Serotonergic genes and suicidal ideation 2 weeks and 1 year after stroke in Korea.
Serotonergic genes are associated with suicidal behavior; this association has not been tested in stroke survivors, however. In this study, we investigated whether serotonin transporter (5-HTT) and serotonin 2a receptor (5-HTR2a) genes were associated with suicidal ideation at 2 weeks and at 1 year after stroke. A total of 286 patients were evaluated 2 weeks after stroke, and 222 (78%) participated in a follow-up evaluation one year later. Suicidal ideation was ascertained using the "suicidal thoughts" item of the Montgomery and Asberg Depression Rating Scale. Associations between suicidal ideation and 5-HTTLPR, STin2 VNTR, 5-HTR2a 1438A/G, and 5-HTR2a 102T/C genotypes were estimated using logistic regression models, and gene-gene interactions were investigated using the generalized multifactor dimensionality reduction method after adjustment for potential covariates, including depression. The 5-HTR2a 1438 A/A genotype was significantly associated with suicidal ideation 2 weeks after stroke, before and after statistical adjustment. The 5-HTTLPR short allele was associated with suicidal ideation 2 weeks after stroke, although the significance of this finding was not evident after adjustment. No significant associations were observed between any genotype and suicidal ideation one year after stroke. No significant gene-gene interactions were detected. Individuals with the 5-HTR2a 1438 A/A genotype were more susceptible to suicidal ideation 2 weeks after stroke. Careful evaluation and management are indicated for those with increased genetic vulnerability, particularly during the acute phase of stroke.


Haloperidol binding to monoclonal antibodies. Predictions of three-dimensional combining site structure via computer modeling.
The amino acid sequences of five monoclonal antibodies (designated mAbs A-E) which bind to the dopaminergic D-2 antagonist, haloperidol, with a variety of affinities (Kd = 4-810 nM), have been used to build theoretical, three-dimensional, computer models of the variable region combining sites. Physiocochemical interactions which have been previously determined from in vitro binding data have been used to orient the drug molecule within the combining site model. The results indicate that hydrophobic, aromatic, and ionic amino acids are involved in specific interactions with the antagonist molecule. For example, fluorescence quenching data suggests that a tryptophan residue is intimately involved in the binding of haloperidol by mAb A. Examination of the modeled structure reveals five tryptophans within the variable fragment, only one of which (H-50) is within the classical beta-barrel binding pocket and is readily accessible to the antigen. Haloperidol's relatively electron poor fluorophenyl ring system stacks with the electron-rich tryptophan ring system at a distance of 3.3 A and in so doing, places haloperidol's positively charged piperidinyl nitrogen atom within hydrogen bond distance of the negatively charged Glu-95 and Asp-100A residues of the H3 loop (Glu-H-95 and Asp-H-100A). This type of analysis for each antibody provides an interesting profile of changes in amino acid composition and hypervariable loop length which markedly effect binding affinity and specificity for a series of proteins which have similar combining site.


1H, 15N and 13C assignment of the amyloidogenic protein medin using fast-pulsing NMR techniques.
Thirty-one proteins are known to form extracellular fibrillar amyloid in humans. Molecular information about many of these proteins in their monomeric, intermediate or fibrillar form and how they aggregate and interact to form the insoluble fibrils is sparse. This is because amyloid proteins are notoriously difficult to study in their soluble forms, due to their inherent propensity to aggregate. Using recent developments in fast NMR techniques, band-selective excitation short transient and band-selective optimized flip-angle short-transient heteronuclear multiple quantum coherence we have been able to assign a 5 kDa full-length amyloidogenic protein called medin. Medin is the key protein component of the most common form of localised amyloid with a proposed role in aortic aneurysm and dissection. This assignment will now enable the study of the early interactions that could influence initiation and progression of medin aggregation. The chemical shifts have been deposited in the BioMagRes-Bank accession Nos. 25399 and 26576.


Avidin binding of radiolabeled biotin derivatives.
Three N-acyl derivatives of biotinylethylenediamine were prepared: I, biotinylamidoethyl-3-(3-[125I]iodo-4-hydroxyphenyl)propionamide; II, biotinylamidoethyl-[3H]acetamide; and III, biotinylamidoethyl-3-(3,5-[125I]diiodo-4-hydroxyphenyl)propionamid e. Each compound was combined with a large excess of avidin, yielding 1:1 molar complexes. Aside from a small fraction of each complex that dissociated more rapidly, the dissociation half-lives of these complexes were: I, 41 days; II, 4.4 days; and III, 148 days. The iodo- (mono or di) hydroxyphenylpropionyl moieties of I and III, therefore, contribute significantly to the binding strength of these compounds toward avidin. We also formed 4:1 complexes of I, II, and III with avidin (compound in excess), each of which exhibited biphasic dissociation, with initial half-lives of 4, 3.2, and 24 days, respectively. Thus, I or especially III potentially can be used as a sensitive tracer in quantitative studies with avidin.


An epidemic outbreak of hepatitis E in Yangon of Myanmar: antibody assay and animal transmission of the virus.
An epidemic outbreak of hepatitis E occurred in an army recruit camp of Yangon, Myanmar, in October 1989. One hundred and eleven patients among 600 residents were hospitalized. As high as 83.7% of these patients were positive for the acute phase antibody against hepatitis E virus by an enzyme-linked immunosorbent assay developed in our laboratory. Also, 30.6% of 49 symptom-free residents examined were positive for the antibody. We prepared a stool extract from six patients and inoculated it into 10 rhesus monkeys for a series of three sub-passages. All of them developed acute biochemical hepatitis along with an elevation of antibody levels. A rechallenge with viruses of the present outbreak failed to provoke hepatitis in two monkeys that had previously recovered from acute hepatitis caused by an isolate of sporadic hepatitis E of the same area. Similarly, the rechallenge of the sporadic strain did not induce hepatitis in two monkeys that had been previously infected with the epidemic virus. These data suggested that the subjects would obtain neutralizing antibodies against the hepatitis E virus once infected, and many adult inhabitants of the endemic area had no protective antibodies and were still susceptible to hepatitis E infection.


Resistance to activated protein C and the leiden mutation: high prevalence in patients with abruptio placentae.
The Leiden mutation, a point mutation in the gene encoding coagulation factor V, is associated with a high frequency of thromboembolic phenomena. It has recently been connected with adverse outcomes of pregnancy. We carried out this study to define its connection with abruptio placentae. Twenty-seven women who had abruptio placentae and 29 control subjects matched for age, parity, and ethnic origin were studied. We studied all women for possible hypercoagulation defects. All women demonstrating resistance to activated protein C were studied for the presence of the factor V Leiden mutation. Seventeen of 27 case patients had an activated protein C ratio </=2.5, compared with 5 of 29 control subjects (odds ratio 8.16, 95% confidence interval 3.6-12.75, P =.00125). Participants with activated protein C ratios </=2.5 underwent deoxyribonucleic acid analysis. Eight case patients were found to have the factor V Leiden mutation (5 heterozygous and 3 homozygous, 29.6%), compared with 1 heterozygote among the control subjects who were tested (3.4%). Factor V Leiden mutation was found quite frequently in patients with abruptio placentae.


A combination of speckled lentiginous nevus with patch-type blue nevus.
A peculiar case of "nevus on nevus" was reported. A 67-year-old man had had a pigmented lesion in the left hypochondrial area since birth. The clinicopathologic findings of the pigmented lesion revealed a combination of speckled lentiginous nevus and patch-type blue nevus. This case of "nevus on nevus" is not described under the term of combined nevus as is current in the literature; it was considered to be a subtype of the type II atypical blue nevus described by Kawamura.


Understanding and supporting law enforcement professionals working with distressing material: Findings from a qualitative study.
This study aimed to extend previous research on the experiences and factors that impact law enforcement personnel when working with distressing materials such as child sexual abuse content. A sample of 22 law enforcement personnel working within one law enforcement organisation in England, United Kingdom participated in anonymous semi-structured interviews. Results were explored thematically and organised in the following headings: "Responses to the material", "Impact of working with distressing evidence", "Personal coping strategies" and "Risks and mitigating factors". Law enforcement professionals experienced heightened affective responses to personally relevant material, depictions of violence, victims' displays of emotions, norm violations and to various mediums. These responses dampened over time due to desensitisation. The stress experienced from exposure to the material sometimes led to psychological symptoms associated with Secondary Traumatic Stress. Job satisfaction, self-care activities, the coping strategies used when viewing evidence, detachment from work outside working hours, social support and reducing exposure to the material were found to mediate law enforcement professionals' resilience. Exposure to distressing material and the risks associated with this exposure were also influenced by specific organisational procedures implemented as a function of the funding available and workload. Recommendations for individual and organisational practices to foster resilience emerged from this research. These recommendations are relevant to all organisations where employees are required to view distressing content.


Activation, cytokine production, and intracellular survival of bacteria in Salmonella-infected human monocyte-derived macrophages and dendritic cells.
Salmonella enterica serovar typhimurium (S. typhimurium) is an intracellular pathogen causing localized gastroenteritis in humans. Macrophages (Mphis) and dendritic cells (DCs) play an important role in innate immunity against Salmonella. In this report, we have compared the consequences of infection of human Mphis and DCs with wild-type S. typhimurium and an isogenic PgtE-defective strain. PgtE is an outer membrane protein hypothesized to have a role in intracellular survival of Salmonella. We observed that DCs undergo full maturation in response to Salmonella infection, as indicated by up-regulation of cell-surface marker proteins CD80, CD83, CD86, and human leukocyte antigen class II. CC chemokine ligand 5 (CCL5), CXC chemokine ligand 10, tumor necrosis factor alpha, interleukin (IL)-12, and IL-18 gene expression and protein production were readily induced by Salmonella-infected Mphis and DCs. CCL20 was preferentially produced by Mphis, whereas DCs secreted higher levels of CCL19 as compared with Mphis. DCs and Mphis infected with S. typhimurium also produced high levels of interferon-gamma (IFN-gamma). Cytokine neutralization and stimulation experiments suggest that the production was partly regulated by Salmonella-induced type I IFNs, IL-12, and IL-18. DC cytokine production induced by Salmonella was much higher as compared with the responses induced by Salmonella lipopolysaccharide or flagellin. Mphis and DCs were capable of internalizing and harboring Salmonella for several days. S. enterica PgtE provided no survival advantage for the bacteria in human Mphis or DCs. Our results demonstrate that although Mphis and DCs share similar functions, they may have different roles during Salmonella infection as a result of differential production of certain chemokines and cytokines.


