Evaluation of scolicidal agents in an experimental hydatid disease model.
The treatment of hydatid disease is largely surgical, with medical treatment being reserved as coadjuvant treatment. The scolicidal agents have been, and are being used mainly during surgical manipulation of the cysts, with the object of avoiding relapses and peritoneal dissemination. Evaluation of the scolicidal agents used in surgery in a hydatid disease model in the mouse. We have used 85 Swiss OF1 mice, weighing more than 30 g, of 90 +/- 10 days of age, in which a picture of hydatid sowing was reproduced by means of intra-peritoneal inoculation with 0.2 ml of a suspension which contained approximately 1,200 viable protoscolex of Echinococcus granulosus which came from the livers of parasite-infested sheep. 24 h after the inoculation, the mice were subjected to a median laparotomy for the introduction of 1 ml of the scolicidal solution to be evaluated: physiologic saline (n = 10); 10% povidone iodine (n = 15); praziquantel (n = 15); 10% hydrogen peroxide (n = 15); 10% hypertonic saline (n = 15); simulated operation (n = 15). After 7 months of follow-up, the mice were sacrificed and the following was evaluated: number of isolated cysts, cyst masses, and total cysts. The number of isolated cysts which developed was significantly lower in the hydrogen peroxide group (tF 2.14 < RC 3.29). The number of cyst masses was significantly reduced in the hydrogen peroxide group (tF 2.14 < RC 2.18), in the povidone iodine group (tF 2.17 < RC 3), and in the hypertonic saline group (tF 2.11 < RC 2.77). The total number of cysts which developed decreased significantly in the hydrogen peroxide (tF 2.14 < RC 2.84) and the povidone iodine (tF 2.17 < RC 3.79) groups. Hydrogen peroxide and povidone iodine show a greater protoscolicidal effect than simple cleansing with physiological saline, hypertonic saline, or praziquantel.


Decreasing Stereotypy Using NCR and DRO With Functionally Matched Stimulation: Effects on Targeted and Non-Targeted Stereotypy.
We conducted a series of studies on multiple forms of repetitive behavior displayed by four children with autism spectrum disorder. Study 1 showed that each participant's highest probability repetitive behavior persisted in the absence of social consequences, thereby meeting the functional definition of stereotypy. Study 2 showed that preferred, structurally matched stimulation decreased each participant's targeted (highest probability) stereotypy, as well as their non-targeted (lower probability) stereotypy. Study 3 showed that for three participants, non-contingent access to preferred stimulation decreased immediate and, to some extent, subsequent engagement in targeted and non-targeted stereotypy. For the fourth participant, non-contingent access to preferred stimulation decreased immediate engagement in the targeted stereotypy, but increased subsequent engagement in non-targeted stereotypy; this subsequent increase was attenuated by reducing the duration of access to the preferred stimulus. Study 4 showed that a trial-based differential reinforcement of other behavior (DRO) procedure systematically increased the period of time for which the targeted stereotypy was not displayed for three of three participants. In addition, results showed that the participants' non-targeted stereotypy either decreased or was unchanged when DRO was provided for the targeted stereotypy.


Implementation strategies for an inpatient women's support group.
The authors believe an inpatient women's group to be a supportive and educative nursing intervention that, when adjunctively combined with other inpatient therapy forms, assists women to resolve sex-role conflicts. Use of the nursing audit, review of relevant literature, development of a group philosophy, objectives, and appropriate credentialing of nurse group facilitators are strategies that maximize group effectiveness. Moreover, group content, which is determined from the client's perspectives of need, and evaluated by behavioral changes among client participants, insures sustained program relevancy.


Premenstrual syndrome.
Premenstrual syndrome (PMS) affects the quality of life of millions of women. The complexity and variety of clinical presentation together with the cyclic recurrence of affective and somatic symptoms increase the difficulty in understanding and treating the disease. The precise pathophysiology of PMS is still unknown, but it is increasingly believed that, in women with PMS, the sensitive equilibrium between sex-steroids and central neurotransmitters is altered. Several studies have been carried out to understand the origin of the syndrome and to discover new ways of treatment. This review summarizes the most accepted PMS theories and treatments currently available based on the results of the best-designed trials.


Role of dopaminergic and GABAergic mechanisms in discrete brain areas in phencyclidine-induced locomotor stimulation and turning behavior.
This study was designed to test whether phencyclidine (PCP)-induced turning behavior and locomotor stimulation result from the action of this drug on functionally different neuronal systems and different sites of the brain. PCP produced turning behavior towards the drug injection side with unilateral injection of PCP (50-100 micrograms) into the globus pallidus, but not the nucleus accumbens and the caudate nucleus. This turning behavior was strongly attenuated by a gamma-aminobutyric acid (GABA) antagonist, bicuculline, and by pimozide which reduces dopaminergic transmission in non-injection sites. Turning behavior induced by intraperitoneal injection of PCP (7.5 mg/kg) was enhanced by a GABA agonist, baclofen, and attenuated by GABA antagonists (bicuculline, picrotoxin). On the other hand, PCP produced significant locomotor stimulation, sniffing, rearing and forward locomotion with unilateral injection of 25-100 micrograms into the nucleus accumbens and the caudate nucleus. These behaviors were strongly antagonized by intraperitoneal injection of pimozide. The locomotor stimulation induced by intraperitoneal injection of PCP (5 mg/kg) was markedly enhanced by a small dose of methamphetamine and, by contrast, attenuated by reserpine, 6-hydroxydopamine, haloperidol, pimozide and a low dose of apomorphine which inhibits the release of dopamine by the stimulation of presynaptic receptors. These results suggest that PCP-induced turning behavior may be produced through stimulation of GABAergic transmission in the globus pallidus, although PCP-induced locomotor stimulation, sniffing, rearing and forward locomotion may be produced by increasing dopaminergic transmission in the nucleus accumbens and the caudate nucleus.


Whole human genome proteogenomic mapping for ENCODE cell line data: identifying protein-coding regions.
Proteogenomic mapping is an approach that uses mass spectrometry data from proteins to directly map protein-coding genes and could aid in locating translational regions in the human genome. In concert with the ENcyclopedia of DNA Elements (ENCODE) project, we applied proteogenomic mapping to produce proteogenomic tracks for the UCSC Genome Browser, to explore which putative translational regions may be missing from the human genome. We generated ~1 million high-resolution tandem mass (MS/MS) spectra for Tier 1 ENCODE cell lines K562 and GM12878 and mapped them against the UCSC hg19 human genome, and the GENCODE V7 annotated protein and transcript sets. We then compared the results from the three searches to identify the best-matching peptide for each MS/MS spectrum, thereby increasing the confidence of the putative new protein-coding regions found via the whole genome search. At a 1% false discovery rate, we identified 26,472, 24,406, and 13,128 peptides from the protein, transcript, and whole genome searches, respectively; of these, 481 were found solely via the whole genome search. The proteogenomic mapping data are available on the UCSC Genome Browser at http://genome.ucsc.edu/cgi-bin/hgTrackUi?db=hg19&g=wgEncodeUncBsuProt. The whole genome search revealed that ~4% of the uniquely mapping identified peptides were located outside GENCODE V7 annotated exons. The comparison of the results from the disparate searches also identified 15% more spectra than would have been found solely from a protein database search. Therefore, whole genome proteogenomic mapping is a complementary method for genome annotation when performed in conjunction with other searches.


Periplasmic nitrate-reducing system of the phototrophic bacterium Rhodobacter sphaeroides DSM 158: transcriptional and mutational analysis of the napKEFDABC gene cluster.
The phototrophic bacterium Rhodobacter sphaeroides DSM 158 is able to reduce nitrate to nitrite by means of a periplasmic nitrate reductase which is induced by nitrate and is not repressed by ammonium or oxygen. Recently, a 6.8 kb PstI DNA fragment carrying the napABC genes coding for this periplasmic nitrate-reducing system was cloned [Reyes, Roldán, Klipp, Castillo and Moreno-Vivián (1996) Mol. Microbiol. 19, 1307-1318]. Further sequence and genetic analyses of the DNA region upstream from the napABC genes reveal the presence of four additional nap genes. All these R. sphaeroides genes seem to be organized into a napKEFDABC transcriptional unit. In addition, a partial open reading frame similar to the Azorhizobium caulinodans yntC gene and the Escherichia coli yjcC and yhjK genes is present upstream from this nap gene cluster. The R. sphaeroides napK gene codes for a putative 6.3 kDa transmembrane protein which is not similar to known proteins and the napE gene codes for a 6.7 kDa transmembrane protein similar to the Thiosphaera pantotropha NapE. The R. sphaeroides napF gene product is a 16.4 kDa protein with four cysteine clusters that probably bind four [4Fe-4S] centres. This iron-sulphur protein shows similarity to the NapF and NapG proteins of E. coli and Haemophilus influenzae. Finally, the napD gene product is a 9.4 kDa soluble protein which is also found in E. coli and T. pantotropha. The 5' end of the nap transcript has been determined by primer extension, and a sigma70-like promoter has been identified upstream from the napK gene. The same transcriptional start site is found for cells growing aerobically or anaerobically with nitrate. Different mutant strains carrying defined polar and non-polar insertions in each nap gene were constructed. Characterization of these mutant strains demonstrates the participation of the nap gene products in the periplasmic nitrate reduction in R. sphaeroides.


Causes of death among Finnish women with cosmetic breast implants, 1971-2001.
Mortality patterns among women with cosmetic breast implants have not been well characterized. We examined cause-specific mortality among women who underwent cosmetic breast implantation at major public hospitals and private clinics in Finland from 1970 through 2000. Causes of death through 2001 were identified through the national mortality register. Expected numbers of deaths were calculated on the basis of mortality rates in the general female population, and standardized mortality ratios (SMR), i.e. ratios of observed to expected deaths, and 95% confidence intervals (CI) were calculated. Among the 2166 women with cosmetic breast implants, we observed 31 deaths versus 32.1 expected. Overall disease mortality was below expectation, mainly due to low mortality from diseases of the circulatory system (SMR, 0.28; 95% CI, 0.03-1.02). Mortality from cancer was close to expectation. There was a statistically significant excess of suicide, based on 10 deaths, which was most pronounced during the first 5 years of follow-up (SMR, 4.26; 95% CI, 1.56-9.26). In conclusion, although based on small numbers, women with cosmetic breast implants did not experience higher mortality overall than women in the general population. The high suicide risk supports other studies and warrants further detailed investigation.


