High Spatiotemporal Resolution ECoG Recording of Somatosensory Evoked Potentials with Flexible Micro-Electrode Arrays.
Electrocorticogram (ECoG) has great potential as a source signal, especially for clinical BMI. Until recently, ECoG electrodes were commonly used for identifying epileptogenic foci in clinical situations, and such electrodes were low-density and large. Increasing the number and density of recording channels could enable the collection of richer motor/sensory information, and may enhance the precision of decoding and increase opportunities for controlling external devices. Several reports have aimed to increase the number and density of channels. However, few studies have discussed the actual validity of high-density ECoG arrays. In this study, we developed novel high-density flexible ECoG arrays and conducted decoding analyses with monkey somatosensory evoked potentials (SEPs). Using MEMS technology, we made 96-channel Parylene electrode arrays with an inter-electrode distance of 700 μm and recording site area of 350 μm2. The arrays were mainly placed onto the finger representation area in the somatosensory cortex of the macaque, and partially inserted into the central sulcus. With electrical finger stimulation, we successfully recorded and visualized finger SEPs with a high spatiotemporal resolution. We conducted offline analyses in which the stimulated fingers and intensity were predicted from recorded SEPs using a support vector machine. We obtained the following results: (1) Very high accuracy (~98%) was achieved with just a short segment of data (~15 ms from stimulus onset). (2) High accuracy (~96%) was achieved even when only a single channel was used. This result indicated placement optimality for decoding. (3) Higher channel counts generally improved prediction accuracy, but the efficacy was small for predictions with feature vectors that included time-series information. These results suggest that ECoG signals with high spatiotemporal resolution could enable greater decoding precision or external device control.


Inertial Sensor Algorithm to Estimate Walk Distance.
The "total distance walked" obtained during a standardized walking test is an integral component of physical fitness and health status tracking in a range of consumer and clinical applications. Wearable inertial sensors offer the advantages of providing accurate, objective, and reliable measures of gait while streamlining walk test administration. The aim of this study was to develop an inertial sensor-based algorithm to estimate the total distance walked using older subjects with impaired fasting glucose (Study I), and to test the generalizability of the proposed algorithm in patients with Multiple Sclerosis (Study II). All subjects wore two inertial sensors (Opals by Clario-APDM Wearable Technologies) on their feet. The walking distance algorithm was developed based on 108 older adults in Study I performing a 400 m walk test along a 20 m straight walkway. The validity of the algorithm was tested using a 6-minute walk test (6MWT) in two sub-studies of Study II with different lengths of a walkway, 15 m (Study II-A, n = 24) and 20 m (Study II-B, n = 22), respectively. The start and turn around points were marked with lines on the floor while smaller horizontal lines placed every 1 m served to calculate the manual distance walked (ground truth). The proposed algorithm calculates the forward distance traveled during each step as the change in the horizontal position from each foot-flat period to the subsequent foot-flat period. The total distance walked is then computed as the sum of walk distances for each stride, including turns. The proposed algorithm achieved an average absolute error rate of 1.92% with respect to a fixed 400 m distance for Study I. The same algorithm achieved an absolute error rate of 4.17% and 3.21% with respect to an averaged manual distance for 6MWT in Study II-A and Study II-B, respectively. These results demonstrate the potential of an inertial sensor-based algorithm to estimate a total distance walked with good accuracy with respect to the manual, clinical standard. Further work is needed to test the generalizability of the proposed algorithm with different administrators and populations, as well as larger diverse cohorts.


Successful migraine prophylaxis with naproxen sodium.
Naproxen sodium, a potent inhibitor of prostaglandin biosynthesis and platelet aggregation, was studied for efficacy in migraine prophylaxis in a randomized, double-blind, placebo-controlled, crossover trial. On naproxen treatment, 52% of the patients had no severe headaches, whereas 19% had no severe headaches during placebo. Naproxen sodium was much better than placebo when patients' diaries were reviewed for severity of attacks, nausea, vomiting, activity reduction, duration of headache, and decreased use of therapeutic medication. The degree of platelet inhibition did not correlate with efficacy in preventing headache. Naproxen sodium can be recommended as a drug of first choice for migraine prevention.


Use of DNA microarray and small animal positron emission tomography in preclinical drug evaluation of RAF265, a novel B-Raf/VEGFR-2 inhibitor.
Positron emission tomography (PET) imaging has become a useful tool for assessing early biologic response to cancer therapy and may be particularly useful in the development of new cancer therapeutics. RAF265, a novel B-Raf/vascular endothelial growth factor receptor-2 inhibitor, was evaluated in the preclinical setting for its ability to inhibit the uptake of PET tracers in the A375M(B-Raf(V600E)) human melanoma cell line. RAF265 inhibited 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) accumulation in cell culture at 28 hours in a dose-dependent manner. RAF265 also inhibited FDG accumulation in tumor xenografts after 1 day of drug treatment. This decrease persisted for the remaining 2 weeks of treatment. DNA microarray analysis of treated tumor xenografts revealed significantly decreased expression of genes regulating glucose and thymidine metabolism and revealed changes in apoptotic genes, suggesting that the imaging tracers FDG, 3-deoxy-3-[(18)F]fluorothymidine, and annexin V could serve as potential imaging biomarkers for RAF265 therapy monitoring. We concluded that RAF265 is highly efficacious in this xenograft model of human melanoma and decreases glucose metabolism as measured by DNA microarray analysis, cell culture assays, and small animal FDG PET scans as early as 1 day after treatment. Our results support the use of FDG PET in clinical trials with RAF265 to assess early tumor response. DNA microarray analysis and small animal PET studies may be used as complementary technologies in drug development. DNA microarray analysis allows for analysis of drug effects on multiple pathways linked to cancer and can suggest corresponding imaging tracers for further analysis as biomarkers of tumor response.


[Modelling the oscillatory electrical activity of mollusk neurons].
A model is suggested describing slow membrane potential oscillations in moluscan neurons. It is based on the assumptions that the depolarization phase of oscillations is induced by slow calcium current and the hyperpolarization phase--by potassium current activated by intracellular Ca ions. It is stated that three types of neuronal electrical activity are possible depending on the values of the model parameters: stable membrane hyperpolarization down to the resting potential (-49 divided by -53 mV); slow oscillations of the membrane potential in a range of -30 divided by -60 mV with the period of 12-17 s; stable membrane depolarization up to -40 divided by -30 mV, which may lead to a repetitive firing behaviour of these neurons. Calculated dependence of the amplitude of membrane potential oscillations upon extracellular concentration of Ca, K and Na ions is in quantitative agreement with experimental data obtained by Barker and Gainer [4].


Superior survival and durability of neurons and astrocytes on 3-dimensional aragonite biomatrices.
Current needs of central nervous system therapy urge for the identification of scaffolds supporting the generation and long-term maintenance of healthy and functional neuronal tissue. We compared for the first time the viability of hippocampal neurons and astrocytes grown on conventional 2-dimensional (2D) conditions with that of cells grown on an aragonite bioactive 3-dimensional (3D) scaffold prepared from coralline exoskeleton. Cultures in 3D showed significantly lower mortality rate and higher neurons/astrocytes ratio than 2D cultures. Moreover, whereas cell survival in 2D was arrested in the absence of the supporting substrates poly-D-lysine and laminin, these substrates had negligible effect on the 3D cultures. Furthermore, aragonite matrices supported cell survival and growth under conditions of calcium and nutrients deprivation, whereas in 2D such treatments led to death of all neurons and of almost all astrocytes. To show that the aragonite matrices are permissive for neural cells also in vivo, aragonite matrices having no substrate coating grafted into postnatal rat cortex were invaded by neurons growing on the surface and in multilayer structures resembling those seen in the 3D culture in vitro. Hence, culture of neurons and astrocytes on 3D aragonite coralline matrices is a novel mean for production of stable neuronal tissue, with significant implication to the field of neuronal tissue restoration.


Accurate determination of phenotypic information from historic thoroughbred horses by single base extension.
Historic DNA data have the potential to identify phenotypic information otherwise invisible in the historical, archaeological and palaeontological record. In order to determine whether a single nucleotide polymorphism typing protocol based on single based extension (SNaPshot™) could produce reliable phenotypic data from historic samples, we genotyped three coat colour markers for a sample of historic Thoroughbred horses for which both phenotypic and correct genotypic information were known from pedigree information in the General Stud Book. Experimental results were consistent with the pedigrees in all cases. Thus we demonstrate that historic DNA techniques can produce reliable phenotypic information from museum specimens.


Communication for patient safety in pediatric hospitalizations.
To analyze the perception of health professionals and companions/family about the development of communication for patient safety in pediatric hospitalizations. It is an exploratory-descriptive study with a qualitative approach, performed in pediatric clinical-surgical hospitalization units of three hospitals in Porto Alegre, RS, Brazil. 44 health professionals and 94 companions of hospitalized children participated in the study, to a total of 138 participants. Data collection took place between 2016 and 2017, through semi-structured interviews. A thematic content analysis was used. Two categories emerged: "Barriers to an effective communication", addressing the failures and difficulties in the communication process and "Tools to improve communication", that present recommendations for improvements, especially instrumentalization of the companion/family member. The barriers to an effective communication involve several factors, and effective communication strategies can assist in the development of improvements for pediatric patient safety.


A Randomized Controlled Trial of Mentoring Interventions for Underrepresented Minorities.
To conduct a randomized controlled trial to evaluate the effects of different mentoring interventions on the basic psychological need satisfaction of underrepresented minorities and women in academia. Participants were 150 mentor/protégé dyads from three academic medical centers and eight other colleges and universities in western and central New York, randomized from 2010 to 2013 into mentor training (using principles of self-determination theory); peer mentoring for protégés; mentor training and peer mentoring for protégés combined; or control/usual practice. Protégé participants were graduate students, fellows, and junior faculty who were from underrepresented groups based on race, ethnicity, gender, or disability.The primary analysis was a comparison of intervention effects on changes in protégés' satisfaction of their basic psychological needs (competence, autonomy, and relatedness) with their mentor. They completed a well-validated, online questionnaire every two months for one year. There was no significant effect at the end of one year of either mentor training or peer mentoring on protégés' psychological basic need satisfaction with mentor specifically or at work in general. Exploratory analyses showed a significant effect of the mentor-based intervention on the protégés' overall psychological need satisfaction with their mentor at two months, the time point closest to completing mentor training. This randomized controlled trial showed a potential short-term effect of mentor training on changing basic psychological need satisfaction of underrepresented scholars with their mentors. Despite the lack of sustained effect of either mentor training or peer mentoring, these short-term changes suggest feasibility and potential for future study.


Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen- and CCl4-induced liver damage in rats.
The hepatoprotective effect of DA-9601, a quality-controlled extract of Artemisia asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride (CCl4) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of DA-9601 (10, 30, or 100 mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or CCl4 (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of DA-9601 reduced the elevation of serum ALT, AST, LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. DA-9601 also prevented APAP- and CCl4-induced hepatic glutathione (GSH) depletion and CCl4-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a dose-dependent manner. These findings suggest that pretreatment with DA-9601 may reduce chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.


Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking.
Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Based on this hypothesis, the relationship between APE1 polymorphism, smoking and the risk of lung cancer was explored. The distribution of the APE1 Asp148Glu polymorphisms in 98 lung cancer patients and 67 healthy individuals were compared using PCR-RFLP analysis. Individuals carrying the APE1 Asp148Glu heterozygous and homozygous variant genotype had a 3.23-fold increased risk of lung cancer compared with these carrying the wild-type (Asp/Asp) genotype (p<0.0001), and those carrying the 148Glu homozygous genotype had a 3.17-fold increased risk (p=0.023). When stratified by smoking status, carriers of the Glu allele of APE1 were at a statistically increased risk of lung cancer among smokers (p=0.001). A statistically significant interaction of current smoking status with APE1 Asp148Glu polymorphism was found. These results suggest that the presence of one or two APE1 Glu allele was associated with the risk of developing lung cancer.


Dissociation of fractional anisotropy and resting-state functional connectivity alterations in antipsychotic-naive first-episode schizophrenia.
Altered resting-state functional connectivity (rsFC) has been demonstrated between multiple brain regions in schizophrenia. However, whether these alterations are related to fractional anisotropy (FA) alterations in pathways that connect regions with altered rsFC remains unknown. In this study, diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed with 181 antipsychotic-naïve first-episode schizophrenia patients and 173 matched healthy controls. FA was measured using tensor-guided tractography in identifiable pathways between selected pairs of brain regions with altered rsFC as determined by prior meta-analysis. Compared with controls, patients showed significantly decreased FA between right caudate nucleus and right pallidum, right caudate nucleus and right putamen, and right hippocampus and right thalamus. Decreased rsFC was observed between right pallidum and right thalamus, and right insula and right superior temporal gyrus. No significant correlation was observed between FA and rsFC. FA between right caudate nucleus and right putamen was inversely correlated with negative symptoms while rsFC between right pallidum and right thalamus was inversely correlated with positive symptoms. The lack of robust correlations between FA and rsFC and no overlap of these abnormalities indicate that regional rsFC alterations in the early course of schizophrenia are not primarily associated with FA alterations. The observation that positive and negative symptoms are related to different functional and structural disturbances is consistent with this dissociation, and with prior work suggests that different pathophysiological mechanism may underlie positive and negative symptoms in the early course of schizophrenia.


Stretch-induced Raf-1 activation in mesangial cells requires actin cytoskeletal integrity.
Glomerular capillary hypertension is a determinant of glomerulosclerosis and is modelled in vitro by exposure of mesangial cells to cyclic mechanical strain. In response to strain, Erk is activated and mediates extracellular matrix accumulation and mesangial cell proliferation. Erk activation is dependent on an intact cytoskeleton. Since Raf-1 lies upstream of Erk in response to numerous stimuli, and since its activation is dependent on membrane recruitment, we postulated that the cytoskeleton was essential for Raf-1 membrane recruitment and Erk activation. Primary rat mesangial cells (passages 8-20) were stretched at 1 Hz and 27 kPa. Raf-1 was both phosphorylated on serine-338 (S338) and activated within 2 min of strain. The Raf-1 inhibitor, GW5074, dose-dependently blocked strain-induced Erk activation and Raf-1 phosphorylation. Although phosphatidylinositol-3-kinase (PI3-K) may mediate Raf-1 activation, PI3-K inhibition with wortmannin or LY294002 had no effect on stretch-induced Raf-1 activation. Cytoskeletal disruption with cytochalasin D and the Rho-kinase inhibitor, Y-27632, however, blocked both Raf-1 phosphorylation and activation. Furthermore, membrane localization of Raf-1 was increased by strain and prevented by cytoskeletal disruption. Thus, strain leads to rapid membrane localization, S338 phosphorylation, and activation of Raf-1. These events are independent of PI3-K, but require Rho-kinase activation and an intact actin cytoskeleton.


Texture analysis of ultrasonic images of the prostate by means of co-occurrence matrices.
As speckle on ultrasonic B-scan may reveal information relative to tissue structure, the present work attempts to discriminate the various prostatic tissues (normal tissue, benign prostatic hypertrophy and cancer) by means of texture analysis. We select regions of interest by their homogeneous appearance. A pre-processing stage is required to obtain stationary samples. The method used measures the second-order statistics, namely co-occurrence matrices. Fairly good tissue signatures have been obtained with parameters derived from these matrices. Of 37 images processed, 78 percent of the samples were classified with success, which is a high score considering that the images cannot be discriminated visually. However, while such results are obtained when wide regions of interest are investigated (64 x 64 pixels), they are not as good with smaller sample sizes, i.e., when the pathological area is very small.


Molecular genetic basis of familial ALS.
Familial amytrophic lateral sclerosis (FALS) is transmitted in a mendelian fashion as an autosomal dominant (DFALS) or an autosomal recessive (RFALS) trait. Both DFALS and RFALS are genetically heterogeneous. Fifteen percent of DFALS families have mutations in the gene for Cu, Zn superoxide dismutase (SOD1) which is coded on chromosome 21. The locus for one form of RFALS maps to chromosome 2q33. Forty-six mutations in the SOD1 gene have been reported in DFALS families. These mutations result in decreased SOD1 activity and shortened half-life of the protein in most instances. Transgenic mice overexpressing mutated SOD1 protein develop an ALS-like disease which suggests that the degeneration of motor neurons in DFALS is caused by the gain of a novel toxic function by mutated SOD1 rather than by the decrease of SOD1 activity. Several possible mechanisms of the novel neurotoxic function of mutated SOD1 are discussed.


Secondary Central Nerve System Lymphoma With Intratumoral Hemorrhage Suggested as Intravascular Lymphoma by Autopsy: A Case Report.
Intravascular large B-cell lymphoma (IVL) is a rare type of extranodal diffuse large B-cell lymphoma (DLBCL), which often infiltrates the central nervous system (CNS) during the clinical course. Cerebral hemorrhage in patients with CNS lymphoma at presentation is rare. Herein, we describe a case of secondary CNS lymphoma with intratumoral hemorrhage, which was suggested as IVL from autopsy findings. A 76-year-old Japanese man with a history of treatment for B-cell non-Hodgkin's lymphoma was transferred to our hospital in an ambulance for generalized convulsions. Brain CT scan revealed a high-density tumor with edema and intratumoral hemorrhage in the left temporal lobes. He died in a rapid course, and autopsy revealed a focal hemorrhage with diffuse infiltration of lymphoma cells in the left temporal lobe and findings suggestive of IVL. Furthermore, the autopsy revealed a discrepancy in the CD20 immunostaining of lymphoma cells between the brain and other organs. Clinicians should not eliminate CNS lymphoma from the differential diagnosis of intracranial tumor with hemorrhage. Although many patients with IVL have rapidly progressive courses, it is very important to diagnose IVL at the initial onset, even in serious situations, to consider CNS prophylaxis.


Abnormalities of peptide-containing nerve fibers in infantile hypertrophic pyloric stenosis.
The distributions of nerve cells and fibers with immunoreactivity for the peptides enkephalin, gastrin-releasing peptide, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide were examined in specimens of myenteric plexus and external muscle from the pylorus of 20 infants with hypertrophic pyloric stenosis. These were compared with peptide distributions in pyloric samples from unaffected infants and adults. In the normal pylorus the circular muscle was richly supplied with fibers reactive for enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide. In pyloric stenosis, these immunoreactive fiber bundles were either missing or less than 5% of normal. In contrast, there were reactive cell bodies and nerve fibers in the myenteric plexuses of both normal and affected specimens. In the samples from cases of stenosis, swollen nerve fibers that appeared to be in the process of degeneration were frequently encountered. It is concluded that infantile hypertrophic pyloric stenosis is associated with a loss of peptide immunoreactivity in nerve fibers in the circular muscle, although the same peptides are still revealed in fibers and in nerve cell bodies in the myenteric plexus.


Mapping quantitative trait loci for stress induced alterations in porcine leukocyte numbers and functions.
To identify quantitative trait loci (QTLs) with effects on 'stress' induced alterations of porcine immune functions, a number of immune capacity traits were analysed in the F2 generation of a Wild Boar--Yorkshire intercross. All traits were measured prior, and one day after, exposure to experimental 'stress' (mixing and transport). The 'stress' protocol induced a decrease in numbers of circulating neutrophils and in spontaneous proliferation in vitro, whereas phagocytic capacity, mitogen induced proliferation and spontaneous IL-2 activity increased. The IFN-alpha production tended to decrease, although the individual variation was pronounced. More than 200 genetic markers have been scored in the entire pedigree and were used to trace the inheritance of individual chromosome segments. Wild Boar alleles were on average associated with higher mitogen induced IL-2 activity and a slightly lower decrease in IFN-alpha production after mixing and transport. Four QTLs with significant effects were identified; one influencing 'stress' induced alteration in numbers of neutrophils (chromosome 8), one influencing spontaneous proliferation after 'stress' (chromosome 2), one influencing mitogen induced IL-2 activity after 'stress' (chromosome 6) and one influencing 'stress' induced alterations in mitogen induced IL-2 activity (chromosome 12). In addition, several suggestive QTLs were indicated.


