Causes of conductive hearing loss after stapedectomy or stapedotomy: a prospective study of 279 consecutive surgical revisions.
To analyze the causes for residual or recurrent conductive hearing loss following stapedectomy or stapedotomy and then propose surgical techniques to avoid these complications. Prospective study of 279 consecutive stapedectomy or stapedotomy revisions performed by the author. Tertiary referral center. The study included 260 patients who presented with a 20 dB or greater average air-bone gap in the speech frequencies 1 month to 35 years following stapedectomy or stapedotomy (19 patients were explored for possible oval window perilymph fistula). Stapedectomy (stapedotomy) surgical revision. Microscopic inspection and palpation assessed the mobility and continuity of the malleus, incus, and prosthesis. Infrared laser vaporization thinned the oval window neomembrane to identify the precise depth and margins of the oval window, the presence of residual stapes footplate, and finally, the relationship of the prosthesis to the fenestra into the vestibule. Prosthesis displacement out of the oval window fenestration with fixation of the prosthesis against the residual stapes footplate or otic capsule margin was demonstrated in 81% (211/260) of the patients. Of these patients, 31% had complete incus erosion, and an additional 60% demonstrated partial incus erosion, usually on the undersurface of the incus. Residual fixed stapes footplate was found in 14%, and malleus fixation in 4%. Incus dislocation was found in 4%, and incus fixation in 2%. Prosthesis migration and subsequent fixation caused the majority of stapedectomy failures. Collagen contracture of the oval window neomembrane lifts the prosthesis out of the oval window fenestration. Prosthesis displacement then results from adhesions pulling the prosthesis or mechanical forces further tilting the prosthesis. Incus erosion results from vibration against the fixed prosthesis. Six specific stapedotomy recommendations are made to minimize postoperative prosthesis migration.


Fingerspelling as a Novel Gateway into Reading Fluency in Deaf Bilinguals.
Studies have shown that American Sign Language (ASL) fluency has a positive impact on deaf individuals' English reading, but the cognitive and cross-linguistic mechanisms permitting the mapping of a visual-manual language onto a sound-based language have yet to be elucidated. Fingerspelling, which represents English orthography with 26 distinct hand configurations, is an integral part of ASL and has been suggested to provide deaf bilinguals with important cross-linguistic links between sign language and orthography. Using a hierarchical multiple regression analysis, this study examined the relationship of age of ASL exposure, ASL fluency, and fingerspelling skill on reading fluency in deaf college-age bilinguals. After controlling for ASL fluency, fingerspelling skill significantly predicted reading fluency, revealing for the first-time that fingerspelling, above and beyond ASL skills, contributes to reading fluency in deaf bilinguals. We suggest that both fingerspelling--in the visual-manual modality--and reading--in the visual-orthographic modality--are mutually facilitating because they share common underlying cognitive capacities of word decoding accuracy and automaticity of word recognition. The findings provide support for the hypothesis that the development of English reading proficiency may be facilitated through strengthening of the relationship among fingerspelling, sign language, and orthographic decoding en route to reading mastery, and may also reveal optimal approaches for reading instruction for deaf and hard of hearing children.


Flexibility of resource allocation in a hermaphroditic-gynomonoecious herb through deployment of female and male resources in perfect flowers.
It has been hypothesized that two flower types permit flexible allocation of resources to female and male functions, yet empirical evidence for the sex-allocation hypothesis remains scarce in gynomonoecious species. To characterize resource allocation to pistillate and perfect flowers and allocation of perfect flowers between gynomonoecious and hermaphroditic individuals, we examined the flexibility and whether female-biased allocation increases with plant size in the hermaphroditic-gynomonoecious herb Eremurus anisopterus. Frequency of gynomonoecious individuals, flower production, and plant size were investigated in different populations. Floral allocation was compared among the three flower types of E. anisopterus. Frequency of gynomonoecious plants varied from 2-17% in nine populations. Only larger plants produced female flowers at the bottom of racemes. Both female and perfect flower production tended to increase proportionately with plant size in gynomonoecious individuals. Female flowers did not produce less biomass than perfect flowers from hermaphroditic or gynomonoecious plants. However, both female and perfect flowers from gynomonoecious individuals had lighter stamen mass, but larger pistil mass, than perfect flowers from hermaphrodites. Although the prediction of an increase in female flower number with plant size was not observed in E. anisopterus, the flexibility of sex allocation in gynomonoecious species was confirmed in that gynomonoecious individuals had a female-biased floral allocation compared to hermaphroditic individuals. Such comparisons of gynomonoecious to hermaphroditic individuals permit us to unveil a sexual adjustment strategy: flexibility of sexual investments within plants.


pH-dependent effects of bepridil on Ca2+-extrusion across rat heart sarcolemma.
The inhibition by bepridil of ATP-dependent Ca2+-uptake and Na+/Ca2+-exchange was studied in isolated rat cardiac sarcolemmal vesicles over a pH range of 6.3 to 7.8. It was found that the protonated and deprotonated species of bepridil induced the same inhibition and no activation of these two transport systems. However, the intrinsic activities of both systems appeared to be strongly dependent on the pH.


Motor plasticity after extra-intracranial bypass surgery in occlusive cerebrovascular disease.
To explore plasticity in patients scheduled for extra-intracranial bypass surgery due to unilateral symptomatic occlusive cerebrovascular disease via navigated transcranial magnetic stimulation. In this observational study, patients were allocated to different substudies and examined before and 3 months after operation. (1) Corticospinal excitability was determined via identification of the resting motor threshold. (2) Intracortical inhibition and facilitation were tested by paired pulse transcranial magnetic stimulation. (3) Area of cortical representation of the first dorsal interosseous muscle was identified. (1) Resting motor thresholds were higher in the affected hemispheres with impaired cerebrovascular reserve capacity compared to the unaffected hemispheres (45.7% ± 2.2% compared to 39.2% ± 1.4%, n = 39, p < 0.05). Reduced excitability normalized 3 months after revascularization (51% ± 2.6% → 45% ± 1.9%, n = 21, p < 0.05). (2) In paired pulse paradigms, there was a motor disinhibition in the operated hemispheres. (3) There was a reduction of the cortical representation areas of the first dorsal interosseous muscle (2.3 ± 0.5 cm(2) → 0.9 ± 0.6 cm(2), n = 9, p < 0.05) after operation. Our data demonstrate a reversibly impaired motor cortical function in the chronically ischemic brain. In carefully selected patients, cerebral revascularization leads to improved motor output indicated by a lower resting motor threshold, intracortical disinhibition, and more focused motor cortical representation.


Uterine cervical tumor metastases and their treatment.
Uterine cervical carcinoma is a locoregional disease. However, particularly in advanced stages, in the presence of N+ and pelvic relapse, it may produce secondary lesions located far from it. In our case series, consisting of 473 portio carcinomas treated at the Institute of Radiology of the U.C.S.C., we found distant metastases in 6.76% of the cases. This study examines the cases of metastasis in relation to stage, histology, risk-factors, treatment of the primary tumour and survival after the treatment of the secondary lesions.


Can thymidine phosphorylase be a predictive marker for gemcitabine and doxifluridine combination chemotherapy in cholangiocarcinoma?: case series.
Unresectable cholangiocarcinoma is poorly responded to chemotherapy, especially for the case refractory to gemcitabine and cisplatin. Here, we tested whether high expression of thymidine phosphorylase (TP) can be a predictive biomarker for the indicator for gemcitabine and doxifluridine combination chemotherapy in the cholangiocarcinoma refractory to gemcitabine and cisplatin. Immunohistochemical staining for TP was performed with a biopsy specimen. We accepted the result as positive when more than 10% of cancer cells were stained with moderate intensity. Here, we report 2 cases of TP-positive cholangiocarcinoma well controlled with gemcitabine and doxifluridine combination chemotherapy, which had been refractory to the first line treatment with gemcitabine and cisplatin combination chemotherapy.


PROTEIN PHOSPHATASE 2C08, a Negative Regulator of Abscisic Acid Signaling, Promotes Internode Elongation in Rice.
Clade A protein phosphatase 2Cs (PP2CAs) negatively regulate abscisic acid (ABA) signaling. Here, we investigated the functions of OsPP2CAs and their crosstalk with ABA and gibberellic acid (GA) signaling pathways in rice (Oryza sativa). Among the nine OsPP2CAs, OsPP2C08 had the highest amino acid sequence similarity with OsPP2C51, which positively regulates GA signaling in rice seed germination. However, OsPP2C08 was expressed in different tissues (internodes, sheaths, and flowers) compared to OsPP2C51, which was specifically expressed in seeds, and showed much stronger induction under abiotic stress than OsPP2C51. Transgenic rice lines overexpressing OsPP2C08 (OsPP2C08-OX) had a typical ABA-insensitive phenotype in a post-germination assay, indicating that OsPP2C08, as with other OsPP2CAs, negatively regulates ABA signaling. Furthermore, OsPP2C08-OX lines had longer stems than wild-type (WT) plants due to longer internodes, especially between the second and third nodes. Internode cells were also longer in OsPP2C08-OX lines than in the WT. As GA positively regulates plant growth, these results suggest that OsPP2C08 might positively regulate GA biosynthesis. Indeed, the expression levels of GA biosynthetic genes including gibberellin 20-oxidase (OsGA20ox4) and Ent-kaurenoic acid oxidase (OsKAO) were increased in OsPP2C08-OX lines, and we observed that GIBBERELLIN 2-OXIDASE 4 (OsGA2ox4), encoding an oxidase that catalyzes the 2-beta-hydroxylation of several biologically active GAs, was repressed in the OsPP2C08-OX lines based on a transcriptome deep sequencing and RT-qPCR analysis. Furthermore, we compared the accumulation of SLENDER RICE 1 (SLR1), a DELLA protein involved in GA signaling, in OsPP2C08-OX and WT plants, and observed lower levels of SLR1 in the OsPP2C08-OX lines than in the WT. Taken together, our results reveal that OsPP2C08 negatively regulates ABA signaling and positively regulates GA signaling in rice. Our study provides valuable insight into the molecular mechanisms underlying the crosstalk between GA and ABA signaling in rice.


