[Prevention of side effects of specific chemotherapy in patients with pulmonary tuberculosis].
Data are given related to a combined examination of 168 pulmonary tuberculosis patients in whom immunomodulating T-activin and levamisole chemotherapy was carried out in 40 subjects. In tuberculosis patients with significantly abnormal parameters of the immunity T-system, side effects of the antituberculosis drugs developed in 67.7%, while in those who were subjected to a general scheme of treatment with inclusion of the immunomodulating drugs in only 17.5%. T-activin was found to be highly effective in preventing side effects of the antituberculosis drugs. A diverse influence of the immunity modulating drugs on some T-lymphocyte classes was registered, which is essential in choosing the suitable modulator and regimen of its use.


Insect pest management in tropical Asian irrigated rice.
Abundant natural enemies in tropical Asian irrigated rice usually prevent significant insect pest problems. Integrated pest management (IPM) extension education of depth and quality is required to discourage unnecessary insecticide use that upsets this natural balance, and to empower farmers as expert managers of a healthy paddy ecosystem. Farmers' skill and collaboration will be particularly important for sustainable exploitation of the potential of new, higher-yielding and pest-resistant rice. IPM "technology transfer" through training and visit (T&V) extension systems failed, although mass media campaigns encouraging farmer participatory research can reduce insecticide use. The "farmer first" approach of participatory nonformal education in farmer field schools, followed by community IPM activities emphasizing farmer-training-farmer and research by farmers, has had greater success in achieving IPM implementation. Extension challenges are a key topic for rice IPM research, and new pest management technology must promote, rather than endanger, ecological balance in rice paddies.


The Raison D'être for the Community Pharmacy and the Community Pharmacist in Sweden: A Qualitative Interview Study.
Community pharmacies are balancing between business (selling medicines and other products) and healthcare (using the pharmacists' knowledge in order to improve drug utilization). This balance could be affected by regulations decided upon by politicians, but also influenced by others. The aim of this study was to explore important stakeholders' views on community pharmacy and community pharmacists in Sweden. The method used was that of semi-structured qualitative interviews. Political, professional, and patient organization representatives were interviewed. The results show that informants who are pharmacists or representatives of a professional pharmacist organization generally have a healthcare-centered view on community pharmacy/pharmacists. However, different views on how this orientation should be performed were revealed, ranging from being specialists to dealing with uncomplicated tasks. Political organization representatives generally had a more business-oriented view, where competition in the market was believed to be the main driving force for development. A third dimension in which competition was not stressed also emerged; that community pharmacies should primarily distribute medicines. This dimension was most prevalent among the political and patient organization representatives. One conclusion to be drawn is that no stakeholder seemed to have a clear vision or was willing to take the lead for the development of the community pharmacy sector.


An official American Thoracic Society workshop report: tobacco control initiatives within the American Thoracic Society.
Cigarette smoking represents the single most preventable cause of premature morbidity and mortality in the United States and the burden of tobacco use is apparent world-wide. Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease, the third leading cause of death in the United States in 2004. The American Thoracic Society (ATS) and its members have contributed significantly to an understanding of the biological and pathophysiologic mechanisms responsible for the development and management of tobacco-attributable disease and disability. The society's active involvement in tobacco control advocacy and policy-related initiatives are central to its mission. Within the ATS, there is also increased interest in accelerating the society's efforts to understand the mechanisms responsible for the uptake, persistence, and cessation of tobacco use. Scientific, clinical, and educational activities that include an examination of these underlying mechanisms are warranted. This paper describes findings from an ATS initiative that developed a preliminary strategy for enhancing scientific, clinical, educational, and policy-related tobacco control efforts that are consistent with the vision of the ATS. The specific aims of this project included the identification of existing mechanisms, as well as the current governance in place within the ATS infrastructure, to address tobacco control issues related to scientific inquiry, policy initiatives, and advocacy for tobacco control. This assessment generated recommendations to inform the ATS leadership with regard to the future development of relevant tobacco control initiatives.


Mechanisms of hydrogen-peroxide-induced biphasic response in rat mesenteric artery.
1. In phenylephrine (PHE) (1 micro M)-precontracted superior mesenteric arteries from adult rats, low concentration of hydrogen peroxide (H(2)O(2), 10-100 micro M) caused only contraction, while high concentration of H(2)O(2) (0.3-1 mM) caused a biphasic response: a transient contraction followed by a relaxation response. 2. Endothelium removal did not affect the biphasic response. 7,7-Dimethyl-(5Z,8Z)-eicosadienoic acid, diclofenac, furegrelate, or SQ 29548 greatly inhibited the contraction but did not affect the relaxation. 17-Octadecynoic acid, eicosatriynoic acid, ICI 198615, SQ 22536, or ODQ did not inhibit the biphasic response. 3. KCl at 40 mM inhibited the relaxation response to H(2)O(2) by 98+/-24%. 4-Aminopyridine (4-AP) inhibited while tetraethylammonium chloride (TEA), charybdotoxin, or glibenclamide attenuated the relaxation response. A combination of 4-AP, TEA and glibenclamide mimicked the effects of 40 mM KCl. Iberiotoxin, apamin, or barium chloride did not inhibit the relaxation response. 4. H(2)O(2) at 1 mM hyperpolarized membrane potential and reversibly augmented K(+) current in smooth muscle cells of mesenteric artery. These effects of H(2)O(2) were attenuated significantly by 4-AP. 5. In summary, in PHE-precontracted rat mesenteric artery: (1) the response to H(2)O(2) shifted qualitatively from contraction to a biphasic response as H(2)O(2) increased to 0.3 mM or higher; (2) the relaxation response is caused by the activation of K(+) channels, with voltage-dependent K(+) channels playing a primary role; and the contraction is likely to be mediated by thromboxane A(2); (3) the K(+) channel activation by H(2)O(2) is independent of phospholipase A(2), cyclooxygenase, lipoxygenase, cytochrome P450 monooxygenase, adenylate or guanylate cyclase.


Changes in Youth Baseball Pitching Biomechanics: A 7-Year Longitudinal Study.
Pitching biomechanics are associated with performance and risk of injury in baseball. Previous studies have identified biomechanical differences between youth and adult pitchers but have not investigated changes within individual young pitchers as they mature. Pitching kinematics and kinetics will change significantly during a youth pitcher's career. Descriptive laboratory study. Pitching biomechanics were captured in an indoor laboratory with a 12-camera, 240-Hz motion analysis system for 51 youth pitchers who were in their first season of organized baseball with pitching. Each participant was retested annually for the next 6 years or until he was no longer pitching. Thirty kinematic and kinetic parameters were computed and averaged for 10 fastballs thrown by each player. Data were statistically analyzed for the 35 participants who were tested at least 3 times. Within-participant changes for each kinematic and kinetic parameter were tested by use of a mixed linear model with random effects ( P < .05). Least squares means for sequential ages were compared via Tukey's honestly significant difference test ( P < .05). Three kinematic parameters that occur at the instant of foot contact-stride length, lead foot placement to the closed side, and trunk separation-increased with age. With age, shoulder external rotation at foot contact decreased while maximum shoulder external rotation increased. Shoulder and elbow forces and torques increased significantly with age. Year-to-year changes were most significant between 9 and 13 years of age for kinematics and between 13 and 15 years for normalized kinetics (ie, scaled by bodyweight and height). During their first few years, youth pitchers improve their kinematics. Elbow and shoulder kinetics increase with time, particularly after age 13. Thus, prepubescent pitchers may work with their coaches to improve the motions and flexibility of the players' bodies and the paths of their arms. Once proper mechanics are developed, adolescent pitchers can focus more on improving strength and power.


The response of early neural genes to FGF signaling or inhibition of BMP indicate the absence of a conserved neural induction module.
The molecular mechanism that initiates the formation of the vertebrate central nervous system has long been debated. Studies in Xenopus and mouse demonstrate that inhibition of BMP signaling is sufficient to induce neural tissue in explants or ES cells respectively, whereas studies in chick argue that instructive FGF signaling is also required for the expression of neural genes. Although additional signals may be involved in neural induction and patterning, here we focus on the roles of BMP inhibition and FGF8a. To address the question of necessity and sufficiency of BMP inhibition and FGF signaling, we compared the temporal expression of the five earliest genes expressed in the neuroectoderm and determined their requirements for induction at the onset of neural plate formation in Xenopus. Our results demonstrate that the onset and peak of expression of the genes vary and that they have different regulatory requirements and are therefore unlikely to share a conserved neural induction regulatory module. Even though all require inhibition of BMP for expression, some also require FGF signaling; expression of the early-onset pan-neural genes sox2 and foxd5α requires FGF signaling while other early genes, sox3, geminin and zicr1 are induced by BMP inhibition alone. We demonstrate that BMP inhibition and FGF signaling induce neural genes independently of each other. Together our data indicate that although the spatiotemporal expression patterns of early neural genes are similar, the mechanisms involved in their expression are distinct and there are different signaling requirements for the expression of each gene.