Responses of rural family physicians and their colleague and coworker raters to a multi-source feedback process: a pilot study.
To describe responses of family physicians, their medical colleagues, and coworker raters to a multisource feedback assessment process. Data collection tools included multisource feedback self-assessment and medical colleague, coworker, and patient rating forms; and program evaluation physician and rater questionnaires. The pilot study included 142 physicians and their raters, with 113 (80%) physicians completing evaluations. Positive correlations were found between familiarity scores and medical colleague and coworker mean ratings. Peer medical colleagues were significantly more familiar with physicians than were consultants. Consultants were unable to rate items most frequently. Physicians disagreed with colleague feedback more frequently. Agreement was positively correlated with scores. Familiarity, ability to observe physicians appropriately to rate them, and physicians' responses to feedback are factors to consider when multisource feedback is used.


Psychometric properties of the painDETECT questionnaire in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: Rasch analysis and test-retest reliability.
Pain is inherent in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA) and traditionally considered to be of nociceptive origin. Emerging data suggest a potential role of augmented central pain mechanisms in subsets of patients, thus, valid instruments that can identify underlying pain mechanisms are needed. The painDETECT questionnaire (PDQ) was originally designed to differentiate between pain phenotypes. The objectives were to evaluate the psychometric properties of the PDQ in patients with inflammatory arthritis by applying Rasch analysis and to explore the reliability of pain classification by test-retest. For the Rasch analysis 900 questionnaires from patients with RA, PsA and SpA (300 per diagnosis) were extracted from 'the DANBIO painDETECT study'. The analysis was directed at the seven items assessing somatosensory symptoms and included: 1) the performance of the six-category Likert scale; 2) whether a unidimensional construct was defined; 3) the reliability and precision of estimates. Another group of 30 patients diagnosed with RA, PsA or SpA participated in a test-retest study. Intraclass Correlation Coefficients (ICC) and classification consistency were calculated. The Rasch analysis revealed: (1) Acceptable psychometric rating scale properties; the frequency distribution peaked in category 0 except for item 5, threshold calibration >10 observations per category, no disorder in the category measures for all items, scale category outfit Mnsq <2.0, small distances (<1.4 logits) between thresholds for category 1, 2 and 3 for all items. (2) The principal component analysis supported unidimensionality; the standardized residuals showed that 53.7% of total variance was explained by the measure and the magnitude of first contrast had an eigenvalue of 1.5, no misfitting items, clinical insignificant different item hierarchies across diagnoses (DIF < 0.5 logits). (3) A targeted item-person map, person and item separation indices of 1.88(reliability = 0.78), and 13.04 (reliability = 0.99). The test-retest revealed: ICC: RA 0.86(0.56-0.96), PsA 0.96(0.74-0.99), SpA 0.93(0.76-98), overall 0.94(0.84-0.98). Classification consistency was: RA 70%, PsA 80%, SpA 90%, overall 80%. The results support that the PDQ can be used as a classification instrument and assist identification of underlying pain-mechanisms in patients suffering from inflammatory arthritis.


Characterization and correction of pulse pile-up in simultaneous emission-transmission computed tomography.
We have developed an emission-transmission CT (ETCT) system capable of both single-photon emission computed tomography (SPECT) imaging and x-ray transmission CT imaging using a common photon counting detector. In principle, SPECT and x-ray CT projection data can be acquired simultaneously with the ETCT system; however, doing so results in contamination of the SPECT projection data due to pulse pile-up caused by the relatively high x-ray fluence rate. In this study, we characterize the effects of pulse pile-up for simultaneous ETCT imaging through computer simulation and experimental studies. We demonstrate that pulse pile-up in the SPECT energy window can be well approximated by a simple quadratic relationship between the pile-up rate and the x-ray fluence rate for sufficiently small x-ray fluence rates. Using this quadratic relationship, we developed a simple pile-up correction scheme that subtracts the pile-up counts from the emission data and also truncates the exterior regions of the emission projection data. Analysis of difference images and profiles indicate that this method permits us to reconstruct SPECT images with no apparent noise or resolution degradation in comparison to those obtained via sequential emission and transmission scans.


[Equity-based considerations for transforming the Ecuadorian health system].
The present study was aimed at analysing socioeconomic inequity regarding the use of health services in Ecuador, inequity regarding the geographic distribution of healthcare-related human resources and reflecting on the challenges concerning equity which the Ecuadorian health system is currently facing. The Ecuadorian Demographic, Maternal and Infant Health Survey (2004) was used as the main data source, as its sample was representative of the Ecuadorian population. Multilevel multivariate analysis (MLWiN 2.02 statistical software) and spatial data analysis regarding health resources (GeoDa 1.0.1) were used for estimating the effects of using health services. It was found that social, economic and geographic inequity limited access to health services in Ecuador. People living in low economic resource households or indigenous housing and people living in rural areas (many of them having all three characteristics at the same time) had less possibility of using health services. In spite of a marked concentration of health-service providers in urban areas, it was found that the presence of healthcare personnel (excluding doctors) in rural public entities increased the possibility of using preventative and curative services. Efforts at transforming the Ecuadorian health system must be aimed at reducing social, cultural and financial barriers and inequality regarding the distribution de healthcare-related human resources, particularly in rural areas. Community and family orientation of the services and increasing spaces for citizen participation are necessary for reducing such inequity.


Filipino nurse recruitment as a staffing strategy.
Challenging times require challenging strategies. The recruitment of nurses from the Philippines is a strategy that makes sense both ethically and economically when the processes are managed by well-capitalized vendors with experience and expertise in the area. A one-stop turnkey approach for a set fee is recommended. Filipino nurse recruitment addresses short-term and intermediate-term strategies that can offer support to hospitals and full-time employed nurses needing more help to do their work. This process benefits the patient who needs access to care, it benefits the employing organization as an economical method to fill vacant positions, it benefits the Filipino nurse who has an opportunity for a better quality of life than she would have access to in her homeland, the colleagues on the rest of the clinical team are benefited by having qualified staff to share the workload, and the home country of the Filipino nurse benefits when the expatriate nurses send money regularly that goes back into the general economy of the country.


Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block.
The total synthesis of TMG-chitotriomycin using an automated electrochemical synthesizer for the assembly of carbohydrate building blocks is demonstrated. We have successfully prepared a precursor of TMG-chitotriomycin, which is a structurally-pure tetrasaccharide with typical protecting groups, through the methodology of automated electrochemical solution-phase synthesis developed by us. The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block.


Four chamber FDG uptake in the heart: an indirect sign of pulmonary embolism.
A 57-year-old-male presented for whole-body PET with CT for restaging of lung cancer. Besides revealing postradiation changes, we noticed an unusual pattern of FDG uptake in the myocardium, with prominent metabolic uptake involving 4 chambers of the heart. Later that day, the patient was referred to the emergency department for increased heart rate, but otherwise asymptomatic. CT angiography was performed, which showed scattered filling defects in bilateral pulmonary arteries consistent with pulmonary embolism. The finding of prominent FDG uptake involving all cardiac chambers in this patient is likely related to heart strain caused by acute pulmonary embolism.


Modified release bi-layered tablet of melatonin using beta-cyclodextrin.
A modified release bi-layered tablet of melatonin incorporating a fast release fraction consisting of melatonin-beta-cyclodextrin inclusion complex and a slow release fraction containing melatonin in HPMC K15M and Carbopol 971 P matrices was prepared. The formulation developed showed an initial burst followed by a near zero order release pattern for a period of 8 h. The drug content, physical characteristics and the release profile were unaffected after 3 months of an accelerated stability study at 40 degrees C and 75% relative humidity.


[Research on carboxymethyl chitosan acting as the adjuvant for implantable degradable microspheres].
As a kind of biomaterial, carboxymethyl chitosan (CMC) has excellent biodegradable and bioacceptable capabilities using. This study was aimed to probe into the feasibility of CMC to prepare the implantable sustained release Ciprofloxacin Hydrochloride (CPX) microspheres(MS), and to go further into the pharmaceutic technology, the morphology and the characteristics of in vitro release of the microspheres. First, we prepared the microspheres by emulsification and cross-linking technology. Then, scanning electron microscopy (SEM), infrared spectrum (IR) and differential thermal analysis (DTA) were used to detect the structure and morphology of the MS. The in vitro release of CPX/CMC-MS and the CPX content of the MS were detected through continuous-flow releasing system. We found that the structure and morphology of the MS were affected by the conditions of preparation such as emulsification and cross-linking temperature, ionic strength and stirring speed, that the releasing time of CPX was more than 7 days, and that the releasing behaviors of the microspheres conformed to the Higuchi model. So we drew the conclusions that CMC could be used as a kind of absorbable and implantable adjuvant for sustained release, the technology of emulsification and cross-linking was proved to be feasible, stable and simple.


Prehabilitation: the anesthesiologist's role and what is the evidence?
Surgery poses major threats to functional independence. Prehabilitation is a preoperative conditioning intervention that aims to prevent or attenuate surgery-related functional decline and its consequences. The present review is to summarize most recent evidence on the effectiveness of prehabilitation on key topics in cancer care, such as perioperative functional capacity, surgical and oncologic outcomes. Recent studies predominantly focus on functional outcomes, demonstrating a positive effect of prehabilitation on perioperative physical fitness. Prehabilitation prevents functional decline associated with major cancer surgery. Evidence is still needed to support its effectiveness in relation to postoperative complication, length of hospital stay, tumor progression, response to medical treatment, and survival. Ongoing and future research is essential to prompt the role of perioperative medicine in cancer care.


A constant-depth laboratory model film fermentor.
A laboratory model constant-depth film fermentor was developed. Film grew on the surface of polytetrafluoroethylene (PTFE) plugs and was limited to a predetermined depth by mechanically removing excess film. Six film-forming organisms were isolated from river water and used to assess the operating characteristics of the fermentor. Film accumulation was logarithmic, and a steady state was maintained. Electron micrographs show early film development. The fermentor enables film to be grown on any substratum and allows discrete, reproducible, and representative samples to be taken.