Nucleotide variation at the dopa decarboxylase (Ddc) gene in natural populations of Drosophila melanogaster.
We studied nucleotide sequence variation at the gene coding for dopa decarboxylase (Ddc) in seven populations of Drosophila melanogaster. Strength and pattern of linkage disequilibrium are somewhat distinct in the extensively sampled Spanish and Raleigh populations. In the Spanish population, a few sites are in strong positive association, whereas a large number of sites in the Raleigh population are associated nonrandomly but the association is not strong. Linkage disequilibrium analysis shows presence of two groups of haplotypes in the populations, each of which is fairly diverged, suggesting epistasis or inversion polymorphism. There is evidence of two forms of natural selection acting on Ddc. The McDonald-Kreitman test indicates a deficit of fixed amino acid differences between D. melanogaster and D. simulans, which may be due to negative selection. An excess of derived alleles at high frequency, significant according to the H-test, is consistent with the effect of hitchhiking. The hitchhiking may have been caused by directional selection downstream of the locus studied, as suggested by a gradual decrease of the polymorphism-to-divergence ratio. Altogether, the Ddc locus exhibits a complicated pattern of variation apparently due to several evolutionary forces. Such a complex pattern may be a result of an unusually high density of functionally important genes.


Involvement of DDAH/ADMA pathway in the pathogenesis of rheumatoid arthritis in rats.
Endothelial dysfunction is the early stage of atherosclerosis, which is typically associated with rheumatoid arthritis (RA), a chronic inflammatory autoimmune disorder. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is not only an independent predictor for endothelial dysfunction but also a proinflammatory mediator. It has been shown that the level of ADMA was elevated in patients with RA. In the present study, we investigated the potential effect of ADMA on inflammation process in collagen-induced arthritis (CIA) animal model and primary cultured fibroblast-like synoviocytes (FLS) exposed to tumor necrosis factor-α (TNF-α). In CIA rats, the plasma levels of inflammatory cytokines TNF-α, interleukin-1β (IL-1β) and IL-6 were markedly increased, while the plasma levels of ADMA did not increase. The expression of dimethylarginine dimethylohydrolase2 (DDAH2), the key enzyme for ADMA degradation, was markedly reduced in inflamed joint synovium of CIA rats. Moreover, the expression of anti-inflammatory factor cortistatin (CST) was markedly decreased in joint synovium of CIA rats. Treatment of cultured FLS with TNF-α significantly increased the levels of ADMA, and decreased the expression of DDAH2 mRNA and protein accompany with an increase in the levels of IL-1β and IL-6 and a reduction in the expression of CST mRNA and protein, and the effects of TNF-α were abolished by DDAH2 overexpression. Treatment of FLS with ADMA also significantly increased the levels of IL-1β and IL-6, and reduced the expression of CST. These findings suggest that DDAH/ADMA participates in the pathogenesis of RA, and that the effect of DDAH/ADMA may be mediated by CST.


Acetylcholinesterase activity rises in rat cerebrospinal fluid post-ictally; effect of a substantia nigra lesion on this rise and on seizure threshold.
The activity of acetylcholinesterase (AChE) in the cerebrospinal fluid (CSF) of rats increased by 53% following an electroconvulsive shock (ECS) while non-specific cholinesterase (nsChE) activity was unchanged. A flurothyl-induced seizure failed to elicit a change in the AChE activity of CSF. A bilateral lesion of the substantia nigra pars reticulata abolished the rise in AChE activity in the CSF but did not diminish the increase of seizure threshold which follows a convulsion. These data suggest that AChE is released from the substantia nigra following a seizure but indicate that the change is not associated with the rise in seizure threshold which occurs.


Comparison of mechanically ruled versus holographically varied line-spacing gratings for a soft-x-ray flat-field spectrograph.
Recent progress in the design of aspheric wave-front recording systems has permitted the manufacture of holographic gratings with highly variable groove densities that are suitable for flat-field spectrographs. A holographic grating thus recorded was processed to produce a laminar profile by use of reactive-ion etching. Measurements are reported of the absolute diffraction efficiency of this grating and of a comparable mechanically ruled grating. It is found that the holographic grating is much more effective in suppressing the higher orders. The spectral resolution was determined by use of a carbon Kalpha x-ray generator and a spectrograph with an imaging detector. The spectral resolution of the holographic grating was approximately 3 times worse than that of the ruled grating.


Oxygen tension of the vaginal surface during sexual stimulation in the human.
An oxygen electrode was maintained by suction on the vaginal wall in seven women. The basal value of pO2 was 9.3 mm Hg +/- 10.7 (mean +/- standard deviation) before clitoral self-stimulation was initiated. When stimulation took place the oxygen tension rose and peaked immediately after orgasm to 39.5 +/- 14.1 mm Hg. It then declined and fell to 20.1 +/- 13.8 mm Hg 10 minutes after the peak value. The changes correlate closely with changes in vaginal blood flow. The increased oxygen tension may be one of the factors that enhance of even initiate the motility of spermatozoa when deposited intravaginally.


[Pain-related disability in adolescents suffering from chronic pain. Preliminary examination of the Pediatric Pain Disability Index (P-PDI)].
Pain-related disability affects many children and adolescents suffering from chronic pain and may exert an impact on all areas of their lives. Reduction of pain-related disability is, therefore, a fundamental aim of treatment; however, no validated means exist to assess pain-related disability in children and adolescents. The aim of this study was to translate the Pediatric Pain Disability Index (P-PDI) of Varni into German and to investigate its psychometric qualities. Principal component and item analyses were conducted on outpatient (n=163) and inpatient samples (n=167) of adolescents suffering from chronic pain. Changes in pain-related disability 3 months after starting treatment were analysed in an outpatient sample of 110 adolescents. Correlations between pain-related disability, emotional variables and school absence as well as concordance with parents' ratings were investigated. The P-PDI is a one-dimensional assessment tool with sufficient reliability. There were significant correlations between pain-related disability and pain intensity and school absence but not with pain duration, fear and depression. Parents and adolescents ratings correlated significantly, but 57% of parents underestimated the pain-related disability of their children. There is now a validated German version of the P-PDI to measure pain-related disability in adolescents suffering from chronic pain, which can be used in studies investigating treatment effectiveness.


Cerebrospinal fluid cyclic AMP and acid monoamine metabolites following probenecid: studies in psychiatric patients.
At probenecid levels greater than 10 microgram/ml, CSF cAMP was independent of CSF probenecid concentration. At these levels of probenecid, cAMP transport out of CSF is probably maximally blocked and cAMP levels reflect cAMP release into CSF. CSF cAMP was significantly higher in RDC-diagnosed schizophrenics than in other psychotics or depressives. A significant decrease in CSF cAMP was found in psychotic patients treated with chlorpromazine, No changes in CSF cAMP were observed in patients treated with tricyclic antidepressants or lithium.


Classification of vertebro-basilar aneurysms.
In continuation of earlier studies concerning the aneurysms of ICA and PCA a proposed detailed classification of vertebro-basilar aneurysms has been given. It has been proved that nearly all the aneurysms originate at the divisions of the main arteries or at the ends of large arteries as direct continuations of the main branches (BA as well as ICA). Aneurysms of the vertebro-basilar junction are of special aetiological interest. These last aneurysms are unique, and demonstrate that congenital defects seem to be more important for the origin of aneurysms than the direction of the blood flow. Origin and projection characterize the different types. Atypically located aneurysms away from arterial divisions exist, as in the ICA system. The relations between aneurysms and the multiplicity of variations and anomalies of the main arteries and the posterior part of the circle of Willis are still unknown, and should be checked in detail. Our studies have convinced us that the exact knowledge of microtopographic classification is the key to correct preoperative diagnosis, access, and treatment.


Antiplatelet Effect of Sequential Administration of Cilostazol in Patients with Acetylsalycilic Acid Resistance.
Acetylsalicylic acid (ASA) resistance in patients with coronary artery disease is an important medical problem that can affect treatment decision-making and outcomes. Cilostazol has been investigated to determine its effectiveness in patients with acetylsalicylic acid resistance. The aim of this study was to evaluate the antiplatelet efficacy of sequential administration of CLZ in patients with ASA resistance. A total of 180 patients were enrolled in our study. Patients with stable coronary artery disease were first given orally ASA 100 for 10 days, followed by collagen/epinephrine induced closure time (CTCEPI) measurements. Those who were found to be resistant to orally 100 mg of ASA were given orally 300 mg of ASA for an additional 10 days after which we repeated CTCEPI measurements. Those patients with resistance to orally 300 mg ASA were then given CLZ at a daily dose of orally 200 mg for 10 days followed by a final CTCEPI measurement. The rate of resistance to 100 mg ASA was 81/180 (45%) compared to a rate of 35/81 (43.2%) with 300 mg ASA. Of the 35 patients found to be resistant to 300 mg ASA, 22 (62.9%) also failed to respond to CLZ treatment. Overall, sequential administration of 300 mg ASA and 200 mg CLZ resulted in a reduction in the number of non-responders from 45% to 12.2%. Initiation of CLZ could be of benefit in some patients with ASA-resistance for whom an effective anti-aggregant effect is of clinical importance.


Ultra Q-bodies: quench-based antibody probes that utilize dye-dye interactions with enhanced antigen-dependent fluorescence.
Recently, we described a novel reagentless fluorescent biosensor strategy named Quenchbody, which functions via the antigen-dependent removal of the quenching effect on a fluorophore that is attached to a single-chain antibody variable region. To explore the practical utility of Quenchbodies, we prepared antibody Fab fragments that were fluorolabeled at either one or two of the N-terminal regions, using a cell-free translation-mediated position-specific protein labeling system. Unexpectedly, the Fab fragment labeled at the heavy chain N-terminal region demonstrated a deeper quenching and antigen-dependent release compared to that observed using scFv. Moreover, when the Fab was fluorolabeled at the two N-termini with either the same dye or with two different dyes, an improved response due to enhanced quenching via dye-dye interactions was observed. On the basis of this approach, several targets, including peptides, proteins, and haptens, as well as narcotics, were quantified with a higher response up to 50-fold. In addition, differentiation of osteosarcoma to osteoblasts was successfully imaged using a similarly fluorolabeled recombinant Fab protein prepared from E. coli. Due to its versatility, this "Ultra-Quenchbody" is expected to exhibit a range of applications from in vitro diagnostics to the live imaging of various targets in situ.


