Low-dose doxycycline prevents inflammatory bone resorption in rats.
Matrix metalloproteinases (MMP) are considered to be key initiators of collagen degradation, thus contributing to bone resorption in inflammatory diseases. We determined whether subantimicrobial doses of doxycycline (DX) (< or =10 mg kg-1 day-1), a known MMP inhibitor, could inhibit bone resorption in an experimental periodontitis model. Thirty male Wistar rats (180-200 g) were subjected to placement of a nylon thread ligature around the maxillary molars and sacrificed after 7 days. Alveolar bone loss (ABL) was measured macroscopically in one hemiarcade and the contralateral hemiarcade was processed for histopathologic analysis. Groups of six animals each were treated with DX (2.5, 5 or 10 mg kg-1 day-1, sc, 7 days) and compared to nontreated (NT) rats. NT rats displayed significant ABL, severe mononuclear cell influx and increase in osteoclast numbers, which were significantly reduced by 5 or 10 mg kg-1 day-1 DX. These data show that DX inhibits inflammatory bone resorption in a manner that is independent of its antimicrobial properties.


Heteroaryl sulfonamide synthesis: scope and limitations.
Heteroaryl sulfonamides are important structural motifs in the medicinal and agrochemical industries. However, their synthesis often relies on the use of heteroaryl sulfonyl chlorides, which are unstable and toxic reagents. Herein, we report a protocol that allows direct oxidative coupling of heteroaryl thiols and primary amines, readily available and inexpensive commodity chemicals. The transformation proceeds under mild reaction conditions and yields the desired N-alkylated sulfonamides in good yields. N-alkyl heteroaryl sulfonamides can be further transformed using a microwave-promoted Fukuyama-Mitsunobu reaction to N,N-dialkyl heteroaryl sulfonamides. The developed protocols thus enable the preparation of previously difficult to prepare sulfonamides (toxic reagents, harsh conditions, and low yields) under mild conditions.


A retrospective study of Creutzfeldt-Jakob disease in England and Wales 1970-79. I: Clinical features.
A comprehensive search yielded 121 confirmed cases of Creutzfeldt-Jakob disease who died in England and Wales in the decade 1970-79, and 31 probable cases. The clinical features and the results of investigation are described. Three subgroups of patients were distinguished by clinical characteristics and contrasting course.


CT evaluation of the pelvic cavity after cystectomy: observation in 40 cases.
This study reports our experience with CT in 40 patients who underwent total cystectomies. This technique permits careful monitoring of post-operative recovery and defects and identifies complications, local recurrences, or diffuse neoplastic spread. In complete cystectomies with or without neobladder, the possibility of recognizing abnormalities depends on the operator's ability to recognize normal postoperative modifications and asymmetry in the muscle masses along the lateral walls and to identify any unusual masses. Local recurrence in the pelvic cavity can show up as alterations in the thickness of the soft structures that cover the pelvic walls or as new masses. A postoperative abscess is suggested by the demonstration of gas in a nonintestinal mass. A urinoma generally presents as a low density mass with a thin wall even if some urinomas communicate with the genitourinary tract and therefore opacify with the use of intravenous contrast medium administration. Despite these limitations, CT remains the best investigative technique for exploring the pelvic cavity after cystectomy, making it an indispensable examination in well-programmed patient follow-up.


Histological and immunohistochemical characterization of the inflammatory and glial cells in the central nervous system of goat fetuses and adult male goats naturally infected with Neospora caninum.
Neospora caninum is an apicomplexan protozoan that is considered one of the main agents responsible for abortion in ruminants. The lesions found in the central nervous system (CNS) of aborted fetuses show multifocal necrosis, gliosis, and perivascular cuffs of mononuclear cells, but the inflammatory and glial cells have not been immunophenotypically characterized. The lesions in the CNS of infected adult animals have rarely been described. Therefore, in this study, we characterized the lesions, the immunophenotypes of the inflammatory and glial cells and the expression of MHC-II and PCNA in the CNS of goats infected with N. caninum. The CNS of eight aborted fetuses and six adult male goats naturally infected with N. caninum were analyzed with lectin histochemistry (RCA1) and immunohistochemistry (with anti-CD3, -CD79α, -GFAP, -MHC-II, and -PCNA antibodies). All animals were the offspring of dams naturally infected with N. caninum. The microscopic lesions in the CNS of the aborted fetuses consisted of perivascular cuffs composed mainly of macrophages (RCA1(+)), rare T lymphocytes (CD3(+)), and rare B lymphocytes (CD79α(+)). Multifocal necrosis surrounded by astrocytes (GFAP(+)), gliosis composed predominantly of monocytic-lineage cells (macrophages and microglia, RCA1(+)), and the cysts of N. caninum, related (or not) to the lesions were present. Similar lesions were found in four of the six male goats, and multinucleate giant cells related to focal gliosis were also found in three adult goats. Anti-GFAP immunostaining showed astrocytes characterizing areas of glial scarring. Cysts of N. caninum were found in three adult male goats. The presence of N. caninum was evaluated with histopathology, immunohistochemistry, and PCR. Immunohistochemistry demonstrated anti-PCNA labeling of macrophages and microglia in the perivascular cuffs and the expression of MHC-II by microglia and endothelial cells in the CNS of the aborted fetuses and adult male goats. Macrophages and microglia were the predominant inflammatory cells in the CNS of aborted fetuses and healthy adult male goats infected with N. caninum. Activated astrocytes were mainly associated with inflamed areas, suggesting that astrocytes were involved in the resolution of the lesions.


mESC-based in vitro differentiation models to study vascular response and functionality following genotoxic insults.
Because of high exposure to systemic noxae, vascular endothelial cells (EC) have to ensure distinct damage defense and regenerative mechanisms to guarantee vascular health. For meaningful toxicological drug assessments employing embryonic stem cell (ESC)-based in vitro models, functional competence of differentiated progeny and detailed knowledge regarding damage defense mechanisms are essential. Here, mouse ESCs (mESC) were differentiated into functionally competent vascular cells (EC and smooth muscle cells [SMC]). mESC, EC, and SMC were comparatively analyzed regarding DNA repair and DNA damage response (DDR). Differentiation was accompanied by both congruent and unique alterations in repair and DDR characteristics. EC and SMC shared the downregulation of genes involved cell cycle regulation and repair of DNA double-strand breaks (DSBs) and mismatches, whereas genes associated with nucleotide excision repair (NER), apoptosis, and autophagy were upregulated when compared with mESC. Expression of genes involved in base excision repair (BER) was particularly low in SMC. IR-induced formation of DSBs, as detected by nuclear γH2AX foci formation, was most efficient in SMC, the repair of DSBs was fastest in EC. Together with substantial differences in IR-induced phosphorylation of p53, Chk1, and Kap1, the data demonstrate complex alterations in DDR capacity going along with the loss of pluripotency and gain of EC- and SMC-specific functions. Notably, IR exposure of early vascular progenitors did not impair differentiation into functionally competent EC and SMC. Summarizing, mESC-based vascular differentiation models are informative to study the impact of environmental stressors on differentiation and function of vascular cells.


Rehabilitation of a patient with bilateral rectus abdominis full thickness tear sustained in recreational strength training: a case report.
Case Report. Abdominal wall muscle injuries have been reported in handball, tennis, and baseball; however, a bilateral full-thickness tear of the rectus abdominis muscle and its rehabilitation have not previously been described. This report aims to describe a case of an acute bilateral full-thickness rectus abdominis tear simulating an acute abdomen that presented to an emergency department. A 25-year-old male (169 cm, 84 kg) was transferred to the emergency room due to severe lancinating (Numerical Pain Rating 10/10) abdominal pain that occurred during weight training at a gym. An orthopedic surgeon, an internist, and a general surgeon assessed him for internal and surgical emergencies. The magnetic resonance imaging of his abdomen revealed a bilateral full-thickness tear of the rectus abdominis muscle. The patient was given an option of surgical repair of the RA, but he refused. Six weeks later, he attended our sports medicine department. A criteria-based rehabilitation program was planned, with weekly follow-ups. The patient could walk pain-free at 4th week and jog at 10th week of rehabilitation. Significant improvements in the range of movement of the trunk, pain levels and functional capacity were noted at discharge and 6 and 12-month follow-ups. Clinical management of this patient is described in detail, with emphasis on diagnostic ultrasonography. The structured rehabilitation program used for this patient resulted in a return to pre-injury level function.


Interface-Driven Ferromagnetism within the Quantum Wells of a Rare Earth Titanate Superlattice.
Here we present polarized neutron reflectometry measurements exploring thin film heterostructures composed of a strongly correlated Mott state, GdTiO_{3}, embedded with SrTiO_{3} quantum wells. Our results reveal that the net ferromagnetism inherent to the Mott GdTiO_{3} matrix propagates into the nominally nonmagnetic SrTiO_{3} quantum wells and tracks the magnetic order parameter of the host Mott insulating matrix. Beyond a well thickness of 5 SrO layers, the magnetic moment within the wells is dramatically suppressed, suggesting that quenched well magnetism comprises the likely origin of quantum critical magnetotransport in this thin film architecture. Our data demonstrate that the interplay between proximate exchange fields and polarity-induced carrier densities can stabilize extended magnetic states within SrTiO_{3} quantum wells.


Common predictors of adverse outcomes in adult deceased donor kidney transplant recipients with varying sensitization.
Our objective was to identify consistent predictors of multiple adverse outcomes of adult deceased donor (DD) kidney transplant recipients (KTRs) of varying sensitization status. We used the national transplant database in studying 62037 adult DD-KTRs between Dec. 2007 and Jun. 2015 stratified into sensitization cohorts based on calculated panel reactive antibody (CPRA) of <10%, 10%-79%, and ≥80%. We used multivariable logistic regressions for the analysis of risks for delayed graft function (DGF), and of acute rejection (AR) and hospitalization in the first year of transplant, and Cox hazard regression for 5-year overall graft loss (OAGL) and death. The kidney donor risk index (KDRI) highest two quartiles ≥1.45 and 1.15-1.44 were the most consistent predictors for 100% of adverse outcomes (OAGL, death, DGF, AR, and hospitalization) with high significance (P<0.0001) across all sensitization cohorts. The two risk factors that were consistently associated with 80% of adverse outcomes across sensitization cohorts were: (1) pre-transplant dialysis duration >2 years was significantly associated with increased risks of overall graft loss, death, DGF, and hospitalization; and (2) Black KTR race was significantly associated with increased risks of DGF, AR, and hospitalization, and decreased risk of death. Diabetes and KTR age >65 (years) were significant risk factors for overall loss and death across sensitization cohorts. The two highest KDRI quartiles, pre-transplant dialysis duration >2 years, and African American recipient race are consistent predictors of multiple adverse outcomes in adult DDKTRs across sensitization strata and should be among the factors considered in clinical decision-making and research models in kidney transplantation.