[The use of the antioxidant drink by healthy workers exposed to chemical factors].
In chemical manufacturing along with alimentary factors, workers are exposed to occupational hazards resulting in reduced antitoxic protective properties of the organism. The purpose of the present work was to develop a preventive method for reducing antitoxic functions of the body of healthy workers exposed to chemical factors. We have produced the drink containing carrot juice, honey, olive oil. The study involved 50 employees (the average age was 37.4±5.5 years) with experience of over 15 years. The main group (25 people) were workers with reduced antitoxic function who received the drink before each day's work shift for 10 days, the control group - workers with normal anti-toxic function, which did not take a drink. It was found that antioxidant drink intake by healthy employees of a chemical complex lead to the decrease of the level of molecules of average mass at λ=254 nm and at λ=280 nm by 15.1±7.2%, the activity of gammaglutamyl transferase - by 19.1%, alaninaminotransferase - by 44.1%, aspartataminotrans-ferase - by 34.7% (indicators of the syndrome of endogenous intoxication), the decrease of the content of malondialdehyde (as an indicator of an excessive accumulation of products of lipid peroxidation) - by 43.8%, while the activity of catalase, that indicates an increase in the antitoxic functions of the organism, increased by 37.5%.


The A312 Allele (c.280A>T) Is Responsible for the Weak A Phenotype.
The ABO*A312 allele was found in a 71-year-old Korean male with ABO discrepancy and in his two sons. Although the ABO*A312 allele (c.280A>T, I94F) in an AwB case was registered in GenBank, the impact of the I94F mutation of the ABO gene on the activity of A transferase has not been studied. Transient transfection experiments were performed in HeLa cells using A101, A102, and A312 alleles synthesized by site-directed mutagenesis, and the functional expression level of A antigen was assessed by flow cytometry. The results showed that the A102 and A312 alleles expressed A antigen levels that were 80.28% and 19.32%, respectively, of that of the A101 allele. Our study results demonstrate that the c.280A>T variant is responsible for the weakened expression of A antigen.


Hydrodynamic modes for granular gases.
The eigenfunctions and eigenvalues of the linearized Boltzmann equation for inelastic hard spheres (d=3) or disks (d=2) corresponding to d+2 hydrodynamic modes are calculated in the long wavelength limit for a granular gas. The transport coefficients are identified and found to agree with those from the Chapman-Enskog solution. The dominance of hydrodynamic modes at long times and long wavelengths is studied via an exactly solvable kinetic model. A collisional continuum is bounded away from the hydrodynamic spectrum, assuring a hydrodynamic description at long times. The bound is closely related to the power law decay of the velocity distribution in the reference homogeneous cooling state.


Butanedione monoxime promotes voltage-dependent inactivation of L-type calcium channels in heart. Effects on gating currents.
The effect of 20 mM extracellularly applied 2,3-Butanedione monoxime (BDM) on L-type Ca2+ channel charge movement current was studied in whole-cell voltage-clamped guinea-pig ventricular myocytes. Intramembraneous charge movement in response to depolarizing pulses (charge 1), was reduced after the application of BDM. The effect was more pronounced at the OFF of the charge transient (41%) than at the ON (7%). The steady-state availability curve of charge 1 was shifted to the left; the magnitude of the voltage shift was similar to the shift in Ca2+ current availability. Charge movement recorded in the negative voltage range (charge 2) after conditioning depolarizing pulses of different duration, was increased by BDM. For a 300-ms conditioning pulse charge 2 measured during a negative test pulse increased 40% (in Ba2+ external solution) or 35% (in Ca2+ external solution). These results show that BDM promotes voltage-dependent inactivation of L-type Ca2+ channels in parallel with charge interconversion between intramembranous charges 1 and 2. Mechanistically they are consistent either with dephosphorylation or a dihydropyridine-like action, but argue against open channel block as the mechanism of the effect of the drug.


Electrodiagnosis and nerve conduction studies.
The use of electrodiagnostic techniques in evaluation of complaints in the lower extremities provides an objective method of assessment. A basic understanding of principles of neurophysiology, EMG and NCV methodology, and neuropathology of peripheral nerves greatly enhances physical diagnosis and improves the state of the art in treatment of the lower extremity, especially foot and ankle injuries. Familiarity with the method of reporting electrodiagnostic studies and appreciation of the electromyographer's interpretation of the EMG/NCV studies also reflects an enhanced fund of knowledge, skills, and attitudes as pertains to one's level of professional expertise. Information regarding the etiology of positive sharp waves, fibrillation potentials, fasciculation, and normal motor action potentials and conduction studies serves as a sound basis for the appreciation of the categories of nerve injury. Competence in understanding the degree of axonal or myelin function or dysfunction in a nerve improve one's effectiveness not only in medical/surgical treatment but in prognostication of recovery of function. A review of the entrapment syndromes in the lower extremity with emphasis on tarsal tunnel syndrome summarizes the most common nerve entrapments germane to the practice of podiatry. With regard to tarsal tunnel syndrome, the earliest electrodiagnostic study to suggest compression was reported to be the EMG of the foot and leg muscles, even before prolonged nerve latency was noted.


Regulation of the ColV plasmid-determined iron (III)-aerobactin transport system in Escherichia coli.
Regulation by iron was studied in Escherichia coli strains whose iron supply was entirely dependent on the iron(III)-aerobactin system determined by the ColV plasmid. By the insertion of phage Mu (Ap lac) into the ColV plasmid, mutants were selected that could no longer grow in iron-limited media. The inserted Mu (Ap lac) strongly reduced the amount of aerobactin and he cloacin receptor protein formed by the cells. Their production was no longer subject to regulation by iron. The Mu (Ap lac) insertion apparently led to a polar effect on the expression of the presumably closely linked genes that control the synthesis of aerobactin and the cloacin receptor protein. The expression of the beta-galactosidase gene on the inserted phage genome came under the control of the iron state of the cells. Under iron-limited growth conditions, the amount of beta-galactosidase synthesized was, depending on the strain studied, 6 to 30 times higher than under iron-sufficient growth conditions. In fur mutants with an impaired iron regulation of ll iron supply systems studied so far, high amounts of beta-galactosidase were synthesized independent of the cells' iron supply. The results demonstrate an iron-controlled promoter on the ColV plasmid which is subject to regulation by the chromosomal fur gene.


Paraoxonases: ancient substrate hunters and their evolving role in ischemic heart disease.
Interest in the role of paraoxonases (PON) in cardiovascular research has increased substantially over the past two decades. These multifaceted and pleiotropic enzymes are encoded by three highly conserved genes (PON1, PON2, and PON3) located on chromosome 7q21.3-22.1. Phylogenetic analysis suggests that PON2 is the ancient gene from which PON1 and PON3 arose via gene duplication. Although PON are primarily lactonases with overlapping, but distinct specificities, their physiologic substrates remain poorly characterized. The most interesting characteristic of PON, however, is their multifunctional roles in various biochemical pathways. These include protection against oxidative damage and lipid peroxidation, contribution to innate immunity, detoxification of reactive molecules, bioactivation of drugs, modulation of endoplasmic reticulum stress, and regulation of cell proliferation/apoptosis. In general, PON appear as "hunters" of old and new substrates often involved in athero- and thrombogenesis. Although reduced PON activity appears associated with increased cardiovascular risk, the correlation between PON genotype and ischemic heart disease remains controversial. In this review, we examine the biochemical pathways impacted by these unique enzymes and investigate the potential use of PON as diagnostic tools and their impact on development of future therapeutic strategies.


Dynamic Susceptibility Contrast-Enhanced Perfusion-Weighted Imaging in Differentiation Between Recurrence and Pseudoprogression in High-Grade Glioma: A Meta-analysis.
In glioma patients that have undergone surgical tumor resection, the ability to reliably distinguish between pseudoprogression (PsP) and a recurrent tumor (RT) is of key clinical importance. Accordingly, this meta-analysis evaluated the utility of dynamic susceptibility contrast-enhanced perfusion-weighted imaging as a means of distinguishing between PsP and RT when analyzing patients with high-grade glioma. The PubMed, Web of Science, and Wanfang databases were searched for relevant studies. Pooled analyses of sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) values were conducted, after which the area under the curve (AUC) for summary receiver operating characteristic curves was computed. This meta-analysis ultimately included 21 studies enrolling 879 patients with 888 lesions. Cerebral blood volume-associated diagnostic results were reported in 20 of the analyzed studies, and the respective pooled sensitivity, specificity, PLR, and NLR values were 86% (95% confidence interval [CI], 0.81-0.89), 83% (95% CI, 0.77-0.87), 4.94 (95% CI, 3.61-6.75), and 0.18 (95% CI, 0.13-0.23) for these 20 studies. The corresponding AUC value was 0.91 (95% CI, 0.88-0.93), and the publication bias risk was low (P = 0.976). Cerebral blood flow-related diagnostic results were additionally reported in 6 of the analyzed studies, with respective pooled sensitivity, specificity, PLR, and NLR values of 85% (95% CI, 0.78-0.90), 85% (95% CI, 0.76-0.91), 5.54 (95% CI, 3.40-9.01), and 0.18 (95% CI, 0.12-0.26). The corresponding AUC value was 0.92 (95% CI, 0.89-0.94), and the publication bias risk was low (P = 0.373). The present meta-analysis results suggest that dynamic susceptibility contrast-enhanced perfusion-weighted imaging represents an effective diagnostic approach to distinguishing between PsP and RT in high-grade glioma patients.


Suppressive effects of electrochemically reduced water on matrix metalloproteinase-2 activities and in vitro invasion of human fibrosarcoma HT1080 cells.
It has been demonstrated that hydrogen peroxide (H(2)O(2)) is directly associated with elevated matrix metalloproteinase-2 (MMP-2) expression in several cell lines. Electrochemically reduced water (ERW), produced near the cathode during electrolysis, and scavenges intracellular H(2)O(2) in human fibrosarcoma HT1080 cells. RT-PCR and zymography analyses revealed that when HT1080 cells were treated with ERW, the gene expression of MMP-2 and membrane type 1 MMP and activation of MMP-2 was repressed, resulting in decreased invasion of the cells into matrigel. ERW also inhibited H(2)O(2)-induced MMP-2 upregulation. To investigate signal transduction involved in MMP-2 downregulation, mitogen-activated protein kinase (MAPK)-specific inhibitors, SB203580 (p38 MAPK inhibitor), PD98059 (MAPK/extracellular regulated kinase kinase 1 inhibitor) and c-Jun NH(2)-terminal kinase inhibitor II, were used to block the MAPK signal cascade. MMP-2 gene expression was only inhibited by SB203580 treatment, suggesting a pivotal role of p38 MAPK in regulation of MMP-2 gene expression. Western blot analysis showed that ERW downregulated the phosphorylation of p38 both in H(2)O(2)-treated and untreated HT1080 cells. These results indicate that the inhibitory effect of ERW on tumor invasion is due to, at least in part, its antioxidative effect.


