Nurses' perceived barriers to the delivery of person-centred care to complex patients: A qualitative study using theoretical domains framework.
To determine nurses' perceived barriers to the delivery of person-centred care to complex patients with multiple chronic conditions in acute care settings. Complex patients have multiple physical and mental health problems, and their life is also greatly affected by sociocultural and economic determinants of health. These patients require person-centred care, but nurses often find it challenging to provide effective care to these patients due to their complex health needs. A descriptive qualitative design was used. The COREQ guidelines were followed for reporting. Semi-structured interviews were conducted with a purposive sample of 19 nurses in two hospitals. Data were analysed using deductive thematic analysis guided by the Theoretical Domains Framework, which entails 14 domains about factors affecting behaviours. The key barriers were identified under environmental context and resources, social influences, emotions, knowledge and skills domains. Deep-rooted social issues delay patients' health-seeking and nurses' abilities to understand patients' needs and discern appropriate care. Interpersonal hostility influenced nurse-patient-families interactions, and doctor-nurses conflicts affected collaborative efforts towards optimal care. Nurses' perceived barriers to care were intertwined with the deep-rooted social and cultural beliefs about nurses' image, patients' expectations and families' preference for home remedies over specialised nursing care. These barriers to person-centred care demonstrate an intricate interplay of personal, social and organisational issues and power struggles. Multifaceted implementation strategies targeting environmental context and resources, social influences, emotions, knowledge and skills domains may be beneficial to enable nurses to provide better person-centred care to complex patients. Designing implementation facilitation teams, organising person-centred care grand rounds, and allocation of stress management resources to address hostility, social-cultural influences, and organisational barriers is essential. Nurses could focus on their self-awareness and collaborative skills to address emotional and interprofessional conflicts.


Preseason Prognostic Factors for Injuries and Match Loss in Collision Sports: A Systematic Review.
This study aimed to identify which preseason factors had strong evidence of risks for physical injury during the season of collision sports including rugby, American football, and Australian rules football using qualitative synthesis. Pubmed, EMBASE, MEDLINE, SPORTDiscus, Scopus, and the Cochrane Library were reviewed. Eligibility criteria for selecting studies were: studies involving the collision sports; prospective cohort studies; and studies with outcomes of relative risks, odds ratios, and correlations between players' preseason conditions and injury during the season. The risk of bias based on the Scottish Intercollegiate Guidelines Network quality checklists for cohort studies was assessed in 57 studies. The current study identified strong evidence that 1) anthropometric characteristics (body mass index and estimated mass moment of inertia of the body around a horizontal axis through the ankle), which are calculated with weight and height; 2) physical function, in particular for the trunk and lower limb (trunk-flexion hold and wall-sit hold); and 3) Oswestry Disability Index disability, which is a patient-reported outcome measure for disability due to low back pain, were positive prognostic factors for injury during the collision sports season, regardless of playing experience.


Quorum Sensing and Quorum Quenching in the Phycosphere of Phytoplankton: a Case of Chemical Interactions in Ecology.
The interactions between bacteria and phytoplankton regulate many important biogeochemical reactions in the marine environment, including those in the global carbon, nitrogen, and sulfur cycles. At the microscopic level, it is now well established that important consortia of bacteria colonize the phycosphere, the immediate environment of phytoplankton cells. In this microscale environment, abundant bacterial cells are organized in a structured biofilm, and exchange information through the diffusion of small molecules called semiochemicals. Among these processes, quorum sensing plays a particular role as, when a sufficient abundance of cells is reached, it allows bacteria to coordinate their gene expression and physiology at the population level. In contrast, quorum quenching mechanisms are employed by many different types of microorganisms that limit the coordination of antagonistic bacteria. This review synthesizes quorum sensing and quorum quenching mechanisms evidenced to date in the phycosphere, emphasizing the implications that these signaling systems have for the regulation of bacterial communities and their activities. The diversity of chemical compounds involved in these processes is examined. We further review the bacterial functions regulated in the phycosphere by quorum sensing, which include biofilm formation, nutrient acquisition, and emission of algaecides. We also discuss quorum quenching compounds as antagonists of quorum sensing, their function in the phycosphere, and their potential biotechnological applications. Overall, the current state of the art demonstrates that quorum sensing and quorum quenching regulate a balance between a symbiotic and a parasitic way of life between bacteria and their phytoplankton host.


