Proportion of 11778 mutant mitochondrial DNA and clinical expression in a thai population with leber hereditary optic neuropathy.
The proportion of mutant mtDNA in blood has been found to correlate with the frequency of visual loss in cases with mtDNA mutations associated with Leber hereditary optic neuropathy (LHON), especially in men. We sought to determine this correlation in a Thai population of LHON. Densitometric quantification of blood mtDNA with the 11,778 LHON mutation in 137 symptomatic cases and their asymptomatic maternal relatives in 30 Asian pedigree families was performed. Asymptomatic maternal relatives under the age of 16 years were excluded. The visual outcome in symptomatic cases with homoplasmy and heteroplasmy was compared. Heteroplasmy was detected in eight (12.9%) symptomatic and 30 (40%) asymptomatic individuals. The quantification of blood mutant mtDNA in the eight symptomatic cases ranged from 44% to 93% (mean=75%). The visual outcome of the cases with heteroplasmy was not different from that of cases with homoplasmy. There was a correlation between the proportion of mutant mtDNA and the likelihood of visual loss. The prevalence of heteroplasmy among pedigrees of the 11,778 LHON mutation in Thailand was similar to that of other Asian populations and may be greater than in 11,778 LHON pedigrees from white backgrounds. The proportion of mutated mtDNA correlated with visual loss, but the effect of heteroplasmy on clinical expression seemed not to relate to gender.


[A case of Sairei-to-induced pneumonitis diagnosed by lymphocyte stimulation test of bronchoalveolar lavage fluid].
A 51-year-old woman was admitted with fever, cough and dyspnea. She had been taking Sairei-to, a traditional Chinese medicine, for 2 months. On admission, chest X-ray revealed a ground-glass appearance in the lung fields bilaterally and serum LDH was elevated. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed that lymphocytes were increased, with a decreased ratio of CD4/CD8 cells. A lymphocyte stimulation test (LST) for Sairei-to using the lymphocytes in BALF was a positive, although a test of peripheral blood was negative. Sairei-to-induced pneumonitis was diagnosed based on the clinical course, laboratory findings, BALF cell analysis and LST of BALF. Only 4 cases of pneumonitis due to Sairei-to have been reported. This case suggests that LST of BALF is useful for diagnosing drug-induced pneumonitis.


Simultaneous Endovascular Treatment of Tandem Internal Carotid Lesions: Case Report and Review of Literature.
The incidence of concomitant extracranial carotid artery stenosis and ipsilateral intracranial carotid aneurysm has been reported to vary between 2.8% and 5%. These complex lesions may present a challenge for treatment decision-making. This case report describes an asymptomatic male patient with severe carotid bifurcation stenosis, coupled with an unruptured supraclinoid internal carotid aneurysm. Both lesions were treated simultaneously. Patient underwent carotid stenting followed by aneurysm coiling in the same setting without any complication.


Multiple hormones stimulate the production of somatomedin by cultured human fibroblasts.
Although immunoreactive somatomedin (IR-SM) secretion by cultured human fibroblasts has been reported, the hormonal control of IR-SM production is not well defined. This study concerns the effects of several hormones and growth factors on IR-SM production by cultured human fibroblasts. Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) had concentration-dependent stimulatory effects on IR-SM production when added to confluent quiescent cultures. When PDGF, FGF, macrophage growth factor (MGF), or epidermal growth factor (EGF) was added transiently for 5 h and the cells subsequently incubated in SM-C deficient, platelet-poor plasma (SM-C-deficient PPP), persistent stimulation of IR-SM production occurred. In contrast, transient exposure to other known stimuli of IR-SM production, such as human GH, T4, and insulin, resulted in no stimulation. Continuous exposure of quiescent, high density fibroblast cultures to EGF, insulin, hydrocortisone, or T4 incubated in the presence of serum-free medium alone resulted in no significant stimulation. During simultaneous incubation with PDGF and SM-C-deficient PPP, however, hydrocortisone, T4, EGF, and insulin produced concentration-dependent increases in IR-SM production. After transient exposure to PDGF, only hydrocortisone and T4 were stimulatory in the presence of SM-C-deficient PPP. We conclude that competence factors, such as PDGF and FGF, are potent stimuli of IR-SM production in the presence of serum-free medium, and that this hormonal signal can be remembered by the cell even after withdrawal of the growth factor. In contrast, progression factors, such as hydrocortisone, T4, and insulin, are effective only in nonquiescent cells. EGF and insulin require simultaneous incubation with PDGF. The PDGF-stimulated cell, therefore, responded differently to hormonal stimuli of IR-SM production than did the quiescent cell.


Physical location of the ilvO determinant in Escherichia coli K-12 deoxyribonucleic acid.
A plasmid carrying the 4,6-kilobase (kb) HindIII-derived fragment from an ilvO mutant derivative of lambda h80dilv imparted a valine-resistant phenotype on strains it carried. This fragment carries a small amount of the promoter-proximal end of ilvE, the ilvO determinant, and apparently the entire ilvG gene, which specifies the valine-insensitive acetohydroxy acid synthase. Comparable deoxyribonucleic acid (DNA) from the original lambda h80dilv did not carry the valine resistance marker. The valine-resistant phenotype was always correlated with the formation of the resistant enzymes. The ilvO determinant was shown to be carried within an approximately 600-based-pair region lying between the SalI and KpnI sites on the HindIII fragment and perhaps within the ilvG gene itself. Ribonucleic acid that hybridizes with the DNA corresponding to the ilvG gene is formed in wild-type K-12 cells. This fact, coupled with the fact that ilvG is transcribed from the same DNA strand as the ilvE, D, and A genes, led to the idea that transcription is normally initiated upstream from ilvG in both wild-type and ilvO strains. In wild-type strains either the formation or the translation of the transcript would be terminated with the ilvG gene, thus preventing expression of that gene.


High frequency of CYP2D6 ultrarapid metabolizers in Spain: controversy about their misclassification in worldwide population studies.
A high frequency (7-10%) of CYP2D6 ultrarapid metabolizers estimated from the genotype (gUMs) has been claimed to exist among Spaniards and Southern Europeans. However, methodological aspects such as the inclusion of individuals carrying non-active multiplied alleles as gUMs may have led to an overestimation. Thus, this study aimed to analyze the gUM frequency (considering only those carrying more than two active genes) in 805 Spanish healthy volunteers studied for CYP2D6*2, *3, *4, *5, *6, *10, *17, *35, *41, and multiplications. Second, all worldwide studies reporting gUM frequencies were reviewed in order to evaluate potential misclassifications. The gUM frequency in this Spanish population was 5.34%, but increased to 8.3% if all individuals with CYP2D6 multiplications were classified as gUMs without considering the activity of the multiplied alleles. Moreover, among all reviewed worldwide studies only 55.6% precisely determined whether the multiplied alleles were active. Present results suggest that the evaluation of CYP2D6 ultrarapid metabolism should be standarized, and that the frequency of gUMs should be reconsidered in Spaniards and globally.


Xanthogranulomatous orchitis after blunt testicular trauma mimicking a testicular tumor: A case report and comparison with published cases.
Xanthogranulomatous orchitis has been reported to be an extremely rare inflammatory change caused by infection and is difficult to distinguish from testicular tumor. We report a 28-year-old man who presented with a lump in his left testis after a blunt testicular trauma. Based on a series of imaging tests, we suspected benign tumor such as epidermoid cyst and performed tumor enucleation (testis-sparing surgery) on the patient. Histopathological findings showed xanthogranulomatous orchitis. It is assumed that xanthogranulomatous orchitis in this case was caused by blunt testicular trauma and this is the first successful case of xanthoglomatous orchitis in salvaging the testis.


Characteristic reaction paths of biochemical reaction systems with time scale separation.
A technique has been developed for characterizing the in vivo behavior of key enzymes from intermediate measurements. The technique is based on the identification of characteristic reaction paths, and it depends on the time scale separation characteristics of the systems. It is shown that useful information can be obtained from the phase plots of properly selected intermediate pairs or combinations which typically show process insensitive algebraic relations approached on time scales short compared to those of most practical interest. These characteristic reaction paths provide useful global measures of enzyme activity. The mathematical basis of reaction path analysis is investigated using linear transformation techniques. General theorems are developed predicting the existence of characteristic reaction paths as asymptotic limits whenever there is effective time scale separation. These limits are reached when fast reactions are relaxed, and available evidence suggests that these conditions will occur for the majority of reaction networks.


Arthropod molting hormone: radioimmune assay.
A radioimmune assay for the arthropod molting hormone, ecdysterone, has been developed. The sensitivity of the assay is 200 picograms or 25 times the maximum sensitivity of the bioassay. Closely related steroids also bind the anti-body, but with lower affinities.


Occurrence of mucoid M-18 Streptococcus pyogenes in a central Ohio pediatric population.
During a 1-year period from October 1986 through September 1987, we recovered 116 mucoid, hemolytic Streptococcus pyogenes isolates from clinical specimens collected from patients seen at our pediatric institution. A total of 102 isolates were from throat cultures (101 for pharyngitis, 1 for acute rheumatic fever), 13 were from other superficial body sites, and 1 was from pleural fluid. All of 40 mucoid isolates tested to date were determined to be M-type 18 strains. A direct latex agglutination test for group A carbohydrate antigen in throat swab specimens was equally sensitive in detecting M-18 mucoid and nonmucoid strains (45 of 77 [58%] and 795 of 1,186 [67%], respectively; not significant, P greater than 0.05). Antimicrobial susceptibility tests performed with 40 mucoid and 40 nonmucoid isolates against penicillin and nine other antimicrobial agents showed all strains to be susceptible, with no difference in MICs. All isolates tested were also considered fully susceptible to the bactericidal activity of penicillin. Further studies are needed to establish the relative virulence of M-18 strains and their possible association with the resurgence of acute rheumatic fever in central Ohio and other areas of the United States.


[Active surveillance: current status and future perspectives].
Widespread use of PSA testing has resulted in decrease in prostate cancer mortality but increase in clinically indolent prostate cancer. Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of biopsy reclassification remain to be debated. Due to inadequate reliability of PSA-kinetics including PSA-doubling time during AS, repeated biopsy is indispensable for every AS program. To reduce physical and psychological burden associated with repeated biopsy, studies on the clinical usefulness of mpMRI and new biomarkers in AS program are warranted.


