The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities.
Subclinical hyperthyroidism has been associated with harmful cardiac effects, but its treatment remains controversial. This study was designed to assess the cardiac effects of the normalization of serum TSH concentration in patients with endogenous subclinical hyperthyroidism. Ten patients (median age, 59 yr; range, 16-72 yr) with normal serum free T(4) and free T(3) concentration and a stable suppression of serum TSH levels were evaluated by Doppler-echocardiography, by standard and 24-h electrocardiography monitoring (Holter), and by the clinical Wayne index. Ten subjects, matched for age and sex, were used as controls. Patients were reevaluated 6 months after achieving stabilized euthyroidism by using methimazole with a median initial dose of 20 mg daily (10-30 mg daily). After reaching euthyroidism, we found a significant decrease in the heart rate (P = 0.008), the total number of beats during 24 h (P = 0.004), and the number of atrial (P = 0.002) and ventricular (P = 0.003) premature beats. Echocardiographical data resulted in a reduction of the left ventricular mass index (P = 0.009), interventricular septum thickness (P = 0.008), and left ventricular posterior wall thickness (P = 0.004) at diastole. Furthermore, the early diastolic peak flow velocity deceleration rate was significantly higher (P = 0.02) in the untreated patients compared with controls. The Wayne clinical index was higher in patients than in controls (P = 0.001) and decreased after treatment (P = 0.004). Serum TSH concentration returned to normal values after 2.5 months (range, 1.0-7.0 months) on methimazole therapy (0.05 vs. 1.42 mU/liter; P = 0.002). Serum free T(4) values were normal in patients before treatment but significantly decreased after reaching the euthyroidism (16.9 vs. 11.5 pmol/liter; P = 0.002). In contrast, serum free T(3) concentration did not differ among the groups. In conclusion, our findings support that early antithyroid therapy should be considered in patients with endogenous subclinical hyperthyroidism, where it is needed to prevent potential progression to a more advanced heart disease.


Structural and functional studies on the human C3b/C4b receptor (CR1) purified by affinity chromatography using a monoclonal antibody.
A procedure was devised that has several advantages over previously described methods to purify CR1 from both erythrocytes (E) and the HL-60 promyelocytic cell line. Using a monoclonal antibody immunoaffinity column, CR1 was purified to homogeneity as assessed by silver staining and 2-D gel analysis. Protein purified by this method comigrates on SDS-PAGE with 125I surface-labeled CR1 isolated by immunoprecipitation or iC3-Sepharose affinity chromatograhy and can be specifically immunoblotted with a second monoclonal anti-CR1 antibody. Employing this method, CR1 can be purified to homogeneity in amounts adequate for both functional studies and biochemical microanalysis. Purified E CR1 is functionally active as assessed by its ability to specifically rebind to an iC3-Sepharose affinity column, act as a cofactor for I-mediated cleavage of C3b to C3c and C3d, g and to accelerate decay of both the classical and alternative pathway C3 convertases. Its specific activity is similar to that of CR1 purified by a method not employing the potentially denaturing washing and eluting conditions of immunoaffinity chromatography. The pIs of the two major E CR1 allotypes are both approximately 7.1. Using pooled human E CR1, an amino acid composition was derived which revealed a relatively high proline content. This has also been found in two functionally related and genetically linked complement-regulatory proteins, H and C4-binding protein, NH2-terminal sequencing of E CR1 and HL-60 CR1 was unsuccessful indicating that the NH2-terminus is blocked.


Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels.
Transcobalamin (TC) I deficiency, like the function of TC I itself, is incompletely understood. It produces low serum cobalamin levels indistinguishable from those of true cobalamin deficiency. Diagnosis is especially elusive when TC I deficiency is mild. To provide new, more substantive definition, the TCN1 gene was examined in two well-characterised families that included members with both severe and mild TC I deficiencies. A severely deficient proposita with undetectable TC I levels displayed compound heterozygosity for two mutations, each causing a premature stop codon. Relatives in both families who had mildly low or low-normal plasma levels of TC I and cobalamin were heterozygous for one or the other of these mutations. An unrelated patient with mild TC I deficiency and unknown familial TC I and cobalamin status was then tested and found to be similarly heterozygous for one of the mutations. The two nonprivate mutations identify a genetic basis for TC I deficiency for the first time. They also add new approaches to studying mild and severe TC I deficiency and to reducing confusion of its low cobalamin levels with those of cobalamin deficiency and its often dramatically different prognosis and management.


Detection and enrichment of disseminated renal carcinoma cells from peripheral blood by immunomagnetic cell separation.
We have established an immunomagnetic separation procedure for the detection of circulating tumor cells in the peripheral blood based on the magnetic cell sorting (MACS) technique. In previous in vitro experiments, renal-cell carcinoma (RCC) cells were mixed with peripheral blood. In dilutions of 1:200 to 1:107 tumor cells per mononuclear blood cells, an average recovery rate of 84% of tumor cells was determined. In our study, 104 peripheral blood samples from 59 renal carcinoma patients were analyzed. MACS resulted in significant depletion of leukocytes, permitting a search for tumor cells on just 1 slide. Analyzing 8 ml of peripheral blood per patient, 19/59 RCC patients carried disseminated tumor cells (32%) in the range of 1 to 38 cells (median 8). Interestingly, for the cytokeratin-positive (CK+) patient group, we found a correlation between tumor cell number and grading (G2 vs. G3) and an increased number of CK+ patients with advanced tumor stage. MACS appears to be an efficient technique to detect disseminated tumor cells in peripheral blood.


[Fractionated irradiation of Ehrlich carcinoma using fast neutrons].
Ehrlich's carcinoma growth inhibition was studied under the conditions of fractionated irradiation with fast neutrons and x-rays. Fast neutrons were obtained from a reaction of 13.6 MeV alpha----Be on the Y-120 cyclotron. Neutron beam irradiation doses were within 2-17 Gy, x-ray doses from 7.5 to 72 Gy. Tumors were subjected to local irradiation with 1-8 fractions at a 3-4 day interval. The results showed that an increase in the total duration of a course of irradiation and a decrease in a dose per fraction resulted in a reduced effect of carcinoma growth inhibition. At the same time, an increase in the fast neutron RBE under these conditions from 3.4 (in single irradiation) to 5.4 (in 8-fold irradiation) indicated more pronounced inhibition of reparation and/or repopulation in a tumor in neutron beam irradiation.


Medicolegal diagnosis of asphyxia--cerebral blood flow and brain oxygen tension.
Over the last several years, using rabbit models the authors analyzed cerebral blood flow (CBF), the brain oxygen tension (PtO2) and other physiological parameters during asphyxiation as means of achieving a practical diagnosis of asphyxiation. The author reports here on the effects of compression of the carotid arteries and obstruction of the airway leading to hypoxia, based on an analysis of CBF and PtO2 during hanging. Immediately after hanging, the CBF dropped but then rose suddenly. After several minutes, it dropped along with blood pressure. The PtO2 continued to decrease until the time of irreversible apnea. These findings suggest the effects of compression of the carotid arteries and the airway occlusion. After death, these results were confirmed with the injection-molded resin specimens of the airway and by the angiograph. But the closure of the vertebral arteries was not produced by the hanging.


A comparison of etidocaine and lidocaine for retrobulbar anesthesia.
In this double-blind study of retrobulbar block for cataract surgery, 62 patients scheduled for cataract surgery were randomly assigned to treatment with either (1) lidocaine 2% with epinephrine 1:200,000 (21 patients); (2) etidocaine 1% plain (20 patients); or (3) etidocaine 1% with epinephrine 1:200,000 (21 patients). The time of onset of sensory and motor block after administration of the three drugs was the same. The duration of motor nerve block produced by etidocaine plain and by etidocaine with epinephrine was considerably longer than that produced by lidocaine with epinephrine, and fewer patients reported postoperative pain after either etidocaine plain or etidocaine with epinephrine than after lidocaine with epinephrine.


Spectroscopic behavior of copper complexes of nonsteroidal anti-inflammatory drugs.
The proposed curative properties of Cu-based nonsteroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous Cu(II) complexes of NSAIDs with enhanced anti-inflammatory activity. Crystalline complexes, Cu(II)-NSAID (ibuprofen, naproxen, tolmetin, and diclofenac), with a carboxylic function have been studied by means of infrared and Raman spectroscopy. All NSAIDs bind the metal through the carboxylate group. On the basis of the comparison between the wavenumber of the COO(-) group vibrations and Delta nu (nu(asimm)COO(-) - nu(simm)COO(-)) between Na salts and Cu(II) complexes, conclusions on the probable structure of the complexes have been drawn. The spectroscopic data support the formation of dimeric [Cu(2)L(4)(H(2)O)(2)] complexes in which the COO(-) group behaves as a bridging bidentate ligand. The low wavenumber region of the Raman spectrum provided information on Cu-O and Cu-Cu bonds in the complexes. Thermogravimetric results gave further support to the vibrational data.


UKT-04 trial of continuous metronomic low-dose chemotherapy with methotrexate and cyclophosphamide for recurrent glioblastoma.
Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Continuous oral low-dose chemotherapy with methotrexate (MTX) and cyclophosphamide (CPM) has modest activity in heavily pretreated patients with breast cancer. We explored the efficacy of 100 mg CPM daily and 5 mg MTX twice weekly in relapsed glioblastoma. Ten patients, 22-59 years old, with a Karnofsky score of 50% or higher who had failed at least two chemotherapies were accrued. No toxicity was observed. No patient showed a complete or partial response. Five of 10 patients progressed within 2 months of therapy. Another five patients progressed after 3-4.5 months. The median time to progression was 2.5 months. The median overall survival after start of MTX/CPM was 6.9 months (range 0.5-18.8 months). Since the progression-free survival rate at 6 months was 0%, the trial was prematurely closed.


Correlations of serum lipids and lipoproteins with gamma-glutamyltransferase and attitude to alcohol consumption.
The correlation of three markers of alcohol consumption: serum concentration of gamma-glutamyltransferase (GT), high density lipoprotein cholesterol (HDL-cholesterol), apolipoprotein AI (Apo AI), and the results of a questionnaire (Mm-MAST) designed to measure the attitude towards alcohol consumption were determined in a population of healthy men aged 48 years. Apo AI (r = 0.27) and GT (r = 0.31) were correlated (P less than 0.001) to the questionnaire score to a similar degree while the correlation between HDL-cholesterol and the questionnaire score was (r = 0.18), somewhat less good but statistically significant (P less than 0.01). There was no correlation between GT and HDL-cholesterol or Apo AI.