Design and performance of magnetic composite particles for the separation of heavy metals from water.
Composite particles have been made by combining nanosized polymer particles with magnetite microparticles using a ball-mill process. The magnetite particle cores were included to facilitate the composite particles separation by use of a magnetic field. Polymer particles carried carboxylic groups as ion-exchange vehicles. The composite particles were used in the extraction/stripping of Zn, Cu, Ni, and Cr from aqueous solutions in a stirred batch reactor of laboratory scale. The extraction behavior of these metals was studied as a function of initial metal concentrations of up to 25 mM, ionic strength at pH (5-7), and temperature (1-80 degrees C). Experimental results showed that the process was very fast and yielded complete metal removal when the initial concentrations of metals were very low. The selectivity series was Cu > Cr > Zn > Ni. The effect of ionic strength was immaterial at pH 7. However, extraction decreased with increasing ionic strength at pH 5. Extraction increased with increasing temperature. A series of extraction/ stripping experiments indicated that the particles can be reused without significant loss in their extraction capacity.


[Analysis on Correlation Between Meridians and Viscera in Book The Yellow Emperor's Internal Classic].
The meridians and Zangfu-organs (viscera) are two major systems in the basic theory of traditional Chinese medicine (TCM). They were primarily emerged together in simple form possibly in the Han Dynasty shown by the unearthed silk manuscripts of Changsha Mawangdui Han Tomb, and became a systematic theory in classical book "Neijing" (The Yellow Emperor's Internal Classic). After classification of the meridians' disease manifestations described in book "Ling Shu-Jing Mai" (Miraculous Pivot: Meridians) we found that more than half of the manifestations appear along the running course of meridians. The symptoms and signs of disorders of the meridians correlated with viscera which have the same name in western medicine account for approximately 10%, and the rest pathologic manifestations correlated with the viscera in terms of TCM are approximately 30%. Current researches about meridian and viscera mainly focus on viscera, particularly on the stomach and heart. The researches on meridians and viscera that use real-time effects of acupuncture as indicators have a complicated relationship with the nerve segments, which presented as that "multiple meridians control one viscus" and the specificity of meridian. Our chronic experiment about blocking the meridians suggested an association between meridian and pathologic manifestations of viscera. Physical index measurement and mathematical analysis can verify certain patterns of meridian-physical appearances, which would be a direction for future meridian research. The stabilities of visceral functions rely on negative feedback regulation, which are probably realized by way of somatic and visceral afferent and efferent nerves and volume transmission of the tissue fluid channels of meridians. Therefore, signals of acupuncture stimulation of the distant acupoints might be transmitted to the central nervous system through neurohumor relay, open of the "negative feedback channels of meridians", achieving a bidirectional regulation, and at the same time, producing a phenomenon of "sensation propagated along the meridian" during signal transmission.


Age Trajectories of Physical Health Among Older Adults of Mexican Descent: Implications of Immigrant Status, Age at Immigration, and Gender.
This study examines consequences of immigrant status, age at immigration, and gender on age trajectories of activities of daily living (ADL) limitations and chronic conditions among older adults of Mexican descent. This research draws on 7 waves of the Hispanic Established Populations for the Epidemiologic Study of the Elderly and employs growth curve models. All men had similar age trajectories of ADL limitations, regardless of immigrant status and age at immigration. All women experienced steeper increases in ADL limitations, although U.S.-born women and those who immigrated by age 19 had lower initial levels. Men who immigrated between ages 20 and 49 had steeper increases in chronic conditions, despite lower initial levels. U.S.-born women and those women who immigrated by age 50 had more chronic conditions at age 65. This study highlights the multidimensional nature of physical health by demonstrating that immigrant status-gender disparities can vary by the health outcome examined.


Enhanced expression of ganglioside GD3 in human and rat hepatocellular carcinoma cells and NIH 3T3 cells transfected with human tumor DNAs.
The gangliosides of human hepatoma biopsies, human hepatoma cell lines, and diethylnitrosamine-induced rat hepatomas were examined. These malignant tissues all expressed increased content of disialolactosylceramide (GD3) with respect to their normal counterparts. During the induction of rat hepatoma by diethylnitrosamine, an increase in GD3 levels appeared as early as 12 wk after initiation of diethylnitrosamine, concurrent with the appearance of precancerous hepatocytes. GD3 levels gradually increased to a peak of 4 times that of normal rat liver at 20 wk. CMP-NeuAc:GM3 sialyltransferase, the enzyme that synthesizes GD3 by transfer of sialic acid to GM3, also had tumor-associated elevation during the course of diethylnitrosamine-induction of rat hepatomas. To investigate the relationship of oncogene transformation and changes in ganglioside biosynthesis, NIH 3T3 cells transfected DNAs from human hepatoma or nasopharyngeal carcinoma were studied. The transfectants each expressed the same ganglioside composition, including a detectable level of GD3, as well as enhanced activity of CMP-NeuAc:GM3 sialyltransferase. A correlation between the tumor DNA transfection and the augmentation of GD3 in malignant cells is discussed. Because of the early appearance of GD3 in hepatoma and its possible relationship to oncogene activation, GD3 may be a potentially useful early tumor marker.


Translucency and color match with a shade guide of esthetic brackets with the aid of a spectroradiometer.
Since the color of esthetic brackets should match that of teeth, the aims of this study were to determine the color and translucency of esthetic brackets by means of the clinically relevant use of a spectroradiometer, and to compare the color of brackets with that of a commercial shade guide. The color of central and tie-wing regions of four plastic and four ceramic brackets was measured according to the CIE L*a*b* color scale over white and black backgrounds. Brackets were classified into five groups based on their composition. The color of Vitapan Classical Shade Guide tabs was also measured. Translucency parameter (TP) and contrast ratio (CR) were calculated to determine translucency. Color differences between brackets and the shade guide tabs were 10.4 - 34.5 ∆E*ab units. TP and CR values for the central region were 16.4 - 27.7 and 0.38 - 0.58, whereas for the tie-wings they were 24.0 - 39.9 and 0.25 - 0.45, respectively. The color coordinates, TP and CR values were significantly influenced by bracket composition and brand (p < 0.05). Esthetic brackets investigated herein showed unacceptable color differences (∆E*ab > 5.5) compared with the shade guide tabs. Differences in the translucency of brackets by brand were within the visually perceptible range (∆CR > 0.07). Therefore, brackets showing the best matching performance for each case should be selected considering esthetic and functional demands.


Paramyxoviruses: Pathogenesis, Vaccines, Antivirals, and Prototypes for Pandemic Preparedness.
The Paramyxoviridae family includes established human pathogens such as measles virus, mumps virus, and the human parainfluenza viruses; highly lethal zoonotic pathogens such as Nipah virus; and a number of recently identified agents, such as Sosuga virus, which remain poorly understood. The high human-to-human transmission rate of paramyxoviruses such as measles virus, high case fatality rate associated with other family members such as Nipah virus, and the existence of poorly characterized zoonotic pathogens raise concern that known and unknown paramyxoviruses have significant pandemic potential. In this review, the general life cycle, taxonomic relationships, and viral pathogenesis are described for paramyxoviruses that cause both systemic and respiratory system-restricted infections. Next, key gaps in critical areas are presented, following detailed conversations with subject matter experts and based on the current literature. Finally, we present an assessment of potential prototype pathogen candidates that could be used as models to study this important virus family, including assessment of the strengths and weaknesses of each potential prototype.


Myelopathy from intracranial dural arteriovenous fistula.
Dural arteriovenous fistulas arising intracranially are an uncommon cause of progressive myelopathy. This report is of a patient in whom the diagnosis of the condition was confounded by coexisting small vessel cerebrovascular disease.


Hypersensitivity to pollen allergens on the Adriatic coast.
In central south Croatia, i.e., the Adriatic coast with the city of Split at the center, year-long pollen concentrations in the air were determined for typical local plants, and the area's plant pollination calendar was established. High concentrations of Parietaria officinalis pollen dominated during the year (up to 20% from April to June). Pollens of Pistacia lentiscus, Olea europaea, Pinus halepensis, Juniperus oxycedrus, Mimosa and Cistus monspeliensis were found in lower concentrations and for shorter time periods. Using both commercially available standard inhalation allergens and specifically prepared pollen allergens, skin testing was performed and the cause of hypersensitivity was determined in a population of 4116 atopic patients with respiratory symptoms. Some 38.8% of patients were allergic to standard pollen allergens (mixed grass pollen, mixed tree pollen, P. officinalis and Pittosporum tobira). Hypersensitivity to more than one allergen was found in 53% of patients, whereas 19% of patients did not react to any of the standard allergens. Additional testing with newly prepared individual allergens (P. lentiscus, O. europaea, P. halepensis, J. oxycedrus, Mimosa and C. monspeliensis) revealed the causes of hypersensitivity in a number of patients, but the testing of patients nonreactive to standard allergens still left 44% of these individuals without reaction to any of the allergens used. Hypersensitivity to the pollens of P. tobira, C. monspeliensis and J. oxycedrus is described for the first time.


Sensory descriptive and comprehensive GC-MS as suitable tools to characterize the effects of alternative winemaking procedures on wine aroma. Part I: BRS Carmem and BRS Violeta.
This study analyzed the volatile composition and aroma profile of BRS Carmem and BRS Violeta red wines elaborated from traditional and two alternative winemaking procedures: grape pre-drying and submerged cap. The wines contained higher concentration of acetates (ranging from 303 mg L-1 to 905 mg L-1) and ethyl and methyl esters (ranging from 138 mg L-1 to 415 mg L-1). The BRS Carmem wines were described as fruity due to the higher concentration of esters and BRS Violeta wines were described as vegetal mainly due to the higher concentration of terpenes and methoxyphenols. C6 alcohols also influenced the vegetal notes of BRS Violeta wines from traditional and submerged cap procedures and the pre-dried wines also presented a relevant jam note possibly due to the presence of 2-phenylethyl acetate. The changes in winemaking procedures can possibly lead to changes in the aromatic profile of red wines in a positive way, improving the wine aroma quality.