Development and use of an Arctic charr cell line to study antiviral responses at extremely low temperatures.
Arctic charr (Salvelinus alpinus) are the northernmost distributed freshwater fish and can grow at water temperatures as low as 0.2 °C. Other teleost species have impaired immune function at temperatures that Arctic charr thrive in, and thus, charr may maintain immune function at these temperatures. In this study, a fibroblastic cell line, named ACBA, derived from the bulbus arteriosus (BA) of Arctic charr was developed for use in immune studies at various temperatures. ACBA has undergone more than forty passages at 18 °C over 3 years, while showing no signs of senescence-associated β-galactosidase activity and producing nitric oxide. Remarkably, ACBA cells survived and maintained some mitotic activity even at 1 °C for over 3 months. At these low temperatures, ACBA also continued to produce MH class I proteins. After challenge with poly I:C, only antiviral Mx proteins were induced while MH proteins remained constant. When exposed to live viruses, ACBA was shown to permit viral infection and replication of IPNV, VHSV IVa and CSV at 14 °C. Yet at the preferred temperature of 4 °C, only VHSV IVa was shown to replicate within ACBA. This study provides evidence that Arctic charr cells can maintain immune function while also resisting infection with intracellular pathogens at low temperatures.


Circulating miRNAs Expression in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multifactorial disease that causes increasing morbidity worldwide, and many individuals with ME/CFS symptoms remain undiagnosed due to the lack of diagnostic biomarkers. Its etiology is still unknown, but increasing evidence supports a role of herpesviruses (including HHV-6A and HHV-6B) as potential triggers. Interestingly, the infection by these viruses has been reported to impact the expression of microRNAs (miRNAs), short non-coding RNA sequences which have been suggested to be epigenetic factors modulating ME/CFS pathogenic mechanisms. Notably, the presence of circulating miRNAs in plasma has raised the possibility to use them as valuable biomarkers for distinguishing ME/CFS patients from healthy controls. Thus, this study aimed at determining the role of eight miRNAs, which were selected for their previous association with ME/CFS, as potential circulating biomarkers of the disease. Their presence was quantitatively evaluated in plasma from 40 ME/CFS patients and 20 healthy controls by specific Taqman assays, and the results showed that six out of the eight of the selected miRNAs were differently expressed in patients compared to controls; more specifically, five miRNAs were significantly upregulated (miR-127-3p, miR-142-5p, miR-143-3p, miR-150-5p, and miR-448), and one was downmodulated (miR-140-5p). MiRNA levels directly correlated with disease severity, whereas no significant correlations were observed with the plasma levels of seven pro-inflammatory cytokines or with the presence/load of HHV-6A/6B genome, as judged by specific PCR amplification. The results may open the way for further validation of miRNAs as new potential biomarkers in ME/CFS and increase the knowledge of the complex pathways involved in the ME/CFS development.


The role of the selective serotonin reuptake inhibitor fluoxetine in temperature regulation in ovariectomized rat models.
Thermoregulation is an integrated network of neuroendocrine, autonomic and somatosensory responses. Thermoregulatory dysfunction occurs during fluctuations or decline of gonadal hormone levels and results in vasomotor symptoms such as hot flushes and/or night-time sweating. The neurotransmitter serotonin (5-HT), has been reported to play a role in thermoregulation via changes in extracellular 5-HT levels and/or activation of various 5-HT receptors. The purpose of this study was to evaluate the role of the selective 5-HT reuptake inhibitor (SSRI), fluoxetine (FLX), on temperature regulation using ovariectomized (OVX) rodent models of thermoregulation. Single, subcutaneous (s.c.) administration of FLX (3, 10, 30 and 60 mg/kg) dose-dependently reduced core body temperature (CBT). FLX at 3 and 10 mg/kg s.c. showed no statistically significant decrease on tail-skin temperature (TST), whereas at higher doses (30 and 60 mg/kg) a significant decrease in TST was noted in the telemetry model. To mimic chronic SSRI treatment, a 5-HT(1A) antagonist (WAY-100635; 0.3 mg/kg) was administered 20 min prior to FLX (10 mg/kg). This combination showed no significant improvement on temperature dysfunction compared to FLX alone. Similarly, in a morphine-dependent model of temperature dysfunction FLX, was inactive at 10 mg/kg whereas the 30 and 60 mg/kg s.c. dose abated the naloxone-induced increase in TST by 55 and 81%, respectively. In summary, FLX affected CBT at all doses, but alleviated thermoregulatory dysfunction only at higher doses that are non-selective for the 5-HT system.


Are you of good report?
Past Medicare credit balance reports may come back to haunt you as current federal enforcement activities indicate they could easily fall under False Claims Act scrutiny.


Direct chemiluminescent immunodetection of proteins in agarose gels.
Chemiluminescent immunodetection of proteins separated by polyacrylamide gel electrophoresis is generally performed only after Western blotting. Agarose gels are adequately permeable to allow immunoprobing directly in the gel. Chemiluminescent substrates had not been applied for direct immunoprobing of agarose gels. In a comparison with direct immunostaining of fibrinogen derivatives with horse radish peroxidase (HRP)-conjugated primary antibody using 3,3'-diaminobenzidene (DAB) yielding a sensitivity in the low nanogram range, a luminol-based chemiluminescent detection extended sensitivity to the mid-picogram range with seemingly no interference from either regular or glyoxyl agarose gels. The high sensitivity of chemiluminescence extends utility of direct immunoprobing of either agarose or glyoxyl agarose composite gels for detection and measurement of both high and low molecular weight proteins/peptides which are not easily detected/measured by Western blotting. However, due to the thickness of the gels, direct immunoprobing can be quite laborious. To eliminate that drawback, we describe a simplified approach, converting the thick gels to thin ones prior to probing, that makes direct immunoprobing as easy as Western blotting.


[Drowsiness and traffic accidents. Importance of diagnosis].
"Tiredness", often cited in civil and penal responsibilities secondary to car accidents, hides neurophysiological phenomena which must now be taken into account. The problems of watchfulness in car-driving, is sleepiness, are indeed linked to a genuine disorder in the sleep-wake rythm and attention should be drawn to them in medico-legal cases. Investigations and clinical examinations concerning 110 experts' reports confirm the role played by sleep' disorders in the occurrence of car accidents. Prevention in actually possible. Early detection can take place at various levels and concerns general practitioners, specialists of industrial medicine and specialists for driving tests. In France, the list of diseases associated with, and retraining of a driving license refer only to concentration disorders induced by drug administration, but do not mention sleep pathologies (sleep apnea syndrome, narcolepsy, etc). What is the responsibility of a driver who ignores or says nothing about a sleep pathology from which he is suffering? Is it really necessary to include these pathologies on such a list? It could be more useful to make a large audience; including children, aware of the physiology and pathology of sleep. It appears, from experts' reports, that the management of the problem requires a "driving hygiene".


Psychiatric aspects of brain tumors: A review.
Infrequently, psychiatric symptoms may be the only manifestation of brain tumors. They may present with mood symptoms, psychosis, memory problems, personality changes, anxiety, or anorexia. Symptoms may be misleading, complicating the clinical picture. A comprehensive review of the literature was conducted regarding reports of brain tumors and psychiatric symptoms from 1956-2014. Search engines used include PubMed, Ovid, Psych Info, MEDLINE, and MedScape. Search terms included psychiatric manifestations/symptoms, brain tumors/neoplasms. Our literature search yielded case reports, case studies, and case series. There are no double blind studies except for post-diagnosis/-surgery studies. Early diagnosis is critical for improved quality of life. Symptoms that suggest work-up with neuroimaging include: new-onset psychosis, mood/memory symptoms, occurrence of new or atypical symptoms, personality changes, and anorexia without body dysmorphic symptoms. This article reviews the existing literature regarding the diagnosis and management of this clinically complex condition.


The Application of Fat-Free Mass Index for Survival Prediction in Cancer Patients With Normal and High Body Mass Index.
Background: Fat-free mass (FFM) depletion can be masked by a stable body weight or weight gain in the presence of a normal or high body mass index (BMI). This study investigated the prognostic value of low fat-free mass index (FFMI) in cancer patients with normal or high BMI. Methods: This multicenter retrospective cohort study included 1,602 cancer patients with normal/high BMI. The association of FFMI with patients' overall survival (OS) was analyzed by the Kaplan-Meier method and a Cox model. Results: In this analysis, there were 974 (60.8%) females and 628 (39.2%) males. Low FFMI was associated with worse OS when compared with those patients with normal FFMI. After multivariate adjustment, low FFMI was demonstrated to be an independent unfavorable prognostic factor (HR: 1.69; 95% CI: 1.28, 2.23; P < 0.001) in cancer patients with normal/high BMI. For specific tumor type, low FFMI was found to be associated with worse prognosis in patients with lung cancer, breast cancer and upper gastrointestinal cancer. In subgroup analysis, the association of low FFMI with worse survival was significantly modified by weight loss (P for interaction = 0.012), and those patients with concurrent low FFMI and weight loss showed the worst prognosis (HR: 3.53; 95% CI: 2.04, 6.11; P < 0.001). Conclusion: Low FFMI was associated with worse prognosis in cancer patients with normal/high BMI. This study highlights the usefulness of FFMI for prognostic estimation in these patients.