Timing precision in continuation and synchronization tapping.
Wing and Kristofferson (1973) have shown that temporal precision in self-paced tapping is limited by variability in a central timekeeper and by variability arising in the peripheral motor system. Here we test an extension of the Wing-Kristofferson model to synchronization with periodic external events that was proposed by Vorberg and Wing (1994). In addition to the timekeeper and motor components, a linear phase correction mechanism is assumed which is triggered by the last or the last two synchronization errors. The model is tested in an experiment that contrasts synchronized and self-paced trapping, with response periods ranging from 200-640 ms. The variances of timekeeper and motor delays and the error correction parameters were estimated from the auto-covariance functions of the inter-response intervals in continuation and the asynchronies in synchronization. Plausible estimates for all parameters were obtained when equal motor variance was assumed for synchronization and continuation. Timekeeper variance increased with metronome period, but more steeply during continuation than during synchronization, suggesting that internal timekeeping processes are stabilized by periodic external signals. First-order error correction became more important as the metronome period increased, whereas the contribution of second-order error correction decreased. It is concluded that the extended two-level model accounts well for both synchronization and continuation performance.


Histamine mediates myocardial damage by an H1 mechanism independent of coronary blood flow.
Administration of histamine to rabbits may result in myocardial damage similar to that produced by catecholamines and the anthracycline antibiotics. To explore the mechanisms involved in histamine-mediated myocardial damage, conscious New Zealand white rabbits were pretreated with H1 and H2 receptor blocking agents, alone and in combination, and then administered histamine. Coronary artery blood flow was measured with radiolabeled microspheres in rabbits that received histamine alone, and in those that received an H1 blocking agent and histamine. Rabbits that received an H1 blocking agent had a significant reduction in morphological injury which was scored as follows: grade 1, minimal or no injury; grade 2, moderate; and grade 3, severe injury (mean pathology score = 1.1 +/- 0.28 for histamine alone vs. 0.06 +/- 0.06 with H1 receptor blockade, p less than 0.05). Animals pretreated with H2 receptor blockade (mean pathology score = 1.2 +/- 0.49) were not protected against morphological injury. Coronary blood flow decreased in animals that received histamine alone: control = 2.61 +/- 0.38 vs. 1.80 +/- 0.30 ml/min/g (p less than 0.05), and in animals pretreated with H1 blockade; control = 3.29 +/- 0.34 vs. 1.91 +/- 0.28 ml/min/g (p less than 0.01). We conclude that histamine-mediated myocardial damage appears to be mediated by the H1 receptor system and that this appears to be independent of initial changes in global coronary blood flow.


p,p'-DDT: effect on calcium metabolism and concentration of estradiol in the blood.
Ringdoves given 10 parts per million p,p'-DDT showed a decrease of estradiol in the blood early in the breeding cycle and egg-laying was delayed. There was also a decrease in deposition of medullary calcium and in eggshell weight. Injection of p,p'-DDE (150 milligrams per kilogram of body weight) caused reduction of eggshell weight and inhibition of carbonic anhydrase in the oviduct.


Changes in phenytoin concentrations in blood and cerebrospinal fluid caused by direct hemoperfusion in a patient intoxicated with phenytoin.
We performed direct hemoperfusion (DHP) 5 times on a patient with consciousness disorder and phenytoin intoxication. We then measured the phenytoin concentrations in her cerebrospinal fluid (CSF) and blood at various times. After the first DHP session, consciousness began to improve, and it normalized after the fourth DHP session when the blood concentration of phenytoin had decreased from 54.0 microg/ml to 16.5 microg/ml. The average plasma phenytoin elimination rate of DHP was 18.0% over 120-180 min. The concentration of phenytoin in the CSF decreased as that in the blood was lowered by DHP. The average reduction rate of phenytoin in the CSF after a DHP session was 23.7%, which was similar to the rate of elimination from the blood. The CSF/blood phenytoin ratio was 0.17, and no marked changes were detected before or after a DHP session.


Overview of the role of Shiga toxins in porcine edema disease pathogenesis.
Shiga toxin-producing Escherichia coli (STEC) have been implicated as the cause of enterotoxemias, such as hemolytic uremic syndrome in humans and edema disease (ED) of pigs. Stx1 and Stx2 are the most common types found in association with illness, but only Stx2e is associated with disease in the animal host. Porcine edema disease is a serious affection which can lead to dead causing great losses of weaned piglets. Stx2e is the most frequent Stx variant found in porcine feces and is considered the key virulence factor involved in the pathogenesis of porcine edema disease. Stx2e binds with higher affinity to Gb4 receptor than to Gb3 which could be due to amino acid changes in B subunit. Moreover, this subtype also binds to Forssman glycosphingolipids conferring upon Stx2e a unique promiscuous recognition feature. Manifestations of edema disease are caused by systemic effects of Stx2e with no significant morphologic changes in enterocytes. Endothelial cell necrosis in the brain is an early event in the pathogenesis of ED caused by Stx2e-producing STEC strains. Further studies are needed to generate techniques and tools which allow to understand the circulation and ecology of STEC strains in pigs even in resistant animals for diagnostic and epidemiological purposes.


Glycopeptides by Linch-Pin C-H Activations for Peptide-Carbohydrate Conjugation by Manganese(I)-Catalysis.
Late-stage C-H glycosylations of structurally complex amino acids and peptides were accomplished by means of racemization-free manganese(I)-catalyzed C-H activation. Thus, glycosylative modifications proved to be viable by a linch-pin approach, featuring chemo- and site-selective C-H transformations. The peptide-saccharide conjugation provided modular access to structurally complex glycopeptides, likewise enabling the assembly of fluorescent-labelled glycopeptides.


Replacement of dynamic cultured biograft improves damaged heart function-comparative study of static cultured biografts-.
To determine whether a dynamic cultured biograft can positively affect the function of the damaged heart. We ligated the coronary artery (LAD) of rats to generate a model of myocardial infarction (MI) and then implanted them with the following grafts comprising vascular smooth muscle cells (VSMCs) derived from the rat aorta and seeded onto biodegradable patches (patch replacement therapy; (PRTx)): control without PRTx, PRTx without seeded cells, PRTx with static cultured VSMCs, PRTx with dynamic cultured VSMCs and sham-operated. Cultured VSMCs were labeled with PKH26 for identification after implantation, and the centre of the MI site was excised and replaced with an implanted biograft. Cardiac performance was monitored for 12 weeks thereafter and followed by a histological study. Although the ejection fraction of the damaged heart improved in all groups that were transplanted with grafts, remodeling was prevented only in groups with a dynamic or static cultured patch. More cells were α-SMA-positive in the group with the dynamic, rather than the static cultured patch. Cells were positive for PKH26 in the biograft and in the infarcted myocardium. Dynamic cultured biografts improved the function of the infarcted myocardium more than statically cultured biografts or those without cells.


Recidivism after treatment in a forensic youth-psychiatric setting: the effect of treatment characteristics.
The aim of this study was to examine the effect of treatment characteristics on recidivism in a forensic youth-psychiatric outpatient clinic. The treatment offered comprised functional family therapy (FFT), individual cognitive behavioural therapy (CBT), or CBT in combination with parent training. Some of the youth additionally participated in aggression replacement training (ART). FFT and ART were implemented as a trial version, meaning that most therapists had not received formal training yet. Treatment characteristics related to recidivism were length of treatment, type of treatment, number of sessions, and the therapist. The longer the period of treatment and the greater the number of sessions, the higher the recidivism, even after controlling for risk of recidivism based on static risk factors. Juveniles who participated in ART reoffended more often than juveniles who had not participated in such training. Given the fact that FFT and ART were not well-implemented trial versions, it can be concluded that poorly implemented treatment leads to poor outcomes.


Review article: hepatic steatosis and insulin resistance.
Hepatic steatosis may be both an adaptive phenomenon and an example of lipotoxicity. Its prevalence ranks in the same order of magnitude of insulin resistance in the general population. Studies support the finding that hepatic steatosis is secondary to insulin resistance and not vice versa. A steatotic liver will further contribute to the development of insulin resistance through impaired clearance of insulin from the portal blood, creating a vicious cycle. Insulin resistance is the leading force in the pathogenesis and natural history of non-alcoholic fatty liver disease. Dysfunction of energetic homeostasis and the interaction of adiponectin, leptin and tumour necrosis factor-alpha are key events in the pathogenesis of steatosis and insulin resistance. Insulin resistance represents the frame within which hepatic and extrahepatic non-alcoholic fatty liver disease-related clinical manifestations are to be anticipated and interpreted.


Abnormal Uterine Bleeding.
Abnormal uterine bleeding (AUB) is a common medical problem, with a direct influence on women's quality of life, utilization of health care resources, and costs. AUB in women older than 40 years and especially in postmenopausal women requires a prompt and efficient evaluation, mainly to exclude the presence of malignant or premalignant lesions of the endometrium. Cancer of the endometrium is the most common gynecologic malignancy, with an incidence in the United States of more than 60,000 cases and mortality estimated at 10,000 women annually. This article outlines the role of transvaginal ultrasonography in the evaluation of cases of AUB.


Activation of nociceptive reflexes by peripheral kainate receptors.
The rat isolated spinal cord-tail preparation was used to examine the ability of peripherally applied excitatory amino acids to stimulate ventral root reflexes. Bolus applications (3 sec) of domoate (0.1-10 microM) or kainate (KA; 10-300 microM) to exposed skin of the rat tail stimulated ventral root responses comparably to those evoked by capsaicin (0.3-10 microM) or bradykinin (0.1-10 microM). The ventral root potential evoked by both capsaicin and KA is thought to be a nociceptive response because both compounds selectively activate peripheral C-fibers. L-Glutamate (0.01-10 mM), quisqualate (0.1-1 mM) and amino-5-methyl-4-isoxazole-propionic acid (0.1-1.0 mM) were of lower potency than KA, whereas N-methyl-D-aspartate (1 mM) and L-aspartate (10 mM) were inactive. Responses evoked by prolonged application of KA faded rapidly. Capsaicin-evoked responses partially faded during prolonged application, but residual spiking activity was recorded for at least 30 min. KA did not evoke any observable response during application of capsaicin. The effects of KA and capsaicin were blocked by spinal application of morphine (0.3-1.0 microM) in a naloxone-reversible manner, consistent with activation of peripheral nociceptive afferents. The action of KA, but not capsaicin, was competitively inhibited by the amino-5-methyl-4-isoxazole-propionic acid/KA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (10-100 microM) applied to the rat tail (pA2 = 5.9). Conversely, ruthenium red (1 microM) selectively blocked capsaicin-evoked nociceptive reflexes. The existence of functional KA receptors on nociceptive afferents suggests that peripherally released glutamate or other excitatory amino acids could be involved in nociception or neurogenic inflammation.


