blood-brain barrier passage and a shorter plasma half-life might be useful for PET imaging of Aβ protofibrils.


Ibuprofen-mediated reversal of fluconazole resistance in clinical isolates of Candida.
In view of the increasing prevalence of invasive Candidiasis in today's health-care scenario and the emergence of fluconazole resistance among clinical isolates of Candida, we sought to determine if Ibuprofen could elicit a reversal of fluconazole resistance and thereby offer a potential therapeutic breakthrough in fluconazole-resistant Candidiasis. We selected 69 clinical isolates of Candida, which demonstrated an MIC of >32 μg/ml for fluconazole, and subjected them to broth microdilution in presence and absence of Ibuprofen. Forty two of the 69 isolates (60.9%) demonstrated reversal of Fluconazole resistance with concomitant use of Ibuprofen. This was characterized by significant species-wise variation (p=0.00008), with all the C. albicans isolates and none of the C. glabrata isolates demonstrating such reversal. Only 22.2% and 37.7% of C. krusei and C. tropicalis isolates respectively showed Ibuprofen-mediated reversal of Fluconazole resistance. Since Ibuprofen is a known efflux pump inhibitor, our findings hint at the possible mechanism of Fluconazole resistance in most of our Candida isolates and suggest a potential therapeutic alternative that could be useful in the majority of Fluconazole-resistant clinical isolates of Candida.


Beta-cell function declines within the first year postpartum in women with recent glucose intolerance in pregnancy.
Both gestational diabetes mellitus (GDM) and mild glucose intolerance in pregnancy identify women at increased risk of future type 2 diabetes. In this context, we queried whether metabolic changes that occur in the 1st year postpartum vary in relation to gestational glucose tolerance status. Three-hundred-and-ninety-two women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy followed by repeat OGTT at both 3 months' postpartum and 12 months' postpartum. The antepartum testing defined four gestational glucose tolerance groups: GDM (n = 107); gestational impaired glucose tolerance (GIGT) (n = 75); abnormal GCT with normal glucose tolerance (NGT) on OGTT (abnormal GCT NGT) (n = 137); and normal GCT with NGT on OGTT (normal GCT NGT) (n = 73). The prevalence of dysglycemia progressively increased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM at both 3 months' postpartum (2.7% to 10.2% to 18.7% to 34.6%, P < 0.0001) and 12 months' postpartum (2.7% to 11.7% to 17.3% to 32.7%, P < 0.0001). Between 3 and 12 months' postpartum, the groups did not differ with respect to changes in waist circumference, weight, or insulin sensitivity. Importantly, however, they exhibited markedly different changes in beta-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]) (P = 0.0036), with ISSI-2 declining in both the GDM and GIGT groups. Furthermore, on multiple linear regression analysis, both GDM (t = -3.06, P = 0.0024) and GIGT (t = -2.18, P = 0.03) emerged as independent negative predictors of the change in ISSI-2 between 3 and 12 months' postpartum. Women with GDM and GIGT exhibit declining beta-cell function in the 1st year postpartum that likely contributes to their future diabetic risk.


Predictive factors for surgical outcome in anterior clinoidal meningiomas: Analysis of 59 consecutive surgically treated cases.
Despite the advances in the microsurgical technique and anatomical understanding of the anterior and middle skull base, anterior clinoidal meningiomas are still challenging lesions to resect completely and safely due to their intimate relationship with vital neurovascular structures. We report predictive factors for tumor recurrence and postoperative complications based on surgical outcome of patients with anterior clinoidal meningiomas treated at our institution.Fifty-nine consecutive patients with anterior clinoidal meningioma who were surgically treated between March, 1993, and July, 2015, were reviewed retrospectively. For microsurgical tumor removal, orbitocranial or orbitozygomatic (78.0%), extended pterional (15.3%) and subfrontal approach (6.8%) were performed.The median follow-up duration was 54.1 months. Gross total resection (GTR, Simpson's grade I or II) was achieved in 38 patients (64.4%). The overall recurrence rate (new lesion in GTR cases and re-growth in non-GTR cases) was 18.6%. GTR (Hazard ratio [HR] 0.014, 95% confidence interval [CI] 0.001-0.256; P = .004), absence of internal feeder (HR 0.058, 95% CI 0.004-0.759; P = .030) and benign pathology (WHO grade I, HR 0.056, 95% CI 0.005-0.674; P = .023) were independent prognostic factors for recurrence-free. Fourteen patients (23.7%) developed permanent complications. The most common complication was cranial nerve injury (n = 6; 10.2%), followed by postoperative hemorrhage/infarction, hydrocephalus and infection. Larger size (≥ 40 mm) was significant as an independent predictive factor for permanent complication (HR 0.139, 95% CI 0.030-0.653; P = .012). Old age (≥60 years, P = .056) and peritumoral edema (thickness ≥ 5 mm, P = .303) did not reach statistical significance in multivariate analysis.In surgical resection of anterior clinoidal meningiomas, various clinicoradiological factors were related with resection degree, complication, and progression rate. Although our results showed acceptable resection degree and morbidity, mortality, and recurrence rate, compared to the results of past, anterior clinoidal meningioma remain as neurosurgical challenges because of their close contact to critical vascular and neural structures.