Phenomics based prediction of plant biomass and leaf area in wheat using machine learning approaches.
Phenomics has emerged as important tool to bridge the genotype-phenotype gap. To dissect complex traits such as highly dynamic plant growth, and quantification of its component traits over a different growth phase of plant will immensely help dissect genetic basis of biomass production. Based on RGB images, models have been developed to predict biomass recently. However, it is very challenging to find a model performing stable across experiments. In this study, we recorded RGB and NIR images of wheat germplasm and Recombinant Inbred Lines (RILs) of Raj3765xHD2329, and examined the use of multimodal images from RGB, NIR sensors and machine learning models to predict biomass and leaf area non-invasively. The image-based traits (i-Traits) containing geometric features, RGB based indices, RGB colour classes and NIR features were categorized into architectural traits and physiological traits. Total 77 i-Traits were selected for prediction of biomass and leaf area consisting of 35 architectural and 42 physiological traits. We have shown that different biomass related traits such as fresh weight, dry weight and shoot area can be predicted accurately from RGB and NIR images using 16 machine learning models. We applied the models on two consecutive years of experiments and found that measurement accuracies were similar suggesting the generalized nature of models. Results showed that all biomass-related traits could be estimated with about 90% accuracy but the performance of model BLASSO was relatively stable and high in all the traits and experiments. The R2 of BLASSO for fresh weight prediction was 0.96 (both year experiments), for dry weight prediction was 0.90 (Experiment 1) and 0.93 (Experiment 2) and for shoot area prediction 0.96 (Experiment 1) and 0.93 (Experiment 2). Also, the RMSRE of BLASSO for fresh weight prediction was 0.53 (Experiment 1) and 0.24 (Experiment 2), for dry weight prediction was 0.85 (Experiment 1) and 0.25 (Experiment 2) and for shoot area prediction 0.59 (Experiment 1) and 0.53 (Experiment 2). Based on the quantification power analysis of i-Traits, the determinants of biomass accumulation were found which contains both architectural and physiological traits. The best predictor i-Trait for fresh weight and dry weight prediction was Area_SV and for shoot area prediction was projected shoot area. These results will be helpful for identification and genetic basis dissection of major determinants of biomass accumulation and also non-invasive high throughput estimation of plant growth during different phenological stages can identify hitherto uncovered genes for biomass production and its deployment in crop improvement for breaking the yield plateau.


A multiplex TaqMan qPCR assay for sensitive and rapid detection of phytoplasmas infecting Rubus species.
Rubus stunt is an economically important disease in the production of raspberries, blackberries, and loganberries. A fast, sensitive, and reliable diagnosis of phytoplasmas, the causal agent of the disease, is of prime importance to stop its spread by vegetative propagation and by insect vectors. Therefore, multiplex qPCR assays using TaqMan probes with different kinds of fluorophores in one reaction were developed, allowing the detection of phytoplasmas in general as well as a more specific detection of phytoplasmas belonging to group 16SrV and host DNA (either plant or insect). This assay now provides a practical tool for the screening of motherplants and monitoring the presence and distribution of phytoplasmas in Rubus plants of different geographic origins, cultivars, and cultivation systems, as well as in putative insect vectors like leafhoppers.


[Effect of carbon substrate concentration on N2, N2O, NO, CO2, and CH4 emissions from a paddy soil in anaerobic condition].
Understanding the effects of carbon and nitrogen substrates concentrations on the emissions of denitrification gases including nitrogen (N2) , nitrous oxide (N2O) and nitric oxide (NO), carbon dioxide (CO2) and methane (CH4) from anaerobic paddy soils is believed to be helpful for development of greenhouse gas mitigation strategies. Moreover, understanding the quantitative dependence of denitrification products compositions on carbon substrate concentration could provide some key parameters or parameterization scheme for developing process-oriented model(s) of nitrogen transformation. Using a silt loam soil collected from a paddy field, we investigated the influence of carbon substrate concentration on the emissions of the denitrification gases, CO2 and CH4 from anaerobically incubated soils by setting two treatments: control (CK) with initial soil nitrate and dissolved organic carbon (DOC) concentrations of ~ 50 mg.kg-1 and -28 mg kg-1 , respectively; and DOC added (C + ) with initial soil nitrate and DOC concentrations of ~50 mg.kg-1 and ~300 mg.kg-1 , respectively. The emissions of denitrification gases, CO2 and CH4, as well as concentrations of carbon and nitrogen substrates for each treatment were dynamically measured, using the gas-flow-soil-core technique and a paralleling substrate monitoring system. The results showed that CH4 emission was not observed in CK treatment while observed in C treatment. Aggregate emission of greenhouse gases for C + treatment was significantly higher comparing with the CK treatment (P <0. 01). The mass fractions of NO, N20 and N2 emissions in total nitrogen gases emissions were approximately 9% , 35% and 56% for CK treatment, respectively; and approximately 31% , 50% and 19% for C+ treatment, respectively, with significant differences between these two treatments (P < 0.01). The results indicated that carbon substrate concentrations can significantly change the composition of nitrogen gas emissions. The results also implicated that organic fertilizer should not be applied to nitrate-rich paddy soils prior to or during flooding so as to mitigate greenhouse gases emissions.


Novel Interface Designs for Patient Monitoring Applications in Critical Care Medicine: Human Factors Review.
The patient monitor (PM) is one of the most commonly used medical devices in hospitals worldwide. PMs are used to monitor patients' vital signs in a wide variety of patient care settings, especially in critical care settings, such as intensive care units. An interesting observation is that the design of PMs has not significantly changed over the past 2 decades, with the layout and structure of PMs more or less unchanged, with incremental changes in design being made rather than transformational changes. Thus, we believe it well-timed to review the design of novel PM interfaces, with particular reference to usability and human factors. This paper aims to review innovations in PM design proposed by researchers and explore how clinicians responded to these design changes. A literature search of relevant databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, identified 16 related studies. A detailed description of the interface design and an analysis of each novel PM were carried out, including a detailed analysis of the structure of the different user interfaces, to inform future PM design. The test methodologies used to evaluate the different designs are also presented. Most of the studies included in this review identified some level of improvement in the clinician's performance when using a novel display in comparison with the traditional PM. For instance, from the 16 reviewed studies, 12 studies identified an improvement in the detection and response times, and 10 studies identified an improvement in the accuracy or treatment efficiency. This indicates that novel displays have the potential to improve the clinical performance of nurses and doctors. However, the outcomes of some of these studies are weakened because of methodological deficiencies. These deficiencies are discussed in detail in this study. More careful study design is warranted to investigate the user experience and usability of future novel PMs for real time vital sign monitoring, to establish whether or not they could be used successfully in critical care. A series of recommendations on how future novel PM designs and evaluations can be enhanced are provided.


Renal stones in Kelantan, Malaysia--has the pattern changed?
Records of 183 patients with renal stones managed at Hospital Universiti Sains Malaysia between 1985 and 1995 were retrospectively evaluated. The commonest symptom was lumbar pain which may be associated with either frequency, blood stained urine or dysuria. One hundred and sixty-one patients (88%) had upper tract stones while the remainder had lower tract stones. Positive urine cultures were seen in 33 patients. The commonest organism isolated was Escherichia coli followed by Klebsiella aeruginosa and Staphylococcus aureus. Almost all of our patients had renal impairment at presentation and 70% of them progressed to chronic renal failure. In contrast to previous findings, the pattern of renal stone in this region is similar to that described in Western society. Its effect on renal function is serious and hence warrant special attention.


Molecular orientation via a dynamically induced pulse-train: wave packet dynamics of NaI in a static electric field.
We regard the rovibrational wave packet dynamics of NaI in a static electric field after femtosecond excitation to its first electronically excited state. The following quasibound nuclear wave packet motion is accompanied by a bonding situation changing from covalent to ionic. At times when the charge separation is present, i.e., when the bond-length is large, a strong dipole moment exists and rotational excitation takes place. Upon bond contraction, the then covalently bound molecule does not experience the external field. This scenario repeats itself periodically. Thus, the vibrational dynamics causes a situation which is comparable to the interaction of the molecule with a train of pulses where the pulse separation is determined by the vibrational period.


Toward a neurogenetic theory of neuroticism.
Recent advances in neuroscience and molecular biology have begun to identify neural and genetic correlates of complex traits. Future theories of personality need to integrate these data across the behavioral, neural, and genetic level of analysis and further explain the underlying epigenetic processes by which genes and environmental variables interact to shape the structure and function of neural circuitry. In this chapter, I will review some of the work that has been conducted at the cognitive, neural, and molecular genetic level with respect to one specific personality trait-neuroticism. I will focus particularly on individual differences with respect to memory, self-reference, perception, and attention during processing of emotional stimuli and the significance of gene-by-environment interactions. This chapter is intended to serve as a tutorial bridge for psychologists who may be intrigued by molecular genetics and for molecular biologists who may be curious about how to apply their research to the study of personality.


[Optimization of the solid-phase extraction procedure for the screening of the medicinal and narcotic substances in the blood by gas chromatography with mass-spectrometric detection].
This paper was designed to describe the application of the method for solid-phase extraction of the medicinal and narcotic substances having different physicochemical composition by gas chromatography with mass-spectrometric detection (GC-MS) for the purpose of their screening in the blood. The solid-phase extraction technique was optimized by means of the Box-Behnken modeling with the evaluation of the influence on the effectiveness of extraction of various factors including pH of the buffer solution, eluent composition, the type and the volume of the solutions used to wash the sorbent.


[Pathomorphological assessment of renal biopsy specimens: principles and directions for clinicians].
The renal biopsy is a principal diagnostic method to provide information on type, activity and the intensity of the disease. The aim of the article is to describe the handling, fixation and processing of the renal tissue in pathomorphological laboratories, as well as to provide any information about histopathological glomerular lesions observed in glomerulopathies. The assessment of the renal biopsies includes light microscopy, immunofluorescence microscopy and electron microscopy. In each case clinicians should provide information on the patient's clinical history and recent laboratory values. Immunomorphological evaluation of the renal biopsy specimen should be done in all cases. In view of the high cost of the electron microscopy it seems that the best solution is to preserve the renal tissue in epon and provide ultrastructural evaluation according to the clinical data and light microscopy and immunofluorescence findings. The diagnosis of glomerulopathies requires a close cooperation between clinicians and pathologists. Pathologists should have access to clinical data, and clinicians should understand the limitations of the pathomorphological techniques.


PPARalpha controls the intracellular coenzyme A concentration via regulation of PANK1alpha gene expression.
Pantothenate kinase (PanK) is thought to catalyze the first rate-limiting step in CoA biosynthesis. The full-length cDNA encoding the human PanK1alpha protein was isolated, and the complete human PANK1 gene structure was determined. Bezafibrate (BF), a hypolipidemic drug and a peroxisome proliferator activator receptor-alpha (PPARalpha) agonist, specifically increased hPANK1alpha mRNA expression in human hepatoblastoma (HepG2) cells as a function of time and dose of the drug, compared with hPANK1beta, hPANK2, and hPANK3, which did not significantly increase. Four putative PPARalpha response elements were identified in the PANKIalpha promoter, and BF stimulated hPANK1alpha promoter activity but did not alter the mRNA half-life. Increased hPANK1alpha mRNA resulted in higher hPanK1 protein, localized in the cytoplasm, and elevated PanK enzyme activity. The enhanced hPANK1alpha gene expression translated into increased activity of the CoA biosynthetic pathway and established a higher steady-state CoA level in HepG2 cells. These data are consistent with a key role for PanK1alpha in the control of cellular CoA content and point to the PPARalpha transcription factor as a major factor governing hepatic CoA levels by specific modulation of PANK1alpha gene expression.


