PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer.
The role of image-guided surveillance as compared with planned neck dissection in the treatment of patients with squamous-cell carcinoma of the head and neck who have advanced nodal disease (stage N2 or N3) and who have received chemoradiotherapy for primary treatment is a matter of debate. In this prospective, randomized, controlled trial, we assessed the noninferiority of positron-emission tomography-computed tomography (PET-CT)-guided surveillance (performed 12 weeks after the end of chemoradiotherapy, with neck dissection performed only if PET-CT showed an incomplete or equivocal response) to planned neck dissection in patients with stage N2 or N3 disease. The primary end point was overall survival. From 2007 through 2012, we recruited 564 patients (282 patients in the planned-surgery group and 282 patients in the surveillance group) from 37 centers in the United Kingdom. Among these patients, 17% had nodal stage N2a disease and 61% had stage N2b disease. A total of 84% of the patients had oropharyngeal cancer, and 75% had tumor specimens that stained positive for the p16 protein, an indicator that human papillomavirus had a role in the causation of the cancer. The median follow-up was 36 months. PET-CT-guided surveillance resulted in fewer neck dissections than did planned dissection surgery (54 vs. 221); rates of surgical complications were similar in the two groups (42% and 38%, respectively). The 2-year overall survival rate was 84.9% (95% confidence interval [CI], 80.7 to 89.1) in the surveillance group and 81.5% (95% CI, 76.9 to 86.3) in the planned-surgery group. The hazard ratio for death slightly favored PET-CT-guided surveillance and indicated noninferiority (upper boundary of the 95% CI for the hazard ratio, <1.50; P=0.004). There was no significant difference between the groups with respect to p16 expression. Quality of life was similar in the two groups. PET-CT-guided surveillance, as compared with neck dissection, resulted in savings of £1,492 (approximately $2,190 in U.S. dollars) per person over the duration of the trial. Survival was similar among patients who underwent PET-CT-guided surveillance and those who underwent planned neck dissection, but surveillance resulted in considerably fewer operations and it was more cost-effective. (Funded by the National Institute for Health Research Health Technology Assessment Programme and Cancer Research UK; PET-NECK Current Controlled Trials number, ISRCTN13735240.).


An HLA-binding-motif-aided peptide epitope library: a novel library design for the screening of HLA-DR4-restricted antigenic peptides recognized by CD4+T cells.
Susceptibility to a series of autoimmune diseases is strongly associated with particular HLA class II alleles. Identification of T cell clones and antigenic epitopes bound by HLA class II molecules involved in autoimmune diseases is critical to understanding the etiology of these HLA class II-associated diseases. However, establishment of T cell clones in autoimmune diseases is difficult because the antigenic peptides are unknown. Peptide library methods which include all possible peptide sequences offer a potentially powerful tool for the detection of cross-reactive antigenic peptides recognized by T cells. Here, we reduced the number of peptides per mixture by utilizing the known binding motifs of peptides for the HLA-DRB1*0405 molecule and evaluated the effectiveness of this library design. Each library mixture evoked a strong proliferative response in the unprimed peripheral blood lymphocytes (PBL) from HLA-DRB1*0405-positive donors but little or no response in the PBL from HLA-DRB1*0405-negative donors. The library also detected antigenic peptides that activated three antigen-specific T cell lines restricted by HLA-DRB1*0405, with different specificities. The motif-based approach thus presents a powerful method for monitoring T cells in large, heterogeneous T cell populations and is useful for the identification of the mimic peptide epitopes of T cell lines and clones.


Obesity Suppresses Estrogen Receptor Beta Expression in Breast Cancer Cells via a HER2-Mediated Pathway.
Obesity is associated with a worse breast cancer prognosis, while greater breast tumor estrogen receptor beta (ERβ) expression is correlated with improved therapy response and survival. The objective of this study was to determine the impact of obesity on breast cancer cell ERβ expression, which is currently unknown. We utilized an in vitro model of obesity in which breast cancer cells were exposed to patient serum pooled by body mass index category (obese (OB): ≥30 kg/m2; normal weight (N): 18.5-24.9 kg/m2). Four human mammary tumor cell lines representing the major breast cancer subtypes (SKBR3, MCF-7, ZR75, MDA-MB-231) and mammary tumor cells from MMTV-neu mice were used. ERβ expression, assessed by qPCR and western blotting, was suppressed in the two HER2-overexpressing cell lines (SKBR3, MMTV-neu) following OB versus N sera exposure, but did not vary in the other cell lines. Expression of Bcl-2 and cyclin D1, two genes negatively regulated by ERβ, was elevated in SKBR3 cells following exposure to OB versus N sera, but this difference was eliminated when the ERβ gene was silenced with siRNA. Herceptin, a HER2 antagonist, and siRNA to HER2 were used to evaluate the role of HER2 in sera-induced ERβ modulation. SKBR3 cell treatment with OB sera plus Herceptin increased ERβ expression three-fold. Similar results were obtained when HER2 expression was silenced with siRNA. OB sera also promoted greater SKBR3 cell viability and growth, but this variance was not present when ERβ was silenced or the cells were modified to overexpress ERβ. Based on this data, we conclude that obesity-associated systemic factors suppress ERβ expression in breast cancer cells via a HER2-mediated pathway, leading to greater cell viability and growth. Elucidation of the mechanism(s) mediating this effect could provide important insights into how ERβ expression is regulated as well as how obesity promotes a more aggressive disease.


A Realist Case Study of a Regional Hospital's Response to Improve Emergency Department Access in the Context of Australian Health Care Reforms.
Major health-care reforms have extended across all Australian public hospitals in recent years. Improving emergency department (ED) access has been a focus of these reforms. This study evaluates how the national reforms have led to improvement in ED access in a regional hospital in remote Australia. Assessing a complex scenario such as national reforms and the challenges faced by the regional hospital to implement these reforms requires in-depth analysis. A realist evaluation theory-based approach was employed, allowing investigation of what, how, why, and for whom change occurred. A case study mixed methods design was adopted within the realist framework to answer these questions about change. The study identified moderate improvement in ED access as a result of the reforms (investment in infrastructure and workforce and the introduction of ED targets). Clinical leadership and support from management were essential for the improvement. Without ongoing investment and clinical redesign activities, however, sustainability of the improvement may prove difficult.


Association of 7-Day Follow-Up With 6-Month Suicide Mortality Following Hospitalization for Suicidal Thoughts or Behaviors Among Older Adults.
To evaluate whether timely follow-up outpatient mental health care is associated with reduced short-term suicide risk following hospitalization for suicidal thoughts or behaviors. Retrospective cohort analysis using 2015 Medicare data for adults aged ≥ 65 years who were hospitalized for suicidal ideation or behaviors (n = 36,557) linked with the National Death Index. Adjusted risk ratios (ARR) estimated the association between 7-day follow-up and suicide risk at 30-, 90-, and 180-days, adjusted for confounding by indication using inverse probability of treatment weights of observable covariates. Overall, 39.3% of patients received 7-day follow-up, which was associated with 41% higher risk of suicide within 180 days. Follow-up care was associated with higher suicide risk for Medicare Advantage enrollees, patients with no recent prior mental health care, and those admitted for suicidal behaviors. Results suggest 7-day follow-up care was not associated with lower post-discharge suicide risk. For this high-risk group, suicide-specific interventions may be needed during the critical postdischarge period.


[The malaria situation in the WHO eastern Mediterranean region].
About 45% of the population of the Eastern Mediterranean Region live under the risk of both falciparum and vivax malaria, and additional 15% under the risk of P. vivax alone. The estimated annual number of malaria cases is about 14 million, out of which 95% occur in four countries: Afghanistan, Somalia, Sudan and Yemen. In Afghanistan malaria is endemic throughout the country at altitude below 1500 m. About 80-90% of malaria cases belong to P. vivax, the rest to P. falciparum (the latter is prevalent mostly in the South and in Badakhshan). In Islamic Republic of Iran 16% of the population live in initially non-malarious areas, 66% in areas freed from malaria, 12% in areas with sporadic transmission, mostly of P. vivax, and only 6% in areas of continuous transmission with a high proportion of P. falciparum. As much as 77% of the recorded cases belong to the latter territories. Iraq. After the Gulf war, the situation deteriorated in the three north-eastern governorates, and malaria spread outside this area and rooted in the south (Basra). Syria. Transmission of P. vivax still occurs, mostly along the western part of the border with Turkey and in the north-eastern corner of the country. At present, there are three areas that causes concern along borders between the European and Eastern Mediterranean Regions: Afghanistan is a source of importation of malaria to all its neighbours; areas on the borders between Iran, Azerbaijan and, to some extent, Armenia; 4 northern governorates of Iraq and parts of southeastern Turkey, with repercussions in Syria and, to a Lesser extent in Iran, along its western border. To some extent, Cyprus is also threatened, since importation of malaria to the northern part of the island from Turkey has been documented. In practical terms, there is a need for co-ordination of antivectorial activities and standardization of control methods between the countries with strong programmes and relatively intense transmission in border areas, i.e. between Iran, and Azerbaijan, Iraq and Turkey, Syria and Turkey.


[The effect of SR 142801, a blocker of tachykinin NK-3 receptors, on synaptic transmission in the rat caudal mesenteric ganglion].
Effects of tachykinin NK-3 receptors antagonist SR 142801 on the synaptic transmission in the rat's caudal mesenteric ganglion were investigated using extracellular recording of compound action potentials (CAPs) from the ganglion nerves. It is shown that antagonist of NK-3 receptors SR 142801 (2.5.10(-7) mol/l) decreased the amplitude and square of CAPs obtained by stimulating of intermesenteric nerve (IMN) and leading off from the colonic nerve, after high-frequency stimulation of IMN. It is suggests that tachykinin NK-3 receptors take part in SP-ergic synaptic transmission through the rat's caudal mesenteric ganglion.


Holographic interferometry with reference beams modulated by the object motion.
Holographic interferometry with a reference beam reflected out of the object illumination beam by a small mirror fixed to the object compensates statistical vibrations and object motions caused by rough environments and yields stable interference patterns with sufficient contrast. Based on theoretical investigations of the fringe formation in this case, methods for determining the object motion and deformation are developed. It is shown that zero-order fringes always pass the reference mirror in the reconstructed holographic image when this method is used. The displacement of the reference mirror is determined by an additional object undergoing no motion between the two exposures of a double-exposure hologram.