Characterization of Bacteriophage Peptides of Pathogenic Streptococcus by LC-ESI-MS/MS: Bacteriophage Phylogenomics and Their Relationship to Their Host.
The present work focuses on LC-ESI-MS/MS (liquid chromatography-electrospray ionization-tandem mass spectrometry) analysis of phage-origin tryptic digestion peptides from mastitis-causing Streptococcus spp. isolated from milk. A total of 2,546 non-redundant peptides belonging to 1,890 proteins were identified and analyzed. Among them, 65 phage-origin peptides were determined as specific Streptococcus spp. peptides. These peptides belong to proteins such as phage repressors, phage endopeptidases, structural phage proteins, and uncharacterized phage proteins. Studies involving bacteriophage phylogeny and the relationship between phages encoding the peptides determined and the bacteria they infect were also performed. The results show how specific peptides are present in closely related phages, and a link exists between bacteriophage phylogeny and the Streptococcus spp. they infect. Moreover, the phage peptide M∗ATNLGQAYVQIM∗PSAK is unique and specific for Streptococcus agalactiae. These results revealed that diagnostic peptides, among others, could be useful for the identification and characterization of mastitis-causing Streptococcus spp., particularly peptides that belong to specific functional proteins, such as phage-origin proteins, because of their specificity to bacterial hosts.


Stunting, wasting and breast-feeding as correlates of body composition in Cambodian children at 6 and 15 months of age.
The study aimed at assessing stunting, wasting and breast-feeding as correlates of body composition in Cambodian children. As part of a nutrition trial (ISRCTN19918531), fat mass (FM) and fat-free mass (FFM) were measured using 2H dilution at 6 and 15 months of age. Of 419 infants enrolled, 98 % were breastfed, 15 % stunted and 4 % wasted at 6 months. At 15 months, 78 % were breastfed, 24 % stunted and 11 % wasted. Those not breastfed had lower FMI at 6 months but not at 15 months. Stunted children had lower FM at 6 months and lower FFM at 6 and 15 months compared with children with length-for-age z ≥0. Stunting was not associated with height-adjusted indexes fat mass index (FMI) or fat-free mass index (FFMI). Wasted children had lower FM, FFM, FMI and FFMI at 6 and 15 months compared with children with weight-for-length z (WLZ) ≥0. Generally, FFM and FFMI deficits increased with age, whereas FM and FMI deficits decreased, reflecting interactions between age and WLZ. For example, the FFM deficits were -0·99 (95 % CI -1·26, -0·72) kg at 6 months and -1·44 (95 % CI -1·69; -1·19) kg at 15 months (interaction, P<0·05), while the FMI deficits were -2·12 (95 % CI -2·53, -1·72) kg/m2 at 6 months and -1·32 (95 % CI -1·77, -0·87) kg/m2 at 15 months (interaction, P<0·05). This indicates that undernourished children preserve body fat at the detriment of fat-free tissue, which may have long-term consequences for health and working capacity.


Mg-supplementation attenuated lipogenic and oxidative/nitrosative gene expression caused by Combination Antiretroviral Therapy (cART) in HIV-1-transgenic rats.
We determined if HIV-1 expression in transgenic (HIV-1-Tg) rats enhanced hepatic genomic changes related to oxidative/nitrosative stress and lipogenesis during cART-treatment, and assessed effects of Mg-supplementation. A clinically used cART (atazanavir-ritonavir+Truvada) was given orally to control and HIV-1-Tg rats (18 weeks) with normal or 6-fold dietary-Mg. Oxidative/nitrosative and lipogenic genes were determined by real-time RT-PCR. cART induced a 4-fold upregulation of sterol regulatory element-binding protein-1 (SREBP-1) in HIV-1-Tg-rats, but not in controls; Tg rats displayed a 2.5-fold higher expression. Both were completely prevented by Mg-supplementation. Nrf2 (Nuclear erythroid-derived factor 2), a master transcription factor controlling redox homeostasis, was down-regulated 50% in HIV-Tg rats, and reduced further to 25% in Tg+cART-rats. Two downstream antioxidant genes, heme oxygenase-1(HmOX1) and Glutathione-S-transferase(GST), were elevated in HIV-Tg alone but were suppressed by cART treatment. Decreased Nrf2 in Tg±cART were normalized by Mg-supplementation along with the reversal of altered HmOX1 and GST expression. Concomitantly, iNOS (inducible nitric oxide synthase) was upregulated 2-fold in Tg+cART rats, which was reversed by Mg-supplementation. In parallel, cART-treatment led to substantial increases in plasma 8-isoprostane, nitrotyrosine, and RBC-GSSG (oxidized glutathione) levels in HIV-1-Tg rats; all indices of oxidative/nitrosative stress were suppressed by Mg-supplementation. Both plasma triglyceride and cholesterol levels were elevated in Tg+cART rats, but were lowered by Mg-supplementation. Thus, the synergistic effects of cART and HIV-1 expression on lipogenic and oxidative/nitrosative effects were revealed at the genomic and biochemical levels. Down-regulation of Nrf2 in the Tg+cART rats suggested their antioxidant response was severely compromised; these abnormal metabolic and oxidative stress effects were effectively attenuated by Mg-supplementation at the genomic level.


An analysis of telephone interview data collected in 1992 from 820 women who reported problems with their breast implants to the food and drug administration.
How health care providers deal with concerns and feelings of women who have problems with their breast implants affects the women's satisfaction with their breast implants, yet in 1992 little was known about the concerns and feelings of these women. A qualitative analysis of in-depth telephone interviews conducted in 1992 with 820 women from all regions of the United States who reported problems with their breast implants to the Food and Drug Administration and responded to an invitation to be interviewed provided data. Respondents were primarily 40 to 69 years of age at the time of interview, Caucasian, married, and educated beyond high school. The sample was almost equally divided in reason for breast implants, with 65 percent being dissatisfied with their breast implants. Nearly all of the women had heard of problems with silicone gel-filled implants. Their main sources of information were television, newspapers, and magazines rather than their physicians or the breast implant manufacturers. Some women tried to avoid hearing the reports, and many tried to put the reported problems out of their minds. However, a majority (88.7 percent) wanted more information. The women expressed feelings of anger, regret, and worry, and repeatedly said they needed more information. Women who contacted the Food and Drug Administration about breast implant problems needed accurate and honest information from health care professionals. They wanted their physicians to explore their symptoms, fears, and concerns.


ED visits, hospital admissions and treatment breaks in head/neck cancer patients undergoing radiotherapy.
Radiation therapy (RT) is an integral part of treatment of head/neck cancer (HNC) but is associated with many toxicities. We sought to evaluate sociodemographic, pathologic, and clinical factors associated with emergency department (ED) visits, hospital admissions (HA), and RT breaks in HNC patients undergoing curative-intent RT. We completed a Level 3 (Oxford criteria for evidence-based medicine) analysis of a cohort of HNC patients who underwent curative-intent RT at our institution from 2013 to 2017. We collected demographic characteristics and retrospectively assessed for heavy opioid use, ED visits or HA during RT as well as RT breaks. Treatment breaks were defined as total days to RT fractions ratio ≥1.6. Multivariable stepwise logistic regression analyses were done to determine the association of various sociodemographic, pathologic, and clinical characteristics with ED visits, HA and RT treatment breaks. The cohort included 376 HNC patients (294 male, 82 female, median age 61). On multivariable analysis, significant factors associated with ED visits during RT were heavy opioid use and black race. Receipt of concomitant chemotherapy was the only factor associated with hospital admissions during RT. Advanced age, lower socioeconomic class, glandular site, and receipt of chemotherapy were all independently associated with RT breaks. Lower cancer stage and lack of substance abuse history were independently associated with lack of treatment breaks. HNC patients with factors such as heavy opioid use, Black race, receipt of concomitant chemotherapy, and lower socioeconomic class may require closer monitoring during RT.


GIMAP5 Deficiency Is Associated with Increased AKT Activity in T Lymphocytes.
Long-term survival of T lymphocytes in quiescent state is essential to maintain their cell numbers in secondary lymphoid organs. In mice and in rats, the loss of functional GTPase of the immune associated nucleotide binding protein 5 (GIMAP5) causes peripheral T lymphopenia due to spontaneous death of T cells. The underlying mechanism responsible for the disruption of quiescence in Gimap5 deficient T cells remains largely unknown. In this study, we show that loss of functional Gimap5 results in increased basal activation of mammalian target of rapamycin (mTOR), independent of protein phosphatase 2A (PP2A) or AMP-activated protein kinase (AMPK). Our results suggest that the constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway may be one of the consequences of the absence of functional GIMAP5.


Reliability of radioisotope-guided sentinel lymph node biopsy in penile cancer: verification in consideration of the European guidelines.
Lymph node (LN) staging in penile cancer has strong prognostic implications. This contrasts with the high morbidity of extended inguinal LN dissection (LND) or over-treatment of many patients. Therefore, inguinal dynamic sentinel node biopsy (DSNB) or modified LND is recommended by the European Association of Urology (EAU) guidelines to evaluate the nodal status of patients with clinically node-negative penile cancer. This study analyzed the reliability and morbidity of radioguided DSNB in penile cancer under consideration of the current EAU recommendations in an experienced center with long-term follow-up. Thirty-four patients who received primary surgery and had radioguided inguinal DSNB for penile cancer (≥ T1G2) were included (July 2004 to July 2013). Preoperative sentinel LN (SLN) mapping was performed using lymphoscintigraphy after peritumoral injection of (99m)Technetium nanocolloid on the day of surgery. During surgery, SLNs were detected using a gamma probe. According to the EAU guidelines, a secondary ipsilateral radical inguinal LND was performed in patients who had positive SLNs. The false-negative and complication rates of DSNB were assessed. A total of 32 patients were analyzed. Two patients were lost to follow-up. A total of 166 SLNs (median, 5; range, 1-15) were removed and 216 LNs (SLNs + non-SLNs; median, 6; range, 2-19) were dissected. LN metastases were found in five of the 32 (15.6 %) patients and nine of the 166 (5.4 %) SLNs were found to contain metastases. None of the remaining 50 non-SLNs contained metastases. In only one of the five SLN-positive patients, a singular further metastasis was detected by secondary radical inguinal LND. During follow-up (median, 30.5; range, 5-95 months) no inguinal nodal recurrence was detected. DSNB-related complications occurred in 11.1 % of explored groins. Radioguided DSNB is a suitable procedure for LN staging in penile cancer considering the EAU recommendations and with the required experience. Under these circumstances, patients can be spared from higher morbidity without compromising the detection of LN metastases or therapeutic implications. Improvement of the methodology used to perform DSNB should be developed further to decrease the risk of missing LN metastases and to simplify the procedure.