[Ultrasound-guided biopsy: screening of prostate cancer with a single set of 14 systematic biopsies].
Standard sextant prostate biopsy may underestimate cancer in men in whom clinical finding and transrectal ultrasound are negative and prostate-specific antigen (PSA) value suspicious for localized prostate cancer (4-10 ng/ml). We describe our experience with a 14 systematic multisite biopsy scheme to detect carcinoma of the prostate (stage T1c). Between January 1999 and February 2000, a total of 177 consecutive patients (mean age 64.1 +/- 7.7 years) underwent systematic transrectal ultrasound (TRUS) guided biopsy for normal digital rectal examination, normal TRUS and abnormal prostate specific antigen 4 ng/ml or greater (4-13 ng/ml). Fourteen core/patient were obtained not depending on prostate size. Biopsies were obtained from conventional sextant biopsies (6 core) and 3 alternate sites which included: the right and left extreme lateral peripheral zone between anterior tissue and posterior gland base (2 core); the right and left transition zone, immediately adjacent to the urethra anterior and posterior (4 core) and the right and left central gland in the mid zone typical of benign prostatic hyperplasia (BPH) (2 core). All specimens were separated for specific location identification. Adenocarcinoma was identified in 61 patients (34.46%). Traditional sextant biopsies showed 23 patients (37.7%) with positive core to detect cancer, while a sextant regimen incorporating lateral peripheral zone biopsies and transitional zone detected 19 cancer (31.1%). The combination of lateral peripheral and transitional zone alone detected cancer in 19 patients. No cancer was detected in central gland. The lateral peripheral zone was the most frequently positive site biopsy with 11 patients (57.9%) followed by the transitional zone with 8 patients (42.1%) in the group of the alternate biopsies sites. Complications of extensive biopsy included hematuria, hematospermia and limited rectal blending in 95% of patients; 1 case of fever (> 38.5 degrees C) for 3 days. Biopsies of the alternate sites are easy, feasible and reproducible. This strategy enhance prostate cancer detection of a 30% compared to conventional sextant biopsies alone. In conclusion, the 6 systematic biopsy of the peripheral zone are inadequate and a minimum of 12 with extensive core in peripheral and transitional zone should routinely be performed to detect a more significant number of men with prostate cancer at stage T1c.


Specific resistances against Pseudomonas syringae effectors AvrB and AvrRpm1 have evolved differently in common bean (Phaseolus vulgaris), soybean (Glycine max), and Arabidopsis thaliana.
*In plants, the evolution of specific resistance is poorly understood. Pseudomonas syringae effectors AvrB and AvrRpm1 are recognized by phylogenetically distinct resistance (R) proteins in Arabidopsis thaliana (Brassicaceae) and soybean (Glycine max, Fabaceae). In soybean, these resistances are encoded by two tightly linked R genes, Rpg1-b and Rpg1-r. To study the evolution of these specific resistances, we investigated AvrB- and AvrRpm1-induced responses in common bean (Phaseolus vulgaris, Fabaceae). *Common bean genotypes of various geographical origins were inoculated with P. syringae strains expressing AvrB or AvrRpm1. A common bean recombinant inbred line (RIL) population was used to map R genes to AvrRpm1. *No common bean genotypes recognized AvrB. By contrast, multiple genotypes responded to AvrRpm1, and two independent R genes conferring AvrRpm1-specific resistance were mapped to the ends of linkage group B11 (Rpsar-1, for resistance to Pseudomonas syringae effector AvrRpm1 number 1) and B8 (Rpsar-2). Rpsar-1 is located in a region syntenic with the soybean Rpg1 cluster. However, mapping of specific Rpg1 homologous genes suggests that AvrRpm1 recognition evolved independently in common bean and soybean. *The conservation of the genomic position of AvrRpm1-specific genes between soybean and common bean suggests a model whereby specific clusters of R genes are predisposed to evolve recognition of the same effector molecules.


The hostile media phenomenon: biased perception and perceptions of media bias in coverage of the Beirut massacre.
After viewing identical samples of major network television coverage of the Beirut massacre, both pro-Israeli and pro-Arab partisans rated these programs, and those responsible for them, as being biased against their side. This hostile media phenomenon appears to involve the operation of two separate mechanisms. First, partisans evaluated the fairness of the media's sample of facts and arguments differently: in light of their own divergent views about the objective merits of each side's case and their corresponding views about the nature of unbiased coverage. Second, partisans reported different perceptions and recollections about the program content itself; that is, each group reported more negative references to their side than positive ones, and each predicted that the coverage would sway nonpartisans in a hostile direction. Within both partisan groups, furthermore, greater knowledge of the crisis was associated with stronger perceptions of media bias. Charges of media bias, we concluded, may reflect more than self-serving attempts to secure preferential treatment. They may result from the operation of basic cognitive and perceptual mechanisms, mechanisms that should prove relevant to perceptions of fairness or objectivity in a wide range of mediation and negotiation contexts.


Dietary protein restriction in chronic renal failure: nutritional efficacy, compliance, and progression of renal insufficiency.
Two findings prompted investigators to examine the effects of dietary manipulation on progression of chronic renal failure: dietary protein restriction is an effective method of ameliorating uremic symptoms and the course of renal insufficiency in an individual patient is predictable. Results from studies of patients and animals with chronic renal failure suggested that a low-protein, phosphorus-restricted diet could slow the rate of loss of renal function. In evaluating these studies, three questions should be considered. First, is the diet nutritionally adequate? Second, has dietary compliance been monitored and achieved? Third, is there evidence that restricting the diet will change the rate of loss of renal function? The scientific basis for each of these questions is addressed in this review.


[Experiences with high-frequency hearing tests in the selection of personnel for noise occupations].
A total of 181 persons aged between 16 and 18 were checked fully audiometrically (conventional and high-frequency audiogram). Dates of history about hereditary hearing damage, own ear diseases, noise exposure during frequent visits to discothecs or usage of Walkman etc. were ascertained by questionnaires. The evaluation of the results was carried out with the help of discrimination analysis allowing a multi-dimensional classification. As a result there could be made a sure discrimination analytic separation in persons with ear diseases during their childhood, when the high frequencies from 10 to 15 kHz were taken in. Thus the damage of the inner ear was to be found mainly on the base of the cochlea. Also in cases of hereditary influence there was to be seen a clear deminution in the high frequency area. The group of persons, who regularly went to discos (more than three times a month) as well as the group often using Walkman revealed a sure separation, when the high frequencies above 8 kHz were considered in the calculation. Altogether there could be seen an early damage more clearly in the high frequency area after ear diseases in childhood as well as a result of sound overloading than in conventional hearing area.


Intranasal Deposition of Accuspray™ Aerosol in Anatomically Correct Models of 2-, 5-, and 12-Year-Old Children.
To our knowledge, quantification of intranasal deposition of aerosol generated by Accuspray(™) (AS) in children has never been published. We hypothesized that deposition would vary significantly with age and with placement of the device within, or outside, of the nostril. We tested these hypotheses in anatomically-correct physical models based on CT scans of 2-, 5-, and 12-year-old children with normal, intranasal airways. Models included a removable anterior nose (AN) with exterior facial features and interior nasal vestibule and nasal valve area and a main nasal airway (MNA), subdivided into upper (superior turbinates and olfactory area), middle (middle turbinates), and lower (inferior turbinates and nasopharynx) thirds. Aerosol was generated from distilled water admixed with (99m)technetium pertechnetate and administered during static airflow by AS inserted inside the right nostril (eight runs/model), or outside the right nostril (six runs/model). Mean aerosol Dv(50) ± standard deviation was 67.8 ± 24.7 μm. Deposition was quantified by 2D gamma scintigraphy and expressed as percentage of the emitted dose. When placed inside the nostril, mean (± standard deviation) deposition within the MNA was significantly less in the 2-year-old, compared to the 5- and 12-year-old, averaging 46.8 ± 33.8% (AN:55.4 ± 29.9%), 75.4 ± 26.7% (AN:23.3 ± 13.6%), and 72.1 ± 18.5% (AN:25.8 ± 18.5%), respectively (p<0.05). When placed outside the nostril, MNA was significantly less in the 2- and 5-year-old compared to the 12-year-old, with 1.4 ± 2.5% (AN:69.7 ± 40.7%), 7.4 ± 9.0% (AN:77.8 ± 32.8%), and 21.1 ± 29.1% (AN:29.2 ± 19.3%), respectively (p<0.05). Deposition in the MNA of all age models was highest when AS was placed inside the nostril (p<0.05). Deposition in the lower third was significantly increased for the 5- and 12-year-old and in the middle third of the 5-year-old when AS was placed inside the nostril. These results indicate that age and device placement play important roles in terms of intranasal deposition, when administering aerosol with Accuspray(™) to children.


Traumatic Tricuspid Regurgitation.
Traumatic tricuspid regurgitation is a rare and progressive disease. Early diagnosis and surgical valve repair are very important. A 57-year-old male was referred to our hospital with a history of blunt chest trauma. Three-dimensional echocardiography showed severe tricuspid regurgitation and demonstrated two main anterior leaflet chordaes of the tricuspid valve rupture and the whole anterior leaflet prolapsed. The diagnosis was severe tricuspid regurgitation due to leaflet chordae rupture secondary to blunt chest trauma. Surgical repair of the tricuspid valve was performed in this patient. At 3-month follow-up, the right ventricle was decreased in size with significantly improved right ventricular function. The signs and symptoms of right heart failure were relieved. In this case, 3-dimensional transthoracic echocardiography enabled fast and non-invasive evaluation of the spatial destruction of the tricuspid valve and subvalvular apparatus to assist in the planning of valve repair.


Field evaluation of personal protection methods against outdoor-biting mosquitoes in Lao PDR.
Protecting people outdoors against mosquito-borne diseases is a major challenge. Here we compared commercially available personal protection methods to identify the most effective method for outdoor use in northern Lao PDR. From June to August 2016 the protective efficacy of treatments were compared in a secondary forest during the afternoon and a village during the evening. Comparisons were made using a replicated Latin square design between: (i) short permethrin-treated overalls; (ii) long permethrin-treated overalls; (iii) short untreated overalls with para-menthane-3,8-diol (PMD) applied topically; (iv) short permethrin-treated overalls plus PMD applied topically; (v) short untreated overalls with metofluthrin coils in a metal casing worn on a belt; and (vi) long untreated overalls. Short untreated overalls served as the control. Cone tests were conducted on the treated and untreated fabric before and after field experiments. A questionnaire survey was used to measure social acceptability. Mosquito coils in a metal casing worn on a belt resulted in 92.3% (95% confidence interval, CI: 88.9-94.6%). landing protection from female mosquitoes in the afternoon and 68.8% (95% CI: 41.7-83.3%) protection in the evening compared to short untreated clothing. PMD was protective both when combined with short permethrin-treated overalls (afternoon, 68.2%, 95% CI: 52.6-78.7%; evening, 52.3%, 95% CI: 33.8-65.7%) and when used in combination with short untreated overalls (afternoon, 55.0%, 95% CI: 41.7-65.2%; evening, 25.2%, 95% CI: 9.4-38.2%). Whilst long permethrin-treated overalls were protective (afternoon, 61.1%, 95% CI: 51.4-68.8%; evening, 43.0%, 95% CI: 25.5-56.4%), short permethrin-treated overalls and long untreated overalls were not. Exposure to new permethrin-treated fabric in cone tests resulted in 25.0% (95% CI, 17.8-32.2%) and 26.2% (95% CI 16.7-35.8%) mortality for susceptible Ae. albopictus and susceptible Ae. aegypti, respectively. There was a loss of efficacy of permethrin-treated clothing after use in the field, with 3 min knockdown rates of Ae. albopictus and 1 h knockdown of Ae. aegypti decreasing over time. Participants considered all treatments acceptable. The portable mosquito coils were highly protective against outdoor biting mosquitoes, although there are safety concerns related to its use. The combination of permethrin-treated clothing and PMD repellent represent an alternative treatment for protection against outdoor-biting mosquitoes.