Analysis of the effects of subcutaneous musculoaponeurotic system facial support on the nasolabial crease.
The idea that traction on the subcutaneous musculoaponeurotic system (SMAS) deepens the nasolabial crease has been propagated through the plastic surgery literature. This notion is contrary to the senior author's experience. The purpose of the present study was to investigate the effects of mobilization of the SMAS on the nasolabial fold and crease. Intraoperative examination on the effect of traction on the SMAS was performed. Ten consecutive primary facelift patients underwent facelift procedures with SMAS support. Following mobilization of the SMAS, traction was placed on the SMAS without traction on the skin. In all cases, the nasolabial fold was effaced and the nasolabial crease did not deepen. The authors concluded that traction on the SMAS did not deepen the nasolabial crease.


Investigation of serotonin-related genes in antidepressant response.
In this study, we sought out to test the hypothesis that genetic factors may influence antidepressant response to fluoxetine. The investigation focused on seven candidate genes in the serotonergic pathway involved in the synthesis, transport, recognition, and degradation of serotonin. Our clinical sample consisted of 96 subjects with unipolar major depression treated with fluoxetine with response variables assessed after a 12-week trial. Patient data were also collected to investigate the pattern of drug response. Using a high-throughput single-nucleotide polymorphism (SNP) genotyping platform and capillary electrophoresis, we genotyped patients at 110 SNPs and four repeat polymorphisms located in seven candidate genes (HTR1A, HTR2A, HTR2C, MAOA, SLC6A4, TPH1, and TPH2). Statistical tests performed included single-locus and haplotype association tests, and linkage disequilibrium (LD) estimation. Little evidence of population stratification was observed in the sample with 20 random SNPs using a genomic control procedure. Our most intriguing result involved three SNPs in the TPH1 gene and one SNP in the SLC6A4 gene, which show significant single-locus association when response to fluoxetine is compared to nonresponse (P=0.02-0.04). All odds ratios indicated an increased risk of not responding to fluoxetine. In the specific response vs nonspecific and nonresponse comparison, three SNPs in the TPH2 gene (P=0.02-0.04) were positively associated and one SNP in the HTR2A gene (P=0.02) was negatively associated. When comparing specific response to nonspecific response, we found significant negative associations in three SNPs in the HTR2A gene (P=0.001-0.03) and two SNPs in the MAOA gene (P=0.03-0.05). We observed variable, although strong LD, in each gene and unexpectedly low numbers of estimated haplotypes, formed from tagged SNPs. Significant haplotype associations were found in all but the HTR1A and HTR2C genes. Although these data should be interpreted cautiously due to the small sample size, these results implicate TPH1 and SLC6A4 in general response, and HTR2A, TPH2, and MAOA in the specificity of response to fluoxetine. Intriguingly, we observe that a number of the less frequent alleles of many of the SNP markers were associated with the nonresponse and nonspecific phenotypes.


Early Age- and Sex-Dependent Regulation of Astrocyte-Mediated Glutamatergic Synapse Elimination in the Rat Prefrontal Cortex: Establishing an Organotypic Brain Slice Culture Investigating Tool.
Clinical and pre-clinical studies of neuropsychiatric (NP) disorders show altered astrocyte properties and synaptic networks. These are refined during early postnatal developmental (PND) stages. Thus, investigating early brain maturational trajectories is essential to understand NP disorders. However, animal experiments are highly time-/resource-consuming, thereby calling for alternative methodological approaches. The function of MEGF10 in astrocyte-mediated synapse elimination (pruning) is crucial to refine neuronal networks during development and adulthood. To investigate the impact of MEGF10 during PND in the rat prefrontal cortex (PFC) and its putative role in brain disorders, we established and validated an organotypic brain slice culture (OBSC) system. Using Western blot, we characterized the expression of MEGF10 and the synaptic markers synaptophysin and PSD95 in the cortex of developing pups. We then combined immunofluorescent-immunohistochemistry with Imaris-supported 3D analysis to compare age- and sex-dependent astrocyte-mediated pruning within the PFC in pups and OBSCs. We thereby validated this system to investigate age-dependent astrocyte-mediated changes in pruning during PND. However, further optimizations are required to use OBSCs for revealing sex-dependent differences. In conclusion, OBSCs offer a valid alternative to study physiological astrocyte-mediated synaptic remodeling during PND and might be exploited to investigate the pathomechanisms of brain disorders with aberrant synaptic development.


An Internet-based symptom questionnaire that is reliable, valid, and available to psychiatrists, neurologists, and psychologists.
The Neuropsych Questionnaire (NPQ) addresses 2 important clinical issues: how to screen patients for a wide range of neuropsychiatric disorders quickly and efficiently, and how to acquire independent verification of a patient's complaints. The NPQ is available over the Internet in adult and pediatric versions. The adult version of the NPQ consists of 207 simple questions about common symptoms of neuropsychiatric disorders. The NPQ scores patient and/or observer responses in terms of 20 symptom clusters: inattention, hyperactivity-impulsivity, learning problems, memory, anxiety, panic, agoraphobia, obsessions and compulsions, social anxiety, depression, mood instability, mania, aggression, psychosis, somatization, fatigue, sleep, suicide, pain, and substance abuse. The NPQ is reliable (patients tested twice, patient-observer pairs, 2 observers) and discriminates patients with different diagnoses. Scores generated by the NPQ correlate reasonably well with commonly used rating scales, and the test is sensitive to the effects of treatment. The NPQ is suitable for initial patient evaluations, and a short form is appropriate for follow-up assessment. The availability of a comprehensive computerized symptom checklist can help to make the day-to-day practice of psychiatry, neurology, and neuropsychology more objective.


Occurrence of perchlorate in groundwater, paired farmland soil, lettuce, and rhizosphere soil from Chengdu, China.
A total of 28 groundwater, paired farmland soil, lettuce, and its rhizosphere soil samples were collected from Chengdu, China to detect perchlorate levels and to evaluate the relationships of perchlorate concentrations among these matrices. The perchlorate concentrations in the groundwater, farmland soil, lettuce, and rhizosphere soil samples ranged from below detection limit to 60.2 μg L-1, from below detection limit to 249 μg kg-1 dry weight (dw), from 2.07 to 1010 μg kg-1 wet weight, and from below detection limit to 314 μg kg-1 dw, respectively. Significant correlation was found in the perchlorate levels among the farmland soil, lettuce, and rhizosphere soil, suggesting that they have common pollution sources, or perchlorate might transfer from farmland soil-rhizosphere soil-plant. However, there is no significant correlation between groundwater and the other three matrices, indicating that infiltration from perchlorate contaminated farmland soil was not the predominant source for groundwater pollution in Chengdu. The perchlorate concentrations in the farmland soil and lettuce samples were significantly higher than those in the rhizosphere soil, primarily due to uptake of perchlorate through the rhizosphere micro-environment by lettuce, or accelerated degradation by rhizospheric microorganisms, which contributed more needs further investigation.


Sorption processes and XRD analysis of a natural zeolite exchanged with Pb(2+), Cd(2+) and Zn(2+) cations.
In this study the Pb(2+), Cd(2+) and Zn(2+) adsorption capacity of a natural zeolite was evaluated in batch tests at a constant pH of 5.5 by polluting this mineral with solutions containing increasing concentrations of the three cations to obtain adsorption isotherms. In addition X-ray powder diffraction (XRD) was used to investigate the changes of zeolite structure caused by the exchange with cations of different ionic radius. The zeolite adsorption capacity for the three cations was Zn>Pb>Cd. Moreover a sequential extraction procedure [H(2)O, 0.05 M Ca(NO(3))(2) and 0.02 M EDTA] was applied to zeolite samples used in the adsorption experiments to determine the chemical form of the cations bound to the sorbent. Using this approach it was shown that low concentrations of Pb(2+), Cd(2+) and Zn(2+) were present as water-soluble and exchangeable fractions (<25% of the Me adsorbed), while EDTA extracted most of the adsorbed cations from the zeolite (>27% of the Me adsorbed). The XRD pattern of zeolite, analysed according to the Rietveld method, showed that the main mineralogical phase involved in the adsorption process was clinoptilolite. Besides structure information showed that the incorporation of Pb(2+), Cd(2+) and Zn(2+), into the zeolite frameworks changed slightly but appreciably the lattice parameters. XRD analysis also showed the occurrence of some isomorphic substitution phenomena where the Al(3+) ions of the clinoptilolite framework were replaced by exchanged Pb(2+) cations in the course of the ion exchange reaction. This mechanism was instead less evident in the patterns of the samples doped with Cd(2+) and Zn(2+) cations.


Tolerance to cadmium of Agave lechuguilla (Agavaceae) seeds and seedlings from sites contaminated with heavy metals.
We investigated if seeds of Agave lechuguilla from contaminated sites with heavy metals were more tolerant to Cd ions than seeds from noncontaminated sites. Seeds from a highly contaminated site (Villa de la Paz) and from a noncontaminated site (Villa de Zaragoza) were evaluated. We tested the effect of Cd concentrations on several ecophysiological, morphological, genetical, and anatomical responses. Seed viability, seed germination, seedling biomass, and radicle length were higher for the non-polluted site than for the contaminated one. The leaves of seedlings from the contaminated place had more cadmium and showed peaks attributed to chemical functional groups such as amines, amides, carboxyl, and alkenes that tended to disappear due to increasing the concentration of cadmium than those from Villa de Zaragoza. Malformed cells in the parenchyma surrounding the vascular bundles were found in seedlings grown with Cd from both sites. The leaves from the contaminated place showed a higher metallothioneins expression in seedlings from the control group than that of seedlings at different Cd concentrations. Most of our results fitted into the hypothesis that plants from metal-contaminated places do not tolerate more pollution, because of the accumulative effect that cadmium might have on them.


