Advance directives: patient preferences in family practice.
The author reports on six months' experience of obtaining advance directives from patients for care in a family practice. Patients were questioned about their preferences for comfort or prolonging life and then were asked to delegate a substitute decision maker. Of 20 patients, all who responded chose comfort over prolonging life. Delegated substitute decision makers included spouses, children, and professionals or friends. In this population, patients overwhelmingly favoured comfort over prolonging life in the event that they might be irreversibly disabled, and they tended to choose spouses or other first-degree relatives as substitute decision makers.


RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress.
The Rho family of GTPases regulates many aspects of cellular behavior through alterations to the actin cytoskeleton . The majority of the Rho family proteins function as molecular switches cycling between the active, GTP-bound and the inactive, GDP-bound conformations . Unlike typical Rho-family proteins, the Rnd subfamily members, including Rnd1, Rnd2, RhoE (also known as Rnd3), and RhoH, are GTPase deficient and are thus expected to be constitutively active . Here, we identify an unexpected role for RhoE/Rnd3 in the regulation of the p53-mediated stress response. We show that RhoE is a transcriptional p53 target gene and that genotoxic stress triggers actin depolymerization, resulting in actin-stress-fiber disassembly through p53-dependent RhoE induction. Silencing of RhoE induction in response to genotoxic stress maintains stress fiber formation and strikingly increases apoptosis, implying an antagonistic role for RhoE in p53-dependent apoptosis. We found that RhoE inhibits ROCK I (Rho-associated kinase I) activity during genotoxic stress and thereby suppresses apoptosis. We demonstrate that the p53-mediated induction of RhoE in response to DNA damage favors cell survival partly through inhibition of ROCK I-mediated apoptosis. Thus, RhoE is anticipated to function by regulating ROCK I signaling to control the balance between cell survival and cell death in response to genotoxic stress.


Varicella zoster virus reactivation and the increased risk of cerebrovascular accidents: the unexpected role dermatologists can play.
Varicella zoster virus (VZV) primary infection usually causes varicella and its reactivation may lead to different clinical manifestations depending on the site of viral reactivation and its subsequent tissue spread. There is a growing recognition of the association between VZV reactivation and ensuing cerebrovascular accidents (CVA). The virus can spread to cerebral arteries, causing a wide clinical spectrum related to VZV vasculopathy. Herein we present an 80-year-old man with a previously undiagnosed immunosuppressive condition, admitted with disseminated herpes zoster, who subsequently developed an acute ischemic CVA and showed a substantial neurologic recovery under antiviral therapy.


Skewed distribution of proinflammatory CD4+CD28null T cells in rheumatoid arthritis.
Expanded populations of CD4+ T cells lacking the co-stimulatory molecule CD28 (CD4+CD28null T cells) have been reported in several inflammatory disorders. In rheumatoid arthritis, increased frequencies of CD4+CD28null T cells in peripheral blood have previously been associated with extra-articular manifestations and human cytomegalovirus (HCMV) infection, but their presence in and contribution to joint manifestations is not clear. In the present article we investigated the distribution of CD4+CD28null T cells in the synovial membrane, synovial fluid and peripheral blood of RA patients, and analysed the association with erosive disease and anti-citrullinated protein antibodies. CD4+CD28null T cells were infrequent in the synovial membrane and synovial fluid, despite significant frequencies in the circulation. Strikingly, the dominant TCR-Vbeta subsets of CD4+CD28null T cells in peripheral blood were often absent in synovial fluid. CD4+CD28null T cells in blood and synovial fluid showed specificity for HCMV antigens, and their presence was clearly associated with HCMV seropositivity but not with anti-citrullinated protein antibodies in the serum or synovial fluid, nor with erosive disease. Together these data imply a primary role for CD4+CD28null T cells in manifestations elsewhere than in the joints of patients with HCMV-seropositive rheumatoid arthritis.


Catheter-induced urethral erosion.
Indwelling bladder catheters are often placed when a patient requires voiding assistance. Long-term use of these catheters has been associated with significant morbidity This case presentation describes a complete erosion of the glans, urethra, and penile skin, up to the penoscrotal junction, as an outcome from long-term use of an indwelling bladder catheter. Appropriate nursing interventions can prevent this devastating health care outcome.


Local synthesis of amyloid fibril precursor in AL amyloidosis of the urinary tract.
An amyloid tumor localized to the urethra was resected and shown by immunohistochemistry to contain fibril deposits that stained with antisera specific for lambda VI immunoglobulin light chain. The amino acid sequence of the fibril protein was homologous to lambda VI Positive staining of subepithelial plasma cells with lambda VI specific monoclonal antibody was consistent with the hypothesis that the fibril precursor light chain protein is synthesized and processed locally to give this type of localized amyloidosis.


Respiratory conditions, including asthma, and height in primary school.
The National Study of Health and Growth (NSHG) of primary school children has examined the relationships between height and each of six separate respiratory conditions, one of which was asthma, in children aged 5-11 years, allowing for a number of genetic and environmental confounding factors, in particular for parental height. The relationships were investigated in a 'representative' sample of 4974 Caucasian English children in 1984 and in an 'ethnic/inner city' sample of 3419 Afro-Caribbean/Indian and Pakistani/Caucasian English children in 1985. None of the respiratory conditions was found to be related to height except for 'wheeze most days', whether or not it was accompanied by an asthma attack in the last 12 months. The Caucasian children in the 'representative' sample who had 'wheeze most days', were 0.17 height standard deviation score (95% confidence interval 0.03 to 0.31) less (approximately 1 cm) than those with no wheeze. Comparisons with previous results for NSHG 'representative' Caucasian English children in 1973 showed good agreement except for children with three or more asthma attacks who were found to be shorter in 1973, but not in 1984, which may reflect improved treatment, or milder asthma being reported in 1984. It was concluded that, in the 1980s, the respiratory conditions were not related to height. The exception was 'wheeze most days'. It is suggested that this is an indicator of sickness, most likely asthma, which is being experienced with sufficient severity to affect growth slightly.


[Quality of life and associated factors in patients with heart failure].
Heart failure is a chronic and exacerbating disease, which often significantly decreases patient quality of life (QOL). Treatments continue to focus on alleviating the physical symptoms of this disease, and data on QOL factors are limited. The purpose of this study was to explore QOL and associated factors in patients with heart failure. A cross-sectional and correlational research design was conducted using the Kansas City Cardiomyopathy Questionnaire, Beck Depression Inventory-II, and the World Health Organization Quality of Life Assessment. A convenience sample of 200 patients aged 20 years old or above and diagnosed with heart failure were recruited from one medical center and one regional teaching hospital in southern Taiwan. Data were analyzed using SPSS 14.0 software. Results found (1) participants had an average QOL index score of 63.0 (moderate); (2) significant differences in QOL scores for the variables of marriage, occupation type, monthly family income, concomitant diabetes/hypertension, number of complications, and treatment type; (3) participants had an average index score for symptoms of 54.1 (moderate) that was significantly correlated with QOL; (4) a majority of participants were classified in NYHA Class II, mean score of depression was 9.13±6.25 (normal), and functional status and depression were significantly related to QOL; and (5) 59.3% of QOL variance was explained by depression, symptoms and family income per month. This study may help health professionals to understand relationships among symptoms, functional status, depression and QOL in heart failure patients. It may also provide healthcare professionals evidence-based data necessary to further improve symptoms, functional status and depression in heart failure patients, and thus significantly improve QOL in patients with heart failure.


Antibodies against EGF-like domains in Ixodes scapularis BM86 orthologs impact tick feeding and survival of Borrelia burgdorferi.
Ixodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the immunization of murine hosts with specific recombinant EGF antigens marginally reduced spirochete loads in the skin, in addition to affecting tick blood meal engorgement and molting. However, given the borderline impact of EGF immunization on tick engorgement and pathogen survival in the vector, it is unlikely that these antigens, at least in their current forms, could be developed as potential vaccines. Further investigations of the biological significance of Is86 (and other tick antigens) would enrich our knowledge of the intricate biology of ticks, including their interactions with resident pathogens, and contribute to the development of anti-tick measures to combat tick-borne illnesses.


Developing An Analytic Approach to Understanding the Patient Care Experience.
The amount of data available to health-care institutions regarding the patient care experience has grown tremendously. Purposeful approaches to condensing, interpreting, and disseminating these data are becoming necessary to further understand how clinical and operational constructs relate to patient satisfaction with their care, identify areas for improvement, and accurately measure the impact of initiatives designed to improve the patient experience. We set out to develop an analytic reporting tool deeply rooted in the patient voice that would compile patient experience data obtained throughout the medical center.


Designing a sub-set of the UMLS knowledge base applied to a clinical domain: methods and evaluation.
The UMLS is a complex collection of interconnected biomedical concepts derived from standard nomenclatures. Designing a specific subset of the UMLS knowledge base relevant to a medical domain is a prerequisite for the development of specialized applications based on UMLS. We have developed a method based on the selection of the appropriate terms in original nomenclatures and the capture of a set of UMLS terms that are linked to them in the network to a certain degree. We have experimented it as the foundation for a concept base applied to urology. Results depend on the exhaustiveness of the relationships between the Metal concepts. A preliminary analysis of the sub-base reveals that some adaptations of vocabulary and ontology are required for clinical applications.


Truncation of Ube3a-ATS unsilences paternal Ube3a and ameliorates behavioral defects in the Angelman syndrome mouse model.
Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by maternal deficiency of the imprinted gene UBE3A. Individuals with AS suffer from intellectual disability, speech impairment, and motor dysfunction. Currently there is no cure for the disease. Here, we evaluated the phenotypic effect of activating the silenced paternal allele of Ube3a by depleting its antisense RNA Ube3a-ATS in mice. Premature termination of Ube3a-ATS by poly(A) cassette insertion activates expression of Ube3a from the paternal chromosome, and ameliorates many disease-related symptoms in the AS mouse model, including motor coordination defects, cognitive deficit, and impaired long-term potentiation. Studies on the imprinting mechanism of Ube3a revealed a pattern of biallelic transcription initiation with suppressed elongation of paternal Ube3a, implicating transcriptional collision between sense and antisense polymerases. These studies demonstrate the feasibility and utility of unsilencing the paternal copy of Ube3a via targeting Ube3a-ATS as a treatment for Angelman syndrome.