Response of LNCaP spheroids after treatment with an alpha-particle emitter (213Bi)-labeled anti-prostate-specific membrane antigen antibody (J591).
A theoretical drawback to alpha-particle therapy with 213Bi is the short range of the particle track coupled with the short half-life of the radionuclide, thereby potentially limiting effective cytotoxicity to rapidly accessible, disseminated individual tumor cells (e.g., as in leukemia). In this work, a prostate carcinoma spheroid model was used to evaluate the feasibility of targeting micrometastatic clusters of tumor cells using 213Bi-labeled anti-prostate-specific membrane antigen (PSMA) antibody, J591. In prostate cancer, vascular dissemination of tumor cells or tumor cell clusters to the marrow constitutes an important step in the progression of this disease to widespread skeletal involvement, an incurable state. Such prevascularized clusters are ideal targets for radiolabeled antibodies because the barriers to antibody penetration that are associated with the capillary basal lamina have not yet formed. Beta- and gamma-emitting radionuclides such as 131I, which are widely used in radioimmunotherapy, are not expected to be effective when targeting single cells or small cell clusters. This is because the range of the emissions is one to two orders of magnitude greater than the target size, and the energy deposited per traversal is insufficient to produce any significant radiobiological effect. Spheroids of the prostate cancer cell line, LNCaP-LN3, were used as a model of prevascularized micrometastases; their response to an anti-PSMA antibody, J591, radiolabeled with the alpha-particle emitter 213Bi (T(1/2), 45.6 min.) has been measured. The time course of spheroid volume reductions was found to be sensitive to the initial spheroid volume. J591 labeled with 0.9 MBq/ml 213Bi resulted in a 3-log reduction in spheroid volume on day 33, relative to control, for spheroids with an initial diameter of 130 microm; 1.8 MBq/ml were required to achieve a similar response for spheroids with an initial diameter of 180 microm. Equivalent spheroid responses were observed after 12 Gy of acute external beam photon irradiation. Monte Carlo-based microdosimetric analyses of the 213Bi decay distribution in individual spheroids of 130-microm diameter yielded an average alpha-particle dose of 3.7 Gy to the spheroids, resulting in a relative biological effectiveness factor of 3.2 over photon irradiation. The activity concentrations used in the experiments were clinically relevant, and this work supports the possibility of using 213Bi-labeled antibodies not only for disseminated single tumor cells, as found in patients with leukemia, but also for micrometastatic tumor deposits up to 180 microm in diameter (1200 cells).


Simultaneous exocrine and endocrine secretion: trophoblast and glands of the endometrial cups.
Invasion of trophoblast cells of the chorionic girdle into the endometrium and their subsequent dependence as endometrial cup cells on the maternal vascular system are unique features of equine gestation. This study of exocrine secretion by the endometrial glands and endocrine secretion by the cup cells was initiated to examine the relationships between and the effects of two disparate epithelial cell types sharing the endometrium. Endometrial cups were examined from day 36 to day 83 of gestation by light and electron microscopy, and immunohistochemical and lectin analysis. As the cup cells invade the endometrium they migrate along the basal lamina of glands, thus preserving the integrity of the glands. The hypertrophied cup cells develop an extensive network of cytokeratin-positive filaments and large Golgi zones that stain positively with antibodies to equine chorionic gonadotrophin and with the lectins SBA (agglutinin from Glycine max) and WGA (agglutinin from Triticum vulgaris). The endometrial glands within and immediately adjacent to the cup undergo substantial hypertrophy. The gland cells within the cup stain with alcian blue and with some lectins (agglutinins from Dolichos biflorus and lectin SBA), whereas gland cells in unmodified endometrium away from the cup stain positively with antibodies to transforming growth factor a, but only poorly with SBA. Secretory material in gland luminae in the cup stain heterogeneously with alcian blue, periodic acid Schiff and lectins. Later in gestation, glands within the cup become progressively disorganized, with some glands rupturing and releasing their contents into the stroma of the cup. Areas of lipid accumulation and apparent degeneration of cup cells were observed in the cups on day 83 of gestation only. In conclusion, it appears that cup cells substantially modify the integrity and secretion of adjacent endometrial glands, and that progressive disruption of gland integrity and isolation of endometrial vessels by extracellular matrix precedes deterioration of the cup cells. Necrosis and disintegration resulting from these factors appear more likely to limit cup lifespan than to cause programmed cell death of individual cup cells.


Synthesis, characterization and optical properties of ligand-protected indium nanoparticles.
Unlike silver and gold, indium has material properties that enable strong resonances extended up to the ultraviolet. This extended response, combined with low cost, and ease of synthesis process, makes indium a highly promising material for applications. In this work, we have synthesized ligand-protected indium nanoparticles by a metal reduction method. Powder X-ray diffraction and EDX analyses are consistent with the presence of metallic indium in the nanoparticles. Ligand binding was proven by IR spectroscopy and TGA experiments. TEM analyses reveal that the particle size ranges from 6.3 to 4.8 nm. Optical measurements show that the absorption maximum is red shifted as the particle size decreases.


How practitioners say they answer the questions of patients about ultraviolet protection.
Patients should be able to rely on optometrists and optical dispensers to provide evidence-based answers to their questions on eye protection, including against ultraviolet radiation. Surveys indicate that there is public concern about the need for protection against ultraviolet radiation, particularly in sunlight. This investigation aimed to evaluate the quality of information provided by practitioners in response to typical questions to which they might reasonably be expected to have ready answers. A cross-sectional study was conducted of on-site responses from attendees of a 3 day optical fair, in Sydney, Australia, in 2017. Subjects were not forewarned about the study. The portion of the questionnaire reported here comprised open answers to four questions intended to represent typical enquiries of patients. The questions were about recommendations for ultraviolet protection in the context of 1) computer use, 2) outdoor use, 3) driving and 4) under office lighting. Eighty-three participants returned completed questionnaires out of 140 issued (61% response). The open-answer question responses were grouped into appropriate, borderline (mostly appropriate but mixed with non-UVR related recommendations) and others (mostly non-UVR related recommendations) and by job title. The proportion of appropriate answers to the four questions were 20%, 30%, 12% and 15%, respectively, which did not differ by job title. A significantly higher proportion of optical dispensers than optometrists selected 'Don't know/no answer' for all questions except office use. Eyecare professionals need to be educated on eye protection against UV radiation to improve the quality of information to be given to the public.