Long-range stress correlations in viscoelastic and glass-forming fluids.
A simple and rigorous approach to obtain stress correlations in viscoelastic liquids (including supercooled liquid and equilibrium amorphous systems) is proposed. The long-range dynamical correlations of local shear stress are calculated and analyzed in 2-dimensional space. It is established how the long-range character of the stress correlations gradually emerges as the relevant dynamical correlation length l grows in time. The correlation range l is defined by momentum propagation due to acoustic waves and vorticity diffusion which are the basic mechanisms for transmission of shear stress perturbations. We obtain the general expression defining the time- and distance-dependent stress correlation tensor in terms of material functions (generalized relaxation moduli). The effect of liquid compressibility is quantitatively analyzed; it is shown to be important at large distances and/or short times. The revealed long-range stress correlation effect is shown to be dynamical in nature and unconnected with static structural correlations in liquids (correlation length ξs). Our approach is based on the assumption that ξs is small enough as reflected in weak wave-number dependencies of the generalized relaxation moduli. We provide a simple physical picture connecting the elucidated long-range fluctuation effect with anisotropic correlations of the (transient) inherent stress field, and discuss its implications.


Metabolism of vitamin K and vitamin K 2,3-epoxide via interaction with a common disulfide.
The effects of thiols and sulfhydryl blocking reagents on the reduction of vitamin K to vitamin K hydroquinone and vitamin K 2,3-epoxide to vitamin K and vitamin K hydroquinone catalyzed by rat hepatic microsomes were investigated to determine the mechanism(s) for these reactions. Both vitamin K and vitamin K 2,3-epoxide reductions were catalyzed more effectively with dithiols than with monothiols as the reductant. The sulfhydryl reagent N-ethylmaleimide (NEM) inhibited vitamin K and vitamin K 2,3-epoxide reduction much more effectively when microsomes were initially treated with dithiothreitol (prereduced). In prereduced microsomes iodoacetamide was approximately half as effective an inhibitor of vitamin K and vitamin K 2,3-epoxide reduction as NEM, but in microsomes not prereduced it was more effective. Iodoacetic acid was ineffective as an inhibitor. Vitamin K or vitamin K 2,3-epoxide added to prereduced microsomes blocked subsequent inhibition by NEM of vitamin K and vitamin K 2,3-epoxide metabolism, respectively. Vitamin K added to prereduced microsomes also blocked inhibition by NEM of vitamin K 2,3-epoxide metabolism, and vitamin K 2,3-epoxide addition blocked inhibition by NEM of vitamin K metabolism. Vitamin K did not diminish the rate of vitamin K 2,3-epoxide metabolism, however, nor did vitamin K 2,3-epoxide diminish the rate of vitamin K metabolism. These data establish that exogenous thiol compounds promote the reduction of at least one protein disulfide which participates in the metabolism of vitamin K and vitamin K 2,3-epoxide. Presumably, the resultant sulfhydryl groups are reoxidized to the disulfide form during the metabolism of either vitamin which protects them from reaction with NEM.


Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment.
Previous studies have shown that treatment with recombinant adropin, a circulating peptide secreted by the liver and brain, restores glucose utilization in the hearts of diet-induced obese mice. This restoration of fuel substrate flexibility, which is lost in obese and diabetic animals, has the potential to improve contractile function in the diabetic heart. Using an ex vivo approach, we examined whether short-term adropin treatment could enhance cardiac function in a mouse model of diet-induced obesity. Our study showed that acute adropin treatment reduces inhibitory phosphorylation of pyruvate dehydrogenase in primary neonatal cardiomyocytes, and leads to moderate improvements in ex vivo cardiac function in mice fed a low fat diet. Conversely, short-term exposure to adropin led to a small decrease in cardiac function in mice fed a long-term high fat diet. Insulin treatment did not significantly alter cardiac function in adropin treated hearts from either low or high fat diet mice, however acute adropin treatment did moderately restore some aspects of downstream insulin signaling in high fat diet fed mice. Overall, these data suggest that in an ex vivo setting, acute adropin treatment alone is not sufficient to promote improved cardiac function in obese animals.


Enhancing circulation to lower limbs during head-down tilt by warming upper body and thighs.
Long-duration spaceflight results in deconditioning of the cardiovascular system, loss of fluid volume, bone demineralization, and atrophy of skeletal muscles, particularly affecting the lower limbs. We hypothesized that it is possible to improve blood circulation to the lower extremities in simulated microgravity by forcing the blood to deliver heat to the feet through heating parts of the upper body and thighs. In Study 1, seven men and four women were assessed in an environmental chamber with head-down tilt (HDT) at 14 degrees, wearing a newly developed shortened multi-compartment liquid cooling/warming garment (SLCWG) with local tubing networks covering parts of the head, torso, thigh, arms, and hands, with fingers, lower leg, and feet exposed. Study 2 was the same as Study 1 with a new cohort of four men and two women, and the assessment of toe blood perfusion on all subjects. Heat was applied as follows: Stage 1--SLCWG inlet water temperature 33 degrees C to stabilize comfort; Stage 2--inlet water temperature 8-10 degrees C (in combination with HDT) to reach a criterion of 25 degrees C finger temperature (Tfing); and Stage 3--inlet water temperature 45 degrees C to restore Tfing to 33 degrees C. Improvement of foot circulation by delivering more heat to the upper body and thighs was noted; increases in toe temperature (Ttoe) suggest enhanced perfusion. From Stage 2 to 3, there were significant increases in Ttoe (p < 0.05), a significant decrease in diastolic BP (DBP) (p < 0.05), and a significant change across stages in subjective perception of foot comfort (p < 0.001) and foot heat (p < 0.06). Further, toe blood perfusion increased significantly from Stage 2 to 3 (p < 0.05). Moderate partial heating of the upper body/thighs improved blood circulation in the feet in simulated microgravity by delivering heat to the lower extremities through restriction of heat exchange with the environment in the heated body parts. This technique could serve as a supplemental countermeasure for increasing blood circulation to the lower extremities.


Retrospective analysis of seven patients with adult-onset langerhans cell histiocytosis syndromes: A single center experience.
Langerhans cell histiocytosis syndromes have been described as encompassing a range of disorders, such as eosinophilic granuloma, Letterer-Siwe syndrome and Hand-Schüller-Christian disease. These disorders have been mainly diagnosed at early ages of life and are relatively rare entities in adult age groups. In this study, we aimed to retrospectively evaluate the patients with Langerhans cell histiocytosis followed-up in our hospital. Seven patients were treated between 1995 and 2005. Median age of patients was 27.5 (18-40) years. Main complaints were classified as bone pain in multiple sites (100%), polydipsia (28%), lung infiltration (14%), oral mucosal infiltration (14%), and cranial nerve infiltration (14%). Two patients were diagnosed as Hand-Schüller-Christian disease, and the others were accepted as eosinophilic granuloma. There was no bone marrow or any other organ infiltration except lung infiltration in one patient. Bone infiltration was the prominent sign in all patients with a minimum of one to maximum of seven different sites. All patients were alive during the follow-up period. All patients were treated with radiotherapy except one patient treated with chemotherapy regimen started with vincristine plus dexamethasone and continued with cladribine. Three of seven patients were treated with combined modality, one patient with only chemotherapy and the others with only radiotherapy. There was no grade 3-4 hematological or systemic side effects of treatment. Relapses were detected in only two patients as new bone infiltrations which responded completely to radiotherapy. Langerhans cell histiocytosis syndromes have a relatively benign course in adult patients and can be treated with either radiotherapy or chemo-radiotherapy successfully.


Molecular Mechanism of Nucleotide-Dependent Allosteric Regulation in AMP-Activated Protein Kinase.
The AMP-activated protein kinase (AMPK), a central enzyme in the regulation of energy homeostasis, is an important drug target for type 2 diabetes, obesity, and cancer. Binding of adenosine nucleotides to the regulatory γ-subunit tightly regulates the activity of this enzyme. Though recent crystal structures of AMPK have provided important insights into the allosteric activation of AMPK, molecular details of the regulatory mechanism of AMPK activation is still elusive. Here, we have performed extensive all-atom molecular dynamics (MD) simulations and shown that the kinase domain (KD) and γ-subunit come closer resulting in a more compact heterotrimeric AMPK complex in AMP-bound state compared to the ATP-bound state. The binding of ATP at site 3 of regulatory γ-subunit allosterically inhibits AMPK by destabilizing different regulatory regions of α-subunit: the autoinhibitory domain, the linker region, and the activation loop of the kinase core. The catalytically important residues experience a change in mechanical stress, and major rearrangements in community structure derived from residue-residue interaction energy-based network are observed in KD and α-linker region upon binding of different nucleotides. Our results also highlight the role of conserved charged residues forming an ionic network near the site 3 of γ-subunit in allosteric communications.


Publication of the first journal of dentistry in Iran.
The first scientific journal of dentistry in Iran was published by the "Iranian Dentists' Syndicate" (called in Persian "Sandikay-e Dandanpezeshkan-e Iran") in 1951. A brief account of the journal and its editorial board is presented here.


Helicobacter pylori and the risk and management of associated diseases: gastritis, ulcer disease, atrophic gastritis and gastric cancer.
This review addresses the role of H. pylori and the effect of H. pylori eradication on gastritis, peptic ulcer disease, atrophic gastritis and gastric cancer. Specific emphasis is given to various factors that influence the clinical course of this infection. H. pylori induces chronic gastritis in virtually all infected subjects. This inflammation can lead to peptic ulceration and atrophic gastritis in a considerable number of infected subjects. A minority eventually develops gastric cancer. The risk of such complications depends upon the severity of gastritis, which is determined by various host- and bacteria-related factors. Among bacterial factors, most of the evidence addresses the cagA pathogenicity island, the presence of which has been associated with more severe gastritis, peptic ulceration, atrophic gastritis and gastric cancer. Among host factors, most of the evidence focuses on acid production in response to H. pylori infection. An increase in acid secretion limits H. pylori gastritis to the antrum at the risk of duodenal ulcer disease; a reduction allows more proximal inflammation at the risk of atrophic gastritis, gastric ulcer disease, and gastric cancer. Gastritis and atrophy negatively influence acid secretion. H. pylori eradication is required in peptic ulcer disease and may be advocated in patients on profound acid suppressive therapy; it has been shown to cure gastritis and prevent ulcer recurrence. Further study is required to determine the efficacy of H. pylori eradication in the primary and secondary prevention of atrophic gastritis and gastric cancer.


