Degradation of brominated flame retardant in computer housing plastic by supercritical fluids.
The degradation process of brominated flame retardant (BFR) and BFR-containing waste computer housing plastic in various supercritical fluids (water, methanol, isopropanol and acetone) was investigated. The results showed that the debromination and degradation efficiencies, final products were greatly affected by the solvent type. Among the four tested solvents, isopropanol was the most suitable solvent for the recovery of oil from BFR-containing plastic for its (1) excellent debromination effectiveness (debromination efficiency 95.7%), (2) high oil production (60.0%) and (3) mild temperature and pressure requirements. However, in this case, the removed bromine mostly existed in the oil. Introduction of KOH into the sc-isopropanol could capture almost all the inorganic bromine from the oil thus bromine-free oil could be obtained. Furthermore, KOH could enhance the depolymerization of the plastic. The obtained oil mainly consisted of single- and duplicate-ringed aromatic compounds in a carbon range of C9-C17, which had alkyl substituents or aliphatic bridges, such as butyl-benzene, (3-methylbutyl)-benzene, 1,1'-(1,3-propanediyl)bis benzene. Phenol, alkyl phenols and esters were the major oxygen-containing compounds in the oil. This study provides an efficient approach for debromination and simultaneous recovering valuable chemicals from BFR-containing plastic in e-waste.


New synthesized polyoxygenated diarylheptanoids suppress lipopolysaccharide-induced neuroinflammation.
In neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease and multiple sclerosis, neuroinflammation induced by the microglial activation plays a crucial role. In effort to develop effective anti-neuroinflammatory compounds, different new linear polyoxygenated diarylheptanoids were synthesized. In LPS-triggered BV-2 microglial cells their ability to reduce the concentration of IL-6 and TNF-α pro-inflammatory cytokines was evaluated. Moreover, their effect on NF-κB and ATP citrate lyase (ACLY), a recently emerged target of metabolic reprogramming in inflammation, was assessed. Finally, we turned our attention to inflammatory mediators derived from the cleavage of citrate catalyzed by ACLY: prostaglandin E2, nitric oxide and reactive oxygen species. All compounds showed null or minimal cytotoxicity; most of them had a great anti-neuroinflammatory activity. Diarylheptanoids 6b and 6c, bearing a halide atom and benzyl ether protective groups, exhibited the best effect since they blocked the secretion of all inflammatory mediators analyzed and reduced NF-κB and ACLY protein levels.


The diagnosis of alcohol-related brain damage: a retrospective study in alcoholics undergoing in-patient rehabilitation.
Alcohol-related brain damage (ARBD) is a common and prognostically relevant complication of alcohol dependence. Clinical sensitivity for ARBD by routine mental state examination (MSE) is important, but unlikely given the documented insensitivity of the MSE in detecting less subtle disorders. We sought to determine the predictive capacity of a well-documented MSE in 32 detoxified alcohol-dependent patients who had undergone neuropsychological testing. Seventeen patients were found to have impaired performance on neuropsychological testing. The initial medical diagnoses and short-term memory tests did not correlate with neuropsychological findings. Ratings of the non-memory component of the MSE were a weak predictor of neuropsychological impairment. In the absence of any adequate 'screening' procedure, we conclude that all alcohol-dependent patients should be considered at high risk for ARBD and require full investigation.


Pilot study of the utility of the synthetic PET amino-acid radiotracer anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid for the noninvasive imaging of pulmonary lesions.
Anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti-3-[(18)F]FACBC) is a synthetic amino acid positron emission tomography (PET) radiotracer with utility in detection of prostate carcinoma and brain tumors and has also been shown to have uptake in lung tumor cell lines. The purpose of this study is to determine the uptake characteristics of anti-3-[(18)F]FACBC in lung carcinoma and if this radiotracer may help characterize pulmonary lesions. Ten patients with pulmonary lesions scheduled for surgical resection or biopsy underwent 45-min dynamic PET-CT imaging of the thorax after IV injection of 214.6-384.8MBq of anti-3-[(18)F]FACBC. Anti-3-[(18)F]FACBC uptake was compared with that of routine 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) PET-CT scans of the same patient and validated with a combination of pathology, imaging and clinical follow-up. Immunohistochemistry for Ki-67 was performed on tissue samples. There were nine malignant (seven lung nodules and two mediastinal nodes), two inflammatory, and one carcinoid lesion ranging from 1 to 3.75 cm. Mean(±SD) SUVmax of malignant lesions was 6.2(±2.6), 5.9(±2.7), 5.9(±3.4), and 5.7(±3.3), at 8, 16, 28, and 40 min, respectively; while for inflammatory lesions at the same time points, 4.1(±0.6), 3.3(±0.9), 2.2(±0.03), and 2.3(±0.03), respectively. The carcinoid tumor had SUVmax of 2.8, 2.6, 1.5, and 0.9 at similar time points. Mean SUVmax of all malignant lesions was higher than that of inflammatory lesions for anti-3-[(18)F]FACBC, and was statistically significant at greater than 28 min post-radiotracer infusion (p < 0.05). There was no significant correlation of anti-3-[(18)F]FACBC activity with Ki67, though there was a positive trend. There was a strong correlation between anti-3-[(18)F]FACBC and [(18)F]FDG uptake. Anti-3-[(18)F]FACBC uptake in malignant lesions is greater than in inflammatory lesions with a higher degree of separation of uptake on delayed imaging. More comprehensive study is required to determine the diagnostic performance of anti-3-[(18)F]FACBC in the characterization of pulmonary lesions.


Trend analysis and prediction of injury death in Xi'an city, China, 2005-2020.
Injury is an important cause of death in China. In the present study, we systematically analyzed the epidemiological characteristics and trends of injury death in Xi'an residents from 2005 to 2020. Data on injury deaths from 2005 to 2020 were obtained from the "Xi'an Center for Disease Control and Prevention", injury deaths were classified according to the International Classification Disease-10th Revision (ICD-10). The data were stratified by gender, age groups, injury types, and then overall and type-specific injury mortality rates were estimated. Joinpoint regression analysis was conducted to estimate annual percent change (APC). The grey interval predicting method was used to predict the future characteristics of injury deaths in Xi'an city. From 2005 to 2020, injury caused 32,596 deaths (5.79% of all deaths; 35.71/100000 population). Injury mortality rates were higher among males than females. Motor vehicle traffic accidents were the commonest injury type. The highest injury mortality rates were in those aged 85 years or older. Overall, Joinpoint regression analysis revealed that injury mortality had significantly (p < 0.05) decreasing trends. GM (1,1) model estimated that injury mortality will be on a declining curve. Motor vehicle traffic accidents, transport accidents other than motor vehicles, unintentional falls, suicide, and accidental poisoning are the main causes of injury. The injury death rate is projected to decline over the next decade.


Mannose-binding lectin haplotypes may be associated with cerebral palsy only after perinatal viral exposure.
The objective of the study was to investigate the associations between infection, polymorphisms in the mannose-binding lectin gene (MBL), and cerebral palsy (CP). This was a case-control study using deoxyribonucleic acid from newborn screening cards of 443 Caucasian CP cases and 883 Caucasian controls to screen for 6 polymorphisms within the MBL gene. These polymorphisms combine to create haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective (HYPD, LYQC, LYPB) circulating MBL levels. chi(2) Analyses demonstrated significant differences between CP cases and controls (less than 37 weeks chi(2) 14.99, P = .02; less than 32 weeks chi(2) 13.62, P = .02). The MBL haplotype LYPA was associated with CP at all gestations (odds ratio [OR] 1.57, 95% confidence interval [CI], 1.00 to 2.46), less than 37 weeks (OR 2.43, 95% CI, 1.41 to 4.18), and less than 32 weeks (OR 2.54, 95% CI, 1.34 to 4.76). LYPA was also associated with hemiplegic CP for babies born at less than 37 weeks (OR 2.77, 95% CI, 1.02 to 7.26) and less than 32 weeks (OR 4.48, 95% CI, 1.55 to 12.65). HYPD was associated with quadriplegic CP at all gestations (OR 3.47, 95% CI, 1.41 to 8.31) as well as for babies born at less than 32 weeks (OR 7.86, 95% CI, 1.67 to 29.48). Subanalysis on samples previously testing positive for exposure to viral infection demonstrated similar patterns of significance as those presented above, whereas analysis on samples negative for exposure to viral infection showed no positive associations between any of the MBL haplotypes and CP. Potential type I error from multiple analyses is a caveat. MBL haplotypes LYPA or HYPD may be associated with an increased risk of CP in the presence of exposure to viral infection and may act as susceptibility factors for CP.


The influence of 1-(N-L-tryptophan)-1-deoxy-D-fructose [Fru-Trp] and its N-nitrosated analogue [NO-Fru-Trp] on the viability and intracellular synthetic activity (DNA, RNA, and protein synthesis) of HeLa S3-carcinoma cells.
Exposing HeLa S3 cells at 37 degrees C to varied concentrations of, respectively, Fru-Trp (0.1 microM - 1 mM), NO-Fru-Trp (0.1 microM - 1 mM), and NaNO2 (0.6 microM - 6 mM) for varied periods of time (1 - 36 hr) does neither affect their viability (trypan blue dye exclusion test) nor capability to synthesize RNA or protein but is of considerable influence on DNA synthesis in the case of NO-Fru-Trp and NaNO2, but not in the case of Fru-Trp which continues to be ineffective. None of the three compounds tested is of significant influence on cell number. Both NO-Fru-Trp and NaNO2 stimulate DNA synthesis: a maximum of activity [( 3H] thymidine incorporation) exists at the 24 hr time point of incubation, with NO-Fru-Trp, for instance, generating a 2.5-fold increase (over control) at 1 mM concentration in the medium while NaNO2, at comparable concentration, increases DNA synthesis by a factor of 1.6 over control. The increase in DNA synthesis is not due to stimulatory influences on (semi-conservative) DNA replication but represents DNA repair. This was verified by keeping the cells under conditions that prevent normal (semi-conservative) replication but permit repair ("unscheduled DNA synthesis"). Two major routes are suggested by which NO-Fru-Trp could impart DNA damage and, thus, assume mutagenic properties.


Seasonal fluctuations of glial fibrillary acidic protein (GFAP) immunoreactivity in the rat suprachiasmatic nucleus.
The pacemaker of the "biological clock", the suprachiasmatic nucleus (SCN) of the hypothalamus was studied in intact male rats for glial fibrillary acidic protein (GFAP) a specific marker for astrocytes. Immunohistochemical reactions were carried out in winter (January-February) and in summer (June-July). In winter the GFAP-immunoreactivity of the SCN was found low whereas in summer it was high. Gonadectomy reduced differences. Since photic stimuli that apparently trigger the observed differences reach the SCN through identified neuronal pathways we conluded that the reaction of astrocytes is an indicator of seasonally altered neuronal function in the SCN.


