Monoclonal gammopathy with neurological signs and symptoms. A clinical, neurophysiological and muscle biopsy study.
Clinical, neurophysiological and muscle biopsy findings in ten patients with monoclonal gammopathy are reported. Three patients had polyneuropathy, one had hemiparkinsonism, one migraine and radicular symptoms and one paresthesiae and radicular symptoms. Amyloidosis was not found in muscle biopsy specimens. All but one patient with neurological findings also had positive immunofluorescence staining for tissue-bound immunoglobulins in muscle biopsy specimens. The tissue-bound immunoglobulins usually belonged to the same class as the M-component. None of the biopsies of patients without neurological findings were positive.


The role of acidic phosphoproteins in biomineralization.
Biomineralization is the process by which living organisms deposit mineral in the extracellular matrix. In nature, almost 50% of biominerals are calcium-bearing minerals. In addition to calcium, we find biominerals formed from silica and magnetite. Calcium-containing biominerals could be either calcium phosphate as in apatite found in vertebrates or calcium carbonate as in calcite and aragonite found in many invertebrates. Since all biomineralization is matrix mediated, an understanding of the nature of the proteins involved is essential in elucidating its mechanism. This review will discuss some of the proteins involved in the process of biomineralization involving calcium. Two proteins, dentin matrix protein 1 and dentin phosphoprotein (Phosphophoryn) will serve as models for the vertebrate system, and two others - P16 and phosphodontin will serve as models for the invertebrate system.


Significance of the presence of bovine milk beta-glucuronidase in mastitis detection.
The presence of beta-glucuronidase enzyme in bovine milk was related both to the existence of major and minor pathogens and to somatic cell counts. The detection of this enzyme in whole milk was made possible by the use of p-nitrophenyl-beta-glucuronide as a substrate. This detection allowed us to determine abnormal udder secretions with a high degree of specificity and sensitivity. The particular method of enzyme determination was considered important for mastitis detection because beta-D-glucuronidase, the most significant enzyme in inflammatory processes, is released selectively. The relationship between enzyme, presence of pathogens, and somatic cell counts was established in 220 milk samples obtained at random from individual quarters of apparently healthy udders of cows from four local dairy farms (Santiago del Estero and Tucuman, Argentina). Four of these samples were from cows of recent parturition and two from cows with severe clinical mastitis. Only 17% of the milk samples were normal with somatic cell counts 500,000 cells/ml or less. This ratio is the usual one throughout the area, and the remaining 83% showed higher somatic cell counts. Taking the latter as 100%, the presence of beta-glucuronidase and the positive bacteriological analyses represented 76 and 74%, respectively.


Children's developing judgments about the physical manifestations of power.
When navigating unfamiliar social environments, it is important to identify who is powerful. Determining who has power can be challenging because observers may have limited social information, and because people achieve influence for many reasons. In experiments with 3- to 5-year-old children (n = 192) and adults (n = 32), we investigated the developmental origins and conceptual structure of power judgments based on physical appearance. At 3 years of age, children already associated physical strength with expansive posture; soon after, expansive postures also supported judgments of normative authority and were joined by similar judgments about masculine facial structure. By the age of 4, children also matched high- and low-power versions of faces and postures together, indicating that they draw connections between different aspects of more or less powerful appearance. The complexity and timing of these changes highlights limitations in current accounts of the origins of adults' intuitions about powerful appearances. This study documents several novel developmental patterns that generate new hypotheses about the mechanisms that support the emergence of children's intuitions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


The efficacy of autologous cord-blood transfusions in neonatal surgical patients.
Allogenic blood transfusions have a risk of infection owing to unknown organisms, graft-versus-host reaction, and immunosupression; however, the use of autologous blood has been reported to be safe. Cord blood has been reported to be useful as a source of stem cell transplantation for the treatment of leukemia and genetic disease. Furthermore, autologous cord-blood transfusions (ACBT) have been reported to be effective for the treatment of anemia in premature infants. The authors examined the efficacy of ACBT in neonatal surgical patients. Autologous cord-blood was stored from 12 infants at delivery, including 2 transvaginal and 10 cesarean section deliveries, from 1998 to 2001. All infants had surgically correctable malformations diagnosed antenatally. The mean gestational age was 37.2 +/- 1.6 weeks, and the birth weight was 2,597 +/- 1.6 g. The results of the blood count, serum electrolyte, and liver function tests of the patients who underwent ACBT only (group 1, n = 7) were compared with those of the 7 neonates who underwent an allogenic transfusion during the same period (group 2, n = 7). The mean volume of the stored blood was 64 +/- 35.6 g (range, 20 to 100). Eleven of the 12 patients underwent transfusions. Ten of 11 patients received autologous cord blood. A mean of 44.1 +/- 37.3 g of cord blood was used. Three of 10 cases also required an allotransfusion because of ECMO circuit preparation and a shortage of the stored blood. One patient underwent allotransfusion only. As a result, 7 of 11 babies (64%) who required transfusion were able to avoid an allotransfusion. The blood potassium levels were lower in group 1 than in group 2. No significant complications were recognized clinically. ACBT is considered beneficial because it enables neonatal surgical patients to avoid allotransfusions. Therefore, autologous cord-blood storage should be considered in the patients antenatally diagnosed to have surgical malformations. However, the storage volume varies for each case. Improved techniques to obtain an adequate amount of blood also should be developed.


Fungal Infection among Diabetic and Nondiabetic Individuals in Nepal.
Low immunity, comorbid clinical conditions, and metabolic disorders may be the underlying factors that determine the severity of infection. Diabetes increases the risk of infection and multiple organ damage. In Nepal, the actual burden of fungal infections has not been estimated or is in a limited progress. This study aimed to investigate the status of fungal infection in diabetic and nondiabetic individuals in Bhaktapur, Nepal. A total of 670 samples were collected from 134 participants. From each participant, five samples were collected from different sites like an oral wash, toe swab, midstream urine, hair shaft, and nail scrapings. All samples were cultured on Sabouraud dextrose agar. Gram stain was used to observe yeast cells and lactophenol cotton blue stain was used for hyphae. Chlamydospore production by Candida species was observed in cornmeal agar medium by Dalmau Plate method. Candida species isolated were characterized by germ-tube test and differentiated using CHROM agar Candida medium. Candida species isolates were tested for antibiotic susceptibility. Overall, 19.4% of the samples showed fungal growth. The prevalence of fungal infection was higher in diabetic (34.0%) than nondiabetic individuals (4.7%). Fungal growth was found to be higher in oral wash followed by toe, urine, hair, and nail samples. Predominant fungi were Candida species (57.5%), Aspergillus species (28.4%), and Trichophyton species (10.7%). Oral wash, toe, and urine samples in diabetics had a significantly higher fungal prevalence when compared between both groups, p value < 0.05. In Candida isolates, higher resistance was seen against fluconazole 36.8% and ketoconazole 28.9%, whereas other drugs showed low resistance. Diabetic participants are more susceptible to fungal infection than the nondiabetics. Overall, Candida species and Aspergillus species are highly predominant fungi. Candida species are highly resistant to fluconazole and ketoconazole.


Estimated effect of an integrated approach to suspected deep venous thrombosis using limited-compression ultrasound.
Deep vein thrombosis (DVT) is both common and serious, yet the desire to never miss the diagnosis, coupled with the low specificity of D-dimer testing, results in high imaging rates, return visits, and empirical anticoagulation. The objective of this study was to evaluate a new approach incorporating bedside limited-compression ultrasound (LC US) by emergency physicians (EPs) into the workup strategy for DVT. This was a cross-sectional observational study of emergency department (ED) patients with suspected DVT. Patients on anticoagulants; those with chronic DVT, leg cast, or amputation; or when the results of comprehensive imaging were already known were excluded. All patients were treated in the usual fashion based on the protocol in use at the center, including comprehensive imaging based on the modified Wells score and serum D-dimer testing. Seventeen physicians were trained and performed LC US in all subjects. The authors identified a priori an alternate workup strategy in which DVT would be ruled out in "DVT unlikely" (Wells score < 2) patients if the LC US was negative and in "DVT likely" (Wells score ≥ 2) patients if both the LC US and the D-dimer were negative. The criterion standard was based on comprehensive imaging interpreted by radiologists blinded to LC US findings and by structured medical record review at 6 months in patients without comprehensive imaging. A total of 227 patients were enrolled (47% DVT likely), of whom 24 had DVT. The LC US was positive in 27 cases (21 actually DVT positive), indeterminate in 28 (one DVT positive), and negative in 172 (two DVT positive). Of 130 patients deemed DVT negative by the new strategy, one had confirmed DVT (miss rate = 0.8%; 95% confidence interval [CI] = 0.1% to 4.0%), but this patient had been misclassified by the treating physician as low risk by Wells criteria. The stand-alone sensitivity and specificity of LC US were 91% (95% CI = 70% to 98%) and 97% (95% CI = 92% to 99%), respectively. Incorporating LC US into the diagnostic approach would have reduced the rate of comprehensive imaging from 70% to 43%, D-dimer testing from 100% to 33%, and the mean time to diagnostic certainty by 5.0 hours and avoided 24 (11%) return visits for imaging and 10 (4.4%) cases of unnecessary anticoagulation. In 19% of cases, the treating and scanning physician disagreed whether the patient was DVT likely or DVT unlikely based on Wells score (κ = 0.62; 95% CI = 0.48 to 0.77). Limited-compression US holds promise as one component of the diagnostic approach to DVT, but should not be used as a stand-alone test due to imperfect sensitivity. Tradeoffs in diagnostic efficiency for the sake of perfect sensitivity remain a difficult issue collectively in emergency medicine (EM), but need to be scrutinized carefully in light of the costs of overinvestigation, delays in diagnosis, and risks of empirical anticoagulation.


Independence of visuotopic representation and orientation map in the visual cortex of the cat.
The representations of visual space and stimulus orientation were mapped in the cat primary visual cortex using electrophysiological recordings supplemented with intrinsic signal optical imaging. The majority of units displaced up to 600 micro m laterally had overlapping RFs both in orientation domains and around singularities of the orientation map. Quantitative comparison of these units revealed only a weak, positive correlation between the difference in their preferred orientations and RF separations (area 17: r = 0.09; area 18: r = 0.15). The occurrence of nonoverlapping RFs could be accounted for by random RF position scatter rather than by orientation difference between the units. Monte Carlo analysis showed that our findings are compatible with a locally smooth and linear representation of visual space that is not coupled to the representation of stimulus orientation. An important functional implication of the above map relationships is that positional information captured by the retina is faithfully transmitted into the cortex.