Red fluorescent protein responsible for pigmentation in trematode-infected Porites compressa tissues.
Reports of coral disease have increased dramatically over the last decade; however, the biological mechanisms that corals utilize to limit infection and resist disease remain poorly understood. Compromised coral tissues often display non-normal pigmentation that potentially represents an inflammation-like response, although these pigments remain uncharacterized. Using spectral emission analysis and cryo-histological and electrophoretic techniques, we investigated the pink pigmentation associated with trematodiasis, infection with Podocotyloides stenometre larval trematode, in Porites compressa. Spectral emission analysis reveals that macroscopic areas of pink pigmentation fluoresce under blue light excitation (450 nm) and produce a broad emission peak at 590 nm (+/-6) with a 60-nm full width at half maximum. Electrophoretic protein separation of pigmented tissue extract confirms the red fluorescence to be a protein rather than a low-molecular-weight compound. Histological sections demonstrate green fluorescence in healthy coral tissue and red fluorescence in the trematodiasis-compromised tissue. The red fluorescent protein (FP) is limited to the epidermis, is not associated with cells or granules, and appears unstructured. These data collectively suggest that the red FP is produced and localized in tissue infected by larval trematodes and plays a role in the immune response in corals.


[Alpha-adrenergic receptors of the human lung parenchyma in destructive tuberculosis].
Adrenergic receptors were studied in human lung parenchyma obtained from 10 patients with tuberculoma after segmental resection within the limits of surrounding normal tissues (controls) as well as from 10 patients with destructive pulmonary tuberculosis. Binding of alpha-adrenergic radioligand 3H-prazosin was saturable with high rate of affinity in lung parenchymal membranes of both normal tissues and tissues impaired with tuberculosis. The Scatchard analysis indicated that the affinity of 3H-prazosin binding was not altered in patients with tuberculosis, while amount of the ligand binding sites was significantly decreased as compared with control preparations (KD = 0.5 +/- 0.9 nM, Bmax = 273.5 +/- 59.9 fmol/mg in controls; KD = 0.5 +/- 0.07 nM, Bmax = 51.7 +/- 7.5 fmol/mg in tuberculous lung parenchyma). beta-Adrenergic and muscarinic acetylcholinergic receptors were studied in lung parenchyma of patients with tuberculosis. Binding parameters of beta-adrenergic ligand 3H-dihydroalprenolol and muscarinic antagonist 3H-quinuclidinyl benzylate were similar to those of control values. Amount of 3H-dihydroalprenolol binding sites was not markedly altered while content of 3H-prazosin binding sites was considerably decreased in lung parenchyma of patients with tuberculosis as compared with normal state. The data obtained suggest that population of alpha-adrenergic receptors was decreased in human lung parenchyma under conditions of destructive tuberculosis.


Serum vascular adhesion protein-1 level predicts risk of incident cancers in subjects with type II diabetes.
Serum vascular adhesion protein-1 (VAP-1) predicts cancer-related mortality in diabetic subjects. However, whether serum VAP-1 predicts cancer incidence or cancer progression remains unclear. We conducted a cohort study to investigate whether serum VAP-1 and related clinical variables predict incident cancers in type II diabetic subjects. From 1996 to 2003, we enrolled 568 type II diabetic subjects who were free of cancer at baseline. Serum VAP-1 at enrollment was measured by time-resolved immunofluorometric assay. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m(2). The subjects were followed until first occurrence of cancer or until December 31, 2011. During a mean follow-up of 11.3 years, 71 subjects developed incident cancers. The HRs for incident cancers in subjects with highest tertile of serum VAP-1 and in subjects with CKD were 2.95 [95% confidence interval (CI), 1.31-6.63; P = 0.009] and 2.29 (95% CI, 1.18-4.44; P = 0.015), respectively, after multivariate adjustment. There was an interaction between serum VAP-1 and CKD on the risk of incident cancers (P = 0.01 for log-transformed VAP-1 × CKD). The relationship among serum VAP-1, CKD, and incident cancers was similar if death was considered in the competing risk models or if subjects with shorter follow-up period were excluded. Higher serum VAP-1 and CKD can independently predict future development of cancers in type II diabetic subjects. Physicians should be aware of the early signs of cancer in diabetic individuals with elevated VAP-1 or renal dysfunction. More aggressive treatment strategies might be considered.


A national survey of implementation of guidelines for gestational diabetes mellitus.
In 2010, national guidelines for the management of gestational diabetes mellitus (GDM) were published by the Health Service Executive (HSE). In 2012, a questionnaire was distributed to all maternity units to survey implementation of the guidelines. All units screened women for GDM, but used different screening tests with fifteen units (79%) using the recommended 75g OGTT, three units (16%) using a 100g OGTT and one unit (5%) using a 50g glucose challenge test. Optimal outcomes are best achieved through multidisciplinary diabetes-obstetric care and this was available in nine of the units (47%). The prevalence of GDM varied from 2.2 - 7.4%. Insulin usage varied from 15-56%. Six centres (31%) had not implemented the national guidelines in full because of lack of resources. Despite national endorsement of the guideline, significant variations remain in implementation. This may lead to differences in clinical outcomes depending on where a woman attends for obstetric care.


Type 1 diabetic drivers with and without a history of recurrent hypoglycemia-related driving mishaps: physiological and performance differences during euglycemia and the induction of hypoglycemia.
Collisions are more common among drivers with type 1 diabetes than among their nondiabetic spouses. This increased risk appears to be attributable to a subgroup of drivers with type 1 diabetes. The hypothesis tested is that this vulnerable subgroup is more at risk for hypoglycemia and its disruptive effects on driving. Thirty-eight drivers with type 1 diabetes, 16 with (+history) and 22 without (-history) a recent history of recurrent hypoglycemia-related driving mishaps, drove a virtual reality driving simulator and watched a videotape of someone driving a simulator for 30-min periods. Driving and video testing occurred in a double-blind, randomized, crossover manner during euglycemia (5.5 mmol/l) and progressive hypoglycemia (3.9-2.5 mmol/l). Examiners were blind to which subjects were +/-history, whereas subjects were blind to their blood glucose levels and targets. During euglycemia, +history participants reported more autonomic and neuroglycopenic symptoms (P≤0.01) and tended to require more dextrose infusion to maintain euglycemia with the same insulin infusion (P<0.09). During progressive hypoglycemia, these subjects demonstrated less epinephrine release (P=0.02) and greater driving impairments (P=0.03). Findings support the speculation that there is a subgroup of type 1 diabetic drivers more vulnerable to experiencing hypoglycemia-related driving mishaps. This increased vulnerability may be due to more symptom "noise" (more symptoms during euglycemia), making it harder to detect hypoglycemia while driving; possibly greater carbohydrate utilization, rendering them more vulnerable to experiencing hypoglycemia; less hormonal counterregulation, leading to more profound hypoglycemia; and more neuroglycopenia, rendering them more vulnerable to impaired driving.


Role of Ramelteon in Reduction of As-Needed Antipsychotics in Elderly Patients with Delirium in a General Hospital Setting.
Abnormalities in melatonin levels have been linked to delirium. This dysregulation may be offset with the use of ramelteon, a melatonin receptor agonist. The purpose of this study was to evaluate the role of ramelteon in decreasing the need for as-needed (PRN) use of antipsychotics in elderly patients with delirium. This was a single-center, retrospective study involving 488 patients who were placed on constant observation and received care by psychiatric service from May 2015 through October 2015. Of these patients, 125 patients were age 65 years or above, had a diagnosis of delirium, and had no standing orders for antipsychotics. These 125 patients were divided into the non-ramelteon group (who received no ramelteon and PRN antipsychotics) and the ramelteon group (who received ramelteon plus PRN antipsychotics). The use of PRN antipsychotics for agitation in each group was recorded. The ramelteon group had a lower incidence of PRN antipsychotic use compared to those not given ramelteon (60 vs. 80%, p value = 0.001). After adjustment for race, age, length of stay, and gender, patients in the non-ramelteon group were more likely to have been given antipsychotics compared to those in the ramelteon group (odds ratio = 4.3, p value = 0.002). Ramelteon use in elderly patients with delirium may be associated with statistically significant reduction of PRN antipsychotic use for agitation.


Relationship between nutritional status and the glomerular filtration rate: results from the MDRD study.
The relationship between the protein-energy nutritional status and renal function was assessed in 1785 clinically stable patients with moderate to advanced chronic renal failure who were evaluated during the baseline phase of the Modification of Diet in Renal Disease Study. Their mean +/- SD glomerular filtration rate (GFR) was 39.8 +/- 21.1 mL/min/1.73 m2. The GFR was determined by 121I-iothalamate clearance and was correlated with dietary and nutritional parameters estimated from diet records, biochemistry measurements, and anthropometry. The following parameters correlated directly with the GFR in both men and women: dietary protein intake estimated from the urea nitrogen appearance, dietary protein and energy intake estimated from dietary diaries, serum albumin, transferrin, percentage body fat, skinfold thickness, and urine creatinine excretion. Serum total cholesterol, actual and relative body weights, body mass index, and arm muscle area also correlated with the GFR in men. The relationships generally persisted after statistically controlling for reported efforts to restrict diets. Compared with patients with GFR > 37 mL/min/1.73 m2, the means of several nutritional parameters were significantly lower for GFR between 21 and 37 mL/min/1.73 m2, and lower still for GFRs under 21 mL/min/1.73 m2. In multivariable regression analyses, the association of GFR with several of the anthropometric and biochemical nutritional parameters was either attenuated or eliminated completely after controlling for protein and energy intakes, which were themselves strongly associated with many of the nutritional parameters. On the other hand, few patients showed evidence for actual protein-energy malnutrition. These cross-sectional findings suggest that in patients with chronic renal disease, dietary protein and energy intakes and serum and anthropometric measures of protein-energy nutritional status progressively decline as the GFR decreases. The reduced protein and energy intakes, as GFR falls, may contribute to the decline in many of the nutritional measures.