Electric-field induced mutation of DNA: a theoretical investigation of the GC base pair.
It is known that intense external electric fields affect the proton transfer (PT) reactions in simple chemical systems, such as hydrated chlorhydric acid or formic acid dimer. Accordingly, electric fields might be used to modulate the PT reactions responsible for the spontaneous mutation mechanism in DNA. In this contribution, we investigate the effect of these fields on the tautomeric equilibria of the guanine-cytosine (GC) base pair in order to gain further insight into this hypothesis. This task is performed with both density functional theory (DFT) and second-order Møller-Plesset (MP2) approaches. Our results demonstrate that electric fields not only drastically alter the rate constants of PT but also tune the mechanism of the PT reactions in the GC base pair.


Extinction and spontaneous recovery of spatial behavior in pigeons.
We investigated extinction and spontaneous recovery of spatial associations using a landmark-based appetitive search task in a touchscreen preparation with pigeons. Four visual landmarks (A, B, C, and D) were separately established as signals of a hidden reinforced target among an 8 × 7 array of potential target locations. The target was located above landmarks (LM) A and C and below B and D. After conditioning, A and B were extinguished. Responding to A and C was assessed on probe tests 2 days following extinction, whereas, B and D were tested 14 days after extinction. We observed spontaneous recovery from spatial extinction following a 14-day, but not a 2-day, postextinction retention interval. Furthermore, by plotting the spatial distribution of responding across the X and Y axes during testing, we found that spontaneous recovery of responding to the target in our task was due to enhanced spatial control (i.e., a change in the overall distribution of responses) following the long delay to testing. These results add spatial extinction and spontaneous recovery to the list of findings supporting the assertion that extinction involves new learning that attenuates the originally acquired response, and that original learning of the spatial relationship between paired events survives extinction. (PsycINFO Database Record


'Ordinariness' in nursing: a study (Part 1).
This is the first of two articles describing aspects of ordinariness in nursing as they were explored in a phenomenological study on clinical nursing. By way of introduction, it provides an overview of the first phase of the study in terms of its background and method, and describes aspects of ordinariness, showing their relevance to nursing practice. In exploring this phenomenon, this study affirmed a shared sense of humanity as a general group and the enhancing effect this affinity can have on interpersonal relationships.


Genetic relatedness among human rotavirus genes coding for VP7, a major neutralization protein, and its application to serotype identification.
Antigenic characterization of human rotaviruses by plaque reduction neutralization assay has revealed four distinct serotypes. The outer capsid protein VP7, coded for by gene 8 or 9, is a major neutralization protein; however, studies of rotaviruses derived from genetic reassortment between two strains have confirmed that another outer capsid protein, VP3, is in some cases equally important in neutralization. In this study, the genetic relatedness of the genes coding for VP7 of human rotaviruses belonging to serotypes 1 through 4 was examined by hybridization of their denatured double-stranded genomic RNAs to labeled single-stranded mRNA probes derived from human-animal rotavirus reassortants containing only the VP7 gene of their human rotavirus parent. A high degree of homology was demonstrated between the VP7 genes of strain D and other serotype 1 human rotaviruses, strain DS-1 and other serotype 2 human rotaviruses, strain P and other serotype 3 human rotaviruses, and strain ST3 and other serotype 4 human rotaviruses. Hybrid bands could not be demonstrated between the VP7 gene of D, DS-1, P, or ST3 and the corresponding gene of human rotaviruses belonging to a different serotype. RNA specimens extracted from the stools of 15 Venezuelan children hospitalized with rotavirus diarrhea were hybridized to each of the reassortant probes representing the four human serotypes. All five viruses with short RNA patterns showed homology with the DS-1 strain VP7 gene; two of these were previously adapted to tissue culture and shown to be serotype 2 strains by tissue culture neutralization. Of the remaining 10 viruses with long RNA patterns, 2 hybridized only to the D strain VP7 gene, 6 hybridized only to the P strain VP7 gene, and 2 hybridized only to the ST3 strain VP7 gene. Hybridization using single human rotavirus gene substitution reassortants as probes may provide an alternative method for identifying the VP7 serotype of field isolates that would circumvent the need for tissue culture adaptation.


Human Epidermal Growth Factor Receptor 3-Specific Tumor Uptake and Biodistribution of 89Zr-MSB0010853 Visualized by Real-Time and Noninvasive PET Imaging.
The human epidermal growth factor receptor 3 (HER3) is an interesting target for antitumor therapy. For optimal HER3 signaling inhibition, a biparatopic Nanobody construct (MSB0010853) was developed that binds 2 different HER3 epitopes. In addition, MSB0010853 contains a third HER3 epitope that binds albumin to extend its circulation time. MSB0010853 is cross-reactive with HER3 and albumin of mouse origin. We aimed to gain insight into MSB0010853 biodistribution and tumor uptake by radiolabeling the Nanobody construct with 89Zr. Methods: MSB0010853 was radiolabeled with 89Zr. Dose- and time-dependent tumor uptake was studied in nude BALB/c mice bearing a subcutaneous HER3 overexpressing H441 non-small cell lung cancer xenograft. Dose-dependent biodistribution of 89Zr-MSB0010853 was assessed ex vivo at 24 h after intravenous injection. Protein doses of 5, 10, 25, 100, and 1,000 μg were used. Time-dependent biodistribution of MSB0010853 was analyzed ex vivo at 3, 6, 24, and 96 h after intravenous administration of 25 μg of 89Zr-MSB0010853. PET imaging and biodistribution were performed 24 h after administration of 25 μg of 89Zr-MSB0010853 to mice bearing human H441, FaDu (high HER3 expression), or Calu-1 (no HER3 expression) tumor xenografts. Results: Radiolabeling of MSB0010853 with 89Zr was performed with a radiochemical purity of greater than 95%. Ex vivo biodistribution showed protein dose- and time-dependent distribution of 89Zr-MSB0010853 in all organs. Uptake of 89Zr-MSB0010853 in H441 tumors was only time-dependent. Tumor could be visualized up to at least 96 h after injection. The highest mean SUV of 0.6 ± 0.2 was observed at 24 h after injection of 25 μg of 89Zr-MSB0010853. 89Zr-MSB0010853 tumor uptake correlated with HER3 expression and was highest in H441 (6.2 ± 1.1 percentage injected dose per gram [%ID/g]) and lowest in Calu-1 (2.3 ± 0.3 %ID/g) xenografts. Conclusion:89Zr-MSB0010853 organ distribution and tumor uptake in mice are time-dependent, and tumor uptake correlates with HER3 expression. In contrast to tumor uptake except for kidney uptake, organ distribution of 89Zr-MSB0010853 is protein dose-dependent for the tested doses. 89Zr-MSB0010853 PET imaging gives insight into the in vivo behavior of MSB0010853.


Qatari intersections with global genetics research and discourse.
Genetic discourses have taken a predominant role in approaches to combating a number of conditions that affect Qataris. This paper is derived from an exploration of Qatari encounters with globalizing discourses of genetics, particularly as they relate to notions of risk. It explores Qataris negotiations of global interactions and influences, including the discourses around genetic risk and cousin marriage. It suggests that family marriage can be seen as one of the main platforms of resistance and a means for modern, cosmopolitan and tradition to be negotiated.


Short-term Outcomes of Ceramic Coated Metal-on-Metal Large Head in Total Hip Replacement Arthroplasty.
This study characterizes the short-term outcomes of ceramic coated metal-on-metal (MoM) large head total hip arthroplasty (THA) in prospectively selected patients aged 70 to 75 years. Eighteen patients (18 hips) between the ages of 70 and 75-years old with THA using ceramic-coated MoM large heads between June 2014 and December 2014 were evaluated. We prospectively selected patients younger than 70 years for bipolar hemiarthroplasty and older than 75 years for conventional THA. There were one case of osteoarthritis, 8 cases of femur neck fracture, and 9 cases of intertrochanteric fracture. All patients underwent clinical and radiological follow-up at 6 weeks, 6 and 12 months, and every year postoperatively. The mean duration of follow-up was 24.2 months (range, 18-34 months). The average Harris hip score at the final follow-up was 81.0, except one case which was ultimately converted to conventional THA due to acetabular cup loosening. Radiographically, mean acetabular cup inclination was 45.8°(range, 38-56°) and anteversion was 20.1° (range, 11-25°). The average femoral head size was 48.7 mm. All stems were neutral-positioned except 1 varus-positioned stem. There was 1 case of a soft tissue infection, 3 patients complained of persistent groin pain, and no dislocations occurred. Ceramic coated large MOM articulation (ACCIS) have many complications: cup loosening, groin pain, which can lead to fatal outcomes in the elderly patients. Especially in patients with communicated intertrochanter fracture (AO 31-A22, 23), careful attention should be paid to the choice of surgical option.


How Sickle Cell Disease Impairs Skeletal Muscle Function: Implications in Daily Life.
Sickle cell disease (SCD) is the most frequent life-threatening genetic hemoglobinopathy in the world and occurs due to the synthesis of abnormal hemoglobin S (HbS). hemoglobin S-containing red blood cells (RBC) are fragile, leading to hemolysis and anemia, and adhere to the endothelium, leading to hemorheological and hemodynamical disturbances. In its deoxygenated form, HbS may polymerize, leading to sickling of red blood cells and potentially to vasoocclusive crises. Recent findings observed that SCD patients demonstrate significant skeletal muscle remodeling and display reduced muscle functional capacities, contributing to exercise intolerance and poor quality of life. Although acute high-intensity exercise is not recommended for SCD patients because it may increase the risk of sickling, regular moderate-intensity physical activity could have beneficial effects on skeletal muscle and more generally on the well-being of SCD patients. This article reviews the literature regarding the impact of the disease on muscular tissue characteristics and function, as well as the corresponding implications for SCD patients' quality of life.