Potential application of voltammetry of microparticles for dating porcine blood-based binding media used in Taiwanese architectural polychromies.
A method for dating Hemoglobine-containing archaeological samples using the voltammetry of microparticles is described. This is based on the record of the voltammetric response of such materials attached to paraffin-impregnated graphite electrodes in contact with aqueous acetate buffer. Signals attributable to the Fe(III)/Fe(II) iron couple and their catalytic enhancement in the presence of H(2)O(2) can be correlated, via first-order reaction kinetics, with the time of aging of the samples. The method has been applied to the study and dating of the polychromed architectural decoration of different parts of the architectural complex of the Longshan Temple in Lukang (18(th) century, Taiwan).


[Recombinant murine cell lines transformed by various vectors based on bovine papillomavirus type 1 and expressing human tissue plasminogen activator].
We have constructed a number of vectors which include transcriptional unit of human tPA cDNA and 100% BPV-1 DNA or 100% Lx DNA (mutant BPV variant with tandem duplication of LCR-E6-E7 region). Additional HSV-1 Tk-promoter was inserted in the flanks of viral DNAa in a set of constructions. A number of recombinant cell lines have been established by means of transformation using the constructed vectors. The increased focus formation activity and the improved vector properties were demonstrated for vector construction which included Lx DNA with additional Tk promoter for activation of early viral transcription. The possibilities of BPV-based vectors design are discussed.


More intense, more frequent, and longer lasting heat waves in the 21st century.
A global coupled climate model shows that there is a distinct geographic pattern to future changes in heat waves. Model results for areas of Europe and North America, associated with the severe heat waves in Chicago in 1995 and Paris in 2003, show that future heat waves in these areas will become more intense, more frequent, and longer lasting in the second half of the 21st century. Observations and the model show that present-day heat waves over Europe and North America coincide with a specific atmospheric circulation pattern that is intensified by ongoing increases in greenhouse gases, indicating that it will produce more severe heat waves in those regions in the future.


Thermodynamics and kinetics of large-time-step molecular dynamics.
Molecular dynamics (MD) simulations provide essential information about the thermodynamics and kinetics of proteins. Technological advances in both hardware and algorithms have seen this method accessing timescales that used to be unreachable only few years ago. The quest to simulate slow, biologically relevant macromolecular conformational changes, is still open. Here, we present an approximate approach to increase the speed of MD simulations by a factor of ∼4.5. This is achieved by using a large integration time step of 7 fs, in combination with frozen covalent bonds and look-up tables for nonbonded interactions of the solvent. Extensive atomistic MD simulations for a flexible peptide in water show that the approach reproduces the peptide's equilibrium conformational changes, preserving the essential properties of both thermodynamics and kinetics. Comparison of this approximate method with state-of-the-art implicit solvation simulations indicates that the former provides a better description of the underlying free-energy surface. Finally, simulations of a 33-residue peptide show that these fast MD settings are readily applicable to investigate biologically relevant systems.


Higher offspring birth weight predicts the metabolic syndrome in mothers but not fathers 8 years after delivery: the Pune Children's Study.
In Europid populations, low birth weight of offspring predicts insulin resistance in the mother and cardiovascular disease in both parents. We investigated the association between birth weight of offspring and obesity and cardiovascular risk in the parents of 477 8-year-old children born at the King Edward Memorial Hospital, Pune, India. Eight years after the birth of the child, mothers (33 years of age, n = 459) of heavier babies were taller and more obese (BMI, fat mass, and waist circumference, all P < 0.001) than mothers of lighter babies. Increasing offspring birth weight predicted higher homeostasis model assessment for insulin resistance (P < 0.01) and metabolic syndrome in mothers (P < 0.001) (adjusted for offspring sex and birth order, maternal age, and socioeconomic status) but not hyperglycemia. Fathers (39 years of age, n = 398) of heavier babies were taller and heavier, independent of maternal size (P < 0.01, both), but were not more insulin resistant. Unlike other reports, lower offspring birth weight did not predict insulin resistance in fathers. Thus, urban Indian parents have a higher risk of being obese 8 years after delivery of a heavier child. Mothers but not fathers of heavier babies also have a higher risk of being insulin resistant and developing the metabolic syndrome. Our findings highlight the need for a better understanding of the relation between fetal growth and future health before contemplating public health interventions to improve fetal growth.


Nuclear Magnetic Resonance (NMR)-Based Quantification on Flavor-Active and Bioactive Compounds and Application for Distinguishment of Chicken Breeds.
The purpose of this study was to use 1H nuclear magnetic resonance (1H NMR) to quantify taste-active and bioactive compounds in chicken breasts and thighs from Korean native chicken (KNC) [newly developed KNCs (KNC-A, -C, and -D) and commercial KNC-H] and white-semi broiler (WSB) used in Samgye. Further, each breed was differentiated using multivariate analyses, including a machine learning algorithm designed to use metabolic information from each type of chicken obtained using 1H-13C heteronuclear single quantum coherence (2D NMR). Breast meat from KNC-D chickens were superior to those of conventional KNC-H and WSB chickens in terms of both taste-active and bioactive compounds. In the multivariate analysis, meat portions (breast and thigh) and chicken breeds (KNCs and WSB) could be clearly distinguished based on the outcomes of the principal component analysis and partial least square-discriminant analysis (R2=0.945; Q2=0.901). Based on this, we determined the receiver operating characteristic (ROC) curve for each of these components. AUC analysis identified 10 features which could be consistently applied to distinguish between all KNCs and WSB chickens in both breast (0.988) and thigh (1.000) meat without error. Here, both 1H NMR and 2D NMR could successfully quantify various target metabolites which could be used to distinguish between different chicken breeds based on their metabolic profile.


A comparison between the macrophage migration inhibition test (MMI) and the leucocyte adherence inhibition test (LAI) in patients with melanoma and carcinoma of the colon.
Patients with progressing tumours have circulating leucocytes which are sensitised to tumour specific antigens and their serum contains blocking factors. Patients who have tumours which have been successfully destroyed do not have circulating blocking factors although their lymphocytes continue to remain sensitised to the tumour antigens. Two tests, known to detect cellular sensitisation and serum blocking activity, the leucocyte adherence inhibition test (LAI) and the macrophage migration inhibition test (MMI) have been compared in a small group of patients with malignant melanoma and carcinoma of the colon. There was agreement between the results of both tests in over three-quarters of the tests performed and in those which failed to agree neither test was favoured in relation to the known tumour state of the patient. Thirty-two tests were performed in 22 patients, there was one false positive with MMI testing, seven false negative results for the LAI test and six for the MMI test.


Effects of selected cooking procedures on the survival of Escherichia coli O157:H7 in inoculated steaks cooked on a hot plate or gas barbecue grill.
Beef steaks (2 cm thick) were each inoculated at three sites in the central plane with Escherichia coli O157:H7 at 5.9 ± 0.3 log CFU per site. Temperatures at steak centers were monitored during cooking on a hot plate or the grill of a gas barbeque. Steaks were cooked in groups of five using the same procedures and cooking each steak to the same temperature, and surviving E. coli O157:H7 at each site was enumerated. When steaks cooked on the hot plate were turned over every 2 or 4 min during cooking to between 56 and 62°C, no E. coli O157:H7 was recovered from steaks cooked to ≥58 or 62°C, respectively. When steaks were cooked to ≤71°C and turned over once during cooking, E. coli O157:H7 was recovered from steaks in groups turned over after ≤8 min but not from steaks turned over after 10 or 12 min. E. coli O157:H7 was recovered in similar numbers from steaks that were not held or were held for 3 min after cooking when steaks were turned over once after 4 or 6 min during cooking. When steaks were cooked on the grill with the barbeque lid open and turned over every 2 or 4 min during cooking to 63 or 56°C, E. coli O157:H7 was recovered from only those steaks turned over at 4-min intervals and cooked to 56°C. E. coli O157:H7 was recovered from some steaks turned over once during cooking on the grill and held or not held after cooking to 63°C. E. coli O157:H7 was not recovered from steaks turned over after 4 min during cooking to 60°C on the grill with the barbeque lid closed or when the lid was closed after 6 min. Apparently, the microbiological safety of mechanically tenderized steaks can be assured by turning steaks over at intervals of about 2 min during cooking to ≥60°C in an open skillet or on a barbecue grill. When steaks are turned over only once during cooking to ≥60°C, microbiological safety may be assured by covering the skillet or grill with a lid during at least the final minutes of cooking.