Rhinolith: a radiographic finding in a dental clinic.
Rhinolith is a calcified mass found within the nasal cavity. This article is a case report of a 51-year-old woman with an unusual radiopaque lesion located in the nasal maxillary antrum cavity. It was asymptomatic and found accidentally on a routine panoramic radiograph. The rhinolith is presented along with the description of its clinical, radiographic (conventional and CT images), and histopathologic aspects. The objective of this report is to describe and discuss the differential diagnosis of the rhinolith with other oral injuries or conditions and to show how important it is for dental practitioners to be aware of their existence.


The evidence for the existence of chymotrypsin-like esterase activity in the plasma membranes of rabbit neutrophils and the specific chemotactic peptide binding activity of the subcellular fractions.
1. Light- and heavy-plasma membrane fractions have been isolated from rabbit neutrophils and a chymotrypsin-like esterase has been shown to be present in these fractions. 2. The molecular weight of the chymotrypsin-like esterase of rabbit neutrophil plasma membrane was estimated to be about 200 000. 3. About 93% of the chymotrypsin-like esterase of the plasma membranes is esterase 1 and the susceptibility to potential inhibitors was similar in light- and heavy-plasma membrane. 4. Chemotactic peptide, [3H]formyl-norleucyl-leucyl-phenylalanine [3H]formyl-Nle-Leu-Phe) binding by subcellular fractions shows that the highest specific binding was observed in the light-plasma membrane was about 2-fold higher than the heavy-plasma membrane, about 37-fold higher than the nuclear fraction, about 3-fold higher than lysosomal fraction and about 10-fold higher than the microsomal fraction.


Extraocular muscle biopsy during surgery for strabismus of unknown etiology.
Most cases of strabismus have a chronic and stable or known etiologic diagnosis prior to surgery. In some cases, however, surgery is undertaken to correct a stable ocular misalignment without a definitive etiology. We present 2 cases, one with euthyroid Graves' orbitopathy and the other with amyloid light-chain amyloidosis, in which extraocular muscle biopsy performed intraoperatively allowed histopathologic confirmation of a clinical diagnosis.


Persistent chylothorax in lymphangioleiomyomatosis treated by intrapleural instillation of povidone.
Lymphangioleiomyomatosis (LAM) is a rare, idiopathic disease affecting young women often complicated by refractory and difficult to manage chylothorax. We report one case of a patient who received a bilateral lung transplantation for LAM presenting a refractory chylothorax. The instillation of povidone iodine in the pleural space was effective in inducing pleurodesis.


Violence in Playboy magazine: a longitudinal analysis.
This paper analyzes the amount of violence in cartoons and pictorials from January 1954, through December 1983 in Playboy magazine. Inasmuch as the Attorney General's Commission on Pornography and Obscenity has focused upon magazines such as Playboy as potentially harmful to society because of the violence merged with sex, such an analysis is appropriate at this time. Each cartoon and pictorial for each issue of Playboy for the 30-year-period was examined for violent depictions. The average number of violent cartoons for the 30-year-period was 6.92/year or 0.58/issue. The average number of violent pictorials was less with an average of 1.89/year or 0.16/issue. The ratio of violent cartoons or pictorials to the total number of cartoons or pictorials was small. The ratio of violent cartoons to all cartoons was 25.2/1000 and for violent pictorials to all pictorials it was 8.6/1000. Moreover, the ratio of violent cartoons to total pages was 2.86/1000 and for violent pictorials 0.78/1000 pages. Although the overall number and ratio of violent cartoons and pictorials in Playboy over the 30-year-period examined was rare, a major question addressed was whether the amount of violence was increasing. Rather than a linear relation, a curvilinear relationship was observed with the amount of violence on the decrease in recent years. Although the effects of violence in sexual material is still being debated, those who argue for greater censorship of magazines such as Playboy because of its depictions of violence need a new rationale to justify their position.


Ultrasound examination of intrinsic foot muscles in patients with 1st metatarsophalangeal joint arthrodesis.
1st MTP arthrodesis often alleviates pain in osteoarthritis of hallux, long term outcomes vary, yet there is little known about potentially modifiable changes in the small muscles of the foot and hallux. This study was performed to determine the changes in the size of the Intrinsic Foot Muscles (IFMs) after the arthrodesis of the 1st metatarsophalangeal (MTP) joint by comparing the cross-sectional area (CSA) and muscle thickness (MT) of Abductor Hallucis (AbH), Flexor Digitorum Brevis (FDB) and Flexor Hallucis Brevis (FHB) between surgical and non-surgical feet. A convenience sample of 18 feet of 9 subjects (age: 57.56±9.07, weight: 81.33±1.32kg, height: 163.26±11.03cm) with a unilateral history of 1st MTP arthrodesis was recruited. B-mode ultrasound images were collected during sitting and standing positions with a wireless 8-MHz transducer. Hand-held dynamometer was used to measure toe flexion strength. CSA and MT of the surgical feet were significantly lower (P<0.05) for AbH and FHB in both positions. For FDB, the significant difference (P<0.05) was smaller MT in standing. Significantly lower (P<0.05) toe strength was observed in involved toe compared to uninvolved. Greater correlations were seen between toe strength and CSA of FHB and AbH in uninvolved toes compared with involved toes. IFMs in the surgical foot exhibited reduced CSA and MT. Weak core muscles of the foot may result in transmission of shock and forces to the foot skeleton which can lead to skeletal problems such as metatarsalgia, IP joint arthritis etc. that are seen as post-surgical complications. There is nothing in literature that delineates the rehabilitation of foot in this group of patients after surgery. This directs surgeons and clinicians to integrate IFM training in the rehabilitation programs after surgery. Developing appropriate rehabilitation protocols for these patients may help in preventions of post-surgical complications.


High-dose copper activates p53-independent apoptosis through the induction of nucleolar stress in human cell lines.
Copper is an essential micronutrient involved in many redox reactions in human cells. However, a high concentration of copper, intake from the environment or abnormal accumulation within cells because of genetic mutation, leads to cell toxicity. This is attributable to oxidative damage, altered gene expression, and functional impairment of the mitochondria. Copper stress also alters the morphology of the nucleolus, but the process has not been fully elucidated. In this study, cells were treated with copper sulfate at 3-9 ppm and examined if a high dose of copper would block ribosome biogenesis. With the incorrect distribution of nucleolar proteins nucleophosmin and fibrillarin to the nucleoplasm, ribosomal RNA (rRNA) processing was impaired; 34S rRNA from an abnormal A2 cut increased, and downstream pre-rRNAs decreased. The under-accumulation of 60S subunits was detected using sucrose gradients. From transcriptome analysis, ribosome synthesis-related genes were misregulated. Blockage in ribosome synthesis under copper-treatment induced nucleolar stress and triggered p53-independent apoptosis pathways. Thus, nucleolar stress is one cause of cell death under copper exposure.


Genotyping isolates and clones of Giardia duodenalis by polymerase chain reaction: implications for the detection of genetic variation among protozoan parasite species.
Detection of genetic variation among microorganisms can be done by DNA fingerprinting using the polymerase chain reaction (PCR). Application of primers directed to polymorphic DNA leads to the amplification of DNA fragments which differ in length when different species or isolates of a single species are compared. It has been demonstrated that PCR primers resembling eukaryotic repeat motifs enable the straightforward genetic differentiation of Giardia duodenalis isolates. Depending on the repeat motif, genetic variation between cloned G. duodenalis lines could also be detected. DNA polymorphisms could also be detected by random amplification of polymorphic DNA (RAPD) analyses. When the results obtained for G. duodenalis are compared to those found for another protozoan parasite, Naegleria fowleri, clear differences are encountered. In contrast to the findings for G. duodenalis, the repeat motif primers did not allow the discrimination of 'N. fowleri isolates. Apparently, as determined by this PCR-mediated genotyping, genetic variation occurs in G. duodenalis with increased frequency at the isolate level as compared to N. fowleri. The possible implications of this observation for clonality or the definition of a species in protozoan parasites will be discussed.


Regulation of expression of the 3 beta-hydroxysteroid dehydrogenases of human placenta and fetal adrenal.
The appropriate expression of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta-HSD) is vital for mammalian reproduction, fetal growth and life maintenance. Several isoforms of 3 beta-HSD, the products of separate genes, have been identified in various species including man. Current investigations are targeted toward defining the processes that regulate the levels of specific isoforms in various steroidogenic tissues of man. High levels of expression of 3 beta-HSD were observed in placental tissues. It has been generally considered that the multinucleated syncytiotrophoblastic cells are the principal sites of 3 beta-HSD expression and, moreover, that 3 beta-HSD expression is intimately associated with cyclic AMP-promoted formation of syncytia. Herein we report the presence of 3 beta-HSD immunoreactive and mRNA species in uninucleate cytotrophoblasts in the chorion laeve, similar to that in syncytia but not cytotrophoblast placenta. In vitro, 3 beta-HSD levels in chorion laeve cytotrophoblasts were not increased with time nor after treatment with adenylate cyclase activators, whereas villous cytotrophoblasts spontaneously demonstrated progressive, increased 3 beta-HSD expression. Moreover, 3 beta-HSD synthesis appeared to precede morphologic syncytial formation. Thus high steroidogenic enzyme expression in placenta is not necessarily closely linked to formation of syncytia. Both Western immunoblot and enzymic activity analyses also indicated that the 3 beta-HSD expressed in these cytotrophoblastic populations was the 3 beta-HSD type I gene product (M(r), 45K) and not 3 beta-HSD type II (M(r), 44K) expressed in fetal testis. In cultures of fetal zone and definitive zone cell of human fetal adrenal, 3 beta-HSD expression was not detected until ACTH was added. ACTH, likely acting in a cyclic AMP-dependent process, induced 3 beta-HSD type II activity and mRNA expression. The higher level of 3 beta-HSD mRNA in definitive zone compared with fetal zone cells was associated with parallel increases in cortisol secretion relative to dehydroepiandrosterone sulfate formation.