A comparison of the effects of Chinese non-pharmaceutical therapies for premature ovarian failure: A PRISMA-compliant systematic review and network meta-analysis.
Premature ovarian failure (POF) is commonly treated with hormone replacement therapy (HRT). Many patients with POF choose acupuncture as a complementary therapy over HRT, due to possible adverse reactions. This systematic review and network meta-analysis (NMA) compares the efficacy of different forms of acupuncture therapies for POF. Seven databases including PubMed, the Cochrane Library, Embase, Wanfang database, China National Knowledge Infrastructure database, VIP Chinese Science, and Chinese Biomedical Database were searched for randomized controlled trials (RCTs) of various acupuncture treatments for POF. This time spanned from the date of database inception to January 13, 2020. RevMan 5.3 was used to assess the bias risk of the studies. A NMA of the included studies was performed using Stata14.0. A total of 408 items were searched in this study, and finally this NMA included 16 RCTS, involving 1,307 patients. It showed that acupuncture (OR:1.35,95%1.24 to 1.47) has the best effectiveness among the four acupuncture (standardized mean difference [SMD]-16.30,95% -31.33 to -1.28) is the most effective and the best in reducing follicle-stimulating hormone levels among the four acupuncture treatments. Acupuncture (SMD 26.67,95%5.95 to 47.40) and acupoint embedding (SMD41.14,95%11.90 to 70.37) were ranked in the top 2 positions, in improving estradiol, whereas acupuncture (SMD-4.90,95% -8.10 to -1.70) was than acupoint embedding and HRT, in reducing luteinizing hormone level. In addition, our conclusions have not changed significantly after the sensitivity analysis.Protocol registration number: CRD42020150508. With clinical evidence summarized by NMA, it is observed that acupuncture is the most promising therapy for improving menopausal symptoms, decreasing serum follicle-stimulating hormone and luteinizing hormone level. Therefore, acupuncture could be effective for patients with POF, who are intolerant to the adverse effects of hormone replacement therapy or who would prefer non-drug therapies. Further multi-center and high-quality RCT studies should be conducted to make our conclusion more rigorous.


Functional antioxidant responsive elements.
Exposure of human and rodent cells to a wide variety of chemoprotective compounds confers resistance against a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes like glutathione S-transferases (GST). Antioxidant responsive elements (AREs) mediate the transcriptional induction of a battery of genes which comprise much of this chemoprotective response system. Past studies identified a necessary ARE "core" sequence of RTGACnnnGC, but this sequence alone is insufficient to mediate induction. In this study, the additional sequences necessary to define a sufficient, functional ARE are identified through systematic mutational analysis of the murine GST Ya ARE. Introduction of the newly identified necessary nucleotides into the regions flanking a nonresponsive, ARE-like, GST-Mu promoter sequence produced an inducible element. A screen of the GenBank database with the newly identified ARE consensus identified 16 genes which contained the functional ARE consensus sequence in their promoters. Included within this group was an ARE sequence from the murine ferritin-L promoter that mediated induction when tested. In an electrophoretic mobility-shift assay, the ferritin-L ARE was bound by ARE-binding protein 1, a protein previously identified as the likely mediator of the chemoprotective response. A three-level ARE classification system is presented to account for the distinct induction strengths observed in our mutagenesis studies. A model of the ARE as a composite regulatory site, where multiple transcription factors interact, is presented to account for the complex characteristics of ARE-mediated chemoprotective gene expression.


[Clinical analysis of 72 epileptic patients treated with alkaline extract of Euphorbia fisheriana].
The effect of 72 epileptic patients treated with alkaline extract of Euphorbia fisheriana (EF) was reported. 22 of them with intractable epilepsy were compared with the treatment of both single-blind and placebo. The results showed that the total effective rate with EF was 78%, its marked effective rate was 42% and the effective rate 36%. The epileptic patients reduced their frequency of seizures significantly (P < 0.05), while the effective rate of 22 epileptic patients with single-blind treatment was 59%, and that with placebo was 32%. There was a significant difference between the two groups (P < 0.05). The active principle of Euphorbia fisheriana was Euphorbia alkaloid. There was no obvious adverse effect in clinical observation. It is considered that Euphorbia fisheriana is rich in resource, cheap, and with marked anticonvulsant effect.


Quantitative trait locus mapping of genes that regulate HDL cholesterol in SM/J and NZB/B1NJ inbred mice.
To investigate the quantitative trait loci (QTL) regulating plasma cholesterol, the female progeny of an (SMxNZB/ B1NJ)xNZB/B1NJ backcross were fed an atherogenic diet. After 18 wk, plasma total cholesterol and high-density lipoprotein cholesterol (HDL-C) was measured. HDL-C concentrations were greater in NZB than in SM mice. For standard chow-fed mice, QTL were found near D5Mit370 and D18Mit34. For mice fed an atherogenic diet, a QTL was found near D5Mit239. The QTL for chow-fed and atherogenic-fed mice on chromosome 5 seem to be two different loci. We used a multitrait analysis to rule out pleiotropy in favor of a two-QTL hypothesis. Furthermore, the HDL-C in these strains was induced by the high-fat diet. For inducible HDL-C, one significant locus was found near D15Mit39. The gene for an HDL receptor, Srb1, maps close to the HDL-C QTL at D5Mit370, but the concentrations of Srb1 mRNA and SR-B1 protein and the gene sequence of NZB/B1NJ and SM/J did not support Srb1 as a candidate gene. With these QTL, we have identified chromosomal regions that affect lipoprotein profiles in these strains.


Examining the Relationship Between Maladaptive Perfectionism and Social Anxiety: The Mediating Role of Self-Compassion.
Previous studies have indicated a relationship between perfectionism and social anxiety symptoms, but the mechanisms between these concepts are not well-defined yet. This study focused on the mediator role of self-compassion in the relationship between maladaptive perfectionism and social anxiety symptoms controlling self-esteem. It is hypothesized that maladaptive perfectionism would be related to lower levels of self-compassion and lower levels of self-compassion related to greater social anxiety symptoms controlling self-esteem. The sample consisted of 389 university students who completed a battery of instruments, including measures of The Liebowitz Social Anxiety Scale (LSAS), The Big Three Perfectionism Scale (BTPS), The Self-Compassion Scale (SCS), and The Rosenberg Self-Esteem Scale (RSES). Simple mediation analyses with bootstrapping demonstrated that self-compassion has a significant mediator role in the relationship between maladaptive perfectionism and social anxiety when self-esteem is not included in the model. However, results also revealed that the indirect effect of self-compassion is no longer significant when self-esteem is included in the model as a covariate. Findings suggest that self-compassion has no mediator role independent from self-esteem in the context of perfectionism and social anxiety.


Diagnosis of left atrial appendage thrombi by multiplane transesophageal echocardiography: interlaboratory comparative study.
Transesophageal echocardiography (TEE) is regarded as the method of choice for imaging left atrial appendage thrombi (LAAT). However, the interobserver variability among 2 independent echocardiographic laboratories in diagnosing LAAT by multiplane TEE has not yet been assessed. The videorecordings of 50 patients in atrial fibrillation (25 from each laboratory) were blindly reviewed by 1 experienced observer from each institution. LAAT were assessed as present, absent or questionable. Indications for TEE were: cardioversion (n=17), valve disease (n=13), endocarditis (n=12), or embolism (n=8). The prevalence of LAAT was 10% (observer 1) vs 12% (observer 2). A questionable LAAT was assessed in 6% vs 12% and a LAAT was excluded in 84% vs 76%, respectively. By head-to-head comparison, disagreement occurred in 11 cases (22%, kappa=0.5). Discrepant results were not related to the echocardiographic equipment. Problems occurred because of reverberation artifacts of the ridge between the left atrial appendage and left upper pulmonary vein (n=5), and in differentiating LAAT from spontaneous echocardiographic contrast (n=4) or an echogenic atrioventricular groove (n=1). The differentiation of pectinate muscles from LAAT was the reason for disagreement in only 1 case. Eliminating the category of questionable thrombi increased the kappa value to 0.65. In 5 patients undergoing cardiac surgery, both observers had agreed on the presence (n=1) or absence (n=4) of LAAT, and intraoperatively the results of TEE were confirmed. Even with multiplane TEE, interobserver variability among 2 independent echocardiographic laboratories for diagnosing LAAT remains high because of problems in differentiating LAAT from spontaneous echocardiographic contrast and reverberation artifacts.


Cauliflower-Like Shaped Osteoma.
Skull osteoma is a benign tumor that slowly and continuously enlarges. It is frequently observed in routine medical practice and many patients show an arc shape. The authors encountered a patient with osteoma with a rare morphology that developed in the occipital region. The patient was a 66-year-old male who had been aware of the presence of a mass in the occipital region for about 50 years, but its uncomfortable feeling had recently increased, and it was resected. The excised tumor showed a pedunculated cauliflower-like shape continuous to the skull. The pathological diagnosis was osteoma. The cause of rare morphologies includes trauma and infection, but this patient had no such past medical history. Since the development site was the occipital region, it was assumed that chronic stimulation caused the rare morphology.


The Effect of Metformin as an Adjunct Therapy in Adolescents with Type 1 Diabetes.
The strict control of blood glucose levels in adolescents with Type 1 Diabetes Mellitus (T1DM) is accompanied with a considerable long term decrease in microvasular and macrovascular complications. This study was conducted to investigate the effect of metformin as an adjunct therapy in adolescents with poorly controlled Type 1 diabetes. It was a quasi-experimental (an uncontrolled before and after) study. The study population consisted of the patients aged over 10 years with T1DM. Metformin tablet was added to patient's insulin therapy for 12 months. Haemoglobin A1c protein was measured in the beginning of the study and repeated with three months intervals till the end of it. Insulin dosage, Body Mass Index (BMI), serum lipid, creatinine and lactate level were measured twice; in the beginning of the study and at the end of it (after 12 months). Data was analysed by SPSS (version 18) software. Paired- t-test, Wilcoxon signed ranks test and Repeated Measure ANOVA were used to examine the study's hypothesis. A p-value <0.05 was considered as significant. Twenty nine patients were included in the study. HbA1c level and insulin dosage was significantly reduced (p<0.001) after one month of metformin as an adjunct therapy. Serum lipid was decreased (p=0.7). Weight (p<0.001) and BMI (p=0.007) were increased. Adjunctive metformin therapy reduced HbA1c value and the insulin dosage received in adolescents with T1DM.