Squamous cell carcinoma of the penis.
Squamous cell carcinoma of the penis (CA Penis) is not a rare disease in P.R. We have reviewed all cases of CA penis diagnosed in our institution from Jan. 79-Jan. 89. Pathology and hospital records were audited. The survival data on all patients was updated via telephone or record review up to May 89. A total of 18 pts were seen in the last decade. Of these 11. (61%) were seen in the last four years. Four of 18 patients were excluded from analysis due to lack of staging and therapy data. The median age 54.9 y (range 23-82y). The following risk factors were identified: phimosis 12/14 (86%) p = .05, leukoplakia 8/14 (57%); prior venereal disease 1/14 (7%). The primary lesion appeared in the prepuce 8/14 (57%) and glans 6/14 (43%). TNM staging was done in all pts. Most pts presented with T3 or T4 disease 10/14 (71%) and palpable regional adenopathy (N1-N3) 9/14 (64%). Of the nine pts with palpable adenopathy, in 5 (56%) microscopic malignant disease was confirmed. A correlation between T3 or T4 disease and the presence of palpable adenopathy was seen (80%). The Stage at diagnosis of the 14 pts: I: 0/14 (29%), II: 5/14 (7%), III: 3/14 (21%), IV: 6/14; (43%). All pts were treated with partial penectomy and 7/14 had unilateral or bilateral inguinal lymphadenectomy. Long term survivors (LTS), greater than 12 mo., were seen 3/4 pts with Stage II disease, 1/3 Stage III, and 2/5 in Stage IV. The most important prognostic factor for LTS was malignant involvement of regional lymph nodes with 0/5 in this group.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of Amyloid and Tau PET on Changes in Diagnosis and Patient Management.
Previous studies have evaluated the diagnostic effect of amyloid PET in selected research cohorts. However, these studies did not assess the clinical impact of the combination of amyloid and tau PETs. Our objective was to evaluate the association of the combination of 2 PETs with changes in diagnosis, treatment, and management in a memory clinic cohort. All participants underwent amyloid [18F]florbetaben PET and tau PET using [18F]PI-2620 or [18F]Florzolotau, which are potentially useful for the diagnosis of non-Alzheimer disease (AD) tauopathies. Dementia specialists determined a pre- and post-PET diagnosis that existed in both a clinical syndrome (cognitive normal [CN], mild cognitive impairment [MCI], and dementia) and suspected etiology, with a confidence level. In addition, the dementia specialists determined patient treatment in terms of ancillary investigations and management. Among 126 registered participants, 84.9% completed the study procedures and were included in the analysis (CN [n = 40], MCI [n = 25], AD [n = 20], and non-AD dementia [n = 22]). The etiologic diagnosis changed in 25.0% in the CN, 68.0% in the MCI, and 23.8% with dementia. Overall changes in management between pre- and post-PET occurred in 5.0% of CN, 52.0% of MCI, and 38.1% of dementia. Logistic regression analysis revealed that tau PET has stronger associations with change management than amyloid PET in all participants and dementia groups. The combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia, and the second-generation tau PET has a strong impact on the changes in diagnosis and management in memory clinics. This study provides Class I evidence that the combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia.


[Construction of vectors for expression of cleavable tandem repeat Thanatin fusion protein in plants].
Thanatin, a 21-residue antimicrobial peptide, is an inducible insect peptide with a broad range of activity against bacteria and fungi. It can improve the expression level of the antimicrobial peptide in plants to express the peptide as tandem repeat fusion protein containing multiple Thanatin copies. However, the fusion protein has no antimicrobial activity. To make the fusion protein automatically break into single Thanatin unit with antimicrobial activity, the fused Thanatin was spaced by a linker peptide, which was cleavable in vivo. The soybean (Glysine max L.) chitinase signal peptide was fused to the N end of the fusion protein to induce the antimicrobial peptide accumulated in intercellular space. To construct the vectors for expression of the fusion protein, the overlapped primers were used to clone the antimicrobial peptide gene and the co-adhesive end restriction and ligation strategy was used to add the repeat unit one by one. Vectors containing 1 to 5 repeat units of Thanatin were constructed respectively. These vectors were being used to transform plants to improve plant disease resistance.


Specific effect of the infusion of glucose on blood volume during haemodialysis.
Intradialytic morbid events such as hypotension and cramps during haemodialysis are generally treated by infusion of iso- or hypertonic solutions. However, differences may exist between solutions with respect to plasma refilling and vascular reactivity. We compared the effect of no infusion (NI) with isovolumetric infusion of isotonic saline 0.9% (IS), saline 3% (HS), isotonic glucose 5% (IG), glucose 20% (HG) and mannitol 20% (HM), in six patients during the first hour of six standardized haemodialysis sessions with ultrafiltration. Relative blood volume was monitored continuously by measurement of the intravascular amount of protein. Blood pressure was measured by an oscillometric method, while cardiac output was measured by a thoracic impedance technique. At baseline, no differences in serum urea, sodium, potassium, glucose and osmolarity were found between the various infusion experiments. The maximum increase in relative blood volume directly after infusion was significantly greater with HG (5.1+/-0.7%) than with all other infusions (P<0.05). Stroke volume increased (21.0+/-19.2%, P<0.05) and total peripheral resistance decreased significantly (15.4+/-16.4%, P<0.05) after HG infusions. Infusion of hypertonic glucose during dialysis results in a greater increase in relative blood volume (RBV) than equal volumes of other solutions. As mannitol has the same osmolarity, molecule mass and charge, the greater increase in RBV following hypertonic glucose appears to be a specific effect, possibly related to a decline in vascular tone. It is therefore uncertain whether the observed increase in plasma volume during hypertonic glucose infusions will be of clinical benefit.


Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study.
Patients with cancer are often treated with glucocorticoids (gcs) as part of therapy, which may cause hyperglycemia. We sought to define the prevalence of, and risk factors for, hyperglycemia in this setting. Adult patients taking gc as part of therapy protocols for primary brain tumour or metastasis, for lymphoma, or for bone marrow transplant (bmt) were screened with random glucometer measurements taken at least 3 hours after the last dose gcs. We screened 90 patients [44.4% women, 55.6% men; mean age: 59.6 years (range: 25-82 years); mean body mass index (bmi): 26.4 kg/m(2) (range: 15.8-45.3 kg/m(2))] receiving gc as part of cancer treatment. Mean total daily gc dose in the group was 238.5 mg (range: 30-1067 mg) hydrocortisone equivalents. Hyperglycemia (glucose ≥ 8.0 mmol/L) was found in 58.9% (53 of 90), and diabetes mellitus (dm)-range hyperglycemia (glucose ≥ 11.1 mmol/L) in 18.9% (17 of 90). The mean time from gc ingestion to glucometer testing was 5.5 hours (range: 3-20 hours). Presence of hyperglycemia did not correlate with traditional dm risk factors such as age, sex, bmi, and personal or family history of dm. A longer interval from gc dose to testing (p < 0.05), a higher gc dose (p = 0.04), and a shorter interval between the preceding meal and testing (p = 0.02) were risk factors for hyperglycemia in some patient groups. Glucocorticoid-induced hyperglycemia is common in patients undergoing cancer treatment and cannot be predicted by traditional risk factors for dm. We recommend that all cancer patients receiving gc be screened for hyperglycemia at least 4-6 hours after gc administration.


Partial nucleotide sequences, and routine typing by polymerase chain reaction-restriction fragment length polymorphism, of the brown trout (Salmo trutta) lactate dehydrogenase, LDH-C1*90 and *100 alleles.
The cDNA nucleotide sequences of the lactate dehydrogenase alleles LDH-C1*90 and *100 of brown trout (Salmo trutta) were found to differ at position 308 where an A is present in the *100 allele but a G is present in the *90 allele. This base substitution results in an amino acid change from aspartic acid at position 82 in the LDH-C1 100 allozyme to a glycine in the 90 allozyme. Since aspartic acid has a net negative charge whilst glycine is uncharged, this is consistent with the electrophoretic observation that the LDH-C1 100 allozyme has a more anodal mobility relative to the LDH-C1 90 allozyme. Based on alignment of the cDNA sequence with the mouse genomic sequence, a local primer set was designed, incorporating the variable position, and was found to give very good amplification with brown trout genomic DNA. Sequencing of this fragment confirmed the difference in both homozygous and heterozygous individuals. Digestion of the polymerase chain reaction products with BslI, a restriction enzyme specific for the site difference, gave one, two and three fragments for the two homozygotes and the heterozygote, respectively, following electrophoretic separation. This provides a DNA-based means of routine screening of the highly informative LDH-C1* polymorphism in brown trout population genetic studies. Primer sets presented could be used to sequence cDNA of other LDH* genes of brown trout and other species.


Optically excited synapse for neural networks.
What can optics with its promise of parallelism do for neural networks which require matrix multipliers? An all optical approach requires optical logic devices which are still in their infancy. An alternative is to retain electronic logic while optically addressing the synapse matrix. This paper considers several versions of an optically addressed neural network compatible with VLSI that could be fabricated with the synapse connection unspecified. This optical matrix multiplier circuit is compared to an all electronic matrix multiplier. For the optical version a synapse consisting of back-to-back photodiodes is found to have a suitable i-v characteristic for optical matrix multiplication (a linear region) plus a clipping or nonlinear region as required for neural networks. Four photodiodes per synapse are required. The strength of the synapse connection is controlled by the optical power and is thus an adjustable parameter. The synapse network can be programmed in various ways such as a shadow mask of metal, imaged mask (static), or light valve or an acoustooptic scanned laser beam or array of beams (dynamic). A milliwatt from LEDs or lasers is adequate power. The neuron has a linear transfer function and is either a summing amplifier, in which case the synapse signal is current, or an integrator, in which case the synapse signal is charge, the choice of which depends on the programming mode. Optical addressing and settling times of microseconds are anticipated. Electronic neural networks using single-value resistor synapses or single-bit programmable synapses have been demonstrated in the high-gain region of discrete single-value feedback. As an alternative to these networks and the above proposed optical synapses, an electronic analog-voltage vector matrix multiplier is considered using MOSFETS as the variable conductance in CMOS VLSI. It is concluded that a shadow mask addressed (static) optical neural network is promising.


[Possibilities of pharmacological modulation of brain glutamatergic system in the treatment of vascular cognitive impairment].
An aim of the study was to investigate the efficacy and safety of noojerone (memantine) in patients with cognitive impairment comorbid to brain ischemia, stages II-III. The main group (30 patients, aged 64-86 years) was treated with noojerone in addition to standard therapy according to dosage scheme during 6 months. The control group (15 patients, aged 61-78 years) received standard therapy only. Patients underwent somatic and neurological examinations, along with neuropsychological testing (MMSE, FAB and other tests). The use of noojerone in complex treatment decreased cognitive impairment in the main group compared to the control one. The most distinct changes were noted on MMSE. Statistically significant changes appeared during the 12th week. The maximal effect was observed when the drug was applied during 6 months. Noojerone was well-tolerated by the patients.


