Yeast two-hybrid screening identifies binding partners of human Tom34 that have ATPase activity and form a complex with Tom34 in the cytosol.
In the accompany paper (Mukhopadhyay, A., Avramova, L. V. and Weiner, H., Arch. Biochem. Biophys.), it was shown that Tom34, a previously proposed putative translocase of the mitochondrial outer membrane, binds to the mature region of a precursor protein and appears to be a cytosol protein. Here Tom34 was used as bait in a yeast two-hybrid screening to search for its potential binding partners. Two of the identified proteins were the ATPase-related valosin-containing protein (VCP) and the lysosomal H(+)-transporting ATPase member M (ATP6M). Tom34 was found primarily in the cytosol while VCP and ATP6M were found in the cytosol as well as in nonmitochondrial organelles. Tom34 formed a approximately 400-kDa complex with them in the cytosol. Tom34 was found to possess a weak ATPase activity that did not change when associated with VCP. The tetratricopeptide repeat (TPR) motif region of Tom34 (residue 201-256) was responsible for binding to the other proteins. Tom34 appears not to be a member of the mitochondrial outer membrane translocase family but might function as a chaperone-like protein during protein translocation.


What Is the Best Initial Empirical Treatment of Suspected Sepsis in a Newborn Readmitted Soon after Discharge Home in an Era of Increased Resistance to Antibiotics? A Report of Two Cases.
Background Colonization/infection by antibiotic-resistant bacteria is becoming a major threat to health care systems. Case report Two septic neonates were readmitted in our hospital few days after hospital discharge. In both of them, microbiological workup revealed an infection caused by multiresistant pathogens. Noteworthy, one baby had received intensive care management for 4 weeks, whereas the other had been vaginally delivered and sent home on his second day of life. Conclusion These cases suggest that in countries and/or hospital with high prevalence of colonization/infection by resistant pathogens in nurseries, neonatal intensive care units, and obstetric wards, the choice of initial therapy of suspected sepsis in a neonate readmitted from home soon after discharge should take into account the possibility of an infection due to a multiresistant pathogen.


Isolation of Sphingoid Bases from Starfish Asterias amurensis Glucosylceramides and Their Effects on Sphingolipid Production in Cultured Keratinocytes.
Starfish Asterias amurensis produces sphingoid bases d18:3, 9-methyl-d18:3 (9Me-d18:3), and d22:2, which possess unique structural features. In this study, sphingoid bases prepared from A. amurensis glucosylceramides displayed unexpected elution behaviors from a general octadecyl silyl high-performance liquid chromatography (HPLC) column. For separation and isolation, sphingoid bases were fractionated by octadecyl silyl HPLC after N-acetylation, yielding d18:3, 9Me-d18:3, and two d22:2 isomers. To compare the biological activities of individual sphingoid bases, their effects on sphingolipid production in normal human keratinocytes were evaluated. Treatment with sphingoid bases increased the content of ceramides, glucosylceramides, and sphingomyelins in keratinocytes. Moreover, ceramides, which contain saturated ultra-long-chain fatty acids (C30-34), were significantly increased by treatment with d18:3, but not with other A. amurensis sphingoid bases. The mRNA level of the early differentiation marker keratin 10 was markedly decreased and sphingolipid synthesis-related genes were slightly increased in keratinocytes exposed to A. amurensis-derived d18:3, 9Me-d18:3, and d22:2 isomers. These results suggest that A. amurensis-derived sphingoid bases induce differentiation to varying degrees, sphingolipid production depends on their chemical structures, and d18:3 is the most promising functional sphingoid base.


Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease.
The deposition of amyloid-beta (Abeta) peptides into amyloid plaques precedes the cognitive dysfunction of Alzheimer's disease (AD) by years. Biomarkers indicative of brain amyloid burden could be useful for identifying individuals at high risk for developing AD. As in AD in humans, baseline plasma Abeta levels in a transgenic mouse model of AD did not correlate with brain amyloid burden. However, after peripheral administration of a monoclonal antibody to Abeta (m266), we observed a rapid increase in plasma Abeta and the magnitude of this increase was highly correlated with amyloid burden in the hippocampus and cortex. This method may be useful for quantifying brain amyloid burden in patients at risk for or those who have been diagnosed with AD.


Aspirin hydrolysis in human and experimental animal plasma and the effect of metal cations on hydrolase activities.
The hydrolyzing properties of plasma esterases for aspirin were investigated in human plasma and plasma from experimental animals. The observed rates of aspirin hydrolysis were in the following order: rabbit > human > monkey > rat > mouse > dog > minipig. In human, monkey, and dog plasma, aspirin was hydrolyzed by their major hydrolases, paraoxonase (PON), butyrylcholinesterase (BChE), and albumin. In rabbit, mouse, and rat plasma, carboxylesterase (CES) was determined to be the enzyme responsible for aspirin hydrolysis, and in mouse and rat plasma, especially the latter, hydrolase activity was increased by the addition of ethopropazine, a specific inhibitor of BChE. Interestingly, divalent cations affected the plasma activity by enhancing or inhibiting the hydrolase activity of plasma BChE. The addition of 2 mM calcium increased the hydrolysis of aspirin in human, monkey, and dog plasma by 2.7-, 1.9-, and 2.3-fold, respectively. Magnesium showed a similar but lesser effect. Increasing concentrations of calcium and magnesium resulted in a two-phase stimulatory effect on aspirin hydrolysis in human plasma. In contrast, the addition of zinc had an inhibitory effect on plasma BChE activity. It is postulated that calcium and magnesium bind to BChE and thereby change the conformation of the enzyme to a more appropriate position for aspirin hydrolysis.


FPR1 is the plague receptor on host immune cells.
The causative agent of plague, Yersinia pestis, uses a type III secretion system to selectively destroy immune cells in humans, thus enabling Y. pestis to reproduce in the bloodstream and be transmitted to new hosts through fleabites. The host factors that are responsible for the selective destruction of immune cells by plague bacteria are unknown. Here we show that LcrV, the needle cap protein of the Y. pestis type III secretion system, binds to the N-formylpeptide receptor (FPR1) on human immune cells to promote the translocation of bacterial effectors. Plague infection in mice is characterized by high mortality; however, Fpr1-deficient mice have increased survival and antibody responses that are protective against plague. We identified FPR1R190W as a candidate resistance allele in humans that protects neutrophils from destruction by the Y. pestis type III secretion system. Thus, FPR1 is a plague receptor on immune cells in both humans and mice, and its absence or mutation provides protection against Y. pestis. Furthermore, plague selection of FPR1 alleles appears to have shaped human immune responses towards other infectious diseases and malignant neoplasms.


Acute pulmonary thromboembolism and occult cancer.
Pulmonary thromboembolism (PTE) is an uncommon disease in Asian population when compared with western countries. The definite answer to such a rarity remains unclear. The association of occult malignancy with acute PTE has been well documented in western countries, but has not been reported in Asia. The purpose of this study is to evaluate the occurrence of malignancy after the episode of acute PTE in Chinese patients. We retrospectively analyzed the patients with acute PTE by chart review (ICD-9:415.9) in Taipei Veterans General Hospital from July, 1993 to June, 1998. Patients were clinically followed in out-patient clinic for at least 12 months. A total of 45 patients with acute PTE were identified under strict diagnostic criteria. In the follow-up period, 9 patients with cancer were identified. After exclusion of the cases without regular follow-up and those who died on the acute phase of PTE, the adjusted cancer occurrence after or concomitant with acute PTE in our study was 47.37%, which was significantly higher than previous reports. The origins of malignancy were mainly gastrointestinal tract and genitourinary system, similar to the reports from western countries. The prevalence of occult malignancy after acute PTE is high among Chinese patients in Taiwan. Physicians should be aware of this association, and cancer survey should be performed after the patients are stabilized from acute PTE.


The 4D Space-Time Dimensions of Facial Perception.
Facial information is a powerful channel for human-to-human communication. Characteristically, faces can be defined as biological objects that are four-dimensional (4D) patterns, whereby they have concurrently a spatial structure and surface as well as temporal dynamics. The spatial characteristics of facial objects contain a volume and surface in three dimensions (3D), namely breadth, height and importantly, depth. The temporal properties of facial objects are defined by how a 3D facial structure and surface evolves dynamically over time; where time is referred to as the fourth dimension (4D). Our entire perception of another's face, whether it be social, affective or cognitive perceptions, is therefore built on a combination of 3D and 4D visual cues. Counterintuitively, over the past few decades of experimental research in psychology, facial stimuli have largely been captured, reproduced and presented to participants with two dimensions (2D), while remaining largely static. The following review aims to advance and update facial researchers, on the recent revolution in computer-generated, realistic 4D facial models produced from real-life human subjects. We delve in-depth to summarize recent studies which have utilized facial stimuli that possess 3D structural and surface cues (geometry, surface and depth) and 4D temporal cues (3D structure + dynamic viewpoint and movement). In sum, we have found that higher-order perceptions such as identity, gender, ethnicity, emotion and personality, are critically influenced by 4D characteristics. In future, it is recommended that facial stimuli incorporate the 4D space-time perspective with the proposed time-resolved methods.


Intravenous iron exposure and mortality in patients on hemodialysis.
Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined. The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding. Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of >150-350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or >350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with >0-150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of >1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and >2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46). Among patients on incident dialysis, receipt of ≤ 1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of >1050 mg in 3 months or >2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.


Synthesis, structures and urease inhibition studies of copper(II) and nickel(II) complexes with bidentate N,O-donor Schiff base ligands.
Five mononuclear copper(II) and nickel(II) complexes of Schiff base ligands derived from 4-hydroxyphenethylamine and 2-phenylethylamine were synthesized and determined by single crystal X-ray analysis. The crystal structures of these complexes presented the square planar coordination geometry at the metal center. The inhibitory activity of all the obtained complexes was tested in vitro against jack bean urease. It was found that Schiff base copper(II) complexes, namely [Cu(C(15)H(13)BrNO(2))(2)]·2(C(6)H(7)N) (1), [Cu(C(15)H(12)Br(2)NO(2))(2)]·2(DMF) (2), Cu(C(19)H(16)NO(2))(2) (3) and Cu(C(19)H(16)NO)(2) (5), showed strong inhibitory activity against jack bean urease (IC(50)=1.45-3.59 μM), while Schiff base nickel(II) complex, [Ni(C(19)H(16)NO(2))(2)]·2(DMF) (4), exhibited weak inhibitory activity (IC(50)>50 μM). Their structure-activity relationships were further discussed.