Pre- and post-target cortical processes predict speech-in-noise performance.
Understanding speech in noise (SiN) is a complex task that recruits multiple cortical subsystems. There is a variance in individuals' ability to understand SiN that cannot be explained by simple hearing profiles, which suggests that central factors may underlie the variance in SiN ability. Here, we elucidated a few cortical functions involved during a SiN task and their contributions to individual variance using both within- and across-subject approaches. Through our within-subject analysis of source-localized electroencephalography, we investigated how acoustic signal-to-noise ratio (SNR) alters cortical evoked responses to a target word across the speech recognition areas, finding stronger responses in left supramarginal gyrus (SMG, BA40 the dorsal lexicon area) with quieter noise. Through an individual differences approach, we found that listeners show different neural sensitivity to the background noise and target speech, reflected in the amplitude ratio of earlier auditory-cortical responses to speech and noise, named as an internal SNR. Listeners with better internal SNR showed better SiN performance. Further, we found that the post-speech time SMG activity explains a further amount of variance in SiN performance that is not accounted for by internal SNR. This result demonstrates that at least two cortical processes contribute to SiN performance independently: pre-target time processing to attenuate neural representation of background noise and post-target time processing to extract information from speech sounds.


[Severe heart insufficiency after acute myocardial infarct: follow up].
An attempt is made to identify and establish the prognostic significance of a subset of patients at high risk after myocardial infarction in need of different therapeutic interventions, using clinical variables of a recently published prospective postinfarction follow-up study. The survivors with anterior myocardial infarction, severe left ventricular dysfunction and ventricular premature depolarizations, making up 15% of the population, have the greatest potential for mortality reduction by appropriate intervention after infarction. The dominance of mechanical and electrical factors in the high risk group necessitates a combined therapeutic approach. The rapid decline in the survivorship curve, with a rapid decline during the first 6 months of the posthospital period implies different intervention regimes at different chronologic intervals in the convalescence phase after myocardial infarction.


Titrating and evaluating multi-drug regimens within subjects.
The dosing of combination therapies is commonly undertaken empirically by practising physicians, and a coherent algorithm to approach the problem of combination dosing is currently lacking. Current methods of evaluating multiple drug combinations in clinical trials fail to provide information regarding the location of more effective doses when the combination is not found to differ from the standard, even though the absence of a difference does not necessarily mean the new combination is ineffective. Moreover, in studies where the new combination is found more effective, often a large proportion of the study participants obtain no benefit from the trial. Even with early stopping rules, the time these subjects spend on inferior treatments can have lasting detrimental effects, leading to problems with patient enrolment and adherence to study protocol. This paper describes an evolutionary operation (EVOP) direct-search procedure to titrate combination doses within individual patients. The Nelder-Mead simplex direct-search algorithm is used to titrate combinations of drugs within individual subjects. Desirability functions are utilized to define the main response of interest and additional responses or constraints. Statistical methodology for determining whether the titrated treatment combination has resulted in an improvement in subject response and for evaluating for therapeutic synergism is developed. Inferences can then be made about the efficacy of the combination or about the individual drugs that comprise the combination. The advantages of this approach include affording every patient the potential to benefit from the combination under study and permitting the consideration of multiple endpoints simultaneously.


Chromosomal characteristics of ribosomal DNA in two extant species of North American mudminnows Umbra pygmaea and U. limi (Euteleostei: Umbridae).
The locations and chromosomal characteristics of ribosomal DNA (rDNA) sites in the karyotypes of two extant North American species of mudminnows, Umbra pygmaea and U. limi (2n = 22, NF = 44), were analyzed sequentially by conventional Giemsa staining, Ag staining, CMA(3) fluorescence and fluorescence in situ hybridization (FISH). The nucleolar organizer regions (NORs) were located in the fourth chromosomal pair in both species (pericentromeric region in U. pygmaea and subtelomeric in U. LIMI). These sites were strongly CMA(3)-positive suggesting that the rDNA sites in these species are associated with GC-rich DNA. FISH with a rDNA probe gave consistently positive signals in the same regions detected by Ag-staining and CMA(3)-fluorescence. However, both species also had additional CMA(3)-positive/Ag-negative heterochromatic blocks at pericentrometric regions of several chromosomal pairs (three in U. pygmaea and five in U. limi). FISH revealed additional rDNA clusters in both species. It is hypothesized that a paracentric inversion of the chromosome arm carrying the NORs might be one of the rearrangements differentiating the karyotypes of two North American species. The presence of additional rDNA sites is indicative of more complex rearrangements. The pericentromeric NOR phenotype of Umbra pygmaea is similar to that seen in U. krameri and in the distantly related genus Esox.