The biological role of non-neuronal acetylcholine in plants and humans.
Acetylcholine, one of the most exemplary neurotransmitters, has been detected in bacteria, algae, protozoa, tubellariae and primitive plants, suggesting an extremely early appearance in the evolutionary process and a wide expression in non-neuronal cells. In plants (Urtica dioica), acetylcholine is involved in the regulation of water resorption and photosynthesis. In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase, have been demonstrated in epithelial (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (granulocytes, lymphocytes, macrophages, mast cells). The widespread expression of non-neuronal acetylcholine is accompanied by the ubiquitous expression of cholinesterase and acetylcholine sensitive receptors (nicotinic, muscarinic). Both receptor populations interact with more or less all cellular signalling pathways. Thus, non-neuronal acetylcholine can be involved in the regulation of basic cell functions like gene expression, proliferation, differentiation, cytoskeletal organization, cell-cell contact (tight and gap junctions, desmosomes), locomotion, migration, ciliary activity, electrical activity, secretion and absorption. Non-neuronal acetylcholine also plays a role in the control of unspecific and specific immune functions. Future experiments should be designed to analyze the cellular effects of acetylcholine in greater detail and to illuminate the involvement of the non-neuronal cholinergic system in the pathogenesis of diseases such as acute and chronic inflammation, local and systemic infection, dementia, atherosclerosis, and finally cancer.


IpgD, a protein secreted by the type III secretion machinery of Shigella flexneri, is chaperoned by IpgE and implicated in entry focus formation.
Invasion of epithelial cells by Shigella flexneri involves entry and intercellular dissemination. Entry of bacteria into non-phagocytic cells requires the IpaA-D proteins that are secreted by the Mxi-Spa type III secretion machinery. Type III secretion systems are found in several Gram-negative pathogens and serve to inject bacterial effector proteins directly into the cytoplasm of host cells. In this study, we have analysed the IpgD protein of S. flexneri, the gene of which is located on the virulence plasmid at the 5' end of the mxi-spa locus. We have shown that IpgD (i) is stored in the bacterial cytoplasm in association with a specific chaperone, IpgE; (ii) is secreted by the Mxi-Spa type III secretion system in amounts similar to those of the IpaA-D proteins; (iii) is associated with IpaA in the extracellular medium; and (iv) is involved in the modulation of the host cell response after contact of the bacterium with epithelial cells. This suggests that IpgD is an effector that might be injected into host cells to manipulate cellular processes during infection.


Papillomavirus life cycle organization and biomarker selection.
Human papillomaviruses (HPVs) are a diverse group of viruses that cause epithelial lesions of varying severity. Of the 100 or so types that have been identified, around 40 can infect the cervix, with a subset of these causing lesions that can progress to high-grade neoplasia and cervical cancer. These high-risk types are prevalent in the general population, and can predispose to the development of cancer in women who cannot resolve their infection. Virus infection usually leads to the establishment of productive flat warts, or to maintenance of the viral genome in an asymptomatic or latent state. Virus synthesis depends on the ordered expression of viral gene products as the infected basal cell migrates towards the epithelial surface. E7 is expressed in the lower epithelial layers, and is followed eventually by the expression of E4 and L1 closer to the epithelial surface. This ordered pattern changes in characteristic ways during neoplastic progression and latency, and can be irreversibly fixed following integration of the viral genome into the host cell chromosome. Our understanding of expression patterns and their significance, is beginning to explain the nature of disease progression, and offers a rational basis for the selection of biomarkers that may be used to predict disease status and prognostic outcome.


Emotional labor among healthcare professionals: the effects are undeniable.
Healthcare professionals encounter a variety of emotion-laden events involving ethical implications and choices. These events may trigger deeply felt negative emotions, which can limit an individual's ability to make ethical decisions, and result in emotional labor. The topic of emotional labor, though studied extensively with customer service workers, has recently been investigated with regard to healthcare professionals, including nurses, clinical psychologists, and physicians. Studies focused on these populations have revealed widespread instances of emotional labor, commonly accompanied by various negative physical and psychological health consequences. Accordingly, emotion regulation strategies are important to explore in order to counteract the negative health outcomes. Recommendations for ways to cope with emotional demands for healthcare employees are provided.


[Motor grammar of the spinal cord--status and revision].
Modern neurophysiological research, mainly in the second third of this century, has led to a set of widely accepted findings on the basic processes and rules of interactions between bodily periphery and the spinal level, which may be called a kind of elementary "grammar" of the spinal cord. As far as these apply to motor control functions, they are expressed here in condensed form as ten "paragraphs", which until recently belonged to the conventional standard teaching of neurophysiology. Each paragraph is then critically reviewed, supplemented and revised, as far as necessary, based on research progress in the last thirty years. The review deals with: Alpha motoneurones and their motor units; the muscle spindle with its sensory and motor structures, and its efferent controls by gamma and beta neurones; the spinal connections and effects of the afferents from primary and secondary spindle endings; properties and spinal effects of the Golgi tendon organs; new aspects of the flexor reflex afferents (FRA), of recurrent Renshaw feedback, and of presynaptic inhibition. The last paragraph stresses the importance of supraspinal controls of the spinal moto- and interneurones.


Reduction of Cryptosporidium, Giardia, and Fecal Indicators by Bardenpho Wastewater Treatment.
Increased demand for water reuse and reclamation accentuates the importance for optimal wastewater treatment to limit protozoa in effluents. Two wastewater treatment plants utilizing advanced Bardenpho were investigated over a 12-month period to determine the incidence and reduction of Cryptosporidium, Giardia, Cyclospora, and fecal indicators. Results were compared to facilities that previously operated in the same geographical area. Protozoa (oo)cysts were concentrated using an electronegative filter and subsequently detected by fluorescent microscopy and/or PCR methods. Cryptosporidium and Giardia were frequently detected in raw sewage, but Cyclospora was not detected in any wastewater samples. Facilities with Bardenpho treatment exhibited higher removals of (oo)cysts than facilities utilizing activated sludge or trickling filters. This was likely due to Bardenpho systems having increased solid wasting rates; however, this mechanism cannot be confirmed as sludge samples were not analyzed. Use of dissolved-air-flotation instead of sedimentation tanks did not result in more efficient removal of (oo)cysts. Concentrations of protozoa were compared with each other, Escherichia coli, somatic coliphage, and viruses (pepper mild mottle virus, Aichi virus 1, adenovirus, and polyomaviruses JC and BK). Although significant correlations were rare, somatic coliphage showed the highest potential as an indicator for the abundance of protozoa in wastewaters.


Engraftment of bone marrow-derived epithelial cells.
Discoveries of the ability of bone marrow-derived cells (BMDCs) to differentiate into nonhematopoietic cells have opened up a new field of inquiry in adult stem cell plasticity. There are far more questions than there are answers to date. We and others have investigated whether differentiation occurs in response to tissue damage, what the underlying mechanisms might be, and whether this plasticity may be useful clinically. BMDC have been shown to differentiate into mature-appearing epithelial cells in the lung, liver, gastrointestinal tract, skin, buccal mucosa, and kidney. The mechanism(s) by which cells transition to these nonhematopoietic phenotypes is not yet clear, but possibilities include cell-to-cell fusion, direct differentiation of a nonhematopoietic precursor cell from the BM, and transdifferentiation of a BM cell that had previously been committed to a different phenotype. Data obtained to date support the first two possibilities, and there are no data proving that transdifferentiation is responsible for the engraftment of marrow-derived epithelial cells. Theoretically, the engraftment of marrow-derived cells as nonhematopoietic cell types could be used in either the autologous or the allogeneic setting to restore functional epithelial cells to a diseased organ. For example, a marrow-derived cell that has been transduced to express a specific transgene can continue to express this transgene after it engrafts as a nonhematopoietic epithelial cell in the lung. Analyses of the kinetics of this engraftment suggest that it can be increased within days to weeks following certain types of injury, depending on the tissue examined. Most reports of adult stem cell plasticity show relatively low frequencies of marrow-derived nonhematopoietic cells, on the order of 1 in 10(3) to 1 in 10(4) epithelial cells in many organs being marrow derived. This frequency is likely to be too low to be of therapeutic relevance. Therefore, future efforts will need to be focused on enhancing levels of engraftment.


Countering the Modern Metabolic Disease Rampage With Ancestral Endocannabinoid System Alignment.
When primitive vertebrates evolved from ancestral members of the animal kingdom and acquired complex locomotive and neurological toolsets, a constant supply of energy became necessary for their continued survival. To help fulfill this need, the endocannabinoid (eCB) system transformed drastically with the addition of the cannabinoid-1 receptor (CB1R) to its gene repertoire. This established an eCB/CB1R signaling mechanism responsible for governing the whole organism's energy balance, with its activation triggering a shift toward energy intake and storage in the brain and the peripheral organs (i.e., liver and adipose). Although this function was of primal importance for humans during their pre-historic existence as hunter-gatherers, it became expendable following the successive lifestyle shifts of the Agricultural and Industrial Revolutions. Modernization of the world has further increased food availability and decreased energy expenditure, thus shifting the eCB/CB1R system into a state of hyperactive deregulated signaling that contributes to the 21st century metabolic disease pandemic. Studies from the literature supporting this perspective come from a variety of disciplines, including biochemistry, human medicine, evolutionary/comparative biology, anthropology, and developmental biology. Consideration of both biological and cultural evolution justifies the design of improved pharmacological treatments for obesity and Type 2 diabetes (T2D) that focus on peripheral CB1R antagonism. Blockade of peripheral CB1Rs, which universally promote energy conservation across the vertebrate lineage, represents an evolutionary medicine strategy for clinical management of present-day metabolic disorders.


Antioxidant activity guided separation of major polyphenols of marjoram (Origanum majorana L.) using flash chromatography and their identification by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
Marjoram extracts have been separated into polar and nonpolar parts using liquid-liquid extraction. Both polar and nonpolar parts of the extracts were further fractionated by flash chromatography. The obtained fractions (90 polar and 45 nonpolar fractions) were investigated for their antioxidant activities by 2,2-diphenylpicrylhydrazyl and ferric ion reducing antioxidant power assays. A direct, positive, and linear relationship between antioxidant activity and total phenolic content of the fractions was observed. Based on antioxidant and total phenolic content data, the three fractions with the high antioxidant activities from polar and nonpolar part of the extract were analyzed for their constituent polyphenols by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Compounds were identified by matching the mass spectral data and retention time with those of authentic standards. Identification of the compounds for which there were no "in-house" standards available was carried out by accurate mass measurement of the precursor ions and product ions generated from collision-induced dissociation. Rosmarinic acid was found to be the strongest antioxidant polyphenol conferring the highest antioxidant activity to fractions 47 and 17 of polar and nonpolar part of the extract, respectively. The identification of the rosmarinic acid was further confirmed by (1) H NMR spectroscopy.