Development and validation of a questionnaire to evaluate medical students' and residents' responsibility in clinical settings.
There is a shortage of quantitative measures for assessing the concept of responsibility as a fundamental construct in medical education, ethics and professionalism in existing literature. This study aimed to develop an instrument for measuring responsibility in both undergraduate and graduate medical students during clinical training. Instrument content was based on literature review and mainly qualitative data obtained from a published grounded theory research. The draft questionnaire (Persian version) was then validated and revised with regard to face and content validity. The finalized 41-item questionnaire consists of four domains that were identified using factor analysis. Test-retest reliability and internal consistency were also assessed. Test-retest reliability was rather high, ranging between 0.70 and 0.75 for all domains. Cronbach's alpha coefficients were 0.75 - 0.76 for all domains and 0.90 for the composite scale of the whole questionnaire. Correlations between the four domains of the instrument were also satisfactory (r ≤ 0.47 for most domains). The correlation between each domain and the composite scale was higher than its correlation with other domains (r ≥ 0.79 for most domains). The instrument demonstrated good construct and internal validity, and can be suitable for measuring the concept of responsibility in practice in different groups of undergraduate and graduate medical trainees (MTs).


Sulfonylmethanesulfonamide inhibitors of carbonic anhydrase.
A series of sulfonylmethanesulfonamide derivatives is described, which are inhibitors of carbonic anhydrase (CA). The most potent of these is the racemic fluoro sulfone 9, which inhibits carbon dioxide hydration catalyzed by human CA II (CA-II) with an IC50 of 3 nM. Binding competition studies versus dansylamide indicate that the enantiomers of 9 have different affinities for CA-II, with equilibrium dissociation constants of 3.6 and 0.6 nM. QSAR analysis suggests that the key factors involved in achieving high affinity in this series are sulfonamide acidity, hydrophobicity, and minimization of steric demands at the carbon atom adjacent to the sulfonamide group.


A double-blind randomised controlled study of a brief intervention of bedtime restriction for adult patients with primary insomnia.
Bedtime restriction is effective for volunteer patients with primary insomnia. To determine the effectiveness of bedtime restriction in adult volunteers with primary insomnia. Patients were recruited in response to articles in local newspapers. The study hypothesis was not given in the articles. Patients were assessed as to whether or not they had primary insomnia. They completed a two-week sleep diary after which they met the investigators and were randomised to either bedtime restriction and basic sleep hygiene or the control group with basic sleep hygiene only. A total of 224 potential participants applied to be in the study. Of the 52 who had primary insomnia, 45 were randomly allocated to either control or intervention group and only two did not complete the study. Randomisation was concealed and participants were blinded regarding the treatment. The primary outcome was also measured in a blinded fashion. The outcome evaluated was patient description of 'better' or 'much better' quality of sleep versus the 'same', 'worse' or 'much worse' quality of sleep at six weeks. Overall, 73% (16/22) of those in the intervention group were either having better or much better quality of sleep after treatment, while in the control group this was 35% (8/23). The number needed to treat was 3 [95% CI 2-11] for bedtime restriction and sleep hygiene versus sleep hygiene alone. This is the first study using bedtime restriction designed to be feasible in primary care by using a brief intervention and a patient-oriented outcome.


Thymoma in multiple endocrine neoplasia type 1: a case report and systematic review.
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that predict poor prognosis in patients with MEN1. We aimed to summarize the clinical characteristics of thymoma in MEN1 by reviewing the current reports from the literature. A patient with multiple endocrine neoplasia type 1 (parathyroid hyperplasia, pituitary adenoma, and insulinoma) was found to have a 2 × 1.5 cm thymic mass during long-term follow-up. Thoracoscope surgery was performed, and a histopathology examination revealed WHO Type B3 thymoma. A pathogenic mutation of c.783 + 1G > A in the MEN1 gene was identified. We further searched PubMed and EMBASE for thymoma in association with MEN1. A comprehensive overview of the literature concerning characteristics of MEN1-related thymoma was summarized. Clinical characteristics and differences between thymoma and thymic carcinoid are highlighted. Besides carcinoid, other tumors, including thymoma, need to be identified for thymic space-occupying lesions in MEN1 patients. The impact of thymoma on the long-term prognosis of MEN1 patients needs further investigation.


Senior residents' opinions about oral surgery programs.
A questionnaire for senior oral surgery residents was distributed to elicit their opinions about various phases of their oral surgical training. Of 206 questionnaires sent to members of house staffs in approved programs, 122 responses (59%) were received. The average senior resident felt well prepared in exodontia, trauma, and orthognathic surgery. He considered himself much less prepared in pediatric oral surgery and tumor management. The average resident believed oral surgery was well regarded and would again choose his own program for training.


Diffraction Effects and Compensation in Passive Acoustic Mapping.
Over the last decade, a variety of noninvasive techniques have been developed to monitor therapeutic ultrasound procedures in support of safety or efficacy assessments. One class of methods employs diagnostic ultrasound arrays to sense acoustic emissions, thereby providing a means to passively detect, localize, and quantify the strength of nonlinear sources, including cavitation. Real array element diffraction patterns may differ substantially from those presumed in existing beamforming algorithms. However, diffraction compensation has received limited treatment in passive and active imaging, and measured diffraction data have yet to be used for array response correction. The objectives of this paper were to identify differences between ideal and real element diffraction patterns, and to quantify the impact of diffraction correction on cavitation mapping beamformer performance. These objectives were addressed by performing calibration measurements on a diagnostic linear array, using the results to calculate diffraction correction terms, and applying the corrections to cavitation emission data collected from soft tissue phantom experiments. Measured diffraction patterns were found to differ significantly from those of ideal element forms, particularly at higher frequencies and shorter distances from the array. Diffraction compensation of array data resulted in cavitation energy estimates elevated by as much as a factor of 5, accompanied by the elimination of a substantial bias between two established beamforming algorithms. These results illustrate the importance of using measured array responses to validate analytical field models and to minimize observation biases in imaging applications where quantitative analyses are critical for assessment of therapeutic safety and efficacy.


Effects of oophorectomy and estrogen treatment on basal levels and 24-h profiles of oxytocin.
The regulation of oxytocin is incompletely understood and data indicate that in addition to several neurotransmitters, estrogens may be involved. The aim of the present study was to investigate the effects of oophorectomy and hormonal replacement therapy (HRT) on basal levels and 24-h profiles of oxytocin. Basal levels of oxytocin were measured in 95 women who had undergone hysterectomy and who were divided into three groups: group A (n = 30), oophorectomized (BSO), not on HRT; group B (n = 32), BSO, receiving HRT; and group C (n = 33), ovaries preserved and not receiving HRT. The 24-h profiles of oxytocin were measured in nine women before and after hysterectomy. Continuous venous blood sampling was performed 1 week before surgery and 6-7 weeks after surgery for all nine women. Thereafter, three of the four oophorectomized women started replacement therapy with transdermal estradiol 50 micrograms/day. After 10 weeks of treatment, a third sampling was performed. Exogenous estrogen administration was associated with increased oxytocin levels and negative correlation between oxytocin and follicle stimulating hormone/luteinizing hormone levels was found. Removal of the ovaries did not reduce oxytocin levels in any of the investigated groups. When 24-h values were analyzed, no specific rhythmic or pulsatile pattern before or after hysterectomy, with or without simultaneous oophorectomy, was found.


Activated platelets but not endothelial cells participate in the initiation of the consolidation phase of blood coagulation.
To address the question of whether initiation of the consolidation phase of coagulation occurs on platelets or on endothelium, we have examined the interaction of coagulation factor XI with human umbilical vein endothelial cells (HUVEC) and with platelets. In microtiter wells factor XI binds to more sites in the absence of HUVEC (1.8 x 10(10) sites/well, K(D) = 2.6 nm) than in their presence (1.3 x 10(10) sites/well, K(D) = 12 nm) when high molecular weight kininogen (HK) and zinc are present. Binding was volume-dependent and abrogated by HUVEC or Chinese hamster ovary cells and was a function of nonspecific binding of HK to the artificial plastic surface. Factor XI did not bind to HUVEC or to HEK293 cell monolayers anchored to microcarrier beads. Activation of HUVEC resulted in von Willebrand's factor secretion, but factor XI binding was not observed. Only activated platelets supported factor XI binding in the presence of HK and zinc (K(D) = 8 nm, B(max) = 1319 sites/cell). Activation of factor XI was observed in plasma in the presence of platelets activated by the thrombin receptor activation peptide but not with activated HUVEC. These results support the concept that activated platelets, but not endothelial cells, expose a procoagulant surface for binding and activating factor XI, thereby initiating the consolidation phase of coagulation.


Sensitive nonradiometric method for determining thymidine kinase 1 activity.
Thymidine kinase 1 (TK1) is a cytoplasmic enzyme, produced only in the S-phase of proliferating cells, that has potential as a tumor marker. Specific determination of TK1 in serum is difficult, in part because of differences in the physical properties of serum TK1 compared with cytoplasmic TK1. The first step in the new assay was phosphorylation of 3'-azido-2',3'-deoxythymidine (AZT) to AZT 5'-monophosphate (AZTMP) by TK1 present in patient material. The AZTMP formed was measured in a competitive immunoassay with specific anti-AZTMP antibodies and AZTMP-labeled peroxidase. Results were compared with those of a TK radioenzyme assay (REA) for 78 samples from patients suffering from hematologic diseases. The detection limit was 78 microIU/L, and within-run CVs <20% were seen for samples with TK1 down to 130 microIU/L. Cross-determination of the mitochondrial isoenzyme TK2 activity was <0.1%. Between-assay imprecision (CV) was 3.5-7.4%, and the within-assay imprecision was 4.1-9.1%. In studies of recovery and linearity on dilution, measured values ranged from 84% to 115% of expected at concentrations of 0.26-10.4 mIU/L. Results of the new assay (mIU/L) = 0.109 x TK REA (U/L) + 0.092. Heterophilic antibodies did not interfere in the assay. The upper 95th percentile, in 100 healthy individuals, was 0.94 mIU/L, and the median value was 0.43 mIU/L. The TK1 enzyme-labeled immunoassay uses a stable substrate, is precise, appears to be accurate, and is resistant to interferences. It may provide a practical tool in the management of hematologic malignancies.


Hidden cavity formations by nanocrystalline self-assembly on various substrates with different hydrophobicities.
The effect of surface hydrophobicity is examined in the formation of hidden complex cavities during evaporation-induced nanocrystalline self-assembly taking place on three different substrates bearing different levels of hydrophobicity, namely, cover glass (CG), a gold thin film (Au), and a polystyrene dish (PS). It turns out that the DLVO theory, the relative thermal conductivities between the substrate and nanofluids, and the relationship between the evaporation and the radial outflow motions of nanoparticles comprehensively explain why the number of cavity cells is proportional to nanoparticle concentration and inversely proportional to surface hydrophobicity.