Optimal three-dimensional reconstruction for lung cancer tissues.
The existing three-dimensional (3D) x-ray reconstruction methods for lung cancer tissue reconstruct the investigated objects based on a series of two-dimensional (2D) image sections and a chosen 3D reconstruction algorithm. However, because these procedures apply the same segmentation method for all 2D image sections, they may not achieve the optimal segmentation for each section. As a result, the reconstructed 3D images have limited spatial resolution. Furthermore, the existing 3D reconstruction method is time-consuming and results in a limited time resolution. This research presents an innovation of 3D reconstruction by reformulating two main components of the method. First, a validity index for fuzzy clustering is used to obtain the optimal segmentations of any 2D x-ray image. The process is realized by automatically determining the optimal number of clusters for the image. Second, unlike the existing 3D reconstruction methods, a fast-FCM algorithm is used to speed up the 2D image segmenting process, thereby raising the time resolution of the 3D reconstruction process. With the aid of commonly used VTK software, the proposed method has been used to visualize four classes of typical lung cancer tissues: adenocarcinoma, large cell carcinoma, small cell carcinoma, and squamous cell carcinoma. Experimental results validate the effectiveness and efficiency of the proposed algorithm. Thus, the method contributes a useful tool for x-ray-based 3D image reconstruction.


Ro 48-8.071, a new 2,3-oxidosqualene:lanosterol cyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin.
2,3-Oxidosqualene:lanosterol cyclase (OSC, E.C. 126.96.36.199) represents a unique target for a cholesterol lowering drug. Partial inhibition of OSC should reduce synthesis of lanosterol and subsequent sterols, and also stimulate the production of epoxysterols that repress HMG-CoA reductase expression, generating a synergistic, self-limited negative regulatory loop. Hence, the pharmacological properties of Ro 48-8.071, a new OSC inhibitor, were compared to that of an HMG-CoA reductase inhibitor, simvastatin. Ro 48-8.071 blocked human liver OSC and cholesterol synthesis in HepG2 cells in the nanomolar range; in cells it triggered the production of monooxidosqualene, dioxidosqualene, and epoxycholesterol. It was safe in hamsters, squirrel monkeys and Göttingen minipigs at pharmacologically active doses, lowering LDL approximately 60% in hamsters, and at least 30% in the two other species, being at least as efficacious as safe doses of simvastatin. The latter was hepatotoxic in hamsters at doses > 30 mumol/kg/day limiting its window of efficacy. Hepatic monooxidosqualene increased dose-dependently after treatment with Ro 48-8.071, up to approximately 20 micrograms/g wet liver or less than 1% of hepatic cholesterol, and it was inversely correlated with LDL levels. Ro 48-8.071 did not reduce coenzyme Q10 levels in liver and heart of hamsters, and importantly did not trigger an overexpression of hepatic HMG-CoA reductase, squalene synthase, and OSC itself. In strong contrast, simvastatin stimulated these enzymes dramatically, and reduced coenzyme Q10 levels in liver and heart. Altogether these findings clearly differentiate the OSC inhibitor Ro 48-8.071 from simvastatin, and support the view that OSC is a distinct key component in the regulation of the cholesterol synthesis pathway.


Co-expression of corticotropin-releasing factor and vasopressin immunoreactivity in parvocellular neurosecretory neurons of the adrenalectomized rat.
To clarify the anatomical organization that allows for the synergy of vasopressin and oxytocin with corticotropin-releasing factor (CRF) in promoting adrenocorticotropic hormone secretion from the anterior pituitary, immunohistochemical double staining methods were used to compare the distribution of these peptides in the hypothalamic paraventricular nucleus of normal, colchicine-treated, and adrenalectomized male rats. In untreated animals, a few CRF-stained cells were found in the parvocellular division of the paraventricular nucleus, while brightly stained oxytocin- and vasopressin-immunoreactive cells were centered in the magnocellular division. In animals treated with colchicine, and inhibitor of axonal transport, large numbers of CRF-stained cells were found in the parvocellular division of the nucleus, and 1-2% of these also stained with antivasopressin. As reported previously, a substantial number of oxytocin-stained cells, centered in a discrete anterior part of the magnocellular division, also expressed CRF immunoreactivity. In contrast, after adrenalectomy, CRF immunostaining of cells in the parvocellular division was enhanced selectively and greater than 70% of these cells also stained positively for vasopressin. The distribution of oxytocin-stained cells was not influenced by adrenalectomy. The unusual localization of vasopressin immunoreactivity in parvocellular neurosecretory neurons in the adrenalectomized rat suggests that a single population of cells can produce CRF and vasopressin, both of which are potent promoters of adrenocorticotropic hormone secretion. These findings indicate that there is a state-dependent plasticity in the expression of biologically active peptides by individual neuroendocrine neurons.


Phenolic Compounds and Organic Acid Composition of Syringa vulgaris L. Flowers and Infusions.
The study aimed to determine the content of phenolic compounds (phenolic acids and flavonoids) and organic acids in dried flowers and water infusions of non-oxidised and oxidised flowers from four lilac cultivars. The diversity in the total phenolic and flavonoid content was in the flowers (18.35-67.14 and 2.03-2.65 mg g-1 DW, respectively) and infusions (14.72-47.78 and 0.20-1.84 mg per 100 mL infusion, respectively) depending the flower colour and form (oxidised and non-oxidised). Phenolic compounds and organic acids were susceptible to oxidation. Compared to infusions, flowers had more phenolic compounds and organic acids. The highest content of most phenolic compounds was confirmed for non-oxidised purple flowers (up to 7825.9 µg g-1 DW for chlorogenic acid) while in infusions for non-oxidised white flowers (up to 667.1 µg per 100 mL infusions for vanillic acid). The phenolic profile of the infusions was less diverse than that of flowers. The scavenging ability ranged from 52 to 87%. The highest organic acid content in flowers was for oxidised blue and purple flowers (2528.1 and 2479.0 µg g-1 DW, respectively) while in infusions the highest organic acid content was for oxidised purple flowers (550.1 µg per 100 mL infusions).


The effect of a wrist brace on injury patterns in experimentally produced distal radial fractures in a cadaveric model.
We compared patterns of bony and ligamentous injury with distal radial fractures in braced and unbraced wrists using 20 paired fresh cadaveric upper extremities. A commercially available wrist brace was placed on one wrist in each pair. Specimens were then placed in a fast-loading gravity-driven device and subjected to loads averaging 16 kg from an average height of 78 cm. Postfracture radiographs were obtained, the specimens were dissected, and fracture patterns and ligamentous integrity were assessed. The following fracture types were produced: distal radial fractures (eight unbraced, seven braced) and intraarticular (seven unbraced, four braced). Radiographically, seven unbraced wrists demonstrated carpal bone fracture and one braced wrist demonstrated carpal fractures. Eight unbraced and three braced wrists sustained carpal intrinsic ligament injuries, four unbraced and one braced wrists demonstrated extrinsic ligament injuries. More capsular tears occurred in the unbraced group (N = 8) than in the braced group (N = 1). This model demonstrated a difference in the patterns of injury in unbraced and braced wrists subjected to the same mechanical conditions, which suggests that use of a wrist brace may alter patterns of wrist injury.


Synapses as dynamic memory buffers.
This article throws new light on the possible role of synapses in information transmission through theoretical analysis and computer simulations. We show that the internal dynamic state of a synapse may serve as a transient memory buffer that stores information about the most recent segment of the spike train that was previously sent to this synapse. This information is transmitted to the postsynaptic neuron through the amplitudes of the postsynaptic response for the next few spikes. In fact, we show that most of this information about the preceding spike train is already contained in the postsynaptic response for just two additional spikes. It is demonstrated that the postsynaptic neuron receives simultaneously information about the specific type of synapse which has transmitted these pulses. In view of recent findings by Gupta et al. [Science, 287 (2000) 273] that different types of synapses are characteristic for specific types of presynaptic neurons, the postsynaptic neuron receives in this way partial knowledge about the identity of the presynaptic neuron from which it has received information. Our simulations are based on recent data about the dynamics of GABAergic synapses. We show that the relatively large number of synaptic release sites that make up a GABAergic synaptic connection makes these connections suitable for such complex information transmission processes.


MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance.
Establishing a diagnosis in patients suspected of having a myelodysplastic syndrome (MDS) can be challenging and could be informed by the identification of somatic mutations. We performed a prospective study to examine the frequency and types of mutations encountered in 144 patients with unexplained cytopenias. Based on bone marrow findings, 17% were diagnosed with MDS, 15% with idiopathic cytopenias of undetermined significance (ICUS) and some evidence of dysplasia, and 69% with ICUS and no dysplasia. Bone marrow DNA was sequenced for mutations in 22 frequently mutated myeloid malignancy genes. Somatic mutations were identified in 71% of MDS patients, 62% of patients with ICUS and some dysplasia, and 20% of ICUS patients and no dysplasia. In total, 35% of ICUS patients carried a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis. We validated these results in a cohort of 91 lower-risk MDS and 249 ICUS cases identified over a 6-month interval. Mutations were found in 79% of those with MDS, in 45% of those with ICUS with dysplasia, and in 17% of those with ICUS without dysplasia. The spectrum of mutated genes was similar with the exception of SF3B1 which was rarely mutated in patients without dysplasia. Variant allele fractions were comparable between clonal ICUS (CCUS) and MDS as were mean age and blood counts. We demonstrate that CCUS is a more frequent diagnosis than MDS in cytopenic patients. Clinical and mutational features are similar in these groups and may have diagnostic utility once outcomes in CCUS patients are better understood.