Comprehensive analysis of in-hospital delirium after major surgical oncology procedures: A population-based study.
Very few population-based assessments of delirium have been performed to date. These have not assessed the implications of delirium after major surgical oncology procedures (MSOPs). We examined the temporal trends of delirium following 10 MSOPs, as well as patient and hospital delirium risk factors. Finally, we examined the effect of delirium on length of stay, inhospital mortality, and hospital charges. We retrospectively identified patients who underwent prostatectomy, colectomy, cystectomy, mastectomy, gastrectomy, hysterectomy, nephrectomy, oophorectomy, lung resection, or pancreatectomy within the Nationwide Inpatient Sample (2003-2013). We yielded a weighted estimate of 3 431 632 patients. Multivariable logistic regression (MLR) analyses identified the determinants of postoperative delirium, as well as the effect of delirium on length of stay, in-hospital mortality, and hospital charges. Between 2003 and 2013, annual delirium rate increased from 0.7 to 1.2% (+6.0%; p<0.001). Delirium rates were highest after cystectomy (predicted probability [PP] 3.1%) and pancreatectomy (PP 2.6%), and lowest after prostatectomy (PP 0.15%) and mastectomy (PP 0.13%). Advanced age (odds ratio [OR] 3.80), maleness (OR 1.38), and higher Charlson comorbidity index (OR 1.20), as well as postoperative complications represent risk factors for delirium after MSOPs. Delirium after MSOP was associated with prolonged length of stay (OR 3.00), higher mortality (OR 1.15), and increased in-hospital charges (OR 1.13). No contemporary population-based assessments of delirium after MSOP have been reported. According to our findings, delirium after MSOP has a profound impact on patient outcomes that ranges from prolonged length of stay to higher mortality and increased in-hospital charges.


Radiation sterilization of prototype military foods. II. Cured ham.
Ten lots of diced cured ham, packed in cans, were inoculated with approximately 10(6)Clostridium botulinum spores per can. Each lot was seeded with a different strain (five type A and five type B strains). All cans were irradiated to various dose levels with Co(60). Evidence provided by swelling, toxicity, and recoverable C. botulinum with 6,350 cans demonstrated that: (i) 4.5 Mrad was more than adequate as a sterilization dose; (ii) the minimal experimental sterilizing dose (ESD) based on nonswollen nontoxic endpoints was 2.0 < ESD </= 2.5 Mrad, and based on non-spoiled sterile cans was 3.0 < ESD </= 3.5 Mrad (the latter was supported by the computed theoretical 12D dose); (iii) D values calculated from botulinal survival data indicated that, as a group, the type A strains were more radioresistant than type B strains; strains 12885A and 41B, with respective D values of 0.242 and 0.175, represented the most resistant of each type; (iv) swollen cans did not always contain toxin, nor were toxic cans always swollen; (v) viable C. botulinum can exist for 6 months at 30 C without producing visible or toxic spoilage at doses of 3.0 Mrad and lower, including, in some instances, 0.0 Mrad; and (vi) a phenomenon similar to heat activation of spores occurred at sublethal radiation doses.


A collection of bioconductor methods to visualize gene-list annotations.
Gene-list annotations are critical for researchers to explore the complex relationships between genes and functionalities. Currently, the annotations of a gene list are usually summarized by a table or a barplot. As such, potentially biologically important complexities such as one gene belonging to multiple annotation categories are difficult to extract. We have devised explicit and efficient visualization methods that provide intuitive methods for interrogating the intrinsic connections between biological categories and genes. We have constructed a data model and now present two novel methods in a Bioconductor package, "GeneAnswers", to simultaneously visualize genes, concepts (a.k.a. annotation categories), and concept-gene connections (a.k.a. annotations): the "Concept-and-Gene Network" and the "Concept-and-Gene Cross Tabulation". These methods have been tested and validated with microarray-derived gene lists. These new visualization methods can effectively present annotations using Gene Ontology, Disease Ontology, or any other user-defined gene annotations that have been pre-associated with an organism's genome by human curation, automated pipelines, or a combination of the two. The gene-annotation data model and associated methods are available in the Bioconductor package called "GeneAnswers " described in this publication.


A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats.
Ellagic acid (EA) has shown antinociceptive and anti-inflammatory effects. Inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) enzymes and also cytokines play a key role in many inflammatory conditions. This study was aimed to investigate the mechanisms involved in the anti-inflammatory effect of EA. Carrageenan-induced mouse paw edema model was used for induction of inflammation. The results showed that intraplantar injection of carrageenan led to time-dependent development of peripheral inflammation, which resulted in a significant increase in the levels of tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) β, nitric oxide (NO) and prostaglandin E2 (PGE2) and also iNOS and COX-2 protein expression in inflamed paw. However, systemic administration of EA (1-30 mg/kg, intraperitoneal [i.p.]) could reduce edema in a dose-dependent fashion in inflamed rat paws with ED50 value 8.41 (5.26-14.76) mg/kg. It decreased the serum concentration of NO, PGE2, aspartate aminotransferase and alanine aminotransferase, and suppress the protein expression of iNOS, COX-2 enzymes, and attenuated the formation of PGE2, TNF-α and IL-1 β in inflamed paw tissue. We also demonstrated that EA significantly decreased the malondialdehyde (MDA) level in liver at 5 h after carrageenan injection. Moreover, histopathological studies indicated that EA significantly diminished migration of polymorphonuclear leukocytes into site of inflammation, as did indomethacin. Collectively, the anti-inflammatory mechanisms of EA might be related to the decrease in the level of MDA, iNOS, and COX-2 in the edema paw via the suppression of pro-inflammatory cytokines (TNFα, IL1 β), NO and PGE2 overproduction.


[Regulation of the excitability of neonatal cardiomyocytes by N-stearoyl- and N-oleoyl-ethanolamines].
N-acylethanolamines (NAE) are biologically active lipids able of modulating ion transport through the cellular plasma membrane, however specific targets of their action and signalling mechanisms involved in cardiac tissue are still poorly understood. Physiological activity of NAEs is known to depend on the level of unsaturation. Therefore, here we investigated the effects of saturated N-stearylethanolamine (NSE) and monounsaturated N-oleylethanolamine on electric excitability of neonatal rat cardiomyocytes. 1 microM of either NSE or OEA decreased the duration of cardiac action potential (AP) from all parts of heart muscle. Shortening of AP was partially reversible, though the reversibility of AP duration upon washout of substances was more complete for endocardial ventricular compared to epicardial and atrial cardiomyocytes. I microM NSE depolarized resting membrane potential (RMP) of epicardial and of 65% of endocardial cells, whilst other cells types showed weakly reversible hyperpolarization. 1 microM OEA caused reversible RMP hyperpolarization of all studied cell types. NSE and OEA decreased the amplitude and upstroke velocity of AP that suggests their effect on sodium channels. NSE and to a lesser extent OEA inhibited the amplitude of AP phase 2 (plateau) which may indicate an inhibition of high-voltage-activated calcium channels. Effects of NSE and OEA on RMP and repolarization phase of AP (phase 3) depended on cardiac cell type suggesting differential regulation of inward rectifier Kir and voltage-gated delayed rectifier potassium channels by these lipids. We cannot also exclude interaction of NSE and OEA with anion channels, backgound K+ channels and ion transporters of the cardiomyocytes' plasma membrane. Overall, NSE-induced changes of AP parameters were less reversible than those induced by OEA, suggesting a slower degradation/ convertion of NSE in plasma membrane compared to OEA.


Transcriptional profiling of defense responses to Botrytis cinerea infection in leaves of Fragaria vesca plants soil-drenched with β-aminobutyric acid.
Grey mold caused by the necrotrophic fungal pathogen Botrytis cinerea can affect leaves, flowers, and berries of strawberry, causing severe pre- and postharvest damage. The defense elicitor β-aminobutyric acid (BABA) is reported to induce resistance against B. cinerea and many other pathogens in several crop plants. Surprisingly, BABA soil drench of woodland strawberry (Fragaria vesca) plants two days before B. cinerea inoculation caused increased infection in leaf tissues, suggesting that BABA induce systemic susceptibility in F. vesca. To understand the molecular mechanisms involved in B. cinerea susceptibility in leaves of F. vesca plants soil drenched with BABA, we used RNA sequencing to characterize the transcriptional reprogramming 24 h post-inoculation. The number of differentially expressed genes (DEGs) in infected vs. uninfected leaf tissue in BABA-treated plants was 5205 (2237 upregulated and 2968 downregulated). Upregulated genes were involved in pathogen recognition, defense response signaling, and biosynthesis of secondary metabolites (terpenoid and phenylpropanoid pathways), while downregulated genes were involved in photosynthesis and response to auxin. In control plants not treated with BABA, we found a total of 5300 DEGs (2461 upregulated and 2839 downregulated) after infection. Most of these corresponded to those in infected leaves of BABA-treated plants but a small subset of DEGs, including genes involved in 'response to biologic stimulus', 'photosynthesis' and 'chlorophyll biosynthesis and metabolism', differed significantly between treatments and could play a role in the induced susceptibility of BABA-treated plants.


Doctors' views about the importance of shared values in HIV positive patient care: a qualitative study.
Robert Veatch has proposed a model of the doctor-patient relationship that has as its foundation the sharing of values between the doctor and the patient. This paper uses qualitative research conducted with six doctors involved in the long term, specialised care of HIV positive patients in South Australia to explore the practical application of Veatch's value sharing model in that setting. The research found that the doctors in this study linked "values" with sexual identity such that they defined value sharing, in part, as a shared set of values and beliefs about sexual identity and practices. They voluntarily identified themselves as either homosexual or heterosexual and they regarded the relation between their own sexual identity and that of their patients as important for the provision of quality care. None of the doctors thought that value sharing, in the way they defined it, was essential to the clinical relationship, but the homosexual doctors attributed a greater degree of importance to it than their heterosexual colleagues.