Diversification of the myofibrillar M-band in rat skeletal muscle during postnatal development.
The fine structure of the M-band in soleus (SOL) and extensor digitorum longus (EDL) muscles in newborn and four-week-old rats was studied using electron-microscopic techniques. In newborn rats, all myotubes and fibres in both muscles had an identical myofibrillar appearance. A five-line M-band pattern was seen in longitudinal sections and distinct M-bridges in cross-sections. The Z-discs were of medium width. On the other hand, in four-week-old rats, different muscle fibre types were observed on the basis of their myofibrillar pattern. In SOL two fibre types were distinguished in longitudinal sections. One had a four-line M-band pattern and very broad Z-discs, whereas the other type had five lines in the M-band and broad Z-discs. In EDL, three different myofibrillar patterns were observed. The M-bands were composed of three, four or five lines. Fibres had either thin, broad or medium Z-disc widths, respectively. In cross-sections of the SOL muscle one group of fibres showed indistinct M-bridges, whereas distinct M-bridges were seen in the other fibres and in all observed EDL muscle fibres. We conclude that initially there seems to be a single intrinsic program for M-band genesis; this program becomes modified upon the induction of functionally differentiated fibres.


Mortality after cardiac arrest in children less than 2 years: relevant factors.
There are only scant studies of predicting outcomes of pediatric resuscitation due to lack of population-based data. This study aimed to determine variable factors that may impact the survival of resuscitated children aged under 24 months. This is a retrospective study of 66 children under 24 months. Cardiopulmonary resuscitation (CPR) with pediatric advanced life support guideline was performed uniformly for all children. Linear regression analysis with variable factors was conducted to determine impacts on mortality. Factors with statistically significant increases in mortality were the number of administered epinephrine (p value < 0.001), total CPR duration (p value < 0.001), in-hospital CPR duration of out-hospital cardiac arrest (p value < 0.001), and changes in cardiac rhythm (p value < 0.040). However, there is no statistically significant association between patient outcomes and remaining factors such as age, sex, underlying disease, etiology, time between last normal to CPR, initial CPR location, initial cardiac rhythm, venous access time, or inotropic usage. More than 10 times of epinephrine administration and CPR duration longer than 30 minutes were associated with a higher mortality rate, while each epinephrine administration and prolonged CPR time increased mortality. This study analyzed various factors influencing mortality after cardiac arrest in patients under 24 months. Increased number of administered epinephrine and prolonged cardiopulmonary resuscitation duration do not increase survival rate in patients under 24 months. In patients with electrocardiogram rhythm changes during CPR, mortality increased when the rhythm changed into asystole in comparison to no changes occurring in the rhythm.


Short prokaryotic Argonaute systems trigger cell death upon detection of invading DNA.
Argonaute proteins use single-stranded RNA or DNA guides to target complementary nucleic acids. This allows eukaryotic Argonaute proteins to mediate RNA interference and long prokaryotic Argonaute proteins to interfere with invading nucleic acids. The function and mechanisms of the phylogenetically distinct short prokaryotic Argonaute proteins remain poorly understood. We demonstrate that short prokaryotic Argonaute and the associated TIR-APAZ (SPARTA) proteins form heterodimeric complexes. Upon guide RNA-mediated target DNA binding, four SPARTA heterodimers form oligomers in which TIR domain-mediated NAD(P)ase activity is unleashed. When expressed in Escherichia coli, SPARTA is activated in the presence of highly transcribed multicopy plasmid DNA, which causes cell death through NAD(P)+ depletion. This results in the removal of plasmid-invaded cells from bacterial cultures. Furthermore, we show that SPARTA can be repurposed for the programmable detection of DNA sequences. In conclusion, our work identifies SPARTA as a prokaryotic immune system that reduces cell viability upon RNA-guided detection of invading DNA.


Risks to aquatic organisms from use of chlorpyrifos in the United States.
The risk of chlorpyrifos (CPY) to aquatic organisms in surface water of North America was assessed using measured concentrations in surface waters and modeling of exposures to provide daily concentrations that better characterize peak exposures.Ecological effects were compared with results of standard laboratory toxicity tests with single species as well as microcosm and mesocosm studies comprised of complex aquatic communities. The upper 90th centile 96-h concentrations(annual maxima) of chlorpyrifos in small streams in agricultural watersheds in Michigan and Georgia were estimated to be :-:;0.02 llg L-1; in a reasonable worstcase California watershed, the 90th centile 96-h annual maximum concentrations ranged from 1.32 to 1.54 llg L - 1• Measured concentrations of chlorpyrifos are less than estimates from simulation models. The 95th centile for more than I 0,000 records compiled by the US Geological Survey was 0.008 llg L -1• Acute toxicity endpoints for 23 species of crustaceans ranged from 0.035 to 457 llg L -I; for 18 species of aquatic insects, from 0.05 to 27 llg L -I; and for 25 species of fish, from 0.53to >806 llg L -I. The No Observed Adverse Effect Concentration (NOAECeco) in more than a dozen microcosm and mesocosm studies conducted in a variety of climatic zones, was consistently 0.1 llg L -1• These results indicated that concentrations of CPY in surface waters are rarely great enough to cause acute toxicity to even the most sensitive aquatic species. This conclusion is consistent with the lack of fish kills reported for CPY's normal use in agriculture in the U.S.Analysis of measured exposures showed that concentrations in surface waters declined after labeled use-patterns changed in 2001, and resulted in decreased risks for crustaceans, aquatic stages of insects, and fish. Probabilistic analysis of 96-h time-weighted mean concentrations, predicted by use of model simulation for three focus-scenarios selected for regions of more intense use of CPY and vulnerability to runoff, showed that risks from individual and repeated exposures to CPY in the Georgia and Michigan watersheds were de minimis. Risks from individual exposures in the intense-use scenario from California were de minimis for fish and insects and low for crustaceans. Risks from repeated exposures in the Californiain tense-use scenario were judged not to be ecologically relevant for insects and fish,but there were some risks to crustaceans. Limited data show that chlorpyrifos oxon(CPYO), the active metabolite of CPY is of similar toxicity to the parent compound.Concentrations of CPYO in surface waters are smaller than those of CPY and less frequently detected. Risks for CPYO in aquatic organisms were judged to be deminimis.Several uncertainties common to all AChE inhibitors were identified. Insufficient data were available to allow interpretation of the relevance of effects of CPY (and other pesticides that also target AChE) on behavior to assessment endpoints such as survival, growth, development, and reproduction. Data on the recovery of AChE from inhibition by CPY in fish are limited. Such data are relevant to the characterization of risks from repeated exposures, and represent an uncertainty in the assessment of risks for CPY and other pesticides that share the same target and toxico dynamics. More intensive monitoring of areas of greater use and more comprehensive models of cumulative effects that include rates of accumulation, metabolism and recovery of AChE in the more sensitive species would be useful in reducing this uncertainty.


Accurate Sequence-Dependent Coarse-Grained Model for Conformational and Elastic Properties of Double-Stranded DNA.
We introduce MADna, a sequence-dependent coarse-grained model of double-stranded DNA (dsDNA), where each nucleotide is described by three beads localized at the sugar, at the base moiety, and at the phosphate group, respectively. The sequence dependence is included by considering a step-dependent parametrization of the bonded interactions, which are tuned in order to reproduce the values of key observables obtained from exhaustive atomistic simulations from the literature. The predictions of the model are benchmarked against an independent set of all-atom simulations, showing that it captures with high fidelity the sequence dependence of conformational and elastic features beyond the single step considered in its formulation. A remarkably good agreement with experiments is found for both sequence-averaged and sequence-dependent conformational and elastic features, including the stretching and torsion moduli, the twist-stretch and twist-bend couplings, the persistence length, and the helical pitch. Overall, for the inspected quantities, the model has a precision comparable to atomistic simulations, hence providing a reliable coarse-grained description for the rationalization of single-molecule experiments and the study of cellular processes involving dsDNA. Owing to the simplicity of its formulation, MADna can be straightforwardly included in common simulation engines. Particularly, an implementation of the model in LAMMPS is made available on an online repository to ease its usage within the DNA research community.


Micro-Multileaf Collimator LINAC Radiosurgery for Vestibular Schwannomas.
This study evaluates the efficacy of linear accelerator (LINAC) radiosurgery using micro multi-leaf collimator technique (μMLC) in the treatment of a consecutive series of patients with vestibular schwannomas. In this retrospective study, we enrolled 50 patients with non-neurofibromatosis type 2 vestibular schwannoma who were treated with μMLC LINAC-based SRS at University Hospital of Cologne, Germany. A minimum clinical follow-up of 24 months was conducted. Thirty-nine out of the 50 tumors (78 %) were treated with μMLC LINAC as a primary treatment (a newly diagnosed tumor). The remaining 11 vestibular schwannomas (22%) were treated as a salvage treatment (5 patients with a residual tumor; and 6 patients with a recurrent tumor following a microsurgical resection). The median tumor volume was 1.4 ml. The median tumor surface dose, median maximal dose and median therapeutic isodose were 12 Gy, 16 Gy and 77% respectively. Follow-up MR images showed that a tumor progression-free status was achieved for 95.7% of patients. Partial tumor shrinkage was observed after μMLC LINAC SRS for 21.3% of patients. No change in tumor size (a stable tumor) was noted for 74.5% of patients. Tumor progression was observed for 4.3% of patients. At the end of follow-up, the actuarial 5- year and 10 year progression-free survival after radiosurgery were both 95.7%. LINAC radiosurgery using a micro multi-leaf collimator for vestibular schwannomas smaller than 3 cm is effective in yielding a high local tumor control, whereas the treatment-related morbidity remains low.


Peptic ulcer is prevalent among shift workers.
To elucidate sleep disturbances in the etiology of peptic ulcers, the prevalence of peptic ulcer disease was compared among shift workers and daytime workers. The subjects (N = 11,657) were employees of various institutions, such as factories, banks, or schools, and had undergone a mass x-ray examination of the upper gastrointestinal tract. With present shift workers (N = 2269), the prevalence of gastric ulcers was 2.38% (N = 54) and that of duodenal ulcers, 1.37% (N = 31). With the past shift workers (N = 2111), the prevalence of gastric ulcers was 1.52% (N = 32) and that of duodenal ulcers, 0.62% (N = 13). On the contrary, with the daytime workers (N = 6525) the prevalence of gastric ulcer was 1.03% (N = 67) and that of duodenal ulcer, 0.69% (N = 45). The working schedule for 752 examinees was unknown. The prevalence of gastric and duodenal ulcers was higher with shift workers than daytime workers. Thus, shift work involving sleep disturbances may play an important role in the development of peptic ulcers.