Haloactinopolyspora alba gen. nov., sp. nov., a halophilic filamentous actinomycete isolated from a salt lake, with proposal of Jiangellaceae fam. nov. and Jiangellineae subord. nov.
A halophilic, filamentous actinomycete strain, designated YIM 93246(T), was isolated from a salt lake in Xinjiang province, north-west China, and subjected to polyphasic taxonomic characterization. The isolate grew in the presence of 7-23 % (w/v) NaCl, but not in the absence of NaCl. Strain YIM 93246(T) had particular morphological properties, forming aerial mycelium that had long spore chains and pseudosporangium-like, rhiziform spore aggregates at maturity. LL-DAP was the cell-wall diamino acid and glucosamine, mannose, glucose, arabinose and galactose were the cell-wall sugars. The major fatty acids were iso-C(16 : 0), anteiso-C(15 : 0) and anteiso-C(17 : 0). MK-9 (H(4)) was the predominant menaquinone and the genomic DNA G+C content was 70.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 93246(T) clustered with the genus Jiangella. The sequence similarities between strain YIM 93246(T) and Jiangella alba, Jiangella gansuensis and Jiangella alkaliphila were 96.9, 96.9 and 96.6 %, respectively. Based on morphological, physiological and chemotaxonomic differences, and phylogenetic analysis, a novel genus and species, Haloactinopolyspora alba gen. nov., sp. nov., is proposed. The type strain of the species is YIM 93246(T) (=DSM 45211(T)=KCTC 19409(T)). Additionally, phylogenetic analysis placed the genus Jiangella together with strain YIM 93246(T) within the order Actinomycetales as an independent lineage, clearly distinguished from other described suborders of the class Actinobacteria. Hence, based on phylogenetic characteristics, the genus Jiangella together with the newly proposed genus Haloactinopolyspora are proposed to be classified as Jiangellaceae fam. nov. and Jiangellineae subord. nov.


Assessment of Pulmonary Artery Pressures by Various Doppler Echocardiographic Parameters and its Correlation with Cardiac Catheterization in Patients with Pulmonary Hypertension.
Measuring pulmonary artery pressures is a routine index in Doppler echocardiography to diagnose, risk stratify, and prognosticate patients with pulmonary hypertension (PH). There are numerous methods in use to measure it in routine clinical practice. The objective of this study was to assess the correlation between the commonly used Doppler-derived parameters such as tricuspid regurgitation (TR)-derived systolic pulmonary artery pressure (SPAP), pulmonary regurgitation (PR)-derived mean pulmonary artery pressure (MPAP), and right ventricular outflow tract acceleration time (RVOT AcT) with right heart catheterization (RHC) data which are the gold standard. In this analytical study, we prospectively measured echo and angiogram parameters such as TR-derived SPAP, PR-derived MPAP, and RVOT AcT and studied its association with RHC data of thirty patients for a span of 2 years. Right ventricular AcT was also included in the study. Their relationship was displayed using Bland-Altman scatter plots. P < 0.05 was considered as statistically significant. Although both TR-derived SPAP and PR-derived MPAP had a moderate correlation with RHC-acquired data, the agreement between them was poor. RVOT AcT showed a strong inverse correlation with invasive MPAP. Among the three Doppler methods that were assessed to measure pulmonary pressures, RVOT AcT had a strong correlation with MPAP. RVOT AcT of <80 ms had a high sensitivity to detect severe PH (defined as MPAP >45 mmHg). Hence, it is recommended to include AcT as a routine measure in the armamentarium of echocardiographic parameters used in patients with PH.


Treatment-related outcomes from blunt cerebrovascular injuries: importance of routine follow-up arteriography.
To assess the impact of routine follow-up arteriography on the management and outcome of patients with acute blunt cerebrovascular injuries (BCVI). During the past 5 years there has been increasing recognition of BCVI, but the management of these lesions remains controversial. The authors previously proposed a grading system for BCVI, with grade-specific management guidelines. The authors have noted that a significant number of injuries evolve within 7 to 10 days, warranting alterations in therapy. A prospective database of a regional trauma center's experience with BCVI has been maintained since 1990. A policy of arteriographic screening for BCVI based on injury mechanism (e.g., cervical hyperextension) and injury patterns (e.g., cervical and facial fractures) was instituted in 1996. A grading system was devised to develop management protocols: I = intimal irregularity; II = dissection/flap/thrombus; III = pseudoaneurysm; IV = occlusion; V = transection. From June 1990 to October 2001, 171 patients (115 male, age 36 +/- 1 years) were diagnosed with BCVI. Mean injury severity score was 28 +/- 1; associated injuries included brain (57%), spine (44%), chest (43%), and face (34%). Mechanism was motor vehicle crash in 50%, fall in 11%, pedestrian struck in 11%, and other in 29%. One hundred fourteen patients had 157 carotid artery injuries (43 bilateral), and 79 patients had 97 vertebral artery injuries (18 bilateral). The breakdown of injury grades was 137 grade I, 52 grade II, 32 grade III, 25 grade IV, and 8 grade V. One hundred fourteen (73%) carotid and 65 (67%) vertebral arteries were restudied with arteriography 7 to 10 days after the injury. Eight-two percent of grade IV and 93% of grade III injuries were unchanged. However, grade I and II lesions changed frequently. Fifty-seven percent of grade I and 8% of grade II injuries healed, allowing cessation of therapy, whereas 8% of grade I and 43% of grade II lesions progressed to pseudoaneurysm formation, prompting interventional treatment. There was no significant difference in healing or in progression of injuries whether treated with heparin or antiplatelet therapy or untreated. However, heparin may improve the neurologic outcome in patients with ischemic deficits and may prevent stroke in asymptomatic patients. Routine follow-up arteriography is warranted in patients with grade I and II BCVIs because most of these patients (61% in this series) will require a change in management. A prospective randomized trial will be necessary to identify the optimal treatment of BCVI.


Update on guidelines and recommendations for enhanced recovery after thoracic surgery.
Enhanced recovery after thoracic surgery (ERATS) has continued its growth in popularity over the past few years, and evidence for its utility is catching up to other specialties. This review will present and examine some of that accumulated evidence since guidelines sponsored by the Enhanced Recovery after Surgery (ERAS) Society and the European Society of Thoracic Surgeons (ESTS) were first published in 2019. The ERAS/ESTS guidelines published in 2019 have not been updated, but new studies have been done and new data has been published regarding some of the individual components of the guidelines as they relate to thoracic and lung resection surgery. While there is still not a consensus on many of these issues, the volume of available evidence is becoming more robust, some of which will be incorporated into this review. The continued accumulation of data and evidence for the benefits of enhanced recovery techniques in thoracic and lung resection surgery will provide the thoracic anesthesiologist with guidance on how to best care for these patients before, during, and after surgery. The data from these studies will also help to elucidate which components of ERAS protocols are the most beneficial, and which components perhaps do not provide as much benefit as previously thought.


Signaling by Folded gastrulation is modulated by mitochondrial fusion and fission.
Mitochondria are increasingly being identified as integrators and regulators of cell signaling pathways. Folded gastrulation (Fog) is a secreted signaling molecule best known for its role in regulating cell shape change at the ventral furrow during gastrulation in Drosophila. Fog is thought to signal, through a G-protein-coupled receptor, to effect downstream cytoskeletal changes necessary for cell shape change. However, the mechanisms regulating Fog signaling that lead to change in cell morphology are poorly understood. This study describes the identification of proteins involved in mitochondrial fusion and fission as regulators of Fog signaling. Pro-fission factors were found to function as enhancers of signaling, whereas pro-fusion factors were found to have the opposite effect. Consistent with this, activation of Fog signaling resulted in mitochondrial fragmentation, and inhibiting this process could attenuate Fog signaling. The findings presented here show that mitochondria, through regulation of fusion and fission, function as downstream effectors and modulators of Fog signaling and Fog-dependent cell shape change.


[Hungry bone syndrome: clinical experience in its diagnosis and treatment].
Hungry bone syndrome is a unusual complication of the postoperative period of primary hyperparathyroidism. This syndrome is characterized by hypocalcemia, hypophosphatemia and hypomagnesemia, due to an excessive bone remineralization. We report the clinical features, laboratory and therapy in four females (aged 39 to 73 years old) with a long standing hyperparathyroidism, elevated alkaline phosphatases and decreased bone mineralization in two. The mean size of the adenoma was 2.9 +/- 1.1 cm. Hypocalcemia appeared between days 1 and 6 of the postoperative period. All were treated with calcium, calcitriol and magnesium at different timing and dosages. The mean hospitalization period was 19.8 +/- 2.1 days. As reported previously, low bone mineralization and a large adenoma are risk factors for the syndrome. Serial monitoring of serum calcium and magnesium and an early supplementation of these minerals could prevent hypocalcemia and decrease the hospitalization time.


Maximizing baculovirus-mediated foreign proteins expression in mammalian cells.
Since the discovery of mammalian cells susceptible to baculovirus transduction in 1995, baculovirus has emerged as a safe, economical and convenient tool for introducing foreign genetic material into mammalian systems. The feasibility of baculovirus as a novel gene transfer vehicle for large scale mammalian protein expression was not obvious at first, as the baculovirus genome is unable to amplify within mammalian cells and expression of the transferred foreign gene does not usually last more than 20 days. However, several recent articles have demonstrated that baculovirus contains both the elements - hr sequences, and the factor - IE2 protein, which can function in mammalian cells to dramatically boost baculovirus-transduced gene expression. The longevity of genes transferred by baculovirus can also be extended by inserting a replication ori with the necessary factors and induce self-replicating episomes. Lastly, peptide-based baculovirus surface modification and two groups of drugs: histone deacetylase inhibitors and microtubule depolymerizing agents, which improve baculovirus gene expression were described. In this article we summarized ways to activate, enhance, and prolong baculovirus-mediated foreign protein expression. The mechanism behind IE2 activation through its unique nuclear body structure was given special emphasis, including our most current data which suggested PML NBs could be disrupted by IE2. Finally, strategies to maximizing mammalian protein production through baculovirus gene transfer are proposed in prospect to current breakthroughs.


[Activity of the microsomal ethanol-oxidizing system of the rat liver in acute and chronic alcohol intoxication].
Activity of the microsomal ethanol-oxidizing system (MEOS) was increased in rat liver tissue after acute and chronic alcohol intoxication of the animals with 40% solution of ethanol at a dose of 0.7 ml/100 g. The most distinct activation of MEOS (per 1 mg of protein and per 1 g of liver tissue) was observed in animals treated with ethanol three times weekly during 3 and 6 months.


Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain.
Evidence suggests that extracellular matrix molecules of perivascular basal laminae help orchestrate the molecular assemblies at the gliovascular interface. Specifically, laminin and agrin are thought to tether the dystrophin-associated protein (DAP) complex to the astrocytic basal lamina. This complex includes α-syntrophin (α-Syn), which is believed to anchor aquaporin-4 (AQP4) to astrocytic endfoot membrane domains. We have previously shown that the size of the perivascular AQP4 pool differs considerably between brain regions in an α-Syn-dependent manner. Also, both AQP4 and α-Syn occur at higher densities in endfoot membrane domains facing pericytes than in endfoot membrane domains facing endothelial cells. The heterogeneous distribution of AQP4 at the regional and capillary level has been attributed to a direct interaction between AQP4 and α-Syn. This would be challenged (1) if the microdistributions of laminin and agrin fail to align with those of DAP and AQP4 and (2) if targeted deletion of α-Syn leads to a loss of laminin and/or agrin. Here, we provide the first detailed and quantitative analysis of laminin and agrin in brain basal laminae of mice. We show that the microdistributions of these molecules vary in a fashion that is well aligned with the previously reported microdistribution of AQP4. We also demonstrate that the expression patterns of laminin and agrin are insensitive to targeted deletion of α-Syn, suggesting that α-Syn deletion affects AQP4 directly and not indirectly via laminin or agrin. These data fill remaining voids in the current model of how key molecules are assembled and tethered at the gliovascular interface.


Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments.
In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus panels, chosen from 200 well-characterized clade C envelope (Env)-pseudotyped viruses from early infection. All 200 Envs were expressed as a single round of replication pseudoviruses and were tested to quantify neutralization titers by 16 broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic clade C infections. We selected large panels of 50 and 100 Envs either to characterize cross-reactive breadth for sera identified as having potent neutralization activity based on initial screening or to evaluate neutralization magnitude-breadth distributions of newly isolated antibodies. We identified these panels by downselection after hierarchical clustering of bnAb neutralization titers. The resulting panels represent the diversity of neutralization profiles throughout the range of virus sensitivities identified in the original panel of 200 viruses. A small 12-Env panel was chosen to screen sera from vaccine trials or natural-infection studies for neutralization responses. We considered panels selected by previously described methods but favored a computationally informed method that enabled selection of viruses representing diverse neutralization sensitivity patterns, given that we do not a priori know what the neutralization-response profile of vaccine sera will be relative to that of sera from infected individuals. The resulting 12-Env panel complements existing panels. Use of standardized panels enables direct comparisons of data from different trials and study sites testing HIV-1 clade C-specific products.IMPORTANCE HIV-1 group M includes nine clades and many recombinants. Clade C is the most common lineage, responsible for roughly half of current HIV-1 infections, and is a focus for vaccine design and testing. Standard reference reagents, particularly virus panels to study neutralization by antibodies, are crucial for developing cost-effective and yet rigorous and reproducible assays against diverse examples of this variable virus. We developed clade C-specific panels for use as standardized reagents to monitor complex polyclonal sera for neutralization activity and to characterize the potency and breadth of cross-reactive neutralization by monoclonal antibodies, whether engineered or isolated from infected individuals. We chose from 200 southern African, clade C envelope-pseudotyped viruses with neutralization titers against 16 broadly neutralizing antibodies and 30 sera from chronic clade C infections. We selected panels to represent the diversity of bnAb neutralization profiles and Env neutralization sensitivities. Use of standard virus panels can facilitate comparison of results across studies and sites.


Sensory disturbances, inhibitory deficits, and the P50 wave in schizophrenia.
Sensory gating disturbances in schizophrenia are often described as an inability to filter redundant sensory stimuli that typically manifest as inability to gate neuronal responses related to the P50 wave, characterizing a decreased ability of the brain to inhibit various responses to insignificant stimuli. It implicates various deficits of perceptual and attentional functions, and this inability to inhibit, or "gate", irrelevant sensory inputs leads to sensory and information overload that also may result in neuronal hyperexcitability related to disturbances of habituation mechanisms. These findings seem to be particularly important in the context of modern electrophysiological and neuroimaging data suggesting that the filtering deficits in schizophrenia are likely related to deficits in the integrity of connections between various brain areas. As a consequence, this brain disintegration produces disconnection of information, disrupted binding, and disintegration of consciousness that in terms of modern neuroscience could connect original Bleuler's concept of "split mind" with research of neural information integration.


Quality of life at 6 years in children treated for West syndrome with hormonal therapy.
West syndrome is a severe epileptic encephalopathy occurring in infancy. Majority of affected children suffer from poor epilepsy control in later life and are dependent on care-givers for daily living. There is no previous study evaluating the Quality of Life (QOL) in children suffered from WS. A prospective cohort study was performed at six years in a group of children with West syndrome, followed up in the Sri Lanka Infantile Spasm Study (SLISS). The quality of life was evaluated using Sri Lankan Health-Related Quality-of-Life Index for school children (SLHRQ-S), an age-specific, primary caregiver proxy-rated, validated questionnaire for Sri Lankan children with epilepsy. Information on epilepsy, medication, and daily activities was obtained from the parents. Fifty parents of initial 97 children treated for WS participated. The majority had no ongoing epilepsy (56%) at time of evaluation. The mean QOL was 67.22 (SD 15.68). Mean QOL scores for individual domains showed that physical domain was the worst affected (58.51 (SD = 22.11)). Psychological and social function domains were 68.73 (SD = 17.74) and 75.2 (SD = 14.87), respectively. Male sex (0.02), using multiple anti-seizure medications (0.00) and lower ILAE epilepsy control scale (0.02) were significantly associated with a poor quality of life. Age at onset, delay in treatment, and early spasm control were among the factors that did not influence quality of life. Despite having control of their epilepsy in the majority, these children suffered from poor quality of life. The greater impact on the physical domain possibly is related to the effect of underlying pathologies.


Postsynaptic K+ current induced by nociceptin in medullary dorsal horn neurons.
The actions of the endogenous ORL1 receptor (opioid receptor-like1) ligand nociceptin on the membrane properties of rat trigeminal nucleus caudalis neurons were examined by use of whole cell and perforated patch clamp recording in brain slices. Nociceptin produced an outward current in all neurons tested (EC50 112 nM). The outward current produced by nociceptin was completely reversed with the addition of the non-peptide ORL1 antagonist J-113397. Outward currents reversed polarity at -99+/-2 mV, close to the potential for K+ of -102 mV, suggesting that they were mediated by an increased K+ conductance. These results suggest that the analgesic action of nociceptin might be mediated by direct postsynaptic inhibition within the dorsal horn.


Lesson of the month (1). Ictal asystole due to unsuspected cocaine abuse.
This lesson describes a patient who had a cardiac arrest during an episode of status epilepticus provoked by a first fit. This is an exceptional sequence of events and should lead to investigation for an underlying cause. Unsuspected cocaine abuse is common and may provoke prolonged status epilepticus, particularly if there is a low seizure threshold. A toxic screen should be undertaken in all patients presenting with unexplained status epilepticus even if abuse of illicit substances is denied.


A dosimetric intercomparison of electron beams in UK radiotherapy centres.
A dosimetry intercomparison has been carried out for all 52 radiotherapy centres in the UK which possess electron treatment facilities. The intercomparison was carried out on one treatment unit in each centre and for three energies across the range of available energies. The position of the depth of maximum dose for a standard field size was independently determined and a subsequent beam calibration made. The factor to convert the reading on a calibrated ionization chamber to absorbed dose in an electron beam is energy dependent, and hence to carry out an independent calibration measurement also requires the beam energy to be determined. In addition a quantitative measure of the difference in the calibration chains between the intercomparison equipment and the host department's field instrument was carried out. In order to provide a follow-up to the initial IPSM national photon intercomparison, a photon beam calibration was measured in one photon beam in each centre. For 156 electron beam measurements, a mean ratio of intercomparison measured dose to locally measured dose of 0.994 was obtained with a standard deviation of 1.8%. For the 52 photon beam measurements, a mean ratio of intercomparison measured dose to locally measured dose of 1.003 was obtained with a standard deviation of 1.0%.


MEG correlates of speech planning in simple vs. interactive picture naming in children and adults.
The picture naming task is common both as a clinical task and as a method to study the neural bases of speech production in the healthy brain. However, this task is not reflective of most naturally occurring productions, which tend to happen within a context, typically in dialogue in response to someone else's production. How the brain basis of the classic "confrontation picture naming" task compares to the planning of utterances in dialogue is not known. Here we used magnetoencephalography (MEG) to measure neural activity associated with language production using the classic picture naming task as well as a minimal variant of the task, intended as more interactive or dialogue-like. We assessed how neural activity is affected by the interactive context in children, teenagers, and adults. The general pattern was that in adults, the interactive task elicited a robust sustained increase of activity in frontal and temporal cortices bilaterally, as compared to simple picture naming. This increase was present only in the left hemisphere in teenagers and was absent in children, who, in fact, showed the reverse effect. Thus our findings suggest a robustly bilateral neural basis for the coordination of interaction and a very slow developmental timeline for this network.


Experimental use of iteratively designed rotation invariant correlation filters.
Iteratively designed filters are incorporated into an optical correlator for position, rotation, and intensity invariant recognition of target images. The filters exhibit excellent discrimination because they are designed to contain full information about the target image. Numerical simulations and experiments demonstrate detection of targets that are corrupted with random noise (SNR approximately 05) and also partially obscured by other objects. The complex valued filters are encoded in a computer generated hologram and fabricated directly using an electron-beam system. Experimental results using a liquid crystal spatial light modulator for realtime input show excellent agreement with analytical and numerical computations.