Validation of the hypomania interview guide-seasonal affective disorder (HIGH-SAD) version in patients with rapid cycling bipolar disorder.
We validated the Hypomania Interview Guide-Seasonal Affective Disorder version (HIGH-SAD) in patients with rapid cycling bipolar disorder (RCBD). Fourteen outpatients were rated on six separate occasions (total = 84 visits). On each visit the patients were rated with the HIGH-SAD and the Young Mania Rating Scale (YMRS) in a counterbalanced order. Clinical assessment was completed at the end of the visit by the treating psychiatrist. Patients were assessed as hypomanic/manic on 22 of the visits. Pearson correlation coefficient between the YMRS total scores and the HIGH-SAD total scores for those 22 visits in which patients were hypomanic/manic was r = 0.629 (P < 0.05) and for all visits was r = 0.769 (P < 0.0001). Analysis with only one rating per patient yielded a Pearson correlation coefficient of r = 0.792 (P < 0.0004). We found that the HIGH-SAD was a valid scale for the measurement of hypomania in patients with RCBD. However, the scale does not differentiate hypomania from mania in this group of patients.


Median cerebrofacial dysgenesis: the syndrome of median facial defects with hypotelorism.
Two patients with almost identical median facial defects are described. Both patients manifested a pure Pitressin responsive diabetes insipidus. These two patients are part of a graded series of median cerebrofacial malformations with orbital hypotelorism, which have been grouped under the heading of Median Cerebrofacial Dysgenesis. A revised classification of this group of anomalies is presented. The importance of distinguishing this group of patients from the group with the Median Cleft Face Syndrome with hypertelorism is stressed. Careful attention to face-brain relationships will help elucidate our understanding of the embryogenesis of the facial region, and extend the number of diagnostic facies which currently can be recognized.


Tetraplegia as a presenting feature of systemic lupus erythematosus complicated by pulmonary hypertension.
A 28-year-old woman presenting with subacute onset of a tetraplegia is described who was shown to have active systemic lupus erythematosus in association with high circulating anticardiolipin binding and lupus anticoagulant activity. The patient later developed severe symptomatic systemic and pulmonary hypertension and required emergency resuscitation. This case provides further support for an association between antiphospholipid antibodies and the clinical features of central nervous system (CNS) involvement and pulmonary hypertension in SLE.


A randomized controlled trial on the value of misoprostol for the treatment of retained placenta in a low-resource setting.
To evaluate the efficacy and safety of misoprostol among patients with retained placenta in a low-resource setting. A prospective, multicenter, randomized, double-blind, placebo-controlled trial was carried out in Tanzania between April 2008 and November 2011. It included patients who delivered at a gestational age of 28 weeks or more and had blood loss of 750 mL or less at 30 minutes after delivery. Sublingual misoprostol (800 μg) was compared with placebo as the primary treatment. Power analysis showed that 117 patients would be required to observe a reduction of 40% in the incidence of manual removal of the placenta (MRP; P=0.05, 80% power), the primary outcome. The secondary outcomes were blood loss and number of blood transfusions. Interim analysis after recruitment of 95 patients showed that incidence of MRP, total blood loss, and incidence of blood transfusions were similar in the misoprostol (MRP, 40%; blood loss, 803 mL; blood transfusion, 15%) and placebo (MRP, 33%, blood loss 787 mL, blood transfusion, 23%) groups. The trial was stopped because continuation would not alter the interim conclusion that misoprostol was ineffective. Treatment with misoprostol was found to have no clinically significant beneficial effect among women with retained placenta. Current Controlled Trials ISRCTN16104753.


Genomic health care: is the future now?
In some areas of health care, genomics is having a steadily increasing impact on clinical practice. Yet, in other areas, genomic developments are considered to be at the periphery of care. Health-care professionals from such areas might feel that the potential of genomics is exaggerated. To explore this issue, genetic nurse specialists were invited to submit case studies and to identify barriers and facilitators in incorporating genomics into mainstream nursing practice. Twenty-five cases were submitted and a total of 10 barriers and seven facilitators were identified. These cases were presented as a basis for debate in a session conducted at the 2006 Annual Conference of the International Society of Nurses in Genetics. The majority of delegates agreed that genomics would have a profound effect on health care and nursing within the next 5 years, particularly in oncology. That nurses do not see genomics as being relevant to their practice was identified as the greatest barrier, by a narrow majority. Specialist nurses in any field have a role in acting as agents of change, educators, and consultants to non-specialists. It is clear that genetics nurse specialists still have a considerable challenge in raising awareness about the relevance of genomics to mainstream nursing practice.


Optimal Route for Tranexamic Acid in Diabetics and Obese Patients Undergoing Primary Total Knee Arthroplasty - a Data from Randomized Study.
PURPOSE OF THE STUDY To determine the optimal strategy for tranexamic acid (TXA) administration in diabetic patients, smokers and obese patients (BMI > 30 kg/m2) undergoing primary total knee arthroplasty (TKA). MATERIAL AND METHODS The total of 400 consecutive patients indicated for primary TKA were randomised into 4 basic groups with different TXA administration regimens. Group 1 (IV1) had a single intravenous dose (15 mg TXA/kg) applied prior to skin incision. Group 2 (IV2) got two intravenous doses (15 mg TXA/kg): one prior to skin incision and one subsequently 6 hours after the first dose. Group 3 (TOP) had 2 g TXA in 50 ml of saline irrigated topically at the end of the surgery. Group 4 (COMB) combined IV1 and TOP regimens. We monitored the amount of total blood loss (TBL), haemoglobin drop, use of blood transfusions (BTs), and complications in each patient. Follow-up period was one year postoperatively. RESULTS In the group of diabetic patients (n = 87; 21.7%) the lowest TBL was observed in the order: IV1, IV2 > COMB > TOP. In the obese patients (BMI > 30 kg/m2; n = 242; 60.5%), TBL was significantly lower in the intravenous regimens (IV1: p = 0.002; IV2: p = 0.005, respectively) than in the TOP regimen. In the smoking patients (n = 30; 7.5%), TBLs were significantly lower in the order: IV1 > IV2 > COMB > TOP. DISCUSSION Individualised approach to prevention and therapy is a recent trend, also because comorbidities significantly affect the result of the intervention. In the case of diabetes, obesity and smoking, there is a proven link to early post-operative infections, mainly due to poorer innate immunity. It is conceivable, though, that the occurrence of infectious complications is also contributed to by larger hematomas or hemarthroses which are largely preventable. CONCLUSIONS In the diabetic and obese patients (BMI > 30 kg/m2), the combined topical/intravenous TXA application and two intravenous doses of TXA interventions were shown to be the most effective. However, no evidence of superiority of any of the TXA administration routes was obtained in the smokers. None of the TXA protocols was associated with a higher incidence of complications or early reoperation following TKA surgery. Key words: tranexamic acid, topical application, intravenous application, combined administration, diabetes, obesity, BMI, smoking, blood loss, hidden blood loss, total knee arthroplasty, complications.


Assessment of Self-Reported Executive Function in Patients with Irritable Bowel Syndrome Using a Machine-Learning Framework.
Introduction: Irritable bowel syndrome (IBS) is characterized as a disorder of the gut-brain interaction (DGBI). Here, we explored the presence of problems related to executive function (EF) in patients with IBS and tested the relative importance of cognitive features involved in EF. Methods: A total of 44 patients with IBS and 22 healthy controls (HCs) completed the Behavior Rating Inventory of Executive Function (BRIEF-A), used to identify nine EF features. The PyCaret 3.0 machine-learning library in Python was used to explore the data, generate a robust model to classify patients with IBS versus HCs and identify the relative importance of the EF features in this model. The robustness of the model was evaluated by training the model on a subset of data and testing it on the unseen, hold-out dataset. Results: The explorative analysis showed that patients with IBS reported significantly more severe EF problems than the HC group on measures of working memory function, initiation, cognitive flexibility and emotional control. Impairment at a level in need of clinical attention was found in up to 40% on some of these scales. When the nine EF features were used as input to a collection of different binary classifiers, the Extreme Gradient Boosting algorithm (XGBoost) showed superior performance. The working memory subscale was consistently selected with the strongest importance in this model, followed by planning and emotional control. The goodness of the machine-learning model was confirmed in an unseen dataset by correctly classifying 85% of the IBS patients. Conclusions: The results showed the presence of EF-related problems in patients with IBS, with a substantial impact of problems related to working memory function. These results suggest that EF should be part of an assessment procedure when a patient presents other symptoms of IBS and that working memory function should be considered a target when treating patients with the disorder. Further studies should include measures of EF as part of the symptom cluster characterizing patients with IBS and other DGBIs.


Cognition enhancement by modafinil: a meta-analysis.
Currently, there are a number of pharmaceuticals available that have potential to enhance cognitive functioning, some of which may ultimately be considered for such use in military operations. Some drugs with potential for cognition enhancement have already been studied for use in military operations specific to their primary effect in sleep regulation (i.e., dextroamphetamine, modafinil, caffeine). There is considerable information available on many of these drugs. However, considerations for military appropriateness must be based on proficient research (e.g., randomly controlled trial design). A meta-analysis was conducted to summarize the current state of knowledge of these potentially cognition-enhancing drugs. The analysis only included studies which met inclusion criteria relevant to military research. The results of the literature review reveal a gap in research of the enhancement properties of the drugs of interest. The results yielded three studies (all of which studied modafinil) that met the criteria. The meta-analysis of these three studies revealed a relatively weak pooled effect of modafinil on some aspects of cognitive performance in normal, rested adults. While the results of this study support the efficacy of modafinil, the main finding is the large literature gap evaluating the short- and long-term effects of these drugs in healthy adults.


Practice characteristics among dental anesthesia providers in the United States.
General descriptions or "snapshots" of sedation/general anesthesia practices during dental care are very limited in reviewed literature. The objective of this study was to determine commonalities in dental sedation/anesthesia practices, as well as to accumulate subjective information pertaining to sedation/anesthesia care within the dental profession. This questionnaire-based survey was completed by participating anesthesia providers in the United States. A standardized questionnaire was sent via facsimile, or was delivered by mail, to 1500 anesthesia providers from a randomized list using an online database. Data from the returned questionnaires were entered onto an Excel spreadsheet and were imported into a JMP Statistical Discovery Software program for analyses. Quantitative evaluations were confined to summation of variables, an estimation of means, and a valid percent for identified variables. A total of 717 questionnaires were entered for data analysis (N=717). Data from this study demonstrate the wide variation that exists in sedation/anesthesia care and those providing its administration during dental treatment in the United States. The demographics of this randomized population show anesthesia providers involved in all disciplines of the dental profession, as well as significant variation in the types of modalities used for sedation/anesthesia care. Data from this study reveal wide variation in sedation/anesthesia care during dental treatment. These distinctions include representation of sedation/anesthesia providers across all disciplines of the dental profession, as well as variations in the techniques used for sedation/anesthesia care.