Oral ingestion of narcotic analgesics by rats.
Rats drank solutions of narcotic analgesics as the only drinking fluid available in their cages. Relative to their daily water intake before the drug solutions were introduced, the rats drank more etonitazene solution, less methadone solution, and about the same volume of morphine, meperidine and levorphanol solution as water, although some rats would not drink the higher concentrations of morphine (1.0 mg/ml), levorphanol (1.0 mg/ml) and methadone (1.0 mg/ml). When naloxone (1.0 mg/kg) was administered after 12 days of drinking the drug solutions, the severity of the abstinence syndromes based on scoring of symptoms and on weight loss was morphine greater than or equal to etonitazine greater than levorphanol greater than meperidine greater than methadone. The animals showing the most severe syndrome after naloxone usually consumed more drug solution than usual during the next 24 hours, so that body weights were normal at the end of the 24-hour period. Nonprecipitated abstinence was also studied in these rats by replacing the drug solutions with water 3 to 5 days after the naloxone injection. Rats that had been drinking morphine, etonitazene and levorphanol lost weight for 2 or 3 days and then began to regain their lost weight. In contrast, rats which had been switched from methadone and meperidine solutions to water gained weight rapidly. Morphine and etonitazene drinkers which had been switched to water drank a lesser volume of water than they had been drinking of drug solution whereas some ex-methadone drinkers drank more water.


A Plant Cryptochrome Controls Key Features of the Chlamydomonas Circadian Clock and Its Life Cycle.
Cryptochromes are flavin-binding proteins that act as blue light receptors in bacteria, fungi, plants, and insects and are components of the circadian oscillator in mammals. Animal and plant cryptochromes are evolutionarily divergent, although the unicellular alga Chlamydomonas reinhardtii (Chlamydomonas throughout) has both an animal-like cryptochrome and a plant cryptochrome (pCRY; formerly designated CPH1). Here, we show that the pCRY protein accumulates at night as part of a complex. Functional characterization of pCRY was performed based on an insertional mutant that expresses only 11% of the wild-type pCRY level. The pcry mutant is defective for central properties of the circadian clock. In the mutant, the period is lengthened significantly, ultimately resulting in arrhythmicity, while blue light-based phase shifts show large deviations from what is observed in wild-type cells. We also show that pCRY is involved in gametogenesis in Chlamydomonas pCRY is down-regulated in pregametes and gametes, and in the pcry mutant, there is altered transcript accumulation under blue light of the strictly light-dependent, gamete-specific gene GAS28 pCRY acts as a negative regulator for the induction of mating ability in the light and for the loss of mating ability in the dark. Moreover, pCRY is necessary for light-dependent germination, during which the zygote undergoes meiosis that gives rise to four vegetative cells. In sum, our data demonstrate that pCRY is a key blue light receptor in Chlamydomonas that is involved in both circadian timing and life cycle progression.


The Role of Experimenter Belief in Social Priming.
Research suggests that stimuli that prime social concepts can fundamentally alter people's behavior. However, most researchers who conduct priming studies fail to explicitly report double-blind procedures. Because experimenter expectations may influence participant behavior, we asked whether a short pre-experiment interaction between participants and experimenters would contribute to priming effects when experimenters were not blind to participant condition. An initial double-blind experiment failed to demonstrate the expected effects of a social prime on executive cognition. To determine whether double-blind procedures caused this result, we independently manipulated participants' exposure to a prime and experimenters' belief about which prime participants received. Across four experiments, we found that experimenter belief, rather than prime condition, altered participant behavior. Experimenter belief also altered participants' perceptions of their experimenter, suggesting that differences in experimenter behavior across conditions caused the effect. Findings reinforce double-blind designs as experimental best practice and suggest that people's prior beliefs have important consequences for shaping behavior with an interaction partner.


The methyl-accepting transducer protein HtrI is functionally associated with the photoreceptor sensory rhodopsin I in the archaeon Halobacterium salinarium.
We have investigated the functional relationship between two proteins involved in the photosensory system of the archaeon Halobacterium salinarium: the photoreceptor sensory rhodopsin I (SRI) and the halobacterial transducer rhodopsin I (HtrI), which has been proposed to be the putative signal transducer of SRI, by genomic DNA analysis of two independent SRI negative mutants, Pho81 and D1. Southern and PCR analyses revealed that both strains bear alterations in the 5' flanking region of the gene encoding SRI, sopI. DNA sequence analysis confirmed the occurrence in this region of htrI, the gene encoding the putative transducer protein. PCR and Northern analyses have shown further that sopI and htrI are expressed as a single transcriptional unit, thus explaining the lack of SRI in mutants with a defective htrI. Expression of the cloned sopI under the control of a heterologous promoter did not restore the SRI-dependent photoresponse in the strain Pho81. Moreover, the photocycling rate of the expressed pigment was clearly lower than in wild type. HtrI is therefore essential for SRI function and most likely modulates the photochemical properties of the photoreceptor via direct physical interaction. Finally, reintroduction of both sopI and htrI into Pho81 and D1 restored the SRI photochemistry and its physiological function. Our results provide the first experimental evidence for the functional coupling between SRI and HtrI and corroborate the proposed model in which HtrI acts as the signal transducer of this archaeal seven-helix photoreceptor in a way analogous to the bacterial chemotaxis transducers.


A miRNA Combination as Promising Biomarker for Hepatocellular Carcinoma Diagnosis: A Study Based on Bioinformatics Analysis.
Background: miRNAs dysregulate in hepatocellular carcinoma (HCC), showing promise for diagnostic biomarkers which may be found through exploration of differentially expressed miRNAs when comparing HCC and normal liver tissues. Materials and Methods: In the present research, candidate miRNAs were selected and verified using screening dataset GSE12717 and training dataset GSE10694, respectively. A miRNA combination was constructed using stepwise logistic regression analysis and validated using two datasets GSE74618 and TCGA. Target genes of miRNAs in the combination were obtained using a miRNA target gene prediction database. Functional analysis was conducted using an online tool DAVID. We also analyzed the mRNA-Seq data of project LIHC from TCGA to identify the hub target genes of the miRNAs. Results: A miRNA combination, which is composed of hsa-miR-221 and hsa-miR-29c was defined in this study. The miRNA combination is more effective in discriminating HCC patients from normal individuals than individual miRNAs. Additionally, the combined miRNAs showed a lower misdiagnosis rate than AFP in HCC diagnosis. In terms of the functional analysis, a total of 27 target genes of hsa-miR-221 and 96 target genes of hsa-miR-29c were obtained. Among which, INSIG1 was the common target of the two miRNAs. It was also found that both previously mentioned miRNAs played important roles in the regulation of transcription, cell proliferation, and involvement in cancer-related pathways. Lastly, 2 hub target genes of hsa-miR-221 and 16 hub target genes of hsa-miR-29c were obtained. Conclusion: We established a miRNA combination as a promising tool for HCC diagnosis, and the target genes we predicted provide possible points of penetration for researching these two miRNAs in HCC.


Prenatal alcohol and drug exposures in adoption.
Prenatal alcohol and drug exposures are a significant concern in many domestic and international adoptions. This article addresses the following substance exposures for children: alcohol, opiates, tobacco, marijuana, cocaine, and methamphetamines. For each substance, we review the teratogenicity of the exposure and identify the spectrum of neurodevelopmental issues that can present in children exposed to this substance. Diagnosis of the spectrum of fetal alcohol outcomes is also discussed. When possible, we provide country-specific statistics on exposure risks for adopted children.


La and S Co-Doping Induced the Synergism of Multiphase Nickel-Iron Nanosheets with Rich Oxygen Vacancies to Trigger Large-Current-Density Oxygen Evolution and Urea Oxidation Reactions.
The development of cost-effective electrocatalysts for oxygen evolution reaction (OER) and urea oxidation reaction (UOR) is of great significance for hydrogen production. Herein, La and S co-doped multiphase electrocatalyst (LSFN-63) is fabricated by metal-corrosion process. FeOOH can reduce the formation energy of NiOOH, and enhance the stability of NiOOH as active sites for OER/UOR. The rich oxygen vacancies can increase the number of active sites, optimize the adsorption of intermediates, and improve electrical conductivity. Beyond, La and S co-doping can also regulate the electronic structure of FeOOH. As a result, LSFN-63 presents a low overpotential of 210/450 mV at 100/1000 mA cm-2 , small Tafel slope (32 mV dec-1 ), and outstanding stability under 1000 mA cm-2 @60 h, and can also display excellent OER activity with 180 mV at 250 mA cm-2 and long-term catalytic durability at 250 mA cm-2 @135 h in 30 wt% KOH under 60 °C. Moreover, LSFN-63 demonstrates remarkable UOR performance in 1 m KOH + 0.5 m urea, which just requires an ultra-small overpotential of 140 mV at 100 mA cm-2 , and maintain long-term durability over 120 h. This work opens up a promising avenue for the development of high-efficiency electrocatalysts by a facile metal-corrosion strategy.


Dislocation of primary total hip arthroplasty with 36 and 40-mm femoral heads.
Some authors suggest the use of larger (36 and 40 mm) femoral heads against highly cross-linked polyethylene acetabular liners will reduce the prevalence of early dislocation after primary total hip arthroplasty (THA). We prospectively followed 61 consecutive patients at high risk for dislocation to determine the prevalence of early dislocation after primary THA with 36 and 40 mm femoral heads. We established specific indications for the use of these larger heads in primary arthroplasty. There were 65 hips in 61 patients with a minimum followup of 1 year (mean 2 years, range 1-4 years). There were 55 36 mm heads and 10 40 mm heads. All arthroplasties were performed by the posterior approach with capsular repair. The prevalence of early dislocation was 4.6% (3 of 65). There was one patient with an anterior dislocation and two with posterior dislocation. No patient underwent reoperation for dislocation. There was no dislocation in the 10 hips that had a 40 mm head. We identified no complications related to the larger femoral heads. The use of larger femoral heads did not notably reduce the prevalence of early dislocation after primary THA in high risk patients compared to historical controls.


Safety Influencing Factors and Management Countermeasures of Patients Transferred from ICU in Transition Period Based on Intelligent Processor Three-Dimensional Quality Model.
With the development of science and technology of the times, the level of medical care is constantly improving. For patients transferred from ICU, the intelligent processor 3D quality model technology has gradually played an important role in clinical treatment and has become a new type of attention. In order to understand the implementation status of transitional care and the feelings of transitional care for patients transferred from ICU and understand the views of transitional care-related department doctors on transitional patient care and the role that the intelligent processor three-dimensional quality model can play, this article passed a review of the city ICU transferred patients from a hospital that conducted related investigations, reviewed related literature, conducted interviews with professionals, etc., collected relevant information, constructed case templates, and created a clinical research model using comprehensive quantitative and qualitative analysis methods. The results of the study found that, after treatment, patients transferred from the ICU based on the intelligent processor's three-dimensional quality model have higher physical activity than patients treated by other methods, the ratio is more than 20%, and the postoperative recovery efficiency of patients is higher than 15% and more. This shows that the three-dimensional quality model based on the intelligent processor can improve the important role in the transition period of patients transferred from ICU.