Barriers to healthcare and a 'triple empathy problem' may lead to adverse outcomes for autistic adults: A qualitative study.
Autistic people live with more mental and physical health conditions and, on average, die younger than non-autistic people. Despite widespread commitments to tackling these issues, autistic people still report various barriers to accessing healthcare. This article aims to explore the area in depth, from the perspective of autistic people. This research benefits from being led by autistic people, for autistic people - all of the researchers are autistic, and most of us are also medical doctors. Data, in the form of written comments and stories, were collected as part of a large survey. Here, we explored these for common themes and possible deeper meaning within the experiences. People who took part reported a variety of barriers. Here, our article gives voice to their stories, in their own words. Themes included: early barriers; communication mismatch; doubt - in oneself and from doctors; helplessness and fear; and healthcare avoidance and adverse health outcomes. Our findings allowed us to create a model that aimed to understand and explain the reported barriers in the context of the previously known consequences. We also built on wider autism theories to explain our findings in more depth.


Systemic transduction of p16INK4a antitumor peptide inhibits lung metastasis of the MBT-2 bladder tumor cell line in mice.
p16INK4a (p16) is a key molecule in bladder tumor (BT) development. We previously reported that a p16 antitumor peptide inhibited the growth of subcutaneous BT grafts in mice through restoration of p16 function using a Wr-T peptide transporter system. In the present study, the efficacy of mouse p16 peptide administration in a mouse lung metastasis model for BT and also the toxicity of peptides by cardiac peptide injection were evaluated. Mouse lung metastases were developed by tail vein injection of a p16-deficient MBT-2 cell line. Six-week-old C3H/He female mice were divided into three groups: A control group (n=12) receiving no treatment; a group treated once on the 3rd experimental day (n=12); and a group treated three times on the 3rd, 5th and 7th experimental days (n=10) with an injection of a mixture of 80 nmol mouse p16 peptide and 50 nmol Wr-T into the tail vein. At the 14th experimental day, the lung metastases were histologically evaluated. Lung metastases were observed in 100% (12/12), 41.7% (5/12) and 30% (3/10) of the aforementioned three groups, respectively. The number and area of metastatic lung tumors were significantly different between control and treatment groups (control vs. triple treatment group for the number and area, P=0.0029 and P=0.0296, respectively). Immunohistochemistry demonstrated that phosphorylated retinoblastoma (Rb) protein was decreased in lung tumors of the treatment groups, compared with the control group. The toxicity of p16 peptide transduction was evaluated by using low-dose treatment (three dosages) and high-dose treatment (two dosages) on three male and three female C3H/He mice in early and late experimental phases. In low and high dose groups, no notable change was determined in body weight or blood analyses in early or late phases following mouse p16 peptide administration. In addition, no notable change was observed histologically in bone marrow of treatment groups. To conclude, systemic p16 peptide administration decreased lung tumor development in a mouse metastatic BT model without severe adverse events, as assessed by blood analyses and histological evaluation.


Complementary and alternative medicine in pediatrics in Turkey.
Complementary and alternative medicine (CAM) is applied both to children and adults widely throughout the world. A previous pan-European survey showed a surprisingly high CAM-use in Turkish children. This review aimed to survey information on the use of CAM in pediatrics in Turkey. A narrative, non-systematic review was conducted by melding expert opinions with a thorough and balanced review of available evidence. An unrestricted literature search using the key words, "alternative", "complementary", "integrative", "prevalence" and "pediatric" or "children" and "Turkey" was performed by internet search in March, 2012 using PubMed and Google Scholar. CAM use was examined in general pediatrics, pediatric oncology, patients with asthma, and patients with diabetes. A frequency of CAM use was 87% in Turkish pediatric patients, with a mean of 60%. The primary sources of information about CAM are family and friends. Communication with patients/parents and health care professionals showed that most parents do not speak about CAM use with their physicians or nurses. CAM is extensively used in Turkish pediatric patients. This might be due to Turkey's status as a developing country in which a traditional medical system still dominates in comparison to developed countries. Thus, larger studies are required to prove an extensive use of CAM in Turkey, as this review article does not have the capacity for in-depth analysis. Knowledge about CAM and its related topics is essential for physicians and nurses in order to meet the patients' wish for a competent consultation concerning all aspects of a possible therapy.


Chemoembolization alone vs combined chemoembolization and hepatic arterial infusion chemotherapy in inoperable hepatocellular carcinoma patients.
To compare the efficacy and safety of chemoembolization alone or chemoembolization combined with hepatic arterial infusion chemotherapy (HAIC), including oxaliplatin (OXA), 5-fluorouracil (5-FU) and folinic acid (CF), in inoperable hepatocellular carcinoma (HCC) without distant metastasis. Eighty-four inoperable HCC patients were enrolled. Thirty-nine patients underwent chemoembolization alone, and the other 45 patients underwent chemoembolization + HAIC (OXA/5-FU/CF) treatment non-randomly. The progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse reactions were compared between the two groups. A significant difference in the ORR was observed between the chemoembolization alone and chemoembolization + HAIC groups. There was no statistically significant difference in DCR between the two groups. The median PFS (mPFS) showed a significant difference between the two groups. For patients with BCLC stage A/B disease, with or without vessel invasion, the chemoembolization + HAIC group showed better mPFS when compared to chemoembolization alone, but no significant difference was found in patients with BCLC stage C disease. The parameter of pain (grade III-IV) in the chemoembolization + HAIC group was increased statistically. Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more effective than chemoembolization alone for inoperable HCC patients without distant metastasis.


Cytoplasmic antineutrophil cytoplasmic antibody positive pauci-immune glomerulonephritis associated with infectious endocarditis.
Renal deterioration often occurs in cases of infectious endocarditis (IE), but, IE- associated nephritis with rapidly progressive glomerulonephritis (RPGN) is rare. Patients with severe infection (e.g., IE) sometimes show positivity for cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA). Therefore, diagnosis and treatment are very difficult in cases of RPGN with IE and positivity for C-ANCA. Such cases are rare, only 12 have been reported in the English literature. Herein, we describe the case of a 50-year-old man who presented with RPGN with IE and tested positively for C-ANCA. He was referred to our hospital because of leg edema, purpura and renal dysfunction. Laboratory tests revealed serum creatinine elevation and positivity for C-ANCA and proteinase 3-specific (PR3)-ANCA. RPGN and acute renal failure were diagnosed. Hemodialysis and steroid therapy were started. Streptococcus oralis was isolated by blood culture. Transthoracic echocardiography revealed grade III mitral valve insufficiency with two vegetations. Therefore, IE was diagnosed. The steroid therapy was stopped, and antibiotic therapy was begun. Because there was no improvement, surgical therapy was performed. The operation was successful, but the patient died of brain hemorrhage. Our experience in this case indicates C/PR3-ANCA positive RPGN must be ruled out in patients with infectious disease, particularly IE, together with renal symptoms, and renal biopsy should be performed.


Immunoblotting of plasma in a pregnant patient with hereditary angioedema.
Hereditary angioedema (HAE), an autosomal disorder caused by a deficiency of C1 inhibitor, is characterized by attacks of localized swelling, laryngeal edema, or abdominal pain. Plasma samples from one pregnant patient were studied serially by functional and quantitative immunochemical assays as well as immunoblot assays for high molecular weight kininogen (HMWK) and/or prekallikrein/kallikrein (PK/K). An immunoblot of this patient's HMWK from plasma obtained before she became pregnant and when she was well revealed that it was mostly an intact protein of 120 kd, similar to immunoblot results of normal plasma HMWK. In plasma samples taken throughout her pregnancy, before, during, and after clinical attacks of angioedema, all of her plasma HMWK was shown to be cleaved into the 45 kd light chain form. After delivery of the infant the 120 kd form of intact plasma HMWK returned to her plasma. In comparison, immunoblot studies on 21 normal and abnormal pregnancies revealed that plasma HMWK was an intact protein at 120 kd. That this patient's plasma during her pregnancy was contact activated was determined by additional immunoblot studies for PK/K. Immunoblot assay for plasma PK/K revealed kallikrein-alpha 2-macroglobulin complexes and a 50 kd PK/K form seen only in activated plasma samples. The findings of kallikrein-alpha 2-macroglobulin complexes and a 50 kd PK/K form disappeared after delivery. These combined studies on this patient show that the structures of HMWK and prekallikrein as indicated by immunoblot assays were altered during pregnancy. Immunoblot assays for detection of changes in the structure of HMWK and prekallikrein may be objective laboratory studies for documenting clinical attacks of hereditary angioedema, their onset, and their resolution.


Respiratory movement of the pancreas: an ultrasonic study.
Respiratory movement of the pancreas was documented ultrasonically in 36 normal patients and volunteers. Pancreatic excursion from full inspiration to full expiration was measured in the plane of the superior mesenteric artery in supine, prone, and decubitus positions. Excursions ranged from 0 to 3.5 cm. The average respiratory excursion was 1.8 cm in the supine position, 1.9 cm when prone, and 2.2 cm in the lateral decubitus position. Such respiratory movement of the pancreas has obvious implications both for static B-mode ultrasound scanning and for CT scanning.


HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation.
The HOX homeodomain proteins are fundamental regulators of organ and tissue development, where they are thought to function as transcription factors, and HOX gene expression has been associated with numerous types of cancers. Previous studies have demonstrated that enforced expression of the HOXB4 protein transforms cultured fibroblasts and leads to a selective expansion of the hematopoietic stem cell pool, suggesting that this protein might play a role in cellular proliferation. In support of this concept, we now show that enforced expression of HOXB4 in human neonatal keratinocytes results in increased cellular proliferation and colony formation as well as decreased expression of the alpha-2-integrin and CD44 cell surface adhesion molecules. We previously have reported HOXB4 gene expression in the basal and suprabasal layers of developing human skin and now show extensive HOXB4 mRNA in psoriatic skin and basal cell carcinoma. In fetal human skin HOXB4 protein expression was both nuclear and cytoplasmic within epidermal basal cells and in hair follicle inner and outer root sheath cells, whereas strong nuclear signals were observed in the bulge region. In adult skin, HOXB4 protein expression was both nuclear and cytoplasmic, but was predominantly localized to the intermediate and differentiated cell layers. In contrast to the striking gradient patterns of HOX gene and protein expression previously described in developing spinal cord and limb, HOXB4 protein was uniformly detected in all regions of the fetal and adult skin. Although little HOXB4 signal localized to proliferative cell layers, as marked by proliferating cell nuclear antigen (PCNA) staining, in normal adult epidermis, nuclear HOXB4 protein expression substantially overlapped with PCNA-positive cell in a series of samples of hyperproliferative skin. Taken together, these data suggest that nuclear HOXB4 protein may play a role in the regulation of cellular proliferation/adhesion in developing fetal human epidermis and in hyperproliferation conditions, including cancers, in adult epidermis. Published 2002 Wiley-Liss, Inc.