Evaluating the Effects of Coping Style on Allostatic Load, by Sex: The Jackson Heart Study, 2000-2004.
The objective of this study was to examine the cross-sectional association between coping styles and allostatic load among African American adults in the Jackson Heart Study (2000-2004). Coping styles were assessed using the Coping Strategies Inventory-Short Form; allostatic load was measured by using 9 biomarkers standardized into z-scores. Sex-stratified multivariable linear regressions indicated that females who used disengagement coping styles had significantly higher allostatic load scores (β = 0.016; 95% CI, 0.001-0.032); no such associations were found in males. Future longitudinal investigations should examine why disengagement coping style is linked to increased allostatic load to better inform effective interventions and reduce health disparities among African American women.


A Novel Memetic Algorithm Based on Multiparent Evolution and Adaptive Local Search for Large-Scale Global Optimization.
In many fields, including management, computer, and communication, Large-Scale Global Optimization (LSGO) plays a critical role. It has been applied to various applications and domains. At the same time, it is one of the most challenging optimization problems. This paper proposes a novel memetic algorithm (called MPCE & SSALS) based on multiparent evolution and adaptive local search to address the LSGO problems. In MPCE & SSALS, a multiparent crossover operation is used for global exploration, while a step-size adaptive local search is utilized for local exploitation. A new offspring is generated by recombining four parents. In the early stage of the algorithm execution, global search and local search are performed alternately, and the population size gradually decreases to 1. In the later stage, only local searches are performed for the last individual. Experiments were conducted on 15 benchmark functions of the CEC'2013 benchmark suite for LSGO. The results were compared with four state-of-the-art algorithms, demonstrating that the proposed MPCE & SSALS algorithm is more effective.


High sensitive troponin-I in patients with slow coronary flow pattern.
We examined the hypothesis that a specific myocardial injury marker, namely high sensitive cardiac troponin-I (HsTn-I), is elevated in patients with slow coronary flow (SCF) pattern. To examine the above hypothesis by studying a group of patients who had undergone coronary angiography for the detection of their chest pain aetiology with SCF pattern despite an angiographically normal coronary arteriogram. We evaluated and performed coronary angiography (CAG) of 97 patients with chest discomfort. The indication forCAG was at least Canada class 3 angina and/or proven myocardial ischaemia according to noninvasive diagnostic tests. We further divided patients into three subgroups according to CAG images and compared HsTn-I plasma levels in 39 patients with SCF pattern, 28 patients with coronary artery disease (CAD), and 30 patients with normal coronary arteries. We researched the association between qualitative HsTn-I positivity and demographic features including cardiovascular risk factors, inflammation markers and TIMI frame count for each of the epicardial coronary arteries. TIMI frame count for each epicardial coronary artery was significantly higher in patients with SCF pattern than in patients with CAD and normal coronary arteries (p < 0.001). HsTn-I positivity was not statistically different between patients with SCF pattern and normal coronary arteries (p = 512), but it was significantly higher in the CAD group than the other two group of patients (p < 0.001). In patients with SCF, HsTn-I may be detectable, but it is not elevated as in patients with normal coronary arteries.


A Simple Technique for Fabricating a Screw-Retained/Cemented Implant-Supported Crown.
Many factors figure into the long-term success of an implant-supported restoration. While some are uncontrollable, others are manageable. The cement-retained implant-supported restoration is easier to fabricate, while the screw-retained implant-supported restoration involves more complicated, timeconsuming laboratory procedures. Most research has found the screw-retained restoration has had more minimal complications than the cement-retained counterpart. This article describes a simple, low-cost technique of converting a cement-retained implant crown to a screw-retained implant crown, which allows for easy retrievability and eliminates a number of laboratory steps and costs.


Cholesterol-Independent Suppression of Lymphocyte Activation, Autoimmunity, and Glomerulonephritis by Apolipoprotein A-I in Normocholesterolemic Lupus-Prone Mice.
Apolipoprotein (Apo)A-I, the major lipid-binding protein of high-density lipoprotein, can prevent autoimmunity and suppress inflammation in hypercholesterolemic mice by attenuating lymphocyte cholesterol accumulation and removing tissue-oxidized lipids. However, whether ApoA-I mediates immune-suppressive or anti-inflammatory effects under normocholesterolemic conditions and the mechanisms involved remain unresolved. We transferred bone marrow from systemic lupus erythematosus (SLE)-prone Sle123 mice into normal, ApoA-I-knockout (ApoA-I(-/-)) and ApoA-I-transgenic (ApoA-I(tg)) mice. Increased ApoA-I in ApoA-I(tg) mice suppressed CD4(+) T and B cell activation without changing lymphocyte cholesterol levels or reducing major ApoA-I-binding oxidized fatty acids. Unexpectedly, oxidized fatty acid peroxisome proliferator-activated receptor γ ligands 13- and 9-hydroxyoctadecadienoic acid were increased in lymphocytes of autoimmune ApoA-I(tg) mice. ApoA-I reduced Th1 cells independently of changes in CD4(+)Foxp3(+) regulatory T cells or CD11c(+) dendritic cell activation and migration. Follicular helper T cells, germinal center B cells, and autoantibodies were also lower in ApoA-I(tg) mice. Transgenic ApoA-I also improved SLE-mediated glomerulonephritis. However, ApoA-I deficiency did not have the opposite effects on autoimmunity or glomerulonephritis, possibly as the result of compensatory increases in ApoE on high-density lipoprotein. We conclude that, although compensatory mechanisms prevent the proinflammatory effects of ApoA-I deficiency in normocholesterolemic mice, increasing ApoA-I can attenuate lymphocyte activation and autoimmunity in SLE independently of cholesterol transport, possibly through oxidized fatty acid peroxisome proliferator-activated receptor γ ligands, and it can reduce renal inflammation in glomerulonephritis.


Diagnosis and Management of Acquired Cystic Kidney Disease and Renal Tumors in ESRD Patients.
The incidence of renal malignancies is markedly increased in end-stage renal disease and appears to be related to the development of acquired cystic kidney disease. Identification and evaluation of simple cysts, complex cysts, and solid masses in these patients rely on imaging studies, including ultrasonography, computed tomography, and magnetic resonance imaging, each of which has advantages and disadvantages. While there are no published data to support screening of ESRD patients, this seems appropriate in at least some patients, based on patient characteristics and the presence or absence of acquired cystic kidney disease. The optimal frequency and modality remain to be determined.


Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase.
A DNA clone complementary to the messenger RNA encoding the human trifunctional enzyme 5,10-methylenetetrahydrofolate dehydrogenase-5,10-methenyl-tetrahydrofolate cyclohydrolase-10-formyltetrahydrofolate synthetase has been isolated from a lambda gt10 library. In vitro transcription-translation of the 3.1-kilobase cDNA clone yields a protein of 101 kDa, which is of identical size and exhibits the same immunoreactivity as the enzyme purified from human liver. A coding region of 2805 base pairs in the cDNA encodes a protein of 935 amino acids. The initiator methionine is absent from the purified enzyme and the amino-terminal 30 amino acids derived by automated sequence analysis are identical (arginine at position 18 was not identified) with that deduced from the nucleotide sequence. The amino acid sequence of the human enzyme shows extensive homology with that of the yeast enzyme, although the amino-terminal bifunctional dehydrogenase-cyclohydrolase domain is less homologous than the carboxyl-terminal synthetase domain. A region was identified which probably serves as a link between these two major domains of the human enzyme. The synthetase domain contains two regions that are homologous to consensus sequences for an ATP-binding site.


[Non-cardiac chest pain and its association with persistent chest pain and poor mental well-being].
An estimated 50-75% of visits to cardiac emergency departments are due to chest pain which is non-cardiac in nature (non-cardiac chest pain (NCCP). This study evaluates the prevalence of NCCP in the emergency departments at Landspitali, and assesses its association with continued chest-pain post discharge, mental well--being and the information-provision provided to NCCP patients during hospitalization. Participants were 390 patients (18-65 years) presenting with chest pain to the cardiac emergency or the general emergency department at Landspitali from October 2015-May 2016. Measurements included questionnaires assessing somatic symptoms, mental well-being and quality of life, and questions regarding continued chest-pain and information-provision during hospitalization. In total 72% of participants (282) were considered having NCCP while 24% (92) had cardiac disease. NCCP patients experienced a similar burden of somatic and depressive symptoms, but slightly more anxiety and mental distress than cardiac patients. Equal proportions (60%) of NCCP and cardiac patients reported having experienced chestpain post discharge. Continued chest-pain was, however, associated with greater anxiety (β=0.18, p<0.001) and depression (β=0.18, p<0.003) among NCCP patients. Thirty percent of NCCP patients lacked instructions of how to respond to continued chest-pain and only 40% received information regarding other possible causes of chest pain. NCCP was prevalent among patients presenting to emergency departments at Landspitali. The majority of NCCP patients experienced continued chest-pain after discharge, and such pain experience was associated with mental distress. A third of NCCP patients lacked information about possible causes for the pain and advice about coping with symptoms.


Conditional immortalization of human thyroid epithelial cells: a tool for analysis of oncogene action.
To overcome the difficulty of assessing oncogene action in human epithelial cell types, such as thyroid, which have limited proliferative potential in culture, we have explored the use of temperature-sensitive (ts) mutants of simian virus 40 (SV40) early region to create conditionally immortalized epithelial cell lines. Normal primary cultures of human thyroid follicular cells were transfected with a plasmid containing the SV40 early region from mutant tsA58. Expanding epithelial colonies were observed after 2 to 3 months, all of which grew to greater than 200 population doublings without crisis. All showed tight temperature dependence for growth. After switch-up to the restrictive temperature (40.5 degrees C), no further increase in cell number was seen after 1 to 2 days. However, DNA synthesis declined much more slowly; the dissociation from cell division led to marked polyploidy. Viability was maintained for up to 2 weeks. Introduction of an inducible mutant ras gene into ts thyroid cells led, as expected, to morphological transformation at the permissive temperature when ras was induced. Interestingly, this was associated with a marked reduction in net growth rate. At the restrictive temperature, induction of mutant ras caused rapid cell death. These results demonstrate the utility of a ts SV40 mutant to permit the study of oncogene action in an otherwise nonproliferative target cell and reveal important differences in the interaction between ras and SV40 T in these epithelial cells compared with previously studied cell types.