¹⁸F-fluoro-deoxy-glucose focal uptake in very small pulmonary nodules: fact or artifact? Case reports.
18F-fluoro-deoxy-glucose (18 F-FDG) positron emission tomography integrated/combined with computed tomography (PET-CT) provides the best diagnostic results in the metabolic characterization of undetermined solid pulmonary nodules. The diagnostic performance of 18 F-FDG is similar for nodules measuring at least 1 cm and for larger masses, but few data exist for nodules smaller than 1 cm. We report five cases of oncologic patients showing focal lung 18 F-FDG uptake on PET-CT in nodules smaller than 1 cm. We also discuss the most common causes of 18 F-FDG false-positive and false-negative results in the pulmonary parenchyma.In patient 1, contrast-enhanced CT performed 10 days before PET-CT did not show any abnormality in the site of uptake; in patient 2, high-resolution CT performed 1 month after PET showed a bronchiole filled with dense material interpreted as a mucoid impaction; in patient 3, contrast-enhanced CT performed 15 days before PET-CT did not identify any nodules; in patients 4 and 5, contrast-enhanced CT revealed a nodule smaller than 1 cm which could not be characterized. The 18 F-FDG uptake at follow-up confirmed the malignant nature of pulmonary nodules smaller than 1 cm which were undetectable, misinterpreted, not recognized or undetermined at contrast-enhanced CT. In all five oncologic patients, 18 F-FDG was able to metabolically characterize as malignant those nodules smaller than 1 cm, underlining that: 18 F-FDG uptake is not only a function of tumor size but it is strongly related to the tumor biology; functional alterations may precede morphologic abnormalities. In the oncologic population, especially in higher-risk patients, PET can be performed even when the nodules are smaller than 1 cm, because it might give an earlier characterization and, sometimes, could guide in the identification of alterations missed on CT.


Epirubicin and medroxyprogesterone acetate versus estramustine phosphate in hormone-resistant prostatic cancer: a prospective randomized study.
The effect of a medroxyprogesterone acetate (MPA) plus epirubicin combination versus estramustine phosphate was evaluated in 149 prospectively randomized patients with hormone-resistant prostatic cancer. The estimated probability of being free from progression after 1 year was 17% for the patients treated with estramustine and 29% for the MPA-epirubicin group. There is a significant difference between the two groups regarding risk of progression (p = 0.013). However, no difference in survival was recorded (p > 0.30) with about 60% of the patients dead during the first year in both groups. Progression was highly correlated to sedimentation rate (p < 0.001) and to performance index (p = 0.002). Heart failure occurred in a substantial number of patients in both groups which must be considered before starting therapy.


Comparison of continuous, stat, and intermittent cardiac output measurements in patients undergoing minimally invasive direct coronary artery bypass surgery.
To compare intermittent cardiac output (ICO) with continuous cardiac output (CCO) and stat cardiac output (SCO) measurements in patients undergoing minimally invasive direct coronary artery bypass (MIDCAB) surgery. Prospective, clinical study. Single, tertiary referral center. Twenty adult patients undergoing off-pump MIDCAB surgery from January through June 2000. Each patient had a 7.5F 5-lumen pulmonary artery thermodilution catheter (CCO catheter, Baxter Healthcare Corporation, Irvine, CA) inserted for measurement of cardiac output (CO). ICO, CCO, and SCO were compared at 10 predefined time points. A total of 400 data pairs for CO were obtained. ICO values ranged from 1.8 to 8.4 L/min; CCO, 1.9 to 7.5 L/min; and SCO, 2.25 to 6.35 L/min. Correlation between ICO and CCO was significant (correlation coefficient, r = 0.78, p < 0.001), accompanied by a bias of -0.095 L/min and precision of 0.729 L/min. Similarly, the correlation between ICO and SCO was significant (r = 0.79, p < 0.001), accompanied by good accuracy (bias, 0.084 L/min) and precision (0.843 L/min). There were statistically significant decreases in mean arterial pressure, CO, cardiac index, stroke volume, stroke volume index, and left and right ventricular stroke work indices during anastomosis of the left internal mammary artery to left anterior descending artery. These parameters returned to baseline preinduction values 1 minute after completion of the anastomosis. Excellent correlation, accuracy, and precision were found among the 3 methods of measuring CO in patients undergoing MIDCAB surgery. Further studies are needed to assess their accuracy in multivessel off-pump coronary artery bypass graft surgery and in patients with poor left ventricular function.


On-line range verification for proton beam therapy using spherical ionoacoustic waves with resonant frequency.
In contrast to conventional X-ray therapy, proton beam therapy (PBT) can confine radiation doses to tumours because of the presence of the Bragg peak. However, the precision of the treatment is currently limited by the uncertainty in the beam range. Recently, a unique range verification methodology has been proposed based on simulation studies that exploit spherical ionoacoustic waves with resonant frequency (SPIREs). SPIREs are emitted from spherical gold markers in tumours initially introduced for accurate patient positioning when the proton beam is injected. These waves have a remarkable property: their amplitude is linearly correlated with the residual beam range at the marker position. Here, we present proof-of-principle experiments using short-pulsed proton beams at the clinical dose to demonstrate the feasibility of using SPIREs for beam-range verification with submillimetre accuracy. These results should substantially contribute to reducing the range uncertainty in future PBT applications.


Certain observations in electrocardiogram and enzyme variation in dogs, following scorpion venom injection.
The effect of scorpion venom of Buthus Tamulus species on blood pressure, ECG, enzyme and electrolytes were studied in dogs. Venom was given in doses of 2 and 4 mg/kg body weight. Hypotension and tachycardia were observed with low dose and bradycardia was significant with high dose. ST segment depression, T wave changes, shortening of PR interval were the important ECG changes apart from ventricular extrasystoles. With high dose, QRS amplitude was reduced and duration prolonged. QTC interval was also significantly prolonged. Significant increase in SGOT, SGPT and LDH levels were observed but no change in serum electolytes was seen.


Isolated glucocorticoid deficiency: Genetic causes and animal models.
Hereditary adrenocorticotropin (ACTH) resistance syndromes encompass the genetically heterogeneous isolated or Familial Glucocorticoid Deficiency (FGD) and the distinct clinical entity known as Triple A syndrome. The molecular basis of adrenal resistance to ACTH includes defects in ligand binding, MC2R/MRAP receptor trafficking, cellular redox balance, cholesterol synthesis and sphingolipid metabolism. Biochemically, this manifests as ACTH excess in the setting of hypocortisolaemia. Triple A syndrome is an inherited condition involving a tetrad of adrenal insufficiency, achalasia, alacrima and neuropathy. FGD is an autosomal recessive condition characterized by the presence of isolated glucocorticoid deficiency, classically in the setting of preserved mineralocorticoid secretion. Primarily there are three established subtypes of the disease: FGD 1, FGD2 and FGD3 corresponding to mutations in the Melanocortin 2 receptor MC2R (25%), Melanocortin 2 receptor accessory protein MRAP (20%), and Steroidogenic acute regulatory protein STAR (5-10%) respectively. Together, mutations in these 3 genes account for approximately half of cases. Whole exome sequencing in patients negative for MC2R, MRAP and STAR mutations, identified mutations in minichromosome maintenance 4 MCM4, nicotinamide nucleotide transhydrogenase NNT, thioredoxin reductase 2 TXNRD2, cytochrome p450scc CYP11A1, and sphingosine 1-phosphate lyase SGPL1 accounting for a further 10% of FGD. These novel genes have linked replicative and oxidative stress and altered redox potential as a mechanism of adrenocortical damage. However, a genetic diagnosis is still unclear in about 40% of cases. We describe here an updated list of FGD genes and provide a description of relevant mouse models that, despite some being flawed, have been precious allies in the understanding of FGD pathobiology.


Role of Alström syndrome 1 in the regulation of glomerular hemodynamics.
Inactivating mutations in the ALMS1 gene in humans cause Alström syndrome, characterized by the early onset of obesity, insulin resistance, and renal dysfunction. However, the role of ALMS1 in renal function and hemodynamics is unclear. We previously found that ALMS1 is expressed in thick ascending limbs, where it binds and decreases Na+-K+-2Cl- cotransporter activity. We hypothesized that ALMS1 is expressed in macula densa cells and that its deletion enhances tubuloglomerular feedback (TGF) and reduces glomerular filtration rate (GFR) in rats. To test this, homozygous ALMS1 knockout (KO) and littermate wild-type Dahl salt-sensitive rats were studied. TGF sensitivity was higher in ALMS1 KO rats as measured by in vivo renal micropuncture. Using confocal microscopy, we confirmed immunolabeling of ALMS1 in macula densa cells (nitric oxide synthase 1 positive), supporting a role for ALMS1 in TGF regulation. Baseline glomerular capillary pressure was higher in ALMS1 KO rats, as was mean arterial pressure. Renal interstitial hydrostatic pressure was lower in ALMS1 KO rats, which is linked to increased Na+ reabsorption and hypertension. GFR was reduced in ALMS1 KO rats. Seven-week-old ALMS1 KO rats were not proteinuric, but proteinuria was present in 18- to 22-wk-old ALMS1 KO rats. The glomerulosclerosis index was higher in 18-wk-old ALMS1 KO rats. In conclusion, ALMS1 is involved in the control of glomerular hemodynamics in part by enhancing TGF sensitivity, and this may contribute to decreased GFR. Increased TGF sensitivity, enhanced glomerular capillary pressure, and hypertension may lead to glomerular damage in ALMS1 KO rats. These are the first data supporting the role of ALMS1 in TGF and glomerular hemodynamics.NEW & NOTEWORTHY ALMS1 is a novel protein involved in regulating tubuloglomerular feedback (TGF) sensitivity, glomerular capillary pressure, and blood pressure, and its dysfunction may reduce renal function and cause glomerular damage.


Androgen-responsive expression and mitogenic activity of schwannoma-derived growth factor on an androgen-dependent Shionogi mouse mammary carcinoma cell line.
We report here, using the androgen-dependent SC2G cell line derived from Shionogi mouse mammary carcinoma SC115, that cDNA encoding mouse homologue of the rat schwannoma-derived growth factor (SDGF) was isolated and its protein product was identified to be an autocrine growth factor which is expressed in response to androgen in this hormone-dependent cell line. The androgen-independent SC1G cells derived from SC115 were shown to express SDGF even in the absence of androgen, while Northern analysis probed with mouse mammary tumor virus (MMTV) DNA showed that the androgen inducible transcriptional machinery remains functional in this hormone independent cell line.


Comparison of postoperative complications and long-term oncological outcomes in minimally invasive versus open pancreatoduodenectomy for distal cholangiocarcinoma: A propensity score-matched analysis.
Pancreatoduodenectomy (PD) is the only curative therapy for distal cholangiocarcinoma (dCC). There has been no study to compare outcomes between minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD) for dCC. The aim of the study is to compare the two operation types for dCC in terms of postoperative and oncologic outcomes. Data from 426 patients who underwent MIPD (n = 91) or OPD (n = 335) for dCC from January 2012 to December 2019 at two tertiary hospitals were retrospectively reviewed. After 1:2 propensity score matching, postoperative and oncologic outcomes were compared. Minimally invasive pancreatoduodenectomy group showed more favorable results than OPD group in terms of blood loss (MIPD vs OPD, 250 [150-400] vs 400 [200-600], mL, P < .001), and length of hospital stay (19.8 ± 11.3 vs 26.6 ± 14.3 days, P < .001). OPD group showed more favorable results than MIPD group in terms of operation time (MIPD vs OPD, 457 ± 70 vs 398 ± 85 min, P < .001) and harvested lymph nodes (14.9 ± 7.8 vs 20.7 ± 11.5, P < .001). There was no statistical difference between the two groups in the R0 resection rate and complications. In long-term survival analysis, there was no significant difference between the two groups. Minimally invasive pancreatoduodenectomy showed comparable postoperative complications and long-term oncologic survival with OPD in the treatment of dCC.


Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults.
To study the pharmacokinetic and -dynamic behavior of landiolol in the presence of dobutamine in healthy subjects of European ancestry. We conducted a single-center, prospective randomized study in 16 healthy subjects each receiving an infusion of dobutamine sufficient to increase heart rate by 30 bpm followed by a 60 min infusion of 10 μg/kg/min landiolol. Dobutamine-induced increases in heart rate were stable for at least 20 min before a 60 min landiolol- infusion was started. The dobutamine effects were rapidly antagonized by landiolol within 16 min. A further slight decrease in heart rate during 20-60 min of the landiolol infusion occurred as well. Upon termination of landiolol infusion, heart rate and blood pressure recovered rapidly in response to the persisting dobutamine infusion but did not return to the maximum values before landiolol infusion. The pharmacokinetic parameters of landiolol in presence of dobutamine showed a short half-life (3.5 min) and a low distribution volume (0.3 l/kg). No serious adverse events were observed. Landiolol can antagonize the dobutamine-induced increases in heart rate and blood pressure in a fast way. A rapid bradycardic effect until steady-state plasma levels is followed by a slow heart rate reduction. The latter can be attributed to an early desensitization to dobutamine. Consequently, after termination of landiolol, the heart rate did not achieve maximum pre-landiolol values. The pharmacokinetics of landiolol during dobutamine infusion are similar when compared to short- and long-term data in Caucasian subjects. Landiolol in the given dose can thus serve as an antagonist of dobutamine-induced cardiac effects. Registration number 2010-023311-34 at the EU Clinical Trials Register, registration date 2010-12-21.


HLA antigens-linked genetic control in multiple sclerosis patients resistant and susceptible to infection.
Patients with multiple sclerosis (MS) from the two Montreal MS clinics, were divided into two groups: one group of 61 patients (MS type I) who had no clinical history of susceptibility to recurrent respiratory tract infections and a second group of 58 patients (MS type II) who had persistent susceptibility to such infections since childhood. All patients were typed for the HLA tissue antigens. The HLA antigen frequencies of the total MS patient population, and of MS type I and MS type II patients were compared to those of a normal control population and each other. The HLA-DR2 and B7 antigen frequencies were significantly increased compared to the normal controls for all MS patients. MS type I patients had an increased frequency for HLA-Bw42 and DRw8 antigens; the frequency of HLA-A29 was lower than in the controls and MS type II patients. MS type II patients had a significantly increased frequency for DR3 and some HLA-DR3-associated phenotypes (A1 + DR3; B8 + DR3; A1 + B8 + DR3) as compared to controls and MS type I patients. These results are consistent with the existence of genes linked to the HLA antigens, such as immune response genes, which control the resistance or susceptibility of the patients to infection, and suggest that these HLA antigens could be associated with a difference in the evolution of MS, as observed in the MS type I and II patients [21].


RNA aptamers specific for transmembrane p24 trafficking protein 6 and Clusterin for the targeted delivery of imaging reagents and RNA therapeutics to human β cells.
The ability to detect and target β cells in vivo can substantially refine how diabetes is studied and treated. However, the lack of specific probes still hampers a precise characterization of human β cell mass and the delivery of therapeutics in clinical settings. Here, we report the identification of two RNA aptamers that specifically and selectively recognize mouse and human β cells. The putative targets of the two aptamers are transmembrane p24 trafficking protein 6 (TMED6) and clusterin (CLUS). When given systemically in immune deficient mice, these aptamers recognize the human islet graft producing a fluorescent signal proportional to the number of human islets transplanted. These aptamers cross-react with endogenous mouse β cells and allow monitoring the rejection of mouse islet allografts. Finally, once conjugated to saRNA specific for X-linked inhibitor of apoptosis (XIAP), they can efficiently transfect non-dissociated human islets, prevent early graft loss, and improve the efficacy of human islet transplantation in immunodeficient in mice.


The Effect of Monthly Anti-CD25+ Treatment with Basiliximab on the Progression of Chronic Renal Dysfunction after Lung Transplantation.
Chronic renal dysfunction (CRD), as predominantly related to calcineurin-inhibitor (CNI) nephrotoxicity, is associated with increased morbidity and mortality after lung transplantation (LTx). Basiliximab (BSX), a recombinant chimeric monoclonal antibody against CD25+ on activated T-lymphocytes, although often employed as an "induction immunosuppression" after solid organ transplantation, may further allow for reduction in CNI exposure with monthly administration and amelioration of CRD. To determine the effect of monthly anti-CD25+ treatment with basiliximab on the progression of chronic renal dysfunction after lung transplantation. Post-LTx recipients with stages IIIB-V CRD were treated with monthly intravenous infusion of BSX 20 mg. They were analyzed for creatinine clearance at 1, 3, 6, and 12 months; rate of the change in the clearance (the slope of the regression line) and FEV1/month; de novo HLA class I or II DSA; and infectious events (IE). Tacrolimus (TAC) trough levels were concurrently targeted at 2-4 ng/mL during BSX therapy. The criteria for BSX discontinuation included acute lung allograft rejection, acute respiratory infection, and progression to end-stage renal disease (ESRD). 9 LTx recipients were treated with BSX for ≥6 months. The median time past after their LTx was 1853 (range: 75-7212) days; the mean±SD age was 64.3±11.3 years; the male:female ratio was 7:2. The baseline mean±SD creatinine clearance 1-3 months prior to BSX initiation was 22.8±5.14 mL/min/1.73 m2 (CI: 3.95) consistent with CRD stages-IIIB (2), IV (6), and V (1). Prior to BSX treatment, all 9 patients had established CLAD-obstructive-phenotype (BOS, n=4) and restrictive-phenotype (RAS, n=5). During the course of BSX treatment, the aggregate creatinine clearance mean slope increased by a mean±SD of 0.747±0.467 mL/min/1.72 m2/month (CI: 0.359), consistent with "stabilization" of renal function in 7 patients; deterioration occurred in 2 with transition to chronic hemodialysis. Spirometric stability in lung allograft function was observed in 5 patients with a mean±SD aggregate FEV1 slope of -1.49±1.08 mL/month (CI: 2.50). 3 deaths occurred due to the following conditions during BSX treatment-HFpEF/Sepsis + CLAD/Parainfluenza type 2 bronchiolitis + CLAD. 2 recipients developed "weak MFI" HLA class II DSA; no HLA class I DSA was detected during the treatment. Renal sparing therapy with monthly BSX infusion with concurrent reduction in CNI exposure (TAC = 2-4 ng/mL) for stages IIIB-V CRD was associated with stability in creatinine clearance in 78% of patients over a treatment course of 6-12 months. Pre-existing CLAD afflicting all patients and inherent variability in progression of chronic rejection, limits our assessment of BSX efficacy in this context. We detected an infrequent de novo HLA class II DSA during BSX therapy.


The development and postnatal organization of primary afferent projections to the rat thoracic spinal cord.
Primary afferent projections to the thoracic spinal cord in fetal and postnatal rats were labelled by applying horseradish peroxidase (HRP) to the central stumps of cut peripheral nerves. Diaminobenzidine (DAB) and tetramethyl benzidine (TMB) histochemical processing procedures were used to reveal the HRP reaction product. In postnatal rats, individual muscle nerves were labelled to reveal the organization of muscle afferent projections to the motor nuclei. The terminals of muscle afferents were distributed widely across the dendritic arbors of motoneurons supplying the same muscles. No spatial segregation of the terminations of different populations of muscle afferents was discernable. Afferents supplying different regions of the skin were labelled by applying HRP to the dorsal and ventral primary rami of the spinal nerves. Afferents in the dorsal rami projected to lateral portions of both the ipsilateral and contralateral dorsal horns while afferents in the ventral rami projected to the medial portions of both dorsal horns. The projections of the dorsal rami were shifted caudally relative to those of the ventral rami. This relationship reflects the fact that the regions of skin innervated by the dorsal rami are displaced caudally relative to those innervated by the corresponding ventral rami. In fetuses, dorsal rami were labelled alone or in combination with ventral rami. These experiments disclosed the time course of development of the projections to different laminae of the spinal gray matter and revealed that afferents in the two primary rami project to appropriate regions in the ipsilateral and contralateral dorsal horns from the very outset.


Genotype versus phenotype variability in Chlorella and Micractinium (Chlorophyta, Trebouxiophyceae).
The most recent revision of the genus Chlorella, based on biochemical and SSU rDNA analyses, suggested a reduction to a set of four "true" spherical Chlorella species, while a growing number of morphologically different species such as Micractinium (formerly Micractiniaceae) were found to cluster within the clade of "true"Chlorella. In this study, the generic concept in Chlorellaceae to Chlorella and Micractinium was evaluated by means of combined SSU and ITS-2 rDNA sequence analyses and biotests to induce development of bristles on the cell wall. Molecular phylogenetic analyses of Chlorella and Micractinium strains confirmed their separation into two different genera. In addition, non-homoplasious synapomorphies (NHS) and compensatory base changes (CBC) in the secondary structures of SSU and ITS-2 rDNA sequences were found for both genera using this approach. The Micractinium clade can be differentiated into three different genotypes. Using culture medium of the rotifer Brachionus calyciflorus, phenotypic plasticity in Chlorella and Micractinium was studied. Non-bristled Micractinium cells developed bristles during incubation with Brachionus culture medium, whereas Chlorella did not produce bristles. Grazing experiments with Brachionus showed the rotifer preferred to feed on non-bristled cells. The dominance of colonies versus solitary cells in the Micractinium culture was not correlated with the "Brachionus factor". These results suggest that morphological characteristics like formation of bristles represent phenotypic adaptations to the conditions in the ecosystem.