Influence of corn variety and cutting height on nutritive value of silage fed to lactating dairy cows.
Two corn varieties predicted to differ in digestibility were harvested at 2 cutting heights (10.2 or 30.5 cm) to determine effects on the nutrient content of the resulting silage, nutrient intake, nutrient digestibility, and production of lactating cows fed such corn silage originally harvested at two-thirds milk line. Acid detergent fiber (ADF) concentration was higher and in vitro true dry matter (DM) digestibility (IVTDMD) was lower for the variety predicted to have average digestibility. An interaction was observed between variety and cutting height because of decreased ADF and increased IVTDMD for the average digestibility variety cut at 30.5 vs. 10.2 cm; no differences were observed for the higher digestibility variety at each cutting height. When silages were fed to 32 Holstein cows in a 5-wk randomized design trial, DM intake, milk yield, and milk composition were similar. There was an interaction between variety and cutting height for DM intake and total tract apparent digestibility of DM, crude protein, and neutral detergent fiber because of lower intake and digestibility for the diets containing either the high cut, average quality variety or low cut, higher quality variety. These results suggest that increasing the cutting height to 30.5 cm does not improve silage quality or improve milk yield of cows. Although the 2 varieties selected for this trial were predicted to differ in digestibility, these differences were not great enough to influence milk yield or composition of lactating cows.


Rejoining of radiation-induced DNA double-strand breaks: pulsed-field electrophoresis analysis of fragment size distributions after incubation for repair.
The repair of radiation-induced DNA double-strand breaks (DSBs) is frequently investigated by measuring the time-dependent decrease in the fraction of fragmented DNA that is able to enter electrophoresis gels. When transformed into equivalent doses without repair, such measurements are thought to reflect the removal of DSBs, and they typically exhibit a fast initial component and a decreasing rate at longer repair intervals. This formalism, however, assumes that the spatial distribution of unrejoined breakage resembles the pattern of induction of DSBs. While the size distributions for initial fragmentation, such as that resolved by conventional pulsed-field gel electrophoresis (PFGE) (between about 10(5) and 10(7) bp), are well known to agree with the prediction of random breakage, no data are available from studies explicitly testing this relationship for residual breakage. Therefore, Chinese hamster V79 cells and MeWo (human melanoma) cells were irradiated with different doses (10-100 Gy) or were incubated for repair for up to 4 h after a single dose of 100 Gy (V79) or 90 Gy (MeWo) before being subjected to PFGE. Fragment size distributions were calculated by convolution of the PFGE profiles with an appropriately generated size calibration function. The results clearly demonstrate an over-representation of smaller fragments (below about 2-3 Mbp) compared to the prediction of randomness for residual breakage. In consequence, the time-dependent decrease of dose-equivalent values calculated from data on the fraction released may not directly reflect DSB rejoining rates. The present findings are compatible with an earlier suggestion of slow rejoining of breaks which have been induced as multiple breaks (two or more) in large chromosomal loops, thus also predicting an increase of the slowly rejoining DSB fraction with increasing dose.


Effect of a combined gamma irradiation and Parylene plasma treatment on the hydrolytic degradation of synthetic biodegradable sutures.
The aim of this study was to alter the hydrolytic degradation property of synthetic absorbable suture fibers so that their mass loss would occur at a shorter time without significantly compromising their tensile strength loss profile. A two-step treatment concept (gamma-irradiation followed by Parylene plasma deposition) was introduced for achieving this aim. Vicryl and Maxon were used as the model compounds to test this new concept. After the treatment, the in vitro hydrolytic degradation properties of Vicryl and Maxon were evaluated by weight loss, tensile breaking strength, heat of fusion and melting temperature, intrinsic viscosity, surface wettability, and surface morphology. The results suggested that gamma-irradiation at a dosage level between 0.2-2.0 Mrad for Vicryl sutures and about 2.0 Mrad for Maxon sutures were the most effective dosages to accelerate the suture mass loss. The subsequent Parylene plasma deposition treatment statistically significantly improved the retention of tensile strength for both gamma-irradiated Vicryl and Maxon sutures and hence counteracted the undesirable gamma-irradiation induced acceleration of tensile strength loss. However, this second-step Parylene plasma treatment extended the suture mass loss to longer periods. These findings were consistent with the observed surface wettability, surface morphology, intrinsic viscosity, and thermal properties. A thin hydrophobic Parylene skin layer wrapped around a suture was responsible for the slower rate in mass and strength loss. This outer skin layer acted as a barrier to not only water but also degradation fragments.


Tadalafil reduces visceral adipose tissue accumulation by promoting preadipocytes differentiation towards a metabolically healthy phenotype: Studies in rabbits.
Development of metabolically healthy adipocytes within dysfunctional adipose tissue may represent an attractive way to counteract metabolic syndrome (MetS). In an experimental animal model of high fat diet (HFD)-induced MetS, in vivo, long- and short-term tadalafil treatments were able to reduce visceral adipose tissue (VAT) accumulation and hypertriglyceridemia, and to induce the expression in VAT of the brown fat-specific marker, uncoupling protein 1 (UCP1). VAT preadipocytes (PAD), isolated from the tadalafil-treated HFD rabbits, showed: i) a multilocular morphology; ii) an increased expression of brown fat-specific genes (such as UCP1 and CIDEA); iii) improved mitochondrial structure and dynamic and reduced superoxide production; iv) improved insulin sensitivity. Similar effects were obtained after in vitro tadalafil treatment in HFD rPAD. In conclusion, tadalafil counteracted HFD-associated VAT alterations, by restoring insulin-sensitivity and prompting preadipocytes differentiation towards a metabolically healthy phenotype.


[Applicability of a clinical score in patients with suspected foreign body aspiration].
To validate the clinical score of Valdivieso et al. in the management of patients with suspected foreign body aspiration in a tertiary hospital. This score raises different scenarios according to the result: bronchoscopy, CT, observation or discharge. Retrospective study of patients who underwent a bronchoscopy due to suspected tracheobronchial foreign body between November-2015 and November-2018. The variables proposed by the score were collected (choking, stridor, wheezing, unilateral hypoventilation, altered chest X-ray and high-risk foreign body) and the score was calculated for each patient, analyzing the performance of the test using the ROC (Receiver Operating Characteristic) curve. Bronchoscopy was performed in 81 patients with a mean age of 2.1 years (7 months-11 years), finding foreign body in 33.3%. The area under the ROC curve of the score was 0.803 (0.695-0.911). In 6 (22.2%) patients with confirmed foreign body the score initially indicated observation in 5 cases and discharge in 1. Excluding the 49 patients with unilateral altered auscultation or when there was a nut suspected, which in our environment are clear indications for bronchoscopy, the score correctly classified the remaining 32 patients, which would have reduced the rate of normal bronchoscopies from 66% to 45%. The score in our sample presents a high diagnostic power but a non-negligible false negative rate. It has a special utility in patients who do not have unilateral altered auscultation and/or choking with nuts, allowing to reduce the rate of normal bronchoscopies.


Molecular attochemistry in non-polar liquid environments: ultrafast charge migration dynamics through gold-thiolate and gold-selenolate linkages.
Molecular attosecond science has already started contributing to our fundamental understanding of ultrafast purely electron dynamics in isolated molecules under vacuum. Extending attosecond science to the liquid phase is expected to offer new insight into the influence of a surrounding solvent environment on the attosecond electron dynamics in solvated molecules. A systematic theoretical investigation of the attochemistry of solvated molecules would help one design attosecond experiments under ambient conditions to explore the attochemistry in a liquid environment. With this goal in mind, for the first time, we have explored the attochemistry of molecules surrounded by different non-polar solvent environments. For this work, we have focused on the attosecond charge conduction through gold-thiolate and gold-selenolate linkages following the vertical ionization of the S/Se(CH3)-CH2-phenyl-X unit anchored to a gold dimeric cluster (Au2), where X represents either a strong electron donating N(CH3)2 group or a strong electron withdrawing NO2 group. To model solvation effects on the attochemistry of molecules containing gold-chalcogen linkages, we have used an implicit solvent model (Polarizable Continuum Model) under the density functional theory (DFT) formalism for non-polar solvents. We have found that the charge migration time scale in molecules becomes faster in the presence of the solvent environment as compared to that under vacuum. Charge oscillation does not damp quickly in molecules surrounded by the solvent environment as compared to that under vacuum. Furthermore, the direction of the charge migration may change in molecules when they are surrounded by the solvent environment as compared to that under vacuum. Thus, the present work has laid the foundation, for the first time, for thinking of the attochemistry into the realm of liquids.


[Uretero-acetabular fistula after removal of a septic total hip prosthesis].
The authors report a case of an uretero-acetabular fistula after a Girdlestone procedure. The reason of ablation was an infected hip prosthesis. The urinary fistula was treated with an uretero-ileoplasty and hip infection with a two stages procedure. There was no recurrence of infection at two years follow-up. Different causes of this urinary complication are discussed.


Effect of contraception provided at termination of pregnancy and incidence of subsequent termination of pregnancy.
To determine the incidence of subsequent termination of pregnancy (TOP) within a 2-year period in relation to the method of contraception provided to women following the index TOP. Case note review. NHS hospital TOP service, Edinburgh, UK. Nine hundred and eighty-six women requesting a TOP in 2008. Case notes were reviewed to determine the contraception provided at index TOP and whether women had subsequent TOP at the same hospital within 2 years. Incidence of subsequent TOP within 2 years amongst women receiving different contraceptive methods. One hundred and twenty-one women (12.3%) of the 986 who attended the clinic requesting a TOP returned requesting another TOP in the subsequent 2 years. Both intrauterine contraception and the progestogen-only implant were associated with the lowest incidence of subsequent TOP. Using the combined oral contraceptive pill as the reference method, the odds ratios (ORs) and 95% confidence intervals (CIs) of a further TOP within 2 years with intrauterine contraception and the implant were OR = 0.05 (95% CI, 0.01-0.41; P < 0.001) and OR =0.06 (95% CI, 0.01-0.23; P < 0.001), respectively. Women choosing the implant were significantly younger than those choosing the intrauterine method (P < 0.001). Women undergoing a TOP who wish to avoid another unintended pregnancy should consider immediate initiation of either intrauterine contraception or the progestogen-only implant. Service providers should be trained and supported to provide these methods to women at the time of TOP.