[Analysis of chemotherapeutic results and prognostic factors of adult acute lymphoblastic leukemia].
To explore the clinical characteristics of adult acute lymphoblastic leukemia (ALL), compare the efficacy of different induction regimens and analyze the prognostic factors. Data of 149 adult ALL patients hospitalized in our institute between June 1998 and December 2005 were retrospectively reviewed. The results were analyzed with the SPSS11.5 software. 1) Out of 133 patients available immunophenotype data, 118 (88.7%) were B-ALL and 15 (11.3%) T-ALL. Cytogenetic analysis was performed in 105 patients, 40 cases (38.1%) of them had a normal karyotype and 65 (61.9%) chromosome aberrations. 2) 149 patients completed the VDCP, VDLP or VDCLP induction therapies (at least 4 weeks treatment for each), 140 (93.7%) of them achieved complete remission (CR) with the first course CR rates of 80.8%, 92.3% and 81.4% , respectively (P=0.618). CR rates in patients after the induction regimens with or without asparaginase were 95.5% versus 92.1% (P=0.566). With a median follow-up of 14.5 (1-75) months, the median disease free survival (DFS) was 12 (1-74) months and median overall survival (OS) 17.5 (1-97) months. DFS of the three regimen groups at 3 and 5 years were 18.5% and 14.8%, 24.7% and 9.9%, 39.5% and 39.5%, respectively (P=0.0066). 3) COX regression analysis showed that the age (over 40 years), white blood cell (WBC) count ( > 40 x 10(9)/L) , t(9;22) (q34;q11)-positive and less than 4 courses consolidation chemotherapy were the unfavorable prognostic factors. Most adult ALL patients are B-ALL and karyotype have more changed. More than 90% patients can achieve CR with induction regimens consisting of 4 or 5 drugs. Induction regimens containing L-asparaginase may not affect the CR rate, but can improve DFS and OS. Age and WBC at diagnosis, presence of t(9;22) (q34;q11) and the courses of post-remission treatment are important prognostic factors.


Laparoscopic surgery for bowel endometriosis.
Diagnosis and treatment of endometriosis is the most frequent reason for gynecologic operative laparoscopy in the United States. It is therefore important for the laparoscopist to be thoroughly familiar with the current standards of diagnosis and management of this complex disease. The most common presentations where endometriosis is found are pelvic pain, infertility, and adnexal mass. The ovaries, the posterior leaf of the broad ligament, and the cul-de-sac are the most frequent locations, and the left side is more frequently affected than the right.


Formation of acellular cementum-like layers, with and without extrinsic fiber insertion, along inert bone surfaces of aging c-Src gene knockout mice.
To investigate the long-term effects of c-src deficiency on skeletal and dental tissues, we examined the lower jaws and long bones of c-src gene knockout (c-src KO) mice by histological and histochemical methods. Numerous multinucleated osteoclasts were distributed throughout the mandible in 5-wk-old c-src KO mice, but by 14 wk they had almost completely disappeared from the alveolar bone, leaving tartrate-resistant acid phosphatase (TRAP)-positive layers along the bone surface. Deposition of osteopontin-positive mineralized tissue, reminiscent of acellular afibrillar cementum (AAC), was confirmed along the TRAP-positive bone surface at 14 wk. The layer progressively thickened up to 21 months. A comparable mineralized layer was noted along the trabeculae of long bones as thickened cement lines. In the periostin-rich areas of jaw bones, but not in the long bones, portions of AAC-like mineralized layers were often replaced with and/or covered by acellular extrinsic fiber cementum (AEFC)-like tissue. These data suggest that the deposition of AAC-like mineralized tissue is a general phenomenon that may occur along inert or slowly remodeling bone surfaces under conditions characterized by reduced bone-resorbing activity, whereas the induction of AEFC-like tissue seems to be associated with the expression of certain molecules that are particularly abundant in the microenvironment of the periodontal ligament.


Extensive expertise in endocrinology. Adrenal crisis.
Adrenal crisis is a life-threatening emergency contributing to the excess mortality of patients with adrenal insufficiency. Studies in patients on chronic replacement therapy for adrenal insufficiency have revealed an incidence of 5-10 adrenal crises/100 patient years and suggested a mortality rate from adrenal crisis of 0.5/100 patient years. Patients with adrenal crisis typically present with profoundly impaired well-being, hypotension, nausea and vomiting, and fever responding well to parenteral hydrocortisone administration. Infections are the major precipitating causes of adrenal crisis. Lack of increased cortisol concentrations during infection enhances pro-inflammatory cytokine release and sensitivity to the toxic effects of these cytokines (e.g. tumour necrosis factor alpha). Furthermore, pro-inflammatory cytokines may impair glucocorticoid receptor function aggravating glucocorticoid deficiency. Treatment of adrenal crisis is simple and highly effective consisting of i.v. hydrocortisone (initial bolus of 100 mg followed by 200 mg over 24 h as continuous infusion) and 0.9% saline (1000 ml within the first hour). Prevention of adrenal crisis requires appropriate hydrocortisone dose adjustments to stressful medical procedures (e.g. major surgery) and other stressful events (e.g. infection). Patient education is a key for such dose adjustments but current education concepts are not sufficiently effective. Thus, improved education strategies are needed. Every patient should carry an emergency card and should be provided with an emergency kit for parenteral hydrocortisone self-administration. A hydrocortisone pen would hold a great potential to lower the current barriers to hydrocortisone self-injection. Improved patient education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are expected to significantly reduce morbidity and mortality from adrenal crisis.


Self-management of stress urinary incontinence via a mobile app: two-year follow-up of a randomized controlled trial.
We investigated the long-term effects of using a mobile app to treat stress urinary incontinence with a focus on pelvic floor muscle training. A previous randomized controlled trial of 123 women aged 27-72 years found that three months of self-managing stress urinary incontinence with support from the Tät® app was effective. We followed up the women in the app group (n = 62) two years after the initial trial with the same primary outcomes for symptom severity (International Consultation on Incontinence Questionnaire Short Form) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptom Quality of Life) and compared the scores with those at baseline. Of the 62 women, 61 and 46 (75.4%), respectively, participated in three-month and two-year follow-ups. Baseline data did not differ between responders and non-responders at follow-up. The mean decreases in International Consultation on Incontinence Questionnaire Short Form and ICIQ-Lower Urinary Tract Symptom Quality of Life scores after two years were 3.1 (95% confidence interval 2.0-4.2) and 4.0 (95% confidence interval 2.1-5.9), respectively. Of the 46 women, four (8.7%) rated themselves as very much better, nine (19.6%) as much better, and 16 (34.8%) as a little better. The use of incontinence protection products decreased significantly (p = 0.04), and the proportion of women who felt they could contract their pelvic muscles correctly increased from 14/46 (30.4%) at baseline to 31/46 (67.4%) at follow-up (p < 0.001). Self-management of stress urinary incontinence with support from the Tät® app had significant and clinically relevant long-term effects and may serve as first-line treatment.


The Effect of Adjunct Mechanical Traction on Penile Length in Men Undergoing Primary Treatment for Peyronie's Disease: A Systematic Review and Meta-analysis.
To accurately characterize the effect of penile traction therapy (PTT) on stretched penile length (SPL) after primary treatment for men with PD. A systematic search was performed for studies that evaluated the correction of PD using penile traction as secondary treatment published through January 2018. Studies were included if (1) a singular primary treatment of PD (injection or surgical treatment) was performed for all included men, (2) if there was a control group with no adjunct traction, and (3) if patients were required to wear the traction device for greater than 2 h/d. Estimates were pooled using random-effects meta-analysis. Data were obtained from 4 studies involving 348 men with an average age of 55.7 ± 2.0 years. Men who used PTT after primary intervention had SPLs 1.02 cm greater [95% CI: 0.64 to 1.40; I2=0%] when compared with men who did not use traction after primary intervention (p = 0.009). When performing subgroup analysis by primary therapy, no difference was seen in men undergoing penile traction after surgical correction when compared with men undergoing penile traction after injection therapy (1.01 vs 1.29 cm, p = 0.84). PTT may be a promising technique to reduce length loss in men undergoing PD treatment. Future work should be done to determine the ideal timing and subpopulations who would benefit from PTT.


Transcranial direct current stimulation in the recovery of postural control after stroke: a pilot study.
This pilot study aimed to evaluate the effectiveness of multiple sessions of transcranial Direct Current Stimulation (tDCS) during 4 weeks on balance and gait parameters after stroke. Thirty-one stroke patients were included in this randomised, double-blind, sham-controlled crossover study. The Tinetti test was used to assess functional balance and gait after stroke. Secondary measures, Rivermead Motor Assessment (RMA) and Trunk Impairment Scale (TIS), were registered to asses both motricity and trunk performance. All tests were administered at baseline, after 4 and 8 weeks. Patients were randomly divided into two groups. Both groups received both sixteen 20-min sessions of tDCS and sixteen 20-min sessions of Sham stimulation. Application method between groups was changed after 4 weeks. A general linear repeated measures model was used to analyse the results of our study. Results revealed an effect on the total score of the Tinetti test (p = 0.049). No significant results were obtained for the RMA (p = 0.166) and the TIS (p = 0.479). This pilot study indicates that 16 tDCS-sessions could have a beneficial effect on balance and gait in stroke patients measured with the Tinetti test. However, further research is needed to elucidate these findings. Implications for Rehabilitation Sixteen sessions of tDCS is beneficial in the recovery of postural control in stroke patients. tDCS has to be applied as soon as possible to enhance beneficial effects.


Focused ion beam lithography and anodization combined nanopore patterning.
In this study, focused ion beam lithography and anodization are combined to create different nanopore patterns. Uniform-, alternating-, and gradient-sized shallow nanopore arrays are first made on high purity aluminum by focused ion beam lithography. These shallow pore arrays are then used as pore initiation sites during anodization by different electrolytes. Depending on the nature of the anodization electrolyte, the nanopore patterns by focused ion beam lithography play different roles in further pore development during anodization. The pore-to-pore distance by focused ion beam lithography should match with that by anodization for guided pore development to be effective. Ordered and heterogeneous nanopore arrays are obtained by the focused ion beam lithography and anodization combined approach.