Ruptured uterus in Kaduna, Nigeria: a six-year review.
A six year review in a Nigerian University Teaching Hospital revealed that the incidence of ruptured uterus is 1 per 137 deliveries. The mean age of patients was 30.5 years. Ruptured uterus occurred in younger women with a scarred uterus compared with the unscarred group. The incidence of ruptured uterus was highest in women who were para 5 and above. Cephalopelvic disproportion was the most important obstetric factor associated with rupture (63.4%). Abdominal tenderness (46.3%), vaginal bleeding (31.7%) and pallor (31.7%) were the commonest clinical features at presentation. Shock (22%) was commonest in the unscarred group. Repair with tubal sterilisation was the commonest method of treatment. Diarrhoea was the commonest postoperative complication (39%). Maternal and perinatal mortality rates were 22% and 88% respectively. Improving the emergency capability of the hospital and more efforts at educating our women and reducing poverty will go a long way towards reducing the incidence and adverse clinical outcome of ruptured uterus.


[Medical emergencies in the Yalgado Ouedraogo national hospital of Ouagadougou: patients' profile and assessment of care practices].
The Emergency Department, the showcase of the hospital, must be functional at all times with sufficient resources for looking after the patients without delay. In the Medical Emergency Department of the Yalgado Ouedraogo national hospital of Ouagadougou (Burkina Faso), problems such as delays and difficulties to obtain medicine, give rise to conflicts thus causing the hospital to be a target for public criticism. The aim of this study is to establish the profile of the patients and to assess how they are taken care of. A cross-sectional survey was carried out for 21 consecutive days spread out over three months, from April 25 to June 25, 1997 and concerned all of the 551 patients consulting on those days. The self referral rate was 50.8%. Patients came mainly from the Kadiogo province (90.7%), with their own transport means (85.1%), more often at the beginning of the week (31 patients per day on average) than during week ends (21 patients per day on average, p<0.001). The age group was 15 to 93 years with a mean of 35.4 ( 14,2) years. Infectious diseases, particularly gastroenteritis (21.3%), malaria (12.1%), and pneumonia (10.2%) were the main diagnoses. The median waiting time was 8 min (from 0 to 3 h 59 min), the median therapeutic time was 56 min (from 5 min to 16 h 19 min). Patients were supplied with medicine in 14.5% of cases. Thus median medicine acquisition time was significantly reduced from 35 min to 21 min (p<0.001) when medicines were bought. Medicine acquisition time significantly contributes to increase the therapeutic delay (rs=0.31; p<0.001). The median therapeutic time was 56 min (5 min to 16 h 19 min). The diagnostic accuracy rate was 77.4%, and the satisfaction index 3.5%. Patients expenditure was 9,002 CFA francs on average, including 7,963 CFA francs for medicine. Thus access to medicine constitutes a major point of malfunction, increasing the caretaking time span as well as patients' expenditure. In addition to quickly and systematically supplying medicines to all patients, organizing the reception and providing comfortable waiting conditions must be considered in order to offer better care delivery services.


Reciprocal interactions between gut microbiota and autophagy.
A symbiotic relationship has set up between the gut microbiota and its host in the course of evolution, forming an interkingdom consortium. The gut offers a favorable ecological niche for microbial communities, with the whole body and external factors (e.g., diet or medications) contributing to modulating this microenvironment. Reciprocally, the gut microbiota is important for maintaining health by acting not only on the gut mucosa but also on other organs. However, failure in one or another of these two partners can lead to the breakdown in their symbiotic equilibrium and contribute to disease onset and/or progression. Several microbial and host processes are devoted to facing up the stress that could alter the symbiosis, ensuring the resilience of the ecosystem. Among these processes, autophagy is a host catabolic process integrating a wide range of stress in order to maintain cell survival and homeostasis. This cytoprotective mechanism, which is ubiquitous and operates at basal level in all tissues, can be rapidly down- or up-regulated at the transcriptional, post-transcriptional, or post-translational levels, to respond to various stress conditions. Because of its sensitivity to all, metabolic-, immune-, and microbial-derived stimuli, autophagy is at the crossroad of the dialogue between changes occurring in the gut microbiota and the host responses. In this review, we first delineate the modulation of host autophagy by the gut microbiota locally in the gut and in peripheral organs. Then, we describe the autophagy-related mechanisms affecting the gut microbiota. We conclude this review with the current challenges and an outlook toward the future interventions aiming at modulating host autophagy by targeting the gut microbiota.


Synthesis of Functionalized Chromene and Chroman Derivatives via Cesium Carbonate Promoted Formal [4 + 2] Annulation of 2'-Hydroxychalcones with Allenoates.
A new strategy has been established for the synthesis of functionalized chromene and chroman derivatives via a Cs2CO3-catalyzed domino addition of 2'-hydroxychalcone derivatives with allenoates, which can serve as a general avenue for the construction of multireplaced chromene derivatives. Chemoselectivity of this synthesis was found to depend on substituents on substrates. Good to excellent yields were achieved under simple and mild conditions at room temperature.


Abjection and the weaponization of bodily excretions in forensic psychiatry settings: A poststructural reflection.
Nurses working in forensic psychiatric settings face unique challenges in practice, where they take on a dual role of custody and caring. Patient resistance is widespread within these restrictive settings and can take many forms. Perhaps the most disturbing form of resistance entails a patient's weaponization of their bodily fluids, with nurses as their target. The tendency in assigning motive for this act is to relegate to the psychopathology of the patient. This paper will adopt a poststructuralist perspective to reexamine this phenomenon as an act of resistance through the lens of Kristeva's concept of abjection. Patients confined in these settings have little sense of control, and in resistance may resort to the only thing available: their bodily fluids. By weaponizing the abject, patients actively violate and permeate the physical and psychological boundaries of nurses-the very boundaries considered crucial to safe and professional forensic psychiatric nursing practice. By recognizing this phenomenon as an act of resistance to confinement and loss of control, nurses may reorient their approach to care in forensic psychiatric settings.


Histone Kinase from Soybean Hypocotyls: PURIFICATION, PROPERTIES, AND SUBSTRATE SPECIFICITIES.
A histone-type protein kinase (EC 220.127.116.11) has been partially purified (320-fold) from the crude extracts of soybean hypocotyls by means of a combination of gel filtration and anion exchange procedures. The purified enzyme fraction is devoid of the activities of phosphoprotein phosphatase (EC 184.108.40.206), histone protease, and casein (or phosvitin)-type kinase. The soybean histone kinase uses ATP to phosphorylate specifically lysine-rich histone H1 from either pea seedlings or calf thymus.The histone kinase requires free sulfhydryl group(s) for activity, but not stability. The pH optimum is around 9 to 10. The apparent K(m) values for histone H1 of pea seedlings and calf thymus are 0.4 and 0.9 micromolar, respectively. The K(m) values for ATP are 40 nanomolar with the optimal concentration of Mn(2+) (50 nanomolar) and 0.4 micromolar with that of Mg(2+) (5 millimolar). The estimated molecular weight of the kinase is 52,000 by gel filtration or 48,600 by sedimentation constant (3.2 S). cAMP does not alter the sedimentation velocity of the kinase. The enzyme activity is unaffected by cyclic nucleoside monophosphates and plant growth substances. Like arginine-rich histones, a variety of divalent cations and polycations (polyamines) are inhibitory.This cAMP-independent soybean histone kinase is not associated with the isolated ribosomes but shows highest specific activity in the nuclearchromatin fraction, suggesting that it may function in the regulation of histone H1 phosphorylation in the soybean hypocotyl.


Fenofibrate induces apoptosis of triple-negative breast cancer cells via activation of NF-κB pathway.
There are a lot of unmet needs in patients with triple-negative breast cancer (TNBC). Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, has been used for decades to treat hypertriglyceridaemia and mixed dyslipidaemia. Recent studies show that it might have anti-tumor effects, however, the mechanism remains unclear. Here, we assessed the ability of fenofibrate to induce apoptosis of TNBC in vitro and in vivo and explored involved mechanisms. MTT method was used to evaluate the anti-proliferation effect of fenofibrate, and invert microscope to observe the apoptotic morphological changes. The percentage of apoptotic cells and distribution ratios of cell cycle were determined by flow cytometric analysis. The related protein levels were measured by Western blot method. The changes of genes and pathways were detected by gene expression profiling. The tumor growth in vivo was assessed by MDA-MB-231 xenograft mouse model. Terminal deoxytransferase-catalyzed DNA nick-end labeling (TUNEL) assay was employed to estimate the percentage of apoptotic cells in vivo. In order to evaluate the safety of fenofibrate, blood sampled from rat eyes was detected. We found that fenofibrate had anti-proliferation effects on breast cancer cell lines, of which the first five most sensitive ones were all TNBC cell lines. Its induction of apoptosis was independent on PPAR-α status with the highest apoptosis percentage of 41.8 ± 8.8%, and it occurred in a time- and dose-dependent manner accompanied by up-regulation of Bad, down-regulation of Bcl-xl, Survivin and activation of caspase-3. Interestingly, activation of NF-κB pathway played an important role in the induction of apoptosis by fenofibtate and the effect could be almost totally blocked by a NF-κB specific inhibitor, pyrrolidine dithiocarbamate (PDTC). In addition, fenofibrate led to cell cycle arrest at G0/G1 phase accompanied by down-regulation of Cyclin D1, Cdk4 and up-regulation of p21, p27/Kip1. In vivo, fenofibrate slowed down tumor growth and induced apoptosis with a good safety profile in the MDA-MB-231 xengograft mouse model. It is concluded that fenofibrate induces apoptosis of TNBC via activation of NF-κB pathway in a PPAR-α independent way, and may serve as a novel therapeutic drug for TNBC therapy.


