Does Cytological Laboratory Holds the Responsibility for the Low Sensitivity of the PAP Test in Detecting Endometrial Cancer?
Endometrial cancer is the most common gynecological cancer but there is no economically justified screening method. Although we can detect endometrial cells in the sample using PAP test, many studies show low sensitivity and positive predictive value of PAP test for the diagnosis of endometrial cancer. The goal of this research was to determine significance of PAP test for the diagnostics of endometrial carcinoma. Sensitivity and specificity were analyzed with statistical parameters. VCE (vaginal, cervical, endocervical) smears of patients with histologically proven endometrial carcinoma were re-examined in order to determine the proportion of false negative results for endometrial cancer cells in the VCE samples. Study group consisted of all consecutive patients with PAP test performed at the Department of Clinical Cytology of the University Hospital Center Osijek from 2002 until the end of 2014. There was one inclusion criteria: subsequent hysterectomy or curettage within the six month after the PAP test, regardless of histological finding. From a total of 263 patients with previous PAP test and histologically proven endometrial cancer, endometrial cancer was cytologicaly diagnosed in 24.7% (including suspicious and positive findings), while 66.2% patients had normal cytological findings. The diagnostic value of PAP test in detection of endometrial cancer was statistically revealed with 25% sensitivity and 99% specificity. To determine false negative rate VCE samples were reviewed for patients with histologically proven endometrial cancer and negative VCE findings. There were a total of five negative results. In one case revision did not changed the original negative diagnosis, but benign endometrial cells, a lot of blood and inadequate cytohormonal status were found. In three out of four reviewed samples there were missed cells of endometrial adenocarcinoma. Review of remaining VCE sample upgraded the diagnosis from negative to suspicious for endometrial cancer. Proportion of error in the detection of endometrial cancer using cytological findings was 3.4% (true false negatives). Negative rate of the cytological findings in the detection of endometrial cancer was 66.2%. PAP test is not a suitable method for detection of endometrial carcinoma due to low sensitivity (25%). The main cause of negative findings in PAP test was lack of diagnostic cells in the sample.


Anterior segment optical coherence tomography parameters in subtypes of primary angle closure.
To compare anterior segment parameters, assessed by anterior segment optical coherence tomography (ASOCT), in subjects categorized as primary angle closure suspect (PACS), primary angle closure (PAC), primary angle closure glaucoma (PACG), and previous acute PAC (APAC); and to identify factors associated with APAC. This was a prospective ASOCT study of 425 subjects with angle closure (176 PACS, 66 PAC, 125 PACG, and 58 APAC). Customized software was used to measure ASOCT parameters, including angle opening distance (AOD750), trabecular-iris space area (TISA750), anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness (IT750), iris area (IAREA), and lens vault (LV). Mean differences in anterior segment parameters were evaluated by analysis of covariance (ANCOVA) adjusted for age, sex, and pupil diameter (PD). Comparison among the different subgroups showed that ACD, ACA, and ACV were smallest, and IT750 thickest in the APAC group compared with the other subgroups (P < 0.001). LV was greatest in the APAC group (1218 ± 34 μm) followed by PAC (860 ± 31 μm), PACG (845 ± 23 μm), and PACS (804 ± 19 μm), respectively (P = <0.001). While the APAC group had the narrowest angles, the PACS group had the widest (P < 0.001 for both AOD750 and TISA750). Logistic regression showed that greater LV (P = <0.001), narrower TISA750 (P = <0.001), and thicker IT750 (P = 0.007) were the major determinants of APAC. Eyes with APAC had the narrowest angles, smallest anterior segment dimensions, thickest iris, and largest LV compared with PACS, PAC, and PACG. LV, TISA750, and IT750 were the major determinants of APAC.


[Sleep and depression (author's transl)].
This critical review of the literature concerns the electrophysiological studies of sleep applied to depressed patients. While the (phenomenological) studies confirm the actual sleep disturbances in most patients and at certain stages of the depressive episodes, the (parallelistic) studies failed to evidence any strict correlation between quantified sleep data and nosographical classifications of depressions. The reductionistic) studies, searching into sleep measurements indices of specific biochemical disturbances also lead to contradictory and questionable conclusions. The explanation of this negative assessment is not to be found in methodological deficiencies but must be searched at the level of the theoretical approach of the problem.


Estimating the correlation of bivariate failure times under censoring.
The analysis of correlations within pairs of survival times is of interest to many research topics in medicine, such as the correlation of survival-type endpoints of twins, the correlation of times till failure in paired organs, or the correlation of survival time with a surrogate endpoint. The dependence of such times is assumed monotonic and thus quantification by rank correlation coefficients appropriate. The typical censoring of such times requires more involved methods of estimation and inference as have been developed in recent years. The paper focuses on semiparametric approaches, and in particular on the normal copula-based estimation of Spearman correlation coefficients. The copula approach, often presented for a mathematically inclined readership, is reviewed from the viewpoint of an applied statistician. As an alternative to the maximum likelihood methodology for the normal copula approach (NCE) we introduce an iterative multiple imputation (IMI) method which requires only about 0.05% of the computing time of NCE, without sacrificing statistical performance. For IMI, survival probabilities at death or censoring times are first transformed to normal deviates. Then, those deviates that relate to censored times are iteratively augmented, by using conditional multiple imputation, until convergence is obtained for the normal scores rank correlation, which is similar to Spearman's rank correlation. Statistical properties of NCE and IMI are compared by means of a Monte Carlo study and by means of three real data sets, which also give an impression of the typical range of applications, and of their problems.


Synthesis of C-terminal glycopeptides via oxime resin aminolysis.
Natural glycopeptides have been shown to possess interesting biological activities. In this work, we have developed a general solid-phase approach to C-terminal glycopeptides. Taking advantage of oxime resin ester bond nucleophile susceptibility, we optimised the nucleophilic cleavage step with glycosylamines and demonstrated the generality and scope of this method. In addition, this reaction has high functional group tolerance and can be used for the preparation of longer C-terminal glycopeptides, demonstrated with the synthesis of a glycododecapeptide in one single step. The results pave the way to access efficiently novel medically relevant compounds.


Diagnostic accuracy of Enzyme-Linked Immunosorbent Assays to detect anti-Leishmania antibodies in patients with American Tegumentary Leishmaniasis: a systematic review.
American Tegumentary leishmaniasis (ATL) is an infectious disease caused by several species of Leishmania . Even though the direct detection of parasites has low sensitivity, it is still the gold standard for the laboratory diagnosis of ATL. Recent studies have shown promising results of Enzyme-Linked Immunosorbent Assays ( ELISAs) using recombinant antigens. The aim of this study is to compare the accuracy of ELISAs using novel antigens with the standard ELISA based on soluble antigens of Leishmania (SLA) to diagnose ATL. Studies that analyzed patients with ATL and studies that evaluated the diagnostic accuracy of ELISAs using novel antigens and SLA were included. The Fourteen studies from PubMed, Regional Portal of the Virtual Health Library (BVS), Brazilian Society of Dermatology, Virtual Health Library (IBECS), Literature in the Health Sciences in Latin America and the Caribbean (LILACS), Medical Literature Analysis and Retrieval System Online (Medline), Elsevier Embase, Cochrane Library, The National Institute for Health and Care Excellence (NICE), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were included. The novel ELISA antigens showed a high sensitivity (93.8%-100%) and specificity (82.5-100%), a better diagnostic performance than SLA-based ELISAs (1-97.4% and 57.5-100%, respectively). Only 10 studies analyzed cross-reactions in serum samples from patients with Chagas disease, and only two studies reported a percentage of cross-reactivity. In this systematic review, the novel ELISA antigens showed better sensitivity and specificity with respect to SLA-based ELISAs. However, a meta-analysis should be performed to confirm this finding.


KANPHOS: A Database of Kinase-Associated Neural Protein Phosphorylation in the Brain.
Protein phosphorylation plays critical roles in a variety of intracellular signaling pathways and physiological functions that are controlled by neurotransmitters and neuromodulators in the brain. Dysregulation of these signaling pathways has been implicated in neurodevelopmental disorders, including autism spectrum disorder, attention deficit hyperactivity disorder and schizophrenia. While recent advances in mass spectrometry-based proteomics have allowed us to identify approximately 280,000 phosphorylation sites, it remains largely unknown which sites are phosphorylated by which kinases. To overcome this issue, previously, we developed methods for comprehensive screening of the target substrates of given kinases, such as PKA and Rho-kinase, upon stimulation by extracellular signals and identified many candidate substrates for specific kinases and their phosphorylation sites. Here, we developed a novel online database to provide information about the phosphorylation signals identified by our methods, as well as those previously reported in the literature. The "KANPHOS" (Kinase-Associated Neural Phospho-Signaling) database and its web portal were built based on a next-generation XooNIps neuroinformatics tool. To explore the functionality of the KANPHOS database, we obtained phosphoproteomics data for adenosine-A2A-receptor signaling and its downstream MAPK-mediated signaling in the striatum/nucleus accumbens, registered them in KANPHOS, and analyzed the related pathways.