Young-onset colorectal cancer in patients with no known genetic predisposition: can we increase early recognition and improve outcome?
Early recognition of colorectal cancer (CRC) in young patients without known genetic predisposition is a challenge, and clinicopathologic features at time of presentation are not well described. We conducted the current study to review these features in a large population of patients with young-onset CRC (initial diagnosis at age <or=50 yr without established risk factors). We reviewed the records of all patients aged 50 years or younger diagnosed with a primary CRC at our institution between 1976 and 2002. Patients with inflammatory bowel disease, polyposis syndromes, or a known genetic predisposition for CRC were excluded. Data regarding clinical and pathologic features at time of initial presentation were abstracted by trained personnel. We identified 1025 patients, 585 male. Mean age at presentation was 42.4 years (standard deviation 6.4). Eight hundred eighty-six (86%) patients were symptomatic at time of diagnosis. Clinical features in symptomatic patients included rectal bleeding (51%), change in bowel habits (18%), abdominal pain (32%), weight loss (13%), nausea/vomiting (7%), melena (2%), and other (26%). Evaluation of asymptomatic patients was pursued with findings of anemia (14%), positive fecal occult blood test (7%), abdominal mass (2%), mass on digital rectal exam (2%), and other (80%). Site of primary tumor was colonic in 51% and rectal in 49%. Synchronous malignant lesions were noted in 1%. Mucinous and signet cell histology was seen in 11% and 2%, respectively. Tumor grade distribution was grade 1 (2%), grade 2 (54%), grade 3 (34%), and grade 4 (7%). The stage distribution was stage I (13%), stage II (21%), stage III (32%), and stage IV (34%). To our knowledge, the current study is the largest cohort of young-onset CRC patients with no known genetic predisposition for disease. Most patients were symptomatic, had left-colon or rectal cancers and presented with more advanced stage disease. Our findings should promote increased awareness and the aggressive pursuit of symptoms in otherwise young, low-risk patients, as these symptoms may represent an underlying colorectal malignancy.


The role of civil society in health policy making in South Africa: a review of the strategies adopted by the Treatment Action Campaign.
The diagnosis of AIDS in 1982 in South Africa was followed by a rapid rise in the number of people living with the virus and dying from AIDS-related illnesses. The 2016 report by the Statistics South Africa indicated that about 7.03 million South Africans were infected with HIV/AIDS - the highest rate in the world. Despite the emergence of effective drugs in the mid-1990s, medical treatment remained unavailable in South Africa, particularly in public hospitals. This prompted civil society groups to establish platforms to discuss health policy change in South Africa. Prominent among these was the Treatment Action Campaign (TAC), formed in 1998, which aimed to advocate for improved HIV/AIDS health service delivery. The efforts succeeded in shaping the current HIV/AIDS policy through various initiatives such as the use of constitutional law in legal action against profiteering drug companies. This paper examines the role of civil society, and particularly the TAC engagement with the state in health policy making, and the subsequent implementation of health policy on HIV/AIDS in post-apartheid South Africa.


The potential for community exposures to pathogens from an urban dairy.
The objectives of the study described in this article were to evaluate the variation and transport of fungal and bacterial concentrations in the air of a northern Mexico dairy cattle confined animal feeding operation (CAFO) and to determine the concentration and incidence of antibiotic-resistant Staphylococcus aureus isolates. Two-stage viable cascade impactors were used to measure the culturable airborne fungal organisms and bacteria. S. aureus resistant to penicillin, ampicillin, or cefaclor was identified. Samples were collected at three locations that were designated as on site, upwind of the cattle, and downwind of the cattle. The highest concentrations of culturable bacterial bioaerosols were consistently recovered from the on-site location. More than half of the organisms were antibiotic resistant at the on-site location. Elevated levels of culturable bacterial bioaerosols were recovered from the upwind site that may have been associated with the surrounding community. Bioaerosol concentrations were found in higher amounts than in a facility in the southwestern U.S. examined in the authors' previous study. The urban setting of the CAFO resulted in a higher potential for immediate community exposures.


Arsenic induces polyadenylation of canonical histone mRNA by down-regulating stem-loop-binding protein gene expression.
The replication-dependent histone genes are the only metazoan genes whose messenger RNA (mRNA) does not terminate with a poly(A) tail at the 3'-end. Instead, the histone mRNAs display a stem-loop structure at their 3'-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism. Here we report that exposure to arsenic, a carcinogenic metal, decreased cellular levels of SLBP by inducing its proteasomal degradation and inhibiting SLBP transcription via epigenetic mechanisms. Notably, arsenic exposure dramatically increased polyadenylation of canonical histone H3.1 mRNA possibly through down-regulation of SLBP expression. The polyadenylated H3.1 mRNA induced by arsenic was not susceptible to normal degradation that occurs at the end of S phase, resulting in continued presence into mitosis, increased total H3.1 mRNA, and increased H3 protein levels. Excess expression of canonical histones have been shown to increase sensitivity to DNA damage as well as increase the frequency of missing chromosomes and induce genomic instability. Thus, polyadenylation of canonical histone mRNA following arsenic exposure may contribute to arsenic-induced carcinogenesis.


Household food security is associated with infant feeding practices in rural Bangladesh.
Although household food security (HHFS) has been shown to affect diet, nutrition, and health of adults and also learning in children, no study has examined associations with infant feeding practices (IFP). We studied 1343 infants born between May 2002 and December 2003 in the Maternal and Infant Nutrition Intervention in Matlab study to investigate the effect of HHFS on IFP in rural Bangladesh. We measured HHFS using a previously developed 11-item scale. Cumulative and current infant feeding scales were created from monthly infant feeding data for the age groups of 1-3, 1-6, 1-9, and 1-12 mo based on comparison to infant feeding recommendations. We used lagged, dynamic, and difference longitudinal regression models adjusting for various infant and maternal variables to examine the association between HHFS and changes in IFP, and Cox proportional hazards models to examine the influence of HHFS on the duration of breast-feeding and the time of introduction of complementary foods. Better HHFS status was associated with poor IFP during 3-6 mo but was associated with better IFP during 6-9 and 9-12 mo of age. Although better HHFS was not associated with the time of introduction of complementary foods, it was associated with the type of complementary foods given to the infants. Intervention programs to support proper IFP should target mothers in food-secure households when their babies are 3-6 mo old and also mothers in food-insecure households during the 2nd half of infancy. Our results provide strong evidence that HHFS influences IFP in rural Bangladesh.