Single-particle and collective excitations of polar water molecules confined in nano-pores within a cordierite crystal lattice.
Recently, the low-temperature phase of water molecules confined within nanocages formed by the crystalline lattice of water-containing cordierite crystals has been reported to comprise domains with ferroelectrically ordered dipoles within the a, b-planes which are antiferroelectrically alternating along the c-axis. In the present work, comprehensive broad-band dielectric spectroscopy is combined with specific heat studies and molecular dynamics and Monte Carlo simulations in order to investigate in more detail the collective modes and single-particle excitations of nanoconfined water molecules. From DFT-MD simulations we reconstruct the potential-energy landscape experienced by the H2O molecules. A rich set of anisotropic temperature-dependent excitations is observed in the terahertz frequency range. Their origin is associated with the complex rotational/translational vibrations of confined H2O molecules. A strongly temperature dependent relaxational excitation, observed at radio-microwave frequencies for the electric field parallel to the crystallographic a-axis, E||a is analyzed in detail. The temperature dependences of loss-peak frequency and dielectric strength of the excitation together with specific heat data confirm a ferroelectric order-disorder phase transition at T0 ≈ 3 K in the network of H2O dipoles. Additional dielectric data are also provided for polarization E||b, too. Overall, these combined experimental investigations enable detailed conclusions concerning the dynamics of the confined water molecules that develop within their microscopic energy landscapes.


Involvement of Cytochrome P-450 in the Biosynthesis of Dhurrin in Sorghum bicolor (L.) Moench.
The biosynthesis of the tyrosine-derived cyanogenic glucoside dhurrin involves N-hydroxytyrosine, (E)- and (Z)-p-hydroxyphenylacetaldehyde oxime, p-hydroxyphenylacetonitrile, and p-hydroxymandelonitrile as intermediates and has been studied in vitro using a microsomal enzyme system obtained from etiolated sorghum (Sorghum bicolor [L.] Moench) seedlings. The biosynthesis is inhibited by carbon monoxide and the inhibition is reversed by 450 nm light demonstrating the involvement of cytochrome P-450. The combined use of two differently prepared microsomal enzyme systems and of tyrosine, p-hydroxyphenylacetaldehyde oxime, and p-hydroxyphenylacetonitrile as substrates identify two cytochrome P-450-dependent monooxygenases: the N-hydroxylase which converts tyrosine into N-hydroxytyrosine and the C-hydroxylase converting p-hydroxyphenylacetonitrile into p-hydroxymandelonitrile. The inhibitory effect of a number of putative cytochrome P-450 inhibitors confirms the involvement of cytochrome P-450. Monospecific polyclonal antibodies raised toward NADPH-cytochrome P-450-reductase isolated from sorghum inhibits the same metabolic conversions as carbon monoxide. No cytochrome P-450-dependent monooxygenase catalyzing an N-hydroxylation reaction has previously been reported in plants. The metabolism of p-hydroxyphenylacetaldehyde oxime is completely dependent on the presence of NADPH and oxygen and results in the production of p-hydroxymandelonitrile with no accumulation of the intermediate p-hydroxyphenylacetonitrile in the reaction mixture. The apparent NADPH and oxygen requirements of the oxime-metabolizing enzyme are identical to those of the succeeding C-hydroxylase converting p-hydroxyphenylacetonitrile to p-hydroxymandelonitrile. Due to the complex kinetics of the microsomal enzyme system, these requirements may not appertain to the oxime-metabolizing enzyme, which may convert p-hydroxyphenylacetaldehyde oxime to p-hydroxyacetonitrile by a simple dehydration.


Employment and risk of female breast cancer in Denmark.
Occupational exposures may play a role in breast cancer etiology, and research focusing on identifying high-risk workplaces is important to advance the understanding and prevention of breast cancer. We undertook a population-based nested case-control study among women who were less than 70 years of age and born in Denmark, based on registry data including 38,375 breast cancer cases and 191,875 controls matched on year of birth, with information on lifetime work history. Odds ratios for women ever employed in a job branch were adjusted for socioeconomic status and reproductive variables. Adjusted odds ratios of less than 0.75 were observed for several occupations in agriculture, hunting, forestry, and fishing, while increased risk patterns (odds ratios greater than 1.50) were noted for a number of production occupations, including employment in graphics and printing, and metal and machinery production. In services, several military professions were also associated with a high increased breast cancer risk. The study shows a variation in the risk of female breast cancer by employment in different industrial and occupational sectors, and suggests that certain occupational exposures, for example, outdoor work, organic solvents, polycyclic aromatic hydrocarbons (PAHs), and night-shift work may play a role in the risk of breast cancer. Further hypothesis-testing studies focusing on these employments with a detailed assessment of specific occupational exposures are warranted.


Sentence processing in Lewy body spectrum disorder: the role of working memory.
Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson's disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body spectrum disorder (LBSD). Thirty-three patients with LBSD were given a two-alternative, forced-choice sentence-picture matching task. Sentence type, working memory, and grammatical structure were systematically manipulated in the sentences. We found that patients with PDD and DLB were significantly impaired relative to non-demented PD patients and healthy controls. The deficit in PDD/DLB was most pronounced for sentences lengthened by the strategic placement of an additional prepositional phrase and for sentences with an additional proposition due to a center-embedded clause. However, there was no effect for subject-relative versus object-relative grammatical structure. An MRI voxel-based morphometry analysis in a subset of patients showed significant gray matter thinning in the frontal lobe bilaterally, and this extended to temporal, parietal and occipital regions. A regression analysis related sentence processing difficulty in LBSD to frontal neocortex, including inferior prefrontal, premotor, and dorsolateral prefrontal regions, as well as right superior temporal cortex. These findings are consistent with the hypothesis that patients with PDD and DLB have difficulty processing sentences with increased working memory demands and that this deficit is related in part to their frontal disease.


A magnesium-sensitive post-synaptic potential in rat cerebral cortex resembles neuronal responses to N-methylaspartate.
In isolated slices of rat cerebral cortex, intracellular recordings were obtained from pyramidal cells that were predominantly in layers II/III. These cells could be antidromically activated from the underlying white matter and had resting potentials of greater than -75 mV, action potentials with amplitudes of greater than 70 mV (measured from threshold), overshoots of 20-30 mV, and thresholds 20-30 mV positive to the resting potential. The responses of these cells to short (1-2 s) pulses of electrophoretically applied N-methylaspartate (NMA) decreased in amplitude with membrane hyperpolarization between -40 and -120 mV, and were associated with an apparent increase in membrane resistance when recorded in the presence of 1 mM-Mg2+. However, in the absence of Mg2+, responses to NMA increased progressively in amplitude with hyperpolarization and were associated with a decrease in membrane resistance. In addition to conventional excitatory post-synaptic potentials (e.p.s.p.s) and inhibitory post-synaptic potentials (i.p.s.p.s), electrical stimulation of the underlying white matter evoked a novel e.p.s.p. This e.p.s.p. displayed a similar voltage relation to the response evoked by NMA and was associated with an apparent increase in membrane resistance. When Mg2+ was removed from the bathing medium, the properties of the novel e.p.s.p. changed, and it displayed a conventional voltage relation and was associated with a decrease in membrane resistance. In the absence of Mg2+, novel e.p.s.p.s showed potentiation on low frequency repetitive stimulation (0.5-2 Hz). A fully potentiated response could evoke bursts of slow potentials each of which could evoke a burst of fast spikes. In contrast, the more conventional e.p.s.p.s and i.p.s.p.s evoked in pyramidal neurones were unaffected by reducing the Mg2+ concentration from 1.0 to near 0 mM and conventional e.p.s.p.s showed no potentiation on repetitive, low frequency repetition, even after several hours exposure to Mg2+-free medium. The NMA antagonists: 2-amino-5-phosphonovaleric acid, ketamine and cyclazocine, applied electrophoretically at doses that blocked responses to NMA, but which had little effect on responses to glutamate, blocked the novel e.p.s.p. and its potentiation.


Evaluation of the users violence in primary health care: Adaptation of an instrument.
Background/Objetivo: According to the World Health Organization, one out of every four violent workplace acts takes place in the health setting. The aims of the study are to study the prevalence of workplace violence in primary healthcare (PHC) professionals by adapting the Healthcare-worker's Aggresive Behaviour Scale-Users (HABS-U), to establish the frequency of exposure to hostile indicators and to determine which professional group is most exposed. Method: Study through qualitative and quantitative methodology in PHC professionals of the Region of Murcia (Spain). In the qualitative phase in-depth interviews were conducted and during the quantitative phase the instrument was used to 574 professionals of 39 PHC centres. Results: The resulting scale shows excellent psychometric properties and correlates significantly with job satisfaction, burnout components, the factors of empathy and psychological well-being. There was a 90.2% prevalence of user violence, and non-medical personnel were found to be the professional group most exposed. Conclusion: The distribution of user violence is not homogeneous among the different professional groups of PHC. The adaptation of the scale may be useful for detection of user violence, as well as to evaluate the efficacy of intervention programs.


[Is serologic screening necessary in the donor bloods for cytomegalovirus seronegative blood transfusion to risky patients?].
Cytomegalovirus (CMV) infections are commonly seen in humans and are usually mild or asymptomatic. However, these infections have significant medical risks in pregnant women, newborns and immunocompromised patients. Seronegative subjects and infants acquire CMV through infected blood products or direct contact with infected people. The use of seronegative blood products for selected patients, as in newborns and/or immunosuppressed patients has vital importance in medical management. Providing seronegative blood in countries where the prevalence of CMV is high (>90%), is difficult since this requires screening of a great number of blood donations. The aim of this study was to detect the CMV seroprevalence among voluntary blood donors in Kocaeli (located at northwestern region of Turkey) and to determine whether the screening procedure was cost-effective. CMV-IgG was investigated by a commercial ELISA method (AXSYM, Abbott, USA) in 1264 blood donors who were voluntarily admitted to donate blood for newborns between January to December 2006. In 1229 (97.2%) of these donors CMV-IgG was found positive while it was negative in 35 (2.8%). It was estimated that CMV-IgG screening was not cost-effective to provide seronegative blood donations because of the high rate of seropositivity in Kocaeli as well as other regions of Turkey, so it would be more favorable to apply alternative methods such as leukocyte reduction.


A matrix of 3,4-diaminobenzophenone for the analysis of oligonucleotides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
A new matrix of 3,4-diaminobenzophenone (DABP) was demonstrated to be advantageous in the analysis of oligonucleotides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. With DABP as a matrix, intact oligonucleotide ions can be readily produced with lower laser powers, resulting in better detection limits, less fragmentation and fewer alkali metal ion adducts compared with the results obtained with conventional matrices. Importantly, minimal fragmentation and fewer alkali metal ion adducts were seen even at low concentrations of oligonucleotides. It was also found that samples prepared with DABP are highly homogenous and therefore reducing the need for finding 'sweet' spots in MALDI. In addition, excellent shot-to-shot reproducibility, resolution and signal-to-noise ratio were seen with DABP as the matrix.


