ZNF307, a novel zinc finger gene suppresses p53 and p21 pathway.
We have cloned a novel KRAB-related zinc finger gene, ZNF307, encoding a protein of 545aa. ZNF307 is conserved across species in evolution and is differentially expressed in human adult and fetal tissues. The fusion protein of EGFP-ZNF307 localizes in the nucleus. Transcriptional activity assays show ZNF307 suppresses transcriptional activity of L8G5-luciferase. Overexpressing ZNF307 in different cell lines also inhibits the transcriptional activities of p53 and p21. Moreover, ZNF307 works by reducing the p53 protein level and p53 protein reduction is achieved by increasing transcription of MDM2 and EP300. ZNF307 might suppress p53-p21 pathway through activating MDM2 and EP300 expression and inducing p53 degradation.


Effects of Sustained Otolith-Only Stimulation on Post-Rotational Nystagmus.
Constant velocity rotations in darkness evoke vestibulo-ocular reflex in form of pre- and post-rotational nystagmus under cerebellar supervision. Reorientation of the head with respect to gravity, stimulating otolith and semicircular canal, during post-rotational phase rapidly suppresses the post-rotational nystagmus. We asked if pure otolith stimulation without semicircular canal signal is sufficient for the suppression of post-rotational nystagmus. The experimental paradigm comprised of on-axis rotations in the horizontal plane when the subject was sitting upright, followed by a novel stimulus that combined off-axis centrifugation in the horizontal plane with amplitude matched, yet out-of-phase, on-axis horizontal rotation-double centrifugation. The resultant effect of double centrifugation was pure otolith stimulation that constantly changed direction, yet completely canceled out angular velocity (no horizontal semicircular canal stimulation). Double centrifugation without pre-existing on-axis rotations evoked mixture of horizontal and vertical eye movements, latter reflected the known uncertainty of the vestibular system to differentiate whether the sensory signal is related to low-frequency translations in horizontal plane or head tilts relative to the gravity. Double centrifugation during post-rotational phase suppressed the peak slow phase eye velocity of the post-rotational nystagmus, hence affecting the vestibular ocular reflex gain (eye velocity/head velocity) matrix. The decay time constant, however, was unchanged. Amount of suppression of the peak slow phase eye velocity of the post-rotational nystagmus during double centrifugation correlated with the peak vertical eye velocity evoked by the pure otolith stimuli in the absence of pre-existing on axis rotations. In post-rotational phase, the pure otolith signal affects vestibular ocular reflex gain matrix but does not affect the time constant.


Formation of donor-specific human leukocyte antigen antibodies after kidney transplantation: correlation with acute rejection and tapering of immunosuppression.
Before kidney transplantation, a serological crossmatch is routinely performed between donor and recipient to prevent hyperacute rejection by donor-specific anti-human leukocyte antigen (HLA) antibodies. After transplantation, the presence of these antibodies is not routinely monitored. We wanted to know whether donor-specific anti-HLA antibodies are detectable during acute rejection (AR), before or after reduction of immunosuppression in kidney transplant recipients who were converted from cyclosporine A (CsA) to the less nephrotoxic azathioprine (AZA) or mycophenolate mofetil (MMF) at 1 year after transplantation. Plasma samples were collected before transplantation, at several time points after transplantation, and during AR. Antibodies were measured in 29 patients: 5 patients with AR during the first year after transplantation (before conversion), 14 patients with AR after conversion or dose-reduction of AZA or MMF, and a control group of 10 patients without AR during a follow-up of 2 years (1 year before and 1 year after conversion of immunosuppression). Antibodies were measured by complement-dependent cytotoxicity assay, enzyme-linked immunosorbent assay (ELISA), and flow-cytometry in a crossmatch with donor spleen cells. Donor-specific antibodies were not detectable after transplantation in the control group without AR, nor in patients with AR shortly after transplantation during CsA therapy. After conversion from CsA to AZA or MMF, antibodies appeared only in one patient after graft failure followed by transplantectomy and in patients during AR on AZA but not on MMF therapy. In this patient group, we could not detect donor-specific antibodies during CsA treatment, not even at the time of AR using three different techniques. Donor-specific antibodies were primarily present during AR in patients converted from CsA to AZA and were not found in the sera from patients converted to MMF.


Distinctions between pituicytoma and ordinary pilocytic astrocytoma. Case report.
The authors present a rare case of pituicytoma. A dynamic magnetic resonance study performed after Gd injection revealed a markedly, homogeneously enhanced, early-phase pituitary lesion in a 32-year-old woman with a 1-year history of amenorrhea. The tumor bled easily during transsphenoidal resection. The lesion consisted of plump spindle cells and lacked Rosenthal fibers and granular bodies, and thus was different from ordinary pilocytic astrocytoma or any other form of this tumor. Although pituicytoma is often confused with pilocytic astrocytoma when it appears in the sellar region, these two kinds of gliomas should be distinguished on the basis of histological differences.


N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction.
Atrial natriuretic factor (ANF) is a peptide hormone secreted from cardiac atria in response to increased atrial pressure. Because of a longer half-life and greater stability, the N-terminal of ANF prohormone (N-terminal proANF) may be a better integrator of atrial peptide secretion than ANF itself. After myocardial infarction, elevation of ANF and other neurohormones has been associated with a poor prognosis. However, when left ventricular ejection fraction (LVEF) and other important clinical variables are included in multivariate analysis, the independent predictive value of these neurohormones has been reduced markedly. To test the prognostic value of N-terminal proANF after myocardial infarction, its plasma concentration was measured a mean of 12 days after infarction in 246 patients in the Survival and Ventricular Enlargement (SAVE) Study. N-terminal proANF was a much stronger predictor of survival than ANF itself. Furthermore, in multivariate analysis of cardiovascular mortality and development of heart failure, N-terminal proANF in contrast to ANF and other neurohormones was still a powerful and independent predictor when the model included age, gender, prior myocardial infarction, hypertension, diabetes, use of thrombolysis, Killip class, infarct location, and LVEF. The measurement of N-terminal proANF supplements presently used clinical and objective assessments and provides an important independent predictor of prognosis with respect to cardiovascular mortality and development of heart failure.


[Psychodermatology: a collaboration between psychiatry and dermatology].
Dermatology is of special importance in consultation-liaison practice. The brain and the skin originate from the same germ layer, the ectoderm, in the embryo. In later periods of life, the various ways these two organs influence each other has been the subject of many studies published in this field. These studies are divided into three groups: 1- studies about stress and dermatologic diseases, 2- psychoanalytic and psychodynamic approaches to psychodermatologic diseases, and 3- clinical research and treatment of psychodermatologic diseases. Recently, in some countries which are aware of the importance of the subject, in the psychodermatology section psychiatrists, dermatologists, psychologists and residents work together as a team. In fact, it has been already accepted that there is a need for association between psychiatry and dermatology in many cases. This association between the two disciplines aims to enhance the success of therapy and psychiatric support for patients who primarily have psychiatric disease, but project that as a dermatologic disease, on the one hand. On the other hand, it provides a more holistic, and satisfying approach for both doctors and patients having primarily dermatologic disease, but who develop psychiatric problems secondarily. In this article, psychodermatology investigations and the relationship between the skin and psyche, diseases discussed in this context, and overlapping areas of psychiatry and dermatology are reviewed, and it is aimed to attract attention to this topic.


Pregnancy and thrombosis: Adrenal vein thrombosis. A retrospective descriptive study of 14 cases.
Adrenal vein thrombosis during pregnancy is a rare thromboembolic event but is not exceptional. The objective of this study was to described the symptoms, diagnosis, treatment and follow-up of patients with this condition. This was a retrospective descriptive study of 14 cases (13 patients, one recurrence) that occurred in the three university maternity hospitals in Lyon (France) from 2008 to 2016. Adrenal vein thrombosis occurred exclusively in the third trimester (gestational age > 28 weeks), with most patients presenting unilateral lumbar pain (13/14 cases, 93%) and vomiting (8 cases, 57%), mimicking renal colic. To establish the diagnosis, all patients were examined by abdominal CT and all but three (79%) by abdominal ultrasonography. Ten patients (71%) were treated by low molecular weight heparin and the remaining four (29%) by unfractionated heparin. The delay between presentation and diagnosis, and thus before treatment was initiated, was greater than 24 h in 50% of cases. Thrombosis occurred predominantly (11 vs 3 cases) on the right adrenal vein. Labor inducing or cervical ripening agents were used after temporarily interrupting treatment for 9/14 patients (64%). Epidural anesthesia was possible for 11 patients (79%) and 2 (14%) had postpartum hemorrhage. Eleven patients received hemostatic function investigations with anomalies detected in four cases (36%). One of the six patients (16%) who had a second full-term pregnancy during the study period had a contralateral recurrence. Adrenal vein thromboses are rare events requiring curative anticoagulant therapy and labor management to minimize the risk of hemorrhage. Patients should receive thromboprophylaxis for subsequent pregnancies and a full thrombophilia investigation.


vilanterol + fluticasone (RELVAR Ellipta). Asthma and COPD: yet another beta-2 agonist and corticosteroid combination.
As expected, the vilanterol + fluticasone combination increases the risk of pneumonia in patients with COPD.


Enhancement of production of superoxide anion by human monocytes exposed to products of HT 29 human colonic adenocarcinoma cell line.
The generation of superoxide anion (O2-) by human blood monocytes in response to stimulation by either phorbol myristate acetate (PMA) or opsonized Zymosan was greatly enhanced (range: 100-200% according to donor) by prior exposure of the peripheral blood mononuclear cells (PBM) to human colonic adenocarcinoma cells (HT 29 line) or their conditioned culture medium (DMEM-HT 29). This priming effect was observed after 5 hr and persisted for up to 15 hr of contact between PBM and endotoxin-free DMEM-HT 29. Beyond this time, primed monocytes gradually lost this ability. However, they maintained a higher capacity (about 100%) to produce O2- when compared to controls. DMEM-HT 29-induced monocyte priming requires that the tumor-active substance(s) act(s) on 2 target cells: first, on non adherent mononuclear cells (NA-PBM) to induce cytokine production and, second, on the monocyte itself. Priming activity was also found in conditioned medium from FR3T3 embryonic fibroblasts but not in conditioned medium from HT 29 repolarized cells (by culture in glucose-free medium) or from non-tumorous human colonic mucosa explants.