First record of Teratopactus nodicollis (Coleoptera: Curculionidae) in dry bean (Phaseolus vulgaris).
Observations on the bioecology and damage of Teratopactus nodicollis Boheman on Phaseolus vulgaris were carried out on field samples by assessing the number of larvae and root damage in 40 ha of a dry bean field from the Federal District, Brazil (16°4'28.41"W; 47°30'21.13"S). Larvae caused the greatest damage at the stage of germination, emergence, and primary leaves, producing 50 % stand reduction. Most larvae pupated in August and September, and adult emergence occurred in middle October. Some larvae were infected with the fungus Metarhizium spp., a biological agent that would be naturally controlling this insect.


Nickel absorption and kinetics in human volunteers.
Mathematical modeling of the kinetics of nickel absorption, distribution, and elimination was performed in healthy human volunteers who ingested NiSO4 drinking water (Experiment 1) or added to food (Experiment 2). Nickel was analyzed by electrothermal atomic absorption spectrophotometry in serum, urine, and feces collected during 2 days before and 4 days after a specified NiSO4 dose (12 micrograms of nickel/kg, n = 4; 18 micrograms of nickel/kg, n = 4; or 50 micrograms of nickel/kg, n = 1). In Experiment 1, each of the subjects fasted 12 hr before and 3 hr after drinking one of the specified NiSO4 doses dissolved in water; in Experiment 2, the respective subjects fasted 12 hr before consuming a standard American breakfast that contained the identical dose of NiSO4 added to scrambled eggs. Kinetic analyses, using a compartmental model, provided excellent goodness-of-fit for paired data sets from all subjects. Absorbed nickel averaged 27 +/- 17% (mean +/- SD) of the dose ingested in water vs 0.7 +/- 0.4% of the same dose ingested in food (a 40-fold difference); rate constants for nickel absorption, transfer, and elimination were not significantly influenced by the oral vehicle. The elimination half-time for absorbed nickel averaged 28 +/- 9 hr. Renal clearance of nickel averaged 8.3 +/- 2.0 ml/min/1.73 m2 in Experiment 1 and 5.8 +/- 4.3 ml/min/1.73 m2 in Experiment 2. This study confirms that dietary constituents profoundly reduce the bioavailability of Ni2+ for alimentary absorption; approximately one-quarter of nickel ingested in drinking water after an over-night fast is absorbed from the human intestine and excreted in urine, compared with only 1% of nickel ingested in food. The compartmental model and kinetic parameters provided by this study will reduce the uncertainty of toxicologic risk assessments of human exposures to nickel in drinking water and food.


Water masses influence bacterioplankton community structure in summer Kongsfjorden.
To ascertain the saying "Everything is everywhere, but the environment selects", it was imperative to find out the main factor influencing bacterioplankton composition at genus level of Kongsfjorden where was influenced both by glacier melting water and Atlantic water. Thus, bacterioplankton diversity was investigated using pyrosequencing. In addition, nutrients, chlorophyll a, in situ temperature and salinity were measured. There were seventeen of 33 identified genera with relative abundance > 0.1%. Redundancy analysis showed that 73.02% of bacterioplankton community variance could be explained by environmental parameters. Furthermore, most of the abundant genera demonstrated significant correlation with environment parameters revealed by correlation analysis. Moreover, phosphate, nitrate and Chl a concentration, and the abundance of top nine identified genera varied with water mass significantly as shown by analysis of variance. Our results supported the notion that environmental factors, especially water mass had significant effect on bacterioplankton distribution at genus level. Considering the high sensitivity to environmental change and low error rate in identification, bacterioplankton at genus level could be potential bio-markers for monitoring environmental changes.


Yeast Two-Hybrid System for Mapping Novel Dengue Protein Interactions.
Yeast two-hybrid (Y2H) systems are one of the principal choices for identifying novel binary protein-protein interactions (PPIs). Since its development, it has contributed for the discovery of several PPIs between pathogens and host, allowing not only a comprehensive look at the disease pathogenesis but also for therapeutic strategies. Identification of viral-host PPIs that impact on viral replication and pathogenesis can lead to new advances in antiviral therapies such as the development of drug candidates and vaccine design. In this chapter, we revise the Y2H key parameters necessary for screening PPIs and discuss the possible approaches for using this technique to identify novel dengue-host protein interactions.


[Chronic diarrhoea: Definition, classification and diagnosis].
Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.


Experimental study on the engineering properties of expansive soil treated with Al13.
This paper investigates the stabilization of expansive soil with hydroxy-aluminium (Al13) with Al/soil ratios of 0.10, 0.14, 0.18, 0.22 and 0.26 mmol/g. A series of laboratory tests were conducted to study the effects of Al13 on the mechanical properties of expansive soil, including Atterberg limits, grain size distribution, swell percent, swell pressure and unconsolidated-undrained (UU) triaxial strength. The results revealed that Al13 reduced the plasticity index, clay content and swelling potential and enhanced the shear strength of expansive soil. The minerals and micro-structural changes in the soil samples were also determined by X-ray diffraction (XRD) and scanning electron microscopy (SEM), and the stabilized soil showed a remarkable flocculated-agglomerated structure characterized by the densification of particle associations. The consistency of the changes in mechanical properties and micro-morphology indicated that expansive soil can be effectively improved with the use of Al13. Additionally, the optimum dosage of polynuclear hydroxy-Al (PHA) solution for stabilizing expansive soil was 0.18 mmol/g under the given properties of expansive soil and PHA utilized in this study.


It could have happened to Van Gogh: a case of fatal purple foxglove poisoning and review of the literature.
Although death owing to the toxic effects of the therapeutic Digitalis lanata extract, digoxin has been reported, there are no reported cases of fatal Digitalis purpurea (digitoxin) plant intoxication in humans in the literature. We describe a case of ingestion of Digitalis purpurea in a 64-year-old man, which was fatal despite administration of Digibind. A review of the literature and aspects of management of plant digitalis poisoning are discussed.


Sarcopenia in chronic liver disease: mechanisms and countermeasures.
Sarcopenia, a condition of low muscle mass, quality, and strength, is commonly found in patients with cirrhosis and is associated with adverse clinical outcomes including reduction in quality of life, increased mortality, and posttransplant complications. In chronic liver disease (CLD), sarcopenia is most commonly defined through the measurement of the skeletal muscle index of the third lumbar spine. A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover, which likely occurs due to a decrease in muscle protein synthesis and an elevation in muscle protein breakdown. This imbalance is assumed to arise due to several factors including accelerated starvation, hyperammonemia, amino acid deprivation, chronic inflammation, excessive alcohol intake, and physical inactivity. In particular, hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to mitochondrial dysfunction and an increase in myostatin expression. Currently, the use of nutritional interventions such as late-evening snacks, branched-chain amino acid supplementation, and physical activity have been proposed to help the management and treatment of sarcopenia. However, little evidence exists to comprehensively support their use in clinical settings. Several new pharmacological strategies, including myostatin inhibition and the nutraceutical Urolithin A, have recently been proposed to treat age-related sarcopenia and may also be of use in CLD. This review highlights the potential molecular mechanisms contributing to sarcopenia in CLD alongside a discussion of existing and potential new treatment strategies.


The study of laparoscopic electrosurgical instruments on thermal effect of uterine tissues.
It is to compare the thermal damage on myometrium tissue caused by five electrosurgical instruments, including monopolar forceps, bipolar forceps, PK scalpel, Ligasure and BiClamp. Normal myometrium in vitro was collected and electric coagulation was conducted with five electrosurgical instruments under corresponding powers. The zones of thermal injury (ZTI) in each coagulation sites were examined histologically, while the width and depth of thermal damage were measured. 1. There were significant differences among various groups' widths of ZTI of myometrium (P < 0.05). Ligasure produced the greatest width of ZTI, and it was statistically greater than that of PK scalpel and BiClamp (P < 0.05). While the widths of ZTI caused by monopolar and bipolar electrocoagulation lied between that of Ligasure and PK scalpel, but the differences were of no statistical significance (P > 0.05). 2. The depths of ZTI in different groups were of significant differences (P < 0.05). Both monopolar and bipolar forceps had greater depths of ZTI compared with BiClamp (P < 0.05) but not had statistical differences with Ligasure and PK scalpel (P > 0.05). As for myometrium, the thermal damage is rather small in the horizontal and vertical directions when using BiClamp and PK scalpel. Ligasure places larger range of thermal damage in horizontal direction with little depth in vertical direction, which is rather safe when acting on uterine surface. Electrocoagulation was conducted with monopolar (the power is 55 W) and bipolar forceps (the power is 40 W) continuously for 3 s, whose thermal damage range is fairly safe to corpus uteri wall and fundus uteri.


[Shock].
Shock is a consequence of disturbed circulation and decreased blood perfusion of tissues which, on the whole, cause functional and morphological impairments of organic systems. Occurrence of shock is not high, but it is significant due to bad prognosis and high mortality rate. This is one of the classifications of shock: cardiogenic, extracardiogenic-obstructive, oligentic and distributive shock. PATHOPHYSIOLOGIC MECHANISMS OF SHOCK: Regardless of the cause of shock, the clinical picture is dominated by hypotension mostly caused by decrease of minute volume (septic shock may be an exception--minute volume might be high). Due to hypotension a lot of compensatory mechanisms are activated and in the beginning showing the compensatory phase of disease and if nothing is done decompensatory and in the end irreversible phase of shock occurs with fatal outcome. The clinical picture depends on the etiology of shock, type of shock, but it also has certain specificities. The prognosis depends on the clinical picture dominated by the following symptoms: hypotension, decreased diuresis, acidosis, consciousness disorders, tachypnea, peripheral cyanosis, cold and damp skin. These patients are managed in intensive care units, where the following parameters are followed-up: arterial pressure, central venous pressure, minute heart volume, systemic vascular resistance, diuresis, continual follow-up of heart rate, breathing and consciousness. In treatment of shock it is necessary to: normalize the circulatory volume, establish electrolyte balance, regulate glycemia and acid-base status, compensate the volume, calm the patient and alleviate pain.