[Individualized surgical management of pulmonary atresia with intact ventricular septum].
To delineate individualized surgical management strategy for the optimal management of pulmonary atresia with intact ventricular septum (PA/IVS). Between 1997 to 2005, 52 consecutive patients with PA/IVS, 31 male and 21 female, aged 2-9, divided into 2 groups according if right ventricle-dependent coronary circulation (RVDCC) existed, underwent individualized surgical treatment. The patients in Group I (with: RVDCC, n = 6) underwent single ventricle repair. Forty-six patients were in Group II (without RVDCC), 13 of which with severe right ventricular hypoplasia (tricuspid valve Z value < -4)underwent single ventricle repair and 33 of which were with mild to moderate right ventricular hypoplasia (Z value > -4). One critical neonate underwent systemic- pulmonary artery shunt. The other 32 of the 33 patients received right ventricular decompression procedures firstly, and 6 of them presented optimal hemodynamics and oxygenation and achieved biventricular repair. If the patients presented unstable hemodynamics or hypoxemia after right ventricular decompression procedure, an additional shunt was added. 13 young infants (0-2 months) underwent additional systemic-pulmonary artery shunt, and 13 patients (> 3 months-old) underwent additional bidirectional cavopulmonary shunt (1.5 ventricular repair)The patients were followed up for 1-10 years. There were 1 early death in Group I and 7 early deaths in Group II. The total early mortality was 15%. A successful definitive repair was achieved in 26 cases (50%). Follow-up reported 3 late deaths. Individualized surgical management based on the presence of RVDCC, right ventricular hypoplasia grading, right ventricular growth potential, hemodynamic situation, and oxygen saturation after the decompression procedure is helpful to improve the surgical results of PA/IVS


Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus.
Feline immunodeficiency virus (FIV) is one of the most common infectious agents affecting cats worldwide .FIV and human immunodeficiency virus (HIV) share many properties: both are lifelong persistent lentiviruses that are similar genetically and morphologically and both viruses propagate in T-lymphocytes, macrophages, and neural cells. Experimentally infected cats have measurable immune suppression, which sometimes progresses to an acquired immunodeficiency syndrome. A transient initial state of infection is followed by a long latent stage with low virus replication and absence of clinical signs. In the terminal stage, both viruses can cause severe immunosuppression. Thus, FIV infection in cats has become an important natural model for studying HIV infection in humans, especially for evaluation of antiviral compounds. Of particular importance for chemotherapeutic studies is the close similarity between the reverse transcriptase (RT) of FIV and HIV, which results in high in vitro susceptibility of FIV to many RT-targeted antiviral compounds used in the treatment of HIV-infected patients. Thus, the aim of this article is to provide an up-to-date review of studies on antiviral treatment of FIV, focusing on commercially available compounds for human or animal use.


Prediction of distribution coefficient from structure. 1. Estimation method.
A method has been developed for the estimation of the distribution coefficient (D), which considers the microspecies of a compound. D is calculated from the microscopic dissociation constants (microconstants), the partition coefficients of the microspecies, and the counterion concentration. A general equation for the calculation of D at a given pH is presented. The microconstants are calculated from the structure using Hammett and Taft equations. The partition coefficients of the ionic microspecies are predicted by empirical equations using the dissociation constants and the partition coefficient of the uncharged species, which are estimated from the structure by a Linear Free Energy Relationship method. The algorithm is implemented in a program module called PrologD.


Characterization of a new in vivo hollow fiber model for the study of progression of prostate cancer to androgen independence.
Research investigating the molecular events underlying progression of prostate cancer to androgen independence has been impeded by the lack of an appropriate in vivo model that yields "pure" populations of prostate cancer cells that are not contaminated with host cells. Here we characterize a new in vivo model that uses hollow fibers and allows for the retrieval of uncontaminated prostate cancer cells during various stages of endocrine progression to androgen independence in male immunocompromised mice. Prostate-specific antigen (PSA) gene expression, proliferation of cells, and histology were examined in these mice before and after castration. LNCaP cells seeded at a density of 1 x 10(7) cells/ml, or a total of approximately 4.8 x 10(6) cells/animal, provided measurable serum PSA levels that increased in intact (noncastrated) animals, decreased by 80% to a nadir after castration, and subsequently increased by 4 weeks after castration, indicating progression to androgen independence. In vivo proliferation of LNCaP cells inside the fibers continued in the presence of androgens and continued to increase, albeit at a slower rate, in the castrated animals. Histology of cells cultivated in hollow fibers demonstrated that initially the cells grew along the wall of the fiber and tended to stack up, forming layers and scaffold structures resembling a solid tumor. Fibers removed from castrated animals with elevated levels of serum PSA contained spheroids of cells that had detached from the fiber wall. The development of the LNCaP hollow fiber model described here provides a reproducible means of obtaining "pure" populations of LNCaP cells during different stages of progression to androgen independence for molecular analysis requiring RNA and protein extracts free of host cell contamination.


Laparoscopic cholecystectomy with full-thickness dissection for potentially cancerous lesions: comparison with standard technique.
With an increase in laparoscopic cholecystectomy (LC) cases, unsuspected gallbladder cancers have been reported and intraabdominal cancer dissemination has been identified as a crucial problem. Since September 1991, we employed LC with full-thickness dissection (LC-F) for polypoid lesions of the gallbladder. In the present study, the utility of the procedure was investigated. For 261 patients who underwent standard LC (S-LC) or LC-F between September 1991 and August 1996, the operation time, intra- and post-operative complications relevant to the operative technique, histological findings of the gallbladders, and prognosis of each patient with gallbladder cancer were evaluated. S-LC and LC-F were performed in 231 and 30 patients, respectively. The mean operation times for S-LC and LC-F were 157 and 120 min, respectively, (p < 0.05). Gallbladder perforation occurred in 29 S-LCs, whereas there was none in 30 LC-Fs (p < 0.05). Bleeding from the gallbladder bed occurred in 1 patient in each of the 2 groups, but was stopped easily. There was neither post-operative bleeding nor bile leakage in either group. Mucosal cancer was diagnosed in 3 gallbladders resected by S-LC and 1 resected by LC-F. One patient of the LC-F group with advanced cancer underwent laparotomy. All the patients have no signs of recurrence. LC-F allows the complete removal of the connective tissue of the gallbladder bed without perforation and, therefore, is considered as a safe and useful procedure for resecting gallbladders with potentially cancerous lesions.


Tongue Root Cyst as a Manifestation of the Variant m.3243A>G.
There are indications that the frequency of cyst formation is increased in mitochondrial disorders (MIDs). Cysts can be found in various organs of MID patients but tongue root cysts have not been reported as a manifestation of a MID. In a 56-year-old male with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) manifesting with recurrent stroke-like episodes, seizures, cognitive impairment, ataxia, psychiatric abnormalities, bilateral visual impairment, bilateral hypoacusis, pre-diabetes, hyperlipidemia, myopathy, and lactic acidosis, an asymptomatic, pre-epiglottic cyst with 1 cm in diameter and protein-rich content in the right tongue root was accidentally detected on ultrasound and confirmed by MRI at the age of 50 years. The patient did not complain about dysarthria or dysphagia but had a mild cerebellar speech. The cyst was confirmed on an MRI six years later, without having changed in diameter, extension, or symptomatology. Due to the atypical location, a branchiogenic cyst was excluded. In conclusion, tongue root cysts may be a manifestation of the m.3243A>G variant.


[Generalized angiomyolipomatosis within the framework of Bournville-Pringle disease--urological aspects].
2 cases of angiomyolipomatosis of the kidneys are taken as the basis for presenting the symptoms, diagnosis and therapy of this rare disease. In one case there was also an angiomyolipomatous change in the retroperitoneal lymph nodes. In differential diagnosis this gave rise to a suspicion of metastasis or a malignant system disease. In another case there was a coincidence with cystic degeneration of the kidneys.


Possible role of Ca ions in the vestibular system.
The Ca++ messenger system is nearly universally present in the control of cell functions by extracellular messengers. It elicits different kinds of responses: either brief, as in neurotransmission and in skeletal muscle contraction, or sustained, as in smooth muscle contraction and in the regulation of transepithelial transport systems. In this latter function the Ca++ messenger system interacts with other cellular modulation systems such as cAMP production and arachidonic acid cascade. In the vestibular apparatus, the Ca++ messenger system is involved in the transduction processes in that it controls both the release of neurotransmitter at the basal pole of the hair cell and the electrical resonance of the cell. It also figures in the contractile properties of cochlear outer hair cells. The Ca++ messenger system as well as adenylate cyclase and prostaglandins may play an important role in the modulation of endolymph secretion.


Optical processing based on conditional higher-order trinary modified signed-digit symbolic substitution.
Techniques for higher-order modified signed-digit trinary arithmetic by using optical symbolic substitution are presented. This method provides fast multibit computation by adopting a two-step symbolicsubstitution scheme. Since more information is represented in fewer digits, this technique leads to a compact design. A content-addressable memory-based and a joint transform correlator-based optical implemention for the proposed technique are also presented.


Children's report of lifestyle counseling differs by BMI status.
This study examined whether children's report of receiving weight, nutrition, and physical activity counseling from their clinicians differs by their BMI status and identified factors associated with higher rates of counseling. Physical assessments and health surveys were collected from a school-based sample of 959 5(th) and 6(th) grade students. Multivariate logistic regression analysis was used to examine how lifestyle counseling differs by BMI status, adjusting for race, gender, socioeconomic status, co-morbidities, site of care provider, and age. Healthy weight children reported receiving the least amount of lifestyle counseling, with nearly one-quarter reporting none at all. Overweight children were no more likely than their healthy weight peers to report receiving weight and nutrition counseling. As expected, obese children were approximately two times more likely to report being counseled on their weight, nutrition, or physical activity as compared to healthy weight children (all p values at least <0.01). However, 23.9% of obese children reported receiving no counseling about their weight. After adjusting for BMI and all other confounding factors, for each lifestyle topic, Hispanics were at least 1.84 times more likely than whites to report being counseled (all p values at least <0.05). Blacks were at least 1.38 times more likely than whites to report being counseled (all p values at least <0.05). Girls were at least 1.38 times more likely than boys to report being counseled (all p values at least <0.05). Although lifestyle counseling is universally recommended, many children report not receiving counseling. Despite clinical indications for more intensive counseling, overweight children report similar counseling rates as their healthy weight peers. Furthermore, a substantial proportion of obese children report not receiving lifestyle counseling. Future research should examine how lifestyle counseling can more effectively reach all children.