Classic identity negative priming involves accessing semantic representations in the left anterior temporal cortex.
Classic identity negative priming (NP) refers to the finding that when an object is ignored, subsequent naming responses to it are slower than when it has not been previously ignored (Tipper, S.P., 1985. The negative priming effect: inhibitory priming by ignored objects. Q. J. Exp. Psychol. 37A, 571-590). It is unclear whether this phenomenon arises due to the involvement of abstract semantic representations that the ignored object accesses automatically. Contemporary connectionist models propose a key role for the anterior temporal cortex in the representation of abstract semantic knowledge (e.g., McClelland, J.L., Rogers, T.T., 2003. The parallel distributed processing approach to semantic cognition. Nat. Rev. Neurosci. 4, 310-322), suggesting that this region should be involved during performance of the classic identity NP task if it involves semantic access. Using high-field (4 T) event-related functional magnetic resonance imaging, we observed increased BOLD responses in the left anterolateral temporal cortex including the temporal pole that was directly related to the magnitude of each individual's NP effect, supporting a semantic locus. Additional signal increases were observed in the supplementary eye fields (SEF) and left inferior parietal lobule (IPL).


Oncostatin M binds directly to gp130 and behaves as interleukin-6 antagonist on a cell line expressing gp130 but lacking functional oncostatin M receptors.
Oncostatin M (OM) and interleukin 6 (IL-6) are functionally related cytokines, which trigger similar biological responses because they share gp130 as a common signal transducing transmembrane receptor. While IL-6 recruits gp130 only upon binding to its specific receptor subunit (IL-6R alpha), reconstitution and cross-linking experiments on cell membranes suggest that OM can directly interact with gp130 and that this interaction is necessary but not sufficient to stimulate cells. However, the issue of the direct binding between gp130 and OM, in the absence of any additional membrane component, remained essentially unclarified. In this paper we show that, uniquely among the family of cytokines that transduce through gp130, OM directly binds in vitro with a 10(-8) M affinity sgp130, a soluble form of gp130. Moreover, titration of sgp130 with OM inhibits the formation of a ternary complex comprising IL-6, sIL-6R alpha, and sgp130. These in vitro properties of OM are consistent with the additional finding that on human hepatoma Hep3B cells, which express gp130 but not functional OM receptors, OM does not mimic IL-6 activity, but rather behaves, at high doses, as an IL-6 antagonist.


Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations.
Autoimmune thyroid disease (AITD) including Graves' disease, Hashimoto's thyroiditis, and idiopathic hypothyroidism (atrophic Hashimoto's thyroiditis) is of vital concern to the dermatologist. This article reviews the cutaneous manifestations of Graves' disease and Hashimoto's thyroiditis. Recognition of dermatologic manifestations of AITD may alert practitioners to investigate for these disorders. The immune response involved in the pathogenesis of AITD is detailed. Current understanding of the role of genetic and environmental factors, antigens, and apoptosis are elaborated. The future holds exciting insight into the etiology, pathogenesis, and treatment of AITD.


Antioxidant profile of nimesulide, indomethacin and diclofenac in phosphatidylcholine liposomes (PCL) as membrane model.
An in vitro assay based on the oxidation of phosphatidylcholine liposomes (PCL) with which we can distinguish the anti-HO zero activity from the antilipoperoxidant (R zero, ROO zero, RO zero) has been developed for testing the free-radical-scavenging ability of antiinflammatory drugs. PCL were exposed to a flux of hydroxyl radicals generated by water sonolysis for different periods, and the spontaneous lipid peroxidative phenomenon (propagation and breakdown phases) was followed for the subsequent 24 hours. Lipid peroxidation was assayed by simultaneous measurements of a) conjugated dienes, by UV spectroscopy (absorbance and second derivative at 233 nm), b) loss of lipid substrate (PC), by HPLC, and c) breakdown products (total carbonyl functions as 2,4-dinitrophenylhydrazones). Diclofenac, nimesulide and indomethacin, added to PCL at the starting of the different stages of lipid peroxidation, were tested for their overall and specific anti-radical properties. All the drugs exhibited a remarkable scavenging activity against oxy and lipid radicals, determined as percent inhibition of the formation of conjugated dienes, at concentrations easily attainable in vivo (IC50:diclofenac 2.5 microM, nimesulide 4.92 microM, indomethacin 6.85 microM), diclofenac being the most effective in quenching the R zero and ROO degree species responsible for the propagation phase. By contrast, the antioxidant activity of nimesulide and indomethacin, less potent as alkyl and peroxyl radical scavengers, is due to their ability to restrain the induction phase of the radical chain reaction mediated by hydroxyl radicals (IC50:nimesulide 1.85 microM, indomethacin 3.57 microM).


Porcine deltacoronavirus (PDCoV) modulates calcium influx to favor viral replication.
Ionic calcium (Ca2+) is a versatile intracellular second messenger that plays important roles in cellular physiological and pathological processes. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus that causes serious vomiting and diarrhea in suckling piglets. In this study, the role of Ca2+ to PDCoV infection was investigated. PDCoV infection was found to upregulate intracellular Ca2+ concentrations of IPI-2I cells. Chelating extracellular Ca2+ by EGTA inhibited PDCoV replication, and this inhibitory effect was overcome by replenishment with CaCl2. Treatment with Ca2+ channel blockers, particularly the L-type Ca2+ channel blocker diltiazem hydrochloride, inhibited PDCoV infection significantly. Mechanistically, diltiazem hydrochloride reduces PDCoV infection by inhibiting the replication step of the viral replication cycle. Additionally, knockdown of CACNA1S, the L-type Ca2+ voltage-gated channel subunit, inhibited PDCoV replication. The combined results demonstrate that PDCoV modulates calcium influx to favor its replication.


Neural cell adhesion molecule (N-CAM) in fetal and mature human heart.
Using Northern blot analysis and immunoblotting techniques we report for the first time, that the neural cell adhesion molecule, N-CAM, is expressed in human heart. We found several different N-CAM transcripts in human fetal (13-17 weeks gestation) and mature heart (left ventricle from a 5-year-old child). Northern blotting showed that a 5.2 kb transcript was the most abundant and progressively increased with age, both in fetal and mature heart. These transcripts may correspond with the different protein isoforms shown by immunoblotting. We also confirmed the presence of N-CAM in fetal and mature myocytes by immunohistochemical techniques, using a monoclonal antibody to human N-CAM. Results demonstrated that N-CAM is mainly confined to the myocyte cell surface.


Synthesis of a nickel tetracarboranylphenylporphyrin for boron neutron-capture therapy: biodistribution and toxicity in tumor-bearing mice.
Nickel-2,3,7,8,12,13,17,18-octaacetic acid-5,10,15,20-tetra-[3-carboranyl-methoxyphenyl]-porphyrin octamethylester (NiTCP) was given in a Cremophor EL, a polyethoxylated castor oil, and propylene glycol emulsion to BALB/c mice bearing transplanted s.c. KHJJ mammary carcinomas. A total dose of 244 microg NiTCP/gram body weight (gbw) (54 microg B/gbw) was given in 6 i.p. injections over a 32 hr period. Observations of behavior and changes in body weight and chemical and hematological blood tests indicated little or no toxicity from NiTCP over a period of 6-90 hr after injections. Boron concentrations near tumor margins were 160-180 microg B/g at 41-90 hr after the last injection. Tumor:normal brain boron concentration ratios reached approx. 10:1 and tumor:blood ratios reached approx. 250:1 after 4 days. There was no evidence of thrombocytopenia or other potentially important toxicities. Our findings place NiTCP among the leading candidates for pre-clinical experiments aimed toward improvement upon the compounds being tested for boron neutron-capture therapy of glioblastoma multiforme.


Attenuated Heart Rate Recovery After Exercise Testing and Risk of Incident Hypertension in Men.
Although attenuated heart rate recovery (HRR) and reduced heart rate (HR) reserve to maximal exercise testing are associated with adverse cardiovascular outcomes, their relation to incident hypertension in healthy normotensive populations is unclear. We examined the hypothesis that both attenuated HRR and reduced HR reserve to exercise testing are associated with incident hypertension in men. A total of 1,855 participants were selected comprising of healthy, initially normotensive men who underwent peak or symptom-limited treadmill testing at baseline. HRR was calculated as the difference between peak HR during exercise testing and the HR at 2 minutes after exercise cessation. HR reserve was calculated as the percentage of HR reserve (peak HR - resting HR)/(220 - age - resting HR) × 100. During an average 4-year follow-up, 179 (9.6%) men developed hypertension. Incident hypertension was associated with HRR quartiles (Q1 (<42 (bpm)) 12.5%, Q2 (43-49 bpm) 8.5%, Q3 (50-56 bpm) 9.3%, and Q4 (>57 bpm) 8.3%; P = 0.05 for trend). The relative risk (RR) of the incident hypertension in the slowest HRR quartile vs. the fastest HRR quartile was 1.78 (95% confidence interval (CI): 1.14-2.78) after adjustment for confounders. Every 1 bpm increment in HRR was associated with a 2% (RR 0.98, 95% CI: 0.97-0.99) lower risk of incident hypertension after adjusting for potential confounders. In contrast, reduced HR reserve did not predict the risk of incident hypertension. Slow HRR after exercise testing is independently associated with the development of hypertension in healthy normotensive men.


[Metabolic and regulatory function of fatty acid synthase].
Fatty acid synthase (FAS)--enzyme present in many tissues, catalyses synthesis of palmitate from malonyl-CoA, acetyl-CoA and NADPH. The highest activity of FAS was found in lipogenic tissues (liver, adipose tissue) and in mammary gland during lactation. Palmitate serves as a substrate for synthesis of saturated and unsaturated long chain fatty acids. In turn, fatty acids (including palmitate) are substrates for the synthesis of triacylglycerols (mainly in liver and adipose tissue), membrane lipids and lipids which play a regulatory role. In this review we discuss the structure, regulation and role of FAS in lipogenic tissues. Moreover, this review presents the recently postulated role of FAS in: a) synthesis of natural ligands of PPARalpha; b) feeding behavior; c) endothelial NO production; d) protection of cardiomiocytes from pathological calcium influx; and e) diet induced atherosclerosis. Finally, the role of FAS in the growth of malignant cells is discussed.