Urogenital sinus cyst in a 21-year-old man.
We report a case of a rare congenital malformation, a urogenital sinus cyst in a young patient with non-specific symptoms for several months. A 21-year-old male presented with vague and intermittent abdominal pain. Ultrasound scan showed a retrovesical hypoechoic collection (approximately 6 cm) and left renal agenesis, compatible with a possible congenital malformation. These findings were confirmed by MRI. A laparoscopic excision of the cyst was performed with no complications. Pathology report confirmed a urogenital sinus cyst. The postoperative recovery was uneventful and the patient was discharged within 48 h. Urogenital sinus cysts are rare entities with few cases described in the literature. Imaging techniques such as ultrasound, CT or MRI may help with diagnosis. Therapeutic modalities range from observation to needle aspiration or surgical removal. In our case, we chose a laparoscopic approach to minimize morbidity and achieve an early recovery.


Selective arterial embolization for hemorrhage following hip arthroplasty.
A case is presented in which selective embolization of gelfoam was used to control late postoperative bleeding, developing in a patient following hip arthroplasty. Although primarily used in gastrointestinal bleeding, diagnostic and therapeutic angiography, selective embolization is clearly applicable to postoperative bleeding encountered in orthopedics.


Factors influencing tumor response to photodynamic therapy sensitized by intratumor administration of methylene blue.
We examined tumor response to methylene blue (MB)-mediated photodynamic therapy (PDT) in a murine tumor model. The goal was to investigate the effects of drug-light interval (DLI), injection vehicle, and fluence on tumor destruction. Fluorescence and reflectance spectroscopy informed our understanding. EMT6 tumor cells were implanted intradermally on the backs of female BALB/c mice and grown to ∼4-mm diameter. Mice were given a 35 µl, single site, intratumor injection of 500 µg/ml MB administered in either a water or a 5% ethanol-5% Cremophor-90% saline vehicle. PDT was begun either immediately or after a 1-hour DLI with a fluence rate of 60 mW/cm(2). Each animal received a fluence of 240 or 480 J/cm(2). Fluorescence and reflectance spectra were captured before and during irradiation. A protocol consisting of the Cremophor-based vehicle, 0 DLI, and a fluence of 480 J/cm(2) was the most effective, with a 55% cure rate as measured by no evidence of tumor 90 days after PDT. Use of the water vehicle with this fluence and DLI reduced the cure rate to 20%. Reducing the fluence to 240 J/cm(2) similarly reduced treatment efficacy with 0 and 1-hour DLIs. Univariate Cox proportional hazards analysis identified increased fluence, 0 versus 1-hour DLI, and the Cremophor versus water vehicle as highly significant independent predictors of long term tumor control (P < 0.01 in each case). Multivariate analysis with model selection revealed fluence and injection vehicle as the best predictors of survival hazards. Fluorescence spectroscopy in vivo showed that MB fluorescence decreased monotonically during a 2-hour dark interval but was restored by irradiation. Reflectance spectroscopy revealed that MB at this injected concentration attenuates the treatment beam significantly. Sensitizer delivery vehicle, drug-light interval, and fluence contribute significantly to the tumor response to MB-mediated PDT.


Psychosocial precursors and physical consequences of workplace violence towards nurses: a longitudinal examination with naturally occurring groups in hospital settings.
Workplace violence towards nurses is prevalent and consequential, contributing to nurses' reduced health and safety, worsened job attitudes, and compromised productivity. To examine if organizational violence prevention climate as perceived by nurses predicts nurses' physical violence exposure and if physical violence exposure predicts nurses' somatic symptoms and musculoskeletal disorder symptoms. A two-wave longitudinal design with naturally occurring groups, with a 6-month interval. Analysis of covariance and logistic regression were applied to test the proposed hypotheses among 176 nurses from two hospitals in the U.S. who participated in both surveys required by this study. All nurses from the two hospitals were recruited to participate voluntarily. The response rate was 30% for the first survey and 36% for the follow-up survey. Among the subjects, only 8 were male. On average, the subjects were about 45 years old, had a job tenure of about 17 years, and worked approximately 37 h per week. Violence prevention climate, specifically the dimension of perceived pressure against violence prevention, predicted nurses' chance of being exposed to physical violence over six months (odds ratio 1.69), with no evidence found that violence exposure affected change in climate reports. In addition, results supported that nurses' physical violence exposure had effects on somatic symptoms, and upper body, lower extremity, and low back pain over six months. Findings of this study suggest that reducing organizational pressure against violence prevention will help decrease the chance of nurses' physical violence exposure and benefit their health and safety.


Neutrophil-mediated clinical nanodrug for treatment of residual tumor after focused ultrasound ablation.
The risk of local recurrence after high-intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. The combination of HIFU with traditional chemotherapy continues to have an unsatisfactory outcome because of off-site drug uptake. Herein, we propose a strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeted therapy for residual tumors after HIFU ablation. We selected neutrophils as carriers and PEGylated liposome doxorubicin (PLD) as a model chemotherapeutic nanodrug to form an innovative cell therapy drug (PLD@NEs). The produced PLD@NEs had a loading capacity of approximately 5 µg of PLD per 106 cells and maintained the natural characteristics of neutrophils. The targeting performance and therapeutic potential of PLD@NEs were evaluated using Hepa1-6 cells and a corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation (most in 4 h) and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy. This effective integrated method fully leverages the advantages of HIFU, chemotherapy and neutrophils to attract more focus on the practice of improving existing clinical therapies.


Quantification of Coffea arabica and Coffea canephora var. robusta in roasted and ground coffee blends.
This study reports direct quantification of arabica in roasted and ground coffee blends of Coffea arabica and Coffea canephora var. robusta. (1)H-NMR analysis of water extracts of coffee blends were combined with multivariate statistical analysis to obtain an OPLS model with high predictive capability. This approach allowed to evaluate the composition of coffee blends of unknown arabica and robusta content, on the basis of multiple chemical components. Differences in geographical origin of the analyzed samples did not affected the compositional determination of coffee blends. This approach represents a valid tool in authentication procedures of arabica and robusta blends of roasted and ground coffee.


A Central Incisor with 4 Independent Root Canals: A Case Report.
The maxillary central incisor is the tooth with the least anatomic variations. Despite the fact that several studies have reported a prevalence of 100% for the presence of a single canal, root canal aberrations of maxillary central incisors with up to 3 canals have also been reported. Such cases represent both a diagnostic and technical challenge to the clinician. The present case describes root canal treatment performed in a maxillary central incisor with 4 canals. The detection of all canals was achieved by examination of the pulp chamber floor with the help of the dental operating microscope as well as careful examination of intraoral radiographs. The canals were prepared with hand and rotary instruments and obturated with a warm gutta-percha technique. The present report is the first to describe a maxillary central incisor with 4 canals in a tooth with no developmental abnormalities. It stresses the importance of using a dental operating microscope during endodontic treatment as well as questioning the routine use of cone-beam computed tomographic imaging for similar cases.


Infant's bilobar thyroid agenesis and mother's I-131 accidental administration.
Bilobar thyroid agenesis is one of rare diseases. Genetic and environmental factors may associate with bilobar thyroid agenesis. But the mechanism is still not completely understood. It had been showed that I-131 administration during pregnancy may induce thyroid dysfunction in newborn. Here we reported a case of female hospital staff who received I-131 accidently during (10-12th gestational weeks) and after her pregnancy. The absorbed dose to fetus was higher than 30mGy. At birth, the infant was found to have no thyroid. It was speculated that the fetal thyroid agenesis may be related with mother' I-131 administration during pregnancy. In addition, this case report also indicated that the radiation dose should be minimized to any developing embryo.


Pseudomyxoma peritonei of appendiceal origin--a report of seven cases and a review of published reports.
To review our experience of different therapeutic regimens in the treatment of pseudomyxoma peritonei originating in the appendix. Retrospective study. University hospital, Germany. 7 Patients with histologically confirmed pseudomyxoma peritonei. Debulking operations. Morbidity and mortality. Complete removal of the tumour was possible at the initial operation only in a patient with a benign tumour. Debulking operations helped the other six patients considerably, but all but one died eventually of complications of the disease (usually bowel obstruction). Two patients developed what were thought to be pulmonary metastases, and one liver metastases, but these were not confirmed histologically. The results of chemotherapy varied; only one patient was free of tumour for about four years and in another progress of the tumour was halted for about a year. Length of follow up ranged from 2-20 years. Operation is the treatment of choice for pseudomyxoma peritonei, although complete resection is rarely feasible. Because of the low morbidity and slow growth of the tumour, reoperation is always indicated for symptoms of recurrence.


First line of biological drugs in rheumatoid arthritis: a medication persistence analysis.
To evaluate the persistence of biological drugs used as the first line of biological treatment in patients diagnosed with rheumatoid arthritis. The predictors associated with persistence have also been verified. We evaluated a historical cohort composed of users of the Brazilian National Health System in the period between 2006 January and 2014 December. The endpoint was the medication persistence at 12 months. A population composed of 66,787 individuals started the first line of biological drug. Out of such individuals, 34,595 (51.80%) persisted in the treatment at 12 months. Abatacept was the drug that presented higher persistence, followed by golimumab, tocilizumab, etanercept, and adalimumab and, with lower persistence certolizumab and infliximab. Younger individuals, living in regions with higher social inequality by Gini coefficient, using certolizumab and infliximab in comparison with adalimumab presented a higher risk of non-persistence to treatment. Individuals from the Southeastern region were more persistent than Northeastern, Central-western, Northern and Southern regions. The medication persistence was different between biological drugs. The rigorous follow-up of patients, by a multidisciplinary team, is important to enable the development of strategies for the adequate use of such drugs.


Transmitter-like L-3,4-dihydroxyphenylalanine tonically functions to mediate vasodepressor control in the caudal ventrolateral medulla of rats.
By microdialysis in the unilateral caudal ventrolateral medulla (CVLM) of anesthetized rats, the spontaneous L-3,4-dihydroxyphenylalanine (L-DOPA) release was in part tetrodotoxin-sensitive or Ca(2+)-dependent and was abolished by i.p. alpha-methyl-p-tyrosine (alpha-MPT), a tyrosine hydroxylase inhibitor. High K+ (50 mM) Ca(2+)-dependently evoked L-DOPA. By unilateral microinjections into the CVLM, L-DOPA (10-100 ng) produced dose-dependent, marked hypotension and bradycardia similarly in rats untreated, treated with i.p. 3-hydroxybenzylhydrazine, a central DOPA decarboxylase inhibitor, or with i.v.t. 6-hydroxydopamine. These responses were antagonized by L-DOPA methyl ester, a competitive L-DOPA antagonist. A depressor response to dopamine or noradrenaline (100 ng) was far smaller and slower in onset than that to L-DOPA (30 ng). D-DOPA (100 ng) produced no effect. Furthermore, L-DOPA methyl ester microinjected into bilateral CVLM produced some hypertension and tachycardia, which were markedly reduced by alpha-MPT. Transmitter-like L-DOPA tonically functions to mediate vasodepressor control in CVLM of rats.