Is high-sensitivity C-reactive protein associated with lower urinary tract symptoms in aging men? Results from the hallym aging study.
The pathogenesis of lower urinary tract symptoms (LUTS) is uncertain. We investigated the potential role of inflammation in the development of LUTS, with the use of high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker, in a population-based study of aging men in Korea. Our study used a multistage stratified design to recruit a random sample of 1,510 men aged 45 years or older in Chuncheon, Korea, in 2003. Men with urologic or neurologic diseases that could cause voiding dysfunction were excluded. Also, men with medical conditions that could affect inflammation, such as infection or the use of nonsteroidal anti-inflammatory drugs, were excluded. LUTS were defined according to the International Prostate Symptom Score (IPSS). Various potential confounding factors were included in the analyses. A total of 330 subjects were included in the final analyses. There were 155 (47.0%) with an IPSS<8 and 175 (53%) with an IPSS≥8. The mean age of all subjects was 69.2±8.4 years. The mean hsCRP level of all subjects was 2.30±3.27 (median, 1.19) mg/l. The hsCRP levels in subjects with an IPSS≥8 differed significantly from those in subjects with an IPSS<8. Also, IPSS, storage symptom, voiding symptom, and quality of life (QoL) scores increased as hsCRP levels increased, respectively. The hsCRP level remained an independent risk factor of LUTS (IPSS≥8, storage symptom score≥4, incomplete voiding, intermittency, and QoL) after adjustment for variable possible confounding factors. Our results suggest that inflammatory processes may play an important role in the pathogenesis of LUTS and that hsCRP levels may indicate the severity of LUTS in aging men.


Effect of a spray formulation on the reproductive parameters of a susceptible population of Rhipicephalus (Boophilus) microplus.
The number of studies emphasizing the possible damage that acaricidal spray formulations can cause on engorged female ticks' reproductive parameters is small. The present study evaluated the deleterious effects of a spray formulation (dichlorvos 60% + chlorpyrifos 20%) on the reproductive parameters of a susceptible population of Rhipicephalus (B.) microplus females, using the Stall Test. The ticks were allocated randomly to treatments according to the mean numbers of females detached from each cow on days -3, -2 and -1 and the cattle pen location. The numbers of engorged female ticks that naturally detached from the cattle were counted daily from day 1 to day 30. For each group, 20 detached engorged female ticks or the available number collected daily were evaluated regarding reproductive parameters. Associations of organophosphates demonstrated elevated acaricidal efficacy, as well as deleterious effects on the reproductive parameters of R. (B.) microplus females. The engorged female weight (days 1 to 7), weight of egg masses (days 5 to 10) and larval hatching percentage (days 5 to 19) were decreased (P ≤ 0.05). It is possible that a formulation can lead to deleterious effects on R. (B.) microplus females when the tick population analyzed shows elevated sensitivity towards a particular formulation. However, further studies need to be conducted.


6,7-dimethoxy-coumarin as a probe of hydration dynamics in biologically relevant systems.
Coumarin derivatives are well known fluorescence reporters for investigating biological systems due to their strong micro-environment sensitivity. Despite having wide range of environment sensitive fluorescence probes, the potential of 6,7-dimethoxy-coumarin has not been studied extensively so far. With a perspective of its use in protein studies, namely using the unnatural amino acid technology or as a substrate for hydrolase enzymes, we study acetyloxymethyl-6,7-dimethoxycoumarin (Ac-DMC). We investigate the photophysics and hydration dynamics of this dye in aerosol-OT (AOT) reverse micelles at various water contents using the time dependent fluorescence shift (TDFS) method. The TDFS response in AOT reverse micelles from water/surfactant ratio of 0 to 20 confirms its sensitivity towards the hydration and mobility of its microenvironment. Moreover, we show that the fluorophore can be efficiently quenched by halide ions. Hence, we conclude that the 6,7-dimethoxy-methylcoumarin fluorophore is useful for studying hydration parameters in biologically relevant systems.


Determination of twelve heparin- and heparan sulfate-derived disaccharides as 2-aminoacridone derivatives by capillary zone electrophoresis using ultraviolet and laser-induced fluorescence detection.
In quest for high sensitivities, we developed an ultrahigh capillary electrophoresis (CE) method for the structural analysis of heparin and heparan sulfate (HS) in biologic samples. Heparin and HS were digested with an equi-unit mixture of heparin lyases I, II and III and the obtained Delta-disaccharides were derivatized with the fluorophore 2-aminoacridone. All known twelve non-, mono-, di- and trisulfated Delta-disaccharides were completely resolved in a single run, using 50 mM phosphate buffer, pH 3.5, and reversed polarity at 30 kV. Relative standard deviation in migration times and peak areas as well as day-to-day variance ranged from 0.9 to 2.4%, suggesting a reproducible and precise method. Detection of 2-aminoacridone (AMAC)-derivatives of Delta-disaccharides by UV at 255 nm showed 2.8 and 10 times higher sensitivity than that of derivatized and non-derivatized ones at 232 nm. Laser-induced fluorescence detection with an Ar-ion laser source showed an approximately 100 times higher sensitivity than that obtained at 232 nm of the non-derivatized species. Application of this method to quantitative analysis of Delta-disaccharides derived from porcine intestinal mucosa heparin and bovine kidney HS showed excellent agreement with previously published methods, suggesting an accurate method. The developed method can be easily applied for the disaccharide analysis of heparin/HS at the attomole level with high accuracy, for distinguishing between heparin and HS and may be of value for studying their interactions with matrix effective molecules.


Older Adults in Public Open Spaces: Age and Gender Segregation.
There is a substantial body of literature on the importance of the environment in the lives of older adults. Nonetheless, to date, there has been limited research on everyday activities of urban older adults in public open spaces. The present study examined the activities of older adults in public open spaces in Israel with a specific focus on age and gender as potential variables of relevance. Using still photography, we systematically photographed four sessions in two different public outdoor settings attended by older Israelis. Still photographs were converted to narrative descriptions, and then coded, quantified, and compared using descriptive statistics. The majority (311, 97%) of older adults arrived alone to the public setting. Of these, 44% formed a social group of two or more people, whereas the remaining older adults stayed alone. When social interactions occurred, they were primarily gender homogenous (69%); women were more likely to integrate in spontaneous social conversations and men were more likely to participate in common games. Our findings call attention to the important role played by the outdoor environment as a venue for social activities among older adults. The findings further stress the high levels of aloneness experienced by older adults, which do not seem to be alleviated by the mere attendance of public spaces.


Toward Defining "Vocal Constriction": Practitioner Perspectives.
This research investigated the terminology used in relation to constriction of the singing voice from a range of practitioner perspectives. It focused on the locality, causes, consequences, management, trends, identification, and vocabulary of constriction. The research aimed to develop a holistic understanding of the term "vocal constriction" from participant experiences and perceptions (N = 10). Data collection occurred through in-depth, semi-structured interviews with a range of voice care professionals. Participants included three professional groups: (1) Ear, Nose, and Throat medical specialists or laryngologists, (2) speech pathologists or speech therapists, and (3) singing teachers. Purposive sampling was used to ensure that the participants from groups 1 and 2 had extensive experience with singers in their practice. The singing teachers were experienced in either classical or contemporary styles, or both. Participant responses highlighted a discrepancy in preferred terminology, with "constriction" being less favored overall. Several anatomical locations were identified including postural, supraglottic (anteroposterior and false fold), articulatory, and in the intrinsic and extrinsic laryngeal musculature; psychological issues were also identified. Primary causes, secondary causes, and influencing factors were identified. Inefficient technique and poor posture or alignment were considered primary causes; similarly, emotion and anxiety or stress were identified as influencing factors by the majority of participants. There was less uniformity in responses regarding other causes. The major findings of this research are the respective participant group distinctions, an uncertainty regarding anteroposterior constriction, and that the location and effects of constriction are individual to the singer and must be considered contextually. A definition is offered, and areas for further research are identified.


Beyond Hygiene: Commensal Microbiota and Allergic Diseases.
Complex communities of microorganisms, termed commensal microbiota, inhabit mucosal surfaces and profoundly influence host physiology as well as occurrence of allergic diseases. Perturbing factors such as the mode of delivery, dietary fibers and antibiotics can influence allergic diseases by altering commensal microbiota in affected tissues as well as in intestine. Here, we review current findings on the relationship between commensal microbiota and allergic diseases, and discuss the underlying mechanisms that contribute to the regulation of allergic responses by commensal microbiota.


Galactose recognition by the carbohydrate-binding module of a bacterial sialidase.
Glycoside hydrolases often possess carbohydrate-binding modules (CBMs) in addition to their catalytic domains, which help target the enzymes to appropriate substrates and thereby increase their catalytic efficiency. Sialidases hydrolyse the release of sialic acid from a variety of glycoconjugates and play significant roles in the pathogenesis of a number of important diseases. The sialidase from Micromonospora viridifaciens has a CBM which recognizes galactose. The CBM is linked to the catalytic domain by an immunoglobulin-like domain, resulting in the galactose binding site sitting above the catalytic site, suggesting an interplay between the two sites. By studying nine crystallographically independent structures of the M. viridifaciens sialidase, the relative flexibility of the three domains was analysed. A detailed study is also presented of the recognition of galactose and lactose by the M. viridifaciens CBM. The striking structure of this sialidase suggests a role for the CBM in binding to galactose residues unmasked by the adjacent catalytic site.