Tolerance of organs at risk in small-volume, hypofractionated, image-guided radiotherapy for primary and metastatic lung cancers.
To determine the organ at risk and the maximum tolerated dose (MTD) of radiation that could be delivered to lung cancer using small-volume, image-guided radiotherapy (IGRT) using hypofractionated, coplanar, and noncoplanar multiple fields. Patients with measurable lung cancer (except small-cell lung cancer) 6 cm or less in diameter for whom surgery was not indicated were eligible for this study. Internal target volume was determined using averaged CT under normal breathing, and for patients with large respiratory motion, using two additional CT scans with breath-holding at the expiratory and inspiratory phases in the same table position. Patients were localized at the isocenter after three-dimensional treatment planning. Their setup was corrected by comparing two linacographies that were orthogonal at the isocenter with corresponding digitally reconstructed images. Megavoltage X-rays using noncoplanar multiple static ports or arcs were used to cover the parenchymal tumor mass. Prophylactic nodal irradiation was not performed. The radiation dose was started at 60 Gy in 8 fractions over 2 weeks (60 Gy/8 Fr/2 weeks) for peripheral lesions 3.0 cm or less, and at 48 Gy/8 Fr/2 weeks at the isocenter for central lesions or tumors more than 3.0 cm at their greatest dimension. Fifty-seven lesions in 45 patients were treated. Tumor size ranged from 0.6 to 6.0 cm, with a median of 2.6 cm. Using the starting dose, 1 patient with a central lesion died of a radiation-induced ulcer in the esophagus after receiving 48 Gy/8 Fr at isocenter. Although the contour of esophagus received 80% or less of the prescribed dose in the planning, recontouring of esophagus in retrospective review revealed that 1 cc of esophagus might have received 42.5 Gy, with the maximum dose of 50.5 Gy. One patient with a peripheral lesion experienced Grade 2 pain at the internal chest wall or visceral pleura after receiving 54 Gy/8 Fr. No adverse respiratory reaction was noted in the symptoms or respiratory function tests. The 3-year local control rate was 80.4% +/- 7.1% (a standard error) with a median follow-up period of 17 months for survivors. Because of the Grade 5 toxicity, we have halted this Phase I/II study and are planning to rearrange the protocol setting accordingly. The 3-year local control rate was 69.6 +/- 10.6% for patients who received 48 Gy and 100% for patients who received 60 Gy (p = 0.0442). Small-volume IGRT using 60 Gy in eight fractions is highly effective for the local control of lung tumors, but MTD has not been determined in this study. The organs at risk are extrapleural organs such as the esophagus and internal chest wall/visceral pleura rather than the pulmonary parenchyma in the present protocol setting. Consideration of the uncertainty in the contouring of normal structures is critically important, as is uncertainty in setup of patients and internal organ in the high-dose hypofractionated IGRT.


[Latent infection of continuous L23 cells caused by the agent of scrapie].
Two models of latent infection of continuous L23 cells caused by scrapie agent were developed using the method of cell cloning as well as DEAE-dextran and lidase preparations. The infectious activity was found only in cell homogenate L-C and L-506 (cells of clone L23 latently infected with the Compton and C-506 strains of the scrapie agent). A direct relationship between the infectious activity of the cell homogenate and the intensity of brain lesions revealed by morphological examinations of brain sections from infected mice was observed. The cytoplasm of L-C and L-506 cells became strongly vacuolated, piknosis of the nuclei and delay in the cell growth rate were noted. Cytogenetic studies established changes in the model class of the experimental cultures as well as the appearance of rearranged chromosomes.


Molar Pregnancy-Induced Hyperthyroidism: The Importance of Early Recognition and Timely Preoperative Management.
Hyperthyroidism due to gestational trophoblastic disease (GTD) is a rare but potentially life-threatening condition. Optimal perioperative management is crucial for favorable outcomes and prevention of thyroid storm. However, scarce data exist defining the ideal approach to this complex clinical presentation. This case report describes a first-time pregnant 32-year-old woman who was found to be biochemically hyperthyroid in the context of a 10-week gestation molar pregnancy. Despite her biochemical values, the patient remained clinically asymptomatic of her thyroid disease. The Gynecology and Anesthesiology services urgently consulted Endocrinology, and empiric treatment for prevention of potential impending thyroid storm was initiated prior to operative uterine evacuation. After 2 uneventful dilation and curettages with chemotherapy and a transient prescription of antithyroid medication, the patient normalized her human chorionic gonadotropin (hCG) level and recovered to biochemical euthyroidism. Other than a pruritic rash that may have been due to propylthiouracil, the patient's hyperthyroidism improved without further complications. This case highlights the importance of recognizing the link between GTD and thyrotoxicosis to allow for timely initiation of appropriate preoperative treatment. Fortunately, the multidisciplinary approach facilitated management to prevent evolution to thyroid storm.


Long non-coding RNA KCNQ10T1/miR-19a-3p/SMAD5 axis promotes osteogenic differentiation of mouse bone mesenchymal stem cells.
Bone fracture is a common orthopedic disease that needs over 3 months to recover. Promoting the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is beneficial for fracture healing. Therefore, this research aimed to study the roles of long non-coding RNA (lncRNA) KCNQ10T1 in osteogenic differentiation of BMSCs. BMSCs were treated with osteogenic medium and assessed by CCK-8 and flow cytometry assays. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), as well as concentration of osteoblast markers were measured to evaluate osteogenic differentiation of BMSCs. Western blot was employed to detect proteins; while, qRT-PCR was for mRNA levels. Additionally, targeted relationships between KCNQ10T1 and miR-19a-3p, as well as miR-19a-3p and SMAD5 were verified by dual luciferase reporter gene assay along with RNA pull-down method. Upregulation of KCNQ10T1 promoted the ALP staining and ARS intensity, increased the cell viability and decreased the apoptosis rate of BMSCs. Besides, KCNQ10T1 overexpression increased the ALP, OPG, OCN and OPN protein levels. KCNQ10T1 sponges miR-19a-3p, which targets Smad5. Upregulated miR-19a-3p reversed the overexpressed KCNQ10T1-induced effects, and depletion of SMAD5 reversed the miR-19a-3p inhibitor-induced effects on osteogenic medium-treated BMSCs. Upregulation of KCNQ10T1 promoted osteogenic differentiation of BMSCs through miR-19a-3p/SMAD5 axis in bone fracture.


Spatial and temporal expression levels of specific microRNAs in a spinal cord injury mouse model and their relationship to the duration of compression.
MicroRNAs, a class of small nonprotein-coding RNAs, are thought to control gene translation into proteins. The latter are the ultimate effectors of the biochemical cascade occurring in any physiological and pathological process. MicroRNAs have been shown to change their expression levels during injury of spinal cord in contusion rodent models. Compression is the most frequent mode of damage of neural elements in spinal cord injury. The cellular and molecular changes occurring in the spinal cord during prolonged compression are not very well elucidated. Understanding the underlying molecular events that occur during sustained compression is paramount in building new therapeutic strategies. The purpose of our study was to probe the relationship between the expression level changes of different miRNAs and the timing of spinal cord decompression in a mouse model. A compression spinal cord injury mouse model was used for the study. A laminectomy was performed in the thoracic spine of C57BL/6 mice. Then, the thecal sac was compressed to create the injury. Decompression was performed early for one group and it was delayed in the second group. The spinal cord at the epicenter of the injury and one level rostral to it were removed at 3, 6, and 24 hours after trauma, and RNA was extracted. Expression levels of six different microRNAs and the relationship to the duration of compression were analyzed. This work was supported in part by the University Research Council Grants Program at the University of Texas Health Science Center San Antonio (Grant 130267). There are no specific conflicts of interest to be disclosed for this work. Expression levels of microRNAs in the prolonged compression of spinal cord model were significantly different compared with the expression levels in the short duration of compression spinal cord injury model. Furthermore, microRNAs show a different expression pattern in different regions of the injured spinal cord. Our findings demonstrate that spinal cord compression causes alterations in the expression of different miRNAs in the acute phase of injury. Their expression is related to the duration of the compression of the spinal cord. These findings suggest that early decompression of the spinal cord may have an important modulating effect on the molecular cascade triggered during secondary injury through the changes in expression levels of specific microRNAs.


Public health education at Michigan State University.
Many reports have highlighted the need for the veterinary profession to fill critical shortages of veterinarians in public health and food safety. Michigan State University's College of Veterinary Medicine offers educational programs within the professional veterinary curriculum, as well as graduate degree programs, to meet these societal needs. Within the scope of the professional veterinary curriculum, educational opportunities in public health include clerkships in veterinary public health and an innovative Web-based curriculum on judicious use of antimicrobials. For graduate degree programs, Michigan State University has a memorandum of understanding with the University of Minnesota for the Master of Public Health degree and an innovative Online Professional Master of Science in Food Safety degree program. A new option available is the opportunity for veterinary students to pursue the Master of Science in Food Safety concurrently with the DVM (DVM/MS in Food Safety). These educational programs will prepare graduates to meet societal needs in public health and food safety.


A DNA vaccine-encoded nucleoprotein of influenza virus fails to induce cellular immune responses in a diabetic mouse model.
Influenza virus infections cause yearly epidemics and are a major cause of lower respiratory tract illnesses in humans worldwide. Influenza virus has long been recognized to be associated with higher morbidity and mortality in diabetic patients. Vaccination is an effective tool to prevent influenza virus infection in this group of patients. Vaccines employing recombinant-DNA technologies are an alternative to inactivated virus and live attenuated virus vaccines. Internal highly conserved viral nucleoprotein (NP) can be delivered as a DNA vaccine to provide heterosubtypic immunity, offering resistance against various influenza virus strains. In this study, we investigated the efficacy of an NP DNA vaccine for induction of cell-mediated immune responses and protection against influenza virus infection in a mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized on days 0, 14, and 28 by injection of NP DNA vaccine. Two weeks after the last immunization, the cellular immune response was evaluated by gamma interferon (IFN-gamma), lymphocyte proliferation, and cytotoxicity assays. The mice were challenged with influenza virus, and the viral titers in the lungs were measured on day 4. Diabetic mice showed significantly smaller amounts of IFN-gamma production, lymphocyte proliferation, and cytotoxicity responses than nondiabetic mice. Furthermore, higher titers of the influenza virus were detected after challenge in the lungs of the diabetic mice. The present data suggest that the NP DNA vaccine with the protocol of immunization described here is not able to induce efficient cellular immune responses against influenza virus infection in diabetic mice.


Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental cells.
Naturally occurring extracellular vesicles (EVs) play essential roles in intracellular communication and delivery of bioactive molecules. Therefore it has been suggested that EVs could be used for delivery of therapeutics. However, to date the therapeutic application of EVs has been limited by number of factors, including limited yield and full understanding of their biological activities. To address these issues, we analyzed the morphology, molecular composition, fusion capacity and biological activity of Cytochalasin B-induced membrane vesicles (CIMVs). The size of these vesicles was comparable to that of naturally occurring EVs. In addition, we have shown that CIMVs from human SH-SY5Y cells contain elevated levels of VEGF as compared to the parental cells, and stimulate angiogenesis in vitro and in vivo.