INDUCED UNRESPONSIVENESS TO SIMPLE ALLERGENIC CHEMICALS. II. INDEPENDENCE OF DELAYED-TYPE HYPERSENSITIVITY AND FORMATION OF CIRCULATING ANTIBODY.
Normal guinea pigs fed chemical haptens develop a specific state of unresponsiveness, inhibiting subsequent development of dermal sensitization with the same hapten and modifying profoundly the synthesis of anaphylactic antibody in response to hapten conjugated to guinea pig proteins. The degree of unresponsiveness has been tested by exposing hapten-fed animals to intense haptenic stimulation. Animals of groups that were demonstrably unresponsive to picryl chloride could be made to form hapten-specific antibody by injecting picrylated bovine gamma globulin. Specific anaphylactic-type antibodies, presumably 7S gamma(1), were synthesized, and in animals given PBGG adsorbed to alumina there arose a measurable concentration of precipitating antibody, presumably 7S gamma(2), perhaps slightly earlier than in similarly treated control animals. Attempts to impose contact-type reactivity on such unresponsive animals met with limited success. Injection of picrylated guinea pig erythrocyte stromata in a complete Freund's adjuvant, with subsequent applications of picryl chloride to the dermis, led to definite contact sensitivity to 0.3 per cent picryl chloride, whereas parallel treatment of normal control animals induced sensitivity to 0.006 or 0.002 per cent. By this double method of stimulation, hapten-fed animals did not advance in sensitivity by reason of the secondary dermal applications of the simple chemical, whereas control animals developed increasingly higher sensitivity by these contacts in what appeared to be a stepwise manner. Picryl chloride-fed guinea pigs injected intradermally with picryl chloride either after or before forming picryl-specific circulating antibody still remained unable to develop picryl-specific contact hypersensitivity. Control animals synthesizing picryl-specific antibody subsequently responded to intradermal injection of picryl chloride with contact-type sensitivity. Interpretations of these results are discussed and the view is presented that delayed-type hypersensitivity and circulating antibodies of the varieties measured here are formed independently of each other.


Randomized clinical trial on closure versus non-closure of mesenteric defects during laparoscopic gastric bypass surgery.
Internal herniation is a well known and potentially life-threatening complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). The aim of this study was to evaluate the benefit and harm of closing the mesenteric defects with clips during LRYGB to prevent internal herniation. This was a single-centre, single-blinded RCT. Patients eligible for LRYGB were randomized to surgery with or without closure of mesenteric defects with clips. The primary endpoint was the incidence of (intermittent) internal herniation after LRYGB with a minimum follow-up of 24 months. Secondary outcomes were duration of surgery, number of clips used, trocars and sutures used, postoperative pain measured by a visual analogue scale (VAS), and postoperative complications. Between 13 August 2012 and 18 May 2017, 401 patients were randomized to closure (201) or non-closure (200) of mesenteric defects. Median follow-up for both groups was 59 months (range 8-67 and 16-67 months in non-closure and closure groups respectively). The cumulated risk of internal herniation after 2 years was 8.0 per cent in the non-closure group compared with 4.5 per cent in the closure group (hazard ratio (HR) 1.81, 95 per cent c.i. 0.80 to 4.12; P = 0.231). At 5 years, rates were 15.5 and 6.5 per cent respectively (HR 2.52, 1.32 to 4.81; P = 0.005). Closure of mesenteric defects increased operating time by a median of 4 min (95 per cent c.i. 52 to 56 min for the non-closure group and 56 to 60 min for the closure group; P = 0.002). There was no difference in postoperative blood transfusion rates and VAS scores between the groups. Routine closure of the mesenteric defects in LRYGB with clips is associated with a lower rate of internal herniation. Registration number: NCT01595230 (http://www.clinicaltrials.gov).


High-Throughput Metabolic Profiling for Model Refinements of Microalgae.
Metabolic models are reconstructed based on an organism's available genome annotation and provide predictive tools to study metabolic processes at a systems-level. Genome-scale metabolic models may include gaps as well as reactions that are unverified experimentally. Reconstructed models of newly isolated microalgal species will result in weaknesses due to these gaps, as there is usually sparse biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology is an effective, high-throughput method that functionally determines cellular metabolic activities in response to a wide array of entry metabolites. Combining the high throughput phenotypic assays with metabolic modeling can allow existing metabolic network models to be rapidly reconstructed or optimized by providing biochemical evidence to support and expand genomic evidence. This work will show the use of PM assays for the study of microalgae by using the green microalgal model species Chlamydomonas reinhardtii as an example. Experimental evidence for over 254 reactions obtained by PM was used in this study to expand and refine a genome-scale C. reinhardtii metabolic network model, iRC1080, by approximately 25 percent. The protocol created here can be used as a basis for functionally profiling the metabolism of other microalgae, including known microalgae mutants and new isolates.


Myrislignan Exhibits Activities Against Toxoplasma gondii RH Strain by Triggering Mitochondrial Dysfunction.
Toxoplasma gondii is a widespread obligatory parasitic protozoon that infects nearly all warm-blooded animals and causes toxoplasmosis. However, the current treatments for toxoplasmosis are limited by severe side effects. Myrislignan is a natural product from Myristica fragrans Houtt with wide pharmacological activities. In the current study, we tested the anti-T. gondii activity of myrislignan both in vitro and in vivo and explored its potential mechanism of action. The cytotoxicity of myrislignan in African green monkey kidney (Vero) cells was assessed using Cell Counting Kit-8 (CCK-8) assays. The in vitro effects of myrislignan on T. gondii were determined by quantitative PCR and Giemsa staining. An in vivo murine model of T. gondii infection was used to determine the efficacy of myrislignan. The changes in tachyzoites after myrislignan exposure were examined by electron microscopy. The impact of myrislignan on mitochondrial function in tachyzoites was assessed by MitoTracker Red CMXRos staining and an ATP detection kit. In vitro, myrislignan inhibited T. gondii tachyzoite proliferation with a 50% effective concentration of 32.41 μg/ml, and reduced the invasion of cells by tachyzoites (14.63 and 1.92% invasion rates for control and 70 μg/ml myrislignan, respectively). Importantly, myrislignan had no significant cytotoxicity against Vero cells at concentrations less than 132 μg/ml. In addition, surface shrinkage and mitochondrial damage were observed in tachyzoites after myrislignan exposure. The reduced ΔΨm and ATP levels in tachyzoites treated with myrislignan further confirmed mitochondrial damage. In the in vivo murine model, myrislignan treatment significantly reduced the parasite burden in tissues compared to no treatment. In conclusion, myrislignan had potent anti-T. gondii activities both in vitro and in vivo, and these activities might involve the interruption of mitochondrial function. These data suggest that myrislignan might be a useful compound for the treatment of toxoplasmosis.


Biomarkers of response to treatment in acromegaly.
Medical treatment of acromegaly is based in a `trial and error` approach. First-generation somatostatin receptor ligands (fg-SRL) are prescribed as first-line medical therapy to the vast majority of patients, despite lack of disease control in approximately 60% of patients. However, other drugs used in acromegaly treatment are available (cabergoline, pasireotide and pegvisomant). In this article, we review and discuss the biomarkers of response to medical treatment in acromegaly. Biomarkers for fg-SRL that can already be applied in clinical practice are: gender, age, pretreatment GH and IGF-I levels, cytokeratin granulation pattern, and the expression of somatostatin receptor type 2. Using biomarkers of response could guide treatment towards precision medicine with greater efficacy and lower costs.


Expression of CXCL12 and CXCR4 in human endometrium; effects of CXCL12 on MMP production by human endometrial cells.
Although several studies have suggested that CXCL12 and its receptor, CXCR4, may play a role in embryo implantation, there are limited reports of expression of CXCR4 and CXCL12 in human endometrium. The aim of this study was to investigate CXCL12 and CXCR4 expression in human endometrium and to see if CXCL12 could affect matrix metalloproteinase (MMP) production by endometrial stromal and epithelial cells. Quantitative real-time RT-PCR (qRT-PCR) was used to detect the expression of CXCL12 and CXCR4 mRNA in endometrial biopsy samples obtained from fertile women (n = 30). Immunohistochemical analysis was carried out to determine where in the endometrium CXCL12 and CXCR4 were expressed. Primary cell culture followed by qRT-PCR and zymography was used to investigate whether CXCL12 affected MMP-2 and -9 production by endometrial stromal and epithelial cells. Both CXCL12 and CXCR4 were detected in the endometrium. There was no difference in CXCL12 expression at different times in the cycle, but expression of CXCR4 mRNA was significantly higher in the early proliferative (P < 0.01) compared with late proliferative and secretory phases of the cycle. CXCL12 expression was strongest in the epithelial compartment, and weaker in blood vessel walls. CXCR4 immunostaining was strong in the epithelium and blood vessel walls and weaker in the stroma. CXCL12 (10 and 100 ng/ml) had no effect on mRNA expression or activity of MMP-2 or MMP-9 in either stromal or epithelial cells. The results show that the expression of CXCL12 in human endometrium does not alter during the menstrual cycle, while the endometrial expression of its receptor, CXCR4, is highest in the early proliferative phase. In contrast to its effects in other cells, CXCL12 had no effect on MMP-2 or MMP-9 production by endometrial stromal or epithelial cells.


Osterix controls cementoblast differentiation through downregulation of Wnt-signaling via enhancing DKK1 expression.
Osterix (Osx), a transcriptional factor essential for osteogenesis, is also critical for in vivo cellular cementum formation. However, the molecular mechanism by which Osx regulates cementoblasts is largely unknown. In this study, we initially demonstrated that overexpression of Osx in a cementoblast cell line upregulated the expression of markers vital to cementogenesis such as osteopontin (OPN), osteocalcin (OCN), and bone sialoprotein (BSP) at both mRNA and protein levels, and enhanced alkaline phosphatase (ALP) activity. Unexpectedly, we demonstrated a sharp increase in the expression of DKK1 (a potent canonical Wnt antagonist), and a great reduction in protein levels of β-catenin and its nuclear translocation by overexpression of Osx. Further, transient transfection of Osx reduced protein levels of TCF1 (a target transcription factor of β-catenin), which were partially reversed by an addition of DKK1. We also demonstrated that activation of canonical Wnt signaling by LiCl or Wnt3a significantly enhanced levels of TCF1 and suppressed the expression of OPN, OCN, and BSP, as well as ALP activity and formation of extracellular mineralized nodules. Importantly, we confirmed that there were a sharp reduction in DKK1 and a concurrent increase in β-catenin in Osx cKO mice (crossing between the Osx loxP and 2.3 Col 1-Cre lines), in agreement with the in vitro data. Thus, we conclude that the key role of Osx in control of cementoblast proliferation and differentiation is to maintain a low level of Wnt-β-catenin via direct up-regulation of DKK1.