Molecular actions of a Mn(III)Porphyrin superoxide dismutase mimetic and peroxynitrite scavenger: reaction with nitric oxide and direct inhibition of NO synthase and soluble guanylyl cyclase.
Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), described as a superoxide dismutase mimetic and peroxynitrite scavenger, has been used previously to investigate the cytotoxic potential of superoxide and peroxynitrite in several pathological models. Here we report on the interference of MnTMPyP with NO/cGMP signaling using cultured endothelial cells as well as purified soluble guanylyl cyclase (sGC) either activated by the NO donor 2,2-diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO) or reconstituted with nitric oxide synthase (NOS). MnTMPyP inhibited endothelial cGMP accumulation induced by A23187 (0.3 microM) with an IC50 of 75.0 +/- 10.4 microM but had no significant effect on the potency of the Ca2+ ionophore. Purified NOS was inhibited by MnTMPyP (IC50 = 5.5 +/- 0.8 microM) because of an interference of the Mn-porphyrin with the reductase domain of the enzyme. The most pronounced actions of MnTMPyP were direct inhibition of sGC and scavenging of NO. Purified sGC stimulated with either Ca2+/calmodulin-activated NOS (in the presence of GSH) or DEA/NO (in the absence of GSH) was inhibited with IC50 values of 0.8 +/- 0.09 microM and 0.6 +/- 0.2 microM, respectively. In the presence of GSH, MnTMPyP was reduced to the Mn(II) complex, resulting in efficient scavenging of NO under these conditions. Our data demonstrate that MnTMPyP (i) interferes with the reductase domain of NOS, (ii) scavenges NO in the presence of GSH, and (iii) is a potent direct inhibitor of sGC. These results cast doubt on the usefulness of MnTMPyP and related Mn-porphyrin complexes as probes to study the involvement of peroxynitrite/superoxide in biological systems.


[Gynecological, hematological and metabolic studies during therapy with an estrogen-gestagen combination preparation].
Twenty women after menopause were submitted to substitution treatment with a biphasic hormone combination (Cyclacur¿). Nine of these had undergone hysterectomy + ovarectomy. Through 11 days each of the women was administered a daily dose of 2 mg estradiol-valerianate as estrogen. Subsequently, for another 10 days each was given the identical dose of estrogen plus 0.5 mg DL-norgestrel as gestagen. Upon this followed an intermission of 7 days without any medication. After 1 cycle of placebo, 7 cycles of medication were followed by 1 cycle of placebo again with regular controls. Climacteric signs and symptoms were eliminated entirely. In those women without hysterectomy withdrawal-menorrhagia occurred promptly 2--3 days after discontinuing medication. During the entire period of investigation there was no significant change in serum lipids, blood sugar values, or serum enzyme tests used as parameter of hepatic function. As far as hematology is concerned there was a moderate rise of hematocrit. No change of serum protein-bound iodine was observed.


Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain.
Developing procedures to delay the mechanisms of acute liver failure-induced death would increase patients' survival by allowing time for liver regeneration or to receive a liver for transplantation. Hyperammonemia is a main contributor to brain herniation and mortality in acute liver failure (ALF). Acute ammonia intoxication in rats leads to N-methyl-D-aspartate (NMDA) receptor activation in brain. Blocking these receptors prevents ammonia-induced death. Ammonia-induced activation of NMDA receptors could contribute to ALF-induced death. If this were the case, blocking NMDA receptors could prevent or delay ALF-induced death. The aim of this work was to assess 1) whether ALF leads to NMDA receptors activation in brain in vivo and 2) whether blocking NMDA receptors prevents or delays ALF-induced death of rats. It is shown, by in vivo brain microdialysis, that galactosamine-induced ALF leads to NMDA receptors activation in brain. Blocking NMDA receptors by continuous administration of MK-801 or memantine through miniosmotic pumps affords significant protection against ALF-induced death, increasing the survival time approximately twofold. Also, when liver injury is not 100% lethal (1.5 g/kg galactosamine), blocking NMDA receptors increases the survival rate from 23 to 62%. This supports that blocking NMDA receptors could have therapeutic utility to improve survival of patients with ALF.


Paucity of biliary ducts: A rare etiology of neonatal cholestasis.
We report a case of a newborn with cholestasis that was diagnosed as nonsyndromic Alagille syndrome. The main feature of the disease is a paucity of biliary ducts. There are two known types of the disease: the syndromic type which is associated with other congenital defects and the nonsyndromic type without other anomalies detected at birth. We describe the case and discuss its clinical and radiologic findings. We also discuss the various etiologies of cholestasis that are included in the differential diagnosis.


[Spirometry in a population of coal miners in Paipa, Colombia].
Respiratory diseases resulting from exposure to particulate matter such as in coal mining remains a research challenge in this country and a public health issue. Spirometry is a basic test of fundamental respiratory function for the diagnosis and monitoring of these types of chronic lung diseases. To determine spirometric values in the coal mining municipality of Paipa and their association with age and occupational exposure times. We conducted a descriptive cross-sectional study. The occupational respiratory disease questionnaire of the American Thoracic Society (ATS) was completed while spirometric measurements were performed and interpreted in accordance with international recommendations for conducting the test. The sample consisted of 226 coal mining workers of the municipality of Paipa. Twenty-eight subjects (12.3%) of the sample showed patterns of obstructive and restrictive respiratory disease with mild degrees of severity. Eighty subjects (35%) showed a decrease in the forced vital capacity ratio/expiratory volume in one second (FVC/FEV1). A statistically significant association between age range (p=0.002) and years of mining work (p=0.34) with the development of restrictive and obstructive disorders was found. Also, there was a statistically significant association between age range (p<0.01) and years of mining work (p<0.01) with various degrees of severity of the spirometric pattern. Spirometry is a useful test for detecting the presence of respiratory disorders in the population of coal miners. The time of exposure was significantly associated with the respiratory disease exhibited by these miners.


Polymorphisms in human immunoglobulin heavy chain variable genes and their upstream regions.
Germline variations in immunoglobulin genes influence the repertoire of B cell receptors and antibodies, and such polymorphisms may impact disease susceptibility. However, the knowledge of the genomic variation of the immunoglobulin loci is scarce. Here, we report 25 potential novel germline IGHV alleles as inferred from rearranged naïve B cell cDNA repertoires of 98 individuals. Thirteen novel alleles were selected for validation, out of which ten were successfully confirmed by targeted amplification and Sanger sequencing of non-B cell DNA. Moreover, we detected a high degree of variability upstream of the V-REGION in the 5'UTR, L-PART1 and L-PART2 sequences, and found that identical V-REGION alleles can differ in upstream sequences. Thus, we have identified a large genetic variation not only in the V-REGION but also in the upstream sequences of IGHV genes. Our findings provide a new perspective for annotating immunoglobulin repertoire sequencing data.


Data-driven course trajectories in primary care patients with major depressive disorder.
The chronic nature of MDD has been acknowledged as one of the key determinants of the burden associated with depression. Unfortunately, so far described prognostic factors have been inconsistent, possibly due to used course outcomes that are often based on arbitrary criteria/cut-offs. Therefore, the aim of the current study was to use data-driven trajectory groups based on closely spaced weekly severity ratings, as outcomes in prognostic research. The sample consisted of primary care patients with MDD (n = 153), who were followed up for a year with 52 consecutive weekly ratings of the nine DSM-IV MDD criterion symptoms. Growth Mixture Modeling (GMM) was used to reduce the interpersonal growth variation to an optimal set of clinically interpretable trajectory groups. Next, baseline course predictors were investigated and the prognostic (added) value of course-group membership was investigated for clinical outcomes after 1, 2, and 3 years. GMM resulted in four trajectory groups: "early remission" (40.2%), "late remission" (9.8%), "remission and recurrence" (17.0%), and "chronic" (33.0%). Multivariate predictors of "chronic" group membership were a prior suicide attempt, comorbid dysthymia, and lower levels of somatic depressive symptoms. Group membership predicted differences in depression severity and/or quality of life after 1, 2, and 3 years. The used data-driven approach provided a parsimonious and clinically informative way to describe course variation across MDD patients. Using the trajectory groups to investigate prognostic factors of MDD provided insight in potentially useful prognostic factors. Importantly, trajectory-group membership was itself a strong predictor of future mental well-being.


Induced modulation instability of surface plasmon polaritons.
We demonstrate the effect of the modulation instability of surface plasmon polariton waves in a layer structure of subwavelength thickness. The expressions describing the dispersion and nonlinear properties of this structure are derived. It is shown that the modulation instability effect could be used for the generation of ultrashort pulse trains and the localization of optical fields with a scale less than 1 micron.


Cardiac angiosarcoma treated with resection and adjuvant radiation therapy.
Primary cardiac angiosarcoma is a rare and aggressive tumor with a remarkably high rate of metastasis. Due to the high rate of metastasis, surgical resection is often limited and survival expectations modest. This report describes the case of a 35-year-old African-American woman with initially non-metastatic primary right atrial angiosarcoma who was treated with surgical resection of the primary tumor, reconstruction of the right atrium, and patch repair of the atrial septum via Gore-Tex patch. She underwent post-operative radiation therapy to the atrial bed with curative intent. However, after eight months of symptom-free survival, she presented with extensive metastases within bone and the right retroperitoneum without local recurrence. Palliative radiation treatment commenced for the metastases in the retroperitoneum and cervical spine.


Phosphate-Induced Reaction to Prepare Coal-Based P-Doped Hard Carbon with a Hierarchical Porous Structure for Improved Sodium-Ion Storage.
The use of coal as a precursor for producing hard carbon is favored due to its abundance, low cost, and high carbon yield. To further optimize the sodium storage performance of hard carbon, the introduction of heteroatoms has been shown to be an effective approach. However, the inert structure in coal limits the development of heteroatom-doped coal-based hard carbon. Herein, coal-based P-doped hard carbon was synthesized using Ca3(PO4)2 to achieve homogeneous phosphorus doping and inhibit carbon microcrystal development during high-temperature carbonization. This involved a carbon dissolution reaction where Ca3(PO4)2 reacted with SiO2 and carbon in coal to form phosphorus and CO. The resulting hierarchical porous structure allowed for rapid diffusion of Na+ and resulted in a high reversible capacity of 200 mAh g-1 when used as an anode material for Na+ storage. Compared to unpretreated coal-based hard carbon, the P-doped hard carbon displayed a larger initial coulombic efficiency (64%) and proportion of plateau capacity (47%), whereas the unpretreated carbon only exhibited an initial coulombic efficiency of 43.1% and a proportion of plateau capacity of 29.8%. This work provides a green, scalable approach for effective microcrystalline regulation of hard carbon from low-cost and highly aromatic precursors.