Publication fate of abstracts presented at British association of clinical anatomists annual meetings.
Dissemination of research is an integral part of the scientific process. Failure to disseminate research limits the scope for critical appraisal and potentially wastes valuable resources. The gold standard for dissemination of research is peer-reviewed publication following presentation at a national meeting. The primary objective of this study was quantitative assessment of the abstracts presented at British Association of Clinical Anatomists (BACA) summer and winter meetings with regards to the rates of subsequent publication and comparison to other medical specialties. Published abstracts from the summer and winter meetings of BACA between the years of 2000 and 2014 were analyzed. MEDLINE was searched to identify peer-reviewed publications arising from each presented abstract. In total, 1,807 abstracts were presented between the years of 2000 and 2014. The mean number of abstracts presented each year was 60.2, (range 26-157). In total, 20.4% of abstracts were subsequently published in MEDLINE-indexed journals with a median publication time of 19 months. The mean number of cadaveric prosections was 45.2 ± 78.8, (range 1-960). Analysis of abstracts focusing on radiographic imaging found the mean number of scans was 224.4 ± 807.1, (range 1-6,439). Biannual meetings of BACA are a forum for the presentation of high-quality anatomical research. BACA meeting abstracts have generally reduced publication rates compared to some surgical specialty meetings; however, there is no analysis available for an equivalent anatomical meeting. Further work should try to identify reasons that may hinder or limit subsequent publication of the anatomy abstracts presented at BACA. Clin. Anat. 30:133-139, 2017. © 2016 Wiley Periodicals, Inc.


[An immunohistochemical study of HLA-DR expression in salivary glands from patients with Sjogren's syndrome].
Specimens of salivary gland tissue from 21 cases of SS were analyzed by ABC immunohistochemistry technicue with a monoclonal antibody to HLA-DR. The results showed that positive immunostaining for HLA-DR were found in duct cells, acinar cells and a part of infiltrating cells respectively. The proportions of duct and acinar cells expressing HLA-DR were not increased between SS and controls. However, there are differences in their staining intensity. The HLA-DR expression on the epithelial cells in SS was most intense than in controls. Our data suggest that the HLA-DR expression of SS may be regarded as an important factor in local immune rections.


Mapping the landscape and structure of global research on binge eating disorder: Visualization and bibliometric analysis.
Binge-eating disorder (BED) is a clinical syndrome and is considered the most common type of eating disorder. However, our understanding of the global performance and progress of BED research is limited. To describe and perform a bibliometric analysis of the state of BED research. The term 'Binge eating' was searched in the title throughout the previous year's up to December 31, 2020. We searched the Scopus and Reference Citation Analysis for publications on Binge eating. The VOSviewer software version 1.6.17 was used to produce the network visualization map of the most frequent author, collaborative relationships between countries/regions, and to determine the hotspots related to binge eating research. In addition, conventional bibliometric indicators were generated. The search strategy found 2713 total articles and an average of 62 articles per year. Among them, 'Article' represented 82.49% of the publications (n = 2238 articles) and was the most frequent type, followed by reviews (n = 243; 8.96%). The number of publications increased steadily during the last decade of the study period. One hundred and thirty-two countries contributed to binge eating research, with 1495 (55.11%) articles published in the United States, followed by Italy with 256 (9.44%), the United Kingdom with 183 (6.75%), and Germany with 182 (6.71%). Currently, the main hot topics related to BED are 'type of treatment and management and treatment provided to BED"; "processes and pathways to binge eating"; and 'diagnosis, signs and symptoms, comorbidities and prevalence and associated factors with BED'. The number of publications has increased noticeably during the previous decade. There are indeed relatively few publications on BED from low-and middle-income nations, so much is to be learned from the experience of all countries. Studies on this topic are critical in all countries to discover risk factors and effective intervention measures. Although our findings are preliminary, they imply that the future prospects for interventions aimed at BED management are bright, focusing on complex models of care and long-term maintenance of therapeutic gains.