Quantitative Assessment of the Immune Microenvironment in Patients With Iatrogenic Laryngotracheal Stenosis.
Iatrogenic laryngotracheal stenosis (iLTS) is characterized by fibroinflammatory narrowing of the upper airway and is most commonly caused by intubation injury. Evidence suggests a key role for CD4 T cells in its pathogenesis. The objective of this study is to validate emerging multiplex immunofluorescence (mIF) technology for use in the larynx and trachea while quantitatively characterizing the immune cell infiltrate in iLTS. In addition to analyzing previously unstudied immune cell subsets, this study aims to validate previously observed elevations in the immune checkpoint PD-1 and its ligand PD-L1 while exploring their spatial and cellular distributions in the iLTS microenvironment. Controlled ex vivo cohort study. Tertiary care center. mIF staining was performed with formalin-fixed, paraffin-embedded slides from 10 patients with iLTS who underwent cricotracheal resection and 10 control specimens derived from rapid autopsy for CD4, CD8, CD20, FoxP3, PD-1, PD-L1, and cytokeratin. There was greater infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, FoxP3+CD4+ Tregs, and FoxP3+CD8+ early effector T cells in the submucosa of iLTS specimens as compared with controls (P < .05 for all). PD-1 was primarily expressed on T cells and PD-L1 predominantly on CD4+ cells and "other" cells. This study leverages the power of mIF to quantify the iLTS immune infiltrate in greater detail. It confirms the highly inflammatory nature of iLTS, with CD4+ cells dominating the immune cell infiltrate; it further characterizes the cellular and spatial distribution of PD-1 and PD-L1; and it identifies novel immunologic targets in iLTS.


Web based scoring is useful for validation and harmonisation of scoring criteria within RENEB.
To establish a training data set of digital images and to investigate the scoring criteria and dose assessment of the dicentric assay within the European network of biodosimetry (RENEB), a web based scoring inter-comparison was undertaken by 17 RENEB partners. Two sets of 50 high resolution images were uploaded onto the RENEB website. One set included metaphases after a moderate exposure (1.3 Gy) and the other set consisted of metaphases after a high dose exposure (3.5 Gy). The laboratories used their own calibration curves for estimating doses based on observed aberration frequencies. The dose estimations and 95% confidence limits were compared to the actual doses and the corresponding z-values were satisfactory for the majority; only the dose estimations from two laboratories were too low or too high. The coefficients of variation were 17.6% for the moderate and 11.2% for the high dose. Metaphases with controversial results could be identified for training purposes. Overall, the web based scoring of the two galleries by the 17 laboratories produced very good results. Application of web based scoring for the dicentric assay may therefore be a relevant strategy for an operational biodosimetry assistance network.


Use of a new myocardial centroid for measurement of regional myocardial dysfunction by electron beam computed tomography: comparison with technetium-99m sestamibi infarct size quantification.
The study compared the performance of conventional endocardial and epicardial centroid algorithms with the new "myocardial" centroid algorithm in patients with anterior myocardial infarction. "Floating" endocardial or epicardial centroid algorithms, commonly used in tomographic imaging methods to assess regional motion, may misrepresent left ventricular regional myocardial function in the presence of markedly asymmetric left ventricular contraction. A new centroid algorithm based on regional myocardial mass distribution was tested in 29 patients with a first anterior myocardial infarction and was compared with conventional centroid algorithms. Direct comparisons in 60 equal sectors at one midventricular level per patient were performed between electron beam computed tomography and technetium-99m sestamibi single-photon emission computed tomography. The thresholds of regional myocardial function used to define infarction were varied for regional ejection fraction from 20% to 40% and for regional wall thickening from 0 to 4 mm. Regression and Bland-Altman analysis were used to compare infarct size by regional myocardial function with infarct size by sestamibi single-photon emission computed tomography. The new myocardial centroid showed the least shift toward infarcted myocardium from diastole to systole and had the highest amplitudes of the measurement curves for regional ejection fraction and regional wall thickening. The optimal regional myocardial function thresholds for each centroid algorithm for regional ejection fraction were endocardial, 30% (R = 0.62; mean difference to sestamibi, -0.5% +/- 22.1% tomographic infarct size points); epicardial, 30% (R = 0.79; mean difference, 2.2% +/- 13.1% tomographic infarct size points); and new myocardial, 25% (R = 0.88; mean difference, -0.6% +/- 9.5% tomographic infarct size points). The optimal thresholds for regional wall thickening were endocardial, 1 mm (R = 0.70; mean difference, -2.2% +/- 14.3% tomographic infarct size points); epicardial, 1 mm (R = 0.78; mean difference, -4.6% +/- 12.7% tomographic infarct size points); and new myocardial, 2 mm (R = 0.71; mean difference, 2.1% +/- 14.1% tomographic infarct size points). The best agreement (R = 0.88) between electron beam computed tomography infarct size and sestamibi single-photon emission computed tomography infarct size was achieved with regional ejection fraction and the new myocardial centroid algorithm. In asymmetrically contracting left ventricles, the new myocardial centroid algorithm is superior to conventional methods for tomographic analysis of regional myocardial function.


Receptor-independent sequestration of beta-adrenergic ligands by alveolar type II cells.
Numerous studies indicate that synthesis and secretion of surfactant by type II pneumocytes are modulated by the interaction of beta-adrenergic agonists with specific cell surface receptors. Two 125I-labeled beta-adrenergic ligands, l-iodopindolol (IPIN) and l-iodocyanopindolol (ICYP), were thus employed to investigate the properties of type II cell beta-receptors. Saturable, high-affinity, stereospecific binding to crude membrane fractions from whole rat lungs was exhibited by both ligands (IPIN, KD 283 pM, Bmax 508 fmol/mg protein; ICYP, KD 18 pM, Bmax 404). Type II cell membranes obtained by N2 cavitation also revealed stereospecific, saturable, high-affinity binding. In intact cells (37 degrees C) however, rapid, highly concentrative (cell/media greater than 1000), nonspecific ligand uptake compromised estimates of specific binding (specific/total binding less than 0.1). Total ligand uptake was inhibited at 4 degrees C, by decreasing pH within the physiological range (7-8) and by the lysosomotropic compound chloroquine (50-200 microM), without a detectable change in specific binding. Other basic drugs were also inhibitory at similar concentrations; acidic drugs had no effect. Even at 4 degrees C, specific binding remained low, as IPIN and ICYP were displaced less than 30% by l-alprenolol (1 microM). Physicochemical properties of IPIN and ICYP considered with the above studies suggest that passive ligand entry into intact pneumocytes and subsequent trapping of the protonated species in a cellular compartment of low pH may account for high nonspecific ligand uptake.


The history of spinal biomechanics.
The history of spinal biomechanics has its origins in antiquity. The Edwin Smith surgical papyrus, an Egyptian document written in the 17th century BC, described the difference between cervical sprain, fracture, and fracture-dislocation. By the time of Hippocrates (4th century BC), physical means such as traction or local pressure were being used to correct spinal deformities but the treatments were based on only a rudimentary knowledge of spinal biomechanics. The Renaissance produced the first serious attempts at understanding spinal biomechanics. Leonardo da Vinci (1452-1519) accurately described the anatomy of the spine and was perhaps the first to investigate spinal stability. The first comprehensive treatise on biomechanics, De Motu Animalium, was published by Giovanni Borelli in 1680, and it contained the first analysis of weight bearing by the spine. In this regard, Borelli can be considered the "Father of Spinal Biomechanics." By the end of the 19th century, the basic biomechanical concepts of spinal alignment and immobilization were well entrenched as therapies for spinal cord injury. Further anatomic delineation of spinal stability was sparked by the anatomic analyses of judicial hangings by Wood-Jones in 1913. By the 1960s, a two-column model of the spine was proposed by Holdsworth. The modern concept of Denis' three-column model of the spine is supported by more sophisticated testing of cadaver spines in modern biomechanical laboratories. The modern explosion of spinal instrumentation stems from a deeper understanding of the load-bearing structures of the spinal column.


Heterogeneity of Harmful Constituent Profiles in Smokeless Tobacco Products from Five African Countries.
Addictive, toxic, and carcinogenic constituents present in smokeless tobacco (SLT) products are responsible for the harmful effects associated with SLT use. There are limited data on levels of such constituents in SLT products used in Africa, a region with high prevalence of SLT use and the associated morbidity and mortality. Manufactured and custom-made SLT products were purchased from five African countries (South Africa, Uganda, Mauritania, Nigeria, and Zambia) using a standard approach for sample collection, labeling, and storage. Moisture content, pH, total and unprotonated (biologically available) nicotine, five tobacco-specific N-nitrosamines (TSNA), 10 polycyclic aromatic hydrocarbons (PAH), five metals and metalloids (As, Cd, Cr, Ni, and Pb), nitrate, and nitrite were analyzed. A total of 54 samples representing 15 varieties of manufactured SLT products and 13 varieties of custom-made SLT products were purchased and analyzed. In all samples, the total nicotine ranged from 1.6 to 20.5 mg/g product and unprotonated nicotine accounted for 5.3-99.6% of the total nicotine content. The sum of all five TSNA ranged from 1.6 to 100 μg/g product, with significant within-country variations observed across both the manufactured and custom-made varieties. Significant variations were also found for PAH, metals and metalloids, nitrates, and nitrites. This is the most comprehensive report on the chemical profiling of products from African countries. This is also the first study illustrating the variability of harmful constituents within the same types and brands of African SLT. Our findings emphasize the need for consumer education and interventions to reduce SLT use in Africa. The data reported here can be useful to regulators in considering measures to prevent the occurrence of high levels of known toxicants and carcinogens in manufactured products.