Estimating population diversity with unreliable low frequency counts.
We consider the classical population diversity estimation scenario based on frequency count data (the number of classes or taxa represented once, twice, etc. in the sample), but with the proviso that the lowest frequency counts, especially the singletons, may not be reliably observed. This arises especially in data derived from modern high-throughput DNA sequencing, where errors may cause sequences to be incorrectly assigned to new taxa instead of being matched to existing, observed taxa. We look at a spectrum of methods for addressing this issue, focusing in particular on fitting a parametric mixture model and deleting the highest-diversity component; we also consider regarding the data as left-censored and effectively pooling two or more low frequency counts. We find that these purely statistical "downstream" corrections will depend strongly on their underlying assumptions, but that such methods can be useful nonetheless.


Development of gelatin nanoparticles conjugated with phytohemagglutinin erythroagglutinating loaded with gemcitabine for inducing apoptosis in non-small cell lung cancer cells.
Gelatin is an efficient drug delivery vehicle for attaching targeting molecules like phytohemagglutinin erythroagglutinating (PHA-E) and carrying the chemotherapeutic agent gemcitabine (GEM). Fluorescent gelatin nanoparticles (GNPs) conjugated with PHA-E and carrying gemcitabine (GNP-(PHA-E)-GEM) were synthesized by nanoprecipitation for guiding gemcitabine-loaded gelatin nanoparticles to NSCLC by PHA-E targeting. GNPs have a uniform narrow size distribution and spherical shape, and their particle size is about 290 nm. The release rate of gemcitabine from nanoparticles reached the plateau of the curve at approximately 30% within 72 hours. PHA-E conjugated nanoparticles could enhance the cellular accumulation of nanoparticles. The results showed that GNP-(PHA-E)-GEM treatment caused an increase of cell growth inhibition and cytotoxicity on NSCLC cells A-549 and H292. In an Annexin V/PI assay, treatment with GNP-(PHA-E)-GEM could induce apoptosis of cancer cells. Treatment of NSCLC cells with GNP-(PHA-E)-GEM firstly resulted in time-dependent inhibition of epidermal growth factor receptor (EGFR) and Akt phosphorylation. And it also could increase p53 phosphorylation. And then it could decrease Bad phosphorylation and increase Bax. Finally, it could result in enhancing the release of cytochrome c, which thus increases caspase-9 and caspase-3. In conclusion, GNP-(PHA-E)-GEM could induce growth inhibition and cytotoxicity, which was mediated through inhibition of EGFR phosphorylation and the switching on of p53 that causes cell apoptosis of NSCLC cells A-549 and H292. It's significant to conjugate PHA-E for targeting cancer and inhibiting EGFR phosphorylation as it could decrease the dosage of gemcitabine, which reduces side effects on normal tissue. GNP-(PHA-E)-GEM has great potential for NSCLC treatment.


The the the the induction of jamais vu in the laboratory: word alienation and semantic satiation.
Jamais vu is a phenomenon operationalised as the opposite of déjà vu, i.e. finding subjectively unfamiliar something that we know to be familiar. We sought to document that the subjective experience of jamais vu can be produced in word alienation tasks, hypothesising that déjà vu and jamais vu are similar experiential memory phenomena. Participants repeatedly copied words until they felt "peculiar", had completed the task, or had another reason to stop. About two-thirds of all participants (in about one-third of all trials) reported strange subjective experiences during the task. Participants reported feeling peculiar after about thirty repetitions, or one minute. We describe these experiences as jamais vu. This experimentally induced phenomenon was related to real-world experiences of unfamiliarity. Although we replicated known patterns of correlations with déjà vu (age and dissociative experiences), the same pattern was not found for our experimental analogue of jamais vu, suggesting some differences between the two phenomena. However, in daily life, those people who had déjà vu more frequently also had jamais vu more frequently. Findings are discussed with reference to the progress that has been made in déjà vu research in recent years, with a view to fast-tracking our understanding of jamais vu.


Bare naked baskets: ureteroscope deflection and flow characteristics with intact and disassembled ureteroscopic nitinol stone baskets.
Lower pole renal access during flexible ureterorenoscopy is often limited by the active deflection capabilities of the ureteroscope. Deterioration in the deflection and flow capabilities of ureteroscopes occurs with the passage of instrumentation through the working channel. We performed in vitro evaluation of a novel technique using unsheathed nitinol baskets to minimize the deterioration in deflection and maximize the irrigant flow associated with instrument passage through the working channel during flexible ureterorenoscopy. Alterations in the irrigant flow and active deflection of 4 ureteroscopes from different manufacturers were evaluated. Each ureteroscope was evaluated with an empty working channel, and then with sheathed and unsheathed 2.2, 3 and 3.2Fr (Cook Urological, Inc., Indianapolis, Indiana), 2.4 and 3Fr (Microvasive Urology, Natick, Massachusetts) nitinol baskets in the working channel. With all baskets tested and in all ureteroscopes the deterioration in active deflection and irrigant flow was improved with the unsheathed baskets. The disassembled basket within the working channel allowed an additional 15 to 20 degrees of active deflection. In addition, the disassembled basket allowed for a 2 to 30-fold increase in irrigant flow compared with an intact basket. The combination of improved deflection and irrigant flow with this technique may improve ureteroscopic access to lower pole renal calculi.