Loadability and Releasing Profiles In Vitro and Pharmacokinetics In Vivo of Vinorelbine and Raltitrexed by CalliSpheres Beads.
Background: This study investigated the loadability and releasing profiles of vinorelbine and raltitrexed from CalliSpheres® Beads (CB) in vitro, and further explored the pharmacokinetic features of vinorelbine and raltitrexed eluting CB in vivo. Materials and Methods: Ten milligrams vinorelbine and 0.2 mg raltitrexed were mixed with 0.15 g CB at two sizes (100-300 and 300-500 μm) for 24 h, respectively, to measure the loadability. Then vinorelbine/raltitrexed loading CBs were placed in 20% phosphate-buffered saline for 24 h to measure the release profiles. Transcatheter arterial chemoembolization (TACE) with 1 mg vinorelbine eluting CBs (two sizes respectively) and transcatheter arterial hepatic infusion (TAI) with 1 mg vinorelbine were performed in 9 rabbits (3 rabbits in each group). The above experiments were repeated with 0.2 mg raltitrexed. Results: Vinorelbine loading efficiency quickly reached 90% within 10 min with maximum loadability >90% by CB with both two sizes, and vinorelbine release rate gradually increased to ∼100% within 1 h. Raltitrexed loading efficiency gradually increased to >40% within 15 min, then slowly increased to >60% within 24 h, with maximum loadability <70% by CB with both sizes, and raltitrexed release rate gradually increased to >90% within 1 h. Besides, vinorelbine/raltitrexed eluting CB showed greatly decreased maximum serum concentration (Cmax) of the drug compared with TAI in rabbits with similar area under the curve (0-t), mean residence time (0-t), and half-time (T1/2). Conclusion: CB exhibits good loadability and an acceptable releasing profile for eluting vinorelbine and raltitrexed, and shows lower Cmax and numerically stable concentration than TAI.


[In vitro fertilization: a comparison with results of the hamster ova penetration test (HOPT)].
The hamster ova penetration test (HOPT) was performed in 82 patients simultaneously with in vitro fertilization of homologous oocytes (IVF). A penetration rate of greater than 20% of inseminated ova was considered to represent a positive test result. The results of HOPT correlated completely with the IVF in all couples with male factor sterility. In couples with female sterility only and in couples with a combination of female and male factors HOPT was falsely negative in 22 and 20% respectively. Despite a negative HOPT in vitro fertilization with formation of two pronuclei 12 to 18 hours after insemination occurred in these patients. Obviously, the interpretation of HOPT is dependent upon the definition of the cut-off point (in our case 20%). Our results support the opinion that there should be no exclusion from an IVF programme based only on a negative HOPT. It appears that any penetration rate greater than 0% should be considered as a sign of potential fertility.


Seropositivity of neurotropic infectious agents in first-episode schizophrenia patients and the relationship with positive and negative symptoms.
According to the neurodevelopmental model, schizophrenia is a disorder that occurs as a result of different etiologic factors during brain development, including viral infections. However, it is unclear whether these infections are related to the disease or whether they affect the symptom pattern. We investigated the presence of four herpes viruses (EBV, CMV, HSV-1 and HSV-2) in first-episode schizophrenia patients and compared seropositive with seronegative patients and healthy volunteers to reveal the etiological role of viral agents on schizophrenia symptoms. Ninety-two first-episode patients who met the DSM-IV diagnostic criteria for schizophreniform disorder were included the study, along with 88 healthy volunteers. The presence of the four herpes viruses was investigated with serological methods (ELISA) in both groups. Positive and negative symptoms were evaluated with Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). There was no difference between the patient and control groups in terms of seropositivity of the four viruses. We found that SANS scores of HSV-1 and CMV seropositive schizophrenia patients were significantly higher than the scores of patients with seronegative schizophrenia. No difference was found in SAPS scores. The results suggest a role of HSV and CMV infections in negative symptoms. This supports the hypothesis that viruses do not directly give rise to schizophrenia, but patients who were previously been infected with these viral agents may be prone to schizophrenia, and some of the symptom patterns may be related to different agents.


Allocation of attention to the eye and mouth region of faces in schizophrenia patients.
The present study examined whether reduced attentiveness to facial features and biased weighting of attention to the eye and mouth region might explain deficits in face processing in schizophrenia. Healthy controls (n=21) and schizophrenia patients (n=28) from an African Xhosa population were asked to detect target stimuli (dots) superimposed on pictures of faces. General attentiveness to facial features was assessed by measuring overall reaction times to targets superimposed on feature areas of faces and attentiveness to the eye versus mouth region by comparing reaction times to targets on the upper and lower parts of faces. Patients exhibited generally slower target detection speed than comparison subjects but the strength of the attentional bias towards the eyes did not differ between groups (i.e., the reaction time gain for targets in the eye region). A regression analysis indicated, however, that generally slower target detection speed and an attentional bias away from the mouth predicted a deficit in the recognition of open-mouth angry facial expressions in schizophrenia patients. The results give partial support for hypothesis that reduced overall attentiveness to faces and a failure to utilise visual information in salient facial features may underlie affect processing deficits in schizophrenia.


[Comparative effect of anti-anginal drugs on myocardial ischemia in patient with effort angina: evaluation by ambulatory electrocardiographic monitoring].
The purpose of this study was to compare the efficacy of three standard antianginal agents, nitrate, Ca antagonist, and beta blocker on myocardial ischemia in patients with effort angina (EA) using ambulatory electrocardiographic monitoring (AEM). Forty-three patients, mean age 57 +/- 11 years, with positive exercise tests were studied. AEM was performed for 24-hours, initially with the patients off all antianginal medication and then after 1-2 weeks treatment with each agent. Antianginal drugs used were long-acting isosorbide dinitrate 40-80 mg/day for nitrate (17 patients), diltiazem 90-180 mg/day for Ca antagonist (13 patients), and propranolol 30-60 mg/day or metoprolol 60-120 mg/day for beta blocker (13 patients). The following results were obtained: 1) The severity of ischemia (total magnitude and duration of ST depression) was improved with each three agent. 2) Although the number of total ischemic episodes was reduced significantly with each three agent, the number of asymptomatic episodes was reduced significantly only with beta blocker. 3) Circadian variation of ischemic episodes displayed a pattern with a peak frequency in daytime. In addition, nitrate and Ca antagonist did not reduce ischemic episodes in daytime (especially asymptomatic episodes), while beta blocker reduced both symptomatic and asymptomatic episodes in daytime resulting in change in the pattern of circadian variation of ischemia. Thus, it was concluded that beta blocker was the most effective means of reducing myocardial ischemia, including silent ischemia, in patients with EA.


Incidence, clinical spectrum, and immunotherapy of non-ischemic cerebral enhancing lesions after endovascular therapy.
Symptomatic and asymptomatic delayed non-ischemic cerebral enhancing (NICE) lesions in magnetic resonance imaging (MRI) have been reported as a rare complication after endovascular therapy (EVT) in recent years with incidence rates between 0.05% and 0.9% in most studies. Information on long-term clinical course and immunotherapies is scarce or has not been reported in detail in the literature. Objective: Aims of our study were to assess the incidence of NICE lesions in patients after cerebral EVT over a period of more than 12 years, describe clinical and EVT characteristics, and immunotherapies applied. A retrospective chart review of all patients treated by endovascular therapy for symptomatic or asymptomatic aneurysms at the University Hospital of Augsburg from May 1, 2008 to December 31, 2020 was performed. Patients were identified retrospectively and followed-up prospectively where appropriate. In addition, one case treated at another institution was included. Five out of 746 patients, 0.67%, developed NICE lesions after EVT, all with non-ruptured aneurysms and all symptomatic upon detection of NICE lesions by MRI. In total, the disease course of 6 female patients is reported. Symptoms occurred after a mean time of 15 days (±13.42, SD) after EVT with headache (6/6 patients), focal neurological signs (6/6 patients), epileptic seizures (2/6 patients) and cognitive deficits (3/6 patients). All 6 patients received glucocorticosteroids (GCS), 1/6 azathioprine (AZA), 4/6 mycophenolate mofetil (MMF), 1/6 methotrexate (MTX), 1/6 rituximab (RTX), 2/6 cyclophosphamide (CYC) and 3/6 tocilizumab (TCZ). A treatment response could be observed for GCS, TCZ and MMF (in two of four cases), RTX and AZA did not result in disease stabilization. Delayed NICE lesions are a rare complication after EVT, requiring immunotherapies in all patients reported here. Physicians should be aware of this disorder in case of new symptoms or contrast enhancing lesions after EVT.


Epidemiology of cancer of the cervix in greater Bombay.
An attempt has been made to study in depth the cervical cancer problem in Greater Bombay by undertaking epidemiological investigations to identify its aetiology, by utilising the data collected by the Bombay Cancer Registry. Although cancer of the uterine cervix is found to occur at all ages in Bombay, it is mainly seen during middle age. Its incidence is highest in the Hindu community and lowest in the Parsi. This neoplasm appears to have a strong association with the degree of sexual activity. Thus it is rarely seen in nuns , and commonly found in women who have had multiple sexual partners. There is also a relative preponderance in the poorer, uneducated section of the community. In order to identify the high-risk groups, a retrospective study was undertaken of proven cases of cancer of the uterine cervix. The results were compared with those of similar controls, equal in number and closely matched for age, religion, and income, in order to examine the risk factors of possible aetiological importance in women with cervical cancer. We have sought to estimate the effects of parity, the age at first marriage and at first delivery. The highest risk was observed in women who had had multiple pregnancies early in life. It is interesting to note that multiparity seems to be an important risk factor in Bombay women, in contrast to the Western experience.