[Impact of pro-environmental behavior on dysmenorrhea].
In this study the impact of pro-environmental behavior, well-being oriented behavior, and use of cloth menstrual pads on dysmenorrhea in Korean female adults was examined according to the theory of reasoned action. A cross-sectional study was conducted with 195 Korean female adults. Data were collected from June to August, 2010 using self-report questionnaires. Data were analyzed using t-test, one-way ANOVA, Pearson correlation coefficients, multiple regression, and logit regression with STATA 10.0. Pro-environmental behavior explained 48% of well-being oriented behavior. Well-being oriented behavior explained 10% of cloth pad use. Use of cloth pad explained 4% of dysmenorrhea and 5% of menstrual pain. The path through well-being oriented behavior had a significant effect from pro-environmental behavior to cloth pad use. Use of cloth pad was significantly related with well-being oriented behavior, pro-environmental behavior, social influence, dysmenorrhea, and menstrual pain. The results of this study suggest that pro-environmental strategies can help health care providers diminish clients' menstrual symptoms. Nursing intervention can support pro-environmental behavioral strategies.


Adaptive mesh computation of polycrystalline pattern formation using a renormalization-group reduction of the phase-field crystal model.
We implement an adaptive mesh algorithm for calculating the space and time dependence of the atomic density field in microscopic material processes. Our numerical approach uses the systematic renormalization-group formulation of a phase-field crystal model of a pure material to provide the underlying equations for the complex amplitude of the atomic density field--a quantity that is spatially uniform except near topological defects, grain boundaries, and other lattice imperfections. Our algorithm employs a hybrid formulation of the amplitude equations, combining Cartesian and polar decompositions of the complex amplitude. We show that this approach leads to an acceleration by three orders of magnitude in model calculations of polycrystalline grain growth in two dimensions.


The PERFUSE study: The experience of patients receiving Adalimumab biosimilar SB5.
SB5 is an EMA-approved adalimumab biosimilar, having demonstrated bioequivalence, equivalent efficacy, and similar safety and immunogenicity to the reference product. Describe patient training and satisfaction using patient-reported outcome measures (PROMs) and assess their impact on 12-month persistence on SB5. The observational PERFUSE study included 318 Crohn's disease (CD) patients and 88 ulcerative colitis (UC) patients in 27 sites across France between October 2018 and December 2020. PROMs were collected at 1-month post-baseline using an online questionnaire (ePRO) designed with patient associations. Treatment persistence was collected during routine visits (up to 15 months post-initiation). Results are presented by prior experience with subcutaneous biologics and training in proper use of the injection device. 57.1% (n = 145) and 44.1% (n = 67) of naïve and pre-treated patients, respectively, answered the ePRO. Naïve patients were offered training more often (86.9% vs 31.3% respectively, p < 0.05), with disparities between sites. All subgroups' satisfaction scores were high. 12-month persistence on SB5 was significantly higher for respondents than for non-respondents (68.0% [60.9; 74.1] vs 52.3% [44.5; 59.6]; p < 0.05) and in patients with a better perception of their illness (OR=1.02, [1.0; 1.05]; p < 0.05). Early patient questionnaires may be useful to identify patients at higher risk of treatment discontinuation.


Percutaneous thermal ablation of hepatocellular carcinomas located in the hepatic dome using artificial carbon dioxide pneumothorax: retrospective evaluation of safety and efficacy.
The targeting of hepatocellular carcinomas (HCC) in the hepatic dome can be challenging during percutaneous thermal ablation (PTA). The aims of this study were (1) to evaluate the safety and efficacy of PTA of HCC in the hepatic dome that cannot be visualized under US, using artificial CO2 pneumothorax and CT-guidance and (2) to compare the results with US-visible HCC located in the liver dome treated under US-guidance. Over a 32-month period, 56 HCC located in the hepatic dome were extracted from a prospectively maintained database. Twenty-eight cases (US-guidance group) were treated under US-guidance, while the others (n = 28, CT-CO2 group) were treated under CT-guidance using artificial CO2 pneumothorax after lipiodol tagging of the tumor. The primary technical success and complications rates of this technique were retrospectively assessed. Local tumor progression (LTP), intrahepatic distant recurrence (IDR), local recurrence-free survival (LRFS) and overall survival (OS) were also compared between both groups. Primary technical success was 100% in both groups. No major complications occurred. After a median follow-up of 13.8 months (range, 1-33.4 months), LTP occurred in 10.7% (3/28) in CT-CO2 vs. 25% (7/28) in the US-guidance group (p = NS). IDR occurred in 39.3% (11/28) in CT-CO2 vs. 28.6% (8/28) in the US-guidance group (p = NS). Death occurred in 17.9% (5/28) of patients in both groups. LRFS and OS did not significantly differ using Kaplan-Meier survival estimates. CT-guided PTA after artificially induced CO2 pneumothorax is a safe and efficient technique to treat HCC located in the hepatic dome.


The management of breakthrough cancer pain--educational needs a European nursing survey.
Poorly managed cancer pain is well known to profoundly impact the patient's daily life and interfere with quality of life. Nurses who cared for patients with cancer from 12 European countries participated in a survey of breakthrough cancer pain practice. The purpose was to investigate how nurses assess breakthrough cancer pain, use of standardised tools, confidence in supporting patients and awareness of medications. Responses from 1241 participants showed country variations. The majority of the sample was female, Germany had the highest proportion of male nurses (21.0%), followed by Greece (15.8%). A significantly larger proportion of nurses with longer experience and more education (78.8%) used a comprehensive definition of breakthrough cancer pain. Significant variations in training were found; 71% of Finnish nurses had received training compared with 6% of Greek nurses. Training and using a standardised assessment tool was associated with a significant increase in the nurses' perceived ability to distinguish between breakthrough and background pain. Nurses in countries with the highest proportion of training were most confident in supporting patients. In conclusion, there still exists problems with effective management of patients' breakthrough cancer pain, continuing inability to define the difference between background and breakthrough cancer pain leads to poor treatment.


Optimal laser parameters for port wine stain therapy: a theoretical approach.
The optimal parameters for laser therapy of port wine stains (PWS) have been deduced from temperature calculations on two models: (i) the four-layer model; and (ii) the tube model in which two plane parallel layers, representing the epidermis and dermis, and a dermal rectangular blood vessel are considered. The calculations were performed with a vessel of average cross section 0.06 mm X 0.08 mm located in the centre of the laser beam. The numerical calculations were performed by an alternate direction-implicit finite difference method. The optimal parameters were: wavelengths lambda = 415, 577 and 540 nm; pulse time, 1 ms less than t1 less than or equal to 10 ms; and beam radius W1 greater than 0.1 mm. The energy densities E1 (for t1 = 1 ms) required to coagulate blood vessels down to a depth of 0.65 mm in order to establish bleaching of the PWS were 0.5, 1.6 and 2 J cm-2 for the different lambda respectively. The value for the argon laser (lambda = 488 and 514.5 nm) was E1 = 6.5 J cm-2 (t1 = 1 ms). Because, for this pulse time, heat summation effects at the boundary of the laser beam cause no drastic increase in local temperature at optimal wavelengths, the stripe technique was again considered and compared with the separated spot technique. The Nd-YAG and CO2 lasers prove even less selective than the argon laser. The influence of cooling the skin with water shows that only for lambda = 577 nm and t1 = 0.1 s is there an increase in E1 from 2.5 to 6 J cm-2 for which dermal damage occurs.


Genomic Sequencing of Ranaviruses Isolated from Edible Frogs (Pelophylax esculentus).
Ranaviruses were isolated from wild edible frogs (Pelophylax esculentus) during epizootics in Denmark and Italy. Phylogenomic analyses revealed that these isolates are closely related and belong to a clade of ranaviruses that includes the Andrias davidianus ranavirus (ADRV), common midwife toad ranavirus (CMTV), Testudo hermanni ranavirus (THRV), and pike-perch iridovirus (PPIV).


Closed-Loop Control with Unannounced Exercise for Adults with Type 1 Diabetes using the Ensemble Model Predictive Control.
This paper presents an individualized Ensemble Model Predictive Control (EnMPC) algorithm for blood glucose (BG) stabilization and hypoglycemia prevention in people with type 1 diabetes (T1D) who exercise regularly. The EnMPC formulation can be regarded as a simplified multi-stage MPC allowing for the consideration of N en scenarios gathered from the patient's recent behavior. The patient's physical activity behavior is characterized by an exercise-specific input signal derived from the deconvolution of the patient's continuous glucose monitor (CGM), accounting for known inputs such as meal, and insulin pump records. The EnMPC controller was tested in a cohort of in silico patients with representative inter-subject and intra-subject variability from the FDA-accepted UVA/Padova simulation platform. Results show a significant improvement on hypoglycemia prevention after 30 min of mild to moderate exercise in comparison to a similarly tuned baseline controller (rMPC); with a reduction in hypoglycemia occurrences (< 70 mg/dL), from 3.08% ± 3.55 with rMPC to 0.78% ± 2.04 with EnMPC (P < 0.05).