[Incidence of leukemia in Krakow in the period 1980-1990].
Based on compiled epidemiological data concerning registered leukemia morbidity in Cracow during the period 1980-1990 a concise calculation of leukemia incidence was made taking into consideration, a year-to-year breakdown of data, leukemia type, sex and age. Our studies showed a rapid increase in total leukemia morbidity in the years 1983-1990 in comparison to 1980-1982. It seems that this increase is caused mainly by the change in leukemia incidence for men.


PTCH2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas.
By a combination of cDNA library screening, rapid amplification of cDNA ends analysis, and BAC sequencing, a novel human patched-like gene (PTCH2) has been cloned and sequenced. The genomic organization is similar to PTCH1 with 22 exons and, by radiation hybrid mapping, PTCH2 has been localized to chromosome 1p33-34, a region often lost in a variety of tumors. Several alternatively spliced mRNA forms of PTCH2 were identified, including transcripts lacking segments thought to be involved in sonic hedgehog binding and mRNAs with differentially defined 3' terminal exons. In situ hybridization revealed high expression of PTCH2 transcripts in both familial and sporadic basal cell carcinomas in similarity to what has been observed for PTCH1, suggesting a negative regulation of PTCH2 by PTCH1. This finding tightly links PTCH2 with the sonic hedgehog/PTCH signaling pathway, implying that PTCH2 has related, but yet distinct, functions than PTCH1.


The elderly mentally retarded person: current perspectives and future directions.
The elderly retarded population continues to grow rapidly, yet there remains a lack of understanding regarding many of the characteristics and needs of these individuals. The aging retarded person presents unique difficulties to care providers because of inconsistencies in population definition, lack of coordination between resources for the aging and retarded, and past neglect in the research literature. The literature regarding the elderly retarded individual is reviewed relative to (1) physical, behavioral, and emotional characteristics, (2) service delivery and programming needs, and (3) suggestions for improved research methodology which emphasize a consumer-oriented knowledge base. Caveats regarding the application of programming mandates for mentally retarded individuals to an aging population are also presented. Future work relating to elderly retarded individuals must take into consideration the rapidly shifting nature of the population through changes in the quality of health care, extent of programming, and governmental policies concerning care of the aged and the mentally retarded person.


The treatment of Barrett's esophagus.
The reflux of the gastric juice in the esophagus can determine the injury of the esophageal epithelium. When the healing of the lesion is done by replacing the normal squamous epithelium with columnar epithelium, the entity is called Barrett's esophagus (BE). Although controversial, some studies showed 0,5% per year the incidence of the esophageal adenocarcinoma in patients with BE, 30 times more often than general population. Taking into consideration the possible development of an adenocarcinoma, the patients with Barrett's esophagus require endoscopic surveillance after a standardized protocol. There is still much controversy about the treatment of patients with Barrett's esophagus, especially in the presence of dysplasia. The aims of the treatment are gastro-esophageal reflux symptoms control, healing of associated esophagitis and prevention of development of adenocarcinoma.


Aestuariimicrobium kwangyangense gen. nov., sp. nov., an LL-diaminopimelic acid-containing bacterium isolated from tidal flat sediment.
Four Gram-positive, catalase-positive, short rod- or coccoid-shaped bacterial strains, R27(T), R44, R45 and R47, were isolated from an enrichment culture with diesel oil-degradation activity and their taxonomic positions were investigated using a polyphasic approach. Phenotypic, phylogenetic and genetic similarities indicated that strains R27(T), R44, R45 and R47 belong to the same species. Phylogenetic analysis based on 16S rRNA gene sequences showed that the four strains form a distinct evolutionary lineage within the family Propionibacteriaceae. The novel four strains had cell-wall peptidoglycan based on LL-diaminopimelic acid, MK-9(H(4)) as the predominant menaquinone and anteiso-C(15 : 0) as the major cellular fatty acid. The DNA G+C contents were 68.8-69.2 mol%. These chemotaxonomic properties, together with phylogenetic distinctiveness, distinguish the four novel strains from recognized members of the family Propionibacteriaceae. On the basis of phenotypic, chemotaxonomic, phylogenetic and genetic data, strains R27(T), R44, R45 and R47 are classified as representatives of a new genus and novel species, Aestuariimicrobium kwangyangense gen. nov., sp. nov., within the family Propionibacteriaceae. The type strain of Aestuariimicrobium kwangyangense sp. nov. is R27(T) (=KCTC 19182(T)=JCM 14204(T)).


Pulmonary sarcoidosis: CT assessment of lesion reversibility.
By comparing serial computed tomographic (CT) scans obtained when sarcoidosis was clinically active and after the onset of remission, an attempt was made to differentiate inflammatory from fibrotic lesions in the lungs of patients with sarcoidosis. Twenty patients with pulmonary infiltration seen on their chest radiographs were studied. For each patient, lesions found on the first CT scan were assessed by two observers as being decreased or increased on the second CT scan. Nodules (n = 8), irregularly marginated nodules (n = 5), and alveolar or pseudoalveolar consolidation (n = 5) always disappeared or clearly decreased. Septal lines (n = 10), nonseptal lines (n = 9), and lung distortion (n = 7) remained unchanged or increased. Some findings varied among patients: Micronodules (n = 9) and subpleural thickening (n = 5) disappeared or decreased in sarcoidosis of recent origin. Many findings of pulmonary infiltration seen on the first CT scan can be considered expressions of either inflammatory (reversible CT findings) or fibrotic (irreversible CT findings) lesions.


Renal medullary carcinoma.
Renal medullary carcinoma is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, mainly sickle cell trait (SCT). Most patients present with metastatic disease and have a worse prognosis. An African-American male with sickle cell disease (HbSCD) who was diagnosed to have renal medullary carcinoma is presented here. The clinical, histologic and radiologic features of this tumor are described. In the setting of advanced disease, treatment modalities have proved largely unsuccessful. Given the shared demographic, clinical and radiographic features of these patients, awareness and early diagnosis may prove essential in improving survival.


Measuring pacemaker dose: a clinical perspective.
Recently in our clinic, we have seen an increased number of patients presenting with pacemakers and defibrillators. Precautions are taken to develop a treatment plan that minimizes the dose to the pacemaker because of the adverse effects of radiation on the electronics. Here we analyze different dosimeters to determine which is the most accurate in measuring pacemaker or defibrillator dose while at the same time not requiring a significant investment in time to maintain an efficient workflow in the clinic. The dosimeters analyzed here were ion chambers, diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to quantify the angular and energy dependence of each dosimeter. Next, 8 patients plans were delivered to a Rando phantom with all the dosimeters located where the pacemaker would be, and the measurements were compared with the predicted dose. A cone beam computed tomography (CBCT) image was obtained to determine the dosimeter response in the kilovoltage energy range. In terms of the angular and energy dependence of the dosimeters, the ion chamber and diode were the most stable. For the clinical cases, all the dosimeters match relatively well with the predicted dose, although the ideal dosimeter to use is case dependent. The dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with many lateral beams. Because of their efficiency, we recommend using a MOSFET or a diode to measure the dose. If a discrepancy is observed between the measured and expected dose (especially when the pacemaker to field edge is <10 cm), we recommend analyzing the treatment plan to see whether there are many lateral beams. Follow-up with another dosimeter rather than repeating multiple times with the same type of dosimeter. All dosimeters should be placed after the CBCT has been acquired.


White-coat hypertension and cardiac organ damage in elderly subjects.
The aim of this study was comparing the cardiac mass in elderly normotensive subjects and elderly white-coat hypertensive patients by examining in perspective, in consecutive patients, office blood pressure (BP), ambulatory BP, and echocardiographically determined left ventricular mass. We studied 42 elderly patients attending a hypertension unit: of these, 22 (mean age 68.7 +/- 3.2 years) had persistent > 90 mm Hg office diastolic blood pressure (DBP), > 140 mm Hg systolic blood pressure (SBP) and < 142/90 mm Hg daytime ambulatory BP (white-coat positives); the remaining 20 (mean age 67.4 +/- 2.2 years) had < 90 mm Hg office DBP, < 140 mm Hg SBP and < 142/90 mm Hg daytime ambulatory BP (normotensives). White coat-patients (n = 22) were selected from a series of 75 consecutive newly diagnosed and never treated patients with mild hypertension (casual DBP constantly between 90 mm Hg and 105 mm Hg). Neither left ventricular mass index (89.9 +/- 23.1 vs 91.8 +/-25.4 P = NS and +/- 25.4 P = NS) and left ventricular mass/height, (115.4 +/- 17.1 vs 119.6 +/- 18.3 P = NS), nor relative wall thickness (0.31 +/- 0.44 vs 0.33 +/- 0.05 P = NS) were significantly higher in white-coat hypertensives as against normotensives. Neither did we find a relevant difference between left atrial diameters in the above considered groups (3.28 +/- 0.41 vs 3.32 +/- 0.37). In fact 81.8% of white-coat hypertensives had left ventricular normal geometry; whilst 13.6% only had concentric remodeling. Age and sex were associated with left ventricular mass index, left ventricular mass/height and relative wall thickness. Multiple regression analysis revealed that it is ambulatory, not office BP that carries independent information about relative wall thickness and left ventricular mass indices. Since elderly white-coat hypertensive subjects did not display a greater cardiac involvement than age-matched normotensives, they should be treated as such.