Future and applications of cloning.
The birth of viable offspring from somatic cell nuclear transfer (SCNT) in mammals caused a major re-examination of the understanding of the commitment of cells to specific tissue lineages during differentiation. The questions of whether cells undergo dedifferentiation or transdifferentiation during the development of offspring and how these changes are controlled is a source of ongoing debate that is yet to be resolved. Irrespective of the outcome of this debate, it is clear that cloning using SCNT has a place and purpose in the future of research and animal breeding. The future uses of SCNT could include the production of transgenic mice, the production of transgenic livestock and assisting with the re-establishment of endangered species. Human medicine also would benefit from future use of SCNT because it would allow the production of patient-specific embryonic stem cells.


[Miliary tuberculosis in a patient with morbus Bechterew treated with tumour necrosis factor-alpha].
Tumour necrosis factor (TNF)-α inhibitors are registered for treatment of several severe dermatologic, rheumatologic and gastrointestinal diseases. Due to TNF-α's important role in the immune system patients have increased risk of serious infections during treatment with TNF-α inhibitor. We here present a case of miliary tuberculosis complicated by pericardial effusion in a Danish man treated with TNF-α inhibitor that emphasizes the need for rapid examination of new symptoms in this patient category.


Detecting and predicting balance decline in Parkinson disease: a prospective cohort study.
The natural progression of balance decline in individuals with Parkinson disease (PD) is not well understood. We aimed to: 1) compare the utility of three standardized clinical measures for detecting balance decline over 1-year, 2) identify components of balance susceptible to decline, and 3) identify factors useful for predicting future balance decline. Eighty people with PD (59% male; mean age 68.2 ± 9.3; Hoehn & Yahr range I-IV) completed Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Berg Balance Scale (BBS) assessments. Baseline predictor variables included the MDS-UPDRS III sub-score, presence of freezing, 6-month fall history, age, gender, and physical activity. Balance and MDS-UPDRS III assessments were repeated at 6 (n = 51) and 12 months (n = 44). BESTest and Mini-BESTest score declined over 6 and 12 months (P < 0.01). Postural responses, stability limits, and sensory orientation were most susceptible to decline. BBS score did not change (P > 0.01). MDS-UPDRS III score was unchanged over 6 months (P > 0.01), but declined over 12 months (P < 0.01). Change in BESTest score over 6 months was related to baseline MDS-UPDRS III, H&Y, freezing, and fall history (P < 0.05). Change in BESTest score over 12 months was related to baseline MDS-UPDRS III and freezing (P < 0.05). Change in Mini-BESTest over 12 months was related to baseline MDS-UPDRS III and age (P < 0.05). The BESTest and Mini-BESTest were responsive to balance decline in individuals with PD and helped to identify decline in underlying balance components. Disease severity and freezing most consistently predicted balance decline in persons with PD.


Changes in spatiotemporal parameters, joint and CoM kinematics and leg stiffness in novice runners during a high-intensity fatigue protocol.
Even though running enjoys growing popularity, the effects of fatigue on the running kinematics of novices have rarely been studied. This is surprising, given the risk of running-related injuries when detrimental movement patterns are adopted. Therefore, the goal of the present study was to characterize the effects of fatigue induced by a high-intensity running protocol on spatiotemporal and stiffness parameters as well as on joint kinematics and center of mass (CoM) motion in novice runners. 14 participants performed a standardized treadmill familiarization and ran at 13 km/h until voluntary exhaustion. Kinematics were captured using a 3D motion capture system. Spatiotemporal and stiffness parameters as well as the range of motion (RoM) of the joints and CoM were compared by use of paired t-tests. Time series of the joint angles and CoM motion were analyzed by the statistical parametric mapping method. The results revealed that novice runners did not change spatiotemporal or stiffness parameters, but showed adaptations in joint kinematics, e.g. decreased dorsiflexion and increased pronation in the ankle joint during the swing phase. The findings of this study underline the importance of strengthening the ankle joint to prevent excessive pronation and increase its stability in novice runners.


Developments in biotechnological production of sweet proteins.
Most proteins are tasteless and flavorless, while some proteins elicit a sweet-taste response on the human palate. Six proteins, thaumatin, monellin, mabinlin, brazzein, egg lysozyme, and neoculin (previously considered as curculin) have been identified as sweet-tasting proteins. However, no common features among them have been observed. Herein, recent advances in the research of sweet-tasting proteins and the production of such proteins by biotechnological approaches are reviewed. Information on the structure-sweetness relationship for these proteins would help not only in the clarification of the mechanism of interaction of sweet-tasting proteins with their receptors, but also in the design of more effective low-calorie sweeteners.


Composite, large spirochetes from microbial mats: spirochete structure review.
Phenomena previously unknown in free-living spirochetes are reported: large-sized cells with variable diameter (length to 100 microns, width between 0.4 and 3.0 microns), composite structure (smaller spirochetes inside larger ones), and positive phototropic behavior. These bacteria, Spirosymplokos, are compared with all other spirochete genera. The large spirochete, grown in mixed culture, was studied live and by transmission EM. The protoplasmic cylinder was replete with spherical granules 20-32 nm in diameter, and three to six periplasmic 26-nm flagella were inserted subterminally. Comparably granulated and flagellated small spirochetes were located inside the protoplasmic cylinder and in the periplasm of the large ones. When exposed to air, movement became erratic, protoplasmic cylinders retracted to lie folded inside the outer membrane, and refractile membranous structures formed. From one to four structures per still-moving spirochete were seen. Spirosymplokos was enriched from laboratory samples exposed to oxygen-rich and desiccating, but not dry, conditions for at least 4 mo after removal of microbial mat from the field.


Variation in adult stress resistance does not explain vulnerability to climate change in copper butterflies.
Ongoing climate change is a major threat to biodiversity. However, although many species clearly suffer from ongoing climate change, others benefit from it, for example, by showing range expansions. However, which specific features determine a species' vulnerability to climate change? Phenotypic plasticity, which has been described as the first line of defence against environmental change, may be of utmost importance here. Against this background, we here compare plasticity in stress tolerance in 3 copper butterfly species, which differ arguably in their vulnerability to climate change. Specifically, we investigated heat, cold and desiccation resistance after acclimatization to different temperatures in the adult stage. We demonstrate that acclimation at a higher temperature increased heat but decreased cold tolerance and desiccation resistance. Contrary to our predictions, species did not show pronounced variation in stress resistance, though plastic capacities in temperature stress resistance did vary across species. Overall, our results seemed to reflect population-rather than species-specific patterns. We conclude that the geographical origin of the populations used should be considered even in comparative studies. However, our results suggest that, in the 3 species studied here, vulnerability to climate change is not in the first place determined by stress resistance in the adult stage. As entomological studies focus all too often on adults only, we argue that more research effort should be dedicated to other developmental stages when trying to understand insect responses to environmental change.


Ethnic Socialization in Neighborhood Contexts: Implications for Ethnic Attitude and Identity Development Among Mexican-Origin Adolescents.
Neighborhood Latino ethnic concentration, above and beyond or in combination with mothers' and fathers' ethnic socialization, may have beneficial implications for minority adolescents' ethnic attitude and identity development. These hypotheses, along with two competing hypotheses, were tested prospectively (from x¯age = 12.79-15.83 years) in a sample of 733 Mexican-origin adolescents. Neighborhood ethnic concentration had beneficial implications for ethnic identity processes (i.e., ethnic exploration and perceived peer discrimination) but not for ethnic attitudes. For Mexico-born adolescents, high maternal ethnic socialization compensated for living in neighborhoods low on ethnic concentration. Findings are discussed vis-à-vis the ways in which they address major gaps in the neighborhood effects literature and the ethnic and racial identity development literature.


Diagnosis and treatment of levothyroxine pseudomalabsorption.
Many causes of malabsorption of levothyroxine in patients with hypothyroidism have been thoroughly described in literature. Pseudomalabsorption, poor compliance of the patient with the therapy regime, is the most common cause of failure of levothyroxine therapy. Pseudomalabsorption is characterised by a deficient diagnostic process, patient denial and difficulties in treatment. The present article provides guidelines in diagnosing and treating pseudomalabsorption in hypothyroidism.


STIP1/HOP Regulates the Actin Cytoskeleton through Interactions with Actin and Changes in Actin-Binding Proteins Cofilin and Profilin.
Cell migration plays a vital role in both health and disease. It is driven by reorganization of the actin cytoskeleton, which is regulated by actin-binding proteins cofilin and profilin. Stress-inducible phosphoprotein 1 (STIP1) is a well-described co-chaperone of the Hsp90 chaperone system, and our findings identify a potential regulatory role of STIP1 in actin dynamics. We show that STIP1 can be isolated in complex with actin and Hsp90 from HEK293T cells and directly interacts with actin in vitro via the C-terminal TPR2AB-DP2 domain of STIP1, potentially due to a region spanning two putative actin-binding motifs. We found that STIP1 could stimulate the in vitro ATPase activity of actin, suggesting a potential role in the modulation of F-actin formation. Interestingly, while STIP1 depletion in HEK293T cells had no major effect on total actin levels, it led to increased nuclear accumulation of actin, disorganization of F-actin structures, and an increase and decrease in cofilin and profilin levels, respectively. This study suggests that STIP1 regulates the cytoskeleton by interacting with actin, or via regulating the ratio of proteins known to affect actin dynamics.