Role of kidney in the catabolic clearance of human platelet antiheparin proteins from rat circulation.
Stimulated platelets release at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4) from which beta-thromboglobulin (beta TG) is derived. We have found previously marked elevation of LA-PF4/beta TG antigen in platelet poor plasma of patients with chronic renal failure, whereas levels of PF4 remained normal. Therefore, we examined the role of the kidneys in the metabolic clearance of LA-PF4/beta TG and PF4. The supernates of aggregates of thrombin-stimulated human platelets were injected into sham operated control rats, nephrectomized rats, and into rats with acute ureteral ligation. The disappearance of human LA-PF4/beta TG antigen and PF4 in rat plasma determined by specific radioimmunoassays followed biphasic exponential curves. The half-lives (t1/2) for the fast and slow components of LA-PF4 in control rats were 6.4 and 68.4 min. Nephrectomy significantly increased these times to 9.7 and 144 min, while ureteral ligation resulted in no significant change. Comparison of the level of LA-PF4/beta TG antigen and of creatinine in aorta and in renal vein showed 25%-30% extraction of these compounds by the kidney. Less than 0.1% of the total LA-PF4 antigen injected was recovered in the urine of control rats. In contrast to these results, the clearance of PF4 was not affected by nephrectomy. (1) functional renal tissue is necessary for normal clearance of LA-PF4/beta TG, but renal excretion does not play a major role in its elimination suggesting that the protein is catabolized by the kidney; and (2) catabolic clearance of PF4 does not depend on functioning kidney tissue.


Thyroid epigenetics: X chromosome inactivation in patients with autoimmune thyroid disease.
The autoimmune thyroid diseases (AITDs) are female-predominant diseases with a ratio of approximately seven females to each male. X chromosome inactivation (XCI), an epigenetic phenomenon, has been suggested to be skewed in many such female patients with AITD. We analyzed female genomic DNA from 87 patients with Graves' disease (GD), 47 patients with Hashimoto's thyroiditis (HT), and 69 healthy controls. Using an XCI assay based on Hpa II digestion and PCR and DNA sequencing, we found skewed heterozygous XCI (>or=80%) in 20 of 70 GD patients (28.6%) and 11 of 43 HT patients (25.6%), giving a total of 31 of 113 AITD patients (27.4%) with skewed XCI. In contrast, only 5 of 58 healthy controls had skewed XCI (8.6%). Statistical analysis confirmed that XCI skewing was significantly associated with AITD (P = 0.004, OR = 4.0), demonstrating that the degree of XCI is an important contributor to the increased risk of females in developing AITD.


Competition between fullerene aggregation and poly(3-hexylthiophene) crystallization upon annealing of bulk heterojunction solar cells.
Concomitant development of [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) aggregation and poly(3-hexylthiophene) (P3HT) crystallization in bulk heterojunction (BHJ) thin-film (ca. 85 nm) solar cells has been revealed using simultaneous grazing-incidence small-/wide-angle X-ray scattering (GISAXS/GIWAXS). With enhanced time and spatial resolutions (5 s/frame; minimum q ≈ 0.004 Å(-1)), synchrotron GISAXS has captured in detail the fast growth in size of PCBM aggregates from 7 to 18 nm within 100 s of annealing at 150 °C. Simultaneously observed is the enhanced crystallization of P3HT into lamellae oriented mainly perpendicular but also parallel to the substrate. An Avrami analysis of the observed structural evolution indicates that the faster PCBM aggregation follows a diffusion-controlled growth process (confined by P3HT segmental motion), whereas the slower development of crystalline P3HT nanograins is characterized by constant nucleation rate (determined by the degree of supercooling and PCBM demixing). These two competing kinetics result in local phase separation with space-filling PCBM and P3HT nanodomains less than 20 nm in size when annealing temperature is kept below 180 °C. Accompanying the morphological development is the synchronized increase in electron and hole mobilities of the BHJ thin-film solar cells, revealing the sensitivity of the carrier transport of the device on the structural features of PCBM and P3HT nanodomains. Optimized structural parameters, including the aggregate size and mean spacing of the PCBM aggregates, are quantitatively correlated to the device performance; a comprehensive network structure of the optimized BHJ thin film is presented.


[The circumstances and background of the discovery of the Rh-factors].
We can hardly meet references in the literature to the various circumstances and factors that played an important role in scientific discoveries, although interesting conclusions could be driven from them. So, e.g., in the case of Landsteiner it is sure, that his idea, to investigate the reason of the mechanism and of the formation of a phenomenon, came from the phenomenon itself: namely, from the agglutination called forth by the fortuitous mixing of the cadavers' blood in the dissecting room. The present paper deals with certain circumstances that played a role in the discovery of the Rh-Factors, resulting not only scientific, but practical consequences as well. The data used here were collected primarily from the memoirs of professors Wiener, Levine, Dahr and from those of Speiser (Vienna). The authors were helped in their research also by their personal contact with professor Dahr (Cologne) established in the sixties. Landsteiner was compelled to emigrate from Austria mainly by the vivid anti-Semitism of the early 20s. Supposedly, without his emigration the Rh Factors would have been discovered much later. Working in the Rockefeller Institute (New York) Landsteiner was provided with everything that was needed for his research. He had organised a team and, helped by his colleagues, he succeeded to open a new field in immunserology. Unfortunately, before he could have completed his scientific project, he had died--already as a Nobel-Prize winner--in 1943. His project was resumed by his colleagues. The method of Rh-examination, exceeding the field of medicine, quickly won a greater significance, in anthropology, genetics and in biology. It is worth to mention, that Landsteiner, had already indicated shortly after his discovery the fields, on which the Rh-examinations later played a significant role.


Perception of breathlessness during early and late asthmatic responses.
We looked at the perception of breathlessness associated with bronchoconstriction during early (EAR) and late (LAR) asthmatic responses to inhaled antigens and its correlation with the rate of fall of expiratory flows. Twenty-eight asthmatics were studied (12 male, 16 female, 18 to 38 yr of age). Breathlessness was evaluated on a modified Borg scale (0 to 10) before each FEV1 measurement, obtained at regular intervals for as long as 8 h after the antigen challenge. The rate of the fall in FEV1 was calculated from the maximal percent fall obtained during the EAR or the LAR and the time lapse from the onset of the reaction to the maximal fall in FEV1. Ten subjects had an isolated early and 18 had a dual asthmatic response after allergen challenge. Dual responders perceived a similar percent fall in FEV1 (mean percent fall: EAR, 20.7 +/- 1.6%; LAR, 21.5 +/- 1.6%) more intensely during the EAR than during the LAR, with median Borg scores (range) of, respectively, 2.0 (0.5 to 4) and 0.5 (0 to 3.0) (n = 18, p < 0.001). The median rate of the fall in FEV1 was: EAR, 2.09 (0.77 to 6.6) %/min; LAR, 0.11 (0.05 to 0.36) %/min (n = 18, p < 0.001). The rate of the fall in FEV1 during either EAR or LAR was strongly correlated with the Borg scores; the slower the fall, the weaker the perception (p < 0.001). We conclude that LAR are poorly perceived compared with EAR and that this may be due to the temporal adaptation to the slow and progressive bronchoconstriction in LAR.


Locally advanced non-small cell lung cancer: current issues and recent trends.
The focus of this paper was to review and summarise the current issues and recent trends within the framework of locally advanced (LA) non-small cell lung cancer (NSCLC). The recently proposed 8th tumour-node-metastases (TNM) staging system exhibited significant amendments in the distribution of the T and M descriptors. Every revision to the TNM classification should contribute to clinical improvement. This is particularly necessary regarding LA NSCLC stratification, therapy and outcomes. While several studies reported the superiority of the 8th TNM edition in comparison to the previous 7th TNM edition, in terms of both the discrimination ability among the various T subgroups and clinical outcomes, others argued against this interpretation. Synergistic cytotoxic chemotherapy with radiotherapy is most prevalent in treating LA NSCLC. Clinical trial experience from multiple references has reported that the risk of locoregional relapse and distant metastasis was less evident for patients treated with concomitant radiochemotherapy than radiotherapy alone. Nevertheless, concern persists as to whether major incidences of toxicity may occur due to the addition of chemotherapy. Cutting-edge technologies such as four-dimensional computed tomography (4D-CT) and volumetric modulated arc therapy (VMAT) should yield therapeutic gains due to their capability to conform radiation doses to tumours. On the basis of the preceding notion, the optimum radiotherapy technique for LA NSCLC has been a controversial and much-disputed subject within the field of radiation oncology. Notably, no single-perspective research has been undertaken to determine the optimum radiotherapy modality for LA NSCLC. The landscape of immunotherapy in lung cancer is rapidly expanding. Currently, the standard of care for patients with inoperable LA NSCLC is concurrent chemoradiotherapy followed by maintenance durvalumab according to clinical outcomes from the PACIFIC trial. An estimated 42.9% of patients randomly assigned to durvalumab remained alive at five years, and free of disease progression, thereby establishing a new benchmark for the standard of care in this setting.


Identification of key proteins of cultured human intestinal cells involved in interaction with enteroaggregative Escherichia coli.
Enteroaggregative Escherichia coli (EAEC) adherence to human intestinal tissue is known to be mediated by aggregative adherence fimbriae (AAF). However, the host cell molecules involved in EAEC adherence remain uncharacterized. In the present study, four key membrane glycoproteins of cultured human intestinal epithelial cells (INT-407) were found to be involved in the interaction with the T8 strain of EAEC. Nine membrane proteins of INT-407 cells were found to interact with EAEC-T8, of which four were identified as fibronectin, epidermal growth factor receptor (EGFR), Thrombospondin-1 (TSP1) and glucose-regulated protein (GRP-94). Our findings were validated by Western blot using antibody against each identified protein. The adherence of EAEC-T8 to INT-407 cells was reduced to c. 26, 29, 37 and 76% in the presence of the antibody against GRP-94, EGFR, fibronectin and TSP-1, respectively. These findings were further substantiated by flow cytometry, where the final mean fluorescence intensity value of the INT-407 cells (c. 1075) resulting from adherent-labelled bacteria was found to be reduced to c. 26, 132, 228 and 597 in the presence of antibody against GRP-94, EGFR, fibronectin and TSP-1. We propose that GRP-94, EGFR, fibronectin and TSP-1 are involved in the aggregative adherence of EAEC-T8 to INT-407 cells.