A solution and practice for combining multi-source heterogeneous data to construct enterprise knowledge graph.
The knowledge graph is one of the essential infrastructures of artificial intelligence. It is a challenge for knowledge engineering to construct a high-quality domain knowledge graph for multi-source heterogeneous data. We propose a complete process framework for constructing a knowledge graph that combines structured data and unstructured data, which includes data processing, information extraction, knowledge fusion, data storage, and update strategies, aiming to improve the quality of the knowledge graph and extend its life cycle. Specifically, we take the construction process of an enterprise knowledge graph as an example and integrate enterprise register information, litigation-related information, and enterprise announcement information to enrich the enterprise knowledge graph. For the unstructured text, we improve existing model to extract triples and the F1-score of our model reached 72.77%. The number of nodes and edges in our constructed enterprise knowledge graph reaches 1,430,000 and 3,170,000, respectively. Furthermore, for each type of multi-source heterogeneous data, we apply corresponding methods and strategies for information extraction and data storage and carry out a detailed comparative analysis of graph databases. From the perspective of practical use, the informative enterprise knowledge graph and its timely update can serve many actual business needs. Our proposed enterprise knowledge graph has been deployed in HuaRong RongTong (Beijing) Technology Co., Ltd. and is used by the staff as a powerful tool for corporate due diligence. The key features are reported and analyzed in the case study. Overall, this paper provides an easy-to-follow solution and practice for domain knowledge graph construction, as well as demonstrating its application in corporate due diligence.


Five-Year Followup Results of a Prospective, Multicenter Study of Patients with Overactive Bladder Treated with Sacral Neuromodulation.
We evaluated the therapeutic success rate, changes in quality of life and safety of sacral neuromodulation 5 years after InterStim™ implantation. Included in study were subjects with bothersome symptoms of overactive bladder, including urinary urge incontinence and/or urgency-frequency, in whom at least 1 anticholinergic medication failed and 1 medication had not been tried. Therapeutic success was defined as a urinary urge incontinence or urgency-frequency response of 50% or greater improvement in average leaks or voids per day, or return to normal voiding, defined as fewer than 8 voids per day. Quality of life was evaluated by ICIQ-OABqol (International Consultation on Incontinence Modular Questionnaire). Safety was evaluated through adverse events. Of the 340 subjects who completed the test stimulation 272 had an implant, of whom 91% were female. Mean age was 57 years. At baseline 202 subjects with urinary urge incontinence had a mean ± SD of 3.1 ± 2.7 leaks per day and 189 with urgency-frequency had a mean of 12.6 ± 4.5 voids per day. The 5-year therapeutic success rate was 67% (95% CI 60-74) using modified completers analysis and 82% (95% CI 76-88) using completers analysis. Subjects with urinary urge incontinence had a mean reduction from baseline of 2.0 ± 2.2 leaks per day and subjects with urgency-frequency had a mean reduction of 5.4 ± 4.3 voids per day (each completers analysis p <0.0001). Subjects showed improvement in all ICIQ-OABqol measures (p <0.0001). The most common device related adverse events were an undesirable change in stimulation in 60 of the 272 subjects (22%), implant site pain in 40 (15%) and therapeutic product ineffectiveness in 36 (13%). This multicenter study shows that sacral neuromodulation had sustained efficacy and quality of life improvements, and an acceptable safety profile through 5 years in subjects with overactive bladder.


[Neoadjuvant chemotherapy for colon cancer based on evidence-based medicine].
The incidence of colon cancer has been increasing in recent years with the improvement in living standard, and becomes one of the leading causes of cancer-related death. While radical surgery remains the primary choice for colon cancer, neoadjuvant chemotherapy has significantly improved the successful rate of surgery and increased postoperative survival. In addition to traditional chemotherapy with 5-Fu or oxliplatin, molecular targeted drugs lead to a higher response rate and show its dramatic effect on disease-recurrence time. However some side effects such as disease progression during chemotherapy, bleeding or liver toxicity should be concerned. In addition, indications for neoadjuvant chemotherapy do not reach a consensus. In the future, these controversies may be solved based on some large randomized controlled trials.


[The effect of nitrous oxide on middle ear pressure in secretory otitis media in children].
The preliminary results of the nitrous oxide application during children anesthesia with secretory otitis media was presented. The different otological operations in which nitrous oxide is contraindicated were mentioned. The nitrous oxide influence on the middle ear pressure increase was emphasized. It was confirmed by tympanograms. Necessity of the further investigations in this subject were emphasized due to encouraging results.


In-Hospital Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Octogenarians.
Background Octogenarians have low physiologic reserve and may benefit more from transcatheter aortic valve replacement ( TAVR ) than surgical aortic valve replacement ( SAVR ). Methods and Results This retrospective cohort study based on the National Inpatient Sample included octogenarians who underwent TAVR or SAVR from 2012 to 2015. Crude and standardized-morbidity-ratio-weighted regression models were used to compare in-hospital outcomes. Among 19 145 TAVR and 9815 SAVR hospitalizations, TAVR patients had higher Charlson Comorbidity Index ( CCI ) scores (2.0 versus 0.8, P<0.0001) than SAVR patients. Before weighting, TAVR was associated with significantly shorter length of stay, more home discharges, and lower incidences of acute kidney injury, bleeding, and cardiogenic shock. Associations were consistent across Charlson Comorbidity Index, except for TAVR being associated with greater length of stay reductions among patients with Charlson Comorbidity Index ≥2, compared with Charlson Comorbidity Index <2 (change in estimate -3.56 versus -2.61 days, P=0.004). After weighting, TAVR patients had significantly shorter length of stay (change in estimate -3.29 days, 95% CI -3.82, -2.75) and lower odds of transfer to skilled nursing facility (odds ratio 0.34, 95% CI 0.29, 0.41), acute kidney injury (odds ratio 0.55, 95% CI 0.45, 0.68), bleeding (odds ratio 0.44, 95% CI 0.37, 0.53), and cardiogenic shock (odds ratio 0.55, 95% CI 0.33, 0.92), compared with SAVR patients. Odds of permanent pacemaker implantation, transient ischemic attack/stroke, vascular complications, and in-hospital mortality were not significantly different. Conclusions TAVR may be preferred over SAVR in high-risk octogenarians because of shorter length of stay, better discharge disposition, and less acute kidney injury, and bleeding. All octogenarians may benefit more from TAVR , irrespective of comorbidity burden, but additional research is needed to confirm our findings.


Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats.
Xian-ling-gu-bao (XLGB) is a well-known patented traditional Chinese prescription widely used to treat osteoporosis, osteoarthritis, aseptic bone necrosis, or climacteric syndrome. However, recent reports have suggested that XLGB may cause liver injury in humans. In the present study, we aimed to evaluate the efficacy of XLGB in the prevention of osteoporosis in the zebrafish and ovariectomized (OVX) rats, both of which have been used as osteoporosis models. The safety of XLGB after long-term administration to OVX rats was also assessed. OVX rats were administered by oral gavage 270 mg/kg (recommended daily dose), 1350 mg/kg, and 1800 mg/kg of XLGB for 26 weeks. Bone mineral density, relative bone surface to bone volume, relative bone volume to total volume, trabecular number, mean trabecular thickness, and mean trabecular spacing in OVX rats were examined at the end of the 26-week dosing period. Additionally, OPG and RANKL expression in the femur were determined by western blot and immunohistochemical staining. To evaluate the safety of XLGB, body weight, hematology, serum biochemistry markers related to toxicology, and organ histopathology were determined in each group of OVX rats. Conversely, the zebrafish was treated with prednisolone to induce osteoporosis in the embryo. Disodium etidronate was used as a treatment control. XLGB was shown to be effective in preventing osteoporosis in both the OVX rats and the prednisolone-treated zebrafish. Similarly, XLGB increased OPG protein and decreased RANKL protein in OVX rats. Interestingly, no obvious toxicity was observed in the heart, liver, kidney, small intestine, or stomach at dosages of up to 1800 mg/kg after treating the OVX rats for 26 weeks. XLGB was shown to be very effective in treating osteoporosis in OVX rats. No obvious toxicity or adverse effects developed in OVX rats at dosages up to 1800 mg/kg, which is equivalent to six times the daily-recommended dose. Therefore, XLGB should be considered a good option for the treatment of post-menopausal osteoporosis.


Total Synthesis of (-)-Carinatine A and (+)-Lycopladine A.
An efficient synthesis of two Lycopodium alkaloids, (-)-carinatine A and (+)-lycopladine A, is achieved in eight steps. The synthesis features an intramolecular aldol reaction for assembling the 6,5-fused ring system, a subsequent Tsuji-Trost allylation for generating a quarternary carbon center, and a 6π-electrocyclization to form the pyridine ring.


Hepatocellular carcinoma in HBsAg-negative chronic active hepatitis.
The occurrence of hepatocellular carcinoma in HBsAg-negative chronic active hepatitis is described in two patients. signs of the tumour appeared 18 years and nine years after the first clinical signs of chronic active hepatitis, although in one patients analysis of stored sera showed the serum alpha-fetoprotein levels had been rising over the previous 33 months. Female preponderance in HBsAg-negative chronic active hepatitis may partly account for the rarity of this complication, and the occurrence of hepatocellular carcinoma may also be a reflection of the better survival now being obtained in HBsAg-negative chronic hepatitis.


Parental education on passive smoking in infancy does work.
Passive smoking is harmful to young children. A protocol has been developed to allow health care workers to communicate with parents about preventing passive smoking. The main message was to refrain from smoking in the presence of the child. The aim of the study was to assess the effectiveness of this education programme. The prevalence of smoking in the presence of infants aged 0-10 months was compared before and after the implementation of the education programme. National samples of mothers completed questionnaires in 1996 (n = 1,129) and in 1999 (n = 2,534). Questions were asked about smoking in the living room in the presence of infants, and about parental smoking, and background characteristics. The prevalence of passive infant smoking decreased from 41% to 18%. The adjusted odds ratio for passive infant smoking in 1999 compared to 1996 was 0.34 (0.26-0.44) when none of the parents smoked, 0.19 (0.14-0.27) when one of the parents smoked, and 0.30 (0.20-0.44) when both parents smoked. The implementation of this health education programme seems to have been very successful in reducing passive smoking in children. Implementation of similar health education programmes in other countries is recommended.