Na+-K+ exchanges in canine arterial and venous smooth muscle.
The effect of altering active sodium transport was compared in the denervated canine femoral artery and saphenous vein, which respond differently to a variety of humoral and physical stimuli. Potassium removal and ouabain caused contractions that were larger in the vein than in the artery. Activation of sodium transport, by exposing sodium-loaded preparations to potassium, caused transient ouabain-sensitive relaxations in both blood vessels; depending on the contractile agonist used, this relaxant effect was comparable (BaCl2) in both preparations or was larger (norepinephrine) in the artery than in the vein. In both the artery and the vein, potassium-induced relaxations were larger during contractions evoked by BaCl2 than those caused by norepinephrine. In the vein, contractions caused by acetylcholine were inhibited by potassium to the same extent as those caused by BaCl2. These results 1) are compatible with a contribution of sodium transport mechanism to the control of cell membrane permeability for extracellular calcium in vascular smooth muscle; 2) suggest that active sodium-calcium exchanges are functionally more important in venous than in arterial smooth muscle; and 3) illustrate that the heterogeneous behavior of vascular smooth muscle of different anatomic origins reflects differences in excitation-contraction coupling.


How the use of chlorothalonil on golf courses impacts Paenibacillus sp., a pathogen of Ataenius spretulus (Coleoptera: Scarabaeidae).
One of the most frequently used fungicides on golf courses, chlorothalonil, was applied to field plots at four different golf courses to determine how Ataenius spretulus Haldeman, Aphodius granarius L., carabids, staphylinids, formicids and Paenibacillus sp. were affected. Chlorothalonil had no influence on the incidence of Paenibacillus sp. infection of A. spretulus larvae in golf course fairways. The incidence of Paenibacillus sp. infection of A. spretulus larvae was much greater in the rough (47.4%) compared with the fairway (26.4%) at Cattails Golf Club despite a more dense population (fourfold) of larvae in the fairway. Chlorothalonil treatment of turf plots had no influence on the number of staphylinids, carabids, formicids, or A. spretulus adults caught in pitfall traps. It also did not affect the density of A. spretulus larvae. Data from this study suggest that the widespread use of chlorothalonil on fairways is not likely to cause outbreaks of A. spretulus on golf courses.


Right heart function during simulated altitude in patients with pulmonary arterial hypertension.
Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown. Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion. The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01). Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function.


Kinetics of bipedal locomotion during load carrying in capuchin monkeys.
Facultative bipedalism during load transport in nonhuman primates has been argued to be an important behavior potentially leading to the evolution of obligate, extended limb bipedalism. Understanding the biomechanics of such behavior may lead to insights about associated morphology, which may translate to interpretation of features in the fossil record. Some populations of bearded capuchin monkeys (Sapajus libidinosus) spontaneously carry heavy loads bipedally during foraging activities. This study provides the first data on all three components of ground reaction force for spontaneous bipedalism during load carriage in a nonhuman primate. Five individual S. libidinosus (mean body mass = 2.4 kg ± 0.96) were videorecorded during bipedalism while carrying a stone (0.93 kg) under natural conditions. A force plate was embedded in the path of the monkeys. Spatiotemporal and force data for all three components of the ground reaction force were recorded for 28 steps. Capuchins exhibited a mean vertical peak force per total weight (Vpk) for the hindlimb of 1.19 (sd = 0.13), consistent with those of unloaded capuchins in the laboratory and for other bipedal primates, including humans. Vertical force records suggest that capuchins, along with most nonhuman primates, maintain a relatively compliant leg during both unloaded and loaded locomotion. Like all other primates, loaded capuchins maintained laterally (outward) directed medio-lateral forces, presumably to stabilize side-to-side movements of the center of mass. Medio-lateral forces suggest that at near-running speeds dynamic stability diminishes the need to generate high lateral forces. Vertical force traces exhibited a measurable impact spike at foot contact in 85% of the steps recorded. An impact spike is common in human walking and running but has not been reported in other bipedal primates. This spike in humans is thought to lead to bone and cartilage damage. The earliest biped may have experienced similar impact spikes during bipedal locomotion, requiring compensatory behaviors or anatomical features.


Acquired salpingo-enteric fistula--a case report.
Hysterosalpingogram a common radiological examination is routinely used in the investigation of infertility and sub-fertility in women. The close proximity of the uterus to adjacent pelvic structures results in various types of pelvic fistulas after pelvic disease, pelvic radiation therapy, trauma or pelvic surgery. The case of a 34 years old Para 0(+1) woman with a diagnosis of secondary infertility and booked for hysterosalpingogram as part of the routine work-up is presented. There was a positive history of chronic pelvic inflammatory disease, myomectomy and appendicectomy. The result showed evidence of opacification of the right fallopian tube with contrast outlining the adjacent large bowels.Asymptomatic pelvic fistulas maybe a silent cause of infertility, and association can only be stated as all other factors of infertility could not be convincingly ruled out.


The potential contribution of dietary factors to breast cancer prevention.
Breast cancer (BC), the leading cancer in women, is increasing in prevalence worldwide, concurrent with western metabolic epidemics, that is, obesity, metabolic syndrome, and diabetes, and shares major risk factors with these diseases. The corresponding potential for nutritional contributions toward BC prevention is reviewed and related to critical stages in the life cycle and their implications for carcinogenic and pathometabolic trajectories. BC initiation potentially involves diet-related pro-oxidative, inflammatory, and procarcinogenic processes, that interact through combined lipid/fatty acid peroxidation, estrogen metabolism, and related DNA-adduct/depurination/mutation formation. The pathometabolic trajectory is affected by high estrogen, insulin, and growth factor cascades and resultant accelerated proliferation/progression. Anthropometric risk factors - high birth weight, adult tallness, adiposity/BMI, and weight gain - are often reflective of these trends. A sex-based nutritional approach targets women's specific risk in western obesogenic environments, associated with increasing fatness, estrogen metabolism, n-6 : n-3 polyunsaturated fatty acid ratio, and n-6 polyunsaturated fatty acid conversion to proinflammatory/carcinogenic eicosanoids, and effects of timing of life events, for example, ages at menarche, full-term pregnancy, and menopause. Recent large-scale studies have confirmed the effectiveness of the evidence-based recommendations against BC risk, emphasizing low-energy density diets, highly nutritious plant-based regimes, physical activity, and body/abdominal adiposity management. Better understanding of dietary inter-relationships with BC, as applied to food intake, selection, combination, and processing/preparation, and recommended patterns, for example, Mediterranean, DASH, plant-based, low energy density, and low glycemic load, with high nutrient/phytonutrient density, would increase public motivation and authoritative support for early/timely prevention, optimally merging with other dietary/health goals, for lifelong BC prevention.


Enzymes--a review.
Enzymes are essential to life and catalyze various metabolic activities. They find application in a number of diseased conditions, and their scope is being widened as knowledge develops.


Rocks from the mantle transition zone: majorite-bearing xenoliths from malaita, southwest pacific
Rocks containing high-pressure mineral assemblages derived from the mantle transition zone between depths of about 400 and 670 kilometers occur as xenoliths and megacrysts on the island of Malaita in the southwest Pacific on the Ontong Java Plateau. Observed ultrahigh pressure mineral chemistries include majorite, calcium- and magnesium-perovskite, aluminous silicate phases, and microdiamond. Based on an empirical barometer, majoritic garnets in these xenoliths record pressures of up to 22 gigapascal. The occurrence of material with perovskite chemistry and several enigmatic aluminous phases indicates pressures of up to 27 gigapascal. Samples were brought to the surface at about 34 million years ago by potassic ultramafic magmas, which evidently originated in the lower mantle.


Paravalvular Regurgitation after Transcatheter Aortic Valve Replacement: Comparing Transthoracic versus Transesophageal Echocardiographic Guidance.
Transcatheter aortic valve replacement (TAVR) is increasingly being performed in cardiac catheterization laboratories using transthoracic echocardiography (TTE) to guide valve deployment. The risk of paravalvular regurgitation (PVR) remains a concern. We retrospectively reviewed 454 consecutive patients (mean age, 82 ± 8; 58% male) who underwent transfemoral TAVR at Emory Healthcare from 2007 to 2014. Two hundred thirty-four patients underwent TAVR in the cardiac catheterization laboratory with TTE guidance (TTE-TAVR; mean Society of Thoracic Surgeons score, 10%), while 220 patients underwent the procedure in the hybrid operating room with transesophageal echocardiography (TEE) guidance (TEE-TAVR; mean Society of Thoracic Surgeons score, 11%). All patients received an Edwards valve (SAPIEN 55%, SAPIEN-XT 45%). Clinical and procedural characteristics, echocardiographic parameters, and incidence of PVR were compared. The incidence of at least mild PVR at discharge was comparable between TTE-TAVR and TEE-TAVR (33% vs 38%, respectively; P = .326) and did not differ when stratified by valve type. However, in the TTE-TAVR group, there was a higher incidence of second valve implantation (7% vs 2%; P = .026) and postdilation (38% vs 17%; P < .001) during the procedure. Although not independently associated with PVR at discharge (odds ratio = 1.12; 95% CI, 0.69-1.79), TTE-TAVR was associated with PVR-related events: the combined outcome of mild PVR at discharge, intraprocedural postdilation, and second valve insertion (odds ratio = 1.58; 95% CI, 1.01-2.46). There were no significant differences in PVR at 30 days, 6 months, and 1 year between the two groups. TTE-TAVR in a high-risk group of patients was associated with increased incidence of intraprocedure PVR-related events, although it was not associated with higher rates of PVR at follow-up. Multicenter randomized trials are required to confirm the cost-effectiveness and safety of TTE-TAVR.