Transgenic animals modelling polyamine metabolism-related diseases.
Cloning of genes related to polyamine metabolism has enabled the generation of genetically modified mice and rats overproducing or devoid of proteins encoded by these genes. Our first transgenic mice overexpressing ODC (ornithine decarboxylase) were generated in 1991 and, thereafter, most genes involved in polyamine metabolism have been used for overproduction of the respective proteins, either ubiquitously or in a tissue-specific fashion in transgenic animals. Phenotypic characterization of these animals has revealed a multitude of changes, many of which could not have been predicted based on the previous knowledge of the polyamine requirements and functions. Animals that overexpress the genes encoding the inducible key enzymes of biosynthesis and catabolism, ODC and SSAT (spermidine/spermine N1-acetyltransferase) respectively, appear to possess the most pleiotropic phenotypes. Mice overexpressing ODC have particularly been used as cancer research models. Transgenic mice and rats with enhanced polyamine catabolism have revealed an association of rapidly depleted polyamine pools and accelerated metabolic cycle with development of acute pancreatitis and a fatless phenotype respectively. The latter phenotype with improved glucose tolerance and insulin sensitivity is useful in uncovering the mechanisms that lead to the opposite phenotype in humans, Type 2 diabetes. Disruption of the ODC or AdoMetDC [AdoMet (S-adenosylmethionine) decarboxylase] gene is not compatible with mouse embryogenesis, whereas mice with a disrupted SSAT gene are viable and show no harmful phenotypic changes, except insulin resistance at a late age. Ultimately, the mice with genetically altered polyamine metabolism can be used to develop targeted means to treat human disease conditions that they relevantly model.


Out of Anatolia: longitudinal gradients in genetic diversity support an eastern origin for a circum-Mediterranean oak gallwasp Andricus quercustozae.
Many studies have addressed the latitudinal gradients in intraspecific genetic diversity of European taxa generated during postglacial range expansion from southern refugia. Although Asia Minor is known to be a centre of diversity for many taxa, relatively few studies have considered its potential role as a Pleistocene refugium or a potential source for more ancient westward range expansion into Europe. Here we address these issues for an oak gallwasp, Andricus quercustozae (Hymenoptera: Cynipidae), whose distribution extends from Morocco along the northern coast of the Mediterranean through Turkey to Iran. We use sequence data for a fragment of the mitochondrial gene cytochrome b and allele frequency data for 12 polymorphic allozyme loci to answer the following questions: (1). which regions represent current centres of genetic diversity for A. quercustozae? Do eastern populations represent one refuge or several discrete glacial refugia? (2). Can we infer the timescale and sequence of the colonization processes linking current centres of diversity? Our results suggest that A. quercustozae was present in five distinct refugia (Iberia, Italy, the Balkans, southwestern Turkey and northeastern Turkey) with recent genetic exchange between Italy and Hungary. Genetic diversity is greatest in the Turkish refugia, suggesting that European populations are either (a). derived from Asia Minor, or (b). subject to more frequent population bottlenecks. Although Iberian populations show the lowest diversity for putatively selectively neutral markers, they have colonized a new oak host and represent a genetically and biologically discrete entity within the species.


Molecular and clinical characteristics of invasive group A streptococcal infection in Sweden.
The incidence and severity of invasive group A streptococcal infection demonstrate great variability over time, which at least, in part, seems to be related to group A streptococcal type distribution among the human population. An enhanced surveillance study of invasive group A streptococcal infection (746 isolates) was performed in Sweden from April 2002 through December 2004. Noninvasive isolates from either the throat or skin (773 isolates) were collected in parallel for comparison. Clinical and epidemiological data were obtained from 88% of patients with invasive disease and were related to isolate characteristics, including T type, emm sequence type, and the presence of 9 superantigen genes, as well as pulsed-field gel electrophoresis pattern comparisons of selected isolates. The annual incidence was 3.0 cases per 100,000 population. Among the patients with invasive disease, 11% developed streptococcal toxic shock syndrome, and 9.5% developed necrotizing fasciitis. The overall case-fatality rate was 14.5%, and 39% of the patients with streptococcal toxic shock syndrome died (P<.001). The T3/13/B3264 cluster accounted for 33% of invasive and 25% of noninvasive isolates. Among this most prevalent type cluster, emm types 89 and 81 dominated. Combined results from pulsed-field gel electrophoresis, emm typing, and superantigen gene profiling identified subgroups within specific emm types that are significantly more prone to cause invasive disease than were other isolates of the same type. This study revealed a changing epidemiology of invasive group A streptococcal infection in Sweden, with emergence of new emm types that were previously not described. The results also suggest that some clones may be particularly prone to cause invasive disease.


An open-label pilot study of an intervention using mobile phones to deliver contingency management of tobacco abstinence to high school students.
This pilot study assessed the feasibility, acceptability, and preliminary efficacy of a smoking cessation intervention that used mobile phones to remotely deliver reinforcements contingent on tobacco abstinence (contingency management [CM]) and weekly in-person cognitive-behavioral therapy to adolescent smokers. Daily adolescent smokers (N = 15; 12 completed study procedures, 3 dropped out) were recruited to participate in a 4-week study. During the first 2 weeks, daily text messages sent at random times prompted participants to transmit a video of themselves providing a carbon monoxide (CO) sample. During the last 2 weeks, text messages sent on 3 randomly chosen days each week prompted participants to transmit a video of themselves providing a saliva sample. Negative samples (CO ≤8 ppm; cotinine ≤100 ng/ml) were reinforced with monetary incentives. Feasibility was assessed using the number of on-time, valid videos, and acceptability was determined using participant perceptions of the intervention. Seven-day point-prevalence (PP) abstinence (self-reported abstinence, cotinine <100 ng/ml) was assessed at end of treatment (EOT) and at a 1-month follow-up. The study findings indicate that remote delivery of CM using mobile phones was feasible (85.8% of the CO videos and 67% of the saliva cotinine videos were on time) and acceptable (positive perceptions of the CM procedures). Seven-day PP was 60% at EOT and 46.7% at the follow-up. Although larger randomized controlled trials are needed to evaluate efficacy, this pilot study suggests that the use of mobile phones to deliver CM for smoking cessation among adolescent smokers was acceptable and feasible. (PsycINFO Database Record


Learned cardiac control with heart rate biofeedback transfers to emotional reactions.
Emotions involve subjective feelings, action tendencies and physiological reactions. Earlier findings suggest that biofeedback might provide a way to regulate the physiological components of emotions. The present study investigates if learned heart rate regulation with biofeedback transfers to emotional situations without biofeedback. First, participants learned to decrease heart rate using biofeedback. Then, inter-individual differences in the acquired skill predicted how well they could decrease heart rate reactivity when later exposed to negative arousing pictures without biofeedback. These findings suggest that (i) short lasting biofeedback training improves heart rate regulation and (ii) the learned ability transfers to emotion challenging situations without biofeedback. Thus, heart rate biofeedback training may enable regulation of bodily aspects of emotion also when feedback is not available.


Changes in cortical excitability with thalamic deep brain stimulation.
Deep brain stimulation (DBS) is an effective treatment for several movement disorders. However, its mechanism of action is largely unknown. Both lesioning and DBS of the ventralis intermedius (VIM) nucleus of thalamus improve essential tremor. Although DBS was initially thought to inhibit the target neurons, recent studies suggest that DBS activates neurons. To test the hypothesis that thalamic DBS activates the target area in patients with essential tremor. Cortical excitability was assessed in seven unmedicated patients with essential tremor using unilateral stimulators implanted in the VIM of the dominant hemisphere and in 11 healthy controls using transcranial magnetic stimulation (TMS). Patients were studied during optimal DBS (ON condition), half the optimal frequency (HALF), and with DBS off (OFF) in random order. Tremor was assessed after a change in DBS setting. Electromyography was recorded from the dominant hand, and TMS was applied over the contralateral motor cortex using single and paired pulses to elicit motor evoked potentials (MEPs). MEP recruitment was determined using stimulus intensities from 100% to 150% of motor threshold. Tremor scores were significantly improved with DBS ON. Analysis of variance showed a significant interaction between condition (ON, HALF, OFF, Normal) and stimulus intensity on MEP amplitude. During DBS ON MEP amplitudes were significantly higher compared with controls at high but not at low TMS intensities. Because the ventralis intermedius (VIM) projects directly to the motor cortex, the high motor evoked potential amplitude with deep brain stimulation ON suggests that VIM DBS activates rather than inhibits the target area.


Efficacy of infliximab for hidradenitis suppurativa: assessment of clinical and biological inflammatory markers.
Treatment of hidradenitis suppurativa (HS) is often unsatisfactory. The efficacy of infliximab for treatment of the disease has been suggested. The main objective of this study was to evaluate the efficacy and side-effects of infliximab in the treatment of moderate to severe HS, resistant to local and systemic treatments. The secondary objective was to determine whether inflammation blood test results were changed. A retrospective monocentric study of all the patients seen consecutively for HS and treated with infliximab was performed. A median of six intravenous infusions (range 3-19) were performed. The end-points were self-improvement of HS (globally and in terms of pain, seeping and quality of life). The condition of six of seven patients improved (by nearly 50%) and none was aggravated. Adverse effects occurred in two patients; eczematous eruption in one case and cervical abscess in another case. We found no significant changes in inflammatory blood marker values. In conclusion, infliximab therapy was shown to be efficient and well tolerated in six of seven patients with HS resistant to previous therapy in our series. This was in agreement with pre-existing literature showing that 52 of 60 patients (87%) were improved after infliximab therapy.


Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health.
Citrus fruits, which are cultivated worldwide, have been recognized as some of the most high-consumption fruits in terms of energy, nutrients and health supplements. What is more, a number of these fruits have been used as traditional medicinal herbs to cure diseases in several Asian countries. Numerous studies have focused on Citrus secondary metabolites as well as bioactivities and have been intended to develop new chemotherapeutic or complementary medicine in recent decades. Citrus-derived secondary metabolites, including flavonoids, alkaloids, limonoids, coumarins, carotenoids, phenolic acids and essential oils, are of vital importance to human health due to their active properties. These characteristics include anti-oxidative, anti-inflammatory, anti-cancer, as well as cardiovascular protective effects, neuroprotective effects, etc. This review summarizes the global distribution and taxonomy, numerous secondary metabolites and bioactivities of Citrus fruits to provide a reference for further study. Flavonoids as characteristic bioactive metabolites in Citrus fruits are mainly introduced.


Determination of monochloramine formation rate constants with stopped-flow spectrophotometry.
The production of monochloramine by the reaction of aqueous ammonia and free chlorine is important in both drinking water and wastewater treatment systems. Accurate prediction of the rate of monochloramine formation is a prerequisite for any modeling work related to this fundamental reaction. There are significant discrepancies between rate constants reported in the literature. Furthermore, little information is available on the temperature dependence of the reaction rate constant. The purposes of this study were to kinetically examine the potential reaction pathways, accurately determine the specific rate constants, and establish the Arrhenius equation for the reaction of monochloramine formation using the stopped-flow technique. Results indicate that the rate constants are highly pH dependent due to the speciation of both free chlorine and ammonia. From a strictly kinetic point of view, monochloramine formation could be explained by either the nonionic pathway between HOCl and NH3 or the ionic pathway between OCl- and NH4+. However, because the ionic pathway is mechanistically implausible the reaction is shown to be between the nonionic species (HOCl and NH3). The specific rate constant for the nonionic pathway at 25 degrees C was determined to be 3.07 x 10(6) (M(-1) x s(-1)). The Arrhenius equation was obtained as k(HOCl,NH3) = 5.40 x 10(9) exp(- 2237/T), which provided an activation energy of 18.6 kJ x mol(-1).


DNA microarray analysis of nitrogen fixation and Fe(III) reduction in Geobacter sulfurreducens.
A DNA microarray representing the genome of Geobacter sulfurreducens was constructed for use in global gene expression profiling of cells under steady-state conditions with acetate as the electron donor and Fe(III) or fumarate as the electron acceptor. Reproducible differences in transcript levels were also observed in comparisons between cells grown with ammonia and those fixing atmospheric nitrogen. There was a high correlation between changes in transcript levels determined with microarray analyses and an evaluation of a subset of the genome with quantitative PCR. As expected, cells required to fix nitrogen had higher levels of transcripts of genes associated with nitrogen fixation, further demonstrating that the microarray approach could reliably detect important physiological changes. Cells grown with Fe(III) as the electron acceptor had higher levels of transcripts for omcB, a gene coding for an outer membrane c-type cytochrome that is essential for Fe(III) reduction. Several other c-type cytochrome genes also appeared to be up-regulated. An unexpected result was significantly higher levels of transcripts for genes which have a role in metal efflux, potentially suggesting the importance of maintaining metal homeostasis during release of soluble metals when reducing Fe(III). A substantial proportion (30%) of significantly expressed genes during Fe(III) reduction were genes of unknown function or hypothetical proteins, suggesting differences in Fe(III) reduction physiology among microorganisms which perform this metabolic process.


A systematic review of the process of regionalization of Brazil's Unified Health System, SUS.
This review focuses only on specific studies into the SUS regionalization process, which were based on empirical results and published since 2006, when the SUS was already under the aegis of the Pact for Health framework. It was found that the regionalization process is now underway in all spheres of government, subject to a set of challenges common to the different realities of the country. These include, primarily, that committee-structured entities are valued as spaces for innovation, yet also strive to overcome the bureaucratic and clientelist political culture. Regional governance is further hampered by the fragmentation of the system and, in particular, by the historical deficiency in planning, from the local level to the strategic policies for technology incorporation. The analyses enabled the identification of a culture of broad privilege for political negotiation, to the detriment of planning, as one of the main factors responsible for a vicious circle that sustains technical deficiency in management.


Sustainable diets: The interaction between food industry, nutrition, health and the environment.
Everyday great amounts of food are produced, processed, transported by the food industry and consumed by us and these activities have direct impact on our health and the environment. The current food system has started causing strain on the Earth's natural resources and that is why sustainable food production systems are needed. This review article discusses the need for sustainable diets by exploring the interactions between the food industry, nutrition, health and the environment, which are strongly interconnected. The most common environmental issues in the food industry are related to food processing loss, food wastage and packaging; energy efficiency; transportation of foods; water consumption and waste management. Among the foods produced and processed, meat and meat products have the greatest environmental impact followed by the dairy products. Our eating patterns impact the environment, but the environment can impact dietary choices as well. The foods and drinks we consume may also affect our health. A healthy and sustainable diet would minimise the consumption of energy-dense and highly processed and packaged foods, include less animal-derived foods and more plant-based foods and encourage people not to exceed the recommended daily energy intake. Sustainable diets contribute to food and nutrition security, have low environmental impacts and promote healthy life for present and future generations. There is an urgent need to develop and promote strategies for sustainable diets; and governments, United Nations agencies, civil society, research organisations and the food industry should work together in achieving this.


The use of d-amphetamine in medically ill depressed patients.
A positive therapeutic response to d-amphetamine is described in three medically ill depressed patients in a general hospital. Two patients were either unable to tolerate or responded poorly to tricyclic antidepressants. In one patient, d-amphetamine was chosen because of the combination of postoperative pain and depression. There was a rapid remission of depressive symptomatology with no adverse side effects, consistent with the findings of other investigators. Further evaluation of the therapeutic role of d-amphetamine in the treatment of medically ill depressed patients is recommended.


Predicting Fatigue in Long Duration Mountain Events with a Single Sensor and Deep Learning Model.
To determine whether an AI model and single sensor measuring acceleration and ECG could model cognitive and physical fatigue for a self-paced trail run. A field-based protocol of continuous fatigue repeated hourly induced physical (~45 min) and cognitive (~10 min) fatigue on one healthy participant. The physical load was a 3.8 km, 200 m vertical gain, trail run, with acceleration and electrocardiogram (ECG) data collected using a single sensor. Cognitive load was a Multi Attribute Test Battery (MATB) and separate assessment battery included the Finger Tap Test (FTT), Stroop, Trail Making A and B, Spatial Memory, Paced Visual Serial Addition Test (PVSAT), and a vertical jump. A fatigue prediction model was implemented using a Convolutional Neural Network (CNN). When the fatigue test battery results were compared for sensitivity to the protocol load, FTT right hand (R2 0.71) and Jump Height (R2 0.78) were the most sensitive while the other tests were less sensitive (R2 values Stroop 0.49, Trail Making A 0.29, Trail Making B 0.05, PVSAT 0.03, spatial memory 0.003). The best prediction results were achieved with a rolling average of 200 predictions (102.4 s), during set activity types, mean absolute error for 'walk up' (MAE200 12.5%), and range of absolute error for 'run down' (RAE200 16.7%). We were able to measure cognitive and physical fatigue using a single wearable sensor during a practical field protocol, including contextual factors in conjunction with a neural network model. This research has practical application to fatigue research in the field.


Lupus and T cells.
T-cell abnormalities and aberrant T helper cytokine profiles have been implicated in the loss of immune tolerance to nuclear and cytoplasmic antigens and linked to a variety of clinical manifestations in systemic lupus erythematosus (SLE). Here, we review the role of T cells in promoting and maintaining SLE in relation to their cellular and molecular abnormalities and provide an update on recent T cell-targeted therapeutic approaches for the restoration of T cell homeostasis in the disease.


Scientific Review Committees as part of institutional review of human participant research: Initial implementation at institutions with Clinical and Translational Science Awards.
Scientific quality and feasibility are part of ethics review by Institutional Review Boards (IRBs). Scientific Review Committees (SRCs) were proposed to facilitate this assessment by the Clinical and Translational Science Award (CTSA) SRC Consensus Group. This study assessed SRC feasibility and impact at CTSA-affiliated academic health centers (AHCs). SRC implementation at 10 AHCs was assessed pre/post-intervention using quantitative and qualitative methods. Pre-intervention, four AHCs had no SRC, and six had at least one SRC needing modifications to better align with Consensus Group recommendations. Facilitators of successful SRC implementation included broad-based communication, an external motivator, senior-level support, and committed SRC reviewers. Barriers included limited resources and staffing, variable local mandates, limited SRC authority, lack of anticipated benefit, and operational challenges. Research protocol quality did not differ significantly between study periods, but respondents suggested positive effects. During intervention, median total review duration did not lengthen for the 40% of protocols approved within 3 weeks. For the 60% under review after 3 weeks, review was lengthened primarily due to longer IRB review for SRC-reviewed protocols. Site interviews recommended designing locally effective SRC processes, building buy-in by communication or by mandate, allowing time for planning and sharing best practices, and connecting SRC and IRB procedures. The CTSA SRC Consensus Group recommendations appear feasible. Although not conclusive in this relatively short initial implementation, sites perceived positive impact by SRCs on study quality. Optimal benefit will require local or federal mandate for implementation, adapting processes to local contexts, and employing SRC stipulations.


Effectiveness of Φ-value analysis in the binding process of Arc repressor dimer.
Φ-value analysis has proved to be a powerful technique in protein folding studies. It has been used to study the transition state structures, to infer microscopic folding pathways, and to identify key residues in the protein folding process. However, its effectiveness in protein binding reaction has not been tested, especially when a fly-casting mechanism is involved. In this article we attempt to answer this question through a coarse-grained study of the binding reaction of Arc repressor dimer. Our simulations show that its binding process proceeds through a fly-casting mechanism, consistent with previous results. We then estimate the importance of the residues for the fly-casting binding by computationally mutating each of them into glycine and calculating their respective effects on the capture radius. It is found that (1) the residues with high Φ values may not be responsible for the large capture radius in the fly-casting binding; (2) mutation of residues with low Φ values may destabilize the denatured states and then increase the capture radius, presumably further increasing the binding rate. Based on our simulations, we conclude that Φ values do not reflect well the importance of residues in the fly-casting binding reaction and need to be combined with other techniques to provide a complete picture.