Effectiveness of interventions by non-professional community-level workers or family caregivers to improve outcomes for physical impairments or disabilities in low resource settings: systematic review of task-sharing strategies.
In low-resource settings, access to basic rehabilitation could be supplemented by community-level interventions provided by community health workers, health volunteers, or family caregivers. Yet, it is unclear whether basic physical rehabilitation interventions delivered to adults by non-professional alternative resources in the community, under task-shifting or task-sharing approaches, are effective as those delivered by skilled rehabilitation professionals. We aim to synthesize evidence on the effectiveness of community-level rehabilitation interventions delivered by non-professional community-level workers or informal caregivers to improve health outcomes for persons with physical impairments or disabilities. We performed a systematic review with a PROSPERO registration. Eight databases were searched for (PubMed, CINAHL, Global Health, PDQ Evidence, Scopus, ProQuest, CENTRAL, and Web of Science), supplemented by snowballing and key-informant recommendations, with no time restrictions, applied. Controlled and non-controlled experiments were included if reporting the effects of interventions on mobility, activities of daily living (ADLs), quality of life, or social participation outcomes. Two independent investigators performed the eligibility decisions, data extraction, risk of bias, and assessed the quality of the evidence using the GRADE approach. Ten studies (five randomized controlled trials [RCTs]) involving 2149 participants were included. Most common targeted stroke survivors (n = 8); family caregivers were most frequently used to deliver the intervention (n = 4); and the intervention was usually provided in homes (n = 7), with training initiated in the hospital (n = 4). Of the four RCTs delivered by family caregivers, one demonstrated a statistically significant improvement in mobility (effect size: 0.3; confidence interval [CI] 121.81-122.19; [p = 0.04]) and another one in ADLs (effect size: 0.4; CI 25.92-35.08; [p = 0.03]). Of the five non-RCT studies by community health workers or volunteers, one demonstrated a statistically significant improvement in mobility (effect size: 0.3; CI 10.143-16.857; [p < 0.05]), while two demonstrated improved statistically significant improvement in ADLs (effect size: 0.2; CI 180.202-184.789 [p = 0.001]; 0.4; CI - 7.643-18.643; [p = 0.026]). However, the quality of evidence, based on GRADE criteria, was rated as low to very low. While task-sharing is a possible strategy to meet basic rehabilitation needs in low-resource settings, the current evidence on the effectiveness of delivering rehabilitation interventions by non-professional community-level workers and informal caregivers is inconclusive. We can use the data and experiences from existing studies to better design studies and improve the implementation of interventions. Trial registration PROSPERO registration number: CRD42022319130.


Biodegradation of high molecular weight PAHs using isolated yeast mixtures: application of meta-genomic methods for community structure analyses.
Bioaugmentation for the removal of polyaromatic hydrocarbons (PAHs) from wastewater using bacteria and yeasts is considered environment-friendly and a cost-effective technique. The effectiveness of this biodegradation system depends on the stability of inoculated microorganisms and the availability of nutrients. This study is aimed to investigate the removal of high molecular weight (HMW)-PAHs from biologically treated produced water using different biological systems. Three systems, inoculated with activated sludge (AS), the mixture of five yeast strains (MY), and the mixture of AS and the five yeast strains (SY), respectively, were constructed, and their performance for the removal of HMW-PAHs was compared over 10 weeks. The effluent of the biologically treated produced water from an oilfield was used as the influent after chrysene and benzo(a)pyrene were spiked as HMW-PAHs. Polymerase chain reaction-based denaturing gradient gel electrophoresis (PCR-DGGE) and fluorescent in situ hybridization (FISH) techniques were used to examine the changes in the structures and abundances of the bacterial and yeast communities in these three systems. Only SY and MY systems were capable to remove chrysene (90.7 % and 98.5 %, respectively) and benzo(a)pyrene (80.7 % and 95.2 %, respectively). PCR-DGGE analysis confirmed that all of the five yeast strains inoculated remained in the SY and MY systems, while FISH results showed that the relative abundance of yeast in the SY and MY systems (10.6 % to 21.9 %, respectively) were significantly higher than AS system (2.3 % to 7.8 %, respectively). The relative abundances of the catechol 2,3-dioxygenase (C23O) indicated that the copy number ratios of benzene ring cleavage gene C23O in the yeast amended systems were much higher than that in the AS system. In this study, all of the three systems were effective in removing the low molecular weight (LMW)-PAHs, while HMW-PAHs including chrysene and benzo(a)pyrene were efficiently removed by MY and SY systems, not by AS system. The high HMW-PAHs removal in the MY and SY bioaugmentation systems possibly attributed to the inoculation of the mixed yeast culture. By combining the PCR-DGGE results with the FISH analyses, it was found that yeast probably consisting mainly of the five inoculated strains inhabited in the two bioaugmentation systems as a dominant population. The relatively higher performance of the SY system might be attributed to the suspended growth type which permitted a more efficient contact between microbial cells and contaminants. The bioaugmentation systems (SY and MY) were successfully established by inoculating with five nonindigenous yeast strains and demonstrated high performance in removal of HMW-PAHs.


The determination of natural killer activity of human peripheral blood lymphocytes by measuring the DNA-synthesis of proliferating target cells (K 562 cell line).
Natural killer (NK) activity of human peripheral blood lymphocytes was determined by measuring 3H-thymidine incorporation into proliferating highly NK-sensitive K 562 target cells alone and in the presence of effector cells. Although the absolute figures varied, depending mostly on the strength of DNA-synthesis of the target cells on the day of the assay, the results were highly reproducible and compared well with those of the 51Cr-release assay (CRA). The method was extremely simple and less tedious than CRA. The interpretation of the data was facilitated by including known control cells of low and high NK activity. The cells less sensitive to NK activity did not seem to be suited for this kind of assay.


Dual actions of some amino acids on spike discharges in the carp retina.
The effects of some amino acids (Glu, Gly and GABA), applied in 3 different manners (electrophoretically, in the superfusate and by pressure-microinjection), were investigated on spontaneous and light-induced spike discharges in the isolated carp retina. When applied electrophoretically or by pressure-microinjection in the inner plexiform layer (IPL), the agents acted directly on spike-generating units. Electrophoretic application of Glu at IPL consistently increased while Gly and GABA always decreased spike discharges regardless of the light-induced response patterns, when the tangential distance between the recording and injection electrodes was 25--100 micron. Increasing the distance up to 400 micron diminished the effects, but did not invert them. When added to the superfusate, the amino acids produced a dual action (two different sequential effects); Glu (5 mM) initially decreased and increased spike discharges, while Gly and GABA (5 mM) produced opposite effects. Gly and GABA tended to suppress selectively off-discharges (of ON--OFF units and certain OFF-center units), leaving on-discharges (of ON--OFF units and certain ON-center units) unaffected. The amino acids produced different effects on some units, when applied by pressure-microinjection into OPL or IPL. When injected in OPL Glu suppressed, while in IPL it activated spike discharges, whereas Gly and GABA caused opposite changes to those observed with Glu. Therefore, the action of the agents when pressure-microinjected in OPL is equivalent to the initial action of the agents applied in the superfusate. The dual actions of the agents are assumed to be mediated by bipolar cells, resulting in disfacilitation (Glu) or in disinhibition (Gly or GABA) of spike-generating units.


Comparison of prevalence of microorganisms on titanium and silicone/polymethyl methacrylate obturators used for rehabilitation of maxillary defects.
Silicone or polymethyl methacrylate obturators, used for rehabilitation of maxillary defects, bear the risk of an enhanced settlement of microorganisms and, therefore, impose the risk of local or systemic infections. Titanium-based obturators offer favorable characteristics in contrast to polymer-based protheses in terms of microbial biofilm formation. The purpose of this study was to compare the prevalence of microorganisms on titanium and silicone/PMMA (polymethyl methacrylate) obturators used for rehabilitation of maxillary defects. The obturators of 36 patients (17 titanium based, 19 polymer based) who underwent maxillectomy due to malignancy were evaluated. Microbiological specimens from obturator surfaces, the adjacent mucous surfaces, and the interior of polymer-based obturators were obtained with a sterile swab. Microbiological analysis was performed using conventional methods, including microscopy and culture, on several agar media. For statistical data analysis, Fisher's exact test (FT) (alpha=.05) and odds ratio (OR) (95% confidence interval) were used. Polymer-based obturators showed a significantly higher quantitative and qualitative presence of nonphysiological microorganisms compared to titanium obturators. There is a significant risk (factor 1.4) for the penetration of bacteria to the depths of polymer-based obturators, especially if the surface is contaminated by pathological bacteria (P=.02). The use of titanium-based obturators for the oral rehabilitation of postmaxillectomy patients significantly reduces the risk of infections with pathogenic oral microorganisms and, therefore, may protect patients from local oral or systemic infections.


Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via bifunctional TRAIL antibody.
The search for strategies to target ion channels for therapeutic applications has become of increasing interest. Especially, the potassium channel K(V)10.1 (Ether-á-go-go) is attractive as target since this surface protein is virtually not detected in normal tissue outside the central nervous system, but is expressed in approximately 70% of tumors from different origins. We designed a single-chain antibody against an extracellular region of K(V)10.1 (scFv62) and fused it to the human soluble TRAIL. The K(V)10.1-specific scFv62 antibody -TRAIL fusion protein was expressed in CHO-K1 cells, purified by chromatography and tested for biological activity. Prostate cancer cells, either positive or negative for K(V)10.1 were treated with the purified construct. After sensitization with cytotoxic drugs, scFv62-TRAIL induced apoptosis only in K(V)10.1-positive cancer cells, but not in non-tumor cells, nor in tumor cells lacking K(V)10.1 expression. In co-cultures with K(V)10.1-positive cancer cells the fusion protein also induced apoptosis in bystander K(V)10.1-negative cancer cells, while normal prostate epithelial cells were not affected when present as bystander. K(V)10.1 represents a novel therapeutic target for cancer. We could design a strategy that selectively kills tumor cells based on a K(V)10.1-specific antibody.


Disconnection from others in autism is more than just a feeling: whole-brain neural synchrony in adults during implicit processing of emotional faces.
Socio-emotional difficulties in autism spectrum disorder (ASD) are thought to reflect impaired functional connectivity within the "social brain". Nonetheless, a whole-brain characterization of the fast responses in functional connectivity during implicit processing of emotional faces in adults with ASD is lacking. The present study used magnetoencephalography to investigate early responses in functional connectivity, as measured by interregional phase synchronization, during implicit processing of angry, neutral and happy faces. The sample (n = 44) consisted of 22 young adults with ASD and 22 age- and sex-matched typically developed (TD) controls. Reduced phase-synchrony in the beta band around 300 ms emerged during processing of angry faces in the ASD compared to TD group, involving key areas of the social brain. In the same time window, de-synchronization in the beta band in the amygdala was reduced in the ASD group across conditions. This is the first demonstration of atypical global and local synchrony patterns in the social brain in adults with ASD during implicit processing of emotional faces. The present results replicate and substantially extend previous findings on adolescents, highlighting that atypical brain synchrony during processing of socio-emotional stimuli is a hallmark of clinical sequelae in autism.


Regional analgesia in early active labour: combined spinal epidural vs. epidural.
We randomly allocated 93 women in early active labour and requesting epidural analgesia to receive either epidural (n = 48) or combined spinal-epidural analgesia (n = 45). For epidural analgesia 15 ml of bupivacaine 0.1% with 75 micrograms of fentanyl were injected into the epidural space. For combined spinal-epidural analgesia 1 ml of bupivacaine 0.25% with 25 micrograms of fentanyl were injected into the subarachnoid space. For both groups subsequent top-ups of 10 ml of bupivacaine 0.1% with fentanyl 20 micrograms were given using a lightweight patient-controlled epidural analgesia (PCEA) pump with a lockout time of 30 min. We assessed analgesia and the degree of motor blockade and found no significant differences in pain or maternal satisfaction scores between the two groups. The time to first top-up was significantly longer in the epidural group than in the CSE group (p = 0.01). The combined spinal-epidural group had significantly greater motor blockade at 30 min than the epidural group (p = 0.01), but there was no difference after this. The PCEA machine failed completely twice and temporarily many times. We conclude that the combined spinal-epidural technique confers no advantages in early active labour. Also, a lightweight PCEA pump needs to be more reliable before we can recommend its use.