Arabidopsis Novel Glycine-Rich Plasma Membrane PSS1 Protein Enhances Disease Resistance in Transgenic Soybean Plants.
Nonhost resistance is defined as the immunity of a plant species to all nonadapted pathogen species. Arabidopsis (Arabidopsis thaliana) ecotype Columbia-0 is nonhost to the oomycete plant pathogen Phytophthora sojae and the fungal plant pathogen Fusarium virguliforme that are pathogenic to soybean (Glycine max). Previously, we reported generating the pss1 mutation in the pen1-1 genetic background as well as genetic mapping and characterization of the Arabidopsis nonhost resistance Phytophthora sojae-susceptible gene locus, PSS1 In this study, we identified six candidate PSS1 genes by comparing single-nucleotide polymorphisms of (1) the bulked DNA sample of seven F2:3 families homozygous for the pss1 allele and (2) the pen1-1 mutant with Columbia-0. Analyses of T-DNA insertion mutants for each of these candidate PSS1 genes identified the At3g59640 gene encoding a glycine-rich protein as the putative PSS1 gene. Later, complementation analysis confirmed the identity of At3g59640 as the PSS1 gene. PSS1 is induced following P. sojae infection as well as expressed in an organ-specific manner. Coexpression analysis of the available transcriptomic data followed by reverse transcriptase-polymerase chain reaction suggested that PSS1 is coregulated with ATG8a (At4g21980), a core gene in autophagy. PSS1 contains a predicted single membrane-spanning domain. Subcellular localization study indicated that it is an integral plasma membrane protein. Sequence analysis suggested that soybean is unlikely to contain a PSS1-like defense function. Following the introduction of PSS1 into the soybean cultivar Williams 82, the transgenic plants exhibited enhanced resistance to F. virguliforme, the pathogen that causes sudden death syndrome.


The cost and cost implications of implementing the integrated chronic disease management model in South Africa.
A cost analysis of implementation of interventions informs budgeting and economic evaluations. To estimate the cost of implementing the integrated chronic disease management (ICDM) model in primary healthcare (PHC) clinics in South Africa. Cost data from the provider's perspective were collected in 2019 from four PHC clinics with comparable patient caseloads (except for one). We estimated the costs of implementing the ICDM model current activities for three (facility reorganization, clinical supportive management and assisted self-management) components and additional costs of implementing with enhanced fidelity. Costs were estimated based on budget reviews, interviews with management teams, and other published data. The standard of care activities such as medication were not included in the costing. One-way sensitivity analyses were carried out for key parameters by varying patient caseloads, required infrastructure and staff. Annual ICDM model implementation costs per PHC clinic and per patient per visit are presented in 2019 US dollars. The overall mean annual cost of implementing the ICDM model was $148 446.00 (SD: $65 125.00) per clinic. Current ICDM model activities cost accounted for 84% ($124 345.00) of the annual mean cost, while additional costs for higher fidelity were 16% ($24 102.00). The mean cost per patient per visit was $6.00 (SD:$0.77); $4.94 (SD:0.70) for current cost and $1.06 (SD:0.33) for additional cost to enhance ICDM model fidelity. For the additional cost, 49% was for facility reorganization, 31% for adherence clubs and 20% for training of nursing staff. In the sensitivity analyses, the major cost drivers were the proportion of effort of assisted self-management staff and the number of patients with chronic diseases receiving care at the clinic. Minimal additional cost are required to implement the ICDM model with higher fidelity. Further research on the cost-effectiveness of the ICDM model in middle-income countries is required.


Enhancing a geriatric emergency department care coordination intervention using automated health information exchange-based clinical event notifications.
In a health care system where patients often have numerous providers and multiple chronic medical conditions, interoperability of health information technology (HIT) is of paramount importance. Regional health information organizations (RHIO) often provide a health information exchange (HIE) as a solution, which gives stakeholders access to clinical data that they otherwise would not otherwise have. A secondary use of preexisting HIE infrastructure is clinical event notification (CEN) services, which send automated notifications to stakeholders. This paper describes the development and implementation of a CEN service enabled by a RHIO in the New York metropolitan area to improve care coordination for patients enrolled in a geriatric emergency department care coordination program. This operational CEN system incorporates several innovations that to our knowledge have not been implemented previously. They include the near real-time notifications and the delivery of notifications via multiple pathways: electronic health record (EHR) "in-baskets," email, text message to internet protocol-based "zone" phones, and automated encounter entry into the EHR. Based on these alerts the geriatric care coordination team contacts the facility where the patient is being seen and offers additional information or assistance with disposition planning with the goal of decreasing potentially avoidable admissions and duplicate testing. During the nearly one-year study period, the CEN program enrolled 5722 patients and sent 497 unique notifications regarding 206 patients. Of these notifications, 219 (44%) were for emergency department (ED) visits; 121 (55%) of those notifications were received during normal business hours when the care coordination team was available to contact the ED where the patient was receiving care. Hospital admissions resulted from 45% of ED visits 17.8% of these admissions lasted 48 hours or less, suggesting some might potentially be avoidable. This study demonstrates the potential of CEN systems to improve care coordination by notifying providers of the occurrence of specific events. Although it could not directly be demonstrated here, we believe that widespread use of CEN systems have potential to reduce potentially avoidable admissions and duplicate testing, likely leading to decreased costs.


Comorbidity of Adult Attention Deficit and Hyperactivity Disorder in Bipolar and Unipolar Patients.
The co-occurrence of attention deficit hyperactivity disorder (ADHD) in affective disorder patients is considerably high. The aims of the present study were to search for the frequency and impact of ADHD co-occurrence on the clinical features of affective disorders and to examine the relationship between the dominant affective temperaments and ADHD. In total, 100 patients with bipolar disorder (BD), 100 patients with major depressive disorder (MDD), and 100 healthy controls (HC) were included. All diagnoses were assigned according to DSM-IV-TR criteria. The Adult Attention Deficit and Hyperactivity Self-Report Scale (ASRS); Wender Utah Rating Scale (WURS); and Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) were applied to all participants. The percentage of BD patients meeting the criteria for a diagnosis of current ADHD was 48% compared with the percentage of MDD patients and HCC subjects, i.e., 25% and 12%, respectively. ADHD was significantly more frequent in bipolar adults than in not only HC but also depressive patients. In the BD group, patients with a comorbid ADHD diagnosis had significantly more suicidal history than those without ADHD. The scores of the temperament traits, namely depressive, cyclothymic, irritable, and anxious, were significantly higher in subjects with ADHD in all groups, including in HC. The most important findings of the present study were the observations that (1) the frequency of ADHD is considerably high among bipolar patients; (2) the frequency of suicide attempts is high in the bipolar patient group with comorbid ADHD; and (3) depressive, cyclothymic, irritable, and anxious temperaments are significantly associated with ADHD comorbidity in bipolar and depressive patients as well as in HC. The high comorbidity and chronic course of ADHD and its possible negative influence on the course of both disorders increase the importance of screening for adult ADHD.


Fluid surface tension evaluation using capillary wave measurement with optical coherence tomography.
The surface tension of biological fluids is an important parameter because the mechanical properties of fluids are closely linked with hematological diseases and other pathophysiologies. Capillary waves are associated with fluid mechanical properties. Here, we propose a method that utilizes the acoustic radiation force (ARF) to generate propagating waves and optical coherence tomography (OCT) to measure the wave motion. This ARF-OCT method is capable of evaluating the surface tension of fluids, water and porcine whole blood in this study, based on the dispersion relation of capillary waves. Two-dimensional Fourier transforms were used to decompose frequency components of wave motion images to obtain a k-space representation and estimate the wave phase velocity. The phase velocity of capillary waves was obtained from the experimental results and compared to theoretical calculations. The surface tensions of water and porcine whole blood were determined from the experimental results. We first report that capillary waves measured with OCT can be a new promising modality for measuring the surface tension of fluids. The proposed method could be used to differentiate actual pathologic fluids or blood from those taken from healthy subjects and as a biomarker in future biomedical applications.


Activation of cyclic AMP signaling pathway in dopaminergic neurons rescues locomotion defects in a Drosophila larval model of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease showing uncontrollable motor symptoms that are primarily caused by the progressive loss of dopaminergic neurons in the brain. Currently no treatment exists to prevent PD progression. Therefore, discovery of new neuroprotective strategies still has great potential to benefit PD patients. A handful of studies show that activation of cAMP pathways is neuroprotective against PD progression. However, the neuroprotective role of this signaling cascade specifically in DA neurons has not been explored. In this study, fruit fly Drosophila melanogaster was used because of its sophisticated and powerful genetic approaches, especially with related to cAMP signaling pathway. We have investigated molecular mechanisms of neuroprotection in a fly larval model of PD by administering an environmental PD toxin rotenone. Increased cAMP signaling in the dunce mutant fly carrying defects in phosphodiesterase (PDE) gene, is neuroprotective against rotenone-induced locomotion deficits. Furthermore, the neuroprotective role of cAMP signaling specifically in DA neurons has been studied as it has not been explored. By using transgenic flies expressing designer receptors exclusively activated by designer drugs (DREADDs), we have shown that an increase of cAMP levels in DA neurons rescues rotenone-induced locomotion deficits. We also showed that this neuroprotection is mediated by activation of Gαs and PKA-C1 subunits. The results provide novel findings that expand our knowledge of neuroprotective mechanisms in DA neurons affecting PD progression, which could contribute to the development of new therapeutic treatments against PD. An important future study will explore downstream targets of cAMP-PKA signaling.