Granular systems on a vibrating wall: the kinetic boundary condition.
Dense granular media, fluidized by a vibrating wall, is studied in the high-vibrating frequency limit, where the plate vibration frequency is much greater than the collision frequency, and the plate acceleration is much greater than gravity. Using kinetic theory, it is shown that, regardless of the fluid density, external field, or restitution coefficient between particles, there is an asymptotic scaling for saying that if Aomega is kept constant, then different amplitudes A (with the corresponding frequencies omega ) produce the same macroscopic result. Furthermore, it is found that in the limit of high frequencies, the boundary condition associated with the vibrating wall can be replaced by a stationary heat source. The value of the heat flux depends linearly with density even for dense fluids. Numerical comparisons with molecular dynamics simulations confirm these predictions and show that the substitution of the vibrating wall by a thermal one gives poor results, while the substitution by a heat source is very accurate.


Case of congenital short small intestine: survival with use of long-term parenteral feeding.
Isolated congenital short small intestine is a rare anomaly. Of six (one male, five females) previously reported cases, four died in infancy from intractable diarrhea. We report the case of 7-year-old boy with this syndrome in whom a 2-year period of parenteral feeding at home allowed normal weight gain, growth, and development while intestinal adaptation occurred. Parenteral feeding was discontinued at age 2 1/3 years, and for the past 5 years his weight has remained between the tenth and 25th percentiles and his stature between the 25th and 50th percentiles. His development has been normal and he functions at or above grade level at school. Coefficient of fat absorption has increased from 54% to 81%. Vitamin B12 absorption has improved but has not normalized. He remains lactose intolerant. We believe his survival, growth, and development would have been compromised if he had not received a prolonged period of parenteral feeding.


A lattice model of ternary mixtures of lipids and cholesterol with tunable domain sizes.
Much of our understanding of the physical properties of raft domains in biological membranes, and some insight into the mechanisms underlying their formation stem from atomistic simulations of simple model systems, especially ternary mixtures consisting of saturated and unsaturated lipids, and cholesterol (Chol). To explore the properties of such systems at large spatial scales, we here present a simple ternary mixture lattice model, involving a small number of nearest neighbor interaction terms. Monte Carlo simulations of mixtures with different compositions show excellent agreement with experimental and atomistic simulation observations across multiple scales, ranging from the local distributions of lipids to the phase diagram of the system. The simplicity of the model allows us to identify the roles played by the different interactions between components, and the interplay between them. Importantly, by changing the value of one of the model parameters, we can tune the size of the liquid-ordered domains, thereby simulating both Type II mixtures exhibiting macroscopic phase separation and Type I mixtures with nanoscopic domains. The Type II mixture simulation results fit well to the experimentally determined phase diagram of mixtures containing saturated DPPC/unsaturated DOPC/Chol. When the tunable parameter is changed, we obtain the Type I version of DPPC/DOPC/Chol, i.e., a mixture not showing thermodynamic phase transitions but one that may be fitted to the same phase diagram if local measures are used to distinguish between the different states. Our model results suggest that short range packing is likely to be a key regulator of the stability and size distribution of biological rafts.


Role of the CD40 and CD95 (APO-1/Fas) antigens in the apoptosis of human B-cell malignancies.
Ligation of CD40 inhibits apoptosis and stimulates proliferation of normal B cells, whereas ligation of CD95 (APO-1/Fas) induces apoptosis of activated lymphocytes. Aberrant signalling through the CD40 and CD95 antigens could thus participate in the pathogenesis of lymphoid malignancies. The expression and function of CD40 and CD95 on neoplastic B cells from patients with acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) were examined. CD40 was expressed by all 30 B-cell tumours, whereas CD95 was detected on neoplastic B cells in only one of 10 cases of ALL, two of 10 cases of CLL, and three of 10 cases of NHL. Incubation with an agonistic CD95 monoclonal antibody (MoAb) did not augment apoptosis in any of the unstimulated B-cell neoplasms. CD40 triggering did not consistently inhibit spontaneous apoptosis, but ultimately stimulated the growth of neoplastic B cells in most cases. Furthermore, CD40 activation led to up-regulation of the CD95 antigen in all 30 B-cell neoplasms. Ligation of CD95 on CD40-activated tumour cells augmented apoptosis in five of 10 ALL, three of 10 CLL, and nine of 10 NHL cases. The degree of apoptosis induced by CD95 triggering was greater for NHL cells than for ALL cells or CLL cells. Bcl-2 expression by ALL and NHL cells was substantially decreased after in vitro culture, whereas Bcl-2 expression by CLL cells was not significantly changed. However, there was no correlation between the level of Bcl-2 expression and sensitivity to CD95-mediated apoptosis. Thus, factors other than levels of CD95 and Bcl-2 determine susceptibility of malignant B cells to apoptosis after CD95 triggering. CD40-activated lymphoma cells appear to be very sensitive to CD95-mediated apoptosis, suggesting potential strategies for treatment of NHL. Elucidation of the mechanisms underlying resistance of ALL and CLL cells to CD95 triggering may facilitate the development of novel therapeutic approaches to these diseases as well.


Effects of an oral prostaglandin E1 agonist on blood pressure and its determinants in essential hypertension.
Arachidonic acid metabolites such as prostaglandins of the E series have well-documented effects on blood pressure (BP). Recently, a stable analogue of prostaglandin E1 (misoprostol) became available for oral use in humans, being primarily indicated for prevention of peptic disease induced by cyclo-oxygenase inhibitors. We hypothesised that misoprostol would exert antihypertensive actions and therefore performed a randomised, placebo-controlled clinical trial in 15 essential hypertensives to characterise the effects of a 400 micrograms oral dose of misoprostol on BP and its haemodynamic, autonomic and biochemical determinants. There was a modest (from 105.3 +/- 2.7 to 101.9 +/- 2.7 mmHg, P = 0.006) decrease in mean arterial pressure 20 minutes after the dose, accompanied by a decrease in systemic vascular resistance and a compensatory rise in cardiac output and heart rate. Baroreflex gain was unaltered by misoprostol, as were plasma renin activity, catecholamines and chromogranin A. Even this transient antihypertensive effect was abolished by cyclooxygenase inhibitor pretreatment. We conclude that oral misoprostol exerts a modest but transient antihypertensive effect that is unlikely to be of either therapeutic benefit or concern in essential hypertension.


Topographically Flat Nanoplasmonic Sensor Chips for Biosensing and Materials Science.
Nanoplasmonic sensors typically comprise arrangements of noble metal nanoparticles on a dielectric support. Thus, they are intrinsically characterized by surface topography with corrugations at the 10-100 nm length scale. While irrelevant in some bio- and chemosensing applications, it is also to be expected that the surface topography significantly influences the interaction between solids, fluids, nanoparticles and (bio)molecules, and the nanoplasmonic sensor surface. To address this issue, we present a wafer-scale nanolithography-based fabrication approach for high-temperature compatible, chemically inert, topographically flat, and laterally homogeneous nanoplasmonic sensor chips. We demonstrate their sensing performance on three different examples, for which we also carry out a direct comparison with a traditional nanoplasmonic sensor with representative surface corrugation. Specifically, we (i) quantify the film-thickness dependence of the glass transition temperature in poly(methyl metacrylate) thin films, (ii) characterize the adsorption and specific binding kinetics of the avidin-biotinylated bovine serum albumin protein system, and (iii) analyze supported lipid bilayer formation on SiO2 surfaces.


Acupuncture Meridian Energies in Patients Who Are Mentally Disturbed.
Acupuncture medicine states that different pathologies exhibit different patterns of excitation in the 24 main acupuncture meridians. Previous exploratory work has shown that groups of patients with the same pathology exhibit such characteristic patterns when limited numbers of acupuncture points are measured with the AcuGraph meridian energy measuring device. This study reports patterns of meridian energies observed in an exploratory assessment of different classes of patient with mental disturbance. This study was a three-group cross-sectional design. Participants were patients who had been diagnosed by their GP with anxiety (n = 21) and depression (n = 26) and who were entering a treatment program, along with age- and sex-matched controls (n = 44). Patients diagnosed with mild mental disturbance who were aged 20-50 years were eligible to take part. Patients with any cut, wart, or mole on their fingertips or with excess sweating, which would interfere with conductance measurements, were excluded. The assessment comprised conductance values at Jing-Well acupuncture points by AcuGraph4 on entry into the treatment program. Patients with anxiety had higher meridian energy levels (81.84 ± 38.63) and significant Upper-Lower imbalances (p < 0.05) favoring the upper meridians. Patients with depression had lower energy levels and lower standard deviations (53.36 ± 33.48) as a group. Controls exhibited intermediate energy levels but recorded the lowest scoring variances (62.61 ± 27.05) of the three groups. Kidney meridians had the lowest energy for both of the pathology groups. For the group suffering with anxiety, bladder meridians were also low. Higher variances in AcuGraph4 measurements were observed in patients with either anxiety or depression compared with controls whose variances were the lowest. These results are in accordance with previous observations of greater variance in conductance values in pathology groups. With regard to meridian energies, the lowest were in those with depression, while those with anxiety were the highest. Controls exhibited intermediate energy levels.