Biomarkers of atherosclerosis: clinical applications.
Current cardiovascular risk prediction models incorporate traditional risk factors to estimate 10-year cardiovascular risk. Numerous blood-based biomarkers have been identified that are associated with increased cardiovascular risk after adjusting for traditional risk factors. Many of these biomarkers, alone or in combination, have been incorporated into risk prediction models to determine whether their addition increases the model's predictive ability. We review the recently published literature on blood-based biomarkers and examine whether incorporating these markers may improve clinical decision making.


Anticipation in Japanese families with schizophrenia.
The identification of anticipation in schizophrenia is a recent focus in the genetic epidemiology of schizophrenia, although it involves some controversial methodological issues. We explored the evidence of anticipation among 44 Japanese two-generation pairs with schizophrenia found by reviewing nine years of admission records (1986-1994) at the Department of Neuropsychiatry, Nagasaki University Hospital and Michino-o Hospital, Nagasaki. The 44 pairs consisted of 27 two-generation pairs of first-degree relatives group (FDRG) and 17 pairs of second-degree relatives group (SDRG). On pairwise comparison and a life table analysis, the age at onset (AO) was significantly earlier in the lower generation (G2) than in the upper generation (G1) in all of the pairs and in the two subgroups, FDRG and SDRG. Earlier AO was shown in G2 even after minimizing some statistical biases for the study of anticipation in schizophrenia. A significant earlier mean AO was found in G2 even when a cohort effect was controlled for. There was no marked difference in AO between paternal and maternal transmission. These results provide further evidence for epidemiological anticipation, suggesting biological anticipation such as the involvement of trinucleotide repeats expansion in G2. The limitations of the study are also discussed.


Coronary arteriography and left ventriculography during spontaneous and exercise-induced ST segment elevation in patients with variant angina.
The present study is an angiographic demonstration of coronary artery spasm during both spontaneous and exercise-induced angina in three patients with variant angina. In each case, clinical, ECG, coronary angiographic, and left ventriculographic observations were made at rest, during spontaneous angina, and during exercise-induced angina. The character of chest pain was similar during spontaneous and exercise-induced episodes. ST segment elevation was present in the anterior ECG leads during both episodes. The left anterior descending coronary artery became partially or totally obstructed during both types of attacks. When coronary spasm was demonstrated during both types of attacks, left ventriculography disclosed akinetic or dyskinetic wall motion in the area supplied by the involved artery. In those patients with reproducible exercise-induced ST segment elevation and chest pain, thallium-201 scintigraphy showed areas of reversible anteroseptal hypoperfusion. Thus in selected patients exercise-induced attacks of angina were similar to spontaneous episodes.


Avian movements in a modern world: cognitive challenges.
Different movement patterns have evolved as a response to predictable and unpredictable variation in the environment with migration being an adaptation to predictable environments, nomadism to unpredictable environments and partial migration to a mixture of predictable and unpredictable conditions. Along different movement patterns, different cognitive abilities have evolved which are reviewed and discussed in relation to an organism's ability to respond to largely unpredictable environmental change due to climate and human-induced change, and linked to population trends. In brief, migrants have a combination of reliance on memory, low propensity to explore and high avoidance of environmental change that in combination with overall small brain sizes results in low flexibility to respond to unpredictable environmental change. In line with this, many migrants have negative population trends. In contrast, while nomads may use their memory to find suitable habitats, they can counteract negative effects of finding such habitats disturbed by large-scale exploratory movements and paying attention to environmental cues. They are also little avoidant of environmental change. Population trends are largely stable or increasing indicating their ability to cope with climate and human-induced change. Cognitive abilities in partial migrants are little investigated, but indicate attention to environmental cues coupled with high exploratory tendencies that allow them a flexible response to unpredictable environmental change. Indeed, their population trends are mainly stable or increasing. In conclusion, cognitive abilities have evolved in conjunction with different movement patterns and affect an organism's ability to adapt to rapidly human-induced changes in the environment.


Ultrarapid staining for cutaneous melanoma: study and protocol.
Immunohistochemistry has revolutionized the use of frozen sections for the removal of melanoma. Two studies were performed to address the best and fastest way to stain melanocytes in frozen tissue sections. Fifty-six standing cones were taken from sun-damaged white skin and stained with combinations of anti-S-100, anti-HMB-45, anti-Melan-A, and azure B with appropriate controls. Anti-Melan-A was the best immunohistochemical stain. Azure B stains melanin granules metachromatically green and allows differentiation of melanocytes and melanophages. Ultrarapid staining worked as well as rapid staining. Dako's EnVision ultrarapid staining protocol and azure B counterstain represent a dramatic improvement and should be considered the easily obtainable histologic standard when excising cutaneous melanoma.


Nucleoside diphosphate kinase enzyme activity of NM23-H2/PuF is not required for its DNA binding and in vitro transcriptional functions.
nm23 genes encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes, although the mechanisms remain undefined. All Nm23 proteins contain nucleoside diphosphate kinase (NDPK) activity whose significance to these regulatory effects is not yet evident. The protein product of the human nm23-H2 gene functions in vitro both as a nucleoside diphosphate kinase enzyme (NDPK-B; Gilles, A.-M., Presecan, E., Vonica, A. and Lascu, I. (1991) J. Biol. Chem. 266, 8784-8789) and as a transcription factor (PuF; Postel, E. H., Berberich, S. J., Flint, S. J. and Ferrone, C. A. (1993) Science 261, 478-480). To understand the significance of these two biochemical activities to NM23-H2 function, we have investigated the relationship between the DNA binding and transcriptional activity of NM23-H2 and its NDPK function. Using site-directed mutagenesis of the cDNA encoding NM23-H2, we have created a mutant substituting for the amino acid histidine 118, the presumed site of phosphorylation in the formation of the phosphoenzyme intermediate, the nonphosphorylatable amino acid phenylalanine. The H118F mutant protein is shown to be catalytically inactive as measured both in a radioisotopic assay that detects formation of the phosphorylated enzyme intermediate and in a coupled enzyme assay that indicates nucleoside diphosphate formation. These results confirm that histidine 118 is the critical residue for NDPK-B activity. In addition, the H118F mutant protein lacking enzymatic activity displayed normal DNA binding affinity for the c-myc promoter in electrophoretic mobility shift assays, and retained full transcriptional activity using the c-myc gene in vitro. These results indicate a lack of correlation between nucleoside diphosphate kinase activity of nm23-H2 on the one hand, and its DNA binding and transcriptional activity on the other, suggesting that the nm23-H2 gene encodes a bifunctional protein molecule.


The relationship between dietary factors and serum lipids in Chinese urban and rural populations of Beijing and Guangzhou. PRC-USA Cardiovascular and Cardiopulmonary Research Group.
Serum cholesterol (TC) levels and coronary heart disease (CHD) are lower in China than in western countries. This report examines the role of diet in determining TC. Data were collected as part of a cross-sectional study of 10,000 men and women, 35-54 years old, conducted in 1983-1984 in four areas in China. A 10% subsample was surveyed for eating patterns and measurement of blood lipids. Six one-day dietary recalls were collected on each participant. Mean daily intake of energy from fat was less than 30%. Mean Keys scores ranged from 20.4 to 32.6. In multivariable regression analysis controlling for age, body mass index (BMI), and alcohol, Keys score was statistically associated with serum TC. A 10-unit greater Keys score was associated with 6.3 mg/dl higher TC and 4.0 mg/dl higher low density lipoprotein cholesterol. We conclude that in China the relation of dietary factors to serum lipids is similar to that in populations having high serum TC levels.


Growth and isotopic labelling of adherent cells in small volumes of medium.
The in vivo labelling of viral or cellular components is usually conducted through the addition of radioactively labelled precursors to the culture medium. A limiting factor for isotope use is often the cost of isotope purchase and disposal. Therefore, significant savings can be achieved if the smallest possible volume of medium is employed. However, in the case of adherent cells growing in tissue culture dishes or multi-well plates, surface tension causes a very uneven distribution of the liquid due to the formation of a meniscus at the edge of the petri. This prevents the use of very small volumes of medium for cell growth and labelling because the cells at the center of the petri dish would dry out and die, especially after longer incubation periods. In this communication, we describe a technique whereby cells are grown in an area surrounded by a hydrophobic ring of Teflon, which greatly improves the distribution of the medium by eliminating the concave meniscus. This translates into a dramatic improvement in the condition of the cells, as well as the efficiency of labelling of phosphoproteins, such as the Simian Virus 40 large tumor antigen with 32P-orthophosphate or labelling of the cellular DNA with 3[H]thymidine. The technique is useful for any application where growth of cells in small volumes of medium is required.


NDRG1 is expressed in human granulosa cells: An implicative role of NDRG1 in the ovary.
N-myc downstream-regulated gene 1 (NDRG1) is expressed in various human tissues and plays a role in regulating cellular proliferation, angiogenesis, and hypoxia sensing. However, the role of NDRG1 in the ovary remains poorly understood. Therefore, we investigated NDRG1 expression and the role of NDRG1 in the human ovary. Follicular fluid (FF) and luteinized granulosa cells were collected from follicles during oocyte retrieval. KGN cells were cultured with cobalt chloride (CoCl2, a hypoxia-mimicking agent) and/or echinomycin. mRNA, protein levels and secretion, and localization were assessed by real-time PCR, Western blotting, ELISA, and immunohistochemical analysis, respectively. KGN cells were also transfected with NDRG1 siRNA for 72 h. NDRG1 protein was expressed in luteinized granulosa cells. NDRG1 concentration was positively correlated with vascular endothelial growth factor (VEGF) and progesterone concentrations in FF. CoCl2-induced hypoxic stress significantly increased NDRG1 and VEGF mRNA and protein and hypoxia-inducible factor-1α expression compared with those in the controls. The CoCl2-induced overexpression of NDRG1 and VEGF was suppressed by echinomycin. Transfection with NDRG1 siRNA significantly suppressed the release of progesterone in the culture medium. These results indicate that ovarian NDRG1 may play important roles in follicular development, especially in the early luteinization of pre-ovulatory follicles.