Tumour necrosis factor-alpha blockade: a new era for effective management of rheumatoid arthritis.
Tumour necrosis factor (TNF)-alpha inhibitors have emerged as a new treatment option for rheumatoid arthritis (RA). The scientific rationale for targeting TNF-alpha in RA derives from extensive work in the laboratory, showing the importance of this pro-inflammatory cytokine as a mediator of joint inflammation. Proof of principle has now been firmly established in clinical trials where TNF-alpha inhibitors have been shown to decrease the signs and symptoms of joint inflammation and slow radiological progression of joint damage. Presently, the two TNF-alpha inhibitors available for use in RA are etanercept and infliximab. Etanercept is a soluble TNF receptor: Fc fusion protein that competes with the endogenous TNF receptors for TNF-alpha binding. Infliximab is a chimeric anti-TNF-alpha monoclonal antibody, which also binds with high affinity to soluble TNF-alpha. Etanercept and infliximab will be rapidly incorporated into current treatment paradigms, which call for early and intensive treatment of RA using disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, sulfasalazine and hydroxychloroquine. A major drawback to the widespread use of these biologics is their high costs. Some patients with limited financial means may be denied access to these effective anti-inflammatory agents. Moreover, long-term experience with TNF-alpha inhibitor therapy has been limited and concerns linger about the possibility that etanercept and infliximab may cause unforeseen side effects or increase the risk for opportunistic infection. Despite these caveats, TNF-alpha inhibitors represent a major advance for the treatment of RA and will likely spawn new indications for anti-TNF-alpha therapy and the development of novel therapeutic compounds with similar biological activity.


Amino acid, carbohydrate, and fat composition of soybean meals prepared at 55 commercial U.S. soybean processing plants.
To quantify variation in U.S. soybean meals (SBM), samples were collected from 55 U.S. soybean (SB) processing plants located in seven of the geographic SB maturity zones at three time points. These samples were analyzed for crude and acid-hydrolyzed fat, oligosaccharide, and amino acid concentrations. Acid-hydrolyzed fat concentrations were poorly correlated (r = 0.28) to crude fat concentrations and were higher for SBM prepared in the southern zones (V-VII) as compared with the northern zones (I and II). Raffinose and verbascose concentrations were lowest (P < 0.05) for SBM prepared in northern maturity zones, while stachyose concentrations were highest for SBM prepared in central maturity zones (III and IV). Total essential, total nonessential, and total amino acid concentrations were lowest for SBM prepared in northern zones. There was variation in oligosaccharide and amino acid concentrations over time, probably due to variation in composition of SB arriving at the plants within maturity zone.


Abstract grammatical processing of nouns and verbs in Broca's area: evidence from fMRI.
The role of Broca's area in grammatical computation is unclear, because syntactic processing is often confounded with working memory, articulation, or semantic selection. Morphological processing potentially circumvents these problems. Using event-related functional magnetic resonance imaging (fMRI), we had 18 subjects silently inflect words or read them verbatim. Subtracting the activity pattern for reading from that for inflection, which indexes processes involved in inflection (holding constant lexical processing and articulatory planning) highlighted left Brodmann area (BA) 44/45 (Broca's area), BA 47, anterior insula, and medial supplementary motor area. Subtracting activity during zero inflection (the hawk; they walk) from that during overt inflection (the hawks; they walked), which highlights manipulation of phonological content, implicated subsets of the regions engaged by inflection as a whole. Subtracting activity during verbatim reading from activity during zero inflection (which highlights the manipulation of inflectional features) implicated distinct regions of BA 44, 47, and a premotor region (thereby tying these regions to grammatical features), but failed to implicate the insula or BA 45 (thereby tying these to articulation). These patterns were largely similar in nouns and verbs and in regular and irregular forms, suggesting these regions implement inflectional features cutting across word classes. Greater activity was observed for irregular than regular verbs in the anterior cingulate and supplementary motor area (SMA), possibly reflecting the blocking of regular or competing irregular candidates. The results confirm a role for Broca's area in abstract grammatical processing, and are interpreted in terms of a network of regions in left prefrontal cortex (PFC) that are recruited for processing abstract morphosyntactic features and overt morphophonological content.


Detection and significance of glutathione-S-transferase pi in osteogenic tumors of dogs.
In this study we describe a relationship between the percentage of tumor cells staining positive for GST pi and the response to cisplatin treatment in dogs with appendicular osteosarcoma. Clinical resistance to platinum compounds has been attributed to tumor cell resistance to the drug. An overexpression of glutathione-S-transferase pi has been implicated in the resistance of tumor cells in vitro to cisplatin. In this study, the relative concentration of GST pi was quantified immunohistochemically in formalin-fixed, paraffin-embedded histologic specimens obtained from dogs with appendicular osteosarcoma prior to cisplatin treatment. The percentage of tumor cells staining positive for GST pi was compared with patient response (remission and survival times) following treatment. Those osteosarcoma-bearing dogs having a low pre-treatment tumor expression of GST pi (<50%; n=13) had a significantly longer (p <0.01) median remission and survival time (24.0 and 33.7 weeks, respectively) than those dogs with a high pre-treatment tumor expression of GST pi (>50%; n=8; median remission and survival times 14.2 and 24.0 weeks, respectively). The relative staining of GST pi in primary canine bone tumors has therapeutic importance and warrants further evaluation as a therapeutic model for human osteosarcoma.


Activated microglia in nociception.
Microglial cells appear to play a vital role in the initiation of certain neuropathic pain states. In order to initiate neuropathic pain, microglia need to be activated. Microglia activation in the spinal cord involves both hypertrophy as well as hyperplasia, progressing through a hypertrophic morphology, with thickened and retracted processes (observed within the first 24 hours after nerve injury), and an increase in cell number (observed around 2-3 days after nerve injury). There seems to be at least 5 major paths to activate microglia. These 5 pathways will be discussed and are identified by their main signaling mediator and/or receptor which include fractalkine, interferon-gamma, monocyte chemoattractant protein-1, TLR4, and P2X4. Thus, one or more of these mediators/pathways which lead to microglial activation might contribute to neuropathic pain. A greater appreciation of the roles of various mediators/paths which activate microglia might help lead to future novel therapeutic targets in efforts to ameliorate severe symptoms of neuropathic pain.


Effects of some drugs on ripening of uterine cervix in nonpregnant castrated and pregnant rats.
The stimulating effect of some drugs on the ripening of the uterine cervix in rats was studied by measuring the wet weight of the uterine cervix and by both light and electron microscopy in nonpregnant castrated and pregnant conditions. Since the light and electron microscopic findings after estrogen (E) administration to castrated rats were similar to those found in the uterine cervix of rats at the end of pregnancy, it was concluded that E (E2 greater than or equal to E3 greater than or equal to E1) plays a major role in the ripening mechanism. It was also found that DHA-S, progesterone and relaxin had stimulating effects on cervical ripening. Oxytocin and PG (PGE2 greater than PGF2 alpha) showed the ripening activity only in pregnant condition. Moreover, oxytocin, PGE2 and PGF2 alpha potentiated the estrogen action. The effects on the increase in wet weight of the uterine cervix and microscopic findings due to DHA-S were different from E in castrated rats. It is therefore postulated that the effect of DHA-S might be mainly due to the secondary increase in E converted from DHA-S in the ovary and, in addition, to a direct effect of this medicament on the uterine cervix. There was essentially no difference in ultrastructure between the cervix of control (nonpregnant, castrated or pregnant) rats and that of rats treated with HCG, isoxsuprine hydrochloride, dihydroergotoxine, diazepam or n-butylscopolammonium bromide.


Studies of erythroblast function in congenital dyserythropoietic anaemia, type I: evidence of impaired DNA, RNA, and protein synthesis and unbalanced globin chain synthesis in ultrastructurally abnormal cells.
Two patients with congenital dyserythropoietic anaemia, type I (CDA) were studied. Their blood reticulocytes showed unbalanced globin chain synthesis with increased alpha:beta globin chain synthesis ratios. A high proportion of the erythroblasts displayed the characteristic "Swiss cheese" abnormality of the nuclear chromatin and some also showed cytoplasmic intrusions lined with nuclear membrane within the nucleus. Occasional erythroblast profiles contained intracytoplasmic inclusions that were ultrastructurally indistinguishable from precipitated alpha chains. The technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography showed gross abnormalities of proliferation in the early polychromatic erythroblasts. The proliferative abnormalities included an arrest of DNA synthesis after the progress of cells through part of the S phase and the formation of several mononucleate and binucleate cells with hypertetraploid total DNA contents. The bone marrow cells gave a normal deoxyuridine suppressed value, indicating that there was no impairment of the methylation of deoxyuridylate. Electron microscope autoradiographic studies showed that a high proportion of the erythroblasts with the "Swiss cheese" nuclear abnormality suffered from a severe impairment, or arrest of DNA, RNA, and protein synthesis.


An objective structured clinical examination for evaluating psychiatric clinical clerks.
To assess the feasibility, reliability, and validity of an objective structured clinical examination (OSCE) for psychiatric clinical clerks. In 1995 two parallel forms of a ten-station OSCE (eight clinical stations, two writing stations) were developed at the University of Toronto Faculty of Medicine Each 12-minute performance-based clinical station was assessed by a faculty psychiatrist using both a checklist for each student's performance content and a global-rating scale of the performance process. The students' clinical-station scores were calculated as the average of their content and process scores (expressed as percentages). Examiners also recorded an overall judgment of each students' performance (pass, borderline, or fail) and wrote [in collaboration with the standardized patient (SP) at that station] comments on each student's performance. There were two criteria for a passing grade: a total mark of 60% or higher across all ten stations and a "pass" or "borderline" mark in at least five of the eight clinical stations. Each OSCE form was administered three times. The first form was used to examine 94 clerks, the second form to examine 98 clerks. The students' mean scores for the two forms were 70.47% (SD, 6.33%) and 67.66% (SD, 7.05%), respectively. In addition to the standard evaluation information collected on the students, several critical incidents occurred (e.g., a student's loss of control of emotions) that may identify potential problems in professional conduct. The direct cost for one administration of the examination was approximately Can$3,300: the largest portion of this was for the SPs' time spent in training and performing their roles. Preliminary evidence suggests that a psychiatry OSCE is feasible for assessing complex psychiatric skills. However, careful attention must be paid to SP training, examination monitoring, detection of critical incidents, and provision of feedback to students, faculty, and SPs. The university's previous system of oral examinations required approximately 600 faculty hours per year. The OSCE requires approximately 450 faculty hours, and the 150 hours saved almost cover the Can$20,000 that the examination costs each year. In all, the OSCE is an evaluation system that has demonstrable reliability and is more enjoyable for both the faculty and the students.