IL-7 Restores T Lymphocyte Immunometabolic Failure in Septic Shock Patients through mTOR Activation.
T lymphocyte alterations are central to sepsis pathophysiology, whereas related mechanisms remain poorly understood. We hypothesized that metabolic alterations could play a role in sepsis-induced T lymphocyte dysfunction. Samples from septic shock patients were obtained at day 3 and compared with those from healthy donors. T cell metabolic status was evaluated in the basal condition and after T cell stimulation. We observed that basal metabolic content measured in lymphocytes by nuclear magnetic resonance spectroscopy was altered in septic patients. Basal ATP concentration, oxidative phosphorylation (OXPHOS), and glycolysis pathways in T cells were decreased as well. After stimulation, T lymphocytes from patients failed to induce glycolysis, OXPHOS, ATP production, GLUT1 expression, glucose entry, and proliferation to similar levels as controls. This was associated with significantly altered mTOR, but not Akt or HIF-1α, activation and only minor AMPKα phosphorylation dysfunction. IL-7 treatment improved mTOR activation, GLUT1 expression, and glucose entry in septic patients' T lymphocytes, leading to their enhanced proliferation. mTOR activation was central to this process, because rapamycin systematically inhibited the beneficial effect of recombinant human IL-7. We demonstrate the central role of immunometabolism and, in particular, mTOR alterations in the pathophysiology of sepsis-induced T cell alterations. Our results support the rationale for targeting metabolism in sepsis with recombinant human IL-7 as a treatment option.


Exploring the activation modes of a rotaxane-based switchable organocatalyst.
The reactivity of a rotaxane that acts as an aminocatalyst for the functionalization of carbonyl compounds through HOMO and LUMO activation pathways has been studied. Its catalytic activity is explored for C-C and C-S bond forming reactions through iminium catalysis, in nucleophilic substitutions and additions through enamine intermediates, in Diels-Alder reactions via trienamine catalysis, and in a tandem iminium-ion/enamine reaction. The catalyst can be switched "on" or "off", effectively controlling the rate of all of these chemical transformations, by the in situ change of the position of the macrocycle between two different binding sites on the rotaxane thread.


Targeting Two-Pore-Domain Potassium Channels by Mechanical Stretch Instantaneously Modulates Action Potential Transmission in Mouse Sciatic Nerves.
Recent reports indicate dominant roles of TRAAK and TREK-1 channels, i.e., mechanosensitive two-pore-domain potassium channels (K2P) at the nodes of Ranvier for action potential repolarization in mammalian peripheral nerves. Functional changes in mammalian peripheral nerve conduction by mechanical stretch studied by recording compound action potentials lack the necessary resolution to detect subtle neuromodulatory effects on conduction velocity. In this study, we developed a novel in vitro approach that enables single-fiber recordings from individual mouse sciatic nerve axons while delivering computer-controlled stepped stretch to the sciatic nerve trunk. Axial stretch instantaneously increased the conduction delay in both myelinated A-fibers and unmyelinated C-fibers. Increases in conduction delay linearly correlated with increases in axial stretch ratio for both A- and C-fibers. The slope of the increase in conduction delay versus stretch ratio was steeper in C-fibers than in A-fibers. Moderate axial stretch (14-19% of in vitro length) reversibly blocked 37.5% of unmyelinated C-fibers but none of the eight myelinated A-fibers tested. Application of arachidonic acid, an agonist to TRAAK and TREK-1 to sciatic nerve trunk, blocks axonal transmission in both A- and C-fibers with delayed onset and prolonged block. Also, the application of an antagonist ruthenium red showed a tendency of suppressing the stretch-evoked increase in conduction delay. These results could draw focused research on pharmacological and mechanical activation of K2P channels as a novel neuromodulatory strategy to achieve peripheral nerve block.


Molecular dynamics simulation study of Plasmodium falciparum and Escherichia coli SufA: Exploration of conformational changes possibly involved in iron-sulfur cluster transfer.
Iron-sulfur (Fe-S) clusters are one of the earliest known metal complexes in biological molecules. Suf system is one of the Fe-S biogenesis pathways. SufA belongs to the Suf pathway. It is an A-type carrier protein that transfers Fe-S clusters from the scaffold to target proteins. Structural studies were performed for the Suf pathway protein, SufA, in order to explore the conformational changes that probably aid in the transfer of Fe-S clusters to target proteins. Three-dimensional (3D) structure of Plasmodium falciparum (Pf) SufA homodimer was obtained by homology modeling using 3D structure of Escherichia coli (Ec) SufA as template. Molecular dynamics (MD) simulation of Pf SufA and Ec SufA homodimers followed by trajectory and pocket analyses were carried out. A co-ordinated displacement of the homodimeric chains in the interfacial region, resembling a swinging trapeze-like movement was observed. Potential involvement of this swinging trapeze-like movement of the residues belonging to the interfacial region has been proposed as a probable mechanism that assists in the transfer of Fe-S cluster from SufA to apo proteins. This was substantiated by protein-protein interaction studies in Pf SufA by performing molecular docking of 3D conformations of Pf SufA obtained from MD trajectory at every 1 ns interval with Pf ferredoxin.Communicated by Ramaswamy H. Sarma.


Two new synonyms in the dung beetle genus Parachorius (Coleoptera: Scarabaeidae: Scarabaeinae) from the Oriental Region.
The dung beetle genus Parachorius Harold, 1873 (= Cassolus Sharp, 1875) belongs to the monotypic tribe Parachoriini Tarasov, 2017 and includes 19 species from the Oriental and southeastern Palaearctic Regions (Tarasov 2017). Two recent studies (Ochi et al. 2017a, b) described two new species of this genus from Laos and Sumatra. The investigation of detailed descriptions and illustrations from those studies and their assessment in the light of the recent revision of Parachorius (Tarasov 2017) revealed that those new species are synonyms of earlier described ones: P. javanus (Boucomont, 1914) = P. singgalangensis Ochi, Kon Hartini, 2017, new synonymy, and P. fukiensis (Balthasar, 1960) = C. laosensis Ochi, Kon Higurashi, 2017, new synonymy. Unfortunately, this oversight happened because the authors of those new species did not check the type material of already described taxa.


Consistently Showing Your Best Side? Intra-individual Consistency in #Selfie Pose Orientation.
Painted and photographic portraits of others show an asymmetric bias: people favor their left cheek. Both experimental and database studies confirm that the left cheek bias extends to selfies. To date all such selfie studies have been cross-sectional; whether individual selfie-takers tend to consistently favor the same pose orientation, or switch between multiple poses, remains to be determined. The present study thus examined intra-individual consistency in selfie pose orientations. Two hundred selfie-taking participants (100 male and 100 female) were identified by searching #selfie on Instagram. The most recent 10 single-subject selfies for the each of the participants were selected and coded for type of selfie (normal; mirror) and pose orientation (left, midline, right), resulting in a sample of 2000 selfies. Results indicated that selfie-takers do tend to consistently adopt a preferred pose orientation (α = 0.72), with more participants showing an overall left cheek bias (41%) than would be expected by chance (overall right cheek bias = 31.5%; overall midline bias = 19.5%; no overall bias = 8%). Logistic regression modellng, controlling for the repeated measure of participant identity, indicated that sex did not affect pose orientation. However, selfie type proved a significant predictor when comparing left and right cheek poses, with a stronger left cheek bias for mirror than normal selfies. Overall, these novel findings indicate that selfie-takers show intra-individual consistency in pose orientation, and in addition, replicate the previously reported left cheek bias for selfies and other types of portrait, confirming that the left cheek bias also presents within individuals' selfie corpora.


Features extraction and multi-classification of sEMG using a GPU-Accelerated GA/MLP hybrid algorithm.
Surface electromyography (sEMG) signal is the combined effect of superficial muscle EMG and neural electrical activity. In recent years, researchers did large amount of human-machine system studies by using the physiological signals as control signals. To develop and test a new multi-classification method to improve performance of analyzing sEMG signals based on public sEMG dataset. First, ten features were selected as candidate features. Second, a genetic algorithm (GA) was applied to select representative features from the initial ten candidates. Third, a multi-layer perceptron (MLP) classifier was trained by the selected optimal features. Last, the trained classifier was used to predict the classes of sEMG signals. A special graphics processing unit (GPU) was used to speed up the learning process. Experimental results show that the classification accuracy of the new method reached higher than 90%. Comparing to other previously reported results, using the new method yielded higher performance. The proposed features selection method is effective and the classification result is accurate. In addition, our method could have practical application value in medical prosthetics and the potential to improve robustness of myoelectric pattern recognition.


A transposon-directed epigenetic change in ZmCCT underlies quantitative resistance to Gibberella stalk rot in maize.
A major resistance quantitative trait locus, qRfg1, significantly enhances maize resistance to Gibberella stalk rot, a devastating disease caused by Fusarium graminearum. However, the underlying molecular mechanism remains unknown. We adopted a map-based cloning approach to identify the resistance gene at qRfg1 and examined the dynamic epigenetic changes during qRfg1-mediated maize resistance to the disease. A CCT domain-containing gene, ZmCCT, is the causal gene at the qRfg1 locus and a polymorphic CACTA-like transposable element (TE1) c. 2.4 kb upstream of ZmCCT is the genetic determinant of allelic variation. The non-TE1 ZmCCT allele is in a poised state, with predictive bivalent chromatin enriched for both repressive (H3K27me3/H3K9me3) and active (H3K4me3) histone marks. Upon pathogen challenge, this non-TE1 ZmCCT allele was promptly induced by a rapid yet transient reduction in H3K27me3/H3K9me3 and a progressive decrease in H3K4me3, leading to disease resistance. However, TE1 insertion in ZmCCT caused selective depletion of H3K4me3 and enrichment of methylated GC to suppress the pathogen-induced ZmCCT expression, resulting in disease susceptibility. Moreover, ZmCCT-mediated resistance to Gibberella stalk rot is not affected by photoperiod sensitivity. This chromatin-based regulatory mechanism enables ZmCCT to be more precise and timely in defense against F. graminearum infection.


A novel method for detection of IFN-lambda 3 binding to cells for quantifying IFN-lambda receptor expression.
Type III interferons (IFN-lambdas) are important antiviral cytokines that also modulate immune responses acting through a unique IFN-λR1/IL-10R2 heterodimeric receptor. Conflicting data has been reported for which cells express the IFN-λR1 subunit and directly respond to IFN-λs. In this study we developed a novel method to measure IFN-λ3 binding to IFN-λR1/IL-10R2 on the surface of cells and relate this to a functional readout of interferon stimulated gene (ISG) activity in various cell lines. We show that Huh7.5 hepatoma cells bind IFN-λ3 at the highest levels with the lowest Kd(app), translating to the highest induction of various ISGs. Raji and Jurkat cell lines, representing B and T cells, respectively, moderately bind IFN-λ3 and have lower ISG responses. U937 cells, representing monocytes, did not bind IFN-λ3 well and therefore, did not have any ISG induction. Importantly, knockdown of IFNLR1 in Huh7.5 cells decreased our binding signal proportionally and reduced ISG induction by up to 93%. IFN-λ3 responsiveness increased over time with maximal ISG responses seen at 24h for all but one gene. These data confirm our new IFN-λ3 binding assay can be used to quantify IFN-λ receptor surface expression on a variety of cell types and reflects IFN-λ3 responsiveness.