An analysis of the spatial arrangement of the myocardial aggregates making up the wall of the left ventricle.
We used the technique of peeling of myocardial aggregates, usually described as 'fibres', to determine the spatial arrangement of the myocytes in the left ventricular wall of a healthy autopsied human heart. We digitised the left ventricular outer and inner boundaries, as well as the pathways in space, of almost 3000 aggregates harvested from the left ventricular myocardium. During the process of gradual peeling, we sought to identify the myocardial aggregates as uniformly as possible. Despite this, interpolation was necessary to complete the pattern so as to construct a unit vector field that represented the preferred direction of the myocardial aggregates throughout the entirety of the walls of the left ventricle of this individual human heart. Apart from the overall systematic arrangement of the aggregates necessary to achieve physiologic ventricular contraction, we documented substantial local heterogeneities in the orientation of the myocardial aggregates. In particular, a significant proportion of aggregates was found to intrude obliquely with respect to the ventricular boundaries, with markedly heterogeneous distribution. Moreover, the distribution of the helical angle of the aggregates relative to the ventricular base varied notably throughout the left ventricular free walls and the septum. Within the generally quite uniform and continuous structure of the ventricular mass, we were, however, unable to identify any organised tracts or functional subunits such as a 'helical ventricular band', nor did we find radial fibrous lamellas coursing across the ventricular wall. We suggest that the impact of local anatomical inhomogeneities, associated with gradients in regional contractile function on global ventricular dynamics, has been systematically underestimated in the past. Our analysis confirms furthermore the continuous nature of the myocardium associated with an overall gross organisation of the fibre direction field; however, there is no evidence of substructures compartmentalising the ventricles.


Shifting into Action: from Data Segmentation to Equitable Interoperability for Adolescents (and Everyone Else).
Technological improvements and, subsequently, the federal 21st Century Cures Act have resulted in increased access to and interoperability of electronic protected health information (ePHI). These not only have many benefits, but also have created unique challenges for privacy and confidentiality for adolescent patients. The inability to granularly protect sensitive data and a lack of standards have resulted in limited confidentiality protection and inequitable access to health information. This study aimed to understand the challenges to safe, equitable access, and interoperability of ePHI for adolescents and to identify strategies that have been developed, ongoing needs, and work in progress. Shift, a national task force formalized in 2020, is a group of more than 200 expert stakeholder members working to improve functionality to standardize efforts to granularly identify and protect sensitive ePHI to promote equitable interoperability. Shift has created high-priority clinical use cases and organized challenges into the areas of Standards and Terminology; Usability and Implementation; and Ethics, Legal, and Policy. Current technical standards and value sets of terminology for sensitive data have been immature and inconsistent. Shift, a national diverse working group of stakeholders, is addressing challenges inherent in the protection of privacy and confidentiality for adolescent patients. The diversity of expertise and perspectives has been essential to identify and address these challenges.


A computation using mutually exclusive processing is sufficient to identify specific Hedgehog signaling components.
A system of more than one part can be deciphered by observing differences between the parts. A simple way to do this is by recording something absolute displaying a trait in one part and not in another: in other words, mutually exclusive computation. Conditional directed expression in vivo offers processing in more than one part of the system giving increased computation power for biological systems analysis. Here, I report the consideration of these aspects in the development of an in vivo screening assay that appears sufficient to identify components specific to a system.


Small bowel transanal evisceration mimicking a rectal prolapse. A case report and review of literature.
Transanal intestinal evisceration is a very uncommon and dramatic occurrence, linked most frequently to rectal prolapse rupture or, very rarely, to traumatic pathology. The Authors describe a case of a 74-year-old female patient who required urgent hospital admission because of a seemingly strangulated rectal prolapse. During surgical preparation the protruding mass was recognized as small bowel loops herniating from the anus. Evisceration was due to spontaneous rectal wall rupture, most likely caused by increased abdominal pressure and consequent breach through the weakened rectum. Surgical treatment consisted in small bowel resection combined with an Hartmann's procedure. Spontaneous rectal rupture without a pre-existing rectal prolapse is a rather infrequent and challenging condition; its mechanism is still incompletely explained. The management is surgical and may range from primary repair up to extensive intestinal resection to include a defunctioning colostomy. Rectal prolapse, Spontaneous rectal rupture, Transanal evisceration.


Relationship between PPARα mRNA expression and mitochondrial respiratory function and ultrastructure of the skeletal muscle of patients with COPD.
Peripheral muscle dysfunction is an important complication in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to explore the relationship between the levels of peroxisome proliferator-activated receptor α (PPARα) mRNA expression and the respiratory function and ultrastructure of mitochondria in the vastus lateralis of patients with COPD. Vastus lateralis biopsies were performed on 14 patients with COPD and 6 control subjects with normal lung function. PPARα mRNA levels in the muscle tissue were detected by real-time PCR. A Clark oxygen electrode was used to assess mitochondrial respiratory function. Mitochondrial number, fractional area in skeletal muscle cross-sections, and Z-line width were observed via transmission electron microscopy. The PPARα mRNA expression was significantly lower in COPD patients with low body mass index (BMIL) than in both COPD patients with normal body mass index (BMIN) and controls. Mitochondrial respiratory function (assessed by respiratory control ratio) was impaired in COPD patients, particularly in BMIL. Compared with that in the control group, mitochondrial number and fractional area were lower in the BMIL group, but were maintained in the BMIN group. Further, the Z-line became narrow in the BMIL group. PPARα mRNA expression was positively related to mitochondrial respiratory function and volume density. In COPD patients with BMIN, mitochondria volume density was maintained, while respiratory function decreased, whereas both volume density and respiratory function decreased in COPD patients with BMIL. PPARα mRNA expression levels are associated with decreased mitochondrial respiratory function and volume density, which may contribute to muscle dysfunction in COPD patients.


[Hemodynamics in donor plasmapheresis].
Several studies have demonstrated that preoperative withdrawal and storage of autologous plasma as fresh frozen plasma is effective in blood conservation. For that purpose patients with elective surgery (orthopaedic surgery, open heart surgery, neurosurgery and others) have to undergo donor plasmapheresis without staying in the hospital. Depending upon the need the procedure can be performed several times preoperatively, taking about 900 ml in a normal weighting subject at once. The collection of autologous plasma should be finished at least 14 days before surgery. In order to investigate the haemodynamic effects of donor plasmapheresis 30 patients scheduled for coronary bypass surgery were devided into two groups. 15 patients underwent plasmapheresis (10 ml plasma/kgbw) by one-needle-technique using a Haemonetics seperator (PCS) after premedication but before onset of anaesthesia. Blood withdrawal was performed with 0.5 ml/kgbw x min. Another 15 patients, serving as control had no plasma withdrawal and were measured at identical times as the other group. Both groups had an identical fluid replacement with 500 ml Ringer's solution during the investigation period. Plasma withdrawn was not substituted by colloidal solution (simulating the situation when plasmapheresis is performed at the outpatient). Haemodynamic measurements (both groups) included heart rate, arterial blood pressure, right- and left-atrial pressure, systemic- and pulmonary-vascular resistance and cardiac output. There were no relevant effects of plasmapheresis on haemodynamic function during and after the investigation period in that patients: neither heart rate, blood pressure or vascular resistance changed significantly nor did pre- and afterload or cardiac index. No differences to the group without plasmapheresis could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Distribution of obesity-related metabolic markers among 5-15 year old children from an urban area of Sri Lanka.
Obesity-associated metabolic consequences are commonly seen among young South Asians. To assess the nutritional status, prevalence of metabolic derangements and to identify the validity of different obesity diagnostic criteria in the detection of metabolic derangements among 5-15 year old school children in the Colombo district of Sri Lanka. MATERIALS AND PROCEDURES: After a 12-hour overnight fast, blood was drawn for glucose, lipid profile and alanine amino transferase (ALT) enzyme. Oral glucose tolerance test (OGTT) was done with blood taken for random blood sugar 2 hours after glucose load. Height, weight, waist circumference (WC) and blood pressure were measured. Nine hundred and twenty children were studied (boys, n = 547). Thirty-two (3.5%) were obese according to IOTF classification. Five (0.5%) and 57 (6.2%) children had systolic and diastolic hypertension. Twelve (1.3%) and three (0.3%) had impaired fasting glucose and 2-hour OGTT, respectively. One hundred and thirty-nine (15.1%) had hypercholesterolemia and 36 (3.9%) hypertriglyceridaemia. Two hundred and fifteen (23.3%) had low HDL. Fifteen (1.6%) had metabolic syndrome according to IDF definition. Two hundred and eighty-three (30.7%) had one metabolic derangement; 95 (10.3%) had two metabolic derangements; and 16 (1.7%) had three or more metabolic derangements. Sri Lankan BMI and WC obesity cut-offs had a higher sensitivity in detecting metabolic abnormalities than international cut-offs. Metabolic derangements are prevalent in children who were detected to be non-obese by anthropometric measures, and clinicians should actively look and correct them. New research is needed to study the long-term effects on health.


Bullous skin disease: an unusual allergic reaction to vancomycin.
Severe reactions due to vancomycin are uncommon. We describe a case of vancomycin-induced linear immunoglobulin A bullous disease and review the literature pertinent to this entity. This is a rare subepidermal blistering disorder, with a heterogenous clinical presentation. It is characterized by IgA deposition in a linear pattern along the basement membrane zone. It seems to be autoantibody-mediated and is not dose-dependent. Spontaneous and complete skin healing follows vancomycin withdrawal; rechallenge reproduces the disease with a more rapid and severe onset. Because vancomycin is almost never suspected to be the cause of such manifestations, awareness of this rare autoimmune reaction is crucial. Early diagnosis through direct immunofluorescence of the perilesional skin would avoid unnecessary laboratory investigations and therapeutic measures and would shorten significantly the pain and suffering of these patients.


Quality control of the proteins associated with neurodegenerative diseases.
Most neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease and other polyglutamine diseases are associated with degeneration and death of specific neuronal populations due to misfolding or aggregation of certain proteins. These aggregates often contain ubiquitin that is the signal for proteolysis by the ubiquitin-proteasome system, and chaperone proteins that are involved in the assistance of protein folding. Here we review the role of protein quality control systems in the pathogenesis of neurodegenerative diseases, and aim to learn more from the cooperation between molecular chaperones and ubiquitin-proteasome system responding to cellular protein aggregates, in order to find molecular targets for therapeutic intervention.