Investigations of intermediates appearing in the reassociation of the light-harvesting 1 complex of Rhodospirillum rubrum.
We investigated the temperature-mediated reassociation of the B820 subunit of Rs. rubrum to form a light-harvesting 1 complex (LH 1). By combining several spectroscopic techniques with global spectral data analysis fitting, we present evidence for the occurence of two spectral intermediates that appear during the reassociation process. At high temperatures, halfway the reassociation reaction, a prominent intermediate appears that has an absorption maximum around 850 nm, a fluorescence maximum around 860-867 nm, a high anisotropy (0.3 to 0.4) and a circular dichroism spectrum with three or four bands with alternating signs. At lower temperatures, more towards the end of the reassociation process, a second intermediate tends to appear that has an absorption maximum around 860 nm, a fluorescence maximum around 885 nm, a medium to high anisotropy (0.1 to 0.3) and a circular dichroism spectrum with two bands with alternating signs. The latter circular dichroism spectrum has a blueshifted zero-crossing compared to the spectrum of the LH 1 complex. Both intermediates have the spectroscopic features of a small oligomer. In the Q(y) region, the fluorescence anisotropy of both intermediates slightly increases at longer excitation wavelengths, indicative for energy transfer among the pigments within the intermediate oligomers.


A label-free impedance-based electrochemical sensor based on self-assembled dendritic DNA nanostructures for Pb2+ detection.
Here, a label-free impedance-based electrochemical sensor was developed for the quantitative detection of Pb2+. Using conductive gold nanomaterials as electrode substrate materials can provide sensors with larger specific surface area, action sites and excellent conductivity. DNA nanostructures are used for the determination of biomolecules due to their good properties. The Y-DNA structure is formed by the annealing of three DNA sequences, which acts as a stable structure and forms a dendritic structure in combination with the hybrid chain reaction. In the presence of the target Pb2+, it induces the conversion of specific aptamers into G-quadruplexes, resulting in HCR and Y-DNA loading on the electrodes and a significant change in the impedance value signal. Therefore, the proposed biosensor realizes the quantitative detection of Pb2+. Under the optimal experimental conditions, the concentration of Pb2+ exhibited a linear correlation range from 0.5 to1000 nmol/L with a limit of detection (LOD) of 0.38 nmol/L. The designed sensors have good recoveries in real samples (tap water and tea). This flexible experimental protocol has broad application prospects.


Polymer based dual drug delivery system for targeted treatment of fluoroquinolone resistant Staphylococcus aureus mediated infections.
The present study attempts to treat S. aureus-induced soft skin infections using a combinatorial therapy with an antibiotic, Ciprofloxacin (CIP), and an efflux pump inhibitor 5-Nitro-2-(3-phenylpropoxy) pyridine (5-NPPP) through a smart hydrogel delivery system. The study aims to reduce the increasing rates of infections and antimicrobial resistance; therefore, an efflux pump inhibitor molecule is synthesized and delivered along with an antibiotic to re-sensitize the pathogen towards antibiotics and treat the infections. CIP-loaded polyvinyl alcohol (PVA) hydrogels at varying concentrations were fabricated and optimized by a chemical cross-linking process, which exhibited sustained drug release for 5 days. The compound 5-NPPP loaded hydrogels provided linear drug release for 2 days, necessitating the need for the development of polymeric nanoparticles to alter the release drug pattern. 5-NPPP loaded Eudragit RSPO nanoparticles were prepared by modified nanoprecipitation-solvent evaporation method, which showed optimum average particle size of 230-280 nm with > 90% drug entrapment efficiency. The 5-NPPP polymeric nanoparticles loaded PVA hydrogels were fabricated to provide a predetermined sustained release of the compound to provide a synergistic effect. The selected 7% PVA hydrogels loaded with the dual drugs were evaluated using Balb/c mice models induced with S. aureus soft skin infections. The results of in vivo studies were evidence that the dual drugs loaded hydrogels were non-toxic and reduced the bacterial load causing re-sensitization towards antibiotics, which could initiate re-epithelization. The research concluded that the PVA hydrogels loaded with CIP and 5-NPPP nanoparticles could be an ideal and promising drug delivery system for treating S. aureus-induced skin infections.


Dinor[7]helicene and Beyond: Divergent Synthesis of Chiral Diradicaloids with Variable Open-Shell Character.
Diradicaloid helicenes constructed formally by non-benzenoid double π-extension of phenanthrene were synthesized by a common strategy involving double electrophilic benzannulation. Steric effects in the second benzannulation step led to considerable structural diversity among the products, yielding a symmetrical dinor[7]helicene 1 and two isomeric unsymmetrical double helicenes 2 and 3, containing a nor[5]helicene and [4]helicene fragment, respectively, in addition to a common nor[6]helicene motif. Geometries, configurational dynamics, and electronic structure of these helicenes were analyzed using solid-state structures, spectroscopic methods, and computational analyses. The open-shell character of the singlet states of these helicenes increases in the order 3<1<2, with strongly varying diradicaloid indexes and singlet-triplet gaps. Compounds 1-3 displayed narrow optical gaps of 0.79-1.25 eV, resulting in significant absorption in the near infrared (NIR) region. They also exhibit reversible redox chemistry, each of them yielding stable radical cations, radical anions, and dianions, in some cases possessing intense NIR absorptions extending beyond 2500 nm.


Impacts of land use change on native plant-butterfly interaction networks from central Mexico.
Land use change is a key catalyst of global biodiversity loss and ecosystem degradation. Deforestation and conversion of natural habitats to agricultural or urban areas can profoundly disrupt plant-flower visitor interactions by altering their abundances and distribution. Yet, specific studies analyzing the effects of land use change on the structure of networks of the interactions between particular groups of flower visitors and their plants are still scarce. Here, we aimed to analyze how converting native habitats affects the species composition of butterfly communities and their plants, and whether this, in turn, leads to changes in the structure of interaction networks in the modified habitats. We performed bi-monthly censuses for a year to record plant-butterfly interactions and assess species diversity across three habitat types, reflecting a land-use change gradient. From original native juniper forest to urban and agricultural zones in central Mexico, one site per land use type was surveyed. Interactions were summarized in matrices on which we calculated network descriptors: connectance, nestedness and modularity. We found highest butterfly diversity in native forest, with the most unique species (i.e., species not shared with the other two sites). Agricultural and urban sites had similar diversity, yet the urban site featured more unique species. The plant species richness was highest in the urban site, and the native forest site had the lowest plant species richness, with most of the plants being unique to this site. Butterfly and plant compositions contrasted most between native forest and modified sites. Network analysis showed differences between sites in the mean number of links and interactions. The urban network surpassed agriculture and native forest networks in links, while the native forest network had more interactions than the agriculture and urban networks. Native plants had more interactions than alien species. All networks exhibited low connectance and significant nestedness and modularity, with the urban network featuring the most modules (i.e., 10 modules). Converting native habitats to urban or agricultural areas reshapes species composition, diversity and interaction network structure for butterfly communities and plants. The urban network showed more links and modules, suggesting intricate urban ecosystems due to diverse species, enhanced resources, and ecological niches encouraging interactions and coexistence. These findings emphasize the impacts of land use change on plant-butterfly interactions and the structure of their interaction networks.


Dealing with supramolecular structure for ionic liquids: a DOSY NMR approach.
Diffusion-ordered spectroscopy (DOSY) is arguably a powerful method for the NMR analysis of ionic liquids, since the self-diffusion coefficients for cations and anions can be measured straightforwardly. In this work, the dynamic-structural behaviour of imidazolium ionic liquids containing different anions has been investigated by experimental measurements of direct 1H diffusion coefficients in chloroform and water solutions. The influence of ion structure has been tested by using six IL salts formed by the association of different cations (1-n-butyl-3-methylimidazolium, 1,2,3-trimethylimidazolium and tetra-n-butylammonium) with different anion structures (prolinate, acetate and o-trifluoromehtylobenzoate). The influence of IL concentration (from 0.01 to 0.5 mol L-1) was also evaluated for BMI·Pro. The contact ion pairs (or aggregates) are maintained in both chloroform and water within the range of concentrations investigated. In the particular case of 1,2,3-trimethylimidazolium imidazolate (TMI·Im) containing confined water in DMSO the maintenance of the contact ion pairs depends on the water content which may even disrupt the IL supramolecular structure.


A simple method for sutureless gastrointestinal anastomosis in rat.
A simple tubing stent was attempted to test a model for sutureless gastrointestinal anastomosis in 6 male rats at the age of 15 weeks. In the 3rd and 4th weeks after the operation, X-ray examination demonstrated that the gastrointestinal passage in the anastomotic site was quite satisfactory. There was no incidence of anastomotic leakage. In the 6th week after the operation, there were no macroscopic or microscopic ruptures, nor were there any obstructions at the anastomotic site. This simple sutureless method was effective at preparing anastomosis in the gastrointestinal tract in the rat and could be applied to other small experimental animals.


Morphological correlates of transformation in cultured C3H/10T1/2 mouse embryo cells.
In efforts to determine common and consistent morphological parameters of transformation in C3H/10T1/2 cells, 15 cell lines transformed by different carcinogens were examined with the scanning electron microscope (SEM) and compared to non-transformed cells. Cell lines were studied at different passages, at different cell densities, and after growth as anchorage dependent or independent cultures. The transformed cell lines could be distinguished in the SEM from non-transformed cultures by the expression of one or more of the following morphological characteristics: formation of mini- or macro-foci (random piling of cells on top of each other), pleiomorphism in cell size and shape, and cell surface complexity. The extent to which these characteristics were expressed varied widely in the different transformed cell lines. Light microscopic scoring for different types of foci also revealed broad variability among the different transformed lines. At the SEM level, cell lines could not be characterized as transformed on an individual cell basis. However, all transformed cell lines could be definitively characterized as transformed on a population basis due to the presence of mini-foci. The various transformed cell lines were classified semi-quantitatively into categories based on the extent of expression of the different morphological characteristics. There was broad correspondence between the morphological classification and the relative plating efficiencies of the cell lines in soft agarose.


Can a single injury cause cancer.
In the absence of positive evidence that a single injury can cause cancer, the tendency is growing to award compensation to persons (particularly employees) with cancers alleged to have originated in trauma, even cancers which are generally conceded to be congenital in origin.Experimental attempts to induce cancer through trauma have been unsuccessful or doubtful in result. War-wounded persons, boxers and railroad accident victims have no higher incidence of cancer than other groups.Physicians and others in a position to educate the public should strive to dispel the error that cancer following injury is demonstrably or even probably the cause.