Lower dietary n-6 : n-3 ratio and high-dose vitamin E supplementation improve sperm morphology and oxidative stress in boars.
A 2×2 factorial experiment (10 boars per treatment) was conducted for 16 weeks to evaluate the effects of the dietary n-6:n-3 ratio (14:1 vs 6:1) and vitamin E (200 vs 400mg kg-1) on boar sperm morphology and oxidative stress. Sperm mitochondrial membrane potential (MMP), reactive oxygen species (ROS), DNA damage (8-hydroxydeoxyguanosine; 8-OHdG), seminal lipoperoxidation (malondialdehyde; MDA) and antioxidant capacity in the serum, spermatozoa and seminal plasma were assessed as indicators of oxidative stress. Sperm production was similar among groups but increased (P<0.05) throughout the 16 weeks of the study. Although sperm α-tocopherol content, ROS and seminal MDA did not differ between the two dietary n-6:n-3 ratio treatments, enhanced antioxidant enzyme activity and MMP, but decreased 8-OHdG, were found in spermatozoa from boars consuming the 6:1 diet. The diet with the 6:1 ratio positively affected sperm morphology at Weeks 12 and 16 (P<0.05). The α-tocopherol content and antioxidant capacity increased in boars with increasing levels of vitamin E supplementation. Compared with low-dose vitamin E, high-dose vitamin E supplementation improved sperm morphology. Overall, the results indicate that an n-6:n-3 ratio of 6:1 and 400 mg/kg vitamin E have beneficial effects on sperm morphology by improving antioxidative stress.


The pituitary-gonadal axis and health in elderly men: a study of men born in 1913.
The results of recent studies suggest that a relative hypogonadism in men is associated with several established risk factors for prevalent diseases. Therefore, we determined total and free testosterone, luteinizing hormone (LH), and sex-hormone binding globulin (SHBG) in a cohort of randomly selected men (n = 659) at 67 years of age. These data were analyzed cross-sectionally in relation to blood glucose and serum insulin, which were measured while fasting and after an oral glucose tolerance test, in addition to plasma lipids and blood pressure. The data were also analyzed in relation to impaired glucose tolerance (IGT) and diabetes, which were discovered at examination or earlier diagnosis. Risk factors for the development of diabetes up to 80 years of age were analyzed with univariate and multivariate statistics. Total and free testosterone and SHBG concentrations correlated negatively with glucose and insulin values; total testosterone and SHBG, with triglycerides; and SHBG, with blood pressure (from P < 0.05 to P < 0.01). Men with IGT or newly diagnosed diabetes had higher BMI values (26.2 +/- 0.31 and 27.0 +/- 0.59 [mean +/- SE], respectively) and waist circumference (99.0 +/- 1.03 and 100.5 +/- 1.57) than nondiabetic men (BMI, 25.1 +/- 0.14; waist circumference, 95.4 +/- 0.47; P < 0.05), indicating abdominal obesity. Such men and men with previously diagnosed diabetes had, in general, lower total and free testosterone and SHBG levels, while those for LH were not different. In multivariate analyses that included BMI, waist-to-hip ratio, total and free testosterone, and SHBG, the remaining independent predictors for the development of diabetes were low total testosterone (P = 0.015) and, on the borderline, low SHBG (P = 0.053). In relation to nondiabetic men, the risk ratio for mortality, myocardial infarction, and stroke increased gradually and significantly from 1.18 to 1.68, from 1.51 to 1.78, and from 1.72 to 2.46 in men with IGT, newly diagnosed diabetes, and previously known diabetes, respectively. It was concluded that low testosterone and SHBG concentrations in elderly men are associated with established risk factors for diabetes and in established diabetes. Moreover, low testosterone levels independently predict the risk of developing diabetes. In different degrees of expression, the diabetic state predicts strongly (and gradually mortality from) myocardial infarction and stroke. It has been suggested that a relative hypogonadism might be a primary event, because other studies have shown that testosterone deficiency is followed by insulin resistance, which is ameliorated by testosterone substitution. The data suggest that the relative hypogonadism involved might be of both central and peripheral origin.


Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent.
The purpose of the study was to evaluate [(18)F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [(18)F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer.


The Global Flood Protection Benefits of Mangroves.
Coastal flood risks are rising rapidly. We provide high resolution estimates of the economic value of mangroves forests for flood risk reduction every 20 km worldwide. We develop a probabilistic, process-based valuation of the effects of mangroves on averting damages to people and property. We couple spatially-explicit 2-D hydrodynamic analyses with economic models, and find that mangroves provide flood protection benefits exceeding $US 65 billion per year. If mangroves were lost, 15 million more people would be flooded annually across the world. Some of the nations that receive the greatest economic benefits include the USA, China, India and Mexico. Vietnam, India and Bangladesh receive the greatest benefits in terms of people protected. Many (>45) 20-km coastal stretches particularly those near cities receive more than $US 250 million annually in flood protection benefits from mangroves. These results demonstrate the value of mangroves as natural coastal defenses at global, national and local scales, which can inform incentives for mangrove conservation and restoration in development, climate adaptation, disaster risk reduction and insurance.


Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.
Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure.


Complete Genome Sequences of Extremely Thermoacidophilic Metal-Mobilizing Type Strain Members of the Archaeal Family Sulfolobaceae, Acidianus brierleyi DSM-1651, Acidianus sulfidivorans DSM-18786, and Metallosphaera hakonensis DSM-7519.
The family Sulfolobaceae contains extremely thermoacidophilic archaea that are found in terrestrial environments. Here, we report three closed genomes from two currently defined genera within the family, namely, Acidianus brierleyi DSM-1651T, Acidianus sulfidivorans DSM-18786T, and Metallosphaera hakonensis DSM-7519T.


Fast left prefrontal rTMS reduces post-gastric bypass surgery pain: findings from a large-scale, double-blind, sham-controlled clinical trial.
A single session of left prefrontal rTMS has been shown to have analgesic effects, and to reduce post-operative morphine use. We sought to test these findings in a larger sample, and try and see if multiple sessions had additive analgesic benefit. 108 patients undergoing laparoscopic gastric bypass surgery received two sessions of 10 Hz rTMS (110% of motor threshold) over the left dorsolateral prefrontal cortex (one immediately following surgery and one 4 h later). Participants were randomly assigned to receive 2 sessions of real rTMS, 2 sessions of sham, 1 real then 1 sham, or 1 sham then 1 real rTMS treatments. Patients and study staff were blind to rTMS conditions. Unlike previous rTMS trials for post-operative pain, no differences emerged between groups with respect to total patient-controlled analgesia usage (IV hydromorphone). However, despite no difference in IV analgesic usage, subjects that received 2 real rTMS sessions rated both the affective and sensory dimensions of their pain significantly lower than those in the sham–sham group at several time points during the post-surgical/post-rTMS period. This study suggests that left prefrontal rTMS may produce significant analgesic effects in the perioperative setting. However, further work is needed to understand this effect and attempt to make it clinically useful in light of the lack of effect on PCA hydromorphone use.


Curative treatment of hypertension by physical exercise.
Hypertension, one of the most common chronic and sporadic conditions, figures among the important worldwide public-health challenges, and it is a major risk for heart disease, stroke, kidney disease and other complications, including dementia. Hypertension is neglected by individuals, and the prevalence of this condition continues to rise across the world. A great number of patients receiving medical intervention is not successfully treated, while adequate curative health services are dependent on the exact update data of the countrywide prevalence of known and undetected cases. This renders elusive the possibility of a public strategy to eradicate hypertension. Accordingly, a global preventive approach in considering the known etiology of the disease established two types of cases hypertension including primary hypertension, which is idiopathic, and secondary hypertension, which is based on a demonstrable organic change in tissues. This is relevant since the secondary hypertension remains the most prevalent and it is associated with physical inactivity and bad nutrition. The environmental condition may be counteracting with an active life style. Physical exercise, which promotes hemodynamic and humoral changes in healthy subjects, may positively impact on hypertensive subjects. Indeed, patients with hypertension might improve their blood pressure, plasma lipoprotein-lipid profile, insulin sensitivity, likely to normotensive people, as well as the regression of the pathology of left ventricular hypertrophy. Exercise training is an important initial or adjunctive step that may be highly efficacious in the prevention and treatment of individuals with hypertension. Herein, we study the role of exercise training in the treatment of hypertension.


Direct and crossover PCR amplification to facilitate Tn5supF-based sequencing of lambda phage clones.
The 264 bp mini-transposon Tn5supF was constructed to sequence DNAs cloned in phage lambda without extensive shotgun subcloning or primer walking. Unique sequences near each transposon end serve as primer binding sites, and a supF gene is used to select transposition to lambda. We describe here PCR methods that facilitate Tn5supF-based sequencing. In a first pass, insertions are mapped relative to the ends of the cloned fragment using pairs of primers specific for vector DNA next to the cloning site and for a Tn5supF end. Most insertions not mapped in this step are near the center of the cloned fragment or in the vector arms, and are then mapped relative to the two innermost insertions by 'crossover' PCR. This involves amplification from primers on different DNA molecules, and generates hybrid DNA products whose lengths correspond to the distances between the two insertions. We routinely amplified more than 6 kb in direct PCR and 3 kb in crossover PCR; at the limit we amplified up to approximately 10 kb in direct PCR and approximately 6 kb in crossover PCR, but not reproducibly. Crossover PCR products were also obtained with insertions separated by only 200 bp, indicating that no rare sites are needed to switch templates. PCR products were purified by adsorption and then elution from glass slurry, and sequenced directly. Ladders of more than 400 bp were obtained from primer sites on each DNA strand; 2 kb was read from crossover PCR products, and showed that they were amplified with fidelity. In conclusion, direct and crossover PCR methods expedite transposon insertion mapping, and yield templates for accurate sequencing of both DNA strands.