Multielectron oxidation in a ferromagnetically coupled dinickel(ii) triple mesocate.
Triple-stranded dinuclear nickel(ii) complexes of the meso-helicate type have been obtained from the new N,N'-1,3-phenylenebis(pyrazine-2-carboxamidate) ligand; they possess a multielectron redox behaviour featuring up to four stepwise, one-electron oxidation reactions of the two ferromagnetically coupled Ni(II) ions to afford the putative high-valent dinickel(iii) and dinickel(iv) species, as supported by theoretical calculations.


Chlamydia pneumoniae and acute aortic syndrome: a call for a multi-institutional study.
Chlamydia Pneumoniae (CP) infection is strongly associated with coronary artery disease, as well as with atherosclerosis of the carotid and peripheral arteries. However, the role of CP in the pathogenesis of aortic disease remains controversial. Our present experience suggests no correlation between a current infection with C. pneumoniae and acute aortic dissection. Well-designed large prospective studies are needed in order to clarify the pathophysiologic role of CP infection in acute and chronic aortic disease.


Abnormal processing of social information from faces in autism.
Autism has been thought to be characterized, in part, by dysfunction in emotional and social cognition, but the pathology of the underlying processes and their neural substrates remain poorly understood. Several studies have hypothesized that abnormal amygdala function may account for some of the impairments seen in autism, specifically, impaired recognition of socially relevant information from faces. We explored this issue in eight high-functioning subjects with autism in four experiments that assessed recognition of emotional and social information, primarily from faces. All tasks used were identical to those previously used in studies of subjects with bilateral amygdala damage, permitting direct comparisons. All subjects with autism made abnormal social judgments regarding the trustworthiness of faces; however, all were able to make normal social judgments from lexical stimuli, and all had a normal ability to perceptually discriminate the stimuli. Overall, these data from subjects with autism show some parallels to those from neurological subjects with focal amygdala damage. We suggest that amygdala dysfunction in autism might contribute to an impaired ability to link visual perception of socially relevant stimuli with retrieval of social knowledge and with elicitation of social behavior.


Mapping phenotypic, expression and transmission ratio distortion QTL using RAD markers in the Lake Whitefish (Coregonus clupeaformis).
The evolution of reproductive isolation in an ecological context may involve multiple facets of species divergence on which divergent selection may operate. These include variation in quantitative phenotypic traits, regulation of gene expression, and differential transmission of particular allelic combinations. Thus, an integrative approach to the speciation process involves identifying the genetic basis of these traits, in order to understand how they are affected by divergent selection in nature and how they ultimately contribute to reproductive isolation. In the Lake Whitefish (Coregonus clupeaformis), dwarf and normal species pairs sympatrically occur in several North American postglacial lakes. The limnetic dwarf whitefish distinguishes from its normal benthic relative by numerous life history, behavioural, morphological and gene expression traits, in relation with the exploitation of distinct ecological niches. Here, we have applied the RAD-Sequencing method to a hybrid backcross family to reconstruct a high-density genetic linkage map and perform QTL mapping in the Lake Whitefish. The 3061 cM map encompassed 3438 segregating RAD markers distributed over 40 linkage groups, for an average resolution of 0.89 cM. We mapped phenotypic and expression QTL underlying ecologically important traits as well as transmission ratio distortion QTL, and identified genomic regions harbouring clusters of such QTL. A narrow genomic region strongly associated with sex determination was also evidenced. Positional and functional information revealed in this study will be useful in ongoing population genomic studies to illuminate our understanding of the genomic architecture of reproductive isolation between whitefish species pairs.


Does informal care from adult children reduce nursing home admissions for the elderly?
Despite the policy importance, particularly as society ages, little is known about the impact of informal care on nursing home admissions. This paper jointly models the receipt of regular help from adult children and subsequent nursing home care, using data from the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD). Results indicate that frequent help from children with basic personal care reduces the likelihood of nursing home use over a subsequent two-year period by about 60% for disabled Americans age 70 and older. However, we found no significant reduction in nursing home admissions when help was measured more broadly to include assistance with chores and errands.


Percutaneous needle washing for the diagnosis of pulmonary thin-walled cavitary lesions filled with air.
It is difficult to obtain sufficient material from pulmonary thin-walled cavitary lesions filled with air by conventional percutaneous aspiration biopsy in order to make a diagnosis. In these cases, we performed percutaneous needle washing (PNW) and ascertained the diagnostic significance of this method. PNW was performed on 27 patients with a pulmonary thin-walled cavitary lesion whose diagnosis could not be made by sputum and bronchoscopic examinations. Before centesis, the depth of the lesion was measured on CT scan. After the 22-gauge needle was inserted under X-ray fluoroscopic guidance, normal saline was injected into the cavity and aspirated. The aspirated material was examined cytologically and microbiologically. The procedure was carried out during one 30-second breath-holding. Upon performing PNW on 27 patients, malignant cells were detected in 10 patients and a bacterial or fungal pathogen was detected in 9 other patients [Aspergillus (4), Mycobacterium (3), Staphylococcus (1), Streptococcus (1)]. The diagnoses of 16 of the 17 patients who were negative for malignant cells on PNW, were ascertained as benign disease during their clinical course including 3 patients who were diagnosed as (or suspected of) having infectious disease clinically, while the diagnosis of one case was unknown. Therefore, the diagnostic sensitivity of PNW for malignant diseases was 91% (10/11), while that for infectious diseases was 69% (9/13). Mild pneumothorax was the only complication of PNW (2 cases). PNW may be an appropriate diagnostic procedure for pulmonary thin-walled cavitary lesions whose diagnosis can not be established by other techniques.


Mobilization and micellar solubilization of NAPL contaminants in aquifer rocks.
Surfactant-enhanced aquifer remediation is often performed to overcome the capillary forces that keep residual NAPL phases trapped within contaminated aquifers. The surfactant selection and displacement mechanism usually depend on the nature of NAPL constituents. For example, micellar solubilization is often used to cleanup DNAPLs from aquifers whereas mobilization is desirable in aquifers contaminated by LNAPLs. Although the majority of crude oils are LNAPLs, they often contain heavy organic macromolecules such as asphaltenes that are classified as DNAPLs. Asphaltenes contain surface-active components that tend to adsorb on rocks, altering their wettability. Previous studies revealed that surfactants that formed Winsor type III microemulsions could promote both mobilization and solubilization. However the extent by which these two mechanisms occur is still unclear, particularly in oil-contaminated aquifers. In this study we investigated the remediation of oil-contaminated aquifers using an environmentally friendly surfactant such as n-Dodecyl β-D-maltoside. Focus was given on asphaltenes to better understand the mechanisms of surfactant cleanup. Through phase behavior, spontaneous imbibition, dynamic interfacial tension and contact angle measurements, we showed that microemulsions formed by this surfactant are able to mobilize bulk NAPL (containing 9wt.% asphaltenes) in the porous rock and solubilize DNAPL (i.e., 4-6wt.% adsorbed asphaltenes) from the rock surface. Spontaneous imbibition tests, in particular, indicated that the ratio of mobilized to solubilized NAPL is about 6:1. Furthermore, aging the cores in NAPL beyond 3days allowed for more NAPL to be trapped in the large pores of the rock but did not alter the amount of asphaltenes adsorbed on the mineral surface.


Association between the transmembrane region polymorphism of MHC class I chain related gene-A and type 1 diabetes mellitus in Sweden.
Major histocompatibility complex (MHC) class I chain related gene-A (MIC-A) is associated with type 1 diabetes mellitus (T1DM) in other populations. We tested the association of MIC-A gene polymorphism with T1DM in Swedish Caucasians; if it has an age-dependent association; and if the association has an effect on gender. We studied 635 T1DM patients and 503 matched controls in the age group of 0-35 years old. MIC-A5 was significantly increased in T1DM compared with controls (odds ratio [OR] =1.81, p(c) < 0.0005). Logistic regression analysis revealed MIC-A5 association was independent of HLA. MIC-A5 with DR4-DQ8 or MIC-A5 with DR3-DQ2 gave higher OR than the OR obtained with either of them alone (OR = 1.81, 7.1, and 3.6, respectively). MIC-A5 was positively (OR = 2.48, p(c) < 0.0005) and MIC-A6 negatively associated (OR = 0.61, p(c) = 0.035) with the disease in < or = 20 years of age. The negative association of MIC-A6 in young onset was confirmed by logistic regression analysis. MIC-A5 was associated with the disease in males (OR = 2.05, p(c) = 0.0005). MIC-A6 conferred protection (OR = 0.098, p(c) = 0.032) in females heterozygous for DR3/DR4. In conclusion, MIC-A5 is associated with T1DM; the association was higher in individuals < or = 20 years old; and negative association of MIC-A6 was stronger in younger onset patients than in older onset patients.


Preservation of segmental hindbrain organization in adult frogs.
To test for possible retention of early segmental patterning throughout development, the cranial nerve efferent nuclei in adult ranid frogs were quantitatively mapped and compared with the segmental organization of these nuclei in larvae. Cranial nerve roots IV-X were labeled in larvae with fluorescent dextran amines. Each cranial nerve efferent nucleus resided in a characteristic segmental position within the clearly visible larval hindbrain rhombomeres (r). Trochlear motoneurons were located in r0, trigeminal motoneurons in r2-r3, facial branchiomotor and vestibuloacoustic efferent neurons in r4, abducens and facial parasympathetic neurons in r5, glossopharyngeal motoneurons in r6, and vagal efferent neurons in r7-r8 and rostral spinal cord. In adult frogs, biocytin labeling of cranial nerve roots IV-XII and spinal ventral root 2 in various combinations on both sides of the brain revealed precisely the same rostrocaudal sequence of efferent nuclei relative to each other as observed in larvae. This indicates that no longitudinal migratory rearrangement of hindbrain efferent neurons occurs. Although rhombomeres are not visible in adults, a segmental map of adult cranial nerve efferent nuclei can be inferred from the strict retention of the larval hindbrain pattern. Precise measurements of the borders of adjacent efferent nuclei within a coordinate system based on external landmarks were used to create a quantitative adult segmental map that mirrors the organization of the larval rhombomeric framework. Plotting morphologically and physiologically identified hindbrain neurons onto this map allows the physiological properties of adult hindbrain neurons to be linked with the underlying genetically specified segmental framework.