Vinasse and Its Influence on Ant (Hymenoptera: Formicidae) Communities in Sugarcane Crops.
Sugarcane is an important crop within the Brazilian socioeconomic landscape. There is a constant need for approaches to increase sustainability at all steps of the production chain. Irrigating sugarcane crops with vinasse is one of these approaches, because vinasse is a residue of sugarcane processing that can be used to fertilize these same crops. However, due to its chemical properties, vinasse may be harmful to soil fauna. Analyzing the structure and functional organization of ant communities is a fast and practical way to monitor sites affected by the addition of chemicals. This study compared the structure of soil ant communities in vinasse-irrigated sugarcane crops to those in secondary forests adjacent to the crops. In total, 32 genera and 107 species of ants were observed; of these, 30 species foraged in crop fields and 102 foraged in forests. Twenty-five percent of the species were present in both crops and forests. Ant communities in crop soil had poorer taxonomic composition and lower richness in each functional group compared to communities in forest remnants. However, regardless of vegetation type, epigeic ants were more diverse, and Dorymyrmex brunneus (crop) and Pachycondyla striata (forest) were very frequent. Vinasse did not increase the diversity of epigeic and hypogeic ants, but it may affect the community composition.


Synthesis, structure, and evaluation of the effect of multiple stacking on the electron-donor properties of pi-stacked polyfluorenes.
A versatile synthesis of pi-stacked polyfluorenes is described. These polyfluorenes retain their cofacial conformations both in solution and in the solid state as was judged by NMR spectroscopy and X-ray crystallography. The experimental electron-detachment energies of F1-F4 showed linear correlations with the quantity 1/n, where n is the number of fluorene moieties. These correlations allowed the estimation of the vertical ionization potential (IP) of 7.10 eV and the oxidation potential (Eox) of 0.97 V versus SCE for the multiply stacked polyfluorene donor with an infinite number of fluorene moieties. These observations with pi-stacked polyfluorenes may prove to be highly relevant to the electron-transport phenomenon observed in DNA through pi-stacked bases.


The neurobiology of the spinal cord in experimental parkinsonism and Parkinson's disease.
The neurobiology of non-motor symptoms in Parkinson's disease (PD) reveals a number of unexpected areas which once were not recognized a priori as part of the neuropathology underlying PD. These areas may belong either to central nervous system or periphery. Among central areas major efforts in the last decade led to recognize a number of brain nuclei as part of the disease spreading or disease onset in PD patients. Unexpectedly recent evidence deriving from pathological studies in PD patients and corroborated by experimental models of PD provided clear evidence that the spinal cord is often recruited in PD pathology. Such an involvement is intriguing since the major degenerative disease of the spinal cord (amyotrophic lateral sclerosis) features the involvement of dopaminergic neurons of the substantia nigra pars compacta, while some environmental (parkinsonism, ALS, and dementia of Guam) and genetic (Kufor-Rakeb syndrome) diseases are known to be characterized by mixed degeneration of pyramidal and extrapyramidal regions. Thus, the clear-cut between degeneration of dopaminergic neurons in the substantia nigra and the loss of pyramidal motor system appears now more as a continuum of degeneration which converge in abnormal activity and cell pathology of motor neurons as a final common pathway. Among motor neurons, visceral efferent cells of the spinal cord are involved and provide a robust neurobiological findings which may justify a variety of non-motor autonomic symptoms which characterize PD. Neurodegeneration in the spinal cord extends to the dorsal horn of the grey matter posing an intriguing link between PD and sensory alterations. The present manuscript reviews the involvement of multiple regions of the spinal cord in PD and experimental parkinsonism in the attempt to provide both a neurobiological background to understand non motor symptoms and to provide the anatomical basis for disease spreading.


Immunohistochemistry for Immunoglobulin G4 in the Diagnosis of Pemphigus.
Pemphigus comprises of a group of autoimmune bullous disorders with intraepithelial lesions involving the skin and mucous membranes. Pemphigus is characterized histologically by an intraepidermal blister and immunopathologically by the finding of in vivo bound immunoglobulin G (IgG) antibodies against desmosomal adhesion proteins on the surface of keratinocytes. Indirect immunofluorescence for IgG is considered as a gold standard method for diagnosis of this group of bullous disorders on the condition that fresh frozen tissue is accessible. We designed a new diagnostic method by immunohistochemistry (IHC) for IgG4 on paraffin sections instead of fresh frozen tissue and evaluated sensitivity, specificity, and positive and negative predictive values of this method. We searched our pathologic archive of pemphigus of 35 patients, including 29 cases of pemphigus vulgaris (PV) and 6 patients with pemphigus foliaceus (PF). In all cases, the diagnosis was confirmed by indirect immunofluorescence studies. Thirty-five specimens served as controls, including 31 specimens of safe margins of basal cell carcinoma and 4 specimens of normal skin. Sections with condensed and continuous immunoreactivity localized to the intercellular junctions of keratinocytes were considered as positive. Sensitivity of IgG4 was estimated to be 72.4% in PV group and 83.3% in PF group. The overall sensitivity and specificity of IgG4 IHC for diagnosis of pemphigus were 74.2% and 82.8%, respectively, in PV and PF groups. Furthermore, positive predictive value and negative predictive value were 81.2% and 76.3%, respectively. Immunohistochemical labeling for IgG4 on paraffin-embedded tissue provides a sensitive and specific test for diagnosing pemphigus in a situation when fresh frozen tissue is unavailable.


Application of the thermally tuned tandem column concept to the separation of several families of environmental toxicants.
Separations of several families of environmental toxicants were optimized by means of the thermally tuned tandem column (T3C) concept. We use a tandem combination of an octadecylsilane (ODS) and a carbon-coated zirconia (C-ZrO2) column; and tune the selectivity by independently adjusting the isothermal temperatures of the two columns. This results in the change in the contribution that each column makes to the overall retention and selectivity. The separation was optimized by locating the optimum pair of column temperatures which give the best separation of the critical solute pair. For both triazine herbicides and carbamate pesticides samples, dramatically different selectivities and different critical pairs were observed for the two types of phases. Although neither individual phase gave adequate separation, the T3C approach provided baseline separations using only four preliminary trial separations. We also showed that, for the triazine samples, the T3C approach gave a better separation than did conventional mobile phase optimization with an ODS column. The combination of superior selectivity of T3C and high flow rate allows the baseline separation of complex mixtures in just a few minutes.