Photosynthetic carbon metabolism of a marine grass.
The delta(13)C value of a tropical marine grass Thalassia testudinum is -9.04 per thousand. This value is similar to the delta(13)C value of terrestrial tropical grasses. The delta(13)C values of the organic acid fraction, the amino acid fraction, the sugar fraction, malic acid, and glucose are: -11.2 per thousand, -13.1 per thousand, -10.1 per thousand, -11.1 per thousand, and -11.5 per thousand, respectively. The delta(13)C values of malic acid and glucose of Thalassia are similar to the delta(13)C values of these intermediates in sorghum leaves and attest to the presence of the photosynthetic C(4)-dicarboxylic acid pathway in this marine grass. The inorganic HCO(3) (-) for the growth of the grass fluctuates between -6.7 to -2.7 per thousand during the day. If CO(2) fixation in Thalassia is catalyzed by phosphoenolpyruvate carboxylase (which would result in a -3 per thousand fractionation between HCO(3) (-) and malic acid), the predicted delta(13)C value for Thalassia would be -9.7 to -5.7 per thousand. This range is close to the observed range of -12.6 to -7.8 per thousand for Thalassia and agree with the operation of the C(4)-dicarboxylic acid pathway in this plant. The early products of the fixation of HCO(3) (-) in the leaf sections are malic acid and aspartic acid which are similar to the early products of CO(2) fixation in C(4) terrestrial plants.Electron microscopy of the leaves of Thalassia reveal thick walled epidermal cells exceedingly rich in mitochondria and C(3)-type chloroplasts. The mesophyll cells have many different shapes and surround air lacunae which contain O(2) and CO(2). The mesophyll cells are highly vacuolated and the parietal cytoplasm contains an occasional chloroplast. This chloroplast contains grana but the lamellar system is not as developed as the system in epidermal chloroplasts. Extensive phloem tissue is present but the xylem elements are reduced in this aquatic grass. The vascular tissue is not surrounded by bundle sheath cells.This work does not establish the exact relation between structure and function in Thalassia, but it does show the C(4)-type photosynthetic carbon metabolism in this grass involves epidermal and mesophyll cells and internally produced O(2) and CO(2) in the air lacunae.


Association of 8q22.3 locus in Chinese Han with idiopathic premature ovarian failure (POF).
Premature ovarian failure (POF) is a complex heritable disorder known to be caused by chromosomal abnormalities and to date a limited number of known mutations, often autosomal. We sought to identify additional genetic loci associated with POF by performing the first large-scale genome-wide association study (GWAS). GWAS, using Affymetrix SNP 6.0 chip, was conducted in an initial discovery set of 391 well-documented (follicle-stimulating hormone >40 IU/ml) Chinese Han POF patients, compared with 895 unrelated Chinese female controls. A replication study on the most significant loci was then performed in an independent set of 400 cases and 800 controls. Suggestive significant associations were observed at 8q22.3. Replication of eight single-nucleotide polymorphisms (SNPs) (rs10464815, rs10808365, rs3847152, rs3847153, rs3847154, rs3843552, rs10955242, rs3843555) (P ≤ 3.86 × 10(-6)) was confirmed in verification sets. No specific candidate gene was found in the immediate region of 8q22.3. This GWAS, involving by far the largest sample of POF cases accumulated to date, revealed heretofore unrecognized association between POF and a novel genetic locus or region of unknown nature on 8q22.3. We speculate existence of a long-distance regulatory region that has relevance to the control of ovarian differentiation or oogenesis. Given failure to find association with any of the other autosomal regions known to harbor genes causing ovarian failure, our findings also underscore the likelihood of considerable genetic and etiologic heterogeneity in POF and the need for additional approaches like whole-genome sequencing.


Preparation, formulation and evaluation of novel photo-cured glass ionomers based on co-polymers of (meth)acrylated amino acids.
A novel photo-cured amino-acid-constructed glass-ionomer cement system has been developed. Glutamic acid- and beta-alanine-based methacrylate and acrylate derivatives were synthesized, characterized and used to construct the polyalkenoic acids and formulated with water and Fuji II glass filler to form self-cured cement. Compressive strength (CS) of the cement and viscosity of the liquid were used as tools for evaluation. The effects of molar ratio and molecular weight (MW) were studied. The optimized co-polymer was further modified with glycidyl methacrylate (GM) and formulated with water, acrylic acid and Fuji II LC filler to form photo-cured cement. The effects of MW, GM tethering ratio, polymer liquid ratio and glass filler powder/polymer liquid (P/L) ratio were investigated. CS, flexural strength (FS) and viscosity were used as screening tools to find the optimal formulation. All the specimens were conditioned in distilled water at 37 degrees C for either 24 h or 7 days prior to testing. The results show that amino-acid-constructed polyalkenoic acids can be formed only from amino acid methacrylate derivatives or by co-polymerization of methacrylate with acrylate derivatives. Among the numerous co-polymers synthesized, poly(methacryloyl glutamic acid-co-acryloyl beta-alanine) or poly(MGA-co-ABA) with the molar ratio of 8:2 and MW of 19.5 kg/mol contributed the highest mechanical strengths and lower working viscosity to the cement. For photo-cured system, the effects of GM tethering ratio, polymer content and P/L ratio were significant. It is found that an appropriate ratio balance between these parameters is very important. The effect of molecular weight was not significant. The self-cured experimental cement was 32% higher in FS than Fuji II and the same in CS and DTS as Fuji II. The photo-cured experimental cement was 19%, 47% and 176% higher in CS, DTS and FS than Fuji II LC.


Types of Glaucoma and Associated Comorbidities Among Patients at King Abdulaziz Medical City, Jeddah.
Aim To identify the types of glaucoma and associated comorbidities among patients attending the ophthalmology clinic at King Abdulaziz Medical City (KAMC) in Jeddah. Methods A cross-sectional study that included all glaucoma patients at KAMC in Jeddah between June 1st, 2016 and November 30th, 2020. Data were collected through retrospective chart review from the electronic medical record system (BestCare) and utilized a structured data collection sheet. Results A total of 283 patients met the inclusion criteria. The most common type was primary open-angle glaucoma (POAG; 53%) followed by secondary glaucomas (SG; 26.5%) then childhood glaucoma and primary angle-closure glaucoma (CG, PACG; 7.4%). The majority of secondary glaucoma cases were due to neovascular glaucoma (NVG; 44.9%), followed by phacomorphic glaucoma (17.9%) and phacolytic glaucoma (10.3%). Hypertension (60.8%) and diabetes (58.3%) were the most prevalent systematic comorbidities, and cataract (49.1%) was the most prevalent ocular comorbidity. Conclusion POAG was the most common glaucoma type, followed by SG, CG, and PACG. Among secondary glaucoma types, neovascular glaucoma was found to be the most common subtype. Hypertension was the most prevalent comorbid condition.


Treatment changes and improved outcomes in RA: an overview of a large inception cohort from 1989 to 2009.
The introduction of effective treatment strategies in the past two decades has changed the management of RA dramatically. The objective was to analyse the changes in disease activity, function, joint damage and incidence of orthopaedic surgery over a period of 20 years (1989-2009) for patients with RA. Data acquired from 1989 to 2008 inclusive from the Nijmegen RA inception cohort were studied. By repeated measures analysis the course of the population mean disease activity score (DAS28) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) corrected for age, gender, RF and disease duration was determined. Orthopaedic interventions were analysed as incidence rates with a Poisson distribution. We calculated the prevalence of the various therapies that patients were receiving. By 2009, 992 patients with RA had been included and 273 had been excluded. From 1989 onwards, the proportion of patients using MTX increased from 5% (8 of 164) to 62% (486 of 780), and biologic response modifiers from 0% to 22% (168 of 780) in 2008. The average MTX dosage increased to 16.1 ± 5.5 mg/week in 2008. The mean DAS28 (3.1) and HAQ-DI (0.47) were least (P < 0.008) in 2008 compared with previous years. There was a significant trend towards lower incidence rates of orthopaedic intervention in the period 2006-2008 than in almost all previous years. Treatment strategy changed in a large inception cohort of patients with RA which coincided with decreased disease activity, increased functional ability and fewer orthopaedic interventions since the early 1990s.


[Accessory mandibular canals in the human].
Besides the persisting mandibular canal accessory ducts pass through the bony lower jaw in fetuses and children. 2 of the ducts are more constant than others. They are named according to the first authors canals of Serres and Robinson. By histological and macroscopical methods and by X-ray technique we studied these ducts during development in human fetuses and children and counted their occurrence in the adult.


Development of the Everyday Life Rehabilitation model for persons with long-term and complex mental health needs: Preliminary process findings on usefulness and implementation aspects in sheltered and supported housing facilities.
This paper describes the initial phases of the design and development of the Everyday Life Rehabilitation (ELR) intervention, and it presents preliminary findings on usefulness and implementation aspects derived from an ongoing larger trial exploring the effect, cost-effectiveness, and usefulness of ELR. ELR is a model designed to meet the absence of meaningful activities and challenges with integrated, activity- and recovery-oriented rehabilitation in sheltered and supported housing facilities for persons with extensive psychiatric disabilities. The aim of the present study was to examine early experiences of implementing the ELR model from the perspectives of managers, housing staff, and occupational therapists. The paper will sum up preliminary findings based on process data included in an internal pilot prior to a full-scale pragmatic clustered RCT. Four Swedish municipalities with 19 housing facility units were involved and provided process data for the study. Thematic analysis were applied. The informants perceived the methodology to be well suited to the target group and context and to contribute to positive changes in participants' lives. The web-based training was also experienced as relevant and easily accessible to staff, as well as elements of collegial learning and feedback. However, they reported that their municipalities lacked basic conditions for making the whole concept work in such a short time. The ELR is overall perceived as useful, but experiences also make complex difficulties visible regarding integrated, coordinated rehabilitation and organizational readiness. Based on findings, a recommendation on basic prerequisites will be added to the ELR guidance for leadership and management. [ClinicalTrials.gov, 24 September 2021], identifier [NCT05056415].


Judgment, 20 March 1986.
The Court in this decision authorized an abortion to be performed on a women who was seventeen weeks' pregnant. The woman was unable to express her will with respect to the abortion because she was suffering from chronic schizophrenia and autism. The Court made its ruling under Article 13 of Law No. 184 of 22 May 1978, which allows a Court to authorize an abortion in such circumstances and requires a court to base its decision on the findings of a physician's report. Here, the physician's report stated that the woman's precarious mental equilibrium could be threatened if the pregnancy were continued.


PDCA expression by B lymphocytes reveals important functional attributes.
We have demonstrated in this study the existence of a PDCA-expressing functional B cell population (PDCA+ B lymphocytes), which differentiates from activated conventional B (PDCA-IgM+) lymphocytes. Stimulation with anti-micro, LPS, CpG oligodeoxynucleotide, HSV-1, or CTLA-4 Ig activates the PDCA+ B lymphocytes, leading to cell division and induction of type I IFNs and IDO. Notably, the PDCA+ B lymphocytes are capable of Ag-specific Ab production and Ig class switching, which is corroborated by transfer experiments in B- and PDCA+ B lymphocyte-deficient microMT mice. Importantly, in lupus-prone MRL-Fas(lpr) mice, PDCA+ B lymphocytes remain the principal source of autoantibodies. The PDCA+ B lymphocytes have phenotypes with plasmacytoid dendritic cells, but are a distinct cell population in that they develop from C-kit+B220+ pro-B precursors. Thus, our data suggest that not all PDCA+ cells are dendritic cell-derived plasmacytoid dendritic cells and that a significant majority is the PDCA+ B lymphocyte population having distinct phenotype and function.