Impact of the H3K27M mutation on survival in pediatric high-grade glioma: a systematic review and meta-analysis.
OBJECTIVE Pediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine glioma, present a prognostic challenge given their lethality and rarity. A substitution mutation of lysine for methionine at position 27 in histone H3 (H3K27M) has been shown to be highly specific to these tumors. Data are accumulating regarding the poor outcomes of patients with these tumors; however, the quantification of pooled outcomes has yet to be done, which could assist in prioritizing management. The aim of this study was to quantitatively pool data in the current literature on the H3K27M mutation as an independent prognostic factor in pHGG. METHODS Searches of seven electronic databases from their inception to March 2018 were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted and pooled using a meta-analysis of proportions. Meta-regression was used to identify potential sources of heterogeneity. RESULTS Six observational studies satisfied the selection criteria for inclusion. They reported the survival outcomes of a pooled cohort of 474 pHGG patients, with 258 (54%) and 216 (46%) patients positive and negative, respectively, for the H3K27M mutation. Overall, the presence of the mutation was independently and significantly associated with a worse prognosis (HR 3.630, p < 0.001). Overall survival was significantly shorter (by 2.300 years; p = 0.008) when the H3K27M mutation was present in pHGG. Meta-regression did not identify any study covariates of heterogeneous concern. CONCLUSIONS According to the current literature, pHGG patients positive for the H3K27M mutation are more than 3 times more susceptible to succumbing to this disease by more than 2 years, compared to patients negative for the mutation. More robust outcome data are required to improve our quantitative understanding of this pathological entity in order to assist in prioritizing clinical management. Future larger prospective studies are required to overcome inherent biases in the current literature to validate the quantitative findings of this study. ABBREVIATIONS CI = confidence interval; GRADE = Grades of Recommendation Assessment, Development and Evaluation; HR = hazard ratio; MD = mean difference; NOS = Newcastle-Ottawa Scale; OS = overall survival; pHGG = pediatric high-grade glioma; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RE = random effects.


Aging of the human lens: changes in lens shape at zero-diopter accommodation.
Scheimpflug photographs of the zero-diopter-accommodated anterior segments of 100 human subjects, aged 18 to 70 yr and evenly spaced over this range, were digitized and analyzed to characterize lens and lens nucleus shape as a function of age by the Hough transform and other image analysis methods. Anterior and posterior lens surface curves exhibit a decrease in radius of curvature with increasing age, in qualitative but not quantitative agreement with the earlier observations of Brown [Exp. Eye Res. 19, 175 (1974)]. In contrast, the shape of the lens nuclear boundaries changes little with age. Overall lens volume at zero diopters increases with age, but the volume of the lens nucleus remains unchanged. The lens center of mass moves anteriorly with increasing age, as does the central clear region of the lens. Although these data sets were found to be more variable than those of Brown, the complementary variability of other factors, such as anterior chamber depth, for each subject leads to a very high statistical correlation between lens shape and lens location relative to the cornea. This supports the finding of previous work that image formation on the retina for a given individual results from the multifactorial balancing of related factors.


"Why am I out of the loop?" attributions influence responses to information exclusion.
Studies show the importance of information sharing in decision making. However, information sharing also affects intrapersonal perceptions and group dynamics. Three experiments demonstrated that out-of-the-loop individuals experienced thwarted needs (e.g., belonging) and decreased trust and liking of group members. Experiment 1 showed these deleterious effects only occurred when information exclusion appeared intentional. Experiment 2 established that constructive motives could mitigate negative effects of intentional information exclusion. Experiment 3 showed that unintentional information exclusion deflated participants only when perceived as preventable. These experiments also provided evidence for a mediating process. Information exclusion, particularly when ill intentioned or preventable, signals poor group standing, leading to deleterious psychological effects.


Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess liver triacylglycerol (TAG), inflammation, and liver damage. The goal of the present study was to directly quantify the biological sources of hepatic and plasma lipoprotein TAG in NAFLD. Patients (5 male and 4 female; 44 +/- 10 years of age) scheduled for a medically indicated liver biopsy were infused with and orally fed stable isotopes for 4 days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipoprotein TAG. Hepatic and lipoprotein TAG fatty acids were analyzed by gas chromatography/mass spectrometry. NAFLD patients were obese, with fasting hypertriglyceridemia and hyperinsulinemia. Of the TAG accounted for in liver, 59.0% +/- 9.9% of TAG arose from NEFAs; 26.1% +/- 6.7%, from DNL; and 14.9% +/- 7.0%, from the diet. The pattern of labeling in VLDL was similar to that in liver, and throughout the 4 days of labeling, the liver demonstrated reciprocal use of adipose and dietary fatty acids. DNL was elevated in the fasting state and demonstrated no diurnal variation. These quantitative metabolic data document that both elevated peripheral fatty acids and DNL contribute to the accumulation of hepatic and lipoprotein fat in NAFLD.


DNA copy number gains in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with an extremely poor prognosis. The incidence of MPM is increasing as a result of widespread exposure to asbestos. The molecular pathogenesis of MPM remains unclear. The present study analyzed the frequency of various genomic copy number gains (CNGs) in MPM using reverse transcription-quantitative polymerase chain reaction. A total of 83 primary MPMs and 53 primary lung adenocarcinomas were analyzed to compare the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2. In MPM, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 12 (14.5%), 8 (9.6%), 5 (6.0%), 4 (4.8%) and 1 (1.2%) of the samples, respectively. In lung adenocarcinomas, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 21 (39.6%), 12 (22.6%), 5 (9.4%), 10 (18.9%) and 0 (0.0%) of the samples, respectively. The CNGs of EGFR, KRAS and FGFR1 were significantly less frequent in the MPMs compared with the lung adenocarcinomas (P=0.0018, 0.048 and 0.018, respectively). Overall, the MPMs exhibited these CNGs less frequently compared with the lung adenocarcinomas (P=0.0002). The differences in CNGs between the two tumor types suggested that they are genetically different.


[99mTc-nanocolloid: clinical results of its use as a new inflammation marker].
Fifty scintigrams were performed on 45 patients using 99mTc-nanocolloid in order to test its affinity for inflammatory lesions; in these patients there was clinical and/or radiological suspicion of an inflammatory process. There was good correlation between the degree of uptake and the activity of the inflammatory process. Specificity is limited because of uptake in certain tumours (eg. sarcomas of the extremities), but difficulties in differential diagnosis are not expected to be serious. Judging by our experience, 99mTc-nanocolloid is a promising substance for the scintigraphic demonstration of inflammatory foci. The advantages of this industrially prepared tracer over In-leucocytes and Ga-citrate are discussed.


Comparison of select hematology and serum chemistry analtyes between wild-caught and aquarium-housed lake sturgeon (Acipenser fulvescens).
Hematology and serum chemistry analytes were compared between wild-caught and aquarium-housed lake sturgeon (Acipenser fulvescens) to potentially improve understanding of medical issues in lake sturgeon. Blood samples were taken from 30 lake sturgeon exhibited in 11 institutions in the United States and from 23 experimentally stocked lake sturgeon caught in gill nets in the lower Genesee River in Rochester, New York, USA. For hematology, only segmented neutrophil count was significantly different, with wild-caught fish having a higher number of circulating neutrophils. For clinical chemistry analytes, chloride, uric acid, calcium, phosphate, glucose, aspartate aminotransferase, triglycerides, and creatine kinase were significantly different between the two cohorts. These differences are likely not clinically significant and are attributable to handling stress, variability in environmental parameters, or differences in nutritional status. This is the first report of hematology and serum chemistry values in aquarium-housed lake sturgeon and provides useful reference intervals for clinicians.


EfrAB, an ABC multidrug efflux pump in Enterococcus faecalis.
A DNA fragment responsible for resistance to antimicrobial agents was cloned from the chromosomal DNA of Enterococcus faecalis ATCC 29212 by using drug-hypersensitive mutant Escherichia coli KAM32 as a host cell. Cells of E. coli KAM32 harboring a recombinant plasmid (pAEF82) carrying the DNA fragment became resistant to many structurally unrelated antimicrobial agents, such as norfloxacin, ciprofloxacin, doxycycline, acriflavine, 4',6-diamidino-2-phenylindole, tetraphenylphosphonium chloride, daunorubicin, and doxorubicin. Since the sequence of the whole genome of E. faecalis is known, we sequenced several portions of the DNA insert in plasmid pAEF82 and identified two open reading frames within the insert. We designated the genes efrA and efrB. A search of the deduced amino acid sequences of EfrA and EfrB revealed that they are similar to each other and that they belong to the ATP-binding cassette (ABC) family of multidrug efflux transporters. Transformed E. coli KAM32 cells harboring efrAB showed energy-dependent efflux of acriflavine. The efflux activity was inhibited by reserpine, verapamil, and sodium-o-vanadate, known inhibitors of ABC efflux pumps.


Complete spontaneous resolution of a giant bulla without rupture or infection: a case report and literature review.
We report a case of complete spontaneous resolution of a giant bulla without ipsilateral pneumothorax or overt infection accompanied by contralateral recurrent pneumothorax. A 67-year-old man visited the emergency room with dyspnea. Chest computed tomography revealed spontaneous pneumothorax on the right side and a giant bulla in the left anterior lung. Closed thoracostomy was performed and the patient was discharged. Two years later, right pneumothorax recurred. Bullectomy in the right lung and pleurodesis were performed. On monthly follow up, the giant bulla in the left lung had abruptly disappeared without any episode of pneumothorax or infection at one year after the operation.


An international survey of tissue banking: a preliminary report.
International Atomic Energy Agency is currently carrying out a survey on the tissue banking activities from the tissue banking organisations worldwide. The purpose of the survey is to establish regional and global overview of the current tissue banking activities and practices in order to assist the International Atomic Energy Agency to provide further guidance about the use of radiation technology to sterilise tissues as well as to promote better collaboration between the regional tissue banking associations. The survey is an on-going exercise and the preliminary data is presented here. This exercise is not completed and the authors urge the remaining tissue banks to participate in the survey.


Assessment of potential probiotic properties of Lactobacillus spp., Lactococcus spp., and Pediococcus spp. strains isolated from kefir.
In this study, the metabolic activities (in terms of quantities of the produced lactic acid, hydrogen peroxide, and exopolysaccharides) of 8 strains of Lactobacillus spp., Lactococcus spp., and Pediococcus spp., were determined. Lactic acid levels produced by strains were 8.1 to 17.4 mg/L. The L. acidophilus Z1L strain produced the maximum amount (3.18 μg/mL) of hydrogen peroxide. The exopolysaccharides (EPS) production by the strains was ranged between 173 and 378 mg/L. The susceptibility of 7 different antibiotics against these strains was also tested. All strains were found to be sensitive to ampicillin. The tolerance of the strains to low pH, their resistance to bile salts of strains, and their abilities to autoaggregate and coaggregate with Escherichia coli ATCC 11229 were also evaluated. High EPS-producing strains showed significant autoaggregation and coaggregation ability with test bacteria (P < 0.01). A correlation also was determined between EPS production and acid-bile tolerance (P < 0.05). EPS production possibly affects or is involved in acid-bile tolerance and aggregation of Lactobacillus spp., Lactococcus spp., and Pediococcus spp. strains and supports the potential of L. acidophilus Z1L strain as new probiotic.