Let's Call it Quits: Break-Even Effects in the Decision to Stop Taking Risks.
"Chasing" behavior, whereby individuals, driven by a desire to break even, continue a risky activity (RA) despite incurring large losses, is a commonly observed phenomenon. We examine whether the desire to break even plays a wider role in decisions to stop engaging in financially motivated RA in a naturalistic setting. We test hypotheses, motivated by this research question, using a large data set: 707,152 transactions of 5,379 individual financial market spread traders between September 2004 and April 2013. The results indicate strong effects of changes in wealth around the break-even point on the decision to cease an RA. An important mediating factor was the individual's historical long-term performance. Those with a more profitable trading history were less affected by a fall in cash balance below the break-even point compared to those who had been less profitable. We observe that break-even points play an important role in the decision of nonpathological risk takers to stop RAs. It is possible, therefore, that these nonpathological cognitive processes, when occurring in extrema, may result in pathological gambling behavior such as "chasing." Our data set focuses on RAs in financial markets and, consequently, we discuss the implications for institutions and regulators in the effective management of risk taking in markets. We also suggest that there may be a need to consider carefully the nature and role of "break-even points" associated with a broader range of nonfinancially-focused risk-taking activities, such as smoking and substance abuse.


Ecological implications of reduced pollen deposition in alpine plants: a case study using a dominant cushion plant species.
The reproductive assurance hypothesis states that self-incompatible female plants must produce twice the number of seeds relative to their self-compatible hermaphroditic counterparts to persist in gynodioecious populations. This is a viable life-history strategy, provided that pollination rates are sufficiently high. However, reduced pollination rates in alpine plants are likely due to climate induced plant-pollinator mismatches and general declines in pollinators. Using a gynodioecious population of the dominant plant Silene acaulis (Caryophyllaceae), we tested the reproductive assurance hypothesis and also the stress gradient hypothesis with a series of pollinator exclusion trials and extensive measurements of subsequent reproductive output (gender ratio, plant size, percent fruit-set, fruit weight, seeds per fruit, total seeds, seed weight, and seed germination). The reproductive assurance hypothesis was supported with female plants being more sensitive to and less likely to be viable under reductions in pollination rates. These findings are the first to show that the stress gradient hypothesis is also supported under a gradient of pollen supply instead of environmental limitations. Beneficiary abundance was negatively correlated to percent fruit-set under current pollen supply, but became positive under reduced pollen supply suggesting that there are important plant-plant-pollinator interactions related to reproduction in these alpine plant species.


Controlling toughness of polymer-grafted nanoparticle composites for impact mitigation.
Toughness in an entangled polymer network is typically controlled by the number of load-bearing topological constraints per unit volume. In this work, we demonstrate a new paradigm for controlling toughness at high deformation rates in a polymer-grafted nanoparticle composite system where the entanglement density increases with the molecular mass of the graft. An unexpected peak in the toughness is observed right before the system reaches full entanglement that cannot be described through the entanglement concept alone. Quasi-elastic neutron scattering reveals enhanced segmental fluctuations of the grafts on the picosecond time scale, which propagate out to nanoparticle fluctuations on the time scale 100s of seconds as evidenced by X-ray photon correlation spectroscopy. This surprising multi-scale dissipation process suggests a nanoparticle jamming-unjamming transition. The realization that segmental dynamics can be coupled with the entanglement concept for enhanced toughness at high rates of deformation is a novel insight with relevance to the design of composite materials.


[Actual cost of complex surgical treatment of patients with neuroischemic form of diabetic foot syndrome].
The results of calculation the average cost of complex surgical treatment of 52 patients with neuroischemic form of diabetic foot syndrome (Wagner 3, 4) are presented in the article. Calculation was performed in the program "Computer-aided system for calculation of patient's treatment cost" developed in A.V. Vishnevsky Institute of Surgery. This program permits you to analyze such components as hospital-stay duration, cost of surgery, pre- and postoperative management, pharmacotherapy, laboratory and instrumental research methods. Actual cost necessary to prevent high lower extremity amputations in patients with neuroischemic form of diabetic foot syndrome is 458 387.8 rubles per person that 10.02 times higher than amount allocated from the state budget.


Scapular Dyskinesia: How to Differentiate Between Etiologies.
It is important to discuss the importance of synchronous balance between periscapular muscles for scapulothoracic motion and resultant scapulohumeral rhythm. Abnormalities in this balance can lead to scapular dyskinesia and winging, affecting shoulder motion and leading to impingement. Strategies exist to diagnose and differentiate between pathologies such as muscle paralysis (eg, trapezius or serratus anterior) or overactivity (eg, pectoralis minor). The physician should be aware of the role of diagnostic imaging, as well as the unique considerations for patients with Ehlers-Danlos syndrome. Overall, a comprehensive physical examination to accurately diagnose and treat scapular pathologies is particularly important.


Positive association between ambient air pollutants and incident kidney stones.
We aimed to assess the association between exposure to various air pollutants, individually or jointly, and incident kidney stones, and examine whether genetic susceptibility for kidney stones may modify this association. 453,977 participants without prior kidney stones from the UK Biobank were included. Annual mean concentrations of PM2.5, PM2.5-10, PM10, NO2, and NOx were estimated with a land use regression model. A weighted air pollution score was constructed that incorporates the five pollutants mentioned above. A genetic risk score (GRS) was calculated based on 20 single-nucleotide polymorphisms associated with kidney stones. The primary outcome was incident kidney stones. During a median follow-up of 11.9 years, 5,375 kidney stones were recorded. The adjusted HRs (95%CI) of incident kidney stones were 1.04 (1.01-1.07), 1.02 (1.00-1.05), 1.03 (1.01-1.06), 1.05 (1.02-1.08), and 1.04 (1.01-1.07), for per standard deviation (SD) increment in PM2.5 (SD:1.06 μg/m3), PM2.5-10 (SD:0.90 μg/m3), PM10 (SD:1.90 μg/m3), NO2 (SD:7.63 μg/m3), and NOx (SD: 15.63 μg/m3), respectively. Moreover, there was a significantly linear association between the air pollution score and incident kidney stones (per SD increment: HR, 1.05, 95%CI: 1.02-1.08), especially in those without diabetes (vs. participants with diabetes; P-interaction = 0.037). In addition, the association between air pollution and kidney stones was statistically significant only in participants within intermediate-high kidney stone GRS, but not in those with low GRS kidney stone, though the interaction was not significant (P-interaction = 0.385). In conclusion, exposure to air pollution was associated with a higher risk of incident kidney stones, calling for the need to improve air quality.


Exploration of Variable Solvent Directed Self-Healable Supramolecular M(II)-Metallogels (M = Co, Ni, Zn) of Azelaic Acid: Investigating Temperature-Dependent Ion Conductivity and Antibacterial Efficiency.
Molecular self-assembly assisted self-healing supramolecular metallogels of azelaic acid with cobalt(II)-, nickel(II)-, and zinc(II)-based metal acetate salts were successfully fabricated. Individually, N,N'-dimethylformamide and dimethyl sulfoxide were immobilized within these distinctly synthesized soft-scaffolds of metallogels to attain their semisolid viscoelastic nature. Rheological experiments such as amplitude sweep, frequency sweep, and thixotropic measurements were executed for these metallogels to ratify their gel features. The different extents of supramolecular interactions operating within these solvent-directed metallogels were clearly reflected in terms of their distinct morphological patterns as investigated through field emission scanning electron microscopy. Comparative infrared (IR) spectral properties of metallogels along with individual metal salts and azelaic acid were analyzed. These experimental data clearly depict the significant shifting of Fourier transform (FT)-IR peaks of xerogel samples of different metallogels from the gel-forming precursors. The networks present within the soft-scaffold are evidently illustrated by the electrospray ionization-mass experimental data. The temperature-dependent ionic conductivity studies with these solvent-directed versatile metallogel systems were investigated through impedance spectroscopy. The temperature-dependent impedance spectroscopic studies clearly demonstrate that the ion-transportation within the gel matrix depends not only on the types of cations but also on the dielectric properties of the immobilized solvents. The antipathogenic effect of these metallogel systems has also been explored by testing their effectiveness against human pathogenic Gram-negative bacteria Klebsiella pneumoniae (MTCC 109) and Vibrio parahemolyticus, and Gram-positive bacteria like Bacillus cereus (MTCC 1272). These gel soft-scaffolds show no significant cytotoxicity against both the human neuroblastoma cell line-SH-SY5Y and the human embryonic kidney cell line-HEK 293.


Clinical outcomes of point-of-care testing in the interventional radiology and invasive cardiology setting.
Point-of-care testing (POCT) can provide rapid test results, but its impact on patient care is not well documented. We investigated the ability of POCT to decrease inpatient and outpatient waiting times for cardiovascular procedures. We prospectively studied, over a 7-month period, 216 patients requiring diagnostic laboratory testing for coagulation (prothrombin time/activated partial thromboplastin time) and/or renal function (urea nitrogen, creatinine, sodium, and potassium) before elective invasive cardiac and radiologic procedures. Overall patient management and workflow were examined in the initial phase. In phase 2, we implemented POCT but utilized central laboratory results for patient management. In phase 3, therapeutic decisions were based on POCT results. The final phase, phase 4, sought to optimize workflow around the availability of POCT. Patient wait and timing of phlebotomy, availability of laboratory results, and therapeutic action were monitored. Split sampling allowed comparability of POCT and central laboratory results throughout the study. In phase 1, 44% of central laboratory results were not available before the scheduled time for procedure (n = 135). Mean waiting times (arrival to procedure) were 188 +/- 54 min for patients who needed renal testing (phase 2; n = 14) and 171 +/- 76 min for those needing coagulation testing (n = 24). For patients needing renal testing, POCT decreased patient wait times (phases 3 and 4 combined, 141 +/- 52 min; n = 18; P = 0.02). For patients needing coagulation testing, wait times improved only when systematic changes were made in workflow (phase 4, 109 +/- 41 min; n = 12; P = 0.01). Although POCT has the potential to provide beneficial patient outcomes, merely moving testing from a central laboratory to the medical unit does not guarantee improved outcomes. Systematic changes in patient management may be required.


Dye-attached magnetic poly(hydroxyethyl methacrylate) nanospheres for albumin depletion from human plasma.
The selective binding of albumin on dye-affinity nanospheres was combined with magnetic properties as an alternative approach for albumin depletion from human plasma. Magnetic poly(hydroxyethyl methacrylate) (mPHEMA) nanospheres were synthesized using mini-emulsion polymerization method in the presence of magnetite powder. The specific surface area of the mPHEMA nanospheres was found to be 1302 m(2)/g. Subsequent to Cibacron Blue F3GA (CB) immobilization onto mPHEMA nanospheres, a serial characterization processing was implemented. The quantity of immobilized CB was calculated as 800 μmol/g. Ultimately, albumin adsorption performance of the CB-attached mPHEMA nanospheres from both aqueous dissolving medium and human plasma were explored.