Initial treatment of epilepsy with antiepileptic drugs: pediatric issues.
The selection of an antiepileptic drug (AED) for initial treatment of epilepsy in infancy, childhood, and adolescence should ideally be made after a clear syndromic diagnosis of the patient's seizure disorder. A common cause of failure of the first AED is erroneous diagnosis. The availability of new-generation AEDs has expanded the choice of available agents with comparable efficacy for most syndromes. Efficacy data based on class I or II evidence are not available for many syndromes of childhood, and selection must therefore be based on the best data available. It is also important to assess the relative toxicity and tolerability of AEDs in making the selection. It is especially important to appreciate age-specific organ toxicities. Moreover, the use of AEDs in childhood requires an understanding of their neurobehavioral effects. Important neuropsychiatric co-morbidities in children with epilepsy include attention deficit/hyperactivity disorder, autistic spectrum disorders, depression and anxiety, and thought disorders. These problems can be exacerbated or ameliorated by specific AEDs. The effect of AEDs on body weight, insulin sensitivity, lipid profile, and bone health is becoming better appreciated. Newer AEDs may offer significant advantages in this regard. Co-morbid migraine in children with epilepsy may benefit from some AEDs. There remains a continuing need for the development of newer AEDs that are targeted for the developing brain to improve the efficacy and tolerability of treatment in childhood seizure disorders.


f-treeGC: a questionnaire-based family tree-creation software for genetic counseling and genome cohort studies.
The Tohoku Medical Megabank project aims to create a next-generation personalized healthcare system by conducting large-scale genome-cohort studies involving three generations of local residents in the areas affected by the Great East Japan Earthquake. We collected medical and genomic information for developing a biobank to be used for this healthcare system. We designed a questionnaire-based pedigree-creation software program named "f-treeGC," which enables even less experienced medical practitioners to accurately and rapidly collect family health history and create pedigree charts. f-treeGC may be run on Adobe AIR. Pedigree charts are created in the following manner: 1) At system startup, the client is prompted to provide required information on the presence or absence of children; f-treeGC is capable of creating a pedigree up to three generations. 2) An interviewer fills out a multiple-choice questionnaire on genealogical information. 3) The information requested includes name, age, gender, general status, infertility status, pregnancy status, fetal status, and physical features or health conditions of individuals over three generations. In addition, information regarding the client and the proband, and birth order information, including multiple gestation, custody, multiple individuals, donor or surrogate, adoption, and consanguinity may be included. 4) f-treeGC shows only marriages between first cousins via the overlay function. 5) f-treeGC automatically creates a pedigree chart, and the chart-creation process is visible for inspection on the screen in real time. 6) The genealogical data may be saved as a file in the original format. The created/modified date and time may be changed as required, and the file may be password-protected and/or saved in read-only format. To enable sorting or searching from the database, the file name automatically contains the terms typed into the entry fields, including physical features or health conditions, by default. 7) Alternatively, family histories are collected using a completed foldable interview paper sheet named "f-sheet", which is identical to the questionnaire in f-treeGC. We developed a questionnaire-based family tree-creation software, named f-treeGC, which is fully compliant with international recommendations for standardized human pedigree nomenclature. The present software simplifies the process of collecting family histories and pedigrees, and has a variety of uses, from genome cohort studies or primary care to genetic counseling.


Transfer Channel of Photoinduced Holes on a TiO2 Surface As Revealed by Solid-State Nuclear Magnetic Resonance and Electron Spin Resonance Spectroscopy.
The detailed structure-activity relationship of surface hydroxyl groups (Ti-OH) and adsorbed water (H2O) on the TiO2 surface should be the key to clarifying the photogenerated hole (h+) transfer mechanism for photocatalytic water splitting, which however is still not well understood. Herein, one- and two-dimensional 1H solid-state NMR techniques were employed to identify surface hydroxyl groups and adsorbed water molecules as well as their spatial proximity/interaction in TiO2 photocatalysts. It was found that although the two different types of Ti-OH (bridging hydroxyl (OHB) and terminal hydroxyl (OHT) groups were present on the TiO2 surface, only the former is in close spatial proximity to adsorbed H2O, forming hydrated OHB. In situ 1H and 13C NMR studies of the photocatalytic reaction on TiO2 with different Ti-OH groups and different H2O loadings illustrated that the enhanced activity was closely correlated to the amount of hydrated OHB groups. To gain insight into the role of hydrated OHB groups in the h+ transfer process, in situ ESR experiments were performed on TiO2 with variable H2O loading, which revealed that the hydrated OHB groups offer a channel for the transfer of photogenerated holes in the photocatalytic reaction, and the adsorbed H2O could have a synergistic effect with the neighboring OHB group to facilitate the formation and evolution of active paramagnetic intermediates. On the basis of experimental observations, the detailed photocatalytic mechanism of water splitting on the surface of TiO2 was proposed.


NMR and quantum chemical study on the OH...pi and CH...O interactions between trehalose and unsaturated fatty acids: implication for the mechanism of antioxidant function of trehalose.
Trehalose is a disaccharide that attracts much attention as a stress protectant. In this study, we investigated the mechanism of the antioxidant function of trehalose. The spin-lattice relaxation times (T(1)) of (1)H and (13)C NMR spectra were measured to investigate the interaction between trehalose and unsaturated fatty acid (UFA). We selected several kinds of UFA that differ in the number of double bonds and in their configurations (cis or trans). Several other disaccharides (sucrose, maltose, neotrehalose, maltitol, and sorbitol) were also analyzed by NMR. The T(1) values for the (1)H and (13)C signals assigned to the olefin double bonds in UFA decrease with increasing concentration of trehalose and the changes reaches plateaus at integer ratios of trehalose to UFA. The characteristic T(1) change is observed only for the combination of trehalose and UFA with cis double bond(s). On the other hand, from the (13)C-T(1) measurements for trehalose, the T(1) values of the C-3 (C-3') and C-6' (C-6) are found to change remarkably by addition of UFA. (1)H[bond](1)H NOESY measurements provide direct evidence for complexation of trehalose with linoleic acid. These results indicate that one trehalose molecule stoichiometrically interacts with one cis-olefin double bond of UFA. Computer modeling study indicates that trehalose forms a stable complex with an olefin double bond through OH...pi and CH...O types of hydrogen bonding. Furthermore, a significant increase in the activation energy is found for hydrogen abstraction reaction from the methylene group located between the double bonds that are both interacting with the trehalose molecules. Therefore, trehalose has a significant depression effect on the oxidation of UFA through the weak interaction with the double bond(s). This is the first study to elucidate the antioxidant function of trehalose.


Students' Perceptions on an Interprofessional Ward Round Training - A Qualitative Pilot Study.
Ward rounds are an essential activity for interprofessional teams in hospital settings and represent complex tasks requiring not only medical knowledge but also communication skills, clinical technical skills, patient management skills and team-work skills. The present study aimed to analyse final year students', nurses' as well as physiotherapists' views on a simulation-based interprofessional ward round training. In two successive passes a total number of 29 final year students, nursing students and physiotherapy students (16 in the first run, 13 in the second) volunteered to participate in two standardized patient ward round scenarios: (1) patient with myocardial infarction, and (2) patient with poorly controlled diabetes. Views on the interprofessional ward round training were assessed using focus groups. Focus group based feedback contained two main categories (A) ward round training benefits and (B) difficulties. Positive aspects enfolded course preparation, setting of the training, the involvement of the participants during training and the positive learning atmosphere. Difficulties were seen in the flawed atmosphere and realization of ward rounds in the daily clinical setting with respect to inter-professional aspects, and course benefit for the different professional groups. The presented inter-professional ward round training represents a well received and valuable model of interprofessional learning. Further research should assess its effectiveness, processes of interprofessional interplay and transfer into clinical practice.


Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy.
Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART). HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. NCT00013871 (www.clinicaltrials.gov).


Unusual features of depletion interactions in soft polymer-based colloids mixed with linear homopolymers.
We investigate the influence of the addition of polymer chains on the effective interaction between star polymers, as a model for the depletion potential in ultrasoft mixtures. The effects of size ratio and chain polymer concentration on the chain-modified star-star interactions at good (athermal) solvent conditions are investigated. For both hard sphere mixtures and colloid-nonadsorbing polymer mixtures the range of the depletion interaction increases with the size ratio. For the systems at hand, the range of the depletion potential is insensitive to the size of the depletant polymer. The physical origin of this and the associated effects, as well as a mapping of the mixtures onto a one-component system, are discusssed.


Modifying the OPLS-AA force field to improve hydration free energies for several amino acid side chains using new atomic charges and an off-plane charge model for aromatic residues.
The hydration free energies of amino acid side chains are an important determinant of processes that involve partitioning between different environments, including protein folding, protein complex formation, and protein-membrane interactions. Several recent papers have shown that calculated hydration free energies for polar and aromatic residues (Trp, His, Tyr, Asn, Gln, Asp, Glu) in several common molecular dynamics force fields differ significantly from experimentally measured values. We have attempted to improve the hydration energies for these residues by modifying the partial charges of the OPLS-AA force field based on natural population analysis of density functional theory calculations. The resulting differences between calculated hydration free energies and experimental results for the seven side chain analogs are less than 0.1 kcal/mol. Simulations of the synthetic Trp-rich peptide Trpzip2 show that the new charges lead to significantly improved geometries for interacting Trp-side chains. We also investigated an off-plane charge model for aromatic rings that more closely mimics their electronic configuration. This model results in an improved free energy of hydration for Trp and a somewhat altered benzene-sodium potential of mean force with a more favorable energy for direct benzene-sodium contact.


Heterologous expression of legumin gene in E. coli isolated from cDNA clones of immature seeds of pigeonpea (Cajanus cajan L.).
Proteins are one of the targets for improving the nutritional quality, and attempts are being made through manipulation of its native gene(s). Pigeonpea (Cajanus cajan L.) is one of the nutritionally important legumes of tropical and subtropical regions of the world, and studies of the structure of seed storage proteins and their interactions have been limited by the difficulty of isolating single-protein subunits in large amounts from a complex mixture of the seed endosperm. One way to overcome this problem is the expression of seed storage protein-encoded gene(s) in heterologous systems that have additional advantages wherein specific gene modifications can be made and the new gene constructs can quickly be expressed. Legumin protein was extracted from pigeonpea seeds of different developmental stages (5th to 25th day after flowering [DAF]) and characterized. The legumin gene (leg) of size 1.482 kb was screened, using the deoxygenin-labeled legumin probe, from the complementary deoxyribonucleic acid (cDNA) library, constructed from 18-day-old (DAF) immature seeds of pigeonpea and sequenced (accession no. AF3555403). The legumin gene was further characterized by DNA blotting, and its probable secondary structure was predicted using online ExPASy server. Significant Protein Data Bank (PDB) alignment of the deduced legumin protein by BLASTP was observed with proglycinin of soybean. Comparative 3D structural homology was predicted by Cn3D software, and the legumin protein showed the 3D structure alignment and interaction homology with proglycinin chain 1FXZA (PDB no. 1FXZ). The legumin gene was subcloned in vector pET-24a driven by the bacterial promoter, and its expression was detected in Escherichia coli by immunoblotting using polyclonal antibodies, raised against the purified legumin protein.