Bathing. Pleasure or pain?
Bathing creates some of the highest levels of discomfort in the lives of individuals diagnosed with dementia. The present study measured the frequency of 14 agitated behaviors during bathing in 15 elderly residents with dementia residing in a continuing care center. Each resident was observed for four sessions of two different bathing methods, the conventional tub bath and a modification of the bed bath, known as the Thermal bath. The summed frequencies of all agitated behaviors was significantly less for the Thermal bath than the tub bath. This overall effect was greater in men than women and in one particular behavior, shivering. The results suggest that for individuals with dementia the Thermal bath offers a viable alternative to the conventional tub method. Further research may clarify other parameters, such as cost effectiveness and long-term effects of the use of non-rinse cleansers for elderly individuals.


Executive functions mediate the association between alcohol use and declarative memory symptoms in daily life.
Alcohol use is associated with memory problems in young adults with HIV, but the cognitive mechanisms of that association are not known. Sixty adults (aged 19-24 years) living with HIV were administered the Alcohol, Smoking, and Substance Involvement Screening Test to assess alcohol use, Behavior Rating Inventory of Executive Function for self-reported executive functions, and the Prospective and Retrospective Memory Questionnaire (PRMQ) for dailiy memory functioning. Controlling for mood, self-reported executive functions fully mediated the relationship between alcohol use and memory (indirect effect b=.568, 95%CI [.209,.888]). Findings suggest that self-reported executive dysregulation of memory processes (e.g., Strategic encoding and retrieval) may drive the effects of alcohol use on daily memory symptoms.


Outcome of endoscopic third ventriculostomy and Chhabra shunt system in noncommunicating non-tumor childhood hydrocephalus.
Endoscopic third ventriculostomy (ETV) the main alternative to ventriculoperitoneal shunt (VPS) is just beginning to have a foothold in West Africa. It provides a great opportunity for a hydrocephalic child to be shunt free. The purpose of this paper is to compare outcome following ETV and VPS (using the cheap Chhabra shunt) in children with noncommunicating non-tumoral hydrocephalus in an environment where late presentation is the norm. Sixty-three pediatric patients (< 6 years) with hydrocephalus who underwent a VPS or ETV at our hospital were included in this study. The study period was of 30 months (January 2006 till June 2008). Clinically successful outcome was defined as no event occurring during or after surgery that resulted in an alternate surgical procedure, or significant post-operative complication that includes death. All complications related to the procedures were also analyzed. The outcome of surgical intervention was not significantly related to the gender, age of the patient at surgery, or type of surgery. The post-operative complication rate was similar in both groups. The clinical outcome of ETV is comparable to that of VPS, with the added benefit of no shunt-related problems; and being a short procedure, patient anesthesia and operation time, hospital stay, and cost are significantly reduced. We consider ETV to be the procedure of choice for the treatment of noncommunicating nontumoral hydrocephalus in the pediatric population.


Inkjet Etching of Polymers and Its Applications in Organic Electronic Devices.
Inkjet printing techniques for the etching of polymers and their application to the fabrication of organic electronic devices are reviewed. A mechanism is proposed for the formation of via holes in polymer layers through inkjet printing with solvent, and recent achievements in the fabrication with inkjet etching of various three-dimensional microstructures (i.e., microwells, microgrooves, hexagonal holes, and concave structures) are discussed. In addition, organic electronic devices are presented that use inkjet-etched subtractive patterns as platforms for the selective depositions of an emissive material, a liquid crystal, an organic conductor, an organic insulator, and an organic semiconductor, and as an optical waveguide.


Adenosine 5'-triphosphate analogues as structural probes for Escherichia coli glutamine synthetase.
Introduction of specific structural probes into substrate binding sites of Escherichia coli glutamine synthetase is now possible. Various analogues of ATP substituted with an amino or sulfhydryl moiety at the 6- or 8-position of the purine ring have been found to substitute for ATP in the autoinactivation reaction of the manganese enzyme with L-Met-(S)-sulfoximine at pH 7. Dissociation of enzyme complexes containing an ADP analogue, L-Met-(S)-sulfoximine phosphate, and 2 equiv of Mn2+ is negligible at neutral pH. Prior to binding of the mercapto nucleotides to active sites, 6-mercaptopurine ribonucleoside triphosphate (6-S-ATP) and 8-mercaptoadenosine 5'-triphosphate (8-S-ATP) also have been further modified with fluorescent and chromogenic probes for energy-transfer measurements [Maurizi, M. R., Kasprzyk, P. G., & Ginsburg, A. (1986) Biochemistry (following paper in this issue)] or with electron-dense markers for electron microscopic and X-ray crystallographic structural analyses. Binding 6-S-ATP or 8-S-ATP to enzyme active sites at pH 7.1 produced red shifts of approximately 6 nm in nucleotide spectra characteristic for transfer of these nucleotide analogues into more acidic and hydrophobic environments. The spectrum of 6-S-ADP at active sites was more red-shifted than that of 6-S-AMP attached to adenylylation sites. The thiol group at the 6- or 8-position of the purine ring of the bound nucleotides was accessible for reactions with alkylating or mercurial reagents. Alkylation or mercaptide formation produced large blue shifts in the spectrum of enzyme-bound 6-S-ADP or 8-S-ADP at active sites or of 6-S-AMP covalently bound at adenylylation sites. At least one of two tryptophanyl residues in each subunit is very near the nucleotide binding site, as evidenced by changes in tryptophanyl residue fluorescence on binding ATP, mercaptonucleotides, or other ATP analogues.


Structural changes in model compounds of sludge extracellular polymeric substances caused by exposure to free nitrous acid.
Previous studies demonstrate that free nitrous acid (FNA i.e. HNO2) detaches sewer biofilms, breaks down flocs of waste activated sludge (WAS) and enhances biogas production from WAS. This suggests possible interactions of FNA with organic extracellular polymeric substances (EPS) that bind the cells into biofilms or sludge flocs. This study evaluates the chemical interactions and reaction mechanisms between FNA and molecules representative of key EPS in biofilm and sludge flocs. Molecules chosen to represent components found in the extracellular polymeric matrix were treated with FNA at 6.09 mgN/L (NO2- = 250 mgN/L, pH = 5.0 ± 0.2, T = 22 °C) for 24 hours (conditions typically used in applications) so as to consider the hypothesized chemical interactions and the consequent reaction pathways. A number of analytical techniques were employed to measure the molecular changes in the EPS molecules including; proton (1H) nuclear magnetic resonance spectroscopy (NMR), electrospray ionisation mass spectrometry (ESI-MS) and gel permeation chromatography (GPC). The results demonstrated that FNA broke down a range of large EPS molecules including carbohydrates, protein and lipids to smaller molecules. Two mechanistic pathways have been proposed including electrophilic substitution, whereby the nitrosium ion (NO+) was the reactive electrophile, and oxidative radical reactions, through which the nitrogen radicals (.NO2, .NO) and reactive nitrogen intermediates (RNIs) (e.g. N2O3 and N2O4) formed from the decomposition of FNA became part of the reaction products. Larger, more complex organic molecules such as humic acid, required higher concentrations of FNA (6.09 mgN/L or greater) to cause molecular breakdown, whereas smaller molecules, such as calcium alginate, was broken down at lower concentrations (3.04 mgN/L). The study contributes to the understanding of the fundamental mechanisms behind the application of FNA for biofilm control and flocular sludge disintegration.


Effect of low-level laser therapy on the release of interleukin-6 and basic fibroblast growth factor from cultured human skin fibroblasts in normal and high glucose mediums.
This study evaluated the effects of low-level laser therapy (LLLT) on human skin fibroblasts (HSFs) that have been cultured in high glucose concentration media. HSFs were cultured under physiological glucose condition medium, and then cultured in high glucose concentration medium (15 mM/L) for 1 or 2 weeks prior to LLLT. Experimental HSFs were irradiated with three energy densities (0.5, 1, and 2 J/cm(2)) once daily for three consecutive days. Release of interleukin-6 (IL-6) and basic fibroblast growth factor (bFGF) was evaluated using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis showed three doses of 0.5 (p = 0.049), 1 (p = 0.027), and 2 J/cm(2) (p = 0.004) stimulated the release of IL-6 in HSFs cultured in high glucose concentration medium compared with that of non-irradiated HSFs that were cultured in the same medium. LLLT with 2 J/cm(2) induced the release of bFGF from HSFs cultured in high glucose concentration medium for 1 or 2 weeks (both p = 0.04). Our study showed that LLLT stimulated the release of IL-6 and bFGF from HSFs cultured in high glucose concentration medium. LLLT was more effective in releasing IL-6 and bFGF while HSFs which were cultured in physiologic glucose concentration medium during laser irradiation.


Isolation of DNA for PCR assays from noncultivable Campylobacter jejuni isolates.
Isolates of Campylobacter jejuni shipped internationally often arrive in a noncultivable state. We describe a PCR-based methodology whereby phylogenetic information can be recovered from noncultivable C. jejuni stored in Wang's transport medium. The robustness of this methodology was initially tested using 5 previously characterized strains of C. jejuni isolated from various sources associated with poultry production. These isolates were stored in Wang's transport medium before being subjected to 1 of 5 treatments designed to render the stored cells noncultivable: prolonged storage at room temperature, prolonged incubation at 42 degrees C, multiple rounds of freezing and thawing, boiling, or contamination with Pseudomonas aeruginosa (ATCC 27853). This method resulted in DNA appropriate for PCR. An approximately 400-nucleotide amplicon from the flaA gene and an approximately 800-nucleotide amplicon from 16S rDNA were readily obtained, and a 1.5-kb section of the flaA locus was amplified from about half of the samples. These results indicate that this method may be useful for isolate typing schemes based on PCR amplification of Campylobacter DNA, including flaA short variable region (flaA SVR) sequencing, multilocus sequence typing (MLST), and flaA PCR-RFLP. By using this method, isolates unrecoverable from transport medium can still be used to provide phylogenetic information for epidemiological studies.