Reactive arthritis associated with group C and group G beta-hemolytic streptococci.
Group A beta-hemolytic streptococci (GAS) are known to be capable of evoking sterile arthritis. Reactive arthritis (ReA) has been reported sporadically following primary infection with group C and group G beta-hemolytic streptococci (GCS, GGS). We prospectively studied 4 cases of ReA secondary to throat infection with GCS and GGS. Four patients with arthritis secondary to throat infection were seen. Three patients were Dutch, one was Indonesian; female/male ratio was 1/3; mean age was 30 years (range 18-46). Diagnostic evaluation included culture of throat swab and serological screening. All patients presented with a nonmigratory asymmetrical arthritis: monoarthritis in one patient, oligoarthritis in 3. Culture of throat swab was positive in all. Antistreptolysin-O (ASO) titer rose significantly in 2 patients, and anti-DNase-B rose in 2 patients. ASO was maximal (mean 1000 U/ml; range 890-1110) and anti-DNase-B was 395 U/ml (range 290-500). Treatment consisted of feneticillin for 5 days; nonsteroidal antiinflammatory drugs were prescribed on demand. All patients recovered fully in 3 to 12 weeks. These cases provide evidence of a benign non-group A streptococcal ReA, i.e., secondary to GCS or GGS. The presence of the organism in the throat along with the elevation of antibody to streptococcal products is important for the diagnosis of GCS/GGS associated ReA. A positive throat culture is needed for differentiation from GAS associated poststreptococcal ReA, because prophylactic measures are effective only in GAS associated sequelae, but not in GCS/GGS associated ReA.


Diagnostic efficacy of contrast-enhanced sonography by combined qualitative and quantitative analysis in breast lesions: a comparative study with magnetic resonance imaging.
The purpose of this study was to evaluate the diagnostic efficacy of contrast-enhanced sonography for differentiation of breast lesions by combined qualitative and quantitative analyses in comparison to magnetic resonance imaging (MRI). Fifty-six patients with American College of Radiology Breast Imaging Reporting and Data System category 3 to 5 breast lesions on conventional sonography were evaluated by contrast-enhanced sonography and MRI. A comparative analysis of diagnostic results between contrast-enhanced sonography and MRI was conducted in light of the pathologic findings. Pathologic analysis showed 26 benign and 30 malignant lesions. The predominant enhancement patterns of the benign lesions on contrast-enhanced sonography were homogeneous, centrifugal, and isoenhancement or hypoenhancement, whereas the patterns of the malignant lesions were mainly heterogeneous, centripetal, and hyperenhancement. The detection rates for perfusion defects and peripheral radial vessels in the malignant group were much higher than those in the benign group (P < .05). As to quantitative analysis, statistically significant differences were found in peak and time-to-peak values between the groups (P < .05). With pathologic findings as the reference standard, the sensitivity, specificity, and accuracy of contrast-enhanced sonography and MRI were 90.0%, 92.3%, 91.1% and 96.7%, 88.5%, and 92.9%, respectively. The two methods had a concordant rate of 87.5% (49 of 56), and the concordance test gave a value of κ = 0.75, indicating that there was high concordance in breast lesion assessment between the two diagnostic modalities. Contrast-enhanced sonography provided typical enhancement patterns and valuable quantitative parameters, which showed good agreement with MRI in diagnostic efficacy and may potentially improve characterization of breast lesions.


The uncoupling effect of flavoglaucin, a quinol pigment from Aspergillus chevalieri (Mangin), on mitochondrial respiration.
The effects of flavoglaucin from Aspergillus chevalieri (Mangin) Thom et Church on mitochondrial reactions have been investigated to obtain insight into the mode of actions on biomembranes by means of isolated rat liver mitochondria. It was found that flavoglaucin exhibited a strong uncoupling effect on oxidative phosphorylation, enhanced the latent ATPase activity, and elicited a drastic swelling of mitochondria. These reactions led to the exhaustion of ATP in cells, which may be, in part, responsible for its cytotoxicity. Flavoglaucin was toxic to isolated rat hepatocytes causing a karyoklasis, but did not show genotoxicity in hepatocyte primary culture (HPC)/DNA repair test.


Old age affects gaze and postural coordination.
Visual tracking of the surrounding environment is an important daily task, often executed simultaneously with the regulation of upright balance. Visual and postural coordination may be affected by aging which is associated with a decline in sensory and motor functions. The aim of the present study was to assess the effects of aging on the control of saccadic and smooth pursuit eye movements when standing on a moving surface. Nineteen young and 12 elderly subjects tracked a visual target presented as unpredictable smooth pursuit or saccadic displacements. Subjects were instructed to maintain gaze on target during quiet stance with or without yaw surface rotations. Elderly subjects followed both saccadic and pursuit targets with less accuracy than young subjects. Moreover, elderly subjects responded with longer time lags during saccadic target shifts and executed more catch-up saccades during smooth pursuits than younger subjects. Standing on a moving surface induced larger target-gaze errors. Catch-up saccades during pursuit occurred more frequently during surface perturbations. Our results suggest that visual tracking abilities decline with age and that postural challenge affects accuracy but not timing of gaze responses. Such declines observed with aging may result from multiple but minor sensory and motor deficits.


Effect of bovine lactoferrin on the internalization of coagulase-negative staphylococci into bovine mammary epithelial cells under in-vitro conditions.
Coagulase-negative staphylococci (CNS) have emerged as bovine mastitis pathogens in many countries. CNS mastitis is generally mild but can persist in the udder for long periods. Pathogenesis of CNS intramammary infection is not well understood. In the present study, adhesion, invasion and intracellular replication of twenty-two CNS strains isolated from bovine mastitis and the effect of bovine lactoferrin (bLf) on the internalization were studied in vitro in a bovine mammary epithelial (BME) cell model. The CNS strains were of Staphylococcus chromogenes, Staph. simulans, Staph. epidermidis, Staph. haemolyticus and Staph. cohnii urealyticus; two strains of Staph. aureus were used as controls. Seven of the CNS strains originated from persistent and five from transient mastitis infections. The in-vitro susceptibility of the strains to bLf was also investigated. All CNS species examined had an adhesive ability equal to that of Staph. aureus, but internalization varied among staphylococcal strains. The antagonistic effect of bLf on the adhesion and invasion of CNS strains was weak, but bLf significantly decreased intracellular replication and replication rates of CNS. No correlation between the in-vitro susceptibility of the strain to bLf or internalization among clinical signs of mastitis was established. No difference between the persistent and transient CNS strains in adhesion, invasion or replication rate was recorded. This in-vitro BME cell model can be used to study the virulence potential of mastitis pathogens, although the severity and persistence of eventual infections shall be further investigated in vivo. The role of bLf in intramammary infection caused by CNS may be limited.


A study of migraine characteristics in joint hypermobility syndrome a.k.a. Ehlers-Danlos syndrome, hypermobility type.
Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associated with musculoskeletal pain, fatigue and headache. Migraine with or without aura is considered the most common form of headache in JHS/EDS-HT. In this population of chronically ill patients, we investigated whether migraine characteristics were different from those of a control population of migraine patients. The study was carried out on 33 selected JHS/EDS-HT patients, diagnosed according to current criteria. Sixty-six migraine subjects matching age and gender were consecutively selected as controls (MO group) among patients attending our Headache Clinic. JHS/EDS-HT and MO were screened for a series of headache characteristics, such as frequency, intensity, age of onset, level of disability, use of rescue and prophylactic medications. Differences between the two groups were tested by using independent group comparisons. Results showed that in JHS/EDS-HT: (1) migraine has an earlier onset (12.6 vs 17 years of age; p = 0.005); (2) the rate of migraine days/month is higher (15 vs 9.3 days/month; p = 0.01); (3) accompanying symptoms are usually more frequent; (4) HIT-6 and MIDAS scores are higher (p = 0.04 and p = 0.03); (5) efficacy of rescue medication is almost identical, although, total drug consumption is significantly lower (p < 0.04). Joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type patients have a more severe headache syndrome with respect to the MO group, therefore demonstrating that migraine has a very high impact on quality of life in this disease.


Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection.
Rare individuals have been multiply exposed to HIV-1 but remain uninfected. The CD4+ T-cells of two of these individuals, designated EU2 and EU3, are highly resistant in vitro to the entry of primary macrophagetropic virus but are readily infectable with transformed T-cell line adapted viruses. We report here on the genetic basis of this resistance. We found that EU2 and EU3 have a homozygous defect in CKR-5, the gene encoding the recently described coreceptor for primary HIV-1 isolates. These individuals appear to have inherited a defective CKR-5 allele that contains an internal 32 base pair deletion. The encoded protein is severely truncated and cannot be detected at the cell surface. Surprisingly, this defect has no obvious phenotype in the affected individuals. Thus, a CKR-5 allele present in the human population appears to protect homozygous individuals from sexual transmission of HIV-1. Heterozygous individuals are quite common (approximately 20%) in some populations. These findings indicate the importance of CKR-5 in HIV-1 transmission and suggest that targeting the HIV-1-CKR-5 interaction may provide a means of preventing or slowing disease progression.


The motion-induced position shift depends on the perceived direction of bistable quartet motion.
Motion can influence the perceived position of nearby stationary objects (Nature Neuroscience 3 (2000) 954). To investigate the influence of high-level motion processes on the position shift while controlling for low-level motion signals, we measured the position shift as a function of the motion seen in a bistable quartet. In this stimulus, motion can be seen along either one or the other of two possible paths. An illusory position shift was observed only when the flashes were adjacent to the path where motion was perceived. If the flash was adjacent to the other path, where no motion was perceived, there was no illusory displacement. Thus for the same physical stimulus, a change in the perceived motion path determined the location where illusory position shifts would be seen. This result indicates that high-level motion processes alone are sufficient to produce the position shift of stationary objects. The effect of the timing of the test flash between the onset and offset of the motion was also examined. The position shifts were greatest at the onset of motion, then decreasing gradually, disappearing at the offset of motion. We propose an attentional repulsion explanation for the shift effect.