Borrelia burgdorferi BBA74, a periplasmic protein associated with the outer membrane, lacks porin-like properties.
The outer membrane of Borrelia burgdorferi, the causative agent of Lyme disease, contains very few integral membrane proteins, in contrast to other gram-negative bacteria. BBA74, a Borrelia burgdorferi plasmid-encoded protein, was proposed to be an integral outer membrane protein with putative porin function and designated as a 28-kDa outer membrane-spanning porin (Oms28). In this study, the biophysical properties of BBA74 and its subcellular localization were investigated. BBA74 is posttranslationally modified by signal peptidase I cleavage to a mature 25-kDa protein. The secondary structure of BBA74 as determined by circular dichroism spectroscopy consists of at least 78% alpha-helix with little beta-sheet structure. BBA74 in intact B. burgdorferi cells was insensitive to proteinase K digestion, and indirect immunofluorescence microscopy showed that BBA74 was not exposed on the cell surface. Triton X-114 extraction of outer membrane vesicle preparations indicated that BBA74 is not an integral membrane protein. Taken together, the data indicate that BBA74 is a periplasmic, outer membrane-associated protein that lacks properties typically associated with porins.


Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow-up.
The long-term outcome and spectrum of disease of nontuberculous mycobacterial immune reconstitution syndrome have not been described. We report the findings of an observational study. Among 51 patients (43 with Mycobacterium avium complex [MAC] infection, 2 with Mycobacterium genavense infection, and 6 whose samples were smear positive but culture negative) from 1993-2004, the median follow-up period was 29 months. The incidence of nontuberculous mycobacterial immune reconstitution syndrome was 3.5% among patients initiating highly active antiretroviral therapy (HAART) with a baseline CD4+ cell count of <100 cells/microL. Three main clinical presentations were peripheral lymphadenitis (in 17 patients), pulmonary-thoracic disease (in 15 patients), and intra-abdominal disease (in 13 patients). Six other patients had cases that involved joint, spine, prostate, skin, soft tissue, and spontaneously resolving MAC bacteremia. Disease was usually localized. Median CD4+ cell counts before initiation of HAART and at diagnosis were 20 and 120 cells/microL, respectively, and the median reduction in human immunodeficiency virus (HIV) RNA load was 2.5 log10 copies/mL. Intra-abdominal disease was frequently preceded by disseminated MAC infection (in 62% of cases, compared with 6%-33% of cases for other groups; P=.003) and accounted for 16 (43%) of 36 hospitalizations (compared with 5%-35% for other groups; P=.008). The relapse rate was not higher among 10 patients who received no MAC therapy or received MAC therapy for < or =2 weeks. Prednisone was associated with clinical responses in 8 (89%) of 9 patients with evaluable cases. In total, 7 patients (14%) had 13 subsequent culture-positive MAC events (6 of which were cases of immune reconstitution syndrome, and 7 of which were cases of disseminated MAC infection). Ten patients (20%) died (2 of disseminated MAC infection, 5 of other opportunistic infections, and 3 of HIV-unrelated causes). Nontuberculous mycobacterial immune reconstitution syndrome has a wide range of clinical presentations and severity. The long-term prognosis is favorable for HAART-adherent patients. Intra-abdominal disease is associated with greater morbidity than is peripheral lymphadenitis. The role of antimycobacterial therapy is uncertain, given the self-limited course of most nonabdominal cases.


Open pancreatic stenting with duct-to-mucosa anastomosis for pancreatic-duct obstruction after pancreaticoduodenectomy with pancreaticogastrostomy.
Pancreatic-duct dilatation is frequently observed in the patients who have undergone pancreaticoduodenectomy (PD). Pancreaticodigestive anastomotic stricture may occasionally develop after PD. Stenosis of the pancreaticoenterostomy induces obstructive chronic pancreatitis, which occurs due to primary stenosis or obstruction of the main pancreatic duct and causes in inflammation of the distal pancreas. The patency of the pancreaticoenterostomy is one of the most important factors affecting the functioning of the remnant pancreas and the quality of life. Endoscopic dilatation is one of the treatment options for stenosis of pancreaticogastrostomy (PG). However, the failure of endoscopic dilatation necessitates surgical approaches. We have described our technique of open pancreatic stenting with a duct-to-mucosa anastomosis for a case which the stenosis of PG could not be resolved by endoscopic dilatation. This technique dose not require re-resected PG or side-to-side pancreaticojejunostomy: the risk of anastomotic leakage is quite low and the procedure is minimally invasive.


MR imaging of solitary fibrous tumors in the head and neck.
Solitary fibrous tumor (SFT) is a very rare tumor. The purpose of this study is to determine the MR imaging features of SFT in the intracranial and extracranial head and neck regions. We retrospectively reviewed six MR images and two CT images of six histologically proven cases of SFT that occurred in four men and two women, and their ages ranged from 46 to 59 years. These imaging findings were correlated with the microscopic findings of their surgical specimens. Six SFTs arose in the meninges (the petrous ridge and the pituitary fossa), the parotid gland, the parapharyngeal space, the buccal space and the maxillary sinus. On the MR images, SFTs in the intracranial and extracranial head and neck regions were mostly isointense to the muscle on the T1-weighted images, they were hyperintense on the T2-weighted images and they all had intense enhancement. On the T1- and T2-weighted images, hypointense lines were observed within in five SFTs. On the CT images, the SFTs were hypodense to the muscle on the unenhanced images and they were heterogeneously enhanced on the contrast-enhanced images. An exceptional case of pituitary SFT was hypointense on the T2-weighted images and it was hyperdense on the unenhanced CT images, which correlated with the increased collagenous component and the cellular compactness. The imaging features of SFT are nonspecific; however, SFT should be included in the differential diagnosis of masses involving the intracranial and extracranial head and neck regions.


Report of a seminar and workshop on Food-based Dietary Guidelines and Nutrition Education: Bridging Science and Communication.
The 3-day seminar-workshop on 'Food-based Dietary Guidelines and Nutrition Education' was held from 22-24 July 1998 in Kuala Lumpur, Malaysia to present the latest scientific information on nutrition and health and to discuss its impact on the rationale and process for the development of food-based dietary guidelines (FBDG). The first two sessions were devoted to a review of the current information on the relation between lifestyle factors and chronic diseases, particularly obesity; the present health status and food consumption patterns in Malaysia; the current consensus on carbohydrates and fats and oils and the importance of considering the glycemic index of foods; and the importance of micronutrients in health and disease. The third and fourth sessions dealt with the rationale of FBDG and the process of their development, drawing from the 1990 FAO/WHO Consultation on Development of FBDG and the experience in the Philippines and in Europe. The importance of effective dissemination of nutrition messages to the public was thoroughhly discussed. The workshop sessions arrived at recommendations on important issues in the development of FBDG in the region, including main research and information needs, the steps in the development of FBDG, and strategies for their dissemination.


Statistical optimization of thermo-tolerant xylanase activity from Amazon isolated Bacillus circulans on solid-state cultivation.
A 2(2) factorial design was performed to find the best conditions of pH and temperature for xylanolytic activity of Bacillus circulans BL53 isolated from the Amazon environment. Solid-state cultivation was carried out on an inexpensive, abundant agro-industrial soybean residue. The central composite design (CCD) used for the analysis of treatment combinations showed that a second-order polynomial regression model was in good agreement with experimental results, with R(2) = 0.9369 (P < 0.05). The maximum activity was obtained at a high temperature (80 degrees C) and over a large pH range (4.0-7.0). Enzymatic activity was maintained in heated extracts up to 50 degrees C, suggesting that the xylanases of B. circulans BL53 are thermo-tolerant biocatalysts, being of interest for industrial processes. The crude enzyme extract hydrolyzed rice straw, sugar cane bagasse and soybean fiber and its activity was stimulated by Co(2+), Fe(3+), and beta-mercaptoethanol but inhibited by Mn(2+), Cu(2+), Ca(2+), Zn(2+), Ba(2+), Mg(2+) and by EDTA.


A computer simulation of the hypothalamic-pituitary-adrenal axis.
This paper describes the construction of a computer model that simulates the hypothalamic-pituitary-adrenal axis (HPA axis) regulation of cortisol production. It is presented to illustrate the process of physiological modeling using standard "off the shelf" technologies. The model simulates components of the HPA axis involved in the continuous secretion and elimination of cortisol, adrenocorticotropin (ACTH), and corticotropin releasing hormone (CRH). The physiological relations of these component pieces were modeled based on the current knowledge of their functioning. Rate constants, half lives, and receptor affinities were assigned values derived from the experimental literature. At its current level of development the model is able to accurately simulate the timing, magnitude and decay of the ACTH and cortisol concentration peaks resulting from the ovine-CRH stimulation test in normal and hypercortisolemic patients. The model will be used to predict the effects of lesions in different components of the HPA axis on the time course of cortisol and ACTH levels. We plan to use the model to explore the experimental conditions required to distinguish mechanisms underlying various disorders of the HPA axis, particularly depression. Efforts are currently underway to validate the model for a large variety of normal and pathological perturbations of the HPA axis.


Antigen-specific desensitization of patients allergic to penicillin.
Three penicillin-allergic patients with life-endangering infections requiring beta-lactam antibiotic therapy were desensitized by means of increasing oral then parenteral doses and were treated with full doses of beta-lactam agents. Malignant otitis externa caused by Pseudomonas aeruginosa, osteomyelitis caused by Staphylococcus aureus, and bacterial endocarditis caused by an enterococcus were treated with carbenicillin, nafcillin, and benzylpenicillin G, respectively. No acute allergic reactions occurred during desensitization or within 1 wk of the onset of therapy. Immediate wheal and flare skin-test reactions to beta-lactam determinants diminished or became negative after the desensitization procedure in each patient. Wheal and flare responses provoked by histamine, compound 48/80, and environmental antigens were not affected by the desensitization procedure or continued beta-lactam drug therapy. Mild urticaria appeared after 15 days of penicillin therapy in one patient and after 23 days of carbenicillin therapy in another patient. Skin-test reactions to penicillin reagents had reverted to positive at the time of the urticarial reactions. One patient developed a severe immune hemolytic anemia after 10 days of therapy with nafcillin. The results of this study indicate that acute clinical desensitization of these three penicillin-allergic patients was associated with antigen-specific desensitization of tissue mast cells.


Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy.
Globally, human immunodeficiency virus type 1 (HIV-1) infection is a major health burden for which successful therapeutic options are still being investigated. Challenges facing current drugs that are part of the established life-long antiretroviral therapy (ART) include toxicity, development of drug resistant HIV-1 strains, the cost of treatment, and the inability to eradicate the provirus from infected cells. For these reasons, novel anti-HIV-1 therapeutics that can prevent or eliminate disease progression including the onset of the acquired immunodeficiency syndrome (AIDS) are needed. While development of HIV-1 vaccination has also been challenging, recent advancements demonstrate that infection of HIV-1-susceptible cells can be prevented in individuals living with HIV-1, by targeting C-C chemokine receptor type 5 (CCR5). CCR5 serves many functions in the human immune response and is a co-receptor utilized by HIV-1 for entry into immune cells. Therapeutics targeting CCR5 generally involve gene editing techniques including CRISPR, CCR5 blockade using antibodies or antagonists, or combinations of both. Here we review the efficacy of these approaches and discuss the potential of their use in the clinic as novel ART-independent therapies for HIV-1 infection.


Induction of transplantation tolerance in humans using fetal cell transplants.
When engrafted with donor stem cells and lymphoid cells, patients develop transplantation tolerance to donor antigens. We analyzed the mechanism of tolerance induction in immunoincompetent recipients whose immunity has been reconstituted by transplantation of mismatched stem cells. Seven infants or human fetuses received fetal liver transplants as a treatment for severe combined immunodeficiency disease. After reconstitution of immunity by lymphocytes developed from donor stem cells, T-cell clones were produced and analyzed. Because donors and recipients were HLA mismatched, it was easy to demonstrate the donor origin of the T-cell clones. These clones were shown to have developed tolerance to histocompatibility antigens of the stem cell donor via a process of clonal deletion (probably as a result of contact with donor-derived macrophages and dendritic cells). They were also tolerant to histocompatibility antigens of the host but through a different mechanism: many clones recognized these antigens but had no detrimental effect on the target cells exhibiting host antigens, either in vitro or in vivo. Clonal anergy was therefore the cause of this tolerance to host determinants, resulting in a lack of graft-versus-host disease and of autoimmunity. The contact between developing T cells of donor origin and host epithelial cells within the host thymus may explain this colonal anergy. It should be noted that all patients had high serum levels of interleukin-10, which might have contributed to the persistent engraftment and tolerance.


Regulation of keratinocyte growth factor and scatter factor in cyclosporin-induced gingival overgrowth.
Epithelial proliferation is a histological characteristic of drug-induced gingival overgrowth. Keratinocyte growth factor (KGF) and scatter factor (SF) are fibroblast-derived growth factors with potent mitogenic and motogenic effects on epithelial cells, and, therefore, could be involved in the pathogenesis of gingival overgrowth. The aims of this study were to investigate: (i) the effects of cyclosporin on KGF and SF expression by gingival fibroblasts; and (ii) the expression levels of KGF and SF mRNA in normal and overgrown gingival tissue. The KGF and SF protein production was determined by enzyme-linked immunosorbent assay. Relative levels of KGF and SF mRNA expression were determined using semi-quantitative reverse transcriptase polymerase chain reaction. Expression levels in biopsies of normal and overgrown gum were also determined. In overgrown fibroblasts, 500 ng/ml cyclosporin significantly inhibited KGF and SF mRNA and protein while 2000 ng/ml cyclosporin induced a stimulatory effect. In normal cells cyclosporin significantly increased both KGF and SF. KGF and SF mRNA was detected in both normal and overgrown tissues with a tendency towards increased expression levels in overgrown tissue. These results suggest that KGF and SF may have an important role in cyclosporin-induced gingival overgrowth.


X reference radiation qualities produced with tube voltages above 300 kV for the calibration and testing of dosemeters.
In the international standard ISO 4037-1, only X reference radiation qualities produced with tube voltages of up to 300 kV and with mean photon energies of lower than 250 keV are defined. Higher energy reference photon fields are given with a mean energy only from 662 keV (S-Cs) upwards. To close this energy gap, four new X radiation qualities, produced with tube voltages of 350 kV and 400 kV, were realised. The filtration of two of these qualities-called N-350 and N-400-was chosen in such a way that they agree with the specifications of the narrow-spectrum series (N-series) defined in ISO 4037-1. The other qualities which have been created-called H-350 and H-400-can be assigned to the high air-kerma rate series (H-series). The fluence spectra of these qualities were measured by using X-ray spectrometry. The values of 23 characteristic parameters were determined and compared with the ISO specifications for X-ray reference fields.


Videocapillaroscopic findings in the microcirculation of the psoriatic plaque.
Videocapillaroscopy (VCP) is a method to study the morphology and dynamics of microcirculation, but information about capillaroscopic features of the psoriatic plaque is limited. To investigate the distribution, morphology and density of capillaries in lesional and perilesional skin of the psoriatic plaque. VCP of a well-delimited plaque of the trunk, arms or legs in 15 consecutive patients with untreated, chronic plaque psoriasis was performed. In the lesional skin, capillaries were tortuous and dilated, homogeneously appearing as 'bushy'. In the perilesional skin, capillary loops seemed to be on a parallel course with respect to the skin surface, with their apex directed towards the marginal zone. The number of capillary loops per area unit was statistically increased in perilesional compared to lesional skin. According to the morphology, distribution and density of capillary loops, two different angiogenetic patterns were found in lesional and perilesional skin.


Elimination of background recombination: somatic induction of Cre by combined transcriptional regulation and hormone binding affinity.
Somatically inducible Cre lines are used extensively to study gene function. However, a background level of spontaneous recombination due to unregulated expression of Cre is particularly confounding for cancer models in which following the pathogenesis of the disease requires the introduction of sporadic mutations that are monitored over time. In three transgenic mouse lines, two with Cre activity controlled at the transcriptional level (Ahcre, Mx1cre), and one controlled at the protein level (R26creER(T)), we have identified sporadic recombination at the R26R reporter locus in multiple tissues. Detailed analysis of the intestinal epithelium suggests that recombination can occur both during development and as an ongoing process in adult life. Here we present a new inducible Cre transgenic line, AhcreER(T), in which control of Cre activity is regulated at two levels: by transcriptional control of the Ah promoter and by a requirement for Tamoxifen binding. There is no detectable background intestinal recombination in adult AhcreER(T) mice on the R26R background. Inducible and dose-dependent recombination can be achieved by a single combined treatment with beta-napthoflavone and Tamoxifen.


Effect of iron-deficiency anemia on hormone levels and thermoregulation during cold exposure.
When exposed to an ambient temperature of 4 degrees C, iron-deficient anemic rats become hypothermic. This lesion is related more to anemia than to tissue iron deficiency, since exchange transfusion to hematocrits over 25 restored normal thermoregulatory performance. Likewise poor cold responses were induced in control rats by transfusion to low hematocrits. Cold sensitivity in all anemic animals was paralleled by poor thyroid responses: there was a significant positive correlation between hematocrit and percent rise in triiodothyronine (r = 0.63) and thyroxine (r = 0.53) during 6 h at 4 degrees C. Basal levels of thyroid-stimulating hormone (TSH) were similar in control and iron-deficient animals: after cold exposure, TSH rose to higher levels in those animals with hematocrits over 25 than in those with lower hematocrits. Diminished O2 delivery to tissues responsible for heat production is probably a major component of the cold sensitivity of anemic rats. The novel finding that thyroid hormone responses are compromised by anemia implies effects on hormonal regulation that may also contribute to this functional lesion.


Apoptotic microparticles mediate the association between bisphenol A and subclinical atherosclerosis in a young population: A population-based study.
Bisphenol A (BPA) exposure is associated with atherosclerotic cardiovascular diseases. The interactions between BPA, extracellular microparticles (MPs), and atherosclerosis are unknown. A total of 103,756 young students participated in the mass urine-screening program in Taiwan between 1992 and 2000 were analyzed. After exclusion, 886 subjects were recruited to test the relationships between serum level of BPA, endothelial and platelet MPs as well as subclinical atherosclerosis represented by carotid artery intima-media thickness (CIMT). We found that an increment of one unit of log-BPA could lead to significant association between thicker CIMT and concentrations of endothelial microparticles and platelet microparticles in the cohort (odds ratio (OR) 1.23, P < 0.001). CD31 + /CD42a- (> 50%, OR 1.229, P = 0.001) and CD31 + /CD42a+ (≦ 50%, OR 1.262, P = 0.017 and > 50%, OR 1.212, P = 0.006) were significantly associated with thicker CIMT in the presence of elevated BPA. When considering the interactions between CD31 + /CD42a- and CD31 + /CD42a+ , we observed increased OR as CD31 + /CD42a- was greater than 50% (CD31 +/CD42a- > 50% and CD31 +/CD42a+ ≦ 50%, OR 1.356, P = 0.029; CD31 +/CD42a- > 50% and CD31 +/CD42a+ > 50%, OR 1.204, P = 0.014). Our study identified a higher risk of thicker CIMT associated with altered MPs in the presence of elevated BPA levels. BPA exposure is associated with endothelial dysfunction and subclinical atherosclerosis in a young population.


Mammary growth pattern in goats during pregnancy and lactation.
Nine groups of five dairy goats from four breeds, with each breed represented at least once in each group, were in our experiment to measure mammary gland growth. Groups were virgins, days 90 to 100 pregnancy, 5 days prepartum (145 days pregnancy), 1 or 2 days prepartum, and 1 or 2, 5, 10, 15, and 30 days in lactation. Virgins were 19 mo old while all others had one pregnancy and lactation prior to experiment. Indices of mammary growth included untrimmed and trimmed wet weights of udders, dried fat-free tissue weights, deoxyribonucleic acid and ribonucleic acid contents. Each index was in a regression equation best to describe the pattern of mammary growth. These included linear, quadratic, cubic, and exponential model Y = AebX in which Y was the index of mammary growth and X was the day of pregnancy. Total deoxyribonucleic acid was the best index of mammary growth with a correlation of .95 in the exponential model. The predictive equation for total deoxyribonucleic acid in milligram was Y = 167e.019X on a daily basis, and the rate of growth on a monthly basis was .57. Mammary growth in goats continued into early lactation, peaking at day 5. Ribonucleic acid doubled on the day after parturition, which reflected the rapid increase in protein synthesis at this time.