Pancreatectomy using the no-touch isolation technique followed by extensive intraoperative peritoneal lavage to prevent cancer cell dissemination: a pilot study.
In pancreatic cancer, even for patients who have undergone curative resection (R0), survival analysis has revealed a poor survival rate due to cancer recurrence. Because the operation itself might have caused the dissemination of these cancer cells, the no-touch isolation technique and extensive intraoperative peritoneal lavage may be a potential operative procedure for improving the outcome. Eight patients treated by the no-touch isolation technique were compared with 10 patients treated using conventional techniques. Cancer cell detection rates in the portal venous blood, frequency of recurrence, and survival rate. We also analyzed the lymphatic fluid squeezed from the resected cancerous pancreatic tissue. In 5 out of 10 cases (50%) in the conventional procedure group, CEA mRNA was identified in the portal blood after tumor manipulation, while only 1 out of 8 cases (13%) in the no-touch isolation technique group was positive for portal CEA mRNA. All lymphatic fluid samples squeezed from the resected cancerous pancreatic tissue were positive (8/8) for CEA mRNA. The recurrence rate was 90% (9/10) in the conventional procedure group, and 38% (3/8) in the no-touch isolation technique group (P=0.043). In the conventional procedure group, hepatic metastasis, local recurrence, peritoneal dissemination, and extraabdominal recurrence were identified in 6 (60%), 4 (40%), 4 (40%), and 2 patients (20%), respectively. On the other hand, among the no-touch isolation technique group, recurrence was identified in 1 (13%), 1 (13%), 0 (0%), and 1 patient (13%), respectively. There was no peritoneal dissemination along with the decreased hepatic recurrence rate. Mean (+/-SEM) survival time was 21.2+/-5.8 months for the conventional procedure group and 41.5+/-5.6 months for the no-touch isolation technique group (P=0.018). The 3-year survival rate was 12.5+/-11.5% for the conventional procedure group and 75.0+/-21.7% for the no-touch isolation technique group. This study presented the potential of cancer dissemination during the intraoperative manipulation of tumors and its contribution to cancer recurrence, as well as the significance of the no-touch isolation technique and extensive intraoperative peritoneal lavage for pancreatic cancer surgery.


Sidedness of carbamazepine accessibility to voltage-gated sodium channels.
Voltage-gated sodium channels are inhibited by many local anesthetics, antiarrhythmics, and antiepileptic drugs. The local anesthetic lidocaine appears to be able to access its binding site in the sodium channel only from the membrane phase or from the internal face of the channel. In contrast, the antiepileptic drug carbamazepine was found to inhibit voltage-gated sodium channels only with external, but not internal, application, implying a major difference. We investigated this point using both whole-cell and inside-out patch recordings from human Na(v)1.7 channels in a stable cell line. In the whole-cell configuration, carbamazepine inhibited sodium current within seconds when applied externally, but had little or no effect when applied internally for up to 15 minutes, confirming previous results. However, carbamazepine inhibited sodium channels effectively and rapidly when applied to the internal face of the membrane using inside-out patch recording. We found that lidocaine also has little or no effect when applied intracellularly in whole-cell recording, but blocks effectively and rapidly when applied to the internal surface using inside-out patches. In contrast, the cationic lidocaine derivative QX-314 (N-ethyl-lidocaine) blocks effectively when applied internally with whole-cell dialysis, as well as when applied to inside-out patches. We conclude that carbamazepine and lidocaine access the sodium channel in similar ways and hypothesize that their lack of effect with internal dialysis in whole-cell recording reflects rapid exit through membrane near the pipette recording site. This effect likely limits the ability of any compound with significant membrane permeability to be applied intracellularly by whole-cell dialysis.


Evaluation of a New, Rapid, Fully Automated Assay for the Measurement of ADAMTS13 Activity.
Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (< 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. A method comparison study was performed on 176 samples from 49 healthy donors and 127 TMA patients (109 TTP, 7 atypical hemolytic uremic syndrome, 11 other TMAs), comparing this new assay with an in-house FRETS-VWF73 assay and a commercial enzyme-linked immunosorbent assay (ELISA) (TECHNOZYM ADAMTS-13 Activity, Technoclone GmbH, Vienna, Austria). Agreement between methods was assessed with focus on ADAMTS13 activity less than 10%, the medical decision level relevant for TTP diagnosis. The HemosIL AcuStar ADAMTS13 Activity showed good correlation with both the FRETS-VWF73 (r = 0.96) and ELISA (r = 0.96) methods. Slope of the Passing-Bablok regression was 1.05 for FRETS-VWF73 and 1.02 for ELISA, and absolute bias at the medical decision level was +0.1 and +0.3%, respectively. The study also revealed high agreement with FRETS-VWF73 (kappa 0.97) and ELISA (kappa 0.98) methods in classifying TTP patients with a severe deficiency of ADAMTS13 activity. Because of its short turnaround time and full automation, the HemosIL AcuStar ADAMTS13 activity assay might become the assay of choice to rapidly test ADAMTS13 activity in plasma and thus establish the diagnosis of acute TTP in emergency settings.