Injection laryngoplasty outcomes in vocal fold paralysis using calcium hydroxylapatite.
This study aims to evaluate our injection laryngoplasty experience in patients with unilateral vocal fold paralysis. Sixty-eight patients (32 males, 36 females; mean age 59.5 years; range 27 to 86 years) who were diagnosed with unilateral vocal fold paralysis at our clinic and who underwent injection laryngoplasty using calcium hydroxylapatite between January 2005 and June 2012 were included in this study. Mean follow-up period was 36 weeks (range 0-340.4 weeks). Data of 29 patients with post-injection Voice Handicap Index (VHI) scores were retrospectively analyzed. Of these patients, 16 (55%) were female, and the mean patient age was 60 (range 27 to 86 years). Seventeen patients underwent suspension laryngoscopy in the operating room, 12 patients underwent in-office percutaneous injection. Post-injection mean VHI score was 36.7 (range 4 to 87). Percutaneous injection laryngoplasty was performed to half of the 20 patients with pre- and post-injection VHI data. Mean VHI scores of these 20 patients improved by 27.9 points. Mean VHI score improved by 35.1 points in the percutaneous group, and by 20.7 points in the suspension group (p=0.29). Post-injection VHI score of one patient with lung cancer decreased, as his general health deteriorated. This study supports injection laryngoplasty in vocal fold paralysis. Calcium hydroxylapatite is a safe and effective treatment method in both percutaneous and operating room procedures.


Characteristics of Executive Functioning in a Small Sample of Children With Tourette Syndrome.
Tourette syndrome (TS) is a disorder that involves at least one vocal tic and two or more motor tics; however, associated symptoms of obsessive-compulsive disorder (OCD) and attention-deficit disorder or attention-deficit hyperactivity disorder (ADHD) are common. Many children with TS exhibit educational difficulties and one possible explanation may be deficits in executive functioning. The focus of this study was to look at the severity of symptoms often associated with TS (tics and OCD and ADHD symptoms) and its potential relationship with the Behavior Rating Inventory of Executive Function (BRIEF) Parent Form in 11 children diagnosed with TS aged 8 to 14 years old. The parent of the child completed the BRIEF along with symptom measures evaluating tics, OCD behaviors, and ADHD symptoms. Despite relatively low mean scores on the symptom measures and just a few children exhibiting clinically significant scores on the BRIEF indexes, at least half the children exhibited abnormal scores on the Working Memory, Inhibit, and Shift subscales of the BRIEF. Varying patterns of relationships were found on the BRIEF subscales for each symptom severity scale. Results suggest that the BRIEF may be useful in determining the specific areas of difficulty in a population with variable symptomatology.


Enhanced Sensitivity of Salmonella to Antimicrobial Blue Light Caused by Inactivating rfaC Gene Involved in Lipopolysaccharide Biosynthesis.
Salmonella is a global foodborne pathogen that causes human diseases ranging from mild gastroenteritis to severe systemic infections. Recently, antimicrobial blue light (aBL) showed effective bactericidal activity against a variety of bacteria (e.g., Salmonella) with varying efficiency. However, the antimicrobial mechanism of aBL has not been fully elucidated. Our previous report showed that the outer membrane (OM) is a key target of aBL. The major component of the OM, lipopolysaccharide (LPS), may play a role in aBL bactericidal effect. Therefore, the influence of LPS truncation on the sensitivity of Salmonella Typhimurium SL1344 to aBL was investigated for the first time. First, the rfaC gene in the SL1344 strain likely involved in linking lipid A to the core region of LPS was inactivated and the influence on LPS structure was verified in the mutant strain SL1344ΔrfaC. SL1344ΔrfaC showed a significant increase in sensitivity to aBL, and the bactericidal efficiency exceeded 8 log CFU at an aBL dose of 383 J/cm2, while that of its parental SL1344 strain approached 4 log CFU. To discover the possible mechanism of higher sensitivity, the permeability of OM was determined. Compared to SL1344, SL1344ΔrfaC showed 2.7-fold higher permeability of the OM at 20 J/cm2, this may explain the higher vulnerability of the OM to aBL. Furthermore, the fatty acid profile was analyzed to reveal the detailed changes in the OM and inner membrane of the mutant. Results showed that the membrane lipids of SL1344ΔrfaC were markedly different to SL1344, indicating that change in fatty acid profile might mediate the enhancement of OM permeability and the increased sensitivity to aBL in SL1344ΔrfaC. Hence, we concluded that disruption of rfaC in Salmonella Typhimurium led to the formation of truncated LPS and thus enhanced the permeability of the OM, which contributed to the increased sensitivity to aBL.


Hexaphenylbenzene-Stabilized Luminescent Silver Nanoclusters: A Potential Catalytic System for the Cycloaddition of Terminal Alkynes with Isocyanides.
A hexaphenylbenzene (HPB)-based derivative bearing thiol groups has been designed and synthesized that undergoes aggregation-induced emission enhancement in mixed aqueous media to form rodlike fluorescent aggregates. These rodlike aggregates behave as a "not quenched" probe for the detection of silver ions and further act as reactors and stabilizers for reducing-agent-free preparation of blue luminescent silver nanoclusters at room temperature. The utilization of fluorescent supramolecular aggregates for the preparation of Ag NCs in mixed aqueous media is unprecedented in the literature. Moreover, the wet chemical method that we are reporting in the present paper for the preparation of luminescent silver nanoclusters is better than the other methods reported in the literature. Further, these in situ generated Ag NCs showed exceptional catalytic activity in the preparation of pyrroles involving cocyclization of isocyanides and terminal alkynes. Interestingly, the catalytic efficiency of in situ generated Ag NCs was found to be better than the other catalytic systems reported in the literature.


L-Asparaginase as potent anti-leukemic agent and its significance of having reduced glutaminase side activity for better treatment of acute lymphoblastic leukaemia.
Acute lymphoblastic leukaemia (ALL) is one of the leading types of malignant disorder seen in children. Viral infections, genetic factors and exposure to chemical carcinogens are some of the factors responsible for causing ALL. Treatment strategies followed for curing ALL include chemotherapy or radiation therapy, wherein, chemotherapy involves the use of the enzymatic drug L-Asparaginase. The enzyme can be produced from various plants, animals, bacterial and fungal sources but, among them, bacterial sources are widely used for production of this enzyme. The enzyme is non-human in origin having certain bottle necks with L-Asparaginase therapy in the form of side effects such as pancreatitis, thrombosis which are mainly due to glutaminase side activity. Hence, present-day research is mainly focussed on minimizing or completely eliminating the glutaminase activity of the enzyme L-Asparaginase. This review is focussed on the complications associated with glutaminase side activity and use of glutaminase free enzymatic drug L-Asparaginase in treating ALL and the other developments related to the modification of the drug for quality treatment.


Microarchitectural analysis of decellularised unscarred and scarred dermis provides insight into the organisation and ultrastructure of the human skin with implications for future dermal substitute scaffold design.
The three-dimensional spatial arrangement of dermal tissue plays a crucial role in directing cellular behaviour during wound healing. It is vital to elucidate a better understanding of the three-dimensional dermal architecture of human skin. We sought to understand the configuration in morphological structure of decellularised human dermis between unscarred skin and normotrophic scars. Skin biopsies underwent decellularisation (DNA removal = 88%). Histological analysis showed no change in gross morphology of decellularised unscarred and scarred dermis. Multiphoton and atomic force microscopies showed that collagen fibres in unscarred decellularised dermis were interwoven akin to a mesh-like structure. Collagen fibres in decellularised unscarred dermis were less stiff (mean: 2.155 ± 0.9595 MPa; p < 0.0001) with a rougher (Rq = 16.5, Ra = 12.5, Rmax = 198; p < 0.0001) surface topography. Scarred dermis had a higher collagen volume density (papillary dermis, p < 0.0082; reticular dermis, p < 0.0332). The results demonstrate that scaffolds should exhibit a mesh-like structure with a biomimetic surface and low stiffness.


Imaging Nutrient Distribution in the Rhizosphere Using FTIR Imaging.
Symbiotic associations in the rhizosphere between plants and microorganisms lead to efficient changes in the distribution of nutrients that promote growth and development for each organism involved. Understanding these nutrient fluxes provides insight into the molecular dynamics involved in nutrient transport from one organism to the other. To study such a nutrient flow, a new application of Fourier transform infrared imaging (FTIRI) was developed that entailed growing Populus tremulodes seedlings on a thin, nutrient-enriched Phytagel matrix that allows pixel to pixel measurement of the distribution of nutrients, in particular, nitrate, in the rhizosphere. The FTIR spectra collected from ammonium nitrate in the matrix indicated the greatest changes in the spectra at 1340 cm-1 due to the asymmetric stretching vibrations of nitrate. For quantification of the nitrate concentration in the rhizosphere of experimental plants, a calibration curve was generated that gave the nitrate concentration at each pixel in the chemical image. These images of the poplar rhizosphere showed evidence for symbiotic sharing of nutrients between the plant and the fungi, Laccaria bicolor, where the nitrate concentration was five times higher near mycorrhizal roots than further out into the rhizosphere. This suggested that nitrates are acquired and transported from the media toward the plant root by the fungi. Similarly, the sucrose used in the growth media as a carbon source was depleted around the fungi, suggesting its uptake and consumption by the system. This study is the first of its kind to visualize and quantify the nutrient availability associated with mycorrhizal interactions, indicating that FTIRI has the ability to monitor nutrient changes with other microorganisms in the rhizosphere as a key step for understanding nutrient flow processes in more diverse biological systems.