A simple method for decellularizing a cell-derived matrix for bone cell cultivation and differentiation.
The extracellular matrix regulates cell survival, proliferation, and differentiation. In vitro two-dimensional cell experiments are typically performed on a plastic plate or a substrate of a single extracellular matrix constituent such as collagen or calcium phosphate. As these approaches do not include extracellular matrix proteins or growth factors, they fail to mimic a complex cell microenvironment. The cell-derived matrix is an alternative platform for better representing the in vivo microenvironment in vitro. Standard decellularization of a cell-derived matrix is achieved by combining chemical and physical methods. In this study, we compared the decellularization efficacy of several methods: ammonium hydroxide, sodium dodecyl sulfate (SDS), or Triton X-100 with cold or heat treatment on a matrix of Saos-2 cells. We found that the protocols containing SDS were cytotoxic during recellularization. Heat treatment at 47 °C was not cytotoxic, removed cellular constituents, inactivated alkaline phosphatase activity, and maintained the levels of calcium deposition. Subsequently, we investigated the differentiation efficiency of a direct bone coculture system in the established decellularized Saos-2 matrix, an inorganic matrix of calcium phosphate, and a plastic plate as a control. We found that the decellularized Saos-2 cell matrix obtained by heat treatment at 47 °C enhanced osteoclast differentiation and matrix mineralization better than the inorganic matrix and the control. This simple and low-cost method allows us to create a Saos-2 decellularized matrix that can be used as an in vivo-like support for the growth and differentiation of bone cells.


Supramolecularly Engineered Conjugate of Bacteria and Cell Membrane-Coated Magnetic Nanoparticles for Enhanced Ferroptosis and Immunotherapy of Tumors.
Although various ferroptosis inducers including magnetic nanoparticles (Fe3 O4 ) and iron-organic frameworks have been applied in cancer treatment, the mild immunogenicity, low targeting efficiency to the tumor, and poor tissue penetration have limited the therapeutic efficacy. Herein, a supramolecularly engineered conjugate between living bacteria (facultative anaerobic Salmonella typhimurium VNP20009, VNP) and cancer cell membranes-coated Fe3 O4 nanoparticles is developed for improving targeted delivery of Fe3 O4 nanoparticles into the tumor tissue and for synergistic ferroptosis and immunotherapy of tumor. The enhanced ferroptosis induced by both Fe3 O4 nanoparticles and the loaded ferroptosis inducing agent (sulfasalazine (SAS)) effectively inhibits tumor growth and generates immune response via immunogenic cell death (ICD). The colonization of VNP in tumors also induces adaptive immune responses and further promotes ferroptosis. Fundamentally, the supramolecular conjugate of VNP and cell membranes-coated Fe3 O4 can potentiate the therapeutic capability of each other through mutually magnifying the ferroptosis and immunotherapy, resulting in significantly enhanced antitumor effects.


The Onset of H + Ketene Products from Vinoxy Radicals Prepared by Photodissociation of Chloroacetaldehyde at 157 nm.
We investigate the unimolecular dissociation of the vinoxy radical (CH2CHO) prepared with high internal energy imparted from the photodissociation of chloroacetaldehyde (CH2ClCHO) at 157 nm. Using a velocity map imaging apparatus, we measured the speed distribution of the recoiling chlorine atoms, Cl((2)P3/2) and Cl((2)P1/2), and derived from this the resulting distribution of kinetic energy, P(ET), imparted to the Cl + vinoxy fragments upon dissociation. Using conservation of energy, the distribution of kinetic energy was used to determine the total internal energy distribution in the radical. The P(ET) derived for the C-Cl bond fission presented in this work suggests the vinoxy radicals are mostly formed in the à state. We also took ion images at m/z = 42 and m/z = 15 to characterize the branching between the unimolecular dissociation channels of the vinoxy radical to H + ketene and methyl + CO products. Our results show a marked change in the branching ratio between the two channels from the previous study on the photodissociation of chloroacetaldehyde at 193 nm by Miller et al. (J. Chem. Phys., 2004, 121, 1830) in that the production of ketene is now favored over the production of methyl. To help analyze the data, we developed a model for the branching between the two channels that takes into account how the change in rotational energy en route to the products affects the vibrational energy available to surmount the barriers to the channels. The model predicts the portion of the C-Cl bond fission P(ET) that produces dissociative vinoxy radicals, then predicts the branching ratio between the H + ketene and CH3 + CO product channels at each ET. The model uses Rice-Ramsperger-Kassel-Marcus rate constants at the correct sums and densities of vibrational states while accounting for angular momentum conservation. We find that the predicted portion of the P(ET) that produces H + ketene products best fits the experimental portion (that we derive by taking advantage of conservation of momentum) if we use a barrier height for the H + ketene channel that is 4.0 ± 0.5 kcal/mol higher than the isomerization barrier en route to CH3 + CO products. Using the G4 computed isomerization barrier of 40.6 kcal/mol, this gives an experimentally determined barrier to the H + ketene channel of 44.6 kcal/mol. From these calculations, we also predict the branching ratio between the H + ketene and methyl + CO channels to be ∼2.1:1.


Session 7: Early nutrition and later health early developmental pathways of obesity and diabetes risk.
Size at birth and patterns of postnatal weight gain have been associated with adult risk for the development of type 2 diabetes in many populations, but the putative pathophysiological link remains unknown. Studies of contemporary populations indicate that rapid infancy weight gain, which may follow fetal growth restriction, is an important risk factor for the development of childhood obesity and insulin resistance. Data from the Avon Longitudinal Study of Pregnancy and Childhood shows that rapid catch-up weight gain can lead to the development of insulin resistance, as early as 1 year of age, in association with increasing accumulation of central abdominal fat mass. In contrast, the disposition index, which reflects the beta-cells ability to maintain insulin secretion in the face of increasing insulin resistance, is much more closely related to ponderal index at birth than postnatal catch-up weight gain. Infants with the lowest ponderal index at birth show a reduced disposition index at aged 8 years associated with increases in fasting NEFA levels. The disposition index is also closely related to childhood height gain and insulin-like growth factor-I (IGF-I) levels; reduced insulin secretory capacity being associated with reduced statural growth, and relatively short stature with reduced IGF-I levels at age 8 years. IGF-I may have an important role in the maintenance of beta-cell mass, as demonstrated by recent studies of pancreatic beta-cell IGF-I receptor knock-out and adult observational studies indicating that low IGF-I levels are predictive of subsequent risk for the development of type 2 diabetes. However, as insulin secretion is an important determinant of IGF-I levels, cause and effect may be difficult to establish. In conclusion, although rapid infancy weight gain and increasing rates of childhood obesity will increase the risk for the development of insulin resistance, prenatal and postnatal determinants of beta-cell mass may ultimately be the most important determinants of an individual's ability to maintain insulin secretion in the face of increasing insulin resistance, and thus risk for the development of type 2 diabetes.


Optimization of ultrasonic-assisted extraction of flavor compounds from shrimp by-products and characterization of flavor profile of the extract.
This study aimed to optimize the ultrasonic-assisted extraction conditions of flavor compounds from white shrimp heads (WSHs). The effects of sonication amplitude, sonication time, and solvent-to-solid ratio on the extraction yield (EY) of flavor compounds and the degree of protein modification (DPM) were evaluated by Box-Behnken design and response surface methodology (RSM). The optimum EY (40.87 %) and DPM (26.28 %) were obtained at amplitude, time, and solvent-to-solid ratios of 63.2 %, 20.5 min, and 20.8 mL/g, respectively. The optimum DPM value indicates that sonication markedly influenced the protein denaturation, as evidenced by the higher TCA soluble protein content. Further, we also investigated the taste active composition of ultrasonic extract of shrimp head (USH). Results show that the equivalent umami concentration (EUC) value was significantly (p < 0.05) increased in the ultrasonic extract of shrimp head (USH) (55.44 ± 3.25 g MSG/100 g) compared to the control shrimp head extract (CSH) (8.32 ± 1.07 g MSG/100 g). This study also deals with the development of shrimp flavor concentrate (SFC) using USH by the conventional heating process. Sensory evaluation of SFC revealed that the shrimp-like aroma and umami taste characteristics were predominant. Thus, USH's improved umami taste composition demonstrates its potential utilization for producing SFC with higher EUC.


An antibacterial vaccination strategy based on a glycoconjugate containing the core lipopolysaccharide tetrasaccharide Hep2Kdo2.
Certain non-mammalian cell wall sugars are conserved across a variety of pathogenic bacteria. This conservation of structure, combined with their structural differences when compared with mammalian sugars, make them potentially powerful epitopes for immunization. Here, we report the synthesis of a glycoconjugate that displays the so-called 'inner core' sugars of Gram-negative bacterial cell walls. We also describe an antibacterial vaccination strategy based on immunization with the glycoconjugate and the subsequent administration of an inhibitor that uncovers the corresponding epitope in pathogenic bacteria. The core tetrasaccharide, Hep2Kdo2, a common motif in bacterial lipopolysaccharides, was synthesized and attached via a chain linker to a diphtheria toxin mutant carrier protein. This glycoconjugate generated titres of antibodies towards the inner core tetrasaccharide of the lipopolysaccharide, which were capable of binding the cell-surface sugars of bacterial pathogenic strains including Neisseria meningitidis, Pseudomonas aeruginosa and Escherichia coli. Exposure of bacterial lipopolysaccharide in in vitro experiments, using an inhibitor of capsular polysaccharide transport, enabled potent bacterial killing with antiserum.