Neonatal screening for biotinidase deficiency: A 30-year single center experience.
We reviewed the outcome of newborn screening for biotinidase deficiency performed at our department since 1987. Among 1,097,894 newborns screened, 461 were recalled, and 18 were identified as affected by complete or partial biotinidase deficiency (incidence 1:61,000, false positive rate 0.04%). The common missense mutation Q456H was found in 80% of patients with profound biotinidase deficiency. Of them, one patient harbored the novel mutation M399I in compound heterozygosity (M399I/Q456H). The complex allele A171T/D444H in cis was found in two patients with profound biotinidase deficiency (in homozygosity and in compound heterozygosity with the R211H mutation, respectively) and in one patient with partial biotinidase deficiency (in compound heterozygosity with the protective allele D444H in trans). All detected patients were treated and followed up at our Center until present. Biotin therapy (10-20 mg/day) allowed the full prevention of clinical symptoms in all patients with no adverse effects. These excellent outcomes confirm that newborn screening for biotinidase deficiency is a very effective secondary prevention program.


The determinants of tumour immunogenicity.
Many standard and targeted therapies, as well as radiotherapy, have been shown to induce an anti-tumour immune response, and immunotherapies rely on modulating the host immune system to induce an anti-tumour immune response. However, the immune response to such therapies is often reliant on the immunogenicity of a tumour. Tumour immunogenicity varies greatly between cancers of the same type in different individuals and between different types of cancer. So, what do we know about tumour immunogenicity and how might we therapeutically improve tumour immunogenicity? We asked four leading cancer immunologists around the world for their opinions on this important issue.


Inflammatory phenotype modulation in the respiratory tract and systemic circulation of e-cigarette users: a pilot study.
Over 40 million people use e-cigarettes worldwide, but the impact of chronic e-cigarette use on health has not been adequately defined. In particular, effects of e-cigarette aerosol inhalation on inflammation and host defenses across the body are not fully understood. We conducted a longitudinal cohort pilot study to explore changes in the inflammatory state and monocyte function of e-cigarette users (n = 20) versus healthy controls (n = 13) and to evaluate effects of e-cigarette use reduction on the same. Saliva, sputum, and blood were obtained from e-cigarette users at baseline and after a 2-wk intervention of decreased e-cigarette use. Overall, across 38 proteins quantified by multiplex, airway samples from e-cigarette users tended to have decreased levels of immunomodulatory proteins relative to healthy controls, whereas levels of cytokines, chemokines, and growth factors in the circulation tended to be elevated. Specifically, e-cigarette users had lower levels of IL-1 receptor antagonist (IL-1Ra) in saliva (P < 0.0001), with higher IL-1Ra and growth-regulated oncogene (GRO) levels in sputum (P < 0.01 and P < 0.05, respectively), and higher levels of both TNFβ (P < 0.0001) and VEGF (P < 0.0001) in plasma. Circulating monocytes from e-cigarette users had alterations in their inflammatory phenotype in response to reduced e-cigarette use, with blunted IL-8 and IL-6 release upon challenge with bacterial lipopolysaccharide (P < 0.001 and P < 0.05, respectively), suggesting a decreased ability to appropriately respond to bacterial infection. Based on these findings, chronic inhalation of e-cigarette aerosols alters the inflammatory state of the airways and systemic circulation, raising concern for the development of both inflammatory and infectious diseases in chronic users of e-cigarettes.


Multidetector-row CT: cardiosurgery indications.
This article critically evaluates the role of multidetector-row CT before and after cardiosurgical procedures. In addition, technical aspects, such as scan protocols, optimal image reconstruction intervals, image reformation techniques, and data evaluation, are presented and briefly discussed.


Optimization of 13 C-urea breath test threshold levels for the detection of Helicobacter pylori infection in a national referral laboratory.
Threshold values for 13 C-urea breath test (13C-UBT) positivity may be affected by various sociodemographic, host, bacterial, and laboratory factors. Manufacturer recommended cutoffs for 13C-UBT assays may not be applicable in all settings. Optimizing 13C-UBT cutoffs may have profound public health ramifications. We aimed to determine the optimal threshold for 13C-UBT positivity in our population. Consecutive test samples collected at our central laboratory from patients undergoing a first-time 13C-UBT between 1 January 2010 and 31 December 2015 were included. The difference between values at 30 minutes and at baseline (T30-T0) was expressed as delta over baseline (DOB). Cluster analysis was performed on the 13C-UBT test results to determine the optimal cutoff point with minimal interclass variance. Two lakhs thirty four thousand eight hundred thirty one patients (87 291 (37.2%) male, age 39.9 ± 19.9) underwent a first-time 13C-UBT, including 124 701 (53.1%) negative and 110 130 (46.9%) positive tests, using the manufacturer-recommended cutoff of 3.5 DOB. Cluster analysis determined an optimized cutoff of 2.74 DOB, representing an additional 2180 (0.93%) positive subjects who had been previously categorized as negative according to the manufacturer-specified cutoff of 3.5 DOB. Mean positive and negative DOB values were 19.54 ± 14.95 and 0.66 ± 0.51, respectively. The cutoffs for male and female subjects were 2.23 and 3.05 DOB, respectively. Threshold values for <45-year-olds, 45-60-year-olds and >60-year-olds were 2.67, 2.55, and 2.93 DOB, respectively. Of the 2180 (0.93%) patients with DOB 2.73-3.49, 289 (13.3%) performed a subsequent 13C-UBT and 140 (48.4%) remained positive when tested at 20.3 ± 14.4 months. Major referral laboratories should optimize threshold values for 13C-UBT positivity for their geographical location. Different cutoff values should be applied for male and female subjects.


Defining normal distributions of coronary artery calcium in women and men (from the Framingham Heart Study).
Coronary artery calcium (CAC) may improve risk stratification for patients with coronary heart disease (CHD) beyond traditional risk factors. Subjects from the Framingham Heart Study Offspring and Third Generation cohorts (48% women; mean age 53 years) underwent noncontrast electrocardiographically triggered cardiac multidetector computed tomography. The prevalence of absolute CAC (Agatston score [AS] >0, >100, and >400) and relative age- and gender-specific strata (25th, 50th, 75th, 90th, and 95th percentiles) were determined in a healthy subset free of clinically apparent cardiovascular disease or CHD risk factors (n = 1,586), the overall sample at risk (n = 3,238), and subjects at intermediate Framingham risk score (FRS; 6% to 20% 10-year CHD event risk; n = 1,177). Absolute AS and relative cutoffs for CAC increased with age and FRS, were higher in men compared with women in each of the 3 cohorts, and increased from the healthy subset to the overall cohort to subjects at intermediate risk. However, in subjects with CAC, there was substantial disagreement between absolute and relative cut-off values for labeling subjects as having increased CAC. In general, more subjects were considered to have increased CAC using relative cut-off values, especially in women and younger subjects. Fewer subjects at intermediate FRS had increased CAC using comparable absolute versus relative cutoffs (men 32% at AS >100 vs 36% at >75th percentile; women 24% at AS >100 vs 34% at >75th percentile). In conclusion, we provided distributions of CAC in a healthy subset, the overall cohort, and subjects at intermediate risk from the Framingham Heart Study for both absolute and relative cut-off values for CAC. Absolute cutoffs underestimated the proportion of subjects with increased CAC, specifically in women, younger persons, and persons at intermediate CHD risk.


The effect of prostaglandin E1 during cardiopulmonary bypass on renal function after cardiac surgery.
We have evaluated the effect of prostaglandin E1 (PGE1) on renal function after cardiac surgery with cardiopulmonary bypass in 20 patients, ten of whom received 0.02 microgram.kg-1.min-1 of PGE1 by infusion into the oxygenator during bypass; ten patients served as controls. Serum beta 2-microglobulin fell significantly and urine beta 2-microglobulin increased significantly after surgery in both groups. Urine N-acetyl-beta-D-glucosaminidase was high after surgery in both groups, but it was significantly lower in the PGE1 group. Free water clearance fell significantly on the 1st, 3rd, and 5th postoperative days compared with preoperative values in the control but not in the PGE1 group. These results suggest that PGE1 may prevent renal dysfunction after cardiopulmonary bypass.


Leaf movement, stress avoidance and photosynthesis in Vitis californica.
Gas exchange and chlorophyll fluorescence techniques were used to evaluate the hypothesis that leaf movement in Vitis californica Benth. (California wild grape) allows a compromise between sunlight interception and stress damage in order to maximize photosynthetic carbon gain over the life of the leaf. Leaves that were restrained horizontally tolerated their increased radiation loads if critical temperatures were not exceeded. Reductions in photosynthetic capacity and the F V/F M fluorescence ratio only occurred in leaves that attained high temperatures. Leaf orientation and canopy position were important determinants of leaf temperature. These results indicate that excessive leaf temperature, not high PFD, can be a principle cause of reduced carbon gain and senescence in this species in the wild. Leaf movement appears to protect photosynthetic components in midsummer.


Genetics and epigenetics of human aggression.
There is substantial variation between humans in aggressive behavior, with its biological etiology and molecular genetic basis mostly unknown. This review chapter offers an overview of genomic and omics studies revealing the genetic contribution to aggression and first insights into associations with epigenetic and other omics (e.g., metabolomics) profiles. We allowed for a broad phenotype definition including studies on "aggression," "aggressive behavior," or "aggression-related traits," "antisocial behavior," "conduct disorder," and "oppositional defiant disorder." Heritability estimates based on family and twin studies in children and adults of this broadly defined phenotype of aggression are around 50%, with relatively small fluctuations around this estimate. Next, we review the genome-wide association studies (GWAS) which search for associations with alleles and also allow for gene-based tests and epigenome-wide association studies (EWAS) which seek to identify associations with differently methylated regions across the genome. Both GWAS and EWAS allow for construction of Polygenic and DNA methylation scores at an individual level. Currently, these predict a small percentage of variance in aggression. We expect that increases in sample size will lead to additional discoveries in GWAS and EWAS, and that multiomics approaches will lead to a more comprehensive understanding of the molecular underpinnings of aggression.