Steroid metabolism in the rabbit. Biliary and urinary excretion of metabolites of [4-14-C]testosterone.
1. [4-(14)C]Testosterone was administered to anaesthetized male and female New Zealand White rabbits as a single injection or as a 45-60min. infusion. 2. After a single dose a total of approx. 56-80% of the radioactivity was excreted in bile and urine. After infusion total recovery of radioactivity was approx. 63-75%. 3. The mean ratio of metabolites in urine to those in bile was 0.77+/-0.41 (range 0.3-1.5). 4. Bile and urine samples were hydrolysed successively by beta-glucuronidase, cold acid and hot acid. In both bile and urine neutral metabolites extracted by ethyl acetate-ether were found mainly after beta-glucuronidase hydrolysis, but a considerable proportion of the dose was converted into substances not extractable from alkaline aqueous solution after all forms of hydrolysis used.


Cross sections for the valence shell excitations of nitrous oxide studied by fast electron impact.
The generalized oscillator strengths, differential cross sections, as well as the integral cross sections for electron impact excitation of the B (1)Delta, C (1)Pi, and D (1)Sigma(+) states of N(2)O have been determined at an incident electron energy of 2500 eV. A generalized oscillator strength analysis reveals that the B (1)Delta<--X (1)Sigma(+) transition is dominated by the quadrupolar component. From the comparison to the previous experimental results, it is found that the first Born approximation is not satisfied for the C (1)Pi excitation while it is valid for the D (1)Sigma(+) excitation at an incident electron energy of 200 eV. The BE-scaled integral cross section for the B (1)Delta excitation from its threshold to 5000 eV was calculated based on its generalized oscillator strength, and the present integral cross sections for the excitation of the C (1)Pi and D (1)Sigma(+) states are in good agreement with the calculations using the BEf-scaling approach.


Territrem and butyrolactone derivatives from a marine-derived fungus Aspergillus terreus.
Seventeen lactones including eight territrem derivatives (1-8) and nine butyrolactone derivatives (9-17) were isolated from a marine-derived fungus Aspergillus terreus SCSGAF0162 under solid-state fermentation of rice. Compounds 1-3 and 9-10 were new, and their structures were elucidated by spectroscopic analysis. The acetylcholinesterase inhibitory activity and antiviral activity of compounds 1-17 were evaluated. Among them, compounds 1 and 2 showed strong inhibitory activity against acetylcholinesterase with IC50 values of 4.2 ± 0.6, 4.5 ± 0.6 nM, respectively. This is the first time it has been reported that 3, 6, 10, 12 had evident antiviral activity towards HSV-1 with IC50 values of 16.4 ± 0.6, 6.34 ± 0.4, 21.8 ± 0.8 and 28.9 ± 0.8 μg·mL-1, respectively. Antifouling bioassay tests showed that compounds 1, 11, 12, 15 had potent antifouling activity with EC50 values of 12.9 ± 0.5, 22.1 ± 0.8, 7.4 ± 0.6, 16.1 ± 0.6 μg·mL-1 toward barnacle Balanus amphitrite larvae, respectively.


[Targeting and role of α4β7 integrin in the pathophysiology of IBD and HIV infection].
Integrins are a large family of heterodimeric cell adhesion molecules that are key regulators in multiple biological functions. They orchestrate cell-cell and cell-extracellular matrix (ECM) adhesive interactions from embryonic development to mature tissue function, and are thus involved in cell migration, proliferation, differentiation, and survival. As such, they are also involved in human diseases, such as thrombotic diseases, inflammation, cancer, fibrosis and infectious diseases. Integrins are exciting pharmacological targets because they are exposed on the cell surface. Indeed, several compounds have been developed that block integrins function, and five have been approved as therapeutic drugs for use in clinic. This review will detail the role of α4β7, an integrin of particular relevance for mucosal diseases such as IBD (inflammatory bowel disease) and also, as reported more recently, HIV infection.


Repair of experimental autologous grafts of cortical bone.
Fresh autologous segmental grafts of fibula, four centimeters long, were obtained from thirteen adult dogs. Holes were drilled in each before replantation. The amount of repair was determined after intervals of from four to twenty-four weeks. Torsional stress testing showed that the six drill holes 500 micrometers in diameter confined within an expanse of two centimeters did not mechanically weaken the transplants at the time of surgery. The drill holes were rapidly filled with cancellous bone which matured to cortical bone within twelve weeks. Microradiography and tetracycline labeling of drilled and non-drilled grafts demonstrated similar biological reparative patterns.


Anti-initiating activity of 3beta-methoxy-13alpha,14alpha-epoxyserratan-21beta-ol (PJJ-34) from the stem bark of Picea jezoensis Carr. var. jezoensis.
Ultraviolet light is the major cause of skin cancers in human, and several effects of ultraviolet light B (UVB) are thought to contribute to skin photocarcinogenesis. 3Beta-methoxy-13alpha,14alpha-epoxyserratan-21beta-ol (PJJ-34; 1) isolated from Picea jezoensis Carr. var. jezoensis showed the strongest antitumor-promoting activity among naturally occurring triterpenoids in the in vivo two-stage mouse skin-carcinogenesis test. To investigate the anti-initiating activity, we further studied mouse models initiated with ultraviolet-B (UVB) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). Oral administration of the PJJ-34 (1) during a period before and after the three times of UVB irradiation led to a remarkable effect: oral administration of a 0.0025% solution of 1 only to the test group, which started one week before and ended one week after the irradiation, showed less than half papillomas, and inhibition of tumor incidence and tumor multiplicity in comparison to the control group. Therefore, it was recognized that PJJ-34 (1) showed strong anti-initiating activity as well as anti-promoting activity. After all, 1 seems to be useful as cancer-chemopreventive agent.


Detrimental Complications Of Meconium Aspiration Syndrome And Their Impact On Outcome.
Meconium aspiration syndrome (MAS) is respiratory distress in an infant born through meconium stained amniotic fluid (MSAF) whose signs cannot be otherwise explained. MAS is associated with different complications. Many studies have been conducted in developed world to find the outcome associated with MAS but data from developing countries is lacking. Present study was conducted to determine the impact of chemical pneumonitis, pulmonary hypertension (PHN) and air leak on outcome of new-borns with MAS. This cross sectional descriptive study was conducted in a tertiary care Neonatology unit. The babies diagnosed with MAS were included in the study. All patients were monitored for development of complications. Outcome in terms of mortality was recorded. Outcome was compared by chisquare test and p-value <0.05 is considered significant. Seventy two babies were included in the study. Mean gestation was 37±0.56 weeks and birth weight was 2.87±0.49 kg. Male to female ratio was 1.57:1 and mean age of admission was 9.59±5.27 hours. Chemical pneumonitis, PHN and chemical pneumonitis with PHN were observed in 23.6%, 20.8% and 26.4% neonates respectively. Mortality rate was 19.44%. The mortality was highest in babies having chemical pneumonitis with PHN (p-value=0.013) followed by chemical pneumonitis group (p-value=0.02) and PHN group (p-value=0.032). About three fourth babies with MAS developed one or more complications. Mortality is significantly increases with the development of complications so as more the complications more is the mortality.


Transient Neonatal Diabetes Mellitus with the Rare Association of Nonsuppurative Sialadenitis and Genetic Defects in 6q24.
Transient neonatal diabetes mellitus (TNDM) is the most common cause of diabetes in the first week of life, with an overall incidence of 1 in 90,000 to 160,000 live births. TNDM occurs soon after birth and undergoes spontaneous remission during infancy; however, it may relapse to a permanent form of diabetes mellitus in childhood or adolescence. We report a case of TNDM due to hypomethylation on chromosome 6q24, associated with a rare clinical finding of nonsuppurative submandibular sialadenitis managed by subcutaneous insulin, and who underwent remission by three months of age. Case Presentation. We report a male neonate of Arab ancestry delivered by caesarean section at 37 weeks of gestation. He had intrauterine growth retardation with a birth weight of 2.099 kg. He presented with hyperglycemia on the first day of life, which was managed with parenteral insulin infusion. Blood glucose control was initially difficult to achieve due to difficulties in preparing such small doses of insulin and the significant variations in blood glucose concentrations, without ketosis. Blood tests revealed low serum insulin and C-peptide levels. Genetic analysis revealed multiple loci hypomethylation of the PLAGL1/HYMAI-DMR in the TNDM region in chromosome 6q24 and two pathogenic heterozygous variants in the ZFP57 gene. Segregation analysis showed that both parents were heterozygous carriers of familial ZFP57 variants. The clinical course was associated with bilateral nonsuppurative sialadenitis, which is extremely rare among newborns. Sialadenitis is a well-known phenomenon that is rarely diagnosed in neonates. To the best of our knowledge, this is the first case report to describe the exceedingly rare association of nonsuppurative submandibular sialadenitis in a neonate with TNDM due to multiple loci hypomethylation of the PLAGL1/HYMAI-DMR in the TNDM region in 6q24 and heterozygous pathogenic variants in the ZFP57 gene.


Extending the reach of an evidence-based theatrical intervention.
BACKGROUND/STUDY CONTEXT: In Experiment 1, the authors investigated whether they could train retirement home activity directors with no previous experience in theatre to successfully execute an evidence-based 4-week theatre-arts intervention. In Experiment 2, they investigated whether an outside professional acting teacher who received only minimal training via e-mail and telephone could successfully execute the same intervention heretofore only carried out by the actor/director/professor who devised it. A total of 115 participants (ages 68-94) in four different retirement homes were taught theatre arts either by their in-house activity director who had no formal training in theatre or a professional acting teacher recruited through a local community college. The intervention consisted of twice-weekly 70-min lessons for 4 weeks. After random assignment to experimental or waiting-list control groups, participants were given pre- and posttests on both functional and cognitive measures. Experiment 1 showed that activity directors were able to run this intervention and achieve significant results on the 28-item functional measure (Observed Tasks of Daily Living, Revised [OTDL-R]) as measured by a mixed-design analysis of variance (ANOVA) and paired-sample t tests (p < .001), and on one cognitive measure, Means-End Problem-Solving (MEPS), as measured by a multivariate ANOVA (MANCOVA) and follow-up univariate ANOVAs. Experiment 2 (outside acting teacher) used the identical measures and revealed significant results on the OTDL-R (p = .002), word recall, MEPS, and verbal fluency (η²(p) ranging from .28 to .59). This study addressed the feasibility of training multiple instructors of varying experience to administer this theatre-arts intervention. Previous iterations had all been administered by the professional actor/director/theatre professor who devised the program. These current results demonstrate that widespread administration of this short-term (4-week) evidence-based intervention is feasible.