[New approaches in neurosurgery and hyperbaric medicine--the importance of preventive and industrial medicine].
Neurosurgical patients have been mainly treated by surgical procedures over the past decades. In addition, hyperbaric oxygen (HBO) therapy in neurosurgery has been used in patients with ischemic cerebrovascular diseases, head trauma, spinal damage, postoperative brain edema and others. However, the main therapeutic methods for neurosurgical diseases have changed dramatically due to developments in radiological techniques, such as radiosurgery and intravascular surgery. With changes in therapeutic methods, HBO therapy may become a very important treatment option for neurosurgical patients. For example, HBO therapy combined with radiotherapy (UOEH regimen) and anticoagulant therapy appear to be very effective in the treatments of malignant brain tumors and ischemic cerebrovascular diseases, respectively. On the other hand, medical examinations under hyper- and hypobaric environments have not yet been fully studied in the central nervous system compared to those in the cardiopulmonary systems. Moreover, the mechanisms of cerebral lesions in decompression sickness and acute mountain sickness remain unclear. Clinical neurologic approaches are very important in these fields. Hence, clinicians and researchers skilled in both neurosurgery and hyperbaric medicine will be required for advanced treatment and preventive and industrial medicine.


A haplotype of the catalase gene confers an increased risk of essential hypertension in Chinese Han.
Our previous study in an isolated population showed an association between a genetic variant in the catalase gene (CAT) and essential hypertension (EH). This study indicates that three variants in the promoter and 5'-UTR region of CAT are predominant in Chinese Han, and they form two major haplotypes. A case-control study showed that the CATH2 haplotype confers susceptibility to EH (Pgenotype=0.0017, and Pallilc=0.00078). Subjects bearing CATH1/CATH2 and CATH2/CATH2 genotypes demonstrated a higher susceptibility to EH than CATH1/CATH1 homozygotes, with odds ratios of 1.474 and 1.625, respectively. Also, CATH1/CATH1 individuals had a later-onset age (P=0.015). Expression analysis using luciferase reporter vectors indicated that the CATH1 haplotype showed a lower transcriptional activity than the haplotype CATH2 (P<0.05 in all four cell lines), and we observed similar results in the endogenous allelic expression ratios of CATH1/CATH2 in cell lines. In contrast, most CATH1 haplotypes showed a higher transcription level than CATH2 haplotypes (10 out of 11 or 90.9%) in blood from normal individuals (P<0.01). We therefore hypothesize that CATH1 and CATH2 may play alternating roles at different level of oxidative stress.


Novelity in GB virus C/hepatitis G virus and its controversy.
Several novel human RNA viruses were identified in 1995-96 and were partially characterized that apparently can cause acute and chronic hepatitis both in monkeys and humans. These new viruses are related to the flavivirus hepatitis C. It is known to be distinct from other human hepatitis viruses (A, B, C, D, E). Three viruses, identified by investigators at Abbott Labs, have been termed GB-A, GB-B and GB-C. GB-A and GB-B are likely tamarin viruses whereas GB-C infects humans only. All these three viruses are the isolates of the same virus termed HGV, which is positive stranded RNA virus. The genomic sequences of these viruses have been determined by different researchers, which were found to be 1600 nucleotide long. Another group at Genelabs Technologies has identified and determined the complete genomic sequence of a virus they termed hepatitis G virus (HGV). Based on genomic sequence comparisons HGV is probably the same as GB-C. It is highly controversial virus regarding pathogenecity, mode of transmission and site of replication.


Interaction between glucocorticoids and epidermal growth factor in vitro in the growth of palatal mesenchymal cells from the human embryo.
Previous studies of ours have shown that palatal mesenchymal cells from the human embryo (HEPM cells) are responsive both to the glucocorticoid dexamethasone (DEX) and epidermal growth factor (EGF) through mechanisms associated with cytoplasmic and cell surface receptors, respectively. HEPM cell growth was inhibited by DEX and was stimulated by EGF. In the present study, the interactions between DEX and EGF were investigated. DEX (10(-6) M) enhanced EGF-stimulated HEPM cell growth as assessed by an increase in cell number and ornithine decarboxylase activity under serum-free cell culture conditions. DEX also enhanced the specific binding of 125I-EGF to these cells, which was reflected in an increase in both the number and the affinity of EGF receptors. EGF (1 ng/ml), on the other hand, decreased the number of sites per cell which specifically bind 3H-DEX. EGF completely prevented the inhibition by DEX of HEPM cell growth. These results indicated that DEX and EGF interact with each other in the process(es) regulating HEPM cell growth. This interaction may be partially influenced by direct modulation of existing receptors for DEX and EGF present in the cells.


The Unique Microbiology and Molecular Pathogenesis of Mycoplasma genitalium.
Mycoplasma genitalium is increasingly appreciated as a common cause of sexually transmitted disease syndromes, including urethritis in men and cervicitis, endometritis, pelvic inflammatory disease, and possibly preterm birth, tubal factor infertility, and ectopic pregnancy in women. Despite these disease associations, which parallel those of Chlamydia trachomatis and Neisseria gonorrhoeae, the mechanisms by which this pathogen elicits inflammation, causes cellular damage, and persists in its only natural host (humans) are unique and are not fully understood. The purpose of this review is to briefly provide a historical background on the discovery, microbiology, and recognition of M. genitalium as a pathogen, and then summarize the recent advances in our understanding of the molecular biology and pathogenesis of this unique urogenital organism. Collectively, the basic scientific discussions herein should provide a framework for understanding the clinical and epidemiological outcomes described in the accompanying articles in this supplemental issue.


Urinary excretions of high molecular weight beta-thromboglobulin and albumin are independently associated with coronary heart disease in women, a nested case-control study of middle-aged women in the Diagnostisch Onderzoek Mammacarcinoom (DOM) Cohort, Utrecht, Netherlands.
Increased plasma levels of beta-thromboglobulin, a platelet activation marker, are observed in coronary artery disease. Urinary albumin excretion, a marker of endothelial cell perturbation, is related to cardiovascular disease in diabetes. To test the value of these markers in predicting forthcoming coronary disease, the relations between urinary excretions of high molecular weight beta-thromboglobulin (HMW-beta TGf) and albumin and subsequent coronary disease in a cohort of 15,484 middle-aged women were investigated in a nested case-control study. Baseline questionnaire data and urine samples were available from a breast cancer screening program in Utrecht during 1982-1985. Cases were Utrecht hospital admissions for myocardial infarction (n = 50) or angiographically confirmed coronary disease (n = 28) from 1982-1985 to 1990-1991. Classifying events occurred a median of 5.1 years after baseline. Controls were a random sample from the cohort, individually case matched for baseline examination date and age, at a 1:2 ratio. HMW-beta TG/creatinine ratios (ng/mmol, mean +/- standard error) were 5.3 +/- 0.3 in cases and 4.7 +/- 0.3 in controls; albumin/creatinine ratios (mg/mmol, median) were, respectively, 0.37 and 0.22. Crude odds ratios for classification in the highest compared with the lowest tertiles of HMW-beta TG/creatinine and albumin/creatinine distributions were elevated for cases compared with controls: HMW-beta TG/creatinine odds ratio = 2.4, 95% confidence interval 1.1-5.0; albumin/creatinine odds ratio = 2.1, 95% confidence interval 1.0-4.1. These relations persisted after adjustment for smoking, hypertension, Quetelet index, and menopausal status. Both urinary HMW-beta TG and albumin excretion are markers of coronary disease risk in middle-aged women, indicating that increased platelet activation and endothelial cell perturbation precede coronary heart disease events in women.


Resident Medical Officer working conditions in New Zealand: results of a recent survey.
To survey Resident Medical Officers (RMOs) and Senior Medical Officers (SMOs) working at Auckland District Health Board (ADHB) on various aspects of RMO-working conditions and to trial the use of electronic keypad responders for this purpose. In April 2004, the Physicians Grand Round at ADHB was used as a forum to conduct a survey on RMO working conditions in New Zealand. Results were collected anonymously using electronic keypad responders and recorded in a spreadsheet to allow analysis and comparison of the two professional groups. 27 RMOs and 32 SMOs attended and participated in the survey, answering 11 questions. Responses showed significant differences between the two groups in 7 of the 11 questions asked. In addition, both groups favoured changes to the status quo on a significant number of issues. RMOs and SMOs in New Zealand have differing opinions regarding the working conditions of RMOs. This study supports the need for wider scale, national discussion of these issues and the development of appropriate strategies to address these differences and their implications.


Analysis of indoor particle size distributions in an occupied townhouse using positive matrix factorization.
From late 1999 to early March 2000, measurements of particle number (particles 0.01-20 microm in aerodynamic diameter) concentrations were made inside of a townhouse occupied by two non-smoking adults and located in Reston, VA (approximately 25 miles northwest of Washington, DC). The particle size measurements were made using an SMPS and an APS as well as a Climet optical scattering instrument. In this study, positive matrix factorization (PMF) was used to study the indoor particle size distributions. The size distributions or profiles obtained were identified by relating the obtained source contributions to the source information provided by the occupants. Nine particle sources were identified, including two sources associated with gas burner use: boiling water and frying tortillas. Boiling water for tea or coffee was found to be associated only with the smallest particles, with a number mode close to the detection limit of the SMPS (i.e., 0.01 microm). Frying tortillas produced particles with a number mode at about 0.09 microm while broiling fish produced particles with a number mode at about 0.05 microm. A citronella candle was often burned during the study period, and this practice was found to produce a 0.2-microm modal number distribution. Other indoor particle sources identified included sweeping/vacuuming (volume mode at 2 microm); use of the electric toaster oven (number mode at 0.03 microm); and pouring of kitty litter (volume mode over 10 microm). Two outdoor sources were also resolved: traffic (number mode at about 0.15 microm) and wood smoke (major number mode at about 0.07 microm). The volume distributions showed presence of coarse particles in most of the resolved indoor sources probably caused by personal cloud emissions as the residents performed the various indoor activities. This study has shown that continuous measurements of indoor particle number and volume concentrations together with records of personal activities are useful for indoor source apportionment models. Each of the particle sources identified in this study produces distinct size distributions that may be useful in studying the mortality and morbidity effects of airborne particulate matter because they will have different penetrability and deposition patterns.