Mechanism of clobazam-induced thyroidal oncogenesis in male rats.
In order to elucidate the mechanisms by which long-term treatment with clobazam (CLB), 1,5-benzodiazepine, induces thyroid follicular cell tumors in male rats, male Sprague-Dawley (SD) rats were treated orally with 400 mg/kg of CLB for up to 4 weeks, and the contribution of feedback through elevated thyroid stimulating hormone (TSH) was investigated. Measurements taken after 1, 2, and 4 weeks of treatment revealed that thyroxine (T4)-UDP-glucuronosyltransferase (T4-UDPGT) activity was higher than that of untreated animals. This change was accompanied by increase in liver weights and centrilobular hepatocyte hypertrophy. In addition, plasma total triiodothyronine (T3) and T4 levels were lower than in the untreated rats when measured after 1 week of treatment. However, a high plasma TSH level was sustained throughout the 4-week treatment. Thyroid follicular cell hypertrophy began after 1 week of treatment, followed by increased thyroid weight after 2 weeks. Clearance of exogenous [125I] T4 from the blood of treated rats, determined after 4 weeks of treatment, was significantly faster than that in untreated rats, whereas iodine uptake and organification in the thyroid glands were not affected. These results suggest that CLB increases hepatic T4-UDPGT activity leading to acceleration of T4-clearance, which results in decreased plasma thyroidal hormones followed by compensatory increase of TSH biosynthesis and secretion. Chronic high levels of TSH would exert a continuous growth pressure on the thyroid, under which hypertrophic follicular cells can ultimately progress to frank neoplasms.


Plasma cholinesterase activity in bank blood.
Plasma cholinesterase activity was periodically measured in bank blood. Of the initial plasma cholinesterase activity 87% was retained after 21 days of storage at 4 C in citrate-phosphate-dextrose solution. In addition, plasma frozen for 7 weeks at -70 C showed no decrease in enzyme activity. No difference could be demonstrated in the stability of the enzyme related to whether the blood was stored in citrate-phosphate-dextrose or in acid-citrate-dextrose solution. Bank blood transfusion prior to or during succinylcholine administration should not significantly alter the duration of action of succinylcholine, and would probably be effective in the management of prolonged apnea resulting from a deficiency of this enzyme.


A simulation tool for brassiness studies.
A frequency-domain numerical model of brass instrument sound production is proposed as a tool to predict their brassiness, defined as the rate of spectral enrichment with increasing dynamic level. It is based on generalized Burger's equations dedicated to weakly nonlinear wave propagation in nonuniform ducts, and is an extension of previous work by Menguy and Gilbert [Acta Acustica 86, 798-810 (2000)], initially limited to short cylindrical tubes. The relevance of the present tool is evaluated by carrying out simulations over distances longer than typical shock formation distances, and by doing preliminary simulations of periodic regimes in a typical brass trombone bore geometry.


[A case of myonephropathic metabolic syndrome treated with limb washout using a roller pump and cell saver].
We operated on a 65 year old male for the saddle embolism presenting the signs of MNMS. Before the reperfusion of the ischemic limbs which were successfully embolectomized with the use of Fogarty catheter, we performed limb washout using roller pump and cell saver. The washout was done in the high flow and large volume by the roller pump. The red blood cells in the efflux were saved using cell saver and retransfused to the patient. The patient recovered without deterioration of MNMS. The limb washout was effective for the prevention of the deterioration of MNMS.


Public health nursing, ethics and human rights.
Public health nursing has a code of ethics that guides practice. This includes the American Nurses Association Code of Ethics for Nurses, Principles of the Ethical Practice of Public Health, and the Scope and Standards of Public Health Nursing. Human rights and Rights-based care in public health nursing practice are relatively new. They reflect human rights principles as outlined in the Universal Declaration of Human Rights and applied to public health practice. As our health care system is restructured and there are new advances in technology and genetics, a focus on providing care that is ethical and respects human rights is needed. Public health nurses can be in the forefront of providing care that reflects an ethical base and a rights-based approach to practice with populations.


The polymerase chain reaction and cancer diagnostics.
In this review, I describe the polymerase chain reaction (PCR) and its application to cancer diagnostics. I present recent improvements to PCR methodology, and describe some state-of-the-art detection methods and approaches used to diagnose various cancer markers, including ras genes, BCR/abl translocations, and G-proteins.


Hypersensitivity to tartrazine (FD&C Yellow No. 5) and other dyes and additives present in foods and pharmaceutical products.
Tartrazine (FD&C Yellow No. 5) and other allowed certified color additives may have an exacerbating effect in chronic urticaria and asthma sufferers. In the individual patient the only way to determine their relevance is to administer test doses. By altering doses, timing and substances and by interspacing controls a battery of tests has been developed. Methods of testing for sensitization to food additives and analgesics are described.


An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics.
The understanding of anesthetic side effects on the heart has been hindered by the lack of sophisticated clinical models. Using micropatterned human-induced pluripotent stem cell-derived cardiomyocytes, we obtained cardiac muscle depressant profiles for propofol, etomidate, and our newly identified anesthetic compound KSEB01-S2. Propofol was the strongest depressant among the 3 compounds tested, exhibiting the largest decrease in contraction velocity, depression rate, and beating frequency. Interestingly, KSEB01-S2 behaved similarly to etomidate, suggesting a better cardiac safety profile. Our results provide a proof-of-concept for using human-induced pluripotent stem cell-derived cardiomyocytes as an in vitro platform for future drug design.


Validation of inertial measurement units with an optoelectronic system for whole-body motion analysis.
The potential of inertial measurement units (IMUs) for ergonomics applications appears promising. However, previous IMUs validation studies have been incomplete regarding aspects of joints analysed, complexity of movements and duration of trials. The objective was to determine the technological error and biomechanical model differences between IMUs and an optoelectronic system and evaluate the effect of task complexity and duration. Whole-body kinematics from 12 participants was recorded simultaneously with a full-body Xsens system where an Optotrak cluster was fixed on every IMU. Short functional movements and long manual material handling tasks were performed and joint angles were compared between the two systems. The differences attributed to the biomechanical model showed significantly greater (P ≤ .001) RMSE than the technological error. RMSE was systematically higher (P ≤ .001) for the long complex task with a mean on all joints of 2.8° compared to 1.2° during short functional movements. Definition of local coordinate systems based on anatomical landmarks or single posture was the most influent difference between the two systems. Additionally, IMUs accuracy was affected by the complexity and duration of the tasks. Nevertheless, technological error remained under 5° RMSE during handling tasks, which shows potential to track workers during their daily labour.


Structural determinants of protein evolution are context-sensitive at the residue level.
Structural properties of a protein residue's microenvironment have long been implicated as agents of selective constraint. Although these properties are inherently quantitative, structure-based studies of protein evolution tend to rely upon coarse distinctions between "surface" and "buried" residues and between "interfacial" and "noninterfacial" residues. Using homology-mapped yeast protein structures, we explore the relationships between residue evolution and continuous structural properties of the residue microenvironment, including solvent accessibility, density and distribution of residue-residue contacts, and burial depth. We confirm the role of solvent exposure as a major structural determinant of residue evolution and also identify a weak secondary effect arising from packing density. The relationship between solvent exposure and evolutionary rate (d(N)/d(S)) is found to be strong, positive, and linear. This reinforces the notion that residue burial is a continuous property with quantitative fitness implications. Next, we demonstrate systematic variation in residue-level structure-evolution relationships resulting from changes in global physical and biological contexts. We find that increasing protein-core size yields a more rapid relaxation of selective constraint as solvent exposure increases, although solvent-excluded residues remain similarly constrained. Finally, we analyze the selective constraint in protein-protein interfaces, revealing two fundamentally different yet separable components: continuous structural constraint that scales with total residue burial and a more surprising fixed functional constraint that accompanies any degree of interface involvement. These discoveries serve to elucidate and unite structure-evolution relationships at the residue and whole-protein levels.


Analysis of sampling errors in biopsy techniques using data from whole muscle cross sections.
Because of the large variability in the proportion of fiber types within a whole muscle, a single biopsy is a poor estimator of the fiber type proportion for a whole muscle. Data on the proportions of type I and II fibers, obtained from cross sections of whole human muscles (vastus lateralis) from young male individuals, have therefore been analyzed statistically in order to determine the sampling errors involved in muscle biopsy techniques. For the purpose of obtaining a good estimate of the fiber type proportion in a whole biopsy, counting all fibers is of great benefit compared with counting only half of the fiber number. The required number of biopsies to obtain a given sampling error of the mean proportion of fiber types in the whole muscle can vary by a factor of six. If less than three biopsies are taken from a muscle, there is a substantial reduction in sampling error taking biopsies with at least 600 fibers. For more than three biopsies there is a small gain in sampling greater than 150 fibers. The precision of the estimate of the mean proportion of fiber types for a group is increased with the number of biopsies per individual and number of individuals. In conclusion, for the muscle in this study, complete counting of three biopsies, each greater than 150 fibers, sampled from different depths of the muscle is recommended.


A hybrid monitoring and modelling approach to assess the contribution of sources of glyphosate and AMPA in large river catchments.
Large river catchments with mixed land use capture pesticides from many sources, and degradable pesticides are converted during downstream transport. Unravelling the contribution of pesticide source and the effect of degradation processes is a challenge in such areas. However, insight and understanding of the sources is important for targeted management, especially when water is abstracted from the river for drinking water production. The river Meuse is such a case. A long-term monitoring data set was applied in a modelling approach for assessing the contribution of waste water treatment plants (WWTPs) and tributaries (sub-basins) to surface water contamination, and to evaluate the effect of decay on the downstream concentrations of glyphosate and AMPA at the point of drinking water abstraction. The results show that WWTPs are important contributors for glyphosate and AMPA in large river catchments with mixed land uses. In the studied area, the river Meuse in the Netherlands, the relative contribution of WWTP effluents is above 29% for glyphosate and around 12% for AMPA. Local industries are found to be potentially big contributors of AMPA. Glyphosate entering the river system is gradually converted to AMPA and other degradation productions, which results in downstream loads that are considerably lower than the sum of all influxes. In summer when the travel time is longer due to lower discharge, the first order decay of glyphosate in the river Meuse is estimated to result in about 50% reduction of the downstream glyphosate concentrations over a river stretch of 250km. The contribution of glyphosate decay to the observed AMPA concentrations ranges between 2% and 10%. Contributions are sensitive to seasonal variations in discharge that influence the concentrations through dilution and degradation.