[Theoretical presuppositions in the precise tomographic study of the temporomandibular joint].
In order to eliminate typical projective distortions of lateral or standard oblique tomography of the temporo-mandibular joint, authors suggest a preliminary evaluation of the long condylar axis inclination by means of axial radiograph. This method allows to personalize, for each side, the slope of X-ray beam to perform an effectual oblique tomography.


[Paroxysmic anarthria in multiple sclerosis].
The paroxystic clinical features of multiple sclerosis (MS) include trigeminal neuralgia, itch, transient diplopia, Lhermitte's sign, akinesia, dystonia, Uhthoff's phenomenon and others which are very characteristic, such as paroxystic ataxia and dysarthria. We present the case of a 30 year old man who consulted for multiple episodes lasting only a few seconds, of complete inability to speak. This symptom recurred several times a day and in many different situations. It was often triggered off by external stimuli such as having to speak in front of several people. The disorder disappeared without treatment seven days after onset. Magnetic resonance using fast spin echo image sequences showed multiple hyperintense lesions in mid right cerebellar peduncle, right pons, left temporal lobe, white substance of both internal capsules, periventricular and semioval centres. Biochemical study of the cerebrospinal fluid showed that there were 9 cells/microliter (mainly lymphocytes), proteins 45 mg/dl and a normal glucose level. The Tibling-Link level was 0.73. Cortical somestesic evoked potentials showed slowed conduction after stimulation of the right median nerve and both peroneal nerves. Acoustic evoked potentials of the brain stem were conducted more slowly by the right acoustic pathway at intraxial level. The patient was diagnosed as having clinically defined MS. We consider that our patient's symptom was a kind of paroxystic dysarthria which we call paroxystic anarthria. Differential diagnosis of this symptom should be basically with phonatory or dysphasic simple partial seizures.


Lip and Perioral Enhancement With Hyaluronic Acid Dermal Fillers in Individuals With Skin of Color.
Individuals with skin of color are underrepresented in studies of lip and perioral enhancement. To examine the effectiveness and safety of hyaluronic acid (HA) dermal filler treatment for lip and perioral enhancement in subjects with skin of color. Data were pooled from subjects with Fitzpatrick skin phototypes IV, V, or VI in 2 pivotal studies of HA dermal fillers. Photonumeric scales were used to assess lip fullness (5-point scale) and perioral lines and oral commissures severity (each 4-point scales). Safety was assessed by injection site responses recorded in patient diaries and adverse events (AEs). The cohort comprised 72 subjects (median age: 49.5 years; 95.8% female). Mean lip fullness improved from baseline by 1.1 points at 3 months after treatment; 85.0% of subjects were responders (≥1-point improvement). Of subjects treated for perioral lines (n = 12) and oral commissures (n = 56), 90.9% and 46.4%, respectively, were responders. Injection site responses were generally mild or moderate in severity, resolved within 2 weeks, and were consistent with those expected for HA dermal filler treatment. The most common AEs were injection site mass (19.4%) and bruising (12.5%). Lip and perioral enhancement with HA dermal fillers is effective and safe in subjects with skin of color.


Oxygen and carbon dioxide dissociation of duck blood.
Oxygen and CO2 dissociation of duck blood was studied in blood samples equilibrated with known gas mixtures at the bird's body temperature (41 degrees C) and analyzed in the Van Slyke manometric apparatus and in pH electrodes. At various pH values between 7.38 and 7.55 the Hill plots yielded straight and parallel lines over a wide range of O2 saturation, the Hill coefficient being 2.9. Half saturation pressure P50 at pH = 7.50 was 36 torr. The Bohr effect factor was -0.53. Buffering properties were analyzed by equilibrating blood samples with gas mixtures of different PCO2 at 41 degrees C. The buffer value for whole blood in the range of 3-7% CO2 was 19.3 mMol-L-1-pH-1, the buffer value for true plasma 22.9 mMol-L-1-pH-1. The CO2 dissociation curve constructed using the buffer values had a slope of 0.17 mMol-L-1-torr-1 in the PCO2 range from 40 to 50 torr. The CO2 content of oxygenated blood at PCO2 = 40 torr was 21.7 mMol-L-1. The Haldane effect factor at PCO2 = 35 torr equalled 0.30 mMol of combined CO2 per mMol HbO2. With the values of PO2, PCO2 and pH measured in arterial blood of undisturbed and unrestrained, resting ducks effective dissociation curves for both O2 and CO2 were constructed assuming a metabolic R.Q. of 0.8. These curves are expected to resemble closely the actual in vitro dissociation curves of resting ducks.


Photoabsorption of green and red fluorescent protein chromophore anions in vacuo.
Photoabsorption properties of green and red fluorescent protein chromophore anions in vacuo were investigated theoretically, based on the experimental results in gas phase [Phys. Rev. Lett. 2001, 87, 228102; Phys. Rev. Lett. 2003, 90, 118103]. Their calculated transition energies in absorption with TD-DFT and ZINDO methods are directly compared to the experimental reports in gas phase, and the calculations with ZINDO method can correctly reproduce the absorption spectra. The orientation and strength of their transition dipole moments were revealed with transition density. We also showed the orientation and result of their intramolecular charge transfer with transition difference density. The calculated results show that with the increase of the extended conjugated system, the orientation of transition dipole moments and the orientation of charge transfer can be reversed. They are the linear responds with the external electric fields. These theoretical results reveal the insight understanding of the photoinduced dynamics of green and red fluorescent protein chromophore anions and cations in vacuo.


N-acetylcysteine.
N-acetylcysteine (NAC) is the acetylated precursor of both the amino acid L-cysteine and reduced glutathione (GSH). Historically it has been used as a mucolytic agent in chronic respiratory illnesses as well as an antidote for hepatotoxicity due to acetaminophen overdose. More recently, animal and human studies of NAC have shown it to be a powerful antioxidant and a potential therapeutic agent in the treatment of cancer, heart disease, HIV infection, heavy metal toxicity, and other diseases characterized by free radical oxidant damage. NAC has also been shown to be of some value in treating Sjogren's syndrome, smoking cessation, influenza, hepatitis C, and myoclonus epilepsy.


Size of external genital organs and somatometric parameters among physically normal men younger than 40 years old.
To estimate the sizes of the external genital organs in physically normal adult males younger than 40 years old, as well as to correlate the resulting values with age and a number of somatometric parameters, to provide data that could be clinically applicable by the practicing urologist. Fifty-two physically normal men, 19 to 38 years old, underwent tape measurements of penile dimensions in the flaccid-stretched state (total, shaft, glanular lengths), penile shaft volume calculation, and ultrasonographic testicular volume estimation. The resultant values were correlated with age, height, weight, body mass index, waist/hip ratio, and index finger length. The mean testicular volume was 16.9 +/- 4.7 cm(3), with the right testis (17.5 +/- 5.8 cm(3)) measuring slightly larger than the left (15.85 +/- 4.9 cm(3); P = not significant). The mean total penile length was 12.18 +/- 1.7 cm, the mean penile shaft length was 7.76 +/- 1.3 cm, the mean glanular length was 4.4 +/- 0.4 cm, and the mean penile shaft volume was 46.5 +/- 17.2 cm(3). Among the various correlations performed, the penile lengths (total, shaft, glanular) to index finger length (P <0.05) and to penile shaft volume (P <0.001) were statistically significant. Data on the size of the external genital organs among physically normal young adult men were provided and a novel formula for penile shaft volume calculation was proposed. Age and somatometric parameters were not associated with the size of the genitalia, excluding the index finger length, which correlated significantly with the dimensions of the flaccid, maximally stretched, penis.


A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease.
Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding. We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density. Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen. Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea.


Factorial structure of the Sensation-Seeking Scale-Form V: confirmatory factorial analyses in nonclinical and clinical samples.
The factor structure of the Sensation-Seeking Scale (SSS)-Form V was studied in 2 large French samples, using confirmatory factorial analyses (CFA) to test the 4-dimensional model of sensation seeking postulated by Zuckerman. The study included 769 healthy subjects and 659 patients who met the DSM-IV criteria for substance use disorders or eating disorders and completed the SSS. The correlation matrices for each of the samples were analyzed using CFA. In each sample, we found the 4-factor model to be replicable. The multidimensionality of sensation seeking is supported by the results, and the 4-dimensional model of sensation seeking identified by Zuckerman can be explored in French-speaking people.


Macrovascular and microvascular endothelium during long-term hypoxia: alterations in cell growth, monolayer permeability, and cell surface coagulant properties.
In bovine aortic or capillary endothelial cells (ECs) incubated under hypoxic conditions, cell growth was slowed in a dose-dependent manner at lower oxygen concentrations, as progression into S phase from G1 was inhibited, concomitant with decreased thymidine kinase activity. Monolayers grown to confluence in ambient air, wounded, and then transferred to hypoxia showed decreased ability to repair the wound, as a result of both decreased motility and cell division. Hypoxic ECs demonstrated a approximately 3-fold increase in the total number of high-affinity fibroblast growth factor receptors, and levels of endogenous FGF were suppressed. Consistent with the presence of functional FGF receptors, addition of basic FGF overcame, at least in part, hypoxia-mediated suppression of EC growth, and enhanced wound repair in hypoxia, stimulating both motility and cell division. Despite slower growth in hypoxia, ECs could achieve confluence, and the monolayers consisted of larger cells with altered assembly of the actin-based cytoskeleton and small gaps between contiguous cells. The permeability of these hypoxic EC monolayers to macromolecules and lower molecular weight solutes was increased. Cell surface coagulant properties were also perturbed: the anticoagulant cofactor thrombomodulin was suppressed, and a novel Factor X activator appeared on the EC surface. These data indicate that micro- and macrovascular ECs can grow and be maintained at low oxygen tensions, but hypoxic endothelium exhibits a range of altered functional properties which can potentially contribute to the pathogenesis of vascular lesions.


Sweet solution?
Research has suggested that chocolate--at least the dark kind--has a number of potential health benefits. But chocolate has its downside too.