Postnatal development of NADPH-diaphorase activity in the rat: the role of nitric oxide in the ontogeny of arginine vasopression and oxytocin.
To clarify the role of nitric oxide (NO) in the ontogeny of arginine vasopressin (AVP) and oxytocin (OXT) neurons in the hypothalamo-neurohypophysial system (HNS), we observed the coexpression pattern of NADPH-diaphorase (NADPH-d) activity and AVP- or OXT-immunoreactivity (IR) in the rat hypothalamus and posterior pituitary during the postnatal period. The enzymatic activity of NADPH-d was observed in the supraoptic nucleus (SON), paraventricular nucleus (PVN), median eminence (ME) and posterior pituitary throughout the postnatal development. AVP-containing neurons were clearly observed from postnatal day 1 in both the SON and PVN, while OXT-containing neurons were recognized from postnatal day 14. The coexistence of NADPH-d and AVP or OXT was detected in the SON from postnatal day 14. At postnatal day 21, the coexpression pattern was approximately the same as that of the SON and PVN in adult rats. Our findings indicated that the expression of NADPH-d and OXT was observed from almost the same postnatal period in both the SON and PVN. In addition, the pattern of increased numbers of NADPH-d positive fibers was similar to that of OXT-immunoreactive fibers in both the inner layer of the ME and the posterior pituitary. A good correlation was thus obtained between OXT expression and NADPH-d activity in the HNS during postnatal development. The present study suggests that NO is more closely involved in the expression and regulation of secretion of OXT than AVP.


Supporting Deaf Students in Undergraduate Research Experiences: Perspectives of American Sign Language Interpreters.
Deaf undergraduates are eager to engage in research but often feel marginalized due to lack of appropriate accommodations to allow for effective communication within heterogeneous research teams consisting of hearing peers and/or mentors. In this case study, we interviewed four American Sign Language (ASL) interpreters who provided full-time accommodations to teams consisting of one deaf student and two hearing peers during a six-week internship. We queried the interpreters on their role and experiences in supporting the research teams. Our findings indicate that the interpreters can be a valuable asset to heterogeneous teams by supporting both deaf and hearing individuals and advocating for the deaf student. That said, interpreters also had to overcome challenges unique to interpreting in the research environment, such as deciding when and how to interpret. The insights provided by the interpreters interviewed here are valuable as undergraduate research programs evaluate how to provide appropriate accommodations to deaf students engaged in research. In addition, they also highlight the need for research experience coordinators and mentors to consider supporting diverse teams in developing effective communication strategies and applying universal design for learning to the research environment.


Exogenous Vasopressin-Induced Hyponatremia in Patients With Vasodilatory Shock: Two Case Reports and Literature Review.
Vasopressin has gained wide support as an adjunct vasopressor in patients with septic shock. This agent exerts its vasoconstriction effects through smooth muscle V1 receptors and also has antidiuretic activity via renal V2 receptors. This interaction with the renal V2 receptors results in the integration of aquaporin 2 channels in the apical membrane of the renal collecting duct leading to free water reabsorption. Thus, water intoxication with subsequent hyponatremia, although rare, is a potentially serious side effect of exogenous vasopressin administration. We present 2 patients who developed hyponatremia within hours of initiation of vasopressin infusion. Extensive diuresis followed its discontinuation with subsequent normalization of serum sodium. One of the patients required the use of hypertonic saline for more rapid normalization of serum sodium due to concerns for potential seizure activity. A review of the literature relevant to the incidence of vasopressin-induced hyponatremia is provided as well as discussion on additional factors relevant to septic shock that should be considered when determining the relative risk of hyponatremia in patients receiving vasopressin.


Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line.
The c-erbB-2 gene is a v-erbB-related proto-oncogene which is distinct from the gene encoding the epidermal growth factor receptor. By using two independent methods, hybridization of both sorted chromosomes and metaphase spreads with cloned c-erbB-2 DNA, we mapped the c-erbB-2 locus on human chromosome 17 at q21, a specific breakpoint observed in a translocation associated with acute promyelocytic leukemia. Furthermore, we observed amplification and elevated expression of the c-erbB-2 gene in the MKN-7 gastric cancer cell line. These data suggest possible involvement of the c-erbB-2 gene in human cancer.


The sensitivity and specificity of a reverse transcription-polymerase chain reaction assay for the avian pneumovirus (Colorado strain).
A reverse transcription-polymerase chain reaction (RT-PCR) assay for the detection of avian pneumovirus (APV), Colorado strain (US/CO), was evaluated for sensitivity and specificity. The single-tube RT-PCR assay utilized primers developed from the matrix (M) gene sequence of the US/CO APV. The RT-PCR amplified the US/CO APV but did not amplify other pneumoviruses, including the avian pneumoviruses subgroups A and B. The RT-PCR was capable of detecting between 10(0.25) mean tissue culture infective dose (TCID50) and 10(-0.44) TCID50 of the US/CO APV. These results have demonstrated that the single-tube RT-PCR assay is a specific and sensitive assay for the detection of US/CO APV.


Remission of active chronic hepatitis after treatment with cyclophosphamide and prednisolone. Report of four cases.
A description is given of four patients with active chronic hepatitis, all of whom were treated with prednisolone and cyclophosphamide. In all the patients diagnosis was established by the finding of a clinical picture of hepatic dysfunction associated with abnormal results of biochemical tests of liver function, evidence of disturbed immunity mechanisms and liver biopsy. After treatment all four patients made a clinical recovery. Three eventually had normal serum tests for liver function, normal bromsulphthalein excretion tests and normal histology in their needle liver biopsies. The fourth patient has shown considerable improvement in her serum tests of liver function, but she has been treated for a much shorter period than the others. Her test results are still improving. It is concluded that the combination of prednisolone and cyclophosphamide therapy is a satisfactory one for active chronic hepatitis, and probably superior to other therapeutic measures based upon the suppression of autoimmune mechanisms.