[Diagnosis of fracture of temporal bone in emergency management-reports of 106 cases].
To summarize the effects of diagnose and therapy the fracture of temporal bone in phase of emergency. Retrospectively analyse clinical data of the 106 cases of fracture of temporal bone from 1997 to 2004. Among there are 4 cases were craniotomy, 14 cases were reduction of fracture and 45 cases were debridement suture in the emergency, 6 cases were mastoid-otomy and hemostasis, 3 cases were mastoid exploratory operation and reconstruction of ossicular chain, 1 cases were mastoid exploratory operation and decompression of facial canal, 5 cases were reduction of fracture on external auditory canal. Fourteen cases were methospital and antodischarge. 7 cases of facial paralysis are recovered and 2 cases are improved. Descent of audile and vertigo are multirecovery, other are amelioration. Diagnoses are based on history of wound and six signs of trauma and the result of CT diagnosis. Critically illed patients are treated according to the principle of "rescue-diagnosis- therapy". Emergency are handling in the sequence: airway were unobstructed, breathing were management, circulatory system were stabilizing, heat preservation, oxygen inhalation and expectant operation. The HRCT were necessary for better instruction therapy with spot of fracture were definition.


Biclonal gammopathy in multiple myeloma: a case report.
Monoclonal gammopathy is a group of B-cell disorders which result in the production of a specific and unique monoclonal immunoglobulin (M-component). Biclonal gammopathy is characterized by the simultaneous appearance of two different M-components. The incidence is about 1% of all monoclonal gammopathy. This paper reports on a 48-year-old male who had a chief complaint of back-pain beginning 7 months earlier. A physical examination was unremarkable, except for anemia and tenderness in the back. Hemoglobin was 5.4 g/dl, white blood cells 4.5 x 10(3)/microliter, platelets 157 x 10(3)/microliter, and reticulocytes 0.9%. Serum iron was 79 mg/dl, and total iron-binding capacity was 210 mg/dl. A blood smear showed the formation of rouleaux, but no plasma cells were found. Serum creatinine was 5.4 mg/dl, with a creatinine clearance of 18.1 ml/min. Serum electrolytes were normal except for serum calcium which was 14.4 mg/dl. The urinalysis showed strongly positive proteinuria (+2), with negative Bence Jones protein. Serum protein electrophoresis showed an increase and a spike pattern of beta-2 globulin (2.8 g/dl) and alpha-2 globulin (1.5 g/dl), with normal gamma globulin. By nephelometry technique, serum IgG was normal (1388 mg/dl), IgA was high (900 mg/dl), and IgM was also high (517 mg/dl). Advanced and extensive osteolytic lesions were found in the clavicle, ribs, skull, humerus, femur, and columna vertebralis. Plasma cells (myeloma cells) in bone marrow were 32%. The clinical diagnosis was multiple myeloma (biclonal gammopathy) stage IIIB (Durie and Salmon staging system). Clinical response was good after two series of conventional chemotherapy, with normal serum electrophoresis, decreasing serum creatinine and serum calcium. Based on the above data, the diagnosis of multiple myeloma with biclonal gammopathy was confirmed. This is a rare case with a combination of IgA and IgM M-components.


High Added Value - but Many Stumbling Blocks along the Way NTN Biotech Identifies where the Shoe Pinches.
The year 1958, when DNA was first made in a test tube, marked the birth of modern biotechnology. DNA has now developed into an important technology that makes a key contribution in various sectors such as agriculture, environment and cleansing, and it has triggered a veritable boom in medicine. Today, biologics account for more than 60% of newly approved drugs. They are efficient, save time and money and have few or minimal side effects, fuelling the appetite of big pharma to take over biotech companies. Where will the journey lead?


[Inhibitory action of bupivacaine on cardiac contraction].
We studied the effects of bupivacaine on the contractility and membrane potentials in isolated dog papillary muscle. Bupivacaine (10(-6)-10(-4) M) produced dose-dependent depression of twitch tension elicited by electrical stimulation. These inhibitory effects were greater at high frequencies of stimulation (2, 3 Hz) than at low frequencies (less than 1 Hz). Bupivacaine did not alter the resting membrane potential, but produced a reduction in Vmax of the action potentials, in a dose-dependent and reversible manner (concentrations from 10(-6) to 10(-4) M). Bupivacaine 10(-4) M often blocked the fast action potentials in normal Tyrode's solution. In high K+ (26 mM) Tyrode's solution, bupivacaine inhibited both slow action potentials and associated contractions in the presence of isoproterenol. These results suggest that low concentrations of bupivacaine decreases the contraction mainly due to Na+ channel block, whereas at higher concentration, this anesthetic may block Ca2+ channels. In addition, isoproterenol may be clinically effective in the treatment of bupivacaine cardiotoxicity due to stimulation of Ca2+ mediated slow action potentials through beta-receptors.


Manifold Regularized Experimental Design for Active Learning.
Various machine learning and data mining tasks in classification require abundant data samples to be labeled for training. Conventional active learning methods aim at labeling the most informative samples for alleviating the labor of the user. Many previous studies in active learning select one sample after another in a greedy manner. However, this is not very effective because the classification models has to be retrained for each newly labeled sample. Moreover, many popular active learning approaches utilize the most uncertain samples by leveraging the classification hyperplane of the classifier, which is not appropriate since the classification hyperplane is inaccurate when the training data are small-sized. The problem of insufficient training data in real-world systems limits the potential applications of these approaches. This paper presents a novel method of active learning called manifold regularized experimental design (MRED), which can label multiple informative samples at one time for training. In addition, MRED gives an explicit geometric explanation for the selected samples to be labeled by the user. Different from existing active learning methods, our method avoids the intrinsic problems caused by insufficiently labeled samples in real-world applications. Various experiments on synthetic datasets, the Yale face database and the Corel image database have been carried out to show how MRED outperforms existing methods.


Folate: a possible role in erectile dysfunction?
A growing body of evidence suggests a role for homocysteine (Hcys) and folate (FA) in erectile function (EF): Hcys appears to impair EF affecting endothelium via several mechanism whereas the role of FA remains to be elucidated, besides decreasing Hcys. To assess correlation between erectile dysfunction (ED) and serum levels of FA, Hcys, and B12, we enrolled 31 patients affected by ED (Group A; age 52.83 ± 11.89 years) and 31 healthy adults (Group B; age 49.14 ± 13.63 years). Fasting blood samples were taken for each subject. ED was assessed by the International Index of Erectile Function-5 (IIEF-5). IIEF-5 mean score was significantly lower in Group A than in Group B (10.71 ± 4.24 versus 23.32 ± 1.33, p < .001). Compared to Group B, Group A also showed significantly lower serum FA levels (5.11 ± 1.79 versus 7.9 ± 3.55 ng/ml, p < .001) and significantly higher serum Hcys levels (13.61 ± 3.55 versus 9.17 ± 2.32 µmol/L, p < .001). No significant correlation was observed between Hcys and FA both groups. Our results showed a significant association among ED, FA deficiency and hyperomocisteinemia. Lack of correlation between FA and Hcys suggests that FA deficit may directly impair EF.


Isolated temporomandibular synovitis as unique presentation of juvenile idiopathic arthritis.
Temporomandibular joint (TMJ) involvement is quite frequent in juvenile idiopathic arthritis (JIA). We describe a 15-year-old girl with isolated TMJ arthritis presenting as a unique manifestation of JIA, and its successful treatment. She underwent arthroscopic synovectomy followed by intraarticular steroid injection. Early use of synovectomy and intraarticular steroids in TMJ arthritis may reduce pain, improve jaw function, and prevent irreversible deformities.


[Oxcarbazepine-induced localized penile edema].
Oxcarbazepine is a analogue of carbamazepine with anticonvulsant and analgesic activity. We report a case of localized penile edema caused by oxcarbazepine. The association between the drug and the adverse reaction was confirmed by rechallenge test. This is the first reported case of oxcarbazepine-induced localized penile edema.


No association between common variants in glyoxalase 1 and autism spectrum disorders.
The autism spectrum disorders (ASDs) are complex diseases with a strong genetic component. Numerous candidate gene studies have tested association between various functional and positional candidate genes and autism, but no common variation predisposing for autism has been identified to date. It has been previously proposed, that glyoxalase 1 (GLO1) might be involved in the pathogenesis of autism as GLO1 protein polarity was significantly changed in the brains of autism patients compared to controls. GLO1 harbors a functional polymorphism that affects the polarity and the enzymatic activity of the protein. In the same study, this polymorphism showed a suggestive association to autism. To investigate whether common variants in GLO1 predispose to autism in the Finnish population, we have genotyped six polymorphisms in GLO1 in families with more than 230 individuals affected with ASDs and carried out both linkage and association analyses. We did not observe significant linkage or association between any SNP and ASDs. Therefore, we suggest that common variants in GLO1 are not significant susceptibility factors for ASDs in the Finnish population.


Solvent abuse in pregnancy: a perinatal perspective.
To review the scope and sequelae of solvent abuse in women presenting to a Manitoba teaching hospital. Fifty-six patient charts with a diagnosis of solvent abuse in pregnancy were identified through computer search in the medical records of Winnipeg Health Sciences Centre, General Hospital. These charts were reviewed and data obtained from birthing records and associated pediatric charts. Renal tubular acidosis was diagnosed in three patients (5.3%). Two patients (3.6%) had adverse neurological sequelae. One patient was diagnosed with brain damage, including expressive aphasia. Twelve patients (21.4%) delivered preterm infants. Nine infants (16.1%) had major anomalies. Seven infants (12.5%) had fetal alcohol syndrome (FAS)-like facial features. Six neonates (10.7%) had hearing loss. Substance abuse in pregnancy is associated with severe maternal and neonatal sequelae. Physicians must be aware of this increasing problem in the obstetrical population and assistance should be offered to each woman, ideally before a woman becomes pregnant, but at least at the first contact a pregnant woman makes with the health care community.


From hagfish to humans: teaching comparative physiology to internal medicine residents.
With more clinical information for trainees to master in the face of increasing time pressures, discussions about underlying physiology and the mechanisms of disease seem to have been de-emphasized during residency training. This reduced focus on pathophysiology and basic science may weaken trainees' clinical effectiveness and reduce their interest in pursuing research careers.In response, the authors helped to develop in 2006 a one-week immersive comparative physiology course for second- and third-year internal medicine residents at Beth Israel Deaconess Medical Center. The course, held at the Mount Desert Island Biological Laboratory, includes four modules (hematology, vascular physiology, secretory physiology, and salt and water homeostasis), each composed of basic science experiments using aquatic species and accompanied by clinical correlation discussions and group presentations.From 2007 to 2010, 72 residents rotated through the course. Most reported that it enhanced their understanding of the mechanisms of disease in their patients. After the course, residents reported that physiology played a more prominent role in their teaching and clinical decision making during both ward and intensive care unit rotations. They also reported being more likely than before the course to read about the pathophysiology of disease when faced with a clinical problem.Although cost-intensive and geographically unique, this model for teaching the mechanisms of disease could be applied elsewhere with the help of physician-scientists and clinician-educators. In this article, the authors describe the development of the course, share preliminary data evaluating progress toward its goals, and discuss future directions and lessons learned.