Towards plug-and-play integration of archetypes into legacy electronic health record systems: the ArchiMed experience.
The dual model approach represents a promising solution for achieving semantically interoperable standardized electronic health record (EHR) exchange. Its acceptance, however, will depend on the effort required for integrating archetypes into legacy EHR systems. We propose a corresponding approach that: (a) automatically generates entry forms in legacy EHR systems from archetypes; and (b) allows the immediate export of EHR documents that are recorded via the generated forms and stored in the EHR systems' internal format as standardized and archetype-compliant EHR extracts. As a prerequisite for applying our approach, we define a set of basic requirements for the EHR systems. We tested our approach with an EHR system called ArchiMed and were able to successfully integrate 15 archetypes from a test set of 27. For 12 archetypes, the form generation failed owing to a particular type of complex structure (multiple repeating subnodes), which was prescribed by the archetypes but not supported by ArchiMed's data model. Our experiences show that archetypes should be customized based on the planned application scenario before their integration. This would allow problematic structures to be dissolved and irrelevant optional archetype nodes to be removed. For customization of archetypes, openEHR templates or specialized archetypes may be employed. Gaps in the data types or terminological features supported by an EHR system will often not preclude integration of the relevant archetypes. More work needs to be done on the usability of the generated forms.


Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer.
A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining the prognostic utility of CTC measurement before initiating therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes and OS at these and other time points. Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetermined Favorable or Unfavorable groups (<5 and > or =5 CTC/7.5mL). Two hundred thirty-one of 276 enrolled patients (84%) were evaluable. Patients with Unfavorable pretreatment CTC (57%) had shorter OS (median OS, 11.5 versus 21.7 months; Cox hazard ratio, 3.3; P < 0.0001). Unfavorable posttreatment CTC counts also predicted shorter OS at 2 to 5, 6 to 8, 9 to 12, and 13 to 20 weeks (median OS, 6.7-9.5 versus 19.6-20.7 months; Cox hazard ratio, 3.6-6.5; P < 0.0001). CTC counts predicted OS better than PSA decrement algorithms at all time points; area under the receiver operator curve for CTC was 81% to 87% and 58% to 68% for 30% PSA reduction (P = 0.0218). Prognosis for patients with (a) Unfavorable baseline CTC who converted to Favorable CTC improved (6.8 to 21.3 months); (b) Favorable baseline CTC who converted to Unfavorable worsened (>26 to 9.3 months). CTC are the most accurate and independent predictor of OS in CRPC. These data led to Food and Drug Administration clearance of this assay for the evaluation of CRPC.


Axial patterning interactions in the sea urchin embryo: suppression of nodal by Wnt1 signaling.
Wnt and Nodal signaling pathways are required for initial patterning of cell fates along anterior-posterior (AP) and dorsal-ventral (DV) axes, respectively, of sea urchin embryos during cleavage and early blastula stages. These mechanisms are connected because expression of nodal depends on early Wnt/β-catenin signaling. Here, we show that an important subsequent function of Wnt signaling is to control the shape of the nodal expression domain and maintain correct specification of different cell types along the axes of the embryo. In the absence of Wnt1, the posterior-ventral region of the embryo is severely altered during early gastrulation. Strikingly, at this time, nodal and its downstream target genes gsc and bra are expressed ectopically, extending posteriorly to the blastopore. They override the initial specification of posterior-ventral ectoderm and endoderm fates, eliminating the ventral contribution to the gut and displacing the ciliary band dorsally towards, and occasionally beyond, the blastopore. Consequently, in Wnt1 morphants, the blastopore is located at the border of the re-specified posterior-ventral oral ectoderm and by larval stages it is in the same plane near the stomodeum on the ventral side. In normal embryos, a Nodal-dependent process downregulates wnt1 expression in dorsal posterior cells during early gastrulation, focusing Wnt1 signaling to the posterior-ventral region where it suppresses nodal expression. These subsequent interactions between Wnt and Nodal signaling are thus mutually antagonistic, each limiting the range of the other's activity, in order to maintain and stabilize the body plan initially established by those same signaling pathways in the early embryo.


Does limb preconditioning reduce pain after total knee arthroplasty? A randomized, double-blind study.
Total knee arthroplasty (TKA) can be associated with considerable postoperative pain. Ischemic preconditioning of tissue before inducing procedure-related underperfusion may reduce the postoperative inflammatory response, which further may reduce associated pain. In this prospective, randomized study, we aimed at evaluating the impact of ischemic preconditioning on postoperative pain at rest and during exercise; use of pain medication; levels of systemic prothrombotic and local inflammatory markers; and length of stay and achievement of physical therapy milestones. Sixty patients undergoing unilateral TKA under tourniquet were enrolled with half (N = 30) being randomized to an episode of limb preconditioning before induction of ischemia for surgery (tourniquet inflation). Pain scores, analgesic consumption, markers of inflammation (interleukin-6 [IL-6], tumor necrosis factor [TNF]-α in periarticular drainage), and periarticular circumference were measured at baseline and during 2 days postoperatively. Changes in prothrombotic markers were evaluated. Patients in the preconditioning group had significantly less pain postoperatively at rest (mean difference = -0.71, 95% confidence interval [CI] = -1.40 to -0.02, p = 0.043) and with exercise (mean difference = -1.38, 95% CI = -2.32 to -0.44, p = 0.004), but showed no differences in analgesic consumption. No differences were seen between the study and the control group in terms of muscle oxygenation and intraarticular levels of IL-6 and TNF-α as well as levels of prothrombotic markers. No differences were found between groups in regard to hospitalization length and time to various physical therapy milestones. Ischemic preconditioning reduces postoperative pain after TKA, but the treatment effect size we observed with the preconditioning routine used was modest. Given the ease of this intervention, ischemic preconditioning may be considered as part of a multimodal analgesic strategy. However, more study into the impact of different preconditioning strategies, elucidation of mechanisms, safety profiles, and cost-effectiveness of this maneuver is needed.


How do you feel? Affective forecasting and the impact bias in track athletics.
The author examined affective forecasting and the impact bias among track athletics. Results show that athletes clearly overestimated the intensity of their experienced negative emotions, whereas they accurately predicted the intensity of their experienced positive emotions. The author discusses these findings in relation to athletes' regulation processes.


Violent offending among juveniles: A 7-year longitudinal study of recidivism, desistance, and associations with mental health.
Serious and violent offending among juveniles is a consistent concern of researchers, practitioners, and policymakers, yet the development of violent offending remains poorly understood because of limited availability of relevant data, small sample sizes, and shortage of longitudinal data sets. This study analyzed developmental patterns of violent offending over 7 years in the complete population of court-referred youth in Connecticut between 2006 and 2012 (N = 58,678; mean age at first offense = 14.7 years). This unique dataset provided several key findings: First, results from a latent class growth analysis showed that violent crimes peaked at age 14-15, with high-rate adolescent offenders (3.7% of the sample) accounting for 31.9% of all violent offenses. Further, 74.2% of this group desisted from violent crimes in adulthood. Higher levels of self-reported anger/irritability slightly increased the odds of violent recidivism (odds ratio, OR = 1.09), where higher levels of depression/anxiety depressed the odds (OR = 0.89). The overrepresentation of males, non-Hispanic Black, and Hispanic youth among high-rate adolescence offenders were traceable through adolescence but not beyond the age of 18. Together, these finding may help to inform new delinquency interventions that target the needs of this proportionally small group of violent adolescent offenders accounting for a large amount of violent crimes. (PsycINFO Database Record


Right atrial emptying fraction non-invasively predicts mortality in pulmonary hypertension.
Right-sided heart failure is the most common cause of death in pulmonary hypertension (PH). Echocardiographic measurements of right atrial (RA) size are associated with worse outcome in PH, however the association between RA function and death in PH has not been well-described. 160 PH patients (World Health Organization groups 1-5) underwent cardiac magnetic resonance imaging (cMRI) and right heart catheterization (RHC) within 6 weeks of each other at a tertiary care academic medical center in the United States. We measured cMRI RA maximum and minimum volumes indexed to body surface area and calculated RA emptying fraction (RAEF). We evaluated the relationship between RAEF and clinical variables with death using Cox proportional hazard models. 57 deaths occurred during a median follow-up of 3.5 years (36 % died overall, 10 % per year). RAEF was directly correlated in univariate analyses with right ventricular (RV) ejection fraction, left ventricular (LV) ejection fraction, LV size, cardiac index, absence of tricuspid and pulmonic regurgitation, absence of pericardial effusion, estimated glomerular filtration rate, 6-minute walk distance, and pulmonary arterial oxygen saturation, whereas it was inversely correlated with death, BNP, heart rate, mean RA pressure, mean PA pressure, pulmonary and systemic vascular resistance, RV size, and RA size. Using multivariate analyses, RAEF had a robust inverse association with death after adjusting for measured risk factors (HR per 5 % change in RAEF: 0.83 [95 % CI 0.73-0.94], p = 0.003). In PH patients, decreased RAEF by cMRI is independently associated with worse survival after adjustment for other risk factors.


NeuroAIDS: contributions of the human immunodeficiency virus-1 proteins Tat and gp120 as well as CD40 to microglial activation.
Microglia are the resident phagocytes of the brain and are an important source of proinflammatory mediators. Human immunodeficiency virus (HIV)-1 infects the central nervous system early in the course of disease, and it is believed that this occurs, in part, through the transmigration of HIV-1-infected cells across the blood-brain barrier. Infected cells release viral proteins, such as Tat and gp120. After microglia interact with these proteins, they become activated and secrete chemokines; up-regulate key surface receptors, such as CD40, and also activate resident cells. This review focuses on the consequences of microglial activation in NeuroAIDS, with an emphasis on chemokine production and CD40 up-regulation after interaction with tat or gp120. The importance of microglial CD40 in two other neurological diseases, Alzheimer's disease and multiple sclerosis, is also discussed.