Identification of specific binding sites for leukotriene C4 in human fetal lung.
Specific leukotriene C4 (LTC4)1 binding sites were identified in membrane preparations from human fetal lung. Specific binding of [3H]-LTC4 represented 95 percent of total binding, reached steady-state within 10 minutes and was rapidly reversible upon addition of excess unlabeled LTC4. Binding assays were performed at 4 degrees C under conditions which prevented metabolism of [3H]-LTC4 (80 mM serine-borate, 10 mM cysteine, 10 mM glycine). Under these conditions, greater than 95 percent of the membrane bound radioactivity, as analyzed by high performance liquid chromatography, co-eluted with the LTC4 standard. Computer-assisted analyses of saturation binding data showed a single class of binding sites with a dissociation constant (Kd) of 26 + 6 nM and a density (Bmax) of 84 + 18 pmol/mg protein. Pharmacological specificity was demonstrated by competition studies in which specific binding of [3H]-LTC4 was displaced by LTC4 and its structural analogs with inhibition constants (Ki) of 10 to 30 nM, whereas LTD4, diastereoisomers of LTD1, LTE4 and the end organ antagonist FPL 55712 were 150 to 700 fold less potent competitors than LTC4. These results provide evidence for specific, reversible, saturable, high affinity binding sites for [3H]-LTC4 in human fetal lung membranes.


Medical considerations in dental treatment of children with Williams syndrome.
Williams syndrome is a rare disorder that was first described in 1961. It is thought to be caused by a microdeletion in the long arm of chromosome 7 at 7q11.23 and is a multisystem, congenital, and panethnic disorder characterized by a number of developmental and physical abnormalities, including congenital cardiovascular abnormalities, mental retardation and neurological features, growth deficiency, genitourinary manifestation, gastrointestinal and musculoskeletal problems, behavioral characteristics, craniofacial features, ophthalmologic features, and dental problems. We describe cases of children with Williams syndrome treated in the department of Pediatric Dentistry of the Hadassah School of Dental Medicine, Jerusalem, Israel. The different treatments rendered to these children are discussed followed by general remarks drawn from those treatments and from a literature review. We conclude that sedation can be helpful in the younger age group to reduce anxiety and uncooperative behavior during minimal dental treatments. Treatment under general anesthesia seems more appropriate for older children and adolescents. Special attention should be given to initial evaluation of these patients, especially because with age aortic stenosis tends to intensify, which together with the progressive renal impairment can escalate blood pressure elevation.


A novel role for Rad17 in homologous recombination.
Replication checkpoint protein Rad17 senses DNA lesions during DNA replication and halts progression of replication fork. The cells derived from Bloom syndrome individuals show some defects in DNA replication. In order to investigate the functional relationship between the replication checkpoint protein Rad17 and BLM, which is the product of the causative gene of Bloom syndrome, we generated BLM/RAD17 double knockout (blm/rad17) cells using chicken DT40 cells. The blm/rad17 cells showed exaggerated growth defects as determined by analysis of their growth curves and plating efficiency compared to those of either of the single gene mutants. These defects seem to be due to an increase in DNA lesions that cause spontaneous cell death, suggesting that Rad17 and BLM execute different functions in the progression of replication forks. We also demonstrate that targeting integration was dramatically compromised by a lack of Rad17. In addition, the elevated frequency of sister chromatid exchange (SCE) due to homologous recombination in BLM knockout (blm) cells was greatly reduced by disruption of the RAD17 gene. Thus, in addition to its role in the replication checkpoint, Rad17 appears to play a role in homologous recombination.


Does laminar flow ventilation reduce the rate of infection? an observational study of trauma in England.
To determine whether there is any difference in infection rate at 90 days between trauma operations performed in laminar flow and plenum ventilation, and whether infection risk is altered following the installation of laminar flow (LF). We assessed the impact of plenum ventilation (PV) and LF on the rate of infection for patients undergoing orthopaedic trauma operations. All NHS hospitals in England with a trauma theatre(s) were contacted to identify the ventilation system which was used between April 2008 and March 2013 in the following categories: always LF, never LF, installed LF during study period (subdivided: before, during and after installation) and unknown. For each operation, age, gender, comorbidity, socio-economic deprivation, number of previous trauma operations and surgical site infection within 90 days (SSI90) were extracted from England's national hospital administrative Hospital Episode Statistics database. Crude and adjusted odds ratios (OR) were used to compare ventilation groups using hierarchical logistic regression. Subanalysis was performed for hip hemiarthroplasties. A total of 803 065 trauma operations were performed during this time; 19 hospitals installed LF, 124 already had LF, 13 had PV and the type of ventilation was unknown in 28. Patient characteristics were similar between the groups. The rate of SSI90 was similar for always LF and PV (2.7% and 2.4%). For hemiarthroplasties of the hip, the rates of SSI90 were significantly higher for LF compared with PV (3.8% and 2.6%, OR 1.45, p = 0·001). Hospitals installing LF did not see any statistically significant change in the rate of SSI90. The results of this observational study imply that infection rate is similar when orthopaedic trauma surgery is performed in LF and PV, and is unchanged by installing LF in a previously PV theatre. Cite this article: Bone Joint J 2016;98-B:1262-9.


Chronic use of continuous dosing of long-term nitrates does not prevent cardiac events in patients with severe acute myocardial infarction.
This study was performed to investigate the effects of the chronic use of continuous, not eccentric, dosing of nitrates on cardiac events in patients with severe acute myocardial infarction. A total of 1,303 patients with healed myocardial infarction were divided into two groups: treatment with nitrates or nontreatment. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure and sudden death. Among the 725 patients treated with nitrates, 45 patients (6.2%) experienced cardiac events during the observation period, whereas only 17 of the 578 patients treated without nitrates (2.9%) had cardiac events. This difference was statistically significant (p < 0.01; odds ratio 2.18, 95% confidence interval 1.24-3.86). In Killip class II-IV patients, the incidence of cardiac events in patients with nitrates was significantly greater than in patients without nitrates (18.8 vs. 3.5%, p < 0.05). The chronic use of continuous, not eccentric, dosing of nitrates did not prevent cardiac events in patients with severe acute myocardial infarction.


The poor, the Black, and the marginalized as the source of cadavers in United States anatomical education.
When the practice of hands-on anatomical dissection became popular in United States medical education in the late 18th and early 19th centuries, demand for cadavers exceeded the supply. Slave bodies and thefts by grave robbers met this demand. Members of the public were aware that graves were being robbed and countered with various protective measures. Since the deterrence of grave robbing took time and money, those elements of society who were least economically and socially advantaged were the most vulnerable. Enslaved and free African Americans, immigrants, and the poor were frequently the target of grave robbing. The politically powerful tolerated this behavior except when it affected their own burial sites. Slave owners sold the bodies of their deceased chattel to medical schools for anatomic dissection. Stories of the "night doctors" buying and stealing bodies became part of African American folklore traditions. The physical and documentary evidence demonstrates the disproportionate use of the bodies of the poor, the Black, and the marginalized in furthering the medical education of white elites.


Cytokine gene expression and activation of NF-kappa B in aniline-induced splenic toxicity.
Exposure to aniline results in selective toxicity to the spleen, leading to a variety of sarcomas on chronic exposure in rats, and fibrosis appears to be an important initiating preneoplastic lesion of the spleen. However, the molecular mechanism(s) by which aniline leads to fibrogenic response is not well understood. Previously, we have shown that aniline exposure leads to iron overload and induction of oxidative stress in the spleen. We hypothesized that aniline-induced oxidative stress in the spleen causes transcriptional up-regulation of fibrogenic cytokines via activation of redox-sensitive transcription factor, nuclear factor-kappa B (NF-kappa B). To test this hypothesis, male SD rats were treated with 0.5 mmol/kg/day aniline hydrochloride via drinking water for 30 days. Cytokine mRNAs were measured by real-time quantitative PCR, while cytokine release was determined in the supernatants of the cultured splenocytes using specific ELISAs. IL-1alpha, IL-6, and TNF-alpha mRNA levels showed 6.9-, 2.9-, and 2.6-fold increases, respectively, in the spleens of aniline-treated rats in comparison to the controls. The increases in mRNA levels were associated with enhanced secretion of these cytokines in the splenocyte culture supernatants. NF-kappa B p65 level in the nuclear extracts of cultured splenocytes of aniline-treated rats showed a 2-fold increase in comparison to the controls as quantitated by NF-kappa B p65-specific ELISA. The binding activity of NF-kappa B, determined by electrophoretic mobility shift assay (EMSA), also showed an increase in NF-kappa B binding in the nuclear extracts of the splenocytes from aniline-treated rats. The specificity of NF-kappa B binding was further confirmed by supershift assays. The results indicate that aniline exposure causes enhanced expression of IL-1alpha, IL-6, and TNF-alpha, both at mRNA and protein levels, suggesting their role in splenic fibrosis. Also, the increased NF-kappa B binding activity suggests that up-regulation of these cytokines in the spleen is a redox-dependent mechanism.


A fluorescent heteroditopic ligand responding to free zinc ion over six orders of magnitude concentration range.
A fluorescent heteroditopic ligand useful in live-cell imaging studies responds to free zinc ion concentration over a range of six orders of magnitude in a buffered aqueous solution via dual-channel fluorescence.


Transesterification of Moz-Asn-Leu-Gly-OEt in methanol. Confirmation of Ca2+ mediated catalysis.
During the recrystallization of the crude protected tripeptide ester Moz-Asn-Leu-Gly-OEt (obtained by an enzymatic coupling reaction) in methanol/water, the transesterification of this compound to methyl ester was observed. The involvement of Ca2+ in this process was indicated by the results obtained in the following experiments: 1) incubation of crude Moz-Asn-Leu-Gly-OEt in methanol solutions of o-phenanthroline and EDTA; 2) recrystallization of the crude Moz-Asn-Leu-Gly-OEt in ethanol/water followed by incubation in methanol; 3) determination of the Ca2+ content of the crude Moz-Asn-Leu-Gly-OEt. After recrystallization Moz-Asn-Leu-Gly-OEt lost the ability to be transesterified in methanol. However, in the presence of crude Moz-Asn-Leu-Gly-OEt, or calcium acetate, or a mixture of calcium chloride/sodium acetate, the compound was transesterified, suggesting that the transesterification of crude and recrystallized compounds occurs through different mechanisms. On the basis of these results, and of the conformational data obtained for these peptides by 1H-NMR, we suggest models for the transesterification reactions.