Case report: fatal Yersinia enterocolitica septicaemia.
Yersinia enterocolitica type 3 was isolated in blood cultures from a previously healthy 81-year-old woman with fever. A high agglutinin titre against this organism was demonstrated in the patient's serum. Antibiotic therapy was given according to sensitivity tests but the outcome was fatal due to uraemia.


Adaptation of the Mishel Uncertainty of Illness Scale (MUIS) for chronic patients in Italy.
Uncertainty is a component of the illness experience and is likely to increase the burden of managing chronic illness, as cardiac pathologies and renal diseases. The impact of uncertainty should be taken into account and addressed with targeted intervention programmes. The purpose of this study is to contribute to the diffusion of the assessment of uncertainty in illness by validating the Mishel uncertainty in illness scale (MUIS) on chronic Italian patients. The MUIS questionnaire was administered to 200 patients suffering from cardiac diseases and 50 patients with renal diseases. A confirmatory factor analysis was run for each of the MUIS dimensions (ambiguity, inconsistency, complexity and unpredictability). After some item reduction, three of the four MUIS scales, namely, ambiguity, inconsistency and complexity, exhibited satisfactory reliability coefficients (with Cronbach's alphas of, respectively, 0.796, 0.778 and 0.705), highly significant standardized regression weights and satisfactory/highly satisfactory fit indexes. Nevertheless, as the correlations among the scales mentioned earlier were high (all above 0.8) and statistically significant, the three subsets of ambiguity, complexity and inconsistency items were allowed to load onto a new single factor. A monodimensional uncertainty construct, grouping the majority of the items encompassed by these three MUIS scales, was successfully validated. This study provides researchers with an easy-to-administer instrument which is useful to investigate a crucial aspect related with patients' quality of life. Although a unique uncertainty construct is proposed, the in-depth analysis of the replies to each single item of the MUIS could help to monitor patients' emotional responses to the diagnosis and to the course of this disease and it might be useful to define appropriate strategies of coping and to focus on patients' quests for simplicity and clarity of treatment.


Measurement of islet cell antibodies in the Type 1 Diabetes Genetics Consortium: efforts to harmonize procedures among the laboratories.
and Three network laboratories measured antibodies to islet autoantigens. Antibodies to glutamic acid decarboxylase (GAD65 [GADA]) and the intracellular portion of protein tyrosine phosphatase (IA-2(ic) [IA-2A]) were measured by similar, but not identical, methods in samples from participants in the Type 1 Diabetes Genetics Consortium (T1DGC). All laboratories used radiobinding assays to detect antibodies to in vitro transcribed and translated antigen, but with different local standards, calibrated against the World Health Organization (WHO) reference reagent. Using a common method to calculate WHO units/mL, we compared results reported on samples included in the Diabetes Autoantibody Standardization Program (DASP), and developed standard methods for reporting in WHO units/mL. We evaluated intra-assay and inter-assay coefficient of variation (CV) in blind duplicate samples and assay comparability in four DASP workshops. Values were linearly related in the three laboratories for both GADA and IA-2A, and intra-assay technical errors for values within the standard curve were below 13% for GADA and below 8.5% for IA-2A. Correlations in samples tested 1-2 years apart were >97%. Over the course of the study, internal CVs were 10-20% with one exception, and the laboratories concordantly called samples GADA or IA-2A positive or negative in 96.7% and 99.6% of duplicates within the standard curve. Despite acceptable CVs and general concordance in ranking samples, the laboratories differed markedly in absolute values for GADA and IA-2A reported in WHO units/mL in DASP over a large range of values. With three laboratories using different assay methods (including calibrators), consistent values among them could not be attained. Modifications in the assays are needed to improve comparability of results expressed as WHO units/mL across laboratories. It will be essential to retain high intra- and inter-assay precision, sensitivity and specificity and to confirm the accuracy of harmonized methods.


NT-proBNP Mediates the Association Between FGF23 and All-Cause Mortality in Individuals With Type 2 Diabetes.
FGF23 (fibroblast growth factor 23) is associated with a higher mortality risk in type 2 diabetes, but the mechanism is unclear. We aimed to study whether NT-proBNP (N-terminal pro-brain natriuretic peptide) mediates the association between FGF23 and mortality. We analyzed C-terminal FGF23 and NT-proBNP levels in 399 patients with type 2 diabetes. Cox regression analyses were performed, followed by mediation analyses using Structural Equation Modeling. During follow-up of 9.2 [7.6-11.3] years, 117 individuals died. FGF23 was associated with all-cause mortality, independent of potential confounders (fully adjusted hazard ratio [HR], 2.32 [95% CI, 1.21-4.43], P=0.01). The association was lost upon further adjustment for NT-proBNP (HR, 1.84; 95% CI, 0.91-3.73). NT-proBNP accounted for 26% of the mediation effect between FGF23 and all-cause mortality. These findings suggest that a higher FGF23 level is associated with increased mortality in individuals with type 2 diabetes through an effect on volume homeostasis.


Anti-inflammatory agents and antioxidants as a possible "third great wave" in cardiovascular secondary prevention.
There are 3 important factors that predispose patients to plaque rupture or recurrent events: plaque burden or multiple arterial plaques, the presence of persistent hyperreactive platelets, and ongoing vascular arterial inflammation. Successful therapeutic strategies focus on these predisposing factors, and the use of low-density lipoprotein-lowering medications (principally statins) and antiplatelet agents (principally aspirin) has had a major impact on the occurrence of cardiovascular outcomes and overall mortality over the last 2 decades. However, despite these interventions, a significant number of patients experience recurrent events or progression of disease. Novel compounds are being studied to determine, for example, whether an increase in high-density lipoprotein will provide additional risk reduction; to date, this has not proved to be sufficiently effective. Although early invasive management has been proved to be superior to medical therapy in patients with plaque rupture producing acute coronary syndromes, its superiority in patients with clinically stable obstructive disease has been questioned. Thus, the search for additional agents to improve the outcomes of patients with atherothrombotic disease continues. The importance of inflammation, a potentially critical element in the initiation, progression, and rupture of plaque, has become increasingly evident. In this supplement, the role of inflammation and its principal cause, oxidative stress, are analyzed as potential targets of pharmacologic therapy. The history of anti-inflammatory and antioxidant therapy in cardiovascular disease is critically examined. Finally, the whole process of contemporary drug discovery and development from lead rationale and identification through biologic screening and testing in animals and then humans is explored, using as an example the xanthophyll carotenoids, a class of potent antioxidants currently under investigation.


[Studies on the mechanism of translocation in ribosomes. V. Comparison of the effect of antibiotic inhibitors of ribosomes on "enzymatic" and "non-enzymatic" translation].
A comparison of the effect of 11 antibiotic inhibitors of protein synthesis on "enzymatic" and para-chloromercuribenzoateactivated "non-enzymatic" translation was made. It was found that fusidic acid which inhibits protein synthesis by blocking the action of one of the elongation factors (EF-G) did not suppress functioning of the "non-enzymatic" system. On the contrary, all the antibiotics blocking different functional sites of the ribosome itself such as tetracycline, chloramphenicol, erythromycin, edeine, thiostreptone, viridogrisein, spectinomycin, streptomycin, kanamycin and neomycin, were shown to inhibit the "non-enzymatic" translation. The data obtained corroborate the idea that the molecular mechanism which the ribosome utilized during "non-enzymatic" translation are similar or identical to the mechanism of normal "enzymatic" translation. It was found that the "non-enzymatic" working ribosome is more sensitive to all the antibiotics as compared to the ribosome synthesizing peptide with the participation of elongation factors (EF-T and EF-G). This suggests that the elongation factors increase the level of general resistance of the working ribosome against very different hindrances.


Functional neighbors: inferring relationships between nonhomologous protein families using family-specific packing motifs.
We describe a new approach for inferring the functional relationships between nonhomologous protein families by looking at statistical enrichment of alternative function predictions in classification hierarchies such as Gene Ontology (GO) and Structural Classification of Proteins (SCOP). Protein structures are represented by robust graph representations, and the fast frequent subgraph mining algorithm is applied to protein families to generate sets of family-specific packing motifs, i.e., amino acid residue-packing patterns shared by most family members but infrequent in other proteins. The function of a protein is inferred by identifying in it motifs characteristic of a known family. We employ these family-specific motifs to elucidate functional relationships between families in the GO and SCOP hierarchies. Specifically, we postulate that two families are functionally related if one family is statistically enriched by motifs characteristic of another family, i.e., if the number of proteins in a family containing a motif from another family is greater than expected by chance. This function-inference method can help annotate proteins of unknown function, establish functional neighbors of existing families, and help specify alternate functions for known proteins.


Structure, antimicrobial activity, DNA- and albumin-binding of manganese(II) complexes with the quinolone antimicrobial agents oxolinic acid and enrofloxacin.
The reaction of MnCl2 with the quinolone antibacterial drug oxolinic acid (Hoxo) results to the formation of [KMn(oxo)3(MeOH)3]. Interaction of MnCl2 with the quinolone Hoxo or enrofloxacin (Herx) and the N,N'-donor heterocyclic ligand 1,10-phenanthroline (phen) results in the formation of metal complexes with the general formula [Mn(quinolonato)2(phen)]. The crystal structures of [KMn(oxo)3(MeOH)3] and [Mn(erx)2(phen)], exhibiting a 1D polymeric and a mononuclear structure, respectively, have been determined by X-ray crystallography. In these complexes, the deprotonated bidentate quinolonato ligands are coordinated to manganese(II) ion through the pyridone oxygen and a carboxylato oxygen. All complexes can act as potential antibacterial agents with [Mn(erx)2(phen)] exhibiting the most pronounced antimicrobial activity against five different microorganisms. Interaction of the complexes with calf-thymus DNA (CT DNA), studied by UV spectroscopy, has shown that they bind to CT DNA. Competitive study with ethidium bromide (EB) has shown that all complexes can displace the DNA-bound EB indicating their binding to DNA in strong competition with EB. Intercalative binding mode is proposed for the interaction of the complexes with CT DNA and has also been verified by DNA solution viscosity measurements and cyclic voltammetry. DNA electrophoretic mobility experiments suggest that [Mn(erx)2(phen)] binds strongly to supercoiled pDNA and to linearized pDNA possibly by an intercalative manner provoking double-stranded cleavage reflecting in a nuclease-like activity. The complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values. The binding constants of the complexes towards CT DNA and albumins have been compared to their corresponding zinc(II) and nickel(II) complexes.