Evaluation of Skin Prick Test Reading Time at 10 versus 15 min in Young Infants.
The optimal time point for reading the mean wheal diameter (MWD) of a skin prick test (SPT) in infants is not established. We aimed to assess if either of two reading time points of the SPT, 10 or 15 min, was superior to detect allergic sensitization (AS) in 6-month-old infants. In 1,431 6-month-old infants from the population-based Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) mother-child cohort, the SPT was performed with standard solutions for egg, cow's milk, peanut, wheat, soy, birch, timothy, dog, and cat. The MWD was measured after 10 and 15 min. AS was defined as a positive SPT with MWD ≥2 mm larger than the negative control. Overall, 149 (10.4%) infants were sensitized to at least one allergen at 10 and/or 15 min, while 138 (9.6%) had a positive SPT at 10 min and 141 (9.9%) at 15 min. A total of 12,873 allergen pricks were performed with 212 (1.6%) being positive at any time point, 194 (1.5%) positive at 10 min, and 196 (1.5%) positive at 15 min. The mean (95% CI) histamine MWD of 3.8 (3.8, 3.9) mm at 10 min was significantly larger than the 3.6 (3.6, 3.7) mm at 15 min. Reading the SPT after both 10 and 15 min increased the number of 6-month-old infants with documented AS compared to reading after one time point only. As neither 10 nor 15 min reading time was superior to the other in detecting AS, our results indicate that readings at both time points should be considered. However, the histamine MWD was significantly larger at 10 min compared to 15 min. Reappraisal of SPT reading in infancy may be warranted.


[Occupational health evaluation of electromagnetic fields in electric trains and subway technologic areas].
The article represents measurements and hygienic evaluation of electromagnetic fields in rolling stock and various technologic areas of subway. Results prove that specification of MALs for electric transport magnetic fields is essential for workers and general population. Before the MALs specification, the authors suggest that temporary allowable levels should be set according to national and foreign research.


Transitions between multiple attractors in a granular experiment.
We report on a granular experiment that produces multiple quasiperiodic pattern solutions in a rotating flat container filled with a bidisperse mixture of grains. The observed dynamics show a pronounced spatiotemporally periodic drift of segregated patterns. In the course of long experiment durations, the system switches between different states that appear to be stable oscillatory solutions over many periods. In the long-term limit, the system does not tend toward a stationary state. The results complement and extend previous observations in cylindrical geometries, and represent a challenge for modeling and theoretical description.


The use of antibodies to gap junction protein to explore the role of gap junctional communication during development.
Antibodies raised against the major 27 kDa protein electrophoretically eluted from isolated gap junctions and affinity purified against the antigen have been used to explore the role of communication through gap junctions in the early amphibian and mouse embryos. In both species, injection of the antibodies into one cell completely blocks both dye transfer and electrical coupling between cells connected by gap junctions. In the amphibian embryo the generation of a communication-incompetent clone of cells leads to patterning defects in the region derived from the antibody-injected cell. In the mouse embryo, blocking cell-to-cell communication leads to decompaction of the communication-incompetent cells. The possible significance of these findings in relation to development in general and to the organization of the first transporting epithelia to appear during development is discussed.


[Myocardial ischemic postconditioning: a brief ischemia causes conversion of resistent reperfusion-induced ventricular fibrillation into the normal rhythm].
Brief episodes of myocardial ischemia-reperfusion were shown to be protective against reperfusion injury when used during early reperfusion after a prolonged ischemic episode. This phenomenon has been termed myocardial ischemic postconditioning. In this study, an effect of ischemic postconditioning on persistent reperfusion-induced ventricular fibrillation was studied in the rat isolated heart. 2 minutes of global ischemia on the 15th minute of reperfusion after 30 minutes of regional ischemia effectively abolished the persistent ventricular fibrillation. In non-postconditioned hearts, the ventricular fibrillation continued to the end of reperfusion. The ischemic postconditioning seems to exert a strong antiarrhythmic effect protecting the heart against persistent reperfusion-induced ventricular tachyarrhythmias.


Marginalization and school nursing.
The concept of marginalization was first analyzed by nursing researchers Hall, Stevens, and Meleis. Although nursing literature frequently refers to this concept when addressing "at risk" groups such as the homeless, gays and lesbians, and those infected with HIV/AIDS, the concept can also be applied to nursing. Analysis of current school nursing literature and research suggests school nursing may be a marginalized specialty, encompassing many of the characteristics of marginalization including isolation, role confusion, and barriers to practice. School nurses can reduce or eliminate these characteristics by increasing their visibility and collaborative opportunities in the educational and nursing communities while also providing mentoring opportunities to new school nurses.


The characteristics and management of patients with recurrent blockage of long-term urinary catheters.
Encrustation and the subsequent blockage of indwelling urinary catheters is a common problem affecting up to 50% of long-term catheterized patients. For community patients, the resultant urinary bypassing or painful retention is particularly distressing since professional help is not immediately available. Catheter blockage also places increased demands on nursing time and resources. A prospective longitudinal study of 47 community patients with long-term catheters was conducted. Demographic, dietary and catheter-care data were collected, and biochemical and microbiological urinalysis conducted. Catheters were changed on three occasions, after 6-week intervals, and the extent of encrustation examined. The results indicated that patients can be classified as 'blockers' and 'non-blockers'. 'Blockers' produced two or more blocked catheters and were characterized by high urinary pH and ammonium concentration. 'Blocker status' was also significantly associated with female sex and with poor mobility, but not with fluid intake and urinary output. 'Blockers' were generally managed by 'crisis care' in response to leakage or retention, rather than by planned recatheterizations prior to catheter blockage. Recognition of individual patients as 'blockers' and the establishment of a 'pattern of catheter life' would be useful to planning individualized care.


Virtual anthropology.
Comparative morphology, dealing with the diversity of form and shape, and functional morphology, the study of the relationship between the structure and the function of an organism's parts, are both important subdisciplines in biological research. Virtual anthropology (VA) contributes to comparative morphology by taking advantage of technological innovations, and it also offers new opportunities for functional analyses. It exploits digital technologies and pools experts from different domains such as anthropology, primatology, medicine, paleontology, mathematics, statistics, computer science, and engineering. VA as a technical term was coined in the late 1990s from the perspective of anthropologists with the intent of being mostly applied to biological questions concerning recent and fossil hominoids. More generally, however, there are advanced methods to study shape and size or to manipulate data digitally suitable for application to all kinds of primates, mammals, other vertebrates, and invertebrates or to issues regarding plants, tools, or other objects. In this sense, we could also call the field "virtual morphology." The approach yields permanently available virtual copies of specimens and data that comprehensively quantify geometry, including previously neglected anatomical regions. It applies advanced statistical methods, supports the reconstruction of specimens based on reproducible manipulations, and promotes the acquisition of larger samples by data sharing via electronic archives. Finally, it can help identify new, hidden traits, which is particularly important in paleoanthropology, where the scarcity of material demands extracting information from fragmentary remains. This contribution presents a current view of the six main work steps of VA: digitize, expose, compare, reconstruct, materialize, and share. The VA machinery has also been successfully used in biomechanical studies which simulate the stress and strains appearing in structures. Although methodological issues remain to be solved before results from the two domains can be fully integrated, the various overlaps and cross-fertilizations suggest the widespread appearance of a "virtual functional morphology" in the near future.


Study of the interfacial viscoelasticity of human serum albumin microcapsules using a viscoelasto-electrohydrodynamic technique.
Crosslinked proteins are widely used as the encapsulating membranes in microcapsules for many biomedical and food industries. The interfacial rheological properties of these capsules are due to the complex microstructure of cross-linked globular proteins owing to structural changes at quaternary, tertiary and secondary levels. These changes in structure can be induced by high protein concentration, hydrophobic-hydrophillic interfaces, and pH. In this work, the interfacial viscoelastic rheological properties of human serum albumin (HSA) microcapsules are estimated using a novel electrodeformation technique exhibiting creep and oscillatory responses. Insights into the microstructure-rheology relationship are obtained using FTIR and SEM studies. The results show a complex dependence of the interfacial properties on the size, concentration and pH of the capsules. An interplay of inter-molecular interactions, adsorption and multilayer formation, accessibility to reactive functional groups, and dependence on the relative content of alpha helix, beta sheet and beta turn is observed. The interfacial rheological properties are estimated using the Burger model and creep is found to sensitively affect the rheological properties due to irreversible changes in microstructure. Furthermore, the electrodeformation technique allows analysis of interfacial rheology at high frequencies, 10 Hz to 1 kHz, which is otherwise not easily possible with conventional rheometers.


Adriamycin in combination with dexamethasone and octreotide lacks activity on the treatment of a 4T1 metastatic breast cancer model.
The aim of this study was to evaluate whether the palliative treatment for metastatic disease with dexamethasone (DEX) plus octreotide (OCT) can improve the anticancer effects of the standard treatment with adriamycin (ADR) on a 4T1 metastatic breast cancer (MBC) model. 4T1 cells were first characterized for the expression of the somatostatin receptors 1-5 and were then inoculated onto the femur of BALB/C mice. Investigation protocols used 4T1 cell proliferation and invasion assays, analysis of radiographic images of the bone metastatic lesions, and overall survival of the diseased animals. The triple combination treatment regime (ADR+OCT+DEX) was ineffective for growth inhibition and showed an antagonistic effect on ADR activity in the 4T1 cell line in both proliferation and invasion assays. ADR treatment following the administration of the DEX+OCT regimen decreased the anticancer activity of ADR both on the grading of the bone metastatic lesions and on the overall survival of diseased animals. Moreover, the palliation treatment with OCT+DEX and in combination with ADR rather caused disease progression of the metastatic disease and bone lesions in a 4T1 MBC model in vivo. These results suggest that the administration of the DEX+OCT regimen, although may preserve palliative effects, neutralizes or reverses the anticancer effects of ADR on a 4T1 MBC model in vitro and in vivo. The simultaneous use of these drugs should be considered carefully in clinical practice.