Culture-proven endogenous endophthalmitis: clinical features and visual acuity outcomes.
To investigate clinical features and visual acuity outcomes associated with endogenous endophthalmitis. Retrospective, observational case series. Twenty-one eyes of 21 patients treated at Bascom Palmer Eye Institute for culture-proven endogenous endophthalmitis between 1996 and 2002 were reviewed. Patients were followed a mean of 3 months (range, 1 to 12 months). Fungal isolates occurred in 13 eyes (62%), gram-positive isolates in 7 (33%), and gram-negative isolates in 1 (5%). Twelve patients (57%) were hospitalized at the time of diagnosis and 6 patients (29%) died within 2 months of diagnosis. Initial treatment included tap and injection of intravitreal medication in 10 eyes (48%) and pars plana vitrectomy with injection of intravitreal medication in 11 eyes (52%). Final visual outcomes were obtainable for 18 eyes (two patients died within 10 days of diagnosis, and one patient was lost to follow-up). Eight (44%) of these 18 eyes achieved a visual acuity of 20/400 or better and 10 (56%) of 18 eyes achieved a visual acuity worse than 20/400, including 3 that were either enucleated or eviscerated. Three eyes with Aspergillus endophthalmitis had worse visual outcomes than eyes with either Candida (P =.036) or bacterial endophthalmitis (P =.024). Compared with published series of postoperative or post-traumatic endophthalmitis, patients with endogenous endophthalmitis are more likely to have fungal isolates with a predominance of Candida albicans. Endogenous endophthalmitis is generally associated with high mortality and poor visual acuity outcomes, particularly when caused by more virulent species such as Aspergillus.


Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma.
The toxicity and clinical response to treatment with the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-gamma with or without IL-2. A 7-day course of subcutaneous IFN-gamma alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval. Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-gamma was established at 0.3 mg/m2 with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-gamma was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these findings, we conclude that further studies looking at this combination treatment are not warranted.


ATP13A2 (PARK9) protein levels are reduced in brain tissue of cases with Lewy bodies.
ATP13A2 (PARK9) loss of function mutations are a genetic cause of an early-onset form of Parkinson's disease (PD), with in vitro studies showing that ATP13A2 deficits lead to lysosomal and mitochondrial dysfunction and α-synuclein accumulation, while elevated ATP13A2 expression reduces α-synuclein toxicity. The three human brain tissue studies assessing changes in ATP13A2 expression in PD produced divergent results; mRNA is increased while protein levels were observed to be either increased or decreased. This apparent conflict in protein levels might have arisen from examining Lewy body disease cases with coexisting Alzheimer-type pathologies.To assess whether ATP13A2 levels in Lewy body disease are modified by Alzheimer-type β-amyloid deposition, we evaluated cases of pure PD and pure dementia with Lewy bodies (DLB) for changes in ATP13A2, α-synuclein and β-amyloid protein levels in cortical regions with and without Lewy bodies. In all Lewy body disease cases, we identified decreased ATP13A2 protein levels that correlated with increases in both α-synuclein and β-amyloid. Partial colocalization was observed between ATP13A2 and α-synuclein in Lewy bodies, whereas ATP13A2 did not colocalize with pathological β-amyloid deposition. Our data show that patients with Lewy body diseases have an overall deficit in ATP13A2 protein levels, with the remaining protein being more insoluble and partially redistributing towards Lewy bodies. This supports the concept that increasing ATP13A2 levels may offer potential therapeutic benefits to patients with Lewy body diseases.


Diabetes induces an impairment in the proteolytic activity against oxidized proteins and a heterogeneous effect in nonenzymatic protein modifications in the cytosol of rat liver and kidney.
It is assumed that increased oxidative stress contributes to the development of complications in diabetes. In this study, several markers of protein structural modifications directly induced by free radicals were investigated in the liver and kidney cytosolic fractions of rats with streptozotocin-induced diabetes. Sulfydryl residue and side-chain amino group analyses, as well as immunoblotting and chromatographic measurements of protein-bound carbonyl, suggest that protein oxidative modification is not increased by diabetes, with the exception of sulfydryl groups in renal cytosol. The levels of the glycation-derived carbonyl N epsilon-fructosyl-lysine are significantly increased by diabetes. Furthermore, unchanged proteolytic activity against in vivo-oxidized proteins, significant decreases both in activity against H2O2-modified proteins and in proteasome activity, measured by the degradation of a specific fluorogenic substrate, suggest that the unchanged oxidative protein modification in the diabetic state cannot be attributed to an increased cytosolic proteolytic activity in these tissues. These results provide evidence against a generalized increase in protein oxidative damage and demonstrate a diabetes-induced alteration in cytosolic proteolytic pathways, suggesting that proteasome activity may be impaired in these organs.


Same-Hospital Re-Admission Rate Is Not Reliable for Measuring Post-Operative Infection-Related Re-Admission.
Post-operative infections cause morbidity, consume resources, and are an important quality measure in assessing and comparing hospitals. Commonly used metrics do not account for re-admission to a different hospital. The Nationwide Readmissions Database (NRD) tracks re-admissions across United States (US) hospitals. Infection-related re-admission across US hospitals has not been studied previously. The 2013 NRD was queried for admissions with a primary International Classification of Diseases and Related Health Problems, 9th revision, Clinical Modification code for the most frequently performed operations. Non-elective all-cause, infection-related, and different hospital 30-day re-admission rates were calculated, using All Patient Refined Diagnosis Related Groups codes. Multi-variable logistic regression identified risk factors for re-admission. Of 826,836 surviving to discharge, 39,281 (4.8%) had an unplanned re-admission within 30 days, occurring at a different hospital 20.5% of the time. The most common reason for re-admission was infection (25.1%). Orthopedic and spinal procedures were at highest risk for all-cause and infection-related different hospital re-admission. Infection-related different hospital re-admission risk factors included: Length of stay >30 days (odds ratio [OR] 2.28 [1.62-3.21], p < 0.01), age ≥65 years (OR 1.56 [1.38-1.76], p < 0.01), and Charlson Comorbidity Index >1 (OR 1.14 [1.01-1.28], p < 0.01) and differed from predictors of same-hospital infectious re-admission. Non-elective surgical procedure (OR 0.79 [0.72-0.87], p < 0.01) and initial hospitalization at a large hospital (OR 0.66 [0.59-0.74], p < 0.01) were protective. A substantial proportion of post-operative re-admissions are missed by same-hospital re-admission data. All-cause and infection-related post-operative re-admissions to a different hospital are affected by unique patient and institution-specific factors. Re-admission reduction programs, quality metrics, and policy based on same hospital re-admission data should be updated to incorporate different hospital re-admission.


α-Lipoic acid attenuates vascular calcification via reversal of mitochondrial function and restoration of Gas6/Axl/Akt survival pathway.
Vascular calcification is prevalent in patients with chronic kidney disease and leads to increased cardiovascular morbidity and mortality. Although several reports have implicated mitochondrial dysfunction in cardiovascular disease and chronic kidney disease, little is known about the potential role of mitochondrial dysfunction in the process of vascular calcification. This study investigated the effect of α-lipoic acid (ALA), a naturally occurring antioxidant that improves mitochondrial function, on vascular calcification in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial membrane potential and ATP production, the disruption of mitochondrial structural integrity and concurrently increased production of reactive oxygen species. These Pi-induced functional and structural mitochondrial defects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol, subsequent activation of caspase-9 and -3, and chromosomal DNA fragmentation. Intriguingly, ALA blocked the Pi-induced VSMC apoptosis and calcification by recovery of mitochondrial function and intracellular redox status. Moreover, ALA inhibited Pi-induced down-regulation of cell survival signals through the binding of growth arrest-specific gene 6 (Gas6) to its cognate receptor Axl and subsequent Akt activation, resulting in increased survival and decreased apoptosis. Finally, ALA significantly ameliorated vitamin D(3) -induced aortic calcification and mitochondrial damage in mice. Collectively, the findings suggest ALA attenuates vascular calcification by inhibiting VSMC apoptosis through two distinct mechanisms; preservation of mitochondrial function via its antioxidant potential and restoration of the Gas6/Axl/Akt survival pathway.


[Potentialities of ultrasound study in diagnosis of endophytic carcinoma of stomach].
The data of studies of 45 patients with gastric cancer are used to consider the potentialities of ultrasonography (USG) in the diagnosis of its endophytic forms. Its use in the diagnosis of "small" gastric carcinomas is evaluated. The USG semiotics of endophytic tumors of the stomach, including its "small" and early forms, is presented. The place of USG in the diagnostic algorithmic of gastric cancer is specified. In the authors' opinion, gastric USG along with traditional X-ray and endoscopic studies should take an appropriate place as it is beneficial in solving a great deal of differential diagnostic problems associated with the intramural spread of tumors.


Anti-inflammatory effect of methanolic extract of Gmelina arborea bark and its fractions against carrageenan induced paw oedema in rats.
Gmelina arborea has been traditionally used for treatment of abdominal pain, burning sensation and as stomachic. The anti-inflammatory effect of aqueous and methanol extract of this plant has been studied but detailed investigations on anti-inflammatory activity of G. arborea stem bark are still not available. Therefore, the present study was designed to evaluate the anti-inflammatory activity of methanol extract and its fractions using carrageenan induced paw oedema model. Methanol extract at the dose of 500 mg/kg and its ethyl acetate fraction at 50 mg/kg showed significant reduction in paw oedema in comparison with standard drug. Ethyl acetate fraction was subjected to column chromatography which resulted in isolation of a new flavonoid (GM-01). Anti-inflammatory effect of methanol extract and its fractions can be attributed to the presence of the flavonoid GM-01. Further studies are underway for evaluation of anti-inflammatory effect of GM-01 and identification of active constituents present in ethyl acetate fraction.