Three-dimensional structure of the radial spokes reveals heterogeneity and interactions with dyneins in Chlamydomonas flagella.
Radial spokes (RSs) play an essential role in the regulation of axonemal dynein activity and thus of ciliary and flagellar motility. However, few details are known about the complexes involved. Using cryo-electron tomography and subtomogram averaging, we visualized the three-dimensional structure of the radial spokes in Chlamydomonas flagella in unprecedented detail. Unlike many other species, Chlamydomonas has only two spokes per axonemal repeat, RS1 and RS2. Our data revealed previously uncharacterized features, including two-pronged spoke bases that facilitate docking to the doublet microtubules, and that inner dyneins connect directly to the spokes. Structures of wild type and the headless spoke mutant pf17 were compared to define the morphology and boundaries of the head, including a direct RS1-to-RS2 interaction. Although the overall structures of the spokes are very similar, we also observed some differences, corroborating recent findings about heterogeneity in the docking of RS1 and RS2. In place of a third radial spoke we found an uncharacterized, shorter electron density named "radial spoke 3 stand-in," which structurally bears no resemblance to RS1 and RS2 and is unaltered in the pf17 mutant. These findings demonstrate that radial spokes are heterogeneous in structure and may play functionally distinct roles in axoneme regulation.


Long-term starvation survival of rod and spherical cells of Arthrobacter crystallopoietes.
Spherical and rod-shaped cells of Arthrobacter crystallopoietes, harvested during exponential growth, were subjected to total starvation for periods of time as long as 80 days. Viability measurements were made by plate count and slide culture procedures. Both cell forms remained 100% viable for 30 days. Thereafter, viability of rods and spheres decreased equally at a slow rate. After 60 days of starvation, more than 65% of both cell forms were viable. No significant cell lysis occurred as evidenced by microscopic examination, the small amount of 260-nm absorbing material found in the starvation buffer, and stability of radioactively labeled deoxyribonucleic acid in the cells. Endogenous respiration decreased 80-fold during the first 2 days of starvation, accompanied by a 30% decrease in dry weight of the cells. Thereafter, cellular carbon was oxidized to CO(2) at the constant level of 0.03%/hr over the remaining 78-day starvation period.


Genomic structure and expression of the soluble guanylyl cyclase alpha2 subunit gene in the medaka fish Oryzias latipes.
A cDNA clone encoding the soluble guanylyl cyclase alpha2 subunit was isolated from medaka fish (Oryzias latipes) and designated as OlGCS-alpha2. The OlGCS-alpha2 cDNA was 3,192 bp in length and the open reading frame (ORF) encodes a protein of 805 amino acids. The deduced amino acid sequence has high similarity to that of the mammalian alpha2 subunit gene except for the N-terminal regulatory domain. The C-terminal 5 amino acids, "RETSL", which have been reported to interact with the post synaptic density protein (PSD)-95 were conserved. An RNase protection assay with adult fish organs showed that OlGCS-alpha2 was expressed mainly in the brain and testis. The complete nucleotide sequence (about 41 kbp) of the OlGCS-alpha2 genomic DNA clone isolated from a medaka fish BAC library indicated that the OlGCS-alpha2 gene consisted of 9 exons and 8 introns. The 5'-flanking region and larger introns, such as introns 1, 4, and 7, contained the several fragments conserved in the nucleotide sequences of Rex6 (non-long terminal repeat retrotransposon), MHC class I genomic region, and OlGC1, the medaka fish homolog of the mammalian guanylyl cyclase B gene. Linkage analysis on the medaka fish chromosome demonstrated that the OlGCS-alpha2 gene was mapped to LG13; this mapping position was different from those for the OlGCS-alpha1 and OlGCS-beta1 genes (LG1).


Antibody-based nanoprobe for measurement of a fluorescent analyte in a single cell.
We report here the application of an antibody-based nanoprobe for in situ measurements of a single cell. The nanoprobe employs antibody-based receptors targeted to a fluorescent analyte, benzopyrene tetrol (BPT), a metabolite of the carcinogen benzo[a]pyrene (BaP) and of the BaP-DNA adduct. Detection of BPT is of great biomedical interest, since this species can serve as a biomarker for monitoring DNA damage due to BaP exposure and for possible precancer diagnosis. The measurements were performed on the rat liver epithelial clone 9 cell line, which was used as the model cell system. Before making measurements, the cells were treated with BPT. Nanoprobes were inserted into individual cells, incubated 5 min to allow antigen-antibody binding, and then removed for fluorescence detection. We determined a concentration of 9.6+/-0.2x10(-11) M for BPT in the individual cells investigated. The results demonstrate the possibility of in situ measurements inside a single cell using an antibody-based nanoprobe.


Assessment of biosafety implementation in clinical diagnostic laboratories in Pakistan during the COVID-19 pandemic.
Laboratory diagnostic capacity is crucial for an optimal national response to a public health emergency such as the COVID-19 pandemic. Preventing laboratory-acquired infections and the loss of critical human resources, especially during a public health emergency, requires laboratories to have a good biorisk management system in place. In this study, we aimed to evaluate laboratory biosafety and biosecurity in Pakistan during the COVID-19 pandemic. In this cross-sectional study, a self-rated anonymous questionnaire was distributed to laboratory professionals (LPs) working in clinical diagnostic laboratories, including laboratories performing polymerase chain reaction (PCR)-based COVID-19 diagnostic testing in Punjab, Sindh, Khyber Pakhtunkhwa, and Gilgit-Baltistan provinces as well as Islamabad during March 2020 to April 2020. The questionnaire assessed knowledge and perceptions of LPs, resource availability, and commitment by top management in these laboratories. In total, 58.6% of LPs performing COVID-19 testing reported that their laboratory did not conduct a biorisk assessment before starting COVID-19 testing in their facility. Only 31% of LPs were aware that COVID-19 testing could be performed at a biosafety level 2 laboratory, as per the World Health Organization interim biosafety guidelines. A sufficiently high percentage of LPs did not feel confident in their ability to handle COVID-19 samples (32.8%), spills (43.1%), or other accidents (32.8%). These findings demonstrate the need for effective biosafety program implementation, proper training, and establishing competency assessment methods. These findings also suggested that identifying and addressing gaps in existing biorisk management systems through sustainable interventions and preparing LPs for surge capacity is crucial to better address public health emergencies.


The immune suppressive function of transforming growth factor-β (TGF-β) in human diseases.
Transforming growth factor-β (TGF-β) functions as an immune suppressor by influencing immune cells' development, differentiation, tolerance induction and homeostasis. In human diseases, TGF-β has been revealed as an essential regulator of both innate and adaptive functions in autoimmune diseases. Furthermore, it plays a significant role in cancer by inhibiting immunosurveillance in the tumor-bearing host. A variety of TGF-β neutralizing anti-cancer therapies have been investigated based on the role of TGF-β in immunosuppression. New studies are focusing on combining TGF-β blockade with tumor vaccinations and immunogene therapies.


In-vitro models of human endometriosis.
Endometriosis is one of the most common benign gynecological diseases in women of reproductive age worldwide. In past decades, a number of in-vitro models have been used to investigate the pathology and therapeutic methods for the treatment of endometriosis. The current review summarized the majority of currently available in-vitro models, which utilize a variety of cell or tissues types, including endometriotic cell lines, primary endometrial stromal cells, endometrial stem cells, endometrial explants, peritoneal explants and immune cells. These cells or tissues are cultured individually, co-cultured in 2D or 3D systems with various matrices or cultured in chicken chorioallantotic membranes and amniotic membranes culture systems. These models are able to represent one or more aspects of the process of endometriosis. These models are helpful and can be used to investigate the development of endometriosis and the underlying mechanisms of this disorder in detail, and help investigators select appropriate models for their experiments. Recently, the new concept of endometriosis as a fibrotic condition will lead research to investigate the differentiation of myofibroblasts and the development of fibrosis in endometriotic lesions, which will increase the development of novel models that can be used to investigate endometriotic fibrosis.


Physical properties of soft contact lens solutions.
To investigate the physical properties of commercially available soft contact lens solutions. The pH, osmolality, surface tension (ST), and viscosity of various soft contact lens solutions were measured at room temperature. Viscosity measurements were also taken at 34 degrees C. The solutions examined were Opti-Free Express (OFX), Opti-Free RepleniSH (OFR), Complete Moisture Plus (COM), UltraCare (UC), ReNu MultiPlus, Sensitive Eyes, AOSept (AO), Clear Care, SoloCare Aqua, and SoftWear saline. The peroxide solutions were measured before and after neutralization. The pH of most solutions was close to neutral (range 7.00-7.36), except for OFX and neutralized AO and Clear Care. The osmolality values of most solutions were in the 275 to 310 mOsm/kg range. OFX exhibited a significantly lower osmolality (225 mOsm/kg; p < 0.001), whereas UC was significantly higher (329 mOsm/kg; p < 0.001). Neutralized AO and SoftWear saline had ST values of approximately 67 mN/m. OFX, OFR, and SoloCare Aqua exhibited low ST values in the 30 to 35 mN/m range. The remaining solutions exhibited intermediate ST values of approximately 40 mN/m. These three groupings were significantly different (p < 0.001). The average viscosity of most solutions at room temperature was between 0.95 and 1.26 cP, except for COM (3.02 cP; p < 0.001). At 34 degrees C, the average viscosity of most solutions was between 0.70 and 0.83 cP, except for COM, which had a viscosity of 1.92 cP (p < 0.001). The un-neutralized peroxide solutions had very different pH and osmolality values from all the solutions that would directly contact the eye (p < 0.001). Their viscosity and ST values were similar (p = NS). This study detailed many physical properties of soft lens solutions that are not readily available and indicated that certain properties vary significantly among these products.