S17834, a new inhibitor of cell adhesion and atherosclerosis that targets nadph oxidase.
microdant stress is involved in the events that accompany endothelial cell expression of adhesion molecules and leukocyte adherence in many disease states, including atherosclerosis. A recently discovered benzo(b)pyran-4-one derivative, S17834 (10 to 50 micromol/L), reduced tumor necrosis factor-stimulated vascular cell adhesion molecule-1 (VCAM) mRNA accumulation and protein expression in human umbilical vein endothelial cells. Intercellular cell adhesion molecule-1 and E-selectin were also inhibited by S17834, but platelet endothelial cell adhesion molecule-1 was not. Adherence of U937 monocytic cells to the endothelial cells as well as to plastic plates coated with soluble VCAM, intercellular cell adhesion molecule-1, P-selectin, and E-selectin was also decreased. Consistent with an antioxidant mechanism of action, S17834 (10 to 50 micromol/L) inhibited tumor necrosis factor-stimulated release of superoxide from endothelial cells measured by cytochrome c reduction. S17834 had no effect on superoxide produced by xanthine oxidase, indicating that rather than by acting as a scavenger of superoxide anion, the drug acts by inhibiting the production of free radicals. Indeed, S17834 inhibited NADPH oxidase activity of endothelial cell membranes. The ability to inhibit superoxide anion production appears to be key in the effect of S17834 on superoxide anion production and VCAM expression, because these actions were mimicked by adenovirus-mediated overexpression of superoxide dismutase. Furthermore, these actions may be relevant in vivo, because S17834 reduced aortic superoxide anion levels by 40% and aortic atherosclerotic lesions by 60% in apolipoprotein E-deficient mice. These results indicate that S17834 inhibits adhesion molecule expression and adherence of leukocytes to endothelial cells as well as aortic atherogenesis and that perhaps these effects can be explained by its ability to inhibit endogenous superoxide anion production.


Protein chips for high-throughput doping screening in athletes.
Sport and doping are a contradiction in terms, however, doping abuse in sports has been a serious problem for many years. The systematic screening of every athlete for all prohibited drugs should be an indispensable feature of the Olympic Games. The gas chromatography mass spectrometry method is reserved as a reference method, but is limited by its low throughput. The advent of protein chip technology may enable the screening of all athletes for any illegal use of drugs.


Ultrastructural studies of mouse thymic reticulum. II. Non-epithelial component.
In this study we describe two types of non-epithelial cells forming a part of the thymic reticulum: macrophages with high phagocytic function, present in the cortex and medulla of the organ, and interdigitated cells present at the corticomedullary junction and in the medulla. These cells, in relation with epithelial cells, form a meshwork, a thymic microenvironment which influences the differentiation and maturation of T lymphocytes. These non-epithelial cells were probably mobile and their precursors exist in bone marrow. It has not yet been determined whether they are both of the same lineage and whether there is or is not common lineage between macrophages and interdigitated cells. Their role as accessory cells in the immune response seems evident. We will compare our observations with those of other authors. We will also discuss several issues concerning these two cell types; their nomenclature, their interrelationship in the thymic reticulum, their function, and their relationship to other similar cells in situ and to cells isolated in vitro, which perhaps are similar.


The effect of zanoterone, a steroidal androgen receptor antagonist, in men with benign prostatic hyperplasia. The Zanoterone Study Group.
Zanoterone (100 to 800 mg.) versus placebo was studied in 463 patients with benign prostatic hyperplasia. Study end points were maximum urinary flow rate, American Urological Association symptom index, prostate volume, prostate specific antigen and sex steroid concentrations after 6 months of treatment. Mean increases in maximum urinary flow rate were 2 to 3-fold over placebo, although only the 200 mg. group had significant results (1.7 ml. per second, p = 0.026). There were no statistically significant differences between the zanoterone and placebo groups in symptom index or prostate volume. Estradiol and testosterone concentrations, and the incidence of breast pain and gynecomastia increased significantly with zanoterone compared with placebo. Prostate specific antigen levels decreased significantly. Zanoterone did not demonstrate a favorable risk-to-benefit profile for the treatment of benign prostatic hyperplasia.


Factors associated with low graft regeneration in the early phase after living donor liver transplantation.
Appropriate graft regeneration after living donor liver transplantation (LDLT) is crucial to avoid small-for-size syndrome. We enrolled 44 recipients who underwent ABO-identical/compatible LDLT from December 2007 to August 2016 and determined possible factors associated with low graft regeneration after LDLT. Liver regeneration was calculated by the ratio of the graft size on postoperative day (POD) 7 ± 1 day (calculated by CT volumetry) to the size of the donated liver at implant. Postoperative outcomes were compared between the low and high regeneration groups. Median regeneration rate was 1.65-fold. Regeneration rate was negatively correlated with graft-to-recipient weight ratio. Postoperative morbidity rates on POD 14-90 were significantly higher in the low group compared with the high group (63% vs 18%, P = .03). Graft and patient survival in the low group were significantly worse than the high group (1-year graft survival 73% vs 100%, P = .002; patient survival 82% vs 100%, P = .01). Cold ischemia time (CIT; per 10 minute; odds ratio [OR] =1.37) and platelet count <60 000/μL on POD 5 (OR = 14.32) were independently associated with low regeneration. In conclusion, longer CIT and postoperative thrombocytopenia were associated with low graft regeneration in the early phase after LDLT, which could consequently lead to poor graft and patient survival.


Hormonal underpinnings of status conflict: Testosterone and cortisol are related to decisions and satisfaction in the hawk-dove game.
A contribution to a special issue on Hormones and Human Competition.Testosterone is theorized to influence status-seeking behaviors such as social dominance and competitive behavior, but supporting evidence is mixed. The present study tested the roles of testosterone and cortisol in the hawk-dove game, a dyadic economic decision-making paradigm in which earnings depend on one's own and the other player's choices. If one person selects the hawk strategy and the other person selects the dove strategy, the player who selected hawk attains a greater financial pay-off (status differentiation). The worst financial outcome occurs when both players choose the hawk strategy (status confrontation). Ninety-eight undergraduate students (42 men) provided saliva samples and played ten rounds of the hawk-dove game with another same-sex participant. In support of the hypothesis that testosterone is related to status concern, individuals higher in basal testosterone made more hawk decisions - decisions that harmed the other player. Acute decreases in cortisol were also associated with more hawk decisions. There was some empirical support for the dual-hormone hypothesis as well: basal testosterone was positively related to satisfaction in the game among low basal-cortisol individuals but not among high basal-cortisol individuals. There were no significant sex differences in these hormonal effects. The present findings align with theories of hormones and status-seeking behavior at the individual level, but they also open up new avenues for research on hormone profiles at the collective level. Our results suggest that the presence of two or more high-testosterone members increases the likelihood of status confrontations over a limited resource that can undermine collective outcomes.


Orbital dissection defatting technique for Graves disease.
Five patients with Graves disease and bilateral proptosis were treated with different incisional approaches. They all underwent orbital decompression by removal of the anterior medial orbital walls, the anterior ethmoidal sinuses, the orbital floors, and multiple incisions of the orbital periosteums . The defatting technique, which consists of applying manual anterior orbital pressure with alternate removing of small lobules of fat, was added when it was intraoperatively decided by Hertel exophthalmometer measurement that more decompression was needed. It is estimated that one-third more reduction in proptosis resulted. An average total decrease in proptosis of 9 mm per orbit occurred. Both visual accuities and visual fields returned to normal. The only important complication was the development of hypertropia in down gaze in one patient. A potential value of this technique is its use with orbital floor decompression alone. It may be possible to avoid removing the medial and lateral walls of the orbit, thereby decreasing complications. Defatting may also be a valuable addition in those rare cases where all decompression techniques available are needed to affect an adequate decompression.


Hospital pharmacy compliance with JCAHO standards and ASHP guidelines for reporting adverse drug reactions.
The extent to which institutional pharmacies comply with the accreditation standards of the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) and the ASHP guidelines for reporting adverse drug reactions (ADRs) was evaluated. A survey was mailed to directors of pharmacy at 444 randomly selected hospitals to collect information on their institutions' ADR programs; the survey addressed each point in the JCAHO accreditation standards and the ASHP guidelines. The 176 usable responses indicated that 89.8% of the institutions met all three of the JCAHO standards and 98.9% met at least two of them; 28.4% of the institutions complied with all 11 of the ASHP guidelines, and 89.2% complied with at least eight of them. Approximately 97% of the institutions had policies for ADR reporting. Respondents reported an average of 70.5 ADRs per hospital during 1989, of which 6.8 per hospital were reported to the FDA. More than 95% of all respondents indicated that they most frequently identified ADRs through voluntary reporting by health-care professionals. Respondents indicated methods and individuals responsible for reporting ADRs, notifying the physician and the FDA, and assessing severity and causality. Sixty-seven percent of the respondents indicated that they did not have a formal ADR committee for monitoring and evaluating ADRs. Almost 90% of the surveyed hospitals complied with all of the JCAHO standards for ADR reporting programs and at least 8 of the 11 ASHP guidelines for ADR monitoring and reporting.


Ursodeoxycholate/Sulindac combination treatment effectively prevents intestinal adenomas in a mouse model of polyposis.
Preclinical studies in animal models, human epidemiological data, and clinical trials in patients with adenomatous polyposis have consistently indicated that sulindac and other nonsteroidal antiinflammatory drugs or cyclooxygenase inhibitors have the greatest potential efficacy among current candidates for colon tumor chemopreventive agents. However, at highly effective doses they all have some risk of toxicity, and their therapeutic profile might be improved by use at lower, more tolerable doses, in combination with a second agent acting via other mechanisms. Sulindac was tested in combination with ursodeoxycholic acid (ursodiol), a naturally occurring 7-B-epimer of the bile component chenodeoxycholic acid, for prevention of adenomas in the Min mouse model of adenomatous polyposis. Ursodeoxycholic acid caused a dose-dependent decrease in the number of intestinal tumors. Unlike sulindac and other nonsteroidal anti-inflammatory drugs, which are quite beneficial in the distal intestine but are somewhat less effective in the proximal small intestine (especially the clinically important periampullary duodenum), ursodeoxycholate had equal efficacy throughout the entire intestine, both proximal and distal. Combined treatment with low-dose sulindac was less toxic, with normal weight gain and fewer gastrointestinal ulcerations than high-dose sulindac. Combined treatment with sulindac and ursodeoxycholate was more effective than either agent alone for the prevention of tumors throughout the entire intestine. These experiments provide the first evidence that ursodeoxycholic acid is effective for preventing adenomas in an animal model. Cyclooxygenase inhibition, when combined with this naturally occurring bile component, may become a promising approach for colon cancer prevention.