Diagnostic accuracy of noninvasive fractional flow reserve derived from computed tomography angiography in ischemia-specific coronary artery stenosis and indeterminate lesions: results from a multicenter study in China.
To determine the diagnostic performance of a novel computational fluid dynamics (CFD)-based algorithm for in situ CT-FFR in patients with ischemia-induced coronary artery stenosis. Additionally, we investigated whether the diagnostic accuracy of CT-FFR differs significantly across the spectrum of disease and analyzed the influencing factors that contribute to misdiagnosis. Coronary computed tomography angiography (CCTA), invasive coronary angiography (ICA), and FFR were performed on 324 vessels from 301 patients from six clinical medical centers. Local investigators used CCTA and ICA to conduct assessments of stenosis, and CT-FFR calculations were performed in the core laboratory. For CCTA and ICA, CT-FFR ≤ 0.8 and a stenosis diameter ≥ 50% were identified as lesion-specific ischemia. Univariate logistic regression models were used to assess the effect of features on discordant lesions (false negative and false positive) in different CT-FFR categories. The diagnostic performance of CT-FFR was analyzed using an invasive FFR ≤ 0.8 as the gold standard. The Youden index indicated an optimal threshold of 0.80 for CT-FFR to identify functionally ischemic lesions. On a per-patient basis, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for CT-FFR were 96% (91%-98%), 92% (87%-96%), 94% (90%-96%), 91% (85%-95%), and 96% (92%-99%), respectively. The diagnostic efficacy of CT-FFR was higher than that of CCTA without the influence of calcification. Closer to the cut point, there was less certainty, with the agreement between the invasive FFR and the CT-FFR being at its lowest in the CT-FFR range of 0.7-0.8. In all lesions, luminal stenosis ≥ 50% significantly affected the risk of reduced false negatives (FN) and false positives (FP) results by CT-FFR, irrespective of the association with calcified plaque. In summary, CT-FFR based on the new parameter-optimized CFD model has a better diagnostic performance than CTA for lesion-specific ischemia. The presence of calcified plaque has no significant effect on the diagnostic performance of CT-FFR and is independent of the degree of calcification. Given the range of applicability of our software, its use at a CT-FFR of 0.7-0.8 requires caution and must be considered in the context of multiple factors.


Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation of uterine cells.
Here we report a novel potential therapeutic strategy using histone deacetylase (HDAC) inhibitors to enhance the action of hormonal therapy agents in estrogen receptor alpha (ER alpha)-positive breast cancer. HDAC inhibitors [trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA)], inhibited proliferation of MCF-7 breast cancer cells and, in combination with tamoxifen inhibited proliferation better than with either agent alone. VPA, an anti-convulsant drug with HDAC inhibitory activity, enhanced tamoxifen action at doses within the concentration range used for anti-convulsive therapy. VPA cooperated with tamoxifen in a variety of ER alpha-positive cell lines and was also effective when combined with other antiestrogens, and with aromatase inhibition. VPA enhanced antiestrogen action by promoting cell death via apoptosis without affecting cell cycling. Some of this action may be due to VPA's ability to induce the pro-apoptotic gene Bik, which is also induced by antiestrogens. Remarkably, VPA blocked the undesirable pro-proliferative action of tamoxifen on uterine endometrial cells. Our in vitro results suggest that VPA and other HDAC inhibitors have the potential to enhance hormonal therapy for ER alpha-positive breast cancer and simultaneously reverse the adverse effects of antiestrogens in the uterus.


Medications which can kill a toddler with one tablet or teaspoonful.
To identify medicinal preparations which can be fatal to a toddler upon ingestion of one standard dose unit, four major texts in medical toxicology were reviewed for reported cases of fatal poisoning in small children as well as for fatal doses in adults when no fatalities were reported in children. Using the Physicians Desk Reference, the largest dose unit commercially available for various drugs was identified. Subsequently, the number of dose units that have to be ingested by a toddler to cause fatality was calculated. To compare these data to the clinical reality, the annual reports by the American Association of Poison Control Centers National Collection System were reviewed between 1983-1989. Very few drugs are fatal for a 10 kg toddler upon ingestion of one commercially available dose unit. These include camphor, chloroquine, tricyclics, phenothiazines, quinine, methyl salicylate and theophylline. This short list of drugs was responsible for almost half (42%) of fatal cases following acute ingestion in young children (< 2 yrs) in the US between 1983-1989. Labelling of these drugs in a unique way may help decrease the number of serious and potentially fatal toxicities in small children.


Evaluation and monitoring of iodine deficiency disorders in school children in north-east Thailand.
The possibility of improving iodine deficiency disorder (IDD) in school children in Khon Kaen province was investigated during the period of 1 year, using an operational research approach. Four schools in Pupaman and Srichompu districts, namely Ban Khoa Wong, Na Fai Witaya, Ban Pa Num Tieng and Ban Non Khom, were selected for this study. Ban Non Khom served as the control school. Different methods were used for iodine fortification. Iodized salt was used for the children of the Ban Khoa Wong school, iodized water was used for Na Fai Witaya school and iodized fish sauce was used for Ban Pa Num Tieng school. The iodized salt, water and fish sauce were provided with the help of the school teachers under the supervision and advice of the team of investigators. Urine iodine excretion as well as palpation of the thyroid gland and the thyroid hormones T4, T3 and TSH were selected for monitoring and evaluation. The proportion of children with low urine iodine excretion, indicated by a cut-off point suggested by the WHO/ICCIDD/UNICEF working group, decreased during the course of the project in all schools receiving iodine supplementation as well as in the control school. However, the decrease was less in the control school in comparison with the implementation schools. Furthermore, the goitre rate decreased in all schools under investigation. The decrease of the goitre rate for the children of the control school might have been due to the activities of a village health volunteer from a nearby village who was using iodized salt for IDD control according to the ongoing national programme initiated by the Ministry of Public Health. No significant difference in the level of thyroid hormones was detected before or at the end of the supplementation for either the experimental schools or the control school. The results from the determination of thyroid hormone serum levels could not be used for assessing the outcome of the project. The measuring of urinary iodine excretion might be helpful in monitoring the iodine intake during the intervention phase. Long-term effects of iodine fortification could be seen best by the declining proportion of children with goitre. However, an observation of 1 year might not have been enough to clearly see the outcome of the project. The other possible contributing error to this study is intra-observer variation of the palpation technique when the sample size was not big enough. Goitrogens in this area might be another risk factor for the high prevalence rate of goitre. Further study in this field should be encouraged. The results of the study indicate that iodine fortification of salt and fish sauce is more effective than iodine fortification of drinking water. Due to the local preference of adding fish sauce (nam pla) instead of salt to almost all dishes, fish sauce proved to be the best vehicle for iodine fortification. The success of the project depended heavily on the understanding and cooperation of the school teachers and the school children. Major constraints in conducting this project were the insufficient distribution of iodized salt and potassium iodide solution for the fortification of drinking water, and the inconsistency of iodide concentration in the salt after fortification.


Recent advances in modeling and analysis of bioelectric and biomagnetic sources.
Determining the centers of electrical activity in the human body and the connectivity between different centers of activity in the brain is an active area of research. To understand brain function and the nature of cardiovascular diseases requires sophisticated methods applicable to non-invasively measured bioelectric and biomagnetic data. As it is difficult to solve for all unknown parameters at once, several strains of data analysis have been developed, each trying to solve a different part of the problem and each requiring a different set of assumptions. Current trends and results from major topics of electro- and magnetoencephalographic data analysis are presented here together with the aim of stimulating research into the unification of the different approaches. The following topics are discussed: source reconstruction using detailed finite element modeling to locate sources deep in the brain; connectivity analysis for the quantification of strength and direction of information flow between activity centers, preferably incorporating an inverse solution; the conflict between the statistical independence assumption of sources and a possible connectivity; the verification and validation of results derived from non-invasively measured data through animal studies and phantom measurements. This list already indicates the benefits of a unified view.


Low-n-6 and low-n-6 plus high-n-3 diets for use in clinical research.
Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; #2·5% of energy (en%)) and arachidonic acid (#60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA a-linolenic acid (ALA; $1·5 en%) and EPA þ DHA ($1000 mg/d). Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to #2·5 en% (median LA 2·45 (2·1, 3·1); P,0·001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1·6 en%, (1·3, 2·0), P,0·001) and EPA þ DHA (1482 mg, (374, 2558), P,0·001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to #2·5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.


Identification of natural recombinants derived from PCV2a and PCV2b.
Porcine circovirus type 2 (PCV2) is considered to be the main pathogen in PC-associated diseases, and significantly affects the global pig-producing industry. PCV2 continuously evolves by point mutations and genome recombinations. In the present study, we aimed to further identify recombinant PCV2 strains. We used polymerase chain reaction to detect PCV2 in the carcasses of pigs with suspected infections from different regions of Guangdong Province in China. DNA was extracted from samples with confirmed infection and full- genome amplification, sequencing, phylogenetic tree construction, gene recombination detection, and sequence alignment were performed in gene recombination analysis. Our results show that recombination occurred between the strains SHC (DQ104421) and ZhuJi2003 (AY579893). The recombination resulted in three recombinants: GD003 (KM503044), GD005 (KM487708), and GD008 (KM487709). Further analyses revealed that these novel recombinants appeared to result from recombination between the PCV2a and PCV2b strains, with crossover regions located in ORF2. This study was a comprehensive analysis that used several different methods, which demonstrated that a cluster of PCV2 strains resulted from the same type of inter-genotypic recombination pattern, with a breakpoint in the structural protein coding region. The results of our study provide both information on the recombination mechanism and disease pathogenesis and useful data for the prevention of PCV2 in the swine industry.


The effects of dopamine D-1 and D-2 receptor subtype agonists on nigrostriatal opioid dynorphin and enkephalin immunostaining in 6-hydroxydopamine lesioned rats.
Using selective neurotoxin lesioning and immunocytochemical techniques, the effects of dopamine receptor subtypes stimulation by selective subtype agonists in the modulation of striatal opioid dynorphin and enkephalin were characterized in the rat basal ganglia. Tissue staining with specific antibodies against either dynorphin A (1-17) or [Met5]-enkephalin was examined in the striatum and substantia nigra following unilateral nigrostriatal dopaminergic lesioning by the neurotoxin 6-hydroxydopamine (6-OHDA). Two weeks later three groups of five 6-OHDA lesioned rats were repeatedly treated with either the dopamine D-1 receptor agonist SKF-38393 (5 mg.kg, i.p.), D-2 receptor agonist LY-171555 (1 mg/kg, i.p.) or saline for 7 days and similar immunostaining procedures were employed. The results indicated that 6-OHDA lesioning alone led to reduction in dynorphin A (1-17) immunostaining in substantia nigra and striatum when compared to the sham-lesioned contralateral side. However, SKF-38393 treatment reversed that pattern and caused more intense dynorphin A (1-17) immunostaining than the lesion side, while LY-171555 had no effect. In contrast, enkephalin immunostaining was increased by 6-OHDA lesioning, and the effect was abolished by SKF-38393 but not LY-171555. These results are in agreement with previously reported radioimmunoassay findings and are compatible with the proposal that dopamine D-1 receptors mediate the excitatory effect on the dynorphinergic system while inhibiting the enkephalinergic system.