Hydroxamate siderophores: occurrence and importance in the Atlantic Ocean.
Siderophores are chelates produced by bacteria as part of a highly specific iron uptake mechanism. They are thought to be important in the bacterial acquisition of iron in seawater and to influence iron biogeochemistry in the ocean. We have identified and quantified two types of siderophores in seawater samples collected from the Atlantic Ocean. These siderophores were identified as hydroxamate siderophores, both ferrioxamine species representative of the more soluble marine siderophores characterized to date. Ferrioxamine G was widely distributed in surface waters throughout the Atlantic Ocean, while ferrioxamine E had a more varied distribution. Total concentrations of the two siderophores were between 3 and 20 pM in the euphotic zone. If these compounds are fully complexed in seawater, they represent approximately 0.2-4.6% of the <0.2 microm iron pool. Our data confirm that siderophore-mediated iron acquisition is important for marine heterotrophic bacteria and indicate that siderophores play an important role in the oceanic biogeochemical cycling of iron.


Analysis of solids by laser ablation and resonance-enhanced laser-induced plasma spectroscopy
An analytical technique based on resonance-enhanced laser-induced plasma spectroscopy was demonstrated. Pellets of potassium iodate containing trace amounts of sodium were ablated by a 532-nm laser pulse in air. After 30 ns, the plasma plume was intercepted by a 404.4-nm laser pulse to resonantly photoionize the potassium atoms in the vapor plume. The 589-nm emissions of the sodium were found to be significantly enhanced. The enhancement was shown to depend critically on the profile of the 532-nm beam as well as the spatial overlap of the two laser pulses. Using this double-pulse scheme, the mass detection limit for sodium was estimated to be about 200 pg, which was five times better than that obtained by using the 532-nm laser pulse alone.


Prostate Specific Antigen Testing Behaviors for Prostate Cancer Screening Among U.S. Immigrants: A Cross-sectional Analysis Using the National Health Interview Survey.
Immigrants constitute 14% of the U.S. population, and this group is especially vulnerable to poor health care access. Prior research demonstrates U.S. immigrants have low rates of guideline-concordant breast and colorectal screening, but prostate cancer screening has not previously been evaluated. We sought to characterize screening behaviors among U.S. immigrants and to consider possible mechanisms to enhance PSA-based screening for this population. Data were obtained from the 2010, 2013, 2015, and 2018 National Health Interview Survey reports, which were the recent survey years that included questions about PSA testing. Complex samples logistic regression was performed to assess the relationship between immigrant-specific characteristics including region of birth, citizenship status, length of residence within the U.S., English language proficiency, and history of PSA testing. There were 22,997 survey respondents; 3,257 were foreign-born and 19,740 were U.S.-born. Rates of PSA testing were much lower among the foreign-born population compared to the U.S.-born population (43% vs 60%). Citizenship status, length of residence in the U.S. for more than 15 years, and English proficiency were directly linked to increased rates of PSA testing. There was significant variability in PSA testing among immigrant subgroups and Asian immigrants had the lowest rate of PSA testing. Annual physician visits and English language proficiency were associated with increased PSA testing among the U.S. immigrant population. Immigrants have relatively low rates of PSA testing. Improving health care utilization and language services may help to narrow the gap in guideline-concordant prostate cancer screening between immigrants and nonimmigrants.


Combined chemical and genetic approach to inhibit proteolysis by the proteasome.
Regulated protein destruction by the proteasome is crucial for the maintenance of normal cellular homeostasis. Much of our understanding of proteasome function stems from the use of drugs that inhibit its activity. Curiously, despite the importance of proteasomal proteolysis, previous studies have found that proliferation of the yeast Saccharomyces cerevisiae is relatively resistant to the effects of proteasome inhibitors such as MG132, even in the presence of mutations that increase inhibitor levels in cells. We reasoned that part of the resistance of S. cerevisiae to proteasome inhibitors stems from the fact that most proteasome inhibitors preferentially target the chymotryptic activity of the proteasome, and that the caspase-like and tryptic sites within the 20S core could compensate for proteasome function under these conditions. To test this hypothesis, we generated a strain of yeast in which the gene encoding the drug efflux pump Pdr5 is deleted, and the tryptic and caspase-like proteasome activities are inactivated by mutation. We find that this strain has dramatically increased sensitivity to the proteasome inhibitor MG132. Under these conditions, treatment of yeast with MG132 blocks progression through the cell cycle, increases the accumulation of polyubiquitylated proteins and decreases the ability to induce transcription of certain genes. These results highlight the contribution of the caspase-like and tryptic activities of the proteasome to its function, and provide a strategy to potently block proteasomal proteolysis in yeast that has practical applications.


Deep Learning-Based Automatic Assessment of Lung Impairment in COVID-19 Pneumonia: Predicting Markers of Hypoxia With Computer Vision.
Hypoxia is a potentially life-threatening condition that can be seen in pneumonia patients. We aimed to develop and test an automatic assessment of lung impairment in COVID-19 associated pneumonia with machine learning regression models that predict markers of respiratory and cardiovascular functioning from radiograms and lung CT. We enrolled a total of 605 COVID-19 cases admitted to Al Ain Hospital from 24 February to 1 July 2020 into the study. The inclusion criteria were as follows: age ≥ 18 years; inpatient admission; PCR positive for SARS-CoV-2; lung CT available at PACS. We designed a CNN-based regression model to predict systemic oxygenation markers from lung CT and 2D diagnostic images of the chest. The 2D images generated by averaging CT scans were analogous to the frontal and lateral view radiograms. The functional (heart and breath rate, blood pressure) and biochemical findings (SpO2, H C O 3 - , K +, Na +, anion gap, C-reactive protein) served as ground truth. Radiologic findings in the lungs of COVID-19 patients provide reliable assessments of functional status with clinical utility. If fed to ML models, the sagittal view radiograms reflect dyspnea more accurately than the coronal view radiograms due to the smaller size and the lower model complexity. Mean absolute error of the models trained on single-projection radiograms was approximately 11÷12% and it dropped by 0.5÷1% if both projections were used (11.97 ± 9.23 vs. 11.43 ± 7.51%; p = 0.70). Thus, the ML regression models based on 2D images acquired in multiple planes had slightly better performance. The data blending approach was as efficient as the voting regression technique: 10.90 ± 6.72 vs. 11.96 ± 8.30%, p = 0.94. The models trained on 3D images were more accurate than those on 2D: 8.27 ± 4.13 and 11.75 ± 8.26%, p = 0.14 before lung extraction; 10.66 ± 5.83 and 7.94 ± 4.13%, p = 0.18 after the extraction. The lung extraction boosts 3D model performance unsubstantially (from 8.27 ± 4.13 to 7.94 ± 4.13%; p = 0.82). However, none of the differences between 3D and 2D were statistically significant. The constructed ML algorithms can serve as models of structure-function association and pathophysiologic changes in COVID-19. The algorithms can improve risk evaluation and disease management especially after oxygen therapy that changes functional findings. Thus, the structural assessment of acute lung injury speaks of disease severity.


Effects of amphetamine on vigilance performance in normal and hyperactive children.
Deficient sustained attention is a symptom of hyperactivity that can be improved by stimulant medication. Recently, amphetamine has been shown to increase detections during a vigilance task in both normal and hyperactive boys. The present study applied signal detection analysis to the vigilance performance of 15 hyperactive and 14 normal boys dsivided into two age groups (6-9 and 10-12). A computerized continuous performance test was administered under amphetamine and placebo. Overall group comparisons indicated that perceptual sensitivity or d' was higher for the normal boys and the older groups, and analysis of drug treatments showed that amphetamine significantly increased d'. Interactions between drugs and age groups demonstrated that amphetamine affected the younger boys to a significantly greater degree than the older children for both d' and response bias or beta. It is notable that the results were essentially parallel for both normal and hyperactive children.


An essential role for water in an enzyme reaction mechanism: the crystal structure of the thymidylate synthase mutant E58Q.
A water-mediated hydrogen bond network coordinated by glutamate 60(58) appears to play an important role in the thymidylate synthase (TS) reaction mechanism. We have addressed the role of glutamate 60(58) in the TS reaction by cocrystalizing the Escherichia coli TS mutant E60(58)Q with dUMP and the cofactor analog CB3717 and have determined the X-ray crystal structure to 2.5 A resolution with a final R factor of 15.2% (Rfree = 24.0%). Using difference Fourier analysis, we analyzed directly the changes that occur between wild-type and mutant structures. The structure of the mutant enzyme suggests that E60(58) is not required to properly position the ligands in the active site and that the coordinated hydrogen bond network has been disrupted in the mutant, providing an atomic resolution explanation for the impairment of the TS reaction by the E60(58)Q mutant and confirming the proposal that E60(58) coordinates this conserved hydrogen bond network. The structure also provides insight into the role of specific waters in the active site which have been suggested to be important in the TS reaction. Finally, the structure shows a unique conformation for the cofactor analog, CB3717, which has implications for structure-based drug design and sheds light on the controversy surrounding the previously observed enzymatic nonidentity between the chemically identical monomers of the TS dimer.


[The gitaigo personality scale for description of self and others].
Gitaigo is a subtype of mimetic words (onomatopoeia) in the Japanese language, which can be regarded as words that imitate actions or states. This study develops a personality scale, with six subscales, using 60 gitaigo words as items for rating the personality of the self and others. We asked 1 054 participants to rate their own personality and 905 participants to rate a close friend's personality, using 158 gitaigo words as items to describe personality. We found that a six-factor model, found in our previous study, was also applicable to the present study of ratings of participants' own personality. We also found six groups of words in the ratings of close friends' personality, although the factor structure is slightly different from the self-rating factors. We selected ten words that exhibited high loadings for each of the six factors to develop a personality scale with six subscales showing high reliability. We named those factors: cowardliness, slowness, preciseness, irritableness, candidness, and frivolousness. The average scores for self-ratings were significantly lower for two subscales (preciseness and candidness) and higher for other four subscales compared to the rating of others.