Analysis of aflatoxins in various food and feed matrices-results of international validation studies.
Collaborative studies were conducted to evaluate the effectiveness of analytical methods based on immunoaffinity column clean-up prior to high performance liquid chromatography (HPLC) for the determination of aflatoxin B1 and total aflatoxins at European regulatory limits in various food products (4 ng/g total aflatoxins, 2 ng/g aflatoxin B1), baby food (0.1 ng/g aflatoxin B1 in discussion) and feeding stuff (1 ng/g aflatoxin B1 in discussion).The methods showed acceptable within-laboratory and between-laboratory precision for all matrices at these low levels for the determination of both, total aflatoxins and aflatoxin B1.


Complete 1H- and 13C-n.m.r. assignments for two sulphated oligosaccharide alditols of hen ovomucin.
The complete 1H- and 13C-n.m.r. assignments for beta-D-Galp-(1----4)-beta-D-GlcpNAc-6-SO3H-(1----6)-[beta-D-Galp-(1----3 )]- D-GalNAcol and alpha-NeuAcp-(2----3)-beta-D-Galp-(1----3)-[beta-D-Galp-(1----4)-b eta-D- GlcpNAc-6-SO3H-(1----6)]-D-GalNAcol were made by a combination of 2-D correlation experiments (Relayed-Cosy; and 13C,1H Correlation-shift n.m.r. spectroscopy), and 1-D n.m.r. spectroscopy. The results illustrate the ability of these methods to locate sulphate and NeuAc groups in anionic mucinous glycoproteins.


Subject-verb agreement in children and adults: serial or hierarchical processing?
Two processes, serial and hierarchical, are generally opposed to account for grammatical encoding in language production. In a developmental perspective, the question addressed here is whether the subject-verb agreement during writing is computed serially, once the words are linearly ordered in the sentence, or hierarchically, as soon as the number features are determined in a hierarchical frame. Adults and children from 3rd to 5th grades were requested to listen to sentences with built-in prepositional phrases or relative clauses and to transcribe them as quickly as possible. A serial hypothesis assumes that subject-verb agreement errors should be equally frequent with both preambles because each has the same length separating the subject head noun and the main verb. Conversely, according to a hierarchical view, errors should be more frequent with a prepositional phrase because the syntactic distance between the subject and the verb is greater than with a relative clause. The results revealed a main effect of the preamble manipulated in 5th graders and adults, but not in 3rd graders. These data were in favor of a hierarchical processing in older writers and a serial one in younger children. However, in 3rd grade, we assumed that the potential serial account was a result of the resource constraint on writing more than of a real serial processing of the agreement.


Asymmetry and tuning shift of the cervical vestibular evoked myogenic potential indicate saccular dysfunction in idiopathic normal pressure hydrocephalus.
The purpose of this study was to investigate the effects of excessive cerebrospinal fluid (CSF) retention on the peripheral vestibular function and the inner ear fluid in patients with idiopathic normal pressure hydrocephalus (iNPH). In 25 patients with iNPH (14 females, age 65-88 years), cervical vestibular evoked myogenic potential (cVEMP) was measured before the spinal tap test. The asymmetry ratios (ARs) and tuning properties in 500 Hz and 1,000 Hz short-tone burst stimuli of cVEMP were evaluated. Furthermore, cVEMP was measured in an age-matched control group of 12 non-iNPH patients. Seven (28%) iNPH patients exhibited a cVEMP asymmetry (AR > 33%). cVEMP tuning was significantly shifted to a higher frequency in the iNPH group than in the age-matched control group. One-fourth of patients with iNPH had obvious saccular dysfunction. A high rate of a shift in cVEMP tuning in the iNPH group indicated that excessive CSF accumulation propagated to the endolymph and perilymph. Saccular dysfunction might be one of the possible causes of imbalance in iNPH, and the shift in cVEMP tuning may be a determining factor in the diagnosis and treatment strategy.


Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen.
Cypress pollen causes respiratory syndromes with different grades of severity, including asthma. IL-33, its receptor ST2, and dendritic cells (DCs) have been implicated in human respiratory allergy. We sought to define a new mouse model of allergy to cypress pollen that recapitulates clinical parameters in allergic patients and to evaluate the implications of DCs and the IL-33/ST2 pathway in this pathology. BALB/c mice, either wild-type or ST2 deficient (ST2(-/-)), were sensitized and challenged with the Cupressus arizonica major allergen nCup a 1. Local and systemic allergic responses were evaluated. Pulmonary cells were characterized by means of flow cytometry. DCs were stimulated with nCup a 1 and tested for their biological response to IL-33 in coculture assays. nCup a 1 causes a respiratory syndrome closely resembling human pollinosis in BALB/c mice. nCup a 1-treated mice exhibit the hallmarks of allergic pathology associated with pulmonary infiltration of eosinophils, T cells, and DCs and a dominant TH2-type immune response. IL-33 levels were increased in lungs and sera of nCup a 1-treated mice and in subjects with cypress allergy. The allergen-specific reaction was markedly reduced in ST2(-/-) mice, which showed fewer infiltrating eosinophils, T cells, and DCs in the lungs. Finally, stimulation of DCs with nCup a 1 resulted in ST2 upregulation that endowed DCs with increased ability to respond to IL-33-mediated differentiation of IL-5- and IL-13-producing CD4 T cells. Our findings define a novel preclinical model of allergy to cypress pollen and provide the first evidence of a functionally relevant linkage between pollen allergens and TH2-polarizing activity by DCs through IL-33/ST2.


[Imaging of actinic porokeratosis by optical coherence tomography (OCT)].
Disseminated superficial actinic porokeratosis (DSAP) is a rare, genetically heterogeneous skin disorder. We report a case of a 73-year-old female patient who was diagnosed with DSAP by optical coherence tomography (OCT) and histology. During the last 4 years prior to diagnosis, she had developed numerous (pre)malignant lesions of the skin of the lower legs including actinic keratoses, squamous cell carcinomas and Bowen's disease. DSAP lesions and actinic keratoses were resistant to topical treatment with imiquimod and retinoids, but improved with photodynamic therapy (PDT).


Adenosine antagonists delay hypoxia-induced depression of neuronal activity in hippocampal brain slice.
Submerged rat hippocampal slices were exposed to hypoxic medium prepared with 95% N2/5% CO2. The population spikes recorded from CA1 cell layer were completely blocked within a range of 5-10 min. The adenosine antagonist theophylline (100 microM) delayed and partially prevented the hypoxia-induced depression. Increasing concentrations of the more potent adenosine antagonist 8-phenyltheophylline (8-PT; 0.1, 1, 10 microM) resulted in progressively less hypoxia-induced depression. The antidromically elicited afterpotentials recorded in the absence of synaptic transmission in low calcium, high magnesium medium were blocked within 8 min of hypoxia. Theophylline (100 microM) and 8-PT (10 microM) delayed to a similar extent the hypoxia-induced depression of the first afterpotential but did not prevent its complete depression.


Reductive titration of cytochrome P-450 in rat liver microsomes.
Microsomal cytochromes b5 and P-450 of rat liver have been titrated with standardized sodium dithionite solution with a newly developed titrating apparatus that allows spectrophotometric monitoring of the reduction process while strictly O2-free conditions are maintained throughout the procedure. Cytochrome b5 and other electron acceptors in the microsomal preparation were saturated with reducing equivalents prior to addition of carbon monoxide to the system. Continued titration in the presence of CO revealed that 1 electron equivalent was required for the formation of P-450(Fe2+)-CO. These results are in agreement with previous findings of 1 electron equivalence for cytochrome P-450 of adrenocortical mitochondria and P-450CAM.


[Conformational isomerization of lactate dehydrogenase complexes formed by pyruvate and coenzyme analogs].
The kinetics of LDH-catalyzed reduction of pyruvate involving APADH were studied. It was shown that under conditions of a single turnover reaction the first order rate constant is equal to 37+/-4 sec-1. The reaction rate (vo) did not change when a deutero-coenzyme was used. The relationship between vo and pyruvate concentration is hyperbolic. It is concluded that isomerization of the ternary LDH-APADH-pyruvate complex limits the reaction rate. The spectral properties and the kinetics of formation and dissociation of abortive LDH complexes with pyruvate and NAD analogs (APAD and PAAD) were studied. The participation of the carboxamide group of NAD in conformational isomerization of the LDH-NADH-pyruvate and LDH-NAD-pyruvate complexes was studied.


1,4-Bis-(4-meth-oxy-phen-yl)naphthalene.
The title naphthalene derivative, C24H20O2, features 4-methy-oxy-substituted benzene rings in the 1 and 4 positions of the naphthalene ring system. There are two crystallographically independent mol-ecules (A and B) in asymmetric unit. The independent mol-ecules have very similar conformations in which the naphthalene ring systems are only slightly bent, exhibiting dihedral angles between the constituent benzene rings of 3.76 (15) and 3.39 (15)° for A and B, respectively. The pendent 4-methyoxybenzene rings are splayed out of the plane through the naphthalene ring system to which they are connected [range of dihedral angles = 59.63 (13) to 67.09 (13)°]. In the crystal, the mol-ecular packing is consolidated by inter-molecular C-H⋯π inter-actions, leading to supra-molecular chains along the b axis. The chains assemble without directional inter-actions between them.


Fathering pregnancies: marking health-risk behaviors in urban adolescents.
To establish self-reported rates and associated correlates of fathering pregnancies in urban teen males, and to explore the possibility of using their pregnancy history as a marker for other health-risk behaviors. A blinded, self-administered questionnaire was given to the predominantly African-American patients of an inner-city adolescent outpatient clinic. Urine was also collected in a blinded, anonymous fashion, matched to the questionnaires, and tested for five drugs of abuse. Males were classified as having or not having a pregnancy history (PH) according to a questionnaire response item. PH and non-PH participants were compared for eight risk factors using univariate and multivariate methods. A total of 24.2% reported a PH. These males were about 14 times more likely to report three or more sex partners in the last year, more than five times as likely to report a sexually transmitted disease history, more than three times as likely to test positive for drugs, and more than 2.5 times as likely to be inconsistent or nonusers of condoms as compared to males without a pregnancy history. An association between violent behavior and PH is unsupported. Pregnancy history can be a valuable marker for other risk factors among inner-city African-American males. With some patients, it may be easier for clinicians to discuss pregnancy history or fatherhood as opposed to drug abuse and other more sensitive risk factors. The topic can then be used as a gateway for discussion of other risk factors.


Vibrational and scaled quantum chemical study of O,O-dimethyl S-methylcarbamoylmethyl phosphorodithioate, dimethoate.
Infrared and Raman spectra of O,O-dimethyl S-methylcarbamoylmethylphosphorodithioate, dimethoate, have been recorded. Density functional theory, DFT, with the B3LYP functional was used for the optimization of the ground state geometry and simulation of the infrared and Raman spectra of this molecule. Calculated geometrical parameters fit very well with the experimental ones. Based on the recorded data, the DFT results and a normal coordinate analysis based on a scaled quantum mechanical (SQM) force field approach, a complete vibrational assignment was made for the first time.