WHO at country level.
WHO's activities at country level have earned the organisation both criticism and praise. The organisation's technical publications are esteemed as authoritative guidelines for disease control. Successful disease-control programmes and contributions to health research have heightened WHO's reputation. The organisation has also provided the focus for evolution of important ideas, such as primary health care and the relevance of equity and other ethical issues. But WHO has been criticised for not adapting rapidly and logically to changes in the health field. With increasing national capacity in the more advanced developing countries, and with the involvement of new participants in the health sphere, the organisation needs to reassess its role at country level. My recommendation is that WHO improves its analytical capacity so that its programmes take into consideration the health needs of the country, its national capacity, and the contributions from other external agencies.


A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor.
Nerve growth factor (NGF) is a trophic agent that promotes the outgrowth of nerve fibers from sympathetic and sensory ganglia. The neuronal differentiation stimulated by this hormone was examined in the NGF-responsive cell line PC12. Differential hybridization was used to screen a complementary DNA library constructed from PC12 cells treated with NGF and cycloheximide. One of the complementary DNA clones that was rapidly induced by NGF was found to have a nucleotide sequence that predicts a 54-kilodalton protein with homology to transcriptional regulatory proteins. This clone, NGFI-A, contains three tandemly repeated copies of the 28- to 30-amino acid "zinc finger" domain present in Xenopus laevis TFIIIA and other DNA-binding proteins. It also contains another highly conserved unit of eight amino acids that is repeated at least 11 times. The NGFI-A gene is expressed at relatively high levels in the brain, lung, and superior cervical ganglion of the adult rat.


[Bioinformatic analysis of potential post-translational modification sites of the human O6-methylguanine-DNA methyltransferase (MGMT) protein].
Using in silico analysis a number of potential sites for post-translational modifications has been revealed within the human O6-methylguanine-DNA methyltransferase (MGMT) protein. In particular these were the acetylation of Gly3 residue in the N-terminus of protein and internal residues Lys132 and Lys135; Arg166 residue methylation; Lys63 SUMOylation and ubiquitination of Lys31, Lys39, Lys49, Lys63, Lys67, Lys135, Lys156, Lys196, Lys209. Also it has been predicted 16 novel potential phosphorylation sites of serine residues (positions 13, 124, 144, 182, 183, 190, 215, 216 and 230), tyrosine residues (positions 100 and 189) and threonine residues (positions 23, 69, 94, 126 and 229), as well as five binding sites for kinases and other proteins (Serl3 with 14-3-3, Val21 and Ile172 with D-domain, Pro78 and Pro111 with SH3-domain, Pro111 with MAPK3). Some kinases predicted by the authors are known as partners of the MGMT protein, that confirms the probability of modification of the given sites. Potential sites require further experimental confirmation of modifications and investigation of their influence on stability and DNA-repair activity of this protein.


Perceived Benefit of Teaching Patient Safety to Pharmacy Students by Integrating Classroom Teaching With Introductory (IPPE) Visits.
Ensuring a culture that prioritizes and implements patient safety requires educating all future health care professionals to prepare them for their active role in reducing medical errors. There is limited literature describing integration of patient safety education into the curriculum of health care professionals, including pharmacists. The purpose of this study was to evaluate the perceived benefit of integrating patient safety education into a pharmacy curriculum. Second-year pharmacy students (P2s) completed a patient safety self-study, followed by in-class and experiential application of a root cause analysis (RCA). An electronic, anonymous postsurvey was administered to P2s and third-year pharmacy students (P3s) who had not had formal patient safety education. Of the 310 students, 53% responded to the survey. Significantly more P2s reported more confidence to describe patient safety and its purpose ( P = .0092), describe factors that influence patient safety ( P = .0055), and conduct an RCA ( P < .001). P2s also reported significantly better ability to conduct a RCA compared to P3s (88.9% positive vs 58.7%, respectively; P ≤ .001). Both classes perceived patient safety education to be valuable; however, formal education resulted in some significant improvements in perceived confidence and understanding, including ability to conduct an RCA.


Job strain and evolution of mental health among nurses.
The objective of this 2nd phase of a 2-year study among female nurses was to provide further empirical validation of the demands-control and social support model. The association of job strain with psychological problems and the potential modifying role of social support at work were examined. A questionnaire was sent at the workplace to 1,741 nurses. The same associations were found between psychological demands, decision latitude, and a combination of the 2 with psychological distress and emotional exhaustion for current exposure and for cumulative exposure. Social support had a direct effect on these psychological symptoms but did not modify their association with job strain. Longitudinal and prospective data are needed to study the occurrence and persistence of health problems when exposure is maintained or retrieved.


Protein engineering of Rubisco.
Modification of the kinetic parameters of enzymes by protein engineering requires extensive knowledge of the structural details of the enzyme and its complexes with different reaction intermediate analogues. Such structural studies are described here for Rubisco, ribulose-1,5-bisphosphate carboxylase/oxygenase, which catalyzes the initial reactions of two important but competing physiological events in green plants; carbon dioxide fixation and photorespiration. Observed functional changes in mutants of Rubisco are correlated with structural details as well as with the defined conformational changes that occur during catalysis. A possible functional role of the small subunit of Rubisco is described based on a comparison of the active-site geometry of a bacterial L2 molecule with that of higher plant L8S8 molecules. The ultimate aim of these studies is to engineer Rubisco mutants that are more efficient than the wild-type enzyme by decreasing the oxygenase/carboxylase ratio.


Skyrmion-Based Dynamic Magnonic Crystal.
A linear array of periodically spaced and individually controllable skyrmions is introduced as a magnonic crystal. It is numerically demonstrated that skyrmion nucleation and annihilation can be accurately controlled by a nanosecond spin polarized current pulse through a nanocontact. Arranged in a periodic array, such nanocontacts allow the creation of a skyrmion lattice that causes a periodic modulation of the waveguide's magnetization, which can be dynamically controlled by changing either the strength of an applied external magnetic field or the density of the injected spin current through the nanocontacts. The skyrmion diameter is highly dependent on both the applied field and the injected current. This implies tunability of the lowest band gap as the skyrmion diameter directly affects the strength of the pinning potential. The calculated magnonic spectra thus exhibit tunable allowed frequency bands and forbidden frequency bandgaps analogous to that of conventional magnonic crystals where, in contrast, the periodicity is structurally induced and static. In the dynamic magnetic crystal studied here, it is possible to dynamically turn on and off the artificial periodic structure, which allows switching between full rejection and full transmission of spin waves in the waveguide. These findings should stimulate further research activities on multiple functionalities offered by magnonic crystals based on periodic skyrmion lattices.


Influence of hemodialysis on plasma chemotactic activity and the chemotactic responsiveness of polymorphonuclear neutrophils.
Thirty patients with chronic renal failure on maintenance hemodialysis (HD) were studied. Plasma chemotactic activity was estimated using the "under agarose" chemotaxis assay during the first 2 h of HD. It was found that in the fifth minute of HD, patients' plasma became chemotactic, reaching the maximum activity at the tenth minute. The chemotactic activity appearance correlated significantly with the decline in the number of the peripheral neutrophils. Patients' neutrophils, after a single passage through the cellophane coil of the dialyzer, revealed significant impairment of directed migration toward both complementary and bacterial chemoattractants. Moreover, the chemotactic properties of neutrophils obtained from dialyzed patients before HD were significantly lower than had been estimated in 15 nondialyzed patients with chronic renal failure. The results confirm HD-induced complement activation and might explain the mechanisms of the increased susceptibility of dialyzed patients to bacterial infections.


cDNA cloning and localization of a band 3-related protein from ileum.
A Cl(-)-HCO3- exchanger in the brush-border membrane mediates active Cl- absorption and regulates intracellular pH in rabbit ileum. The molecular identity of the ileal Cl(-)-HCO3- exchanger has not been established. The best-characterized plasma membrane Cl(-)-HCO3- exchanger is erythroid band 3. Structurally related proteins in nonerythroid tissues comprise an anion exchanger (AE) family. We used the polymerase chain reaction to amplify and clone a cDNA encoding an ileal band 3-related protein (B3RP) from rabbit ileal enterocytes. The composite sequence is 3,909 bp and is predicted to encode a protein of 136 kDa. The deduced amino acid sequence is 95% identical to murine renal AE2, indicating that ileal B3RP is rabbit AE2. Antisera generated against a cytoplasmic fragment of ileal B3RP recognized a 160- to 170-kDa polypeptide in the brush-border membrane, but not the basolateral membrane, of ileal crypt and villus enterocytes. This correlates with previous studies indicating that a Cl(-)-HCO3- exchange is present in brush-border but not basolateral membrane vesicles from rabbit ileal enterocytes. We conclude that ileal B3RP is a product of the AE gene family, and is present in the brush-border of ileal enterocytes, where it may mediate Cl(-)-HCO3- exchange.