Elastofibromatous polyp of the sigmoid colon--a case report and review of gastrointestinal elastofibromas.
Elastofibromatous change in the gastrointestinal tract is a rarely reported, usually polypoid lesion of unknown etiology with submucosal stromal change that may mimic amyloid deposition. The constituent amorphous material of the polyp stroma has distinctive features that permit an accurate assessment and diagnosis including: distribution of the material predominantly in the submucosa; distinctive fibrillar and granular appearance of the deposits; thick, irregular, haphazardly arranged bundles of elastic fibres positive for Verhoeff's elastic stain; ultrastructural fibres with an electron dense curvilinear or beaded appearance; lack of amyloid type vascular wall deposits; and lack of amyloid congophilia or crystal violet metachromasia. The clinical, light microscopic, histochemical and ultrastructural characteristics of this deposited material are reviewed in detail in the present report of a patient who presented with an asymptomatic polypoid lesion of the sigmoid colon. Other reported cases are summarized, and their clinical and pathological features are compared with the current case.


Syncope in aircrew.
In a study of 47 aviator patients consecutively referred to U.S. Air Force School of Aerospace Medicine for evaluation of alteration of consciousness, 34 cases of syncope were identified. Mechanisms of etiology included 24 with vasovagal syncope, 4 with micturition syncope, and 6 with miscellaneous causes. Each diagnostic group was separately compared to a group of 26 control (nonsyncopal) patients. Clinical findings of the different diagnostic groups are presented. Notable differences in antecedent factors, clinical findings, and consequences of syncope are discussed.


Unusual lectin-binding properties of a herpes simplex virus type 1-specific glycoprotein.
Lysates from herpes simplex virus type 1-infected cells were subjected to affinity chromatography on soybean and Helix pomatia lectins. One of the virus-specified glycoproteins, probably the herpes simplex virus type 1-specific gC glycoprotein, bound to the lectins and was eluted with N-acetylgalactosamine. The affinity chromatography permitted a high degree of purification of the type-specific glycoprotein with respect to both host cell components and other viral glycoproteins. The lectin affinity pattern of this glycoprotein indicates the presence of a terminal alpha-N-acetylgalactosamine in an oligosaccharide, a finding not reported previously for glycoproteins of enveloped viruses.


Efficacy of the biocontrol yeast Pichia anomala during long-term storage of moist feed grain under different oxygen and carbon dioxide regimens.
The yeast Pichia anomala inhibits the spoilage mold Penicillium roqueforti in laboratory experiments with high-moisture wheat in malfunctioning airtight storage. The ability of P. anomala to prevent mold growth during 14 months of grain storage was evaluated in outdoor silos with different air permeabilities. Freshly harvested wheat in 160-kg portions was inoculated with 10(2) colony-forming units (cfu) g(-1) P. roqueforti, alone or together with 10(4) cfu g(-1) P. anomala. During the first month P. anomala increased to about 10(6) cfu g(-1) in the treated silos to reach 10(7) cfu g (-1) after 9 months. Naturally occurring P. anomala in the untreated silos increased from 10(2) to about 10(3) cfu g(-1) during the first month and reached the same level as the treated silos after 9 months. Oxygen levels were reduced below the detection limit within 1 day, while carbon dioxide levels increased to 80-90% during the first month. P. roqueforti did not grow in wheat treated with P. anomala, regardless of silo permeability, but had increased to 10(5) cfu g(-1) in the untreated silos after 14 months of storage.


Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition.


Random Neural Network Based Epileptic Seizure Episode Detection Exploiting Electroencephalogram Signals.
Epileptic seizures are caused by abnormal electrical activity in the brain that manifests itself in a variety of ways, including confusion and loss of awareness. Correct identification of epileptic seizures is critical in the treatment and management of patients with epileptic disorders. One in four patients present resistance against seizures episodes and are in dire need of detecting these critical events through continuous treatment in order to manage the specific disease. Epileptic seizures can be identified by reliably and accurately monitoring the patients' neuro and muscle activities, cardiac activity, and oxygen saturation level using state-of-the-art sensing techniques including electroencephalograms (EEGs), electromyography (EMG), electrocardiograms (ECGs), and motion or audio/video recording that focuses on the human head and body. EEG analysis provides a prominent solution to distinguish between the signals associated with epileptic episodes and normal signals; therefore, this work aims to leverage on the latest EEG dataset using cutting-edge deep learning algorithms such as random neural network (RNN), convolutional neural network (CNN), extremely random tree (ERT), and residual neural network (ResNet) to classify multiple variants of epileptic seizures from non-seizures. The results obtained highlighted that RNN outperformed all other algorithms used and provided an overall accuracy of 97%, which was slightly improved after cross validation.


Altimeter-derived seasonal circulation on the southwest Atlantic shelf: 27°-43°S.
Altimeter sea surface height (SSH) fields are analyzed to define and discuss the seasonal circulation over the wide continental shelf in the SW Atlantic Ocean (27°-43°S) during 2001-2012. Seasonal variability is low south of the Rio de la Plata (RdlP), where winds and currents remain equatorward for most of the year. Winds and currents in the central and northern parts of our domain are also equatorward during autumn and winter but reverse to become poleward during spring and summer. Transports of shelf water to the deep ocean are strongest during summer offshore and to the southeast of the RdlP. Details of the flow are discussed using mean monthly seasonal cycles of winds, heights, and currents, along with analyses of Empirical Orthogonal Functions. Principle Estimator Patterns bring out the patterns of wind forcing and ocean response. The largest part of the seasonal variability in SSH signals is due to changes in the wind forcing (described above) and changes in the strong boundary currents that flow along the eastern boundary of the shelf. The rest of the variability contains a smaller component due to heating and expansion of the water column, concentrated in the southern part of the region next to the coast. Our results compare well to previous studies using in situ data and to results from realistic numerical models of the regional circulation.


Phase I clinical investigation of 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942).
9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942) is a new anthracene bishydrazone derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection repeated at 4-week intervals. Twenty-eight patients received a total of 61 courses of the drug in a dose range of 20 to 280 mg/sq m. Leukopenia was the dose-limiting toxicity. It was of short duration and reversible. A drug-induced hypotension was noted at higher doses in three patients. The hypotension was not dose limiting, it was reversible, and it could largely be avoided by prolonging the drug infusion time to 1 hr. One patient with unsuspected severe coronary artery disease died of complications of myocardial infarction subsequent to a hypotensive episode. Significant phlebitis was also noted at higher doses of drug. This degree of phlebitis could be lessened by diluting the drug in larger volumes of fluid. Three patients experienced diaphoresis, nausea, palpitations, and chest discomfort at the conclusion of the infusions. None of the patients had electrocardiographic changes. Mild fever, alopecia, and nausea and vomiting were noted occasionally. One patient with a hypernephroma and one patient with hepatocellular carcinoma experienced partial responses of their tumors secondary to the drug. Phase II studies of CL216,942 are planned at a starting dose of 260 mg/sq m as a single dose repeated at 21- to 28-day intervals.


Ricin B chain targeted to the endoplasmic reticulum of tobacco protoplasts is degraded by a CDC48- and vacuole-independent mechanism.
The B chain of ricin was expressed and delivered to the endoplasmic reticulum of tobacco protoplasts where it disappeared with time in a manner consistent with degradation. This turnover did not occur in the vacuoles or upon secretion. Indeed, several lines of evidence indicate that, in contrast to the turnover of endoplasmic reticulum-targeted ricin A chain in the cytosol, the bulk of expressed ricin B chain was degraded in the secretory pathway.


Cardiac 123I-MIBG reflects left ventricular functional reserve in patients with nonobstructive hypertrophic cardiomyopathy.
Little is known about the relation between left ventricular (LV) functional reserve in response to exercise and cardiac sympathetic nervous function in patients with nonobstructive hypertrophic cardiomyopathy (HCM). We investigated whether an assessment of cardiac sympathetic nervous function by myocardial (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy might provide a sign of an abnormal LV functional reserve in response to exercise-induced beta-adrenergic stimulation in patients with HCM. Thirty HCM patients underwent (123)I-MIBG scintigraphy and echocardiography at rest and subsequent biventricular cardiac catheterization at rest and during dynamic exercise. LV pressures were measured using a micromanometer-tipped catheter system. The early and delayed (123)I-MIBG images were quantified as a heart-to-mediastinum ratio (H/M). The plasma levels of brain natriuretic peptide (BNP) and norepinephrine (NE) were also measured. Patients were divided into 2 groups according to the delayed (123)I-MIBG H/M: group I consisted of 12 patients with a delayed H/M of < or =1.8 and group II had 18 patients with a delayed H/M of >1.8. Both the percentage increase from rest to exercise in LV isovolumic contraction (LV dP/dt(max)) and the percentage shortening of LV pressure half-time (T(1/2)) as an index of isovolumic relaxation were significantly less in group I than in group II (P < 0.05, respectively). A significant linear correlation was observed between the percentage increase in LV dP/dt(max) and (123)I-MIBG H/Ms (early H/M: r = 0.49, P < 0.01; delayed H/M: r = 0.54, P < 0.005, respectively). A significant linear correlation was also observed between the percentage shortening in T(1/2) and (123)I-MIBG H/Ms (early H/M: r = 0.58, P < 0.001; delayed H/M: r = 0.64, P < 0.0005, respectively). The plasma NE levels were significantly higher in group I than in group II (P < 0.01), whereas the plasma BNP levels were comparable in the 2 HCM groups. beta-Adrenergic enhancement of LV function during exercise may depend on the extent of cardiac sympathetic nervous innervation in HCM patients. Resting myocardial (123)I-MIBG scintigraphy can noninvasively evaluate LV functional reserve in response to exercise in patients with nonobstructive HCM.