Influence of various air-abrasive powders on the viability and density of periodontal cells: An in vitro study.
Remnants of air-abrasive powders on treated surfaces and tissues may affect tissue healing. The purpose of this in vitro study was to investigate the possible effect of five commercially available air-abrasive powders on the viability and cell density of three types of periodontal cells. A sodium bicarbonate powder, two amino acid glycine powders, an amino acid glycine and tricalcium phosphate powder and an erythritol powder were tested. Suspensions of these powders in three different concentrations were prepared and incubated with gingival epithelial cells, gingival fibroblasts, and periodontal ligament (PDL) fibroblasts for 6 hours. Mitochondrial activity, as a measure for cell viability, was evaluated by means of fluorescence activity of a redox indicator. Amount of DNA was measured as indication of cell density. All powders affected in different degrees cell viability and/or density. The most pronounced adverse effect was observed with the sodium bicarbonate followed by the erythritol-containing powder and at the highest concentration. A fivefold reduction or more in the number of cells was observed. The tricalcium phosphate containing powder had the least effect on all types of cells. Even, increased numbers of epithelial cells (twofold) were observed. Within the limits of the present study, it was concluded that careful selection of the powder is important to improve the clinical outcomes of air powder abrasive treatment. A tricalcium phosphate containing powder may improve the biologic responses. A sodium bicarbonate powder should be used with caution. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1955-1963, 2018.


Multiple lingual cusps trait on mandibular premolars and hypoconulid reduction trait on mandibular first molar in living Jordanian population. Intra- and inter-trait interactions.
The objective was to determine the expression and fluctuating asymmetry of two dental morphological traits in the living Jordanians: The lingual cusp number on the lower premolars (LP1 and LP2) and the hypoconulid (distal cusp) reduction on the lower first molar (LM1). In addition, both intra- trait and inter- trait interactions were analyzed. Three hundred school children (15.5 +/- 0.4 years) were involved. Impressions for the mandibular dental arches were taken, and dental casts were reproduced. The above-mentioned traits were observed. Paired sample t test and nonparametric correlation analysis were used for data analysis. Three-cusped LP1 was found in 11.40 % of the examined students, while the two-cusped LP1 was found in 88.60%. In comparison, the Three-cusped LP2 was found in 61.40% while the two-cusped LP2 was found in 38.60% of the observed subjects. The frequencies of the 4-cusped and 5-cusped LM1 were found to be 8.65% and 91.35%, respectively. Nonparametric correlation analysis revealed positive and statistically significant association between the expression of two lingual cusps on LP1 and on LP2 in both genders (p < 0.01), while there was no significant correlation between expression of two lingual cusps on either LP1 or LP2 and the hypoconulid loss on LM1 in both genders (p > 0.05). Bilateralism was highly significant in the tested traits in both genders (p < 0.001). This finding might be a sign of relatively low environmental stresses experienced by the living Jordanians and/or great ability of its individuals to buffer the adverse effects of such stresses on dental development. This study is a useful addition to the existing literature in that it examines a previously poorly characterized population and assists in placing the contemporary Jordanian population within the current framework of human population groups globally.


Enrollment in early head start and oral health-related quality of life.
Dental problems in young children are widespread and can negatively impact quality of life. We examined the effect of enrollment in North Carolina Early Head Start (EHS)-a federally funded early education program for children under three years of age and their families-on oral health-related quality of life (OHRQoL). In this quasi-experimental study, we interviewed 479 EHS and 699 Medicaid matched parent-child dyads at baseline (children's average age 10 months) and 24 months later. Parents reported OHRQoL using the Early Childhood Oral Health Impact Scale (ECOHIS), a 0-52 point scale with higher scores representing more negative impacts. We used a marginalized semicontinuous two-part model to estimate: (1) the effect of EHS on the probability of reporting any follow-up impacts (ECOHIS ≥ 1), and (2) the difference in overall mean ECOHIS follow-up scores. We controlled for baseline ECOHIS, language, and EHS and non-EHS group imbalances using a propensity score. At follow-up, negative OHRQoL impacts were more often reported by parents of non-EHS than EHS children (45 versus 37%, P < .01). In the adjusted model, EHS parents reported a lower odds of negative OHRQoL impacts (OR 0.70; 95% CI 0.52, 0.94). Mean adjusted ECOHIS scores were not significantly different (EHS: 1.59 ± 3.34 versus non-EHS: 2.11 ± 3.85, P > 0.05). This study is the first to demonstrate that families of young children enrolled in EHS report improved OHRQoL compared to their non-enrolled peers. These results highlight the potential effectiveness of improving the quality of life of low-resource families through early childhood education.


Principles and practice of conjoint psychoanalytic treatment.
The authors describes the advantages of conjoint analytic treatment, which occurs when two or more analysts treat a patient in different settings: one provides the one-to-one relationship, and the other leads the group experience. The goal of this treatment is to increase the therapeutic possibilities for the patient. The advantages come from the use of multiple settings, transferences, observers, interpreters, and maturational agents. The author illustrates the advantages of the treatment with several case reports. He also points out the value of conjoint treatment for the analysts involved.


Doubting what you already know: Uncertainty regarding state transitions is associated with obsessive compulsive symptoms.
Obsessive compulsive (OC) symptoms involve excessive information gathering (e.g., checking, reassurance-seeking), and uncertainty about possible, often catastrophic, future events. Here we propose that these phenomena are the result of excessive uncertainty regarding state transitions (transition uncertainty): a computational impairment in Bayesian inference leading to a reduced ability to use the past to predict the present and future, and to oversensitivity to feedback (i.e. prediction errors). Using a computational model of Bayesian learning under uncertainty in a reversal learning task, we investigate the relationship between OC symptoms and transition uncertainty. Individuals high and low in OC symptoms performed a task in which they had to detect shifts (i.e. transitions) in cue-outcome contingencies. Modeling subjects' choices was used to estimate each individual participant's transition uncertainty and associated responses to feedback. We examined both an optimal observer model and an approximate Bayesian model in which participants were assumed to attend (and learn about) only one of several cues on each trial. Results suggested the participants were more likely to distribute attention across cues, in accordance with the optimal observer model. As hypothesized, participants with higher OC symptoms exhibited increased transition uncertainty, as well as a pattern of behavior potentially indicative of a difficulty in relying on learned contingencies, with no evidence for perseverative behavior. Increased transition uncertainty compromised these individuals' ability to predict ensuing feedback, rendering them more surprised by expected outcomes. However, no evidence for excessive belief updating was found. These results highlight a potential computational basis for OC symptoms and obsessive compulsive disorder (OCD). The fact the OC symptoms predicted a decreased reliance on the past rather than perseveration challenges preconceptions of OCD as a disorder of inflexibility. Our results have implications for the understanding of the neurocognitive processes leading to excessive uncertainty and distrust of past experiences in OCD.


Characterisation of two serine protease inhibitors expressed in the pituitary gland.
Serine protease inhibitors (serpins) are a family of structurally related proteins that play key roles in the regulation of proteolytic homeostasis. We have isolated a novel intracellular serpin, termed raPIT5a, from the rat pituitary gland. Northern blot analysis indicated raPIT5a mRNA expression in a range of tissues, including the adrenal gland and the brain. In situ hybridisation histochemistry revealed raPIT5a mRNA expression in specific cell populations in the rat pituitary gland, adrenal gland, and pancreas. Based on sequence similarities to other intracellular serpins, we predicted raPIT5a may inhibit the pro-apoptotic serine protease granzyme B. We confirmed this experimentally by identification of a stable inhibitory complex between granzyme B and raPIT5a. To determine whether granzyme B or granzyme B-related enzymes were expressed in the rat pituitary gland, we performed PCR using primers predicted to amplify granzyme B and two other published granzyme sequences. We identified rat natural killer protease-1 (RNKP-1), the rat homologue of granzyme B, and a novel putative serine protease highly similar to granzyme-like protein III (GLP III), which we termed GLP IIIa. These data suggest raPIT5a may regulate apoptosis in the pituitary by inhibition of granzyme B or GLP IIIa, or members of the caspase enzyme family which have similar substrate specificity. We have also identified expression of a second serpin, called neuroserpin, in pituitary tissue and found that it alters the morphology of the AtT20 corticotrope cell line, presumably through changes in cell adhesion. These results identify new roles for serpins in pituitary cell function.


Analysis of miRNA-199-5p expression levels in serum samples of patients with lumbar disc degeneration.
Lumbar disc degeneration is a condition caused by damage to the disc due to various causes, which results in disc material coming out of the disc space. MicroRNAs are small, non-coding RNAs that play a role in the regulation of gene expression by binding to mRNA. MiRNA-199 has previously been studied in the context of intervertebral disc degeneration, and its role in the disease has been reported. The purpose of this study was to look into the role of miRNA 199 in Lumbar Disc Degeneration. This study included 26 patients with Lumbar Disc Degeneration who were admitted to the Neurosurgery Clinic at Yeditepe University Hospital and 26 completely healthy volunteer controls. After isolating microRNA from control and patient sera, was converted into cDNA, concentration measurements were taken, and PCR was used to analyze miRNA-199 expression. miRNA-199-5p expression levels were found to be statistically significantly higher in patients than in controls (P = 0.024). miRNA-199-5p Delta CT levels were also evaluated by ROC analysis (p = 0.014). miRNA-199-5p may be a candidate for a biomarker believed to play a role in disease prognosis in patients with Lumbar Disc Degeneration.