MiRNA-384-5p targets GABRB1 to regulate ketamine-Induced Neurotoxicity in Neurons.
Ketamine is an anesthetic adjunct widely applied in the clinic that can induce hippocampal neurodegeneration in the brain. MicroRNAs (miRNAs) have been shown to be related to the regulation of ketamine-mediated neurotoxicity. This investigation aimed to determine the function of miR-384-5p in ketamine-induced neurotoxicity. Neonatal hippocampal neurons were isolated from rats and treated with varying doses of ketamine. RT-qPCR was utilized to measure the miR-384-5p level in ketamine-treated neurons. Neuronal viability was evaluated by MTT assay. TUNEL staining and flow cytometry were applied to measure neuronal apoptosis. H2-DCFDA staining was utilized to detect the intracellular ROS level. Protein levels were measured using Western blotting. A luciferase reporter experiment was used in HEK293T cells to verify the interaction of miR-384-5p with GABRB1. Ketamine induced neurotoxicity and miR-384-5p upregulation in hippocampal neurons. MiR-384-5p downregulation mitigated ketamine-induced neurotoxicity by restraining apoptosis and ROS activity in neurons. GABRB1 was demonstrated to be targeted by miR-384-5p. GABRB1 depletion worsened ketamine-induced neurotoxicity. Moreover, GABRB1 depletion lessened the protective effect of miR-384-5p inhibition against ketamine-mediated neurotoxicity. MiR-384-5p regulates ketamine-induced neurotoxicity in hippocampal neurons by targeting GABRB1.


A Comparative Study on Birth Outcomes between Korean Women and Immigrant Women.
The purpose of this study was to compare birth outcomes between Korean women and immigrant women. Medical records were reviewed retrospectively from 201 immigrant women and 201 Korean women who delivered babies at K women's hospital in U city from January 2006 to December 2009. Maternal outcomes related factors included nationality, age, obstetric history, delivery type, indications of cesarean section, and complications of pregnancy and delivery. Principal neonatal outcomes were birth weight, Apgar scores, and complications of newborns. Immigrant women were younger and had fewer pregnancies, abortions, and surviving children than Korean women. The rate of primary cesarean section and its indication in immigrant women were not significantly different from Korean women. However, immigrant women's newborn were more likely to have low birth weight and meconium staining. The results of this study indicate less equity of immigrant women in women's health care, although immigrant women's babies had lower Apgar score and more meconium staining. Nurses should help immigrant women cope with labor process effectively to prevent adverse health outcomes for their newborns.


Immediate transepithelial photorefractive keratectomy for treatment of laser in situ keratomileusis flap complications.
To study the role of photorefractive keratectomy (PRK) in the management of laser in situ keratomileusis (LASIK) flap complications. A retrospective analysis was performed of seven patients (14 eyes) who had bilateral, simultaneous LASIK (single surgeon [TGA], Summit Apex Plus laser, Hansatome microkeratome in six patients [12 eyes], Automated Corneal Shaper keratome in one patient [two eyes]). One eye of each patient received PRK for a flap complication. The seven patients (four women, three men) had a mean age of 39.2 years (range, 22 to 64 yr). The uncomplicated LASIK eyes had moderate to high myopia (-2.25 to -8.75 D) and the eyes with LASIK flap complications had mild to moderate myopia (-1.50 to -5.75 D). Immediate transepithelial PRK was performed in all eyes after repositioning the defective flap. All seven patients had excellent visual outcome at 6 months follow-up; one patient required an enhancement (astigmatic keratotomy). Six of the seven LASIK eyes had best spectacle-corrected visual acuity of 20/20 or better and one LASIK eye had 20/25. In the transepithelial PRK eyes, six of the seven eyes had best spectacle-corrected visual acuity of 20/20 or better and one eye had 20/30. Immediate transepithelial PRK treatment of irregular and incomplete LASIK flaps at the time of surgery is an excellent therapeutic option to delayed surgical treatment.


Neural feedback for instantaneous spatiotemporal modulation of afferent pathways in bi-directional brain-machine interfaces.
In bi-directional brain-machine interfaces (BMIs), precisely controlling the delivery of microstimulation, both in space and in time, is critical to continuously modulate the neural activity patterns that carry information about the state of the brain-actuated device to sensory areas in the brain. In this paper, we investigate the use of neural feedback to control the spatiotemporal firing patterns of neural ensembles in a model of the thalamocortical pathway. Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is achieved based on microstimulation of thalamic relay cells through multiple-input multiple-output (MIMO) feedback controllers. This closed loop feedback control mechanism is achieved by simultaneously varying the stimulation parameters across multiple stimulation electrodes in the thalamic circuit based on continuous monitoring of the difference between reference patterns and the evoked responses of the cortical PY cells. We demonstrate that it is feasible to achieve a desired level of performance by controlling the firing activity pattern of a few "key" neural elements in the network. Our results suggest that neural feedback could be an effective method to facilitate the delivery of information to the cortex to substitute lost sensory inputs in cortically controlled BMIs.


Partial nitrification achieved by pulse sulfide doses in a sequential batch reactor.
A nitrifying sequential batch reactor operated under 2-day cyclic aerobic and anoxic conditions was pulse dosed with incremental sulfide concentrations during anoxic conditions. The nitrite-oxidizing bacteria were found to be more sensitive to sulfide than the ammonia oxidizers. A maximum of nitrite-N to (nitrite-N + nitrate-N) accumulation ratio of 0.75 was obtained at an initial pulse sulfide-S concentration of 45 mg/L under pH control at 7.5 +/- 0.2 and fully mixing conditions. Total ammonium nitrogen was removed almost 100% at a removal rate of 0.73 +/- 0.05 g/L x day, achieved during the aerobic days of the cycles. Denaturing gradientgel electrophoresis (DGGE) and fluorescence in situ hybridization (FISH) analyses indicated the shift in the ammonia- and nitrite-oxidizing populations triggered by sulfide addition, partial nitrification, and subsequent recovery to complete nitrification. Interestingly, archaeal amoA genes were retrieved under the conditions of sulfide addition. These results indicate that the pulse sulfide application can be used as a tool to accumulate nitrite, which is of importance for the subsequent anaerobic ammonium oxidation (anammox) process in the achievement of complete nitrogen removal.


In Sickness and in Health: Expert Discussions on Abortion Indications, Risks, and Patient-Doctor Relationships in Postwar Poland.
This article analyzes expert debates relating to abortion in Poland between 1956 and 1993, a period when the procedure was legal and accessible. Through the pages of the primary Polish journal for gynecology and obstetrics, Ginekologia Polska, the author traces continuities and ruptures around three major intersecting themes: the procedure's indications, its (dis)connection to health, and the patient-doctor relationship. The journal became a forum showcasing interpretative tensions over indications for abortion and the malleability of the categories "therapeutic" and "social." In addition to these tensions, abortion was represented throughout this period as a potentially risky surgery, although this was initially nuanced with parallel representations of legal abortion combating maternal mortality. During the 1970s, abortion began to be linked to infertility, often in simplistic cause-and-effect terms. Simultaneously, opposition to abortion based on the idea of defense of the nation and fetal "life," surfaced in expert discourse.


Correlation of the extracellular glutamate concentration with extent of blood flow reduction after subdural hematoma in the rat.
The excitatory neurotransmitters glutamate and aspartate are an important factor in the causation of ischemic brain damage. The concentration of glutamate and aspartate was serially measured in extracellular fluid using in vivo microdialysis after induction of a subdural hematoma or after a sham operation in the rat. Measurements were made in the cortex underlying the hematoma and in the ipsilateral hippocampus, and these findings were correlated with regional cerebral blood flow (CBF), measured autoradiographically 2 hours after hematoma induction. In the severely ischemic cortex underlying the hematoma (mean CBF less than 25 ml/100 gm/min), glutamate and aspartate content increased more than 750% over basal levels. In individual animals the magnitude of glutamate release correlated with the extent of the focal ischemic zone under the hematoma (r = 0.907). Hippocampal glutamate levels rose 339%, yet regional CBF was preserved (114 ml/100 gm/min). This accords with focal hypermetabolism in this model, and may imply a glutamate-mediated "excitotoxic" process after subdural hematoma.


Impact of collaborative management and early admission in labor on method of delivery.
This study compared the effects of early admission in labor and perinatal care provider on delivery method. Higher spontaneous vaginal delivery rates for certified nurse midwives as compared with physicians have been reported in observational studies and randomized clinical trials. Certified nurse midwives, with their more expectant approach to labor management, would be expected to admit women later in labor than obstetricians. Prospective cohort study of 2,196 low-risk pregnancies, with singleton, vertex infants admitted in spontaneous labor. Independent and joint effects of perinatal care provider and cervical dilation at admission on delivery method were evaluated. Confounding was addressed using restriction and multiple regression. Fewer (23.4%) women in collaborative care were admitted in early labor (< 4 cm cervical dilation) than women managed by obstetricians (95% CI = -27.6 to -19.2). Obstetrician care had 9% to 30% fewer spontaneous vaginal deliveries. Women admitted early in labor also had 6% to 34% fewer spontaneous vaginal deliveries. Evaluation of joint effects suggested that interaction between obstetrician provider and earlier admission increased the risk of operative delivery. Later admission in labor (at 4 cm or greater cervical dilation) and management of perinatal care by certified nurse midwives in collaboration with obstetricians increased the rate of spontaneous vaginal delivery in low-risk women.


[Life expectancy of the residents of St. Petersburg].
The dynamics of the mean life expectancy (LE) were analyzed for the residents of Saint-Petersburg in 1979-2001. The trends of the above index were compared for Saint-Petersburg, Russia and a number of countries in the Eastern, Central and Western Europe. The influence of different age- and sex-groups on the mortality-intensity changes observed at crucial stage of the mentioned period were analyzed and evaluated. An LE increase at removing certain mortality causes from some age intervals were assessed. The specificity of mortality processes in Russia and Saint Petersburg was found to be essentially different from that observed in other countries. The conclusion was substantiated on that the social-and-economic situation in the country and in the city has a significant impact on the mortality level among population and, primarily, among the able-bodied population.