Cytokine gene expression and T-cell proliferative responses in lymph node mononuclear cells from children with early stage human immunodeficiency virus infection.
The immunologic events taking place in secondary lymphoid tissue from children with early stage human immunodeficiency virus (HIV) infection are poorly understood. The aim of this study was to investigate cytokine gene expression and proliferative responses in lymph node (LN) biopsies from five children with early stage HIV infection, in the context of LN morphology and viral load. The design of the study was approved by the local Ethical Committee. Cytokine gene expression was studied in LN biopsies and in paired peripheral blood (PB) samples from HIV-infected children by reverse transcriptase-polymerase chain reaction. T-cell proliferation was assessed by 3H-thymidine incorporation. Viral burden in germinal centers was assessed by video densitometric analysis following immunohistochemical staining for HIV p24. Interleukin (IL)-2, IL-4 and IL-5 mRNA were not detected in any LN or PB sample from HIV-infected children. Interferon (IFN)-gamma mRNA was found only in CD8+ cells. IL-12 p35, IL-10, transforming growth factor-(TGF)-beta1, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and IL-16 transcripts were detected in all samples. Proliferation of LN and PB mononuclear cells to polyclonal mitogens and soluble (recall and HIV-related) antigens was impaired as compared with the responses in a group of age-matched healthy controls. Changes in cytokine gene expression and T-cell proliferative responses are already detectable in lymph nodes from HIV-infected children at an early stage of disease.


An integrated pharmacodynamic analysis of erythropoietin, reticulocyte, and hemoglobin responses in acute anemia.
To determine by pharmacodynamic (PD) analysis physiologically relevant parameters of the cellular kinetics of erythropoiesis in acute anemia. The PD relationships among erythropoietin (EPO), reticulocyte, and RBC (Hb) responses were investigated in young adult sheep in acute anemia induced twice by two controlled phlebotomies separated by a 4-week recovery period. The phlebotomies resulted in rapid increases in plasma EPO, with maximal levels occurring at 3 to 8 days, followed by a reticulocyte response with a delay of 0.5 to 1.5 days. The Hb returned to prephlebotomy base line at the end of the 4-week recovery period. The EPO, reticulocyte count, and Hb responses were well described by a PK/PD model (r = 0.975) with the following cellular kinetics parameters: the lag time between EPO activation of erythroid progenitor cells and reticulocyte formation; the reticulocyte-to-RBC maturation time; the reticulocyte and Hb formation efficacy coefficients, quantifying EPO's efficacy in stimulating the formation of reticulocytes and Hb, respectively; the C50 PK/PD transduction parameter defined as the EPO level resulting in half the maximum rate of erythropoiesis. Physiologically relevant cellular kinetics parameters can be obtained by an endogenous PK/PD analysis of phlebotomy data and are useful for elucidating the pathophysiologic etiology of various anemias.


A colorimetric 96-well microtiter plate assay for the determination of enzymatically formed citrulline.
l-Citrulline constitutes a product of a number of enzymatic reactions. In the past a number of colorimetric methods for the determination of l-citrulline, upon its chemical modification with diacetyl monoxime at 95 degrees C, have been reported. However, all these methods are time- and material-consuming. In this work, using the same chemical reaction, a new method for the use in 96-well polystyrene microtiter plates was developed. The method is fast and requires substantially less material as the enzymatic reaction is performed in a volume of 60 microl. The applicability of this enzymatic assay was established using l-N(omega), N(omega)-dimethylarginine dimethylaminohydrolase, which generates l-citrulline from side-chain methylated derivatives of l-arginine. The detection limit for l-citrulline is about 0.2 nmol. In addition, our studies show that most commonly used biochemical buffers and buffer additives do not affect the assay. This method may prove useful in the studies of other l-citrulline producing enzymes including nitric oxide synthase.


Comparison of a recombinant thromboplastin with Thrombotest for oral anticoagulant control.
Thrombotest results expressed in international normalized ratio (INR) values, obtained in 108 patients on oral anticoagulant treatment, were compared with prothrombin time (PT) results with a recombinant thromboplastin. The former results were obtained on an Amelung coagulometer, the latter on a photo-optical instrument. Using the Thrombotest method, performed within 2 h after sampling as the reference method, a first group of 63 patients had an INR value between 2 and 4. This group was considered as adequately anticoagulated and served as a true positive population in further analysis. The remaining 45 patients (true-negative group) had an INR value below 2 or higher than 4 and could thus be considered as inadequately anticoagulated. Using these definitions, a sensitivity of 86% and a specificity of 96% could be calculated for the PT with the recombinant thromboplastin. All tests from patients on oral anticoagulant treatment were also performed after 24 h storage of the blood or plasma samples at room temperature. When we compared the reference Thrombotest results with those of the late Thrombotest and the late PT recombinant thromboplastin, sensitivities of 86 and 86% as well as specificities of 91 and 96% were found, respectively. In conclusion, PT with a recombinant thromboplastin on a photo-optical instrument, even after prolonged storage of the plasma samples at room temperature, can be considered as suitable for oral anticoagulation control.


Lower-limb performance disparities: implications for exercise prescription in multiple sclerosis.
The purpose of this study was to examine unilateral lower-limb exercise tolerance during fixed-load cycling to quantify performance disparities of the legs. Eight individuals with relapsing-remitting multiple sclerosis (MS) and seven controls performed submaximal single-leg cycling. Individuals with MS performed significantly more work with the stronger leg than the weaker leg (stronger leg: 6.4 +/- 1.7 kJ, weaker leg: 4.7 +/- 2.5 kJ, p = 0.02). The control group displayed no statistical differences between limbs (p = 0.36). These results highlight a need for individualized exercise testing when prescribing training programs for those with MS.


Coffee consumption and risk of non-Hodgkin's lymphoma.
There is no adequate information on the carcinogenicity of coffee and, specifically, on a potential association of coffee drinking with non-Hodgkin's lymphoma. Consumption of coffee and other methylxanthine-containing beverages has been researched in a case-control study conducted in northern Italy. A total of 429 cases of incident histologically confirmed non-Hodgkin's lymphoma and 1,157 controls in hospital for acute, non-neoplastic, non-immunological, non-digestive tract diseases were interviewed during their hospital stay. Relative risk (RR) estimates and their 95% confidence intervals (CI), according to consumption of coffee and other methylxanthine-containing beverages, were derived from multiple logistic regression equations including terms for age, sex, study centre, body mass index, alcohol and smoking status. Compared with non-drinkers, the RR was 1.2 (95% CI, 0.8-1.7) for coffee drinkers. No trend in risk emerged with number of cups of coffee consumed/day (RR = 1.1 for one and three cups; RR = 1.2 for two; or RR = 0.9 for four cups/day), or duration of coffee intake (RR = 1.2 for less than 20 years; RR = 1.3 for 21-30 years; and RR = 1.1 for more than 30 years). Similarly, no significant association was observed with consumption of decaffeinated coffee (RR = 0.9) or tea (RR = 1.2). Consumption of cola was associated with a borderline risk (RR = 1.7; 95% CI 1.0-2.7). We found no association between non-Hodgkin's lymphoma and consumption of regular or decaffeinated coffee and tea.


Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts.
The existence and importance of tumor-initiating cells (TICs) have been supported by increasing evidence during the past decade. These TICs have been shown to be responsible for tumor initiation, metastasis, and drug resistance. Therefore, it is important to develop specific TIC-targeting therapy in addition to current chemotherapy strategies, which mostly focus on the bulk of non-TICs. In order to further understand the mechanism behind the malignancy of TICs, we describe a method to isolate and to characterize TICs in human sarcomas. Herein, we show a detailed protocol to generate patient-derived xenografts (PDXs) of human sarcomas and to isolate TICs by fluorescence-activated cell sorting (FACS) using human leukocyte antigen class I (HLA-1) as a negative marker. Also, we describe how to functionally characterize these TICs, including a sphere formation assay and a tumor formation assay, and to induce differentiation along mesenchymal pathways. The isolation and characterization of PDX TICs provide clues for the discovery of potential targeting therapy reagents. Moreover, increasing evidence suggests that this protocol may be further extended to isolate and characterize TICs from other types of human cancers.


Adenovirus-mediated p53 gene transfer sensitizes hepatocellular carcinoma cells to heavy-ion radiation.
The purpose of this study was to investigate whether adenovirus-mediated p53 transfer could sensitize hepatocellular carcinoma to heavy-ion irradiation. HepG2 cells were preexposed to a (12)C(6+) beam, and then infected with replication-deficient adenovirus recombinant vectors containing human wild-type p53 (AdCMV-p53) ((12)C(6+) irradiation + AdCMV-p53 infection). The survival fraction was determined by clonogenic assay. The cell cycle, cell apoptosis, and p53 expression were monitored by flow cytometric analysis. p53 expression in (12)C(6+) irradiation + AdCMV-p53 infection groups was markedly higher than that in (12)C(6+) irradiation only groups (P < 0.05), suggesting that the preexposure to the (12)C(6+) beam promoted the expression of exogenous p53 in HepG2 cells infected with AdCMV-p53 only. The G(1)-phase arrest and cell apoptosis in the (12)C(6+) irradiation + AdCMV-p53 infection groups were significantly more than those in the (12)C(6+) irradiated groups (P < 0.05). The survival fractions of the (12)C(6+) irradiation + AdCMV-p53 infection groups decreased by 30%-49% compared with those of the (12)C(6+) beam-irradiated only groups (P < 0.05). Adenovirus-mediated p53 gene transfer can promote G(1)-phase arrest and cell apoptosis, thus sensitizing hepatocellular carcinoma cells to heavy-ion irradiation.


Human assay of antimotion sickness drugs.
The present study was undertaken to improve previous testing procedures, involving the use of a slow rotation room, for assessing the efficacy of antimotion sickness drugs which had validity for groups of subjects but not for each individual in the group. Three major changes were introduced: first, the use of an incremental increase in the intensity of the stressful stimuli of constant intensity; second, a systematic distribution of placebos, rather than a random distribution, in using a modified Latin-square design; third, categorizing the responses as "inconsquential," "beneficial," and "detrimental"--the range of the "placebo responses" was doubled to define the inconsequential range and response above or below were, respectively, beneficial or detrimental. Only drugs known to have antimotion sickness effectiveness were tested and the cardinal findings can be briefly summarized: 1) The group responses were similar to the data previously reported; 2) Great individual differences in response to antimotion sickness drugs were revealed, implying that individual assessments must be made for maximal benefits; 3) The fixed-dose combination of promethazine hydrochloride and ephedrine sulfate (25 mg each) proved to be outstanding as this combination of homergic drugs clearly exhibited a suprasummation effect; and 4) A few tests were conducted using larger than usual doses and the results supported previous findings that, for a maximal beneficial effect in response to a single dose, individuals may vary both with regard to the choice of drug and the amount administered.