Patterns of civilian and child deaths due to war-related violence in Syria: a comparative analysis from the Violation Documentation Center dataset, 2011-16.
Since March, 2011, the Syrian civil war has lowered life expectancy by as much as 20 years. We describe demographic, spatial, and temporal patterns of direct deaths of civilians and opposition combatants from conflict-related violence in 6 years of war. We analysed conflict-related violent deaths with complete information on date, place, and cause of death and demographic group occurring from March 18, 2011, to Dec 31, 2016, recorded by the Violation Documentation Center (VDC). We included civilian and combatant deaths in all Syrian governorates, excluding government-controlled areas. We did not include detainees and missing persons, nor deaths from siege conditions or insufficient medical care. We categorised deaths based on VDC weapon type. We used χ2 testing to compare deaths from different weapons in civilian men, women, boys, and girls and adult and child combatants. We analysed deaths by governorate and over time. The VDC recorded 143 630 conflict-related violent deaths with complete information between March 18, 2011, and Dec 31, 2016. Syrian civilians constituted 101 453 (70·6%) of the deaths compared with 42 177 (29·4%) opposition combatants. Direct deaths were caused by wide-area weapons of shelling and air bombardments in 58 099 (57·3%) civilians, including 8285 (74·6%) civilian women and 13 810 (79·4%) civilian children, and in 4058 (9·6%) opposition combatants. Proportions of children among civilian deaths increased from 8·9% (388 of 4254 civilian deaths) in 2011 to 19·0% (4927 of 25 972) in 2013 and to 23·3% (2662 of 11 444) in 2016. Of 7566 deaths from barrel bombs, 7351 (97·2%) were civilians, of whom 2007 (27·3%) were children. Of 20 281 deaths by execution, 18 747 (92·4%) were civilians and 1534 (7·6%) were opposition combatants. Compared with opposition child soldiers who were male (n=333), deaths of civilian male children (n=11 730) were caused more often by air bombardments (39·2% vs 5·4%, p<0·0001) and shelling (37·3% vs 13·2%, p<0·0001) and less often by shooting (12·5% vs 76·0%, p<0·0001). Aerial bombing and shelling rapidly became primary causes of direct deaths of women and children and had disproportionate lethal effects on civilians, calling into question the use of wide-area explosive weapons in urban areas. Increased reliance on aerial bombing by the Syrian Government and international partners is likely to have contributed to findings that children were killed in increasing proportions over time, ultimately comprising a quarter of civilian deaths in 2016. The inordinate proportion of civilians among the executed is consistent with deliberate tactics to terrorise civilians. Deaths from barrel bombs were overwhelmingly civilian rather than opposition combatants, suggesting indiscriminate or targeted warfare contrary to international humanitarian law and possibly constituting a war crime. None.


S-100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke.
Better techniques are needed to monitor infarction volume and predict neurological outcome after ischemic brain infarction. We evaluated the usefulness of serial measurements of S-100 protein versus neuron-specific enolase (NSE) in blood samples from patients with acute stroke. Using nonisotopic sandwich immunoassays, we measured plasma concentrations of S-100 protein and NSE on admission and on days 3, 4, 7, and 14 after infarction in 44 patients (age range, 22 to 86 years; mean age, 65.1 years; 12 female, 32 male). Infarct volume was measured by volumetric CT on day 4 after ictus, and clinical outcome was assessed at discharge from hospital with the Activities of Daily Living Scale and 6 months after infarction with the Glasgow Outcome Scale. Peak blood levels of S-100 protein were found on day 2.5 +/- 1.3, and peak levels of NSE were found on day 1.9 +/- 0.8 after infarction. Peak plasma levels of S-100 protein correlated well with infarct volume (r = .75, P < .001) and with clinical outcome assessed with the Glasgow Outcome Scale (r = .51, P < .001). Serum levels of NSE correlated with infarct volume (r = .37, P < .05) but not with clinical outcome (r = .18, P > .05). The results of our study indicate that measuring blood concentrations of S-100 protein periodically in the first 10 days after cerebral infarction helps to predict infarct volume and the long-term neurological outcome more accurately than periodic measurements of blood concentrations of NSE.


28-hour profiles of blood glucose (BG), plasma immunoreactive insulin (IRI) and IRI/BG ratio in four insulinomas.
Nycthemeral variations in blood glucose (BG) and insulinemia (IRI) of four subjects with insulin-secreting pancreatic tumors were determined. Blood samples were drawn every 15 min over a 28-h period. After surgery, two of the subjects were retested. Meals were distributed during testing so that there was a minimum of eight meals per test. The meals before and after surgery were qualitatively, quantitatively and chronologically the same. Even though the circadian profiles of the glycemia and insulinemia varied greatly among the subjects, there were three common characteristics during the noctural period (24 h-8 h): Existence of one or several phases of at least 1 hour where the glycemia was less than 2.78 mmol/l, Existence of IRI peaks, without eating. Existence of a peak or of increased values (as compared to normal values) of the IRI/BG ratio, without eating. The IRI/BG ratio is a very sensitive index for insulin secretion dysfunction as compared to glycemia. The results suggest that the measurement of glycemia and insulinemia of sleeping subjects and then calculation of the IRI/BG ratio is sufficient to affirm the presence of an insulin-secreting adenoma.


Examining the correspondence of breastfeeding and bottle-feeding couples' infant feeding attitudes.
Examining the correspondence of breastfeeding and bottle-feeding couples' infant feeding attitudes This report focuses on the comparison of infant feeding attitudes within breastfeeding (n = 126) and bottle-feeding (n = 101) couples and their socio-demographic details. The findings from this study reinforce the view that socio-demographic factors are associated with the mothers' choice of feeding method. However, this study highlights the influence of maternal and of paternal knowledge and attitudes which distinguish between breastfeeding and bottle-feeding couples. Fathers of bottle-feeding babies were found to have limited knowledge of health benefits of breastfeeding to both mothers and infants. However, bottle-feeding mothers, when compared with their partners, were more supportive towards bottle feeding and less negative towards breastfeeding. Fathers of breastfeeding babies, compared with their partners were found to be less aware of the benefits of breastfeeding. Furthermore, breastfeeding mothers when compared with their partners were more supportive towards breastfeeding. Fathers of both bottle and breast feeding babies were also found to be more embarrassed than their partners about mothers in general breastfeeding in front of nonfamily members. It seems that bottle-feeding mothers and all fathers could be better prepared in many aspects of breastfeeding by the nursing professions to allay the many misconceptions and the social embarrassment associated with breastfeeding, by providing appropriate information and support.


[Risk factors associated with preterm birth in a second level hospital].
Preterm birth is one of the biggest problems in obstetrics and gynecology, given that it has an incidence of 10-11%. The objective was to identify the risk factors associated with a preterm birth. A retrospective, observational, transversal and analytic case-control study was made. All premature birth incidences were determined as study objects and controls were integrated with term deliveries. A sample size of 344 patients with a control per case was calculated. A total of 688 patients were studied. Statistical analysis was descriptive, univariate and bivariate and we used the Pearson chi square test, with a p < 0.05, odds ratios (OR) and 95% confidence intervals (95% CI). The risk factors associated with a preterm labor were placenta praevia: OR = 10.2 (p = 0.005); previous preterm delivery: OR = 10.2 (p = 0.005); preeclampsia: OR = 6.38 (p = 0.00); twin pregnancy: OR = 5.8 (p = 0.000); oligohydramnios: OR = 5.8 (p = 0.000); tobacco use: OR = 4.6 (p = 0.002); premature rupture of membranes (PROM): OR = 4.1 (p = 0.000); cervicovaginitis: OR = 3 (p = 0.000); urinary tract infections (UTI): OR = 1.5 (p = 0.010). Maternal history of prenatal care, preclampsia, PROM, twin pregnancy, placenta praevia, cervicovaginitis, previous preterm delivery and UTI are risk factors with statistical significance associated with preterm delivery.


An assessment of the recidivism rates of substantiated and unsubstantiated maltreatment cases.
This study assembles information about the large number of maltreatment reports that are determined by social services to be unsubstantiated. Specifically, we assess whether the status of a maltreatment case (substantiated vs. unsubstantiated) has implications for recidivism. Recidivism rates for substantiated and unsubstantiated maltreated juveniles were also compared to juvenile offenders. Juvenile court records for 15,812 juveniles were assessed over a 3 year period. The data included 2558 maltreatment cases. Fifty-four percent of these cases were unsubstantiated. Logistic regression analysis was employed to assess the probability of recidivism based on time one referral status. Youth whose maltreatment allegations were unsubstantiated had significantly lower odds of recidivating than abused youth. Having a case recorded as unsubstantiated lowered a youth's odds of subsequent offending by 55% relative to being abused. The probability of recidivating was highest for juvenile offenders, followed in order by maltreated youth and youth whose reports were unsubstantiated. This is one of the first studies to examine the court histories of substantiated and unsubstantiated maltreatment cases. If the subsequent outcomes following maltreatment investigations are used as an indicator of seriousness, our results suggest that assessment caseworkers are successfully sorting out the serious from the less serious cases.


[Repeated transient paraparesis due to solitary spinal epidural arterio-venous malformation. A case report].
A case of spinal epidural AVM with unusual clinical course was presented. A 28-year-old male had repeated episodes of paraparesis and complete recovery in several hours. Metrizamide myelography revealed the dorsal epidural mass at the level of L2 and L3. Accidental epidurogram during the procedure indicated extradural angioma. Surgical intervention proved solitary spinal epidural AVM. Ninety-nine cases in literature were reviewed. Among them, 14 cases of spinal epidural hematoma were due to ruptured angioma which were verified histologically. Others were unknown causes. Age distribution was discussed. It was suggested that the younger patients in the group of unknown causes might have angiomas. It was emphasized that it should not be overlooked even the insignificant transient symptoms and should schedule the extensive radiological examination in such cases.


Stimulation of active potassium transport in LK sheep red cells by blood group-L-antiserum.
Anti-L serum prepared by immunization of a high-potassium-type (HK) (blood type MM) sheep with blood from a low-potassium-type (LK) (blood type ML) sheep contained an antibody which stimulated four- to sixfold K(+)-pump influx in LK (LL) sheep red cells. In long-termin vitro incubation experiments, LK sheep red cells sensitized with anti-L showed a net increase in K(+) after two days of incubation at 37°C, whereas HK-nonimmune (NI)-serum-treated control cells lost K(+). The antibody could be absorbed by LK (LL) sheep red cells but not by HK sheep red cells. Kinetic experiments showed that the concentration of external K(+) ([K(+)]0) required to produce halfmaximum stimulation of the pump ([Na(+)]0=0, replaced by Mg(++)) was the same (0.25 mM) in L-antiserum-treated or untreated LK cells. LK cells with different [K(+)]i (Na(+) replacement) were prepared by the p-chloromercuribenzene sulfonate (PCMBS) method. At [K(+)]0=5 mM, pump influx decreased as [K(+)]i increased from 1 to 70 mM in L-antiserum-treated LK cells, whereas LK cells treated with HK-NI-serum ceased to pump at [K(+)]i=35 mM. Exposure to anti-L serum produced an almost twofold increase in the number of pump sites of LK cells as measured by the binding of tritiated ouabain by LK sheep red cells. These findings indicate that the formation of a complex between the L-antigen and its antibody stimulates active transport in LK sheep red cells both by changing the kinetics of the pump and by increasing the number of pump sites.