S100A4 mRNA expression level is a predictor of radioresistance of pancreatic cancer cells.
Improving poor outcomes in patients with pancreatic cancer requires a greater understanding of the biological mechanisms contributing to radioresistance. We, therefore, sought to identify genes involved in the radioresistance of pancreatic cancer cells. Two pancreatic cancer cell lines, CFPAC-1 and Capan-1, were repeatedly exposed to radiation, establishing two radioresistant cell lines. Gene expression profiling using cDNA microarrays was performed to identify genes responsible for radioresistance. The levels of expression of mRNAs encoded by selected genes and their correlation with radiation dose resulting in 50% survival rate were analyzed in pancreatic cancer cell lines. The radiation dose resulting in a 50% survival rate was significantly higher in irradiated (IR) compared to parental CFPAC-1 cells (8.31 ± 0.85 Gy vs. 2.14 ± 0.04 Gy, P<0.0001), but was lower in IR compared with parental Capan-1 cells (2.66 ± 0.24 Gy vs. 2.25 ± 0.03 Gy, P=0.04). cDNA microarray analysis identified 4 genes, including S100 calcium binding protein A4 (S100A4), overexpressed and 23 genes underexpressed in the IR compared with the parental cell lines. The levels of S100A4 mRNA expression were correlated with radiation dose resulting in a 50% survival rate (Pearson's test, R2=0.81, P=0.0025). S100A4 mRNA expression may predict radioresistance of pancreatic cancer cells and may play an important role in the poor response of pancreatic cancer cells to radiation therapy.


The effect of adriamycin on cell cycle progression and DNA replication in chinese hamster ovary cells.
Administration of[3H]aflatoxin B2 (2,3-dihydroaflatoxin B1)(AFB2) to male rats resulted in levels of hepatic DNA- and ribosomal (r)RNA-aflatoxin adducts that were about 1% of those for rats given [3H]aflatoxin B1(AFB1). The levels of hepatic protein-aflatoxin adducts were 35 to70% as great for AFB2-treated as compared to AFB1-treated rats...


RAS mutation status in combination with the JSHBPS nomogram may be useful for preoperative identification of colorectal liver metastases with high risk of recurrence and mortality after hepatectomy.
To investigate the prognostic impact of RAS mutations on the Japanese Society of Hepatobiliary and Pancreatic Surgeons (JSHBPS) nomogram score in patients with colorectal cancer liver metastasis (CRLM) following hepatectomy. We included 218 consecutive patients undergoing hepatectomy for CRLM between 2004 and 2020. The JSHBPS nomogram score was calculated using six preoperative clinical factors. The score ranged from 0 to 25, and higher scores indicated greater tumor burden. Associations of RAS mutations with disease-free survival (DFS) and overall survival (OS) by the JSHBPS nomogram score were examined. Multivariable Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and confidence intervals (CIs). RAS mutations were detected in 72 (33%) of the 218 patients. Multivariate analyses revealed that RAS mutations were independently associated with poor DFS (HR, 1.93; 95% CI: 1.20-3.10; p = .007) and OS (HR, 2.65; 95% CI: 1.59-4.71; p = .001) compared with wild-type RAS with JSHBPS nomogram scores ≤ 10. However, in patients with scores ≥ 11, the association of RAS mutations with DFS or OS was not statistically significant (p > .08). RAS mutation status in combination with the JSHBPS nomogram may be useful for preoperatively identifying CRLM with high risk of recurrence and mortality after hepatectomy.


Preparation of carbon nanotube-alginate nanocomposite gel for tissue engineering.
A novel scaffold material based on an alginate hydrogel which contained carbon nanotubes (CNTs) was prepared, and its mechanical property and biocompatibility evaluated. Soluble CNTs were prepared with acid treatment and dispersed in sodium alginate solution as a cross-linker. After which, the mechanical property (elastic deformation), saline sorption, histological reaction, and cell viability of the resultant nanocomposite gel (CNT-Alg gel) were evaluated. The CNT-Alg gel showed faster gelling and higher mechanical strength than the conventional alginate gel. Saline sorption amount of freeze-dried CNT-Alg gel was equal to that of the alginate gel. In terms of histological evaluation and cell viability assay, CNT-Alg gel exhibited a mild inflammatory response and non-cytotoxicity. These results thus suggested that CNT-Alg gel could be useful as a scaffold material in tissue engineering with the sidewalls of CNTs acting as active sites for chemical functionalization.


Patient and family co-developed participant information to improve recruitment rates, retention, and patient understanding in the Rehabilitation Strategies Following Oesophago-gastric and Hepatopancreaticobiliary Cancer (ReStOre II) trial: Protocol for a study within a trial (SWAT).
Background: Whilst the potential benefits of exercise rehabilitation in cancer survivorship are plentiful, recruitment to survivorship rehabilitation trials remains suboptimal. There is growing evidence that Public and Patient Involvement (PPI) initiatives can increase the rate of recruitment to research. This study within a trial (SWAT) will examine if participant information co-developed by patients and their families can lead to greater recruitment rates, retention and understanding of the Rehabilitation Strategies in Oesophago-gastric and Hepatopancreaticobiliary Cancer (ReStOre II) trial when compared to standard participant information. Methods: This SWAT will be carried out over two phases. Phase I will utilise qualitative methods to develop (Phase Ia) and refine (Phase Ib) the new participant information. Phase Ia will recruit up to 20 survivors of upper gastrointestinal or hepatopancreaticobiliary cancer, or their family members, to take part in a focus group or interview to develop the new participant information. Focus groups/interviews will be recorded, transcribed verbatim and analysed thematically. In Phase Ib, participants will return for a second focus group/interview to refine the participant information. Once finalised, the participant information will be submitted to ethics for approval. In Phase II, potential participants for the ReStOre II trial will be randomly assigned to receive either the standard or patient and family co-developed participant information. The two forms of participant information will be compared by recruitment and retention rates, and participant understanding of the trial (Decision-Making Questionnaire). Discussion: We anticipate that engaging with patients and their families to develop participant information will help to increase patient understanding of the ReStOre II trial and therefore recruitment and retention rates. The results of this SWAT will indicate the usefulness of this strategy for optimising recruitment to exercise rehabilitation trials in cancer survivorship. Registration: SWAT: Northern Ireland Hub for Trials Methodology Research SWAT Repository Store ( SWAT-100). ReStOre II: ClinicalTrials.gov ( NCT03958019).


Factors influencing movement of chronic psychiatric patients from the orientation to the working phase of the nurse-client relationship on an inpatient unit.
To identify factors influencing movement of nurse-patient dyads from Peplau's orientation phase to the working phase of the nurse-client relationship in a tertiary care psychiatric setting. Ten nurse-client dyads were interviewed after the initial nurse-client assignment until a consensus was reached between client, nurse, and investigator/CNS that the relationship was in the working phase. Factors causing the relationship to progress, from the clients' perspective, were the perceived attitude of the nurse, the nature of the planned therapeutic sessions, and what happened between therapeutic sessions. Factors hindering the development of the relationship included a nurse's or client's unavailability, a sense of distance/inequity, differences in realities/values, and mutual withdrawal. The relationship was perceived as supportive and "powerful" when it progressed to the working phase, but as very negative and like "limbo" if instead it moved to a phase of mutual withdrawal. Nurses can help clients move from the orientation phase to the working phase by remaining available, consistent, and acting in a way that promotes trust. When the relationship does not progress to the working phase within 6 months, a therapeutic transfer should be considered.


Extracorporeal clearance of colistin methanesulphonate and formed colistin in end-stage renal disease patients receiving intermittent haemodialysis: implications for dosing.
Colistin, administered intravenously as its inactive prodrug colistin methanesulphonate (CMS), is being increasingly used. However, there is very limited information available on the impact of haemodialysis (HD) on the pharmacokinetics of CMS and formed colistin. A single 30 min intravenous dose of CMS (150 mg of colistin base activity) was administered to 10 patients undergoing HD. HD was performed from 1.5 to 5.5 h after the start of the CMS infusion. Serial blood samples were collected over 50 h, additional blood samples pre- and post-dialysis membrane at three timepoints during HD, dialysate samples at four timepoints during HD, and a cumulative urine sample over 24 h. CMS and colistin were determined by HPLC. Population modelling and determination of HD clearance by multiple methods was conducted. The average amount of CMS recovered in the dialysate was 30.6% of the dose administered. The concentrations of CMS and colistin in the plasma and the amounts of CMS recovered in the dialysate were well described by the population disposition model. The clearance of CMS by dialysis as estimated by population analysis based on systemic plasma concentrations and amounts in the dialysate was 4.26 L/h (26% coefficient of variation). The dialysis clearance determined from the pre- and post-membrane plasma concentrations was 5.67 L/h (21%) for CMS and 3.99 L/h (44%) for colistin. Thus, CMS clearance by dialysis from trans-cartridge extraction was ∼30% higher than when calculated based on the amount in dialysate, suggesting adsorption to the membrane. Due to the extensive removal of CMS by dialysis, HD should be conducted at the end of a dosing interval and a supplemental dose should be administered.


Influence of lifetime food restriction on causes, time, and predictors of death in dogs.
To describe effects of lifetime food restriction on causes of death and the association between body-mass characteristics and time of death in dogs. Paired-feeding study. 48 dogs from 7 litters. Dogs were paired, and 1 dog in each pair was fed 25% less food than its pair mate from 8 weeks of age until death. Numerous morphometric and physiologic measures were obtained at various intervals throughout life. Associations of feeding group to time and causes of death were evaluated, along with important associated factors such as body composition components and insulin-glucose responses. Median life span was significantly longer for the group that was fed 25% less food, whereas causes of death were generally similar between the 2 feeding groups. High body-fat mass and declining lean mass significantly predicted death 1 year prior to death, and lean body composition was associated with metabolic responses that appeared to be integrally involved in health and longevity. Results were similar to results of diet restriction studies in rodents and primates, reflecting delayed death from species- and strain-specific intrinsic causes. Clinicians should be aware that unplanned body mass changes during mid- and later life of dogs may indicate the need for thorough clinical evaluation.


Genetics of Sex-linked yellow in the Syrian hamster.
Alternating patches of black and yellow pigment are a ubiquitous feature of mammalian color variation that contributes to camouflage, species recognition, and morphologic diversity. X-linked determinants of this pattern--recognized by variegation in females but not in males--have been described in the domestic cat as Orange, and in the Syrian hamster as Sex-linked yellow (Sly), but are curiously absent from other vertebrate species. Using a comparative genomic approach, we develop molecular markers and a linkage map for the euchromatic region of the Syrian hamster X chromosome that places Sly in a region homologous to the centromere-proximal region of human Xp. Comparison to analogous work carried out for Orange in domestic cats indicates, surprisingly, that the cat and hamster mutations lie in nonhomologous regions of the X chromosome. We also identify the molecular cause of recessively inherited black coat color in hamsters (historically referred to as nonagouti) as a Cys115Tyr mutation in the Agouti gene. Animals doubly mutant for Sly and nonagouti exhibit a Sly phenotype. Our results indicate that Sly represents a melanocortin pathway component that acts similarly to, but is genetically distinct from, Mc1r and that has implications for understanding both the evolutionary history and the mutational mechanisms of pigment-type switching.