A study of 185 foster children 5 years after placement.
This study's findings are similar to those of other studies. The majority of children who enter foster care return to their families within a relatively short time. A small group, because of the severity of their problems or those of their parents, need extended care. This group of children, over time, form the hard core of foster care placements. Our findings also bear out those of others that the foster care experience is a relatively stable one for children, with the majority having one or two placements while in care. Clearly, the need for and use of foster care is frequently misunderstood. The methodology used in research studies has gradually improved, adding to objective knowledge about this aspect of the child welfare system. Longitudinal studies, such as Jenkins [1967], Fanshel and Shinn [1978], and the one reported here, point to the need for deeper, more refined studies that examine not only the going and coming of children in foster care but the professional service component that can make foster care a constructive experience for children placed in it. Meyer issued an intelligent and timely challenge to the field of child welfare to give up "debates about permanency" and, if it is not too late, to "retrieve child welfare from the control of lawyers and MBAs" [1984: 499]. If the profession of social work can more clearly define the components of foster care service and can differentiate among the children needing care those who can best be served by this type of placement, then the field will be well on its way to offering an appropriate service for certain children. Attempts to denigrate a potentially helpful service for needy children simply destroy one aspect of a complex system. A wide range of services is necessary to serve all children appropriately. Without this kind of continuum, children are more likely to receive inappropriate services and to be placed at risk.


Balloon assisted, ultrasound guided percutaneous thrombin injection of a large radial artery pseudoaneurysm using a trans-venous approach via an Ipsilateral Arteriovenous Fistula.
Pseudoaneurysm formation is known to complicate arteriovenous haemodialysis access. Ultrasound guided thrombin injection is a recognised treatment option, but is not possible in pseudoaneurysms with no measurable neck. Balloon assisted techniques have been described in such cases, which transiently obstruct flow out of the pseudoaneurysm and thereby prevent non-target embolization during ultrasound guided percutaneous thrombin injection. We describe a balloon assisted technique for the treatment of a radial artery pseudoaneurysm, via retrograde access from the draining cephalic vein of an arteriovenous fistula. A 61-year-old male with a radio-cephalic fistula was found on duplex ultrasound to have a large radial artery pseudoaneurysm with no measurable neck, as well as a juxta-anastomotic cephalic vein stenosis. Endovascular treatment was selected over open surgery. Retrograde cephalic venous access was established, which allowed for concurrent treatment of both the venous stenosis and the arterial pseudoaneurysm. After balloon dilation of the juxta-anastomotic stenosis, a percutaneous transluminal angioplasty balloon catheter was advanced across the arteriovenous anastomosis and inflated across the neck of the radial artery pseudoaneurysm, to transiently obstruct blood flow. This allowed for safe injection of thrombin into the pseudoaneurysm by direct ultrasound guided sac puncture; thereby achieving thrombosis. Balloon assisted ultrasound guided thrombin injection is an endovascular treatment option that can obviate the need for open surgery in cases involving pseudoaneurysms with no measurable neck. The technique described allowed both concurrent treatment of a juxta-anastomotic venous stenosis and treatment of an arterial pseudoaneurysm from a single venous puncture. This technique avoided arterial access and its inherent complications.


Second-order spectral lineshapes from charged interfaces.
Second-order nonlinear spectroscopy has proven to be a powerful tool in elucidating key chemical and structural characteristics at a variety of interfaces. However, the presence of interfacial potentials may lead to complications regarding the interpretation of second harmonic and vibrational sum frequency generation responses from charged interfaces due to mixing of absorptive and dispersive contributions. Here, we examine by means of mathematical modeling how this interaction influences second-order spectral lineshapes. We discuss our findings in the context of reported nonlinear optical spectra obtained from charged water/air and solid/liquid interfaces and demonstrate the importance of accounting for the interfacial potential-dependent χ (3) term in interpreting lineshapes when seeking molecular information from charged interfaces using second-order spectroscopy.


Detection of pET-vector encoded, recombinant S-tagged proteins using the monoclonal antibody ATOM-2.
The 15-meric S-tag is a truncated form of the S-peptide, which builds together with the 103 amino acid large S-protein the whole ribonuclease S-protein. Its small size and excessive solubility have made the S-tag an excellent fusion partner in the production of recombinant proteins, and a large variety of applications have been reported using the S-tag as a carrier. While S-tagged proteins were mostly detected and analyzed so far by use of their affinity to S-proteins, monoclonal antibodies (MAbs) for this tag have been not available. The generation of antibodies specific for S-tagged proteins is expected to broaden the range of applications of such S-tag fused recombinant proteins, and in this context, a novel MAb termed ATOM-2 was generated that specifically binds S-tagged proteins, which have been expressed using pET-vectors. Antigen specificity of ATOM-2 was confirmed in Western blot and enzyme-linked immunoadsorbent assay analysis, and using a series of amino acid deletion mutants, the binding epitope of ATOM-2 was precisely mapped. This showed that ATOM-2 recognizes the C-terminal part of the 15-meric S-tag in context with a few residues of vector encoded sequences. The core sequence for ATOM-2 binding epitope is "His-Met-Asp-Ser-Pro-Asp-Leu-Gly-Thr," which is present in all pET-expression vectors encoding S-tag fusion proteins. Because the ATOM-2 binding region does not overlap with the S-protein binding sequence, a convenient tool is provided for the simultaneous or alternative detection, purification, and analysis of recombinant S-tagged proteins to conventional S-proteins.


[The clinical pharmacist, an essential element in the new gradation of care for ambulatory patients].
Pharmaceutical presence in oncology allows the clinical pharmacist to integrate tripartite consultations for primary prescription of oral anticancer drugs. The aim of the study is to describe the deployment of the clinical pharmacy activity in 2 oncology departments since its implementation in 2019, to assess the financial gain of the pharmaceutical interventions through the new gradation of outpatient management published on September 10, 2020, and finally to assess their satisfaction following the deployment of this pathway. A retrospective study was conducted to collect pricing data for oral therapy interviews in patients between January 2019 and December 2022. To complement this, a satisfaction survey was conducted by the oral therapy pharmaceutical team between 01/01/2022 and 12/31/2022 among patients undergoing treatment. 579 patients received a targeted pharmaceutical interview as part of the oral therapy patient pathway. The average invoiced amount of a pharmaceutical consultation carried out as part of a tripartite first prescription was 355.44 euros. The 579 patients who benefited from a targeted pharmaceutical interview generated a revenue of 87,545 euros for the hospital. In terms of evaluating patient satisfaction, 163 usable responses were received out of 267 patients questioned, representing a response rate of 61%, with an overall score of 9.1/10. Pending the introduction of a specific remuneration for clinical pharmacy activities, the valuation of tripartite consultations is a lever for financing clinical pharmacy activities in hospitals.


Biomembrane-Derived Nanoparticles in Alzheimer's Disease Therapy: A Comprehensive Review of Synthetic Lipid Nanoparticles and Natural Cell-Derived Vesicles.
Current therapies for Alzheimer's disease used in the clinic predominantly focus on reducing symptoms with limited capability to control disease progression; thus, novel drugs are urgently needed. While nanoparticles (liposomes, high-density lipoprotein-based nanoparticles) constructed with synthetic biomembranes have shown great potential in AD therapy due to their excellent biocompatibility, multifunctionality and ability to penetrate the BBB, nanoparticles derived from natural biomembranes (extracellular vesicles, cell membrane-based nanoparticles) display inherent biocompatibility, stability, homing ability and ability to penetrate the BBB, which may present a safer and more effective treatment for AD. In this paper, we reviewed the synthetic and natural biomembrane-derived nanoparticles that are used in AD therapy. The challenges associated with the clinical translation of biomembrane-derived nanoparticles and future perspectives are also discussed.


Depression and cardiac disease: a review.
Depression is highly prevalent in cardiac patients, with 20% to 40% of patients meeting criteria for major depressive disorder or experiencing an elevation in depressive symptoms. These depressive symptoms are often chronic and persistent, and they have been associated with the development and progression of coronary artery disease, worse health-related quality of life, poor physical functioning, recurrent cardiac events, and a 2- to 2.5-fold increased risk of mortality. Impaired adherence to health behaviors and adverse physiological effects of depression, including inflammation, endothelial dysfunction, platelet hyperactivity, and autonomic nervous system abnormalities, may link depression with adverse cardiac outcomes. Pharmacologic and psychotherapeutic interventions appear to be safe and effective at reducing depressive symptoms in patients with cardiovascular disease and may impact cardiac outcomes. Unfortunately, depression often is unrecognized and untreated in this population, despite the availability of brief screening tools that can be used for this purpose. We recommend the routine screening of cardiac patients for depression when there are adequate mechanisms for management and referral, such as available consulting psychiatrists or care management programs that facilitate the delivery of pharmacologic and psychotherapeutic treatments in this vulnerable population.


Lumbar canal stenosis in Paget's disease. The staging of the clinical syndrome, its diagnosis, and treatment.
The lumbar syndrome of Paget's disease is classified according to its severity, clinical findings, biochemical factors, and radiological pattern. Pagetoid spinal stenoses may occur in three stages as a progressive clinical syndrome. Several diagnostic procedures, including computerized tomography, (CT) are analyzed to introduce the concept of Spinal Reserve Capacity (SRC). Treatment with calcitonin is recommended at the appropriate stages of the syndrome.


[The sound and musical preferences of tympanic chord].
The tympanic chord is a part of the 7th cranial nerve (facial nerve), from which it branches off, runs through the middle ear and then joins the lingual nerve, a part of the 5th cranial nerve (mandibular nerve/trigeminal nerve). Despite its course through the ear, the tympanic chord does not carry auditory fibers, but rather sensory and parasympathetic fibers to the front part of the tongue and to the salivary glands.The cranial nerves V and VII have a common phylogenetic origin, establishing a close relationship between auditory and gustative sense.In German language "Geschmack" means both gustative sense and the preference for different ways of thinking or styles in music, art or fashion. "Musikgeschmack" is the preference for special music styles or composers. "Musikgeschmack" therefore forms an interface between the anatomy of the tympanic chord and music preferences.The effect of parallel processing of music and taste is used, for example, in music therapy or as part of marketing strategies. But it could also be used to treat Covid-19 patients who suffer from a loss of sense of smell and taste. However, there are still no studies on this specific question.