Pacific decadal oscillation causes fewer near-equatorial cyclones in the North Indian Ocean.
Tropical cyclones do not form easily near the equator but can intensify rapidly, leaving little time for preparation. We investigate the number of near-equatorial (originating between 5°N and 11°N) tropical cyclones over the north Indian Ocean during post-monsoon season (October to December) over the past 60 years. The study reveals a marked 43% decline in the number of such cyclones in recent decades (1981-2010) compared to earlier (1951-1980). Here, we show this decline in tropical cyclone frequency is primarily due to the weakened low-level vorticity modulated by the Pacific Decadal Oscillation (PDO) and increased vertical wind shear. In the presence of low-latitude basin-wide warming and a favorable phase of the PDO, both the intensity and frequency of such cyclones are expected to increase. Such dramatic and unique changes in tropical cyclonic activity due to the interplay between natural variability and climate change call for appropriate planning and mitigation strategies.


Higher Incidence of Stroke on the Last Day of the Month in Hungary-a Role for Psychosocial Factors and Financial Insecurity?
The seasonal cumulation of acute ischemic stroke events is a well-known phenomenon. Critical days are determined by both biological and psychosocial factors. We hypothesized that the financial stability of those with a monthly income living in an economically unpredictable environment rises upon the arrival of their salary and decreases in the preceding days, leading to anxiety and existential insecurity, which may increase the incidence of acute ischemic stroke. We assessed the daily average number of thrombolytic treatments due to acute ischemic stroke in Hungary between December 1, 2005, and November 30, 2013, calculating the ratio of thrombolytic treatments on the last day of the month (irrespectively whether it was the 28th-31st days) to thrombolytic treatments on the other days, and determined 95% confidence intervals. In this period, 7880 thrombolytic treatments were performed nationwide (2.70/day), out of which 1867 occurred on the last day of the month (19.45/day). If the 28th, 29th, or 30th was not the last day of the month, 15.8, 20.6, and 22 times less thrombolytic treatments, respectively, were performed than on the last day of that month. We propose that financial insecurity on the days prior to the receipt of a salary might play a role in the elevation of stroke incidence observed on the last day of the month in Hungary. Further analysis of this phenomenon and its psychosocial effects is needed to adequately allocate healthcare resources and to take preventive measures in the high-risk population.


Activation of isoflavone biosynthesis in excised cotyledons of Lupinus seedlings by jasmonoids and excess light.
Exogenous jasmonic acid (JA) and methyl jasmonate (MJ) induced accumulation of isoflavone constituents in cotyledons prepared from imbibed seeds of white lupin (Lupinus albus L.). Exogenous 0.2 mM MJ enhanced the levels of 7-O-(6"-O-malonyl)glucosylgenistein and 7-O-glucosylgenistein in the cotyledons of etiolated seedlings that had been incubated in the dark for 48 h. Regarding isoflavone induced by excision and slicing in the cotyledons as background level, the effect of light was 2- to 3-fold higher than that of 0.2 mM MJ. Cotyledons exposed to MJ along with a 24-h light period displayed a higher level of isoflavone accumulation than that of light alone. Total molar amounts of isoflavone accumulated in the cotyledons treated with MJ under continuous light were approximately the sum of those induced by MJ alone and light alone, respectively. The additive-like effect of MJ and light on isoflavone accumulation in lupin tissues suggested the presence of two different signaling systems independently responsible for those two stimuli. Excised cotyledons from etiolated yellow lupin (L. luteus L. cv. Topaz) seedlings also supported this hypothesis. The cotyledons could accumulate both an isoflavone and a flavone, and MJ selectively increased some of the isoflavone constituents, whereas light enhanced the levels of both. The selective accumulation mechanism of isoflavonoids in cotyledons, in which jasmonoids are involved, clearly differed from that activated by light.


Esterification of cholesterol by a type III secretion effector during intracellular Salmonella infection.
Survival of Salmonella typhimurium within a vacuole in host cells depends on secreted virulence factors encoded by the Salmonella pathogenicity island 2 (SPI-2). High levels of cholesterol are detected at the Salmonella-containing vacuole (SCV). Here we show that the SPI-2 effector SseJ esterifies cholesterol in vitro, in cells and during infection. Intracellular infections with wild-type as compared with DeltasseJ bacteria led to higher levels of cholesterol ester production in HeLa cells and RAW macrophages and were shown to increase levels of lipid droplets (structures enriched in cholesterol esters). Ectopic expression of SseJ reduced cholesterol levels in cellular membranes and antagonized a major membrane activity of a second bacterial effector known to be important to the stability of the SCV. Previous studies in mouse models of infection have established a virulence defect in DeltasseJ bacteria and have suggested a role for SseJ in regulating SCV dynamics. Our data indicating the molecular activity of SseJ suggest that cholesterol and its esterification at the SCV are functionally important for intracellular bacterial survival.


Serotonin2C receptors (5-HT2C R) control expression of cocaine-induced conditioned hyperactivity.
Environmental cues can become classically conditioned to cocaine exposure and are known to contribute to drug craving and relapse in addicts. The 5-HT2C receptor (5-HT2C R) has been shown to control the behavioral effects of acute cocaine administration and, in the present study, we investigated the role of this receptor in the expression of cocaine-induced conditioned hyperactivity. Rats received repeated pairings of a distinct test environment with either saline or cocaine (15 mg/kg, i.p.) for 7 days. In a drug-free test 2 days after the last pairing, expression of conditioned hyperactivity was seen in the rats previously exposed to cocaine in the test environment. The 5-HT2C R agonist MK 212 (0.0625-0.5 mg/kg, i.p., 5 min before test) significantly decreased, while the 5-HT2C R antagonist SB 242084 (0.5-1 mg/kg, i.p. 30 min prior to test) enhanced, expression of cocaine-induced conditioned hyperactivity. The effective doses of MK 212 and SB 242084 did not alter basal activity on the test session. These results suggest that the 5-HT2C R controls expression of cocaine-induced conditioned hyperactivity and suggest that such ligands may be useful in preventing relapse and promoting abstinence in cocaine-dependent individuals.


Glaucoma hypothesis: application of the law of Laplace.
The objective of the proposed research is to design a test for anticipating glaucoma damage. In this project, the author is utilizing a mathematical equation defined by Laplace's law as applied to a hollow organ. Eye wall stress should be evaluated concomitantly with the intraocular pressure, in order to define the susceptibility of the eye to develop glaucoma. The idea presented in this paper allows for better understanding of different factors responsible for the pathogenesis of open angle glaucoma, of low pressure glaucoma, and of ocular hypertension. It allows one to predict how a given eye will react to a given pressure, that is, whether damage will occur or not. It might answer the question whether to treat right away, or wait and follow. It explains the higher prevalence of glaucoma in myopic eyes. It outlines easy, noninvasive, inexpensive preventive measures, which do not require new and costly facilities. The next step, in further elaboration of this project, should probably be to evaluate the relationship between the ocular pulse and pressure curve. This will be discussed and presented in the future.


Nutritional markers following duodenal switch for morbid obesity.
Laparoscopic duodenal switch with gastric reduction (LapDS) is a minimally invasive hybrid operation combining moderate intake restriction with moderate malabsorption for treatment of morbid obesity. In LapDS, both the quantity of food ingested and the efficiency of digestion are reduced. A cohort of 589 sequential LapDS patients had laboratory studies drawn annually. Serum markers for calcium, iron and protein metabolism and for hepatic function were analyzed using SAS statistical software. There were 95 men and 494 women. Mean age was 44 years, mean BMI 50 kg/m(2) and mean preoperative weight 142 kg. Although mean hemoglobin decreased below reference and mean parathyroid hormone (PTH) increased above reference, similar to abnormal values reported after Roux-en-y gastric bypass, both hemoglobin and calcium in LapDS readily returned to within the reference range following supplementation with iron and calcium respectively. Mean iron, corrected calcium, alkaline phosphatase, albumin, total protein, aspartate aminotransferase (AST), alanine transaminase (ALT), and bilirubin remained within the normal range. LapDS is not associated with broad nutritional deficiencies. Annual laboratory studies, which are required following any type of bariatric operation, appear to be sufficient to identify unfavorable trends. In selected patients, additional iron and calcium supplementation are effective when indicated.


Resistance issues and community-acquired respiratory infections.
Antimicrobial resistance, associated with both excessive and inappropriate use of antimicrobial agents, is a global problem. It is a particular problem in the management of community-acquired respiratory infections, which most often result in the use of antimicrobial therapy. Infections caused by resistant and multiresistant pathogens may also result in high hospitalization rates, long lengths of stay, severe illness, and high mortality, all of which have a great impact on health care costs. The Tracking Resistance in the United States Today (TRUST) Program, the largest longitudinal continuous-surveillance program of its kind, has been conducted every year since 1996 and tracks consecutive respiratory seasons on a year-to-year basis to monitor resistance patterns of respiratory pathogens. This article discusses some of the findings of the TRUST Program, particularly trends in Streptococcus pneumoniae resistance.


Immunophenotyping in pemphigus reveals a TH17/TFH17 cell-dominated immune response promoting desmoglein1/3-specific autoantibody production.
TH2 cells were thought to be a pivotal factor for initiation of the autoimmune blistering disease pemphigus. However, the role of other T-cell subsets in pemphigus pathogenesis remained unclear. We aimed to characterize the exact phenotype of T cells responsible for the development of pemphigus. Whole transcriptome shotgun sequencing was performed to determine differential gene expression in pemphigus lesions and skin of healthy individuals. The cutaneous cytokine signature was further evaluated by real-time quantitative PCR. In peripheral blood, the distribution of TH cell and folliclular helper (TFH) cell subsets was analyzed by flow cytometry. Finally, the capacity of TH and TFH cell subsets to induce desmoglein (Dsg)-specific autoantibodies by memory B cells was evaluated in coculture experiments. Transcriptome analysis of skin samples identified an IL-17A-dominated immune signature in patients with pemphigus, and Kyoto Encyclopedia of Genes and Genomes pathway analysis confirmed the dominance of the IL-17A signaling pathway. Increased expression of IL17A and associated cytokines was also detected by real-time quantitative PCR comparing lesional with perilesional or healthy skin. Interestingly, utilization of flow cytometry showed that patients with active pemphigus had elevated levels of circulating IL-17+, TH17, TFH17, and TFH17.1 cells. Notably, levels of TH17 and TFH17 cells correlated with levels of Dsg-specific CD19+CD27+ memory B cells, and patients with acute pemphigus showed higher levels of Dsg3-autoreactive TFH17 cells. Coculture experiments revealed TFH17 cells as primarily responsible for inducing Dsg-specific autoantibody production by B cells. Our findings show that TFH17 cells are critically involved in the pathogenesis of pemphigus and offer novel targets for therapeutic intervention.