An unusual cause of generalised seizure following cardiac surgery: with bolus cefazolin administration.
Although some of the aetiological factors of seizure, such as cerebral microemboli, cerebral oedema, hypoperfusion, cerebral hypoxia and metabolic encephalopathy cannot be completely controlled during cardiac surgery, cautious management of all steps in the procedure may prevent the administrative causes of seizure. Cefazolin, which is known to be a proconvulsant agent, may be a suspected agent of seizure complications in patients with renal insufficiency. Surprisingly, intravenous bolus administration of cefazolin may also trigger seizure in patients with normal renal function. In this case report, a complication of generalised seizure after cardiac surgery with intravenous bolus administration of cefazolin is described, along with a brief review of the literature.


Measuring the impact of therapy on medication use: data-linkage study.
The psychological therapies service (PTS) in the Northern Health and Social Care Trust, in Northern Ireland, provides therapies to adults with moderate or severe mental health difficulties. Psychometric outcomes data are routinely collected to assess if a patient demonstrates significant improvement in their main presenting problem area following therapy. The wider impact of therapy is not fully measured in the outcomes database as this would be disproportionately burdensome for both patient and therapist. The present study, to our knowledge, is the first to use data linkage to link patient therapy outcomes data with prescriptions data. To widen our understanding of patient medication use before and after therapy. Using Health and Care Number as a unique identifier, the Psychological Therapies Service - Routine Outcome Measurement Database (n = 3625) and data from 72 500 controls were linked with data from the Enhanced Prescribing Database (EPD). The EPD data were sourced from the Honest Broker Service. Key findings from the study were: (a) the odds of PTS clients using antipsychotics in the year before therapy were 25 times greater compared with controls (odds ratio (OR) = 24.53, 95% CI 20.16-29.84); (b) in the 1st year post discharge, PTS clients who clinically improved post therapy discharge were more likely than 'non-engagers' and 'non-improvers' to come off antianxiety medication (OR = 0.61, 95%, CI 0.38-0.98); and (c) therapy did not have an impact on antidepressant use. The results highlight the need for discussion between therapy services, GPs and psychiatry about whether more engagement and collaboration is needed to plan phased reduction in medication.


[Growth of exclusively breast-fed Chilean infants in relation to new 1994 WHO Reference Charts].
The aim of this study was to evaluate the growth of Chilean infants from medium-to-low socioeconomic status fed according to the current WHO guidelines. Growth pattern was compared to a recent reference chart published by WHO for infants, and the NCHS/WHO growth standards. The source of information was a nation-wide infant feeding survey conducted in 1993. From this database, infants aged 1-12 month +/- 5 days, with exclusive breast feeding until the fourth or sixth month were selected (939 males, 940 females). The weight-for-age z-score (WAZ), and the height-for-age z-score (HAZ) were calculated using both the NCHS/ WHO and the new WHO reference growth charts. At each month of age, WHZ and HAZ results were grouped in the following categories: < = -2.0; -1.9 to -1.0; 0 +/- 0.9; 1.0 to 1.9; and > = 2.0. Observed WAZ at the first month of age was below the new WHO reference chart (0.32 z-score), increasing up to 1.29 z-score at the tenth month. The HAZ results were lower the WHO reference chart throughout the period studied, although a trend to improved values was noted during the second semester (F = 6.01 p < 0.001). Growth pattern of the studied group was more similar to the NCHS/WHO chart than the new chart proposed by WHO. As a consequence, the new WHO reference chart identifies a higher proportion of the infants as having a subnormal nutritional status during the first semester of life, compared to those classified in this category by the NCHS/WHO standards (p < 0.001). This can be a factor for the introduction of complementary foods early in life. The relative homogeneity of the population used as source of the WHO reference chart may limit it use in developing countries.


Common carotid intima-media thickness and framingham risk score predict incident carotid atherosclerotic plaque formation: longitudinal results from the study of health in Pomerania.
Cross-sectional studies describe a positive association between common carotid artery intima-media thickness (CCA-IMT) and carotid plaques (CP). However, longitudinal data on the predictive value of CCA-IMT for occurrence of CP are limited. Therefore, the role of increasing CCA-IMT in the atherosclerotic process is still discussed controversially. We investigated the predictive value of CCA-IMT and the Framingham risk score (FRS) for incident CP formation in a population-based longitudinal study of 1922 subjects aged 45 to 81 years who underwent ultrasonography of both carotid arteries and received vascular risk factor assessment at baseline and after 5 years. CP was defined as any protruding focal thickening of the intima-media complex. Incident CP formation during follow-up was defined as the appearance of at least 1 CP in a previously plaque-free arterial segment (right and left common, internal, and external carotid arteries and carotid bifurcation). Among the 636 subjects without CP at baseline, 418 (66%) had at least 1 incident CP during follow-up. In a multivariable negative binominal regression model adjusted for age, gender, and the FRS, the number of arterial segments affected by incident CP was 1.53-fold higher (CI, 1.12-2.07; P<0.01) for subjects in the highest quartile of the overall CCA-IMT distribution compared to those in the lowest quartile. Both CCA-IMT and FRS independently predict incident CP formation. The risk of CP formation may actually be underestimated in subjects with low FRS and high IMT.


Abrogation of the Cripto gene in mouse leads to failure of postgastrulation morphogenesis and lack of differentiation of cardiomyocytes.
Cripto-1(Cr1) protein encoded by the tdgf1 gene, is a secreted growth factor that is expressed early in embryonic development and is re-expressed in some tumors of the breast and colon. During embryonic development, Cr1 is expressed in inner cell mass cells and the primitive streak, and later is restricted to the developing heart. To investigate the role of Cr1 during mouse development, mice were generated that contain a null mutation of both Cr1 genes, derived from homologous recombination in embryonic stem cells. No homozygous Cr1-/- mice were born, indicating that Cr1 is necessary for embryonic development. Embryos initiated gastrulation and some embryos produced mesoderm up to day E7.5. Increasingly aberrant morphogenesis gave rise to disordered neuroepithelium that failed to produce a recognizable neural tube, or head-fold. Although some biochemical markers of differentiating ectoderm, mesoderm and endoderm were expressed, all the cardiac-specific markers were absent from day E8.7 embryos: (&agr;)MHC, betaMHC, MLC2A, MLC2V and ANF, whereas they were expressed in wild-type embryos. The yolk sac and placental tissues continued development in the absence of the embryo until day E9.5 but lacked large yolk sac blood vessels. Chimeric mice were constructed by microinjection of double targeted Cr1(-/- )embryonic stem cells into normal C57BL/6 blastocysts. The Cr1 produced by the normal C57BL/6 cells fully rescued the phenotype of Cr1(-/-) cells, indicating that Cr1 protein acted in a paracrine manner. Cells derived from the embryo proliferated and migrated poorly and had different adhesion properties compared to wild type. Therefore, lethality in the absence of Cr1, likely resulted largely from defective precardiac mesoderm that was unable to differentiate into functional cardiomyocytes.


Stenting with Acclino (flex) for symptomatic intracranial stenosis as secondary stroke prevention.
Stroke recurrence is high in patients with symptomatic intracranial stenosis despite best medical treatment. Based on evidence from past studies using previous stent generations, elective intracranial stenting (eICS) is considered in a minority of patients. This study aims to report on experience performing eICS with a novel device combination. We retrospectively reviewed data from three high volume stroke centers and analyzed patients that were treated with eICS for symptomatic intracranial stenosis using the Acclino (flex) stent and the NeuroSpeed balloon catheter (Acandis GmbH, Pforzheim, Germany). Study endpoints were periprocedural rates of stroke regardless of territory or death at discharge and at the time of follow-up after eICS. Safety evaluation included asymptomatic and symptomatic intracranial hemorrhage, serious adverse events related to the intervention, and evaluation of stent patency at the time of follow-up. The median age of patients that met the inclusion criteria (n=76) was 69 years. Target vessels were located in the anterior circulation in 55.3% (42/76) of patients. The periprocedural stroke rate was 6.5% (fatal stroke 2.6%; non-fatal stroke 3.9%) at discharge after eICS. Asymptomatic intracranial hemorrhage was observed in 5.2% (4/76) of patients. Follow-up DSA revealed in-stent restenosis of 25% (15/60), and percutaneous transluminal angioplasty was performed again in 11.6% (7/60) of patients. Stenting for symptomatic intracranial stenosis with the Acclino (flex)/NeuroSpeed balloon catheter seemed to be safe and reinforces eICS as an endovascular therapy option for secondary stroke prevention. Future studies are warranted to confirm these findings and investigate antithrombotic strategies and in-stent restenosis to minimize periprocedural complications and guarantee long term stent patency.


Toward orthogonal non-individualised head-related transfer functions for forward and backward directional sound: cluster analysis and an experimental study.
Individualised head-related transfer functions (HRTFs) have been shown to accurately simulate forward and backward directional sounds. This study explores directional simulation for non-individualised HRTFs by determining orthogonal HRTFs for listeners to choose between. Using spectral features previously shown to aid forward-backward differentiation, 196 non-individualised HRTFs were clustered into six orthogonal groups and the centre HRTF of each group was selected as representative. An experiment with 15 listeners was conducted to evaluate the benefits of choosing between six centre-front and six centre-back directional sounds rather than the single front/back sounds produced by MIT-KEMAR HRTFs. Sound localisation error was significantly reduced by 22% and 65% of listeners reduced their front-back confusion rates. The significant reduction was maintained when the number of HRTFs was reduced from six to five. This represents a preliminary success in bridging the gap between individual and non-individual HRTFs for applications such as spatial surround sound systems. STATEMENT OF RELEVANCE: Due to different pinna shapes, directional sound stimuli generated by non-individualised HRTFs suffer from serious front-back confusion. The reported work demonstrates a way to reduce front-back confusion for centre-back sounds generated from non-individualised HRTFs.