The immunogenicity of milk from various species for the guinea-pig.
Young guinea-pigs, sensitized and challenged by the parenteral administration of bovine and human milks, died of anaphylaxis while others, sensitized and challenged with guinea-pig milk, were unaffected. The type of milk fed to young guinea-pigs from birth did not alter the basic immunogenicity of cow's milk or the lack of immunogenicity of guinea-pig milk for the young guinea-pig.


Machine learning modelling of a membrane capacitive deionization (MCDI) system for prediction of long-term system performance and optimization of process control parameters in remote brackish water desalination.
Membrane Capacitive Deionization (MCDI) is a promising electrochemical technique for water desalination. Previous studies have confirrmed the effectiveness of MCDI in removing contaminants from brackish groundwaters, especially in remote areas where electricity is scarce. However, as with other water treatment technologies, performance deterioration of the MCDI system still occurs, hindering the stability of long-term operation. Herein, a machine learning (ML) modelling framework and various ML models were developed to (i) investigate the performance deterioration due particularly to insufficient charging/discharging of the electrode caused by accumulation of ions and electrode scaling and (ii) optimise MCDI operating parameters such that the impacts of these deleterious effects on unit performance were minimized. The ML models developed in this work exhibited a prediction accuracy of cycle time with average mean absolute percentage error (MAPE) values of 16.82% and 16.09% after 30-fold cross validation for Random Forest (RF) and Multilayer Perceptron (MLP) models respectively. The pre-trained ML model predicted different declining trends of water production for two different operating conditions and provided corresponding recommendations on frequencies of chemical cleaning. A case study on the adjustment of operating parameters using the results suggested by the optimization ML model was conducted. The model validation results showed that the overall water production and water recovery of the system using the cycle-based optimized process control parameters (SCN 1) exceeds the MCDI system performance under three fixed parameter settings that were used at each stage of SCN 1 by 1.78% to 4.48% and 2.95% to 9.46%, respectively. Permutation-based and Shapley additive explanation (SHAP) coefficients were also employed for variable importance (VIMP) analysis to uncover the "black-box" nature of the ML models and to better understand the various features' contributions to overall MCDI system performance.


Partnering with healthcare systems to improve HPV vaccination:The perspective of immunization program managers.
The US's 64 CDC-funded immunization programs are at the forefront of efforts to improve the quality of adolescent vaccination services. We sought to understand immunization program managers' perspectives on partnering with healthcare systems to improve HPV vaccine uptake. Managers of 44 state and local immunization programs completed our online survey in 2019. Immunization managers strongly endorsed the importance of partnering with systems to improve HPV vaccine uptake (mean = 3.8/4.0), and most wanted to do so in the next year (mean = 3.5). Immunization managers reported that common barriers included difficulty contacting systems' leadership (57%), differing organizational cultures (52%), and time (52%). Many perceived systems as not prioritizing HPV vaccination (77%). Immunization managers expressed strong interest in participating in a training on partnering with systems (mean = 3.5). Overall, immunization managers are highly interested in partnering with systems to improve HPV vaccine uptake. Training and other support are needed to expand programs' capacity for such partnerships.


The pan-genome of Lactobacillus reuteri strains originating from the pig gastrointestinal tract.
Lactobacillus reuteri is a gut symbiont of a wide variety of vertebrate species that has diversified into distinct phylogenetic clades which are to a large degree host-specific. Previous work demonstrated host specificity in mice and begun to determine the mechanisms by which gut colonisation and host restriction is achieved. However, how L. reuteri strains colonise the gastrointestinal (GI) tract of pigs is unknown. To gain insight into the ecology of L. reuteri in the pig gut, the genome sequence of the porcine small intestinal isolate L. reuteri ATCC 53608 was completed and consisted of a chromosome of 1.94 Mbp and two plasmids of 138.5 kbp and 9.09 kbp, respectively. Furthermore, we generated draft genomes of four additional L. reuteri strains isolated from pig faeces or lower GI tract, lp167-67, pg-3b, 20-2 and 3c6, and subjected all five genomes to a comparative genomic analysis together with the previously completed genome of strain I5007. A phylogenetic analysis based on whole genomes showed that porcine L. reuteri strains fall into two distinct clades, as previously suggested by multi-locus sequence analysis. These six pig L. reuteri genomes contained a core set of 1364 orthologous gene clusters, as determined by OrthoMCL analysis, that contributed to a pan-genome totalling 3373 gene clusters. Genome comparisons of the six pig L. reuteri strains with 14 L. reuteri strains from other host origins gave a total pan-genome of 5225 gene clusters that included a core genome of 851 gene clusters but revealed that there were no pig-specific genes per se. However, genes specific for and conserved among strains of the two pig phylogenetic lineages were detected, some of which encoded cell surface proteins that could contribute to the diversification of the two lineages and their observed host specificity. This study extends the phylogenetic analysis of L. reuteri strains at a genome-wide level, pointing to distinct evolutionary trajectories of porcine L. reuteri lineages, and providing new insights into the genomic events in L. reuteri that occurred during specialisation to their hosts. The occurrence of two distinct pig-derived clades may reflect differences in host genotype, environmental factors such as dietary components or to evolution from ancestral strains of human and rodent origin following contact with pig populations.


[Monoamine oxidase activity and brain levels of histamine and polyamines in various extreme exposures].
The activity and kinetic properties of monoaminoxidase, the level of histamine and polyamines are studied under three extreme factors--hyperoxia, hypoxia and cold stress. The similarity of the metabolic responses of the organism to the investigated extreme factors is shown. All studied parameters indicate that the selected regime of hyperoxia has the most negative effect on the organism; hypoxia has the slightest effect and cold stress takes an intermediate position.


High-resolution diffusion-weighted imaging increases lesion detectability in patients with transient global amnesia.
DWI can detect small punctate hyperintense lesions of the hippocampus in patients with TGA. We investigated whether small TGA lesions can be detected more often by increasing the resolution of DWI. Of 31 consecutive patients with TGA, 27 underwent DWI, twice at the first visit (range 1.5-22 hours; mean 10 hours) and at follow-up (range 50-87 hours; mean 72.5 hours) after the onset of their symptoms. Each DWI included 2 different spatial resolutions with the same b-value (2000 seconds/mm(2)): conventional resolution in a 128 × 128 matrix with 3-mm section thickness and high resolution in a 220 × 220 matrix with 2-mm section thickness. The number and contrast of hyperintense lesions were compared between the 2 resolutions. Twenty-two of the 27 patients had single or multiple TGA lesions. The total number of lesions detected on conventional and high-resolution DWI was 11 and 22, respectively, at the first visit, and was 24 and 37, respectively, at follow-up. The number of lesions was significantly larger on high-resolution DWI than on conventional resolution at the first visit (P < .01) and at the follow-up (P < .01). Lesion contrast was significantly increased on high-resolution DWI (P < .01). Higher DWI resolution increased lesion detectability in patients with TGA. Considering the small size of TGA lesions, the resolution of DWI is an important parameter influencing lesion detectability.


Incorporation of potassium halides in the mechanosynthesis of inorganic perovskites: feasibility and limitations of ion-replacement and trap passivation.
Potassium halides (KX; X = I, Br, or Cl) were incorporated as partial replacements of CsBr in the mechanosynthesis of CsPbBr3. This led to partial substitution of both monovalent ions forming mixed Cs1-x K x PbBr3-y X y perovskites. Longer photoluminescence lifetimes were also observed, possibly linked to the formation of a non-perovskite KPb2X5 passivating layer.


[Effect of VATS wedge resection and mediastinal lymph node sampling in elderly patients with early peripheral lung cancer].
The treatment for early-stage non-small cell lung cancer is primarily surgical. However, the optimal extent of mediastinal lymph node resection remains to be determined. The aim of the current study is to investigate the effect of a pulmonary wedge resection on aged patients with lung cancer. A total of 15 lung cancer patients aged over 70 years were treated via video-assisted thoracoscopic surgery (VATS) wedge resection and mediastinal lymph node sampling from June 2004 to February 2008. Mediastinal lymph node sampling included stations 2R, 4R, 8 and 9 for the right-sided cancers and stations 5, 6, 8 and 9 for the left-sided cancers. VATS wedge resection and mediastinal lymph node sampling for aged patients with peripheral lung cancer are minimally invasive treatments with a short operative time and low postoperative morbidity. The 1-year and 3-year survival rates were 100% and 86.6%, respectively. VATS wedge resection and mediastinal lymph node sampling can be an alternative treatment for aged patients with early peripheral lung cancer.


Patient perceived improvement and medication resumption rates after intradetrusor onabotulinumtoxina for idiopathic urgency urinary incontinence.
Intradetrusor onabotulinumtoxinA (BTX-A) is a third-line therapy for overactive bladder (OAB), however several gaps exist in periprocedural care. Prior studies have demonstrated BTX-A efficacy at 2-3 weeks, but there are limited data documenting when patients should begin to note symptom improvement. The primary aim of this study was to evaluate patient-reported temporal improvement in symptoms, with secondary aim to evaluate medication resumption rates, following initial BTX-A injection. A prospective, single-arm cohort study of patients with non-neurogenic urgency incontinence undergoing initial BTX-A injection was performed. Intradetrusor 100 units BTX-A was administered in standard 20-site template. Patients discontinued OAB medication(s) at BTX-A injection and completed a daily Patient Global Impression of Improvement (PGI-I) diary for 3 weeks. Data were collected at 1 month, including final satisfaction score, medication resumption rates, and adverse outcomes. Fifty-one patients were included, with 25 patients (49%) actively taking an OAB medication. Median time to first improvement was 3 days, at least "much better" (PGI-I <2) was 5 days, and maximal improvement was 7 days. Twenty of 25 patients (80%) opted to remain off OAB medications at 1 month based on symptomatic improvement following injection. Adverse outcomes included urinary tract infection in three patients (6%) and symptomatic incomplete emptying requiring temporary intermittent catheterization in two patients (4%). Median time to first and maximal improvement was 3 and 7 days, respectively, following initial 100 units BTX-A. Eighty percent of patients on medications opted to remain off at 1 month. These data may help further counsel patient expectations following initial BTX-A therapy.