We Do Too Many Parathyroidectomies for Calciphylaxis.
Calciphylaxis, a disorder of dermal arteriolar calcification with a distinct predilection for patients with advanced kidney disease, remains an enigmatic condition that challenges clinicians. Observations regarding positive associations between levels of circulating parathyroid hormone (PTH) and the risk of calciphylaxis, combined with experimental data suggesting a pathogenic role of secondary hyperparathyroidism in vascular calcification, have led to the assumption that reducing PTH levels will improve the outcomes in patients with calciphylaxis. This editorial communicates the contemporary data regarding surgical parathyroidectomy as a treatment option for these patients. We raise concerns regarding the quality of available data and discuss the direction of future comparative effectiveness research in this field.


Conversion of laser-frequency noise to optical-rotation noise in cesium vapor.
We have studied the noise in the optical rotation of a linearly polarized laser beam transmitted through a spin-polarized (133)Cs vapor as a function of its frequency detuning from the optical resonance. Our measurements demonstrate the direct conversion of the laser-frequency noise into optical rotation noise by the dispersive response of the atomic vapor. We describe this noise-conversion process in terms of a simple model that can be used to optimize the performance of atomic devices, such as atomic magnetometers, that use optical rotation as their operational signal.


Preactivated thiolated poly(methacrylic acid-co-ethyl acrylate): synthesis and evaluation of mucoadhesive potential.
The study was aimed to developed and investigate a novel polymer for intestinal drug delivery with improved mucoadhesive properties. Therefore Eudragit® L 100-55 (poly(methacrylic acid-co-ethyl acrylate)) was thiolated by covalent attachment of L-cysteine. The immobilized thiol groups were preactivated by disulfide bond formation with 2-mercaptonicotinic acid. Resulting derivative (Eu-S-MNA) was investigated in terms of mucoadhesion via three different methods: tensile studies, rotating cylinder studies and rheological synergism method, as well as water-uptake capacity and cytotoxicity. Different derivatives were obtained with increasing amount of bound L-cysteine (60, 140 and 266 μmol/g polymer) and degree of preactivation (33, 45 and 51 μmol/g polymer). Tensile studies revealed a 30.5-, 35.3- and 52.2-fold rise of total work of adhesion for the preactivated polymers compared to the unmodified Eudragit. The adhesion time on the rotating cylinder was prolonged up to 17-fold in case of thiolated polymer and up to 34-fold prolonged in case of the preactivated polymer. Rheological synergism revealed remarkable interaction of all investigated modified derivatives with mucus. Further, water-uptake studies showed an over 7h continuing weight gain for the modified polymers whereat disintegration took place for the unmodified polymer within the first hour. Cell viability studies revealed no impact of modification. Accordingly, the novel preactivated thiolated Eudragit-derivative seems to be a promising excipient for intestinal drug delivery.


[Amino acid metabolism in liver tissue].
Following determination by the method of ion-exchange chromatography of free amino acids in the blood drawn from the portal and liver veins and the abdominal aorta 30 minutes after introduction of a casein suspension to rats it was found that only 50 per cent of amino acids with ramified chain are retained in the liver. Most of the other amino acids, however, become metabolized largely in the liver and it is only their insignificant part that goes into the general circulation. These data may be of use in considering problems related to the peculiarities of metabolism of amino acids with ramified chain.


Synthesis and Self-Assembly of Multistimulus-Responsive Azobenzene-Containing Diblock Copolymer through RAFT Polymerization.
This paper gathered studies on multistimulus-responsive sensing and self-assembly behavior of a novel amphiphilic diblock copolymer through a two-step reverse addition-fragmentation transfer (RAFT) polymerization technique. N-Isopropylacrylamide (NIPAM) macromolecular chain transfer agent and diblock copolymer (poly(NIPAM-b-Azo)) were discovered to have moderate thermal decomposition temperatures of 351.8 and 370.8 °C, respectively, indicating that their thermal stability was enhanced because of the azobenzene segments incorporated into the block copolymer. The diblock copolymer was determined to exhibit a lower critical solution temperature of 34.4 °C. Poly(NIPAM-b-Azo) demonstrated a higher photoisomerization rate constant (kt = 0.1295 s-1) than the Azo monomer did (kt = 0.088 s-1). When ultraviolet (UV) irradiation was applied, the intensity of fluorescence gradually increased, suggesting that UV irradiation enhanced the fluorescence of self-assembled cis-isomers of azobenzene. Morphological aggregates before and after UV irradiation are shown in scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses of the diblock copolymer. We employed photoluminescence titrations to reveal that the diblock copolymer was highly sensitive toward Ru3+ and Ba2+, as was indicated by the crown ether acting as a recognition moiety between azobenzene units. Micellar aggregates were formed in the polymer aqueous solution through dissolution; their mean diameters were approximately 205.8 and 364.6 nm at temperatures of 25.0 and 40.0 °C, respectively. Our findings contribute to research on photoresponsive and chemosensory polymer material developments.


Antioxidant treatment attenuates cytokine and chemokine levels in murine macrophages following silica exposure.
Alveolar macrophages play a key role in the development of silicosis by releasing a host of mediators, such as, cytokines and chemokines, which contribute to a complex network of interactions that result in the onset of lung injury, inflammation, and potentially fibrosis. Using a murine macrophage cell line, RAW 264.7, we exposed the cells to cristobalite-silica (35 micrograms/cm(2)) in the presence or absence of antioxidants and various modifiers of cellular antioxidant status. Treatment with dimethyl sulfoxide, extracellular glutathione, or N-acetyl-L-cysteine (NAC) decreased cristobalite-induced tumor necrosis factor (TNF)-alpha mRNA levels by 40%, 20%, and 42%, respectively. TNF-alpha protein levels were decreased by 90%, 32%, and 53%, respectively. Cristobalite-induced macrophage inflammatory protein (MIP)-2 mRNA levels were reduced by 52%, 38%, and 57%, with DMSO, GSH, and NAC treatment, respectively. Both MIP-1alpha and MIP-1beta mRNA levels were reduced at a magnitude similar to the reduction in TNF-alpha mRNA levels, whereas monocyte chemotactic protein (MCP)-1 mRNA levels were reduced at a magnitude similar to the reduction in MIP-2 mRNA levels following antioxidant treatment. These results suggests that the macrophage response to cristobalite exposure is mediated at least in part by oxidant stress.


Inhalation a significant exposure route for chlorinated organophosphate flame retardants.
Chlorinated organophosphate flame retardants (ClOPFRs) are widely used as additive flame retardants in consumer products including furniture, children's products, building materials, and textiles. Tests of indoor media in homes, offices, and other environments have shown these compounds are released from products and have become ubiquitous indoor pollutants. In house dust samples from Washington State, U.S.A., ClOPFRs were the flame retardants detected in the highest concentrations. Two ClOPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP or TDCIPP) and tris(2-chloroethyl)phosphate (TCEP), have been designated as carcinogens, and there is growing concern about the toxicity of the homologue tris(1-chloro-2-propyl)phosphate (TCPP or TCIPP). In response to concerns about exposure to these compounds, the European Union and a number of U.S. states have taken regulatory action to restrict their use in certain product categories. To better characterize exposure to ClOPFRs, inhalation exposure was assessed using active personal air samplers in Washington State with both respirable and inhalable particulate fractions collected to assess the likelihood particles penetrate deep into the lungs. Concentrations of ∑ClOPFRs (respirable and inhalable) ranged from 97.1 to 1190 ng m(-3) (mean 426 ng m(-3)), with TCPP detected at the highest concentrations. In general, higher levels were detected in the inhalable particulate fraction. Total intake of ClOPFRs via the inhalation exposure route was estimated to exceed intake via dust ingestion, indicating that inhalation is an important route that should be taken into consideration in assessments of these compounds.


Ocular pathology in disialotransferrin developmental deficiency syndrome.
Disialotransferrin developmental deficiency (DDD) syndrome is a recently described disease consisting of hepatopathy, mental retardation and neuropathy. The biochemical findings indicate a defect in the assembly of the carbohydrate moiety that is common to the secretory glucoproteins. It is believed to be of autosomal recessive inheritance. An ophthalmological examination of ten children suffering from this syndrome showed that all had ocular involvement. Esotropia (and deficient abduction) was found in all ten patients. Seven children had retinitis pigmentosa which was verified by an ERG in three. One patient had retinal signs suggestive of retinitis pigmentosa. The high incidence of ocular findings in the DDD syndrome, which are reported for the first time, indicate that an ophthalmological examination is a helpful diagnostic tool in this disease.


Body mass index, midwifery intrapartum care, and childbirth lacerations.
Weight status is an important determinant of many health indices. Data from a clinical trial on measures to lower genital tract trauma in vaginal birth were used for a secondary analysis. The goal was to describe the relationship of body mass index and pregnancy weight gain to clinical intrapartum care, infant birthweight, and genital tract trauma with vaginal birth. Intrapartum care measures and labor events did not vary by maternal weight status. Overweight and obese women were more likely to be parous, and Hispanic or American Indian. Total pregnancy weight gain decreased, and infant birthweight increased as body mass index category increased. Obese women who gained 40 or more pounds during pregnancy had elevated rates of macrosomia and genital tract lacerations.


Non-pharmacological measures in preterm newborns submitted to arterial puncture.
to assess pain in preterm newborns and to compare the neonatal and therapeutic variables with the total scores of the Neonatal Facial Coding System of preterm newborns submitted to arterial puncture exposed to music and 25% oral glucose. a comparative study with 48 recordings of preterm newborns - Group 1, music (26); Group 2, glucose 25% (22) - individually analyzed by three trained nurses, after Kappa of at least 80%. the variables and the pain scores of the groups did not present statistical significance (p < 0.05) according to the Neonatal Facial Coding System. 80.8% of the preterm infants in Group 1 had a higher quantitative score ≥ 3 in the neonatal variables (gender, type of delivery), and therapeutic variables (type of oxygen therapy, place of hospitalization, type of puncture). There was no difference when comparing the music and glucose 25% groups and the variables studied.