Ln2Ga[B3O6(OH)]2[B7O9(OH)2](CH3CO2)2 (Ln = Y, Sm, Eu, Gd, Dy): A Series of Lanthanide Galloborates Decorated by Acetate Anions.
The first examples of mixed-anion lanthanide galloborates, namely, Ln2Ga[B3O6(OH)]2[B7O9(OH)2](CH3CO2)2 [Ln = Y (1), Sm (2), Eu (3), Gd (4), Dy (5)], have been obtained through hydrothermal synthesis. The title compounds are isomorphic and belong to monoclinic space group C2/c (No. 15). Their structures possess [B7O13(OH)2] borate layers further bridged with [B3O7] clusters to give a three-dimensional (3D) borate framework displaying two types of rhombus-like B14O14 14-membered-ring (14-MR) channels along the b axis. The Ga(3+) ions are octahedrally coordinated and located at one end of the B14O14 14-MR channels, forming small tunnels of B7Ga 8-MRs, which are filled by the Ln(III) ions. The Ln ions and Ga cations are further held together by bridging acetate anions. It is worth noting that in these compounds there are two different types of borate clusters and two types of anions that are uncommon in the borates reported. Luminescent studies revealed the characteristic emission bands of Ln ions for compounds 2-5, and the luminescent lifetimes are 3.6, 0.86, and 3.05 ns for compounds 2, 3, and 5, respectively. Magnetic measurements suggest that there are antiferromagnetic interactions between magnetic centers for compounds 2-5.


Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility.
There is increasing evidence identifying the crucial role of numerous dietary components in modifying the process of carcinogenesis. The varied effects exerted by nutrient and non-nutrient dietary compounds on human health and cancer risk are one of the new challenges for nutritional sciences. In the present paper, an attempt is made to review the most recent epidemiological data on interactions between dietary factors and metabolic gene variants in terms of cancer risk. The majority of case-control studies indicate the significant relationship between cancer risk and polymorphic xenobiotic metabolising enzymes in relation to dietary components. The risk of colorectal cancer is associated not only with CYP2E1 high-activity alleles, but also GSTA1 low-activity alleles, among consumers of red or processed meat. Genetic polymorphisms of NAT1 and NAT2 may be also a breast-cancer susceptibility factor among postmenopausal women with a high intake of well-done meat. On the other hand, phytochemicals, especially isothiocyanates, have a protective effect against colorectal and lung cancers in individuals lacking GST genes. Moreover, polymorphism of GSTM1 seems to be involved in the dietary regulation of DNA damage. The European Prospective Investigation into Cancer and Nutrition study shows a significant inverse association between the polycyclic aromatic hydrocarbon-DNA adduct level and dietary antioxidants only among GSTM1-null individuals. However, the absence of a modulatory effect of polymorphic xenobiotic metabolising enzymes and diet on the development of cancer has been indicated by some epidemiological investigations. Studies of interactions between nutrients and genes may have great potential for exploring mechanisms, identifying susceptible populations/individuals and making practical use of study results to develop preventive strategies beneficial to human health.


Economic evaluation of stepped care for the management of childhood anxiety disorders: Results from a randomised trial.
Stepped care has been promoted for the management of mental disorders; however, there is no empirical evidence to support the cost-effectiveness of this approach for the treatment of anxiety disorders in youth. This economic evaluation was conducted within a randomised controlled trial comparing stepped care to a validated, manualised treatment in 281 young people, aged 7-17, with a diagnosed anxiety disorder. Intervention costs were determined from therapist records. Administrative data on medication and medical service use were used to determine additional health care costs during the study period. Parents also completed a resource use questionnaire to collect medications, services not captured in administrative data and parental lost productivity. Outcomes included participant-completed quality of life, Child Health Utility - nine-dimension and parent-completed Assessment of Quality of Life - eight-dimension to calculate quality-adjusted life years. Mean costs and quality-adjusted life years were compared between groups at 12-month follow-up. Intervention delivery costs were significantly less for stepped care from the societal perspective (mean difference -$198, 95% confidence interval -$353 to -$19). Total combined costs were less for stepped care from both societal (-$1334, 95% confidence interval -$2386 to $510) and health sector (-$563, 95% confidence interval -$1353 to $643) perspectives but did not differ significantly from the manualised treatment. Youth and parental quality-adjusted life years were not significantly different between groups. Sensitivity analysis indicated that the results were robust. For youth with anxiety, this three-step model provided comparable outcomes and total health sector costs to a validated face-to-face programme. However, it was less costly to deliver from a societal perspective, making it an attractive option for some parents. Future economic evaluations comparing various models of stepped care to treatment as usual are recommended.


Body art in 4,277 Italian secondary school adolescents: prevalence and associations with personal and family characteristics.
This study's purpose was to investigate, in a large cohort of adolescents, the prevalence and association of personal and family characteristics with having or considering body piercing or tattoo. We surveyed students from the Veneto Region of northeast Italy with a self-administered questionnaire that asked about body piercing and tattoo and about personal and family characteristics. Multinomial weighted regression analysis was used to generate adjusted relative risk ratios with 95% confidence interval (CI) for piercing and tattooing separately. A total of 4,277 of 4,524 surveyed students completed and returned a usable questionnaire. For piercing, the prevalence was 20%. Girls, students with a less educated father, and those dissatisfied with their physical appearance were more likely to be interested in and to have undergone this procedure. For tattooing, the prevalence was 6%. Boys and students whose father was younger than 48 were more likely to have experienced tattooing. A strong association was found between having a piercing and having a tattoo. Fify-six percent of pierced students and 48% of tattooed students were underage (<18 years). We found that male gender (for tattoo), female gender (for piercing), dissatisfaction with physical appearance, positive attitudes toward either piercing or tattoo, and having a younger and less educated father were associated with having or desiring body modification. These factors could be considered for targeted patient education.


Acute alcohol intoxication.
Acute alcohol intoxication is a clinically harmful condition that usually follows the ingestion of a large amount of alcohol. Clinical manifestations are heterogeneous and involve different organs and apparatuses, with behavioral, cardiac, gastrointestinal, pulmonary, neurological, and metabolic effects. The management of an intoxicated patient occurs mainly in the emergency department and is aimed at stabilizing the clinical condition of the patient, depending on his/her clinical presentation. One specific drug that is useful in the treatment of acute alcohol intoxication is metadoxine, which is able to accelerate ethanol excretion. In patients presenting an acute alcohol intoxication, alcohol-related disorders should be detected so that the patient can be directed to an alcohol treatment unit, where a personalized, specific treatment can be established.


A fatal case of primary basaloid squamous cell carcinoma in the intrahepatic bile ducts.
Primary squamous cholangiocellular carcinomas are very rare. We describe a case of a 67-year-old man, who underwent chemotherapy and surgery for a right-sided liver tumor with an unusual presentation of metastasis to a lymph node in the left armpit. The patient was asymptomatic at the time of diagnosis but expired 20 months after surgery with epidural, lung, and spine metastasis. In addition to the unusual clinical presentation, the diagnosis of the liver tumor was that of a primary basaloid squamous cell carcinoma of the intrahepatic bile ducts, an entity with only one previous report in the literature.


Expression of epidermal growth factor receptors in human endometrial carcinoma.
Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent at the cell membranes, with a varying pattern in individual carcinomas. EGF-R expression was not correlated with histologic grade, surgical stage, or estrogen/progesterone receptor status evaluated immunohistochemically or biochemically in adjacent tissue sections of the tumor. Ten of 13 (77%) atrophic/inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas.


Mutagenesis of Glycine 179 modulates both catalytic efficiency and reduced pyridine nucleotide specificity in cytochrome b5 reductase.
Cytochrome b5 reductase (cb5r), a member of the ferredoxin:NADP+ reductase family of flavoprotein transhydrogenases, catalyzes the NADH-dependent reduction of cytochrome b5. Within this family, a conserved "GxGxxP" sequence motif has been implicated in binding reduced pyridine nucleotides. However, Glycine 179, a conserved residue in cb5r primary structures, precedes this six-residue "180GxGxxP185" motif that has been identified as binding the adenosine moiety of NADH. To investigate the role of G179 in NADH complex formation and NAD(P)H specificity, a series of rat cb5r variants were generated, corresponding to G179A, G179P, G179T, and G179V, recombinantly expressed in Escherichia coli and purified to homogeneity. Each mutant protein was found to incorporate FAD in a 1:1 cofactor/protein stoichiometry and exhibited absorption and CD spectra that were identical to those of wild-type cb5r, indicating both correct protein folding and similar flavin environments, while oxidation-reduction potentials for the FAD/FADH2 couple (n = 2) were also comparable to the wild-type protein (E(o)' = -272 mV). All four mutants showed decreased NADH:ferricyanide reductase activities, with kcat decreasing in the order WT > G179A > G179P > G179T > G179V, with the G179V variant retaining only 1.5% of the wild-type activity. The affinity for NADH also decreased in the order WT > G179A > G179P > G179T > G179V, with the Km(NADH) for G179V 180-fold greater than that of the wild type. Both Ks(H4NAD) and Ks(NAD+) values confirmed that the G179 mutants had both compromised NADH- and NAD+-binding affinities. Determination of the NADH/NADPH specificity constant for the various mutants indicated that G179 also participated in pyridine nucleotide selectivity, with the G179V variant preferring NADPH approximately 8000 times more than wild-type cb5r. These results demonstrated that, while G179 was not critical for either flavin incorporation or maintenance of the appropriate flavin environment in cb5r, G179 was required for both effective NADH/NADPH selectivity and to maintain the correct orientation and position of the conserved cysteine in the proline-rich "CGpppM" motif that is critical for optimum NADH binding and efficient hydride transfer.


Electricity production and microbial characterization of thermophilic microbial fuel cells.
Thermophilic microbial fuel cell (TMFC) offers many benefits, but the investigations on the diversity of exoelectrogenic bacteria are scarce. In this study, a two-chamber TMFC was constructed using ethanol as an electron donor, and the microbial dynamics were analyzed by high-throughput sequencing and 16S rRNA clone-library sequencing. The open-circuit potential of TMFC was approximately 650mV, while the maximum voltage was around 550mV. The maximum power density was 437mW/m2, and the columbic efficiency in this work was 20.5±6.0%. The Firmicutes bacteria, related to the uncultured bacterium clone A55_D21_H_B_C01 with a similarity of 99%, accounted for 90.9% of all bacteria in the TMFC biofilm. This unknown bacterium has the potential to become a new thermophilic exoelectrogenic bacterium that is yet to be cultured. The development of TMFC-involved biotechnologies will be beneficial for the production of valuable chemicals and generation of energy in the future.