Infrared Spectroscopic Studies of Oxygen Atom Quantum Diffusion in Solid Parahydrogen.
The thermally induced diffusion of atomic species in noble gas matrices was studied extensively in the 1990s to investigate low-temperature solid-state reactions and to synthesize reactive intermediates. In contrast, much less is known about the diffusion of atomic species in quantum solids such as solid parahydrogen (p-H2). While hydrogen atoms were shown to diffuse in normal-hydrogen solids at 4.2 K as early as 1989, the diffusion of other atomic species in solid p-H2 has not been reported in the literature. The in situ photogeneration of atomic oxygen, by ArF laser irradiation of an O2-doped p-H2 solid at 193 nm, is studied here to investigate the diffusion of O(3P) atoms in a quantum solid. The O(3P) atom mobility is detected by measuring the kinetics of the O(3P) + O2 → O3 reaction after photolysis via infrared spectroscopy of the O3 reaction product. This reaction is barrierless and is thus assumed to be diffusion-controlled under these conditions such that the reaction rate constant can be used to estimate the oxygen atom diffusion coefficient. The O3 growth curves are well fit by single exponential expressions allowing the pseudo-first-order rate constant for the O(3P) + O2 → O3 reaction to be extracted. The reaction rates are affected strongly by the p-H2 crystal morphology and display a non-Arrhenius-type temperature dependence consistent with quantum diffusion of the O(3P) atom. The experimental results are compared to H(2S) atom reaction studies in p-H2, analogous studies in noble gas matrices, and laboratory studies of atomic diffusion in astronomical ices and surfaces.


Unprecedented multiplicity of Ig transmembrane and secretory mRNA forms in the cartilaginous fish.
In most jawed vertebrates including cartilaginous fish, membrane-bound IgM is expressed as a five Ig superfamily (Igsf)-domain H chain attached to a transmembrane (Tm) region. Heretofore, bony fish IgM was the one exception with IgM mRNA spliced to produce a four-domain Tm H chain. We now demonstrate that the Tm and secretory (Sec) mRNAs of the novel cartilaginous fish Ig isotypes, IgW and IgNAR, are present in multiple forms, most likely generated by alternative splicing. In the nurse shark, Ginglymostoma cirratum, and horn shark, Heterodontus francisci, alternative splicing of Tm exons to the second or the fourth constant (C(H)) exons produces two distinct IgW Tm cDNAs. Although the seven-domain IgW Sec cDNA form contains a canonical secretory tail shared with IgM, IgNAR, and IgA, we report a three-domain cDNA form of shark IgW (IgW(short)) having an unusual Sec tail, which is orthologous to skate IgX(short) cDNA. The IgW and IgW(short) Sec transcripts are restricted in their tissue distribution and expression levels vary among individual sharks, with all forms expressed early in ontogeny. IgNAR mRNA is alternatively spliced to produce a truncated four-domain Tm cDNA and a second Tm cDNA is expressed identical in Igsf domains as the Sec form. PBL is enriched in the Tm cDNA of these Igs. These molecular data suggest that cartilaginous fish have augmented their humoral immune repertoire by diversifying the sizes of their Ig isotypes. Furthermore, these Tm cDNAs are prototypical and the truncated variants may translate as more stable protein at the cell surface.


Risk Factors of Pneumocystis jirovecii Pneumonia in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study.
: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients. : This nationwide, population-based study was conducted in Korea using claims data. Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics. : During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days. : PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients.


The Effect of Shyness on Adolescent Network Problem Behavior: The Role of Gender and Loneliness.
With the latest, rapid developments of the Internet, young people have become the main group in the online world. Congruently, Internet problem behaviors have shown a significant growth trend among adolescents. The present paper explores the factors affecting adolescents' problem network behavior from the perspective of their shyness, gender, and loneliness, and provides suggestions for guiding these young people toward using the network rationally. The study surveyed 5,130 teenagers from Shandong province in China to investigate the moderating effect of gender on the relationship between shyness and problem network behavior, and the mediating effect of loneliness on the moderating effect. The results indicated that the level of shyness among girls was significantly higher than that among boys, whereas the prevalence of cyberbullying, pathological Internet use, and Internet gaming disorder was significantly lower for girls than for boys. The relationship among shyness, cyberbullying, and Internet gaming disorder was found to be moderated by gender, and the problems of cyberbullying and Internet gaming disorder faced by shy boys were greater than those faced by shy girls. In addition, the moderating effect of gender on cyberbullying and Internet gaming disorder was found to occur through the mediating factor of loneliness. The paper concludes with a discussion of the theoretical significance and generalizability of our research results.


Mucosa-associated lymphoid tissue (MALT) in Barrett's esophagus: prospective evaluation and association with gastric MALT, MALT lymphoma, and Helicobacter pylori.
Prospective evaluation of the prevalence of mucosa-associated lymphoid tissue (MALT) within Barrett's esophagus and its association with gastric MALT, gastric MALT lymphoma, and H. pylori infection. From Barrett's esophagus patients, a minimum of six gastric biopsies were obtained, in addition to Barrett's surveillance biopsies. Additional gastric biopsies were taken from any ulcer(s), nodule(s), polyp(s), or other lesions. Patients with gastroesophageal reflux symptoms without Barrett's esophagus served as controls. One hundred and thirty-nine Barrett's patients were included in the study. One hundred and twenty-two of these patients had gastric biopsies for gastric MALT and H. pylori determination. H. pylori was noted in the stomach of 48 patients and within Barrett's mucosa in 14. Barrett's MALT was noted in seven cases, gastric MALT in 16, and gastric MALT lymphoma in two. None of the 101 control patients had esophageal MALT. Two of the seven patients with Barrett's MALT had gastric MALT. Barrett's MALT was associated with esophageal H. pylori in 57.1% cases and gastric H. pylori in 71.4%. The prevalence of gastric and esophageal H. pylori in patients with Barrett's MALT was significantly higher compared to patients with Barrett's without MALT (p < 0.0001 and p < 0.007, respectively). Barrett's MALT was very focal and its esophageal location variable. Barrett's MALT was associated with both esophageal and gastric H. pylori colonization. Esophageal MALT was associated with Barrett's esophagus. Gastric biopsy sampling is warranted in any patient with Barrett's MALT to detect gastric MALT and H. pylori, which, if found, should be eradicated.


Brucella suis carbonic anhydrases and their inhibitors: Towards alternative antibiotics?
Carbonic anhydrases have started to emerge as new potential antibacterial targets for several pathogens. Two β-carbonic anhydrases, denominated bsCA I and bsCA II, have been isolated and characterized from the bacterial pathogen Brucella suis, the causative agent of brucellosis or Malta fever. These enzymes have been investigated in detail and a wide range of classical aromatic and heteroaromatic sulfonamides as well as carbohydrate-based compounds have been found to inhibit selectively and efficiently Brucella suis carbonic anhydrases. Inhibition of these metalloenzymes constitutes a novel approach for the potential development of new anti-Brucella agents. This review aims at discussing the recent literature on this topic.


On Psilorhynchus sucatio and P. nudithoracicus, with the description of a new species of Psilorhynchus from northeastern India (Ostariophysi: Psilorhynchidae).
Psilorhynchus sucatio (Hamilton) is redescribed based on the examination of 462 specimens, 13-67 mm standard length (SL). Psilorhynchus nudithoracicus Tilak & Husain is redescribed based on the examination of 97 specimens, 10-68 mm SL. Psilorhynchus gracilis Rainboth is placed in the synonymy of P nudithoracicus. Psilorhynchus hamiltoni, a new species and a member of the P. balitora species group, is described from the Tista River in West Bengal, India. It is distinguished from all other members of the P. balitora species group by having a well-developed lateral stripe, 6-7 poorly developed saddles that do not make contact with the lateral blotches, 7-11 lateral blotches, 34-35 lateral line scales, 9+8-9 principal caudal-fin rays, 36 total vertebrae, and the ventral surface between paired fins with a broad rectangular scaleless patch. A key to the species groups of Psilorhynchus is also provided, as are revised diagnoses for the P. balitora and P. nudithoracicus species groups.


Comparison measurement of unattached radon progeny concentration in three different environments.
Accurate measurement of unattached radon progeny is important for dose evaluation of radon exposure. For quality control of field surveys, a series of comparison measurements were carried out using three commercial unattached radon progeny monitors in real environments as well as in a radon chamber. The results show that the radon equilibrium equivalent concentrations (EECs) of different monitors agree very well, mostly within ±3.0% where there is no thoron progeny interference in the radon chamber. However, the unattached fraction of radon progeny is not so consistent, and the relative difference is 3.3% ~ 39.5% in different environments. The unattached fraction of radon progeny is affected by aerosol concentration. Anomalously high unattached fraction was found in the environment with extremely high humidity and low aerosol concentration. For accurate measurement of unattached radon progeny, specific attention should be paid to the collection efficiency of unattached radon progeny and the interference of attached radon progeny on a wire screen.


Outcome after heroin overdose and cardiopulmonary resuscitation.
The survival of heroin overdose patients resuscitated from cardiac arrest is reported to be poor. The aim of our study was to investigate the outcome and characteristics of survivors after cardiac arrest caused by heroin overdose. This was a retrospective study in a medium-sized city (population, 560,000). Between 1 January 1997 and 31 December 2000, there were 94 combined cardiac arrests caused by acute drug poisonings. The main outcome measure was survival to discharge. Cardiopulmonary resuscitation was attempted in 19 heroin overdose patients (group A) and in 53 patients with cardiac arrest caused by other poisonings (group B). Three (16%) vs. six (11%) patients were discharged alive (group A vs. B, respectively). The survivors in group A had an Emergency Medical Service (EMS)-witnessed cardiac arrest or the Emergency Dispatching Centre was called before the arrest occurred. There was no statistically significant difference between the two groups in terms of survival. Survivors in both groups suffered from acute renal failure (two), hypoglycaemia (four) and hypothermia (three). Survival after cardiac arrest caused by heroin overdose is possible if the arrest is EMS witnessed or the Emergency Dispatching Centre is called before the cardiac arrest occurs. In comparison with cardiac arrests caused by other poisonings, there was no difference in survival. The incidence and mechanism of hypoglycaemia should be examined in further studies.