Distribution of nucleosomes on reconstituted chromatin from cloned mouse beta-globin DNA.
Relative abundance of nucleosomes on reconstituted chromatin was estimated with cloned mouse beta-globin gene DNA. Mononucleosomal DNA was isolated from reconstituted chromatin after digestion with micrococcal nuclease, nick-translated and used as a probe for blot hybridization. DNA fragments of restriction nuclease-digested globin DNA were transferred to DBM-paper and hybridized with mononucleosomal [32P] DNA probe. The results showed non-random distribution of nucleosomes.


Gas chromatographic and mass fragmentographic assays of carcinogenic polycyclic hydrocarbon epoxide hydratase activity.
A specific and very sensitive procedure for the determination of epoxide hydratase activity in hepatic microsomes is described. Any polycyclic hydrocarbon epoxide can be used as a substrate; in this study, benzo(a)anthracene-5,6-oxide, benzo(a)pyrene-4,5-oxide and 3-methylcholanthrene-11,12-oxide were utilized. The corresponding trans-diols formed during incubation are separated and evaluated using either an electron-capture gas chromatographic method for the determination of their chloromethyldimethylsilylated derivatives or gas chromatographic-mass fragmentographic measurement of their trimethylsilylated derivatives. Concentrations as low as 1 ng per millilitre of incubation mixture can be estimated.


Perioperative cardiovascular mortality in noncardiac surgery: validation of the Lee cardiac risk index.
The Lee risk index was developed to predict major cardiac complications in noncardiac surgery. We retrospectively evaluated its ability to predict cardiovascular death in the large cohort of patients who recently underwent noncardiac surgery in our institution. The administrative database of the Erasmus MC, Rotterdam, The Netherlands, contains information on 108 593 noncardiac surgical procedures performed from 1991 to 2000. The Lee index assigns 1 point to each of the following characteristics: high-risk surgery, ischemic heart disease, heart failure, cerebrovascular disease, renal insufficiency, and diabetes mellitus. We retrospectively used available information in our database to adapt the Lee index calculated the adapted index for each procedure, and analyzed its relation to cardiovascular death. A total of 1877 patients (1.7%) died perioperatively, including 543 (0.5%) classified as cardiovascular death. The cardiovascular death rates were 0.3% (255/75 352) for Lee Class 1, 0.7% (196/28 892) for Class 2, 1.7% (57/3380) for Class 3, and 3.6% (35/969) for Class 4. The corresponding odds ratios were 1 (reference), 2.0, 5.1, and 11.0, with no overlap for the 95% confidence interval of each class. The C statistic for the prediction of cardiovascular mortality using the Lee index was 0.63. If age and more detailed information regarding the type of surgery was retrospectively added, the C statistic in this exploratory analysis improved to 0.85. The adapted Lee index was predictive of cardiovascular mortality in our administrative database, but its simple classification of surgical procedures as high-risk versus not high-risk seems suboptimal. Nevertheless, if the goal is to compare outcomes across hospitals or regions using administrative data, the use of the adapted Lee index, as augmented by age and more detailed classification of type of surgery, is a promising option worthy of prospective testing.


Postoncological lacrimal duct reconstruction: A practical classification system for reconstructive planning and short-term results of a case series.
Surgical resection of skin tumors in the medial canthal area may damage the lacrimal duct and can result in chronic epiphora. Postoncologic reconstruction of the lacrimal duct has not been studied extensively. The current study discusses the anatomical and functional features of the lacrimal duct. It describes short-term functional outcomes after monocanalicular reconstruction of the lacrimal duct in a case series of 10 patients. From February 2015 to October 2017, all patients with a postoncological lacrimal duct defect were analyzed to make an anatomical classification. The functional outcomes of patients after monocanalicular reconstruction were measured with the Munk scale up to 3 months after stent removal. Twelve patients had lacrimal duct defects after Mohs resection. Anatomical characteristics were used to create a clinical classification for lacrimal duct defects. This classification divides the upper (U) and lower (L) proximal lacrimal duct into two sections which can be damaged: the punctum and pars verticalis (1), the canaliculus horizontalis (2), or combined (3). The Common lacrimal duct (C) is the distal part of the lacrimal duct and can also be affected. Ten patients were analyzed after lacrimal duct reconstruction. Three months after stent removal, none of the patients suffered from epiphora. This article proposes an anatomical classification for lacrimal duct defects in the proximal lacrimal drainage system. The classification can be applied in comparing cases and determining reconstructive strategies after oncologic skin tumor resection. Short-term results are promising for future efforts to reconstruct the lacrimal duct.


Ultrasensitive analysis of genetic instability related to chemical exposure.
Our concerns have been raised about whether prolonged exposure to ammunition-related chemicals could correlate with genomic instability predisposing to lung carcinogenesis. The group of professional soldiers engaged in routine ammunition analysis and its explosive properties testing. To assess the presence of an innate genetic profile, DNA isolated from swabs was analyzed with LungCarta and HS Lung Panels and MassARRAY Analyzer 4 mass spectrometry. The presence of new somatic single nucleotide polymorphisms (SNPs) was detected with liquid biopsy technique and circulating cell-free DNA (ccfDNA) isolation, which was further analyzed with UltraSeek Lung Panel. Both genetic profiles obtained for each individual were compared. Genetic analysis revealed that in professional soldiers with long-term exposure to ammunition-related toxic chemicals, new SNPs in genes related to lung carcinogenesis are present. The preliminary data indicate that using modern molecular techniques could be a valuable tool for monitoring the genome instability in context of occupational risk of harmful volatile toxic compounds and improving personnel safety. The analyzed group will be further enlarged, and follow-up studies will be continued.


Correspondence between cognitive and neural representations for phonology, orthography, and semantics in supramarginal compared to angular gyrus.
The angular and supramarginal gyri (AG and SMG) together constitute the inferior parietal lobule (IPL) and have been associated with cognitive functions that support reading. How those functions are distributed across the AG and SMG is a matter of debate, the resolution of which is hampered by inconsistencies across stereotactic atlases provided by the major brain image analysis software packages. Schematic results from automated meta-analyses suggest primarily semantic (word meaning) processing in the left AG, with more spatial overlap among phonological (auditory word form), orthographic (visual word form), and semantic processing in the left SMG. To systematically test for correspondence between patterns of neural activation and phonological, orthographic, and semantic representations, we re-analyze a functional magnetic resonance imaging data set of participants reading aloud 465 words. Using representational similarity analysis, we test the hypothesis that within cytoarchitecture-defined subregions of the IPL, phonological representations are primarily associated with the SMG, while semantic representations are primarily associated with the AG. To the extent that orthographic representations can be de-correlated from phonological representations, they will be associated with cortex peripheral to the IPL, such as the intraparietal sulcus. Results largely confirmed these hypotheses, with some nuanced exceptions, which we discuss in terms of neurally inspired computational cognitive models of reading that learn mappings among distributed representations for orthography, phonology, and semantics. De-correlating constituent representations making up complex cognitive processes, such as reading, by careful selection of stimuli, representational formats, and analysis techniques, are promising approaches for bringing additional clarity to brain structure-function relationships.


Phospholipid functional groups involved in protein kinase C activation, phorbol ester binding, and binding to mixed micelles.
The specificity of the phospholipid cofactor requirement of rat brain protein kinase C was investigated using Triton X-100 mixed micellar methods. Sixteen analogues of phosphatidylserine were prepared and tested for their ability to support protein kinase C activity, [3H]phorbol 12,13-dibutyrate binding, and protein kinase C binding to mixed micelles. Phosphatidylserinol, -L-serine methyl ester, -N-acetyl-L-serine, -2-hydroxyacetate, -3-hydroxypropionate, and -4-hydroxybutyrate did not activate protein kinase C in mixed micelles containing 2 mol % of sn-1,2-dioleoylglycerol. This indicates that both the carboxyl and amino moieties are important for activation. Phosphatidyl-D-serine and -L-homoserine were incapable of supporting full activation; this demonstrates stereospecificity and the importance of the distance between the phosphate and carboxyl and amino moieties. Since 1,2-rac-phosphatidyl-L-serine and 1,3-phosphatidyl-L-serine fully supported protein kinase C activity, the stereochemistry within the glycerol backbone at the interface was not necessary for maximal activation. Neither lysophosphatidyl-L-serine nor 1-oleoyl-2-acetyl-sn-glycero-3-phospho-L-serine supported protein kinase C activity implying that the interfacial conformation is critical to the activation process. The phospholipid dependencies of [3H]phorbol 12,13-dibutyrate binding and of protein kinase C binding to mixed micelles containing sn-1,2-dioleoylglycerol did not mirror those for activation. The data demonstrate that protein kinase C possesses a high degree of specificity with respect to phospholipid activation and implicate several functional groups within the phospho-L-serine polar head group in binding and activation.


[Effect of creatine phosphate on the slow inward calcium current, action potentials and the strength of myocardial contraction].
The effect of creatine phosphate on the frog heart muscle involved maintenance of its contraction at high level even after inhibition of mitochondrial oxidative phosphorylation by sodium cyanide. The effect of creatine phosphate on the contractile force and action potential is similar for the frog heart ventricle and atrium. The voltage--clamp technique showed that creatine phosphate controlled the slow inward calcium current through the surface membrane of the frog atrium cells.


Affinity of anti-peptide antibodies measured by resonance energy transfer.
Because of the increasing use of monoclonal anti-peptide antibodies we have undertaken to formulate a general method for the measurement of intrinsic association constants characterizing complex formation between peptide and antibody. The method is based on the phenomenon of resonance energy transfer between tryptophan-excited antibody and an appropriate fluorophor conjugated to the amino terminus of the peptide. The fluorophor we have employed is 8-(2-N-succinylaminoethylamino)-1-naphthalene-sulfonic acid with an absorption maximum at 344 nm and an emission maximum at 500 nm. The model peptide used was the sequence corresponding to residues 48-60 of the regulatory subunit of aspartyltranscarbamoylase. Three IgG and two IgM affinity-purified monoclonal anti-peptide antibodies were used in the fluorescence titration experiments. A maximum value of 2.1 X 10(6) M-1 was found for the IgG antibodies and a maximum of 2.7 X 10(4) M-1 for the IgM antibodies. These limited results suggest similar behavior for the anti-peptide B cell response with respect to affinity maturation as observed for other specificities. In particular it is likely that the IgM affinities are restricted to the potential available in the germline repertoire of variable region genes and, therefore, express only germline affinities.