Effect of Structure on Polypeptide Blobs: A Model Study Using Poly(l-lysine).
The conformation of a series of pyrene-labeled poly(l-lysine)s (Py-PLLs) in 60:40 and 90:10 (v/v) acetonitrile:water mixtures was determined by comparing the results obtained from the fluorescence blob model (FBM) analysis of their fluorescence decays with those obtained from molecular mechanics optimizations (MMOs). PLL aggregates formed in both solutions as demonstrated by FRET experiments between naphthalene- and pyrene-labeled PLLs. Addition of an excess of unlabeled PLL allowed the conformational study of isolated Py-PLL embedded in a matrix of unlabeled PLLs. By varying the acetonitrile (ACN) content of the solution from 60 to 90 vol % ACN, Py-PLL was found to undergo a conformational change from a random coil to an α-helix. The conformational change induced an increase in the maximum number of lysines (Nblob) separating two pyrene-labeled lysines that could still form an excimer between an excited- and a ground-state pyrene. Nblob obtained from the FBM analysis increased from 15.2 ± 2.1 to 25.2 ± 1.2 lysines as PLL changed its conformation from a random coil to an α-helix. AFM revealed that the α-helical PLLs organized themselves into structured bundles ∼22 nm in diameter. The FBM analysis of the decays acquired with a solution of aggregated Py-PLLs in a 90:10 ACN:water mixture yielded a larger Nblob value of 36.6 ± 3.4. The increase in Nblob indicated that the Py-PLL constructs could now interact with one another in the helical bundles. This increase in Nblob was then used in conjunction with MMOs to determine an interhelical spacing of 2.9 ± 0.1 nm for Py-PLLs in a bundle. This interhelical spacing resulted in a local density of 0.25 ± 0.01 g·cm-3 for the bundles of PLL α-helices, which was a reasonable density for a protein in solution. This study describes an experimental means to probe the number of amino acids that interact with each other as the conformation of a polypeptide evolves from that of a random coil to that of an α-helix to finally that of a bundle of α-helices.


Macrocyclic diketopiperazine receptors: effect of macrocyclization on the binding properties of two-armed receptors.
The synthesis of macrocyclic two-armed diketopiperazine receptors and their binding properties toward peptides is described. Macrocyclization with short linkers led to receptors with significantly modified binding properties compared to their flexible open chain parent receptors, whereas with long linkers the original binding selectivities were largely retained.


Multiple marginal tissue recession treated with a simplified lateral sliding flap technique.
Marginal tissue recession is a common esthetic problem that is usually accompanied by dentin sensitivity, and patients frequently report a fear of dental loss. Lateral sliding flaps have been used for localized recession, but they are rarely used for multiple recessions. The aim of this paper was to report a case of coverage of multiple marginal tissue recessions by means of a lateral sliding flap associated with a connective tissue graft. This was a modification of Nelson's technique, which was originally described as the combination of the double papilla technique, lateral sliding flap, and connective tissue graft. In the present case, double papilla was not performed, rendering the maneuver less complicated. After surgery on teeth #23 to #25, total root coverage, decreased dentin sensitivity, and increased keratinized tissue band and gingival thickness were achieved. In the present case, modified Nelson technique proved to be a more simple procedure for the treatment of multiple recessions in one session, resulting in adequate healing, predictable root coverage, and, more importantly, esthetic and functional success.


[Q-methodology, an innovative technique for nursing research].
Q-Methodology offers an alternative to traditional methodological approaches. It is similar to qualitative methods while at the same time guaranteeing a statistical data analysis. It can be particularly interesting for the development of nursing sciences.


HI-bone: a scoring system for identifying phenylisothiocyanate-derivatized peptides based on precursor mass and high intensity fragment ions.
Peptide sequence matching algorithms used for peptide identification by tandem mass spectrometry (MS/MS) enumerate theoretical peptides from the database, predict their fragment ions, and match them to the experimental MS/MS spectra. Here, we present an approach for scoring MS/MS identifications based on the high mass accuracy matching of precursor ions, the identification of a high intensity b1 fragment ion, and partial sequence tags from phenylthiocarbamoyl-derivatized peptides. This derivatization process boosts the b1 fragment ion signal, which turns it into a powerful feature for peptide identification. We demonstrate the effectiveness of our scoring system by implementing it on a computational tool called "HI-bone" and by identifying mass spectra of an Escherichia coli sample acquired on an Orbitrap Velos instrument using Higher-energy C-trap dissociation. Following this strategy, we identified 1614 peptide spectrum matches with a peptide false discovery rate (FDR) below 1%. These results were significantly higher than those from Mascot and SEQUEST using a similar FDR.


In vitro metabolism of 1,3-dioxane, 1,3-oxathiolane, and 1,3-dithiane derivatives of theophylline: a structure-metabolism correlation study.
Correlation between structure and metabolism was studied within a series of cyclic acetal and thioacetal theophylline derivatives. All the compounds showed marked regioselectivity in in vitro metabolism, the metabolites arising only from 7-cycloalkyl side chain transformation. The 1,3-dioxane derivative, besides N-dealkylation to theophylline, underwent enzymatic ring cleavage, through the oxidation of the acetal carbon and subsequent rearrangement. Thus the acetal group was converted enzymatically to an ester. A similar transformation, catalyzed by cytochrome P450-dependent monooxygenases, was previously found for the 1,3-dioxolane ring of doxophylline. The cyclic thioacetal derivatives (i.e. 1,3-oxathiolane and 1,3-dithiane) were not cleaved during oxidative metabolism. The metabolites arise only from the oxidation of the sulfur atom, the major nucleophilic center in the molecule. No N-dealkylation to theophylline was observed. Enzymatic sulfoxidation proceeded diastereoselectively in both the 1,3-oxathiolane and 1,3-dithiane rings, the trans isomers being the major ones with a ratio trans: cis 75:25 and 60:40 respectively. The sulfoxides were stable to hydrolysis and were not further metabolized. Neither disulfoxides nor sulfones were detected in the incubations.


[The place of tumor markers in breast and gynecologic neoplasms].
The main tumor markers used in breast and gynaecological neoplasias are reviewed with their individual characteristics: carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP), chorionic gonadotropin hormone (CGH), CA 125, CA 15.3 and Squamous Cell Carcinoma Antigen (SCC). Their indications are specified according to the following cancer locations: breast, trophoblast, ovary, endometrium and cervix. The major clinical applications of the tumor markers routinely used are emphasized.


Management of Jehovah's Witnesses in otolaryngology, head and neck surgery.
It is imperative that surgeons should have some knowledge and understanding of the beliefs of Jehovah's Witnesses to respect the patient's wishes and effectively minimize and manage blood loss. The objective of this review was to provide a management strategy for Jehovah's Witness patients undergoing otolaryngology, head and neck surgery, because there is paucity of information regarding this within our literature. A systematic review of medical literature was conducted. Articles were identified using MEDLINE (1966-2007). The search strategy used Medical Subject Heading terms Jehovah's Witnesses, Beliefs, Ethical and Legal issues, Blood transfusion alternatives, ENT, Head and Neck surgery in Jehovah' witnesses. There is a broad range of nonblood surgical management strategies available in other specialities, making major surgery possible within this population. This review suggests recommendations in elective surgery, trauma, and emergencies.


Effects of breakfast with different calorigenic amounts on blood glucose, insulin and glucagon levels.
This study was aimed to investigate the relationship between breakfast and serum glucose, insulin and glucagon concentrations in order to establish a model breakfast appropriate for Chinese. Twenty-four volunteers were randomly assigned to four study groups: high carbohydrate breakfast, high fat and protein breakfast, the typical breakfast and fasting. Each subject had serum and urine samples collected while fasting and at 1,2 and 3.5 hours following the meal. The concentration of serum glucose, insulin and glucagon was measured. The levels of serum glucose in group A, B and C differed significantly at 1 and 2 hour after meal compared to those at fasting (P<0.05). The serum glucose in group A increased insignificantly after meal. The serum insulin levels were in group A, B and C significant different compared with control group(P<0.05). Those peaked at 1 hour after meal, with group C rising the furthest. Compared with the fasting group, the serum glucagons rose and maintained the increase after breakfast in group A, B and C (P<0.05). The data suggested that various diets with different calorigenic amounts increased hormone concentration to various extents. We found that a breakfast rich in carbohydrates could maintain proper blood glucose level.


[The Impact of Migration Background on Health: Results of the Austrian Health Interview Survey (ATHIS 2014)].
Previous research has shown migrants to have a poorer health status than those without a migration background in many respects. So far, it is not completely clear whether the poorer health results of migrants are mainly the cause of their socioeconomic status (SES), which on average is lower than the SES of people without a migration background. The present study explores the question whether the fact of having a migration background has an impact on health, even though SES and health-related behavior are taken into account. Based on data from the current Austrian Health Interview Survey (ATHIS 2014) multiple linear regression models, adjusted for age and stratified by gender, were conducted. The dependent variables were physical quality of life, psychological quality ofZ life, self-perceived health, body-mass-index (BMI), headaches/musculoskeletal pain, and diabetes/cardiovascular diseases (n=15,748). We found differences in health between men and women with migration background and men and women without migration background. After adjusting for age, SES and health-related behavior, almost all of the revealed differences got smaller. The strongest link between migrant status and health status was detected for migrants from countries with a lower Inequality-adjusted Human Development Index (IHDI) in comparison to Austria. The results lead to the conclusion that although SES and health-related behavior do not fully explain health differences between people with migration background and those without, they can explain the differences to a large extent. However, for the health status of migrants who stem from countries with a lower standard of living and a weaker distributive justice in comparison to Austria, further factors might play a role. With respect to this group of migrants, differences in health compared to non-migrants are not solely attributable to SES and health-related behavior.