Next-generation sequencing identifies a novel heterozygous I229T mutation on LMNA associated with familial cardiac conduction disease.
LMNA gene encodes Lamin A and C (Lamin A/C), which are intermediate filament protein implicating in DNA replication and transcription. Mutations in LMNA are validated to cause cardiac conduction disease (CCD) and cardiomyopathy.In a Chinese family, we identified 5 members harboring the identical heterozygous LMNA (c.686T>C, I229T) disease-causing mutation, which was not found in the 535 healthy controls. In silico analysis, we revealed structural alteration in Lamin A/C I229T mutant. Furthermore, molecular docking identified human polycomb repressive complex 2 and Lamin A/C interact with higher affinity in the presence of I229T, thus may downregulate Nav1.5 channel expression.Our findings expanded the spectrum of mutations associated with CCD and were valuable in the genetic diagnosis and clinical screening for CCD. Molecular docking analysis provided useful information of increased binding affinity between mutant Lamin A/C and polycomb repressive complex 2. However, the concrete mechanism of LMNA mutation (I229T) remains undetermined in our study, future genetics and molecular studies are still needed.


Moving beyond methods: the need for a diverse programme in climate change research.
Understanding effects of climate change on ecosystems will require a diverse range of approaches. We proposed using downscaled climate models to generate realistic weather scenarios as experimental treatments. Kreyling et al. propose a gradient approach to determine the shape of response functions. These approaches are different, but highly complementary.


Ruminal metabolism of flaxseed ( Linum usitatissimum) lignans to the mammalian lignan enterolactone and its concentration in ruminal fluid, plasma, urine and milk of dairy cows.
Secoisolariciresinol diglucoside is the main flax (Linum usitatissimum) lignan that is converted to the mammalian lignans enterodiol (ED) and enterolactone (EL) by gastrointestinal microbiota. The objectives of the present study were to investigate the role of ruminal microbiota and the effects of flax oil on in vivo metabolism of flax lignans and concentration of EL in biological fluids. Four rumen-cannulated dairy cows were used in a 4 x 4 Latin square design. There were four periods of 21 d each and four treatments utilising flax hulls (1800 g/d) and oil (400 g/d) supplements. The treatments were: (1) oil and hulls administered in the rumen and abomasal infusion of water; (2) oil and hulls administered in the abomasum; (3) oil infused in the abomasum and hulls placed in the rumen; (4) oil placed in the rumen and hulls administered in the abomasum. Samples were collected during the last week of each period and subjected to chemical analysis. The site of supplementation of oil and hulls had no effect on ruminal EL concentration. Supplementing flax oil in the rumen and the abomasum led to similar EL concentrations in urine, plasma and milk. Concentrations of EL were higher in the urine, plasma and milk of cows supplemented with hulls in the rumen than in those placed with hulls in the abomasum. The present study demonstrated that ruminal microbiota play an important role in the metabolism of flax lignans.


Cardiorespiratory capacity of Thai workers in different age and job categories.
The objective of this study was to assess the cardiorespiratory capacity of Thai male and female blue-collar workers in different age and occupational categories. The maximal oxygen uptake (VO2max) of 70 men and 56 women was assessed using a submaximal bicycle-ergometer test supplemented with ventilatory gas analyses. The age of the subjects varied from 16 to 55 years. They worked in construction, manual materials handling and metal jobs. For the male subjects the VO2 max ranged from 1.43 to 3.50 l/min and from 21.3 to 66.3 ml/min/kg. The corresponding values for the female subjects were 0.97-2.97 l/min and 16.2-42.4 ml/min/kg. According to the European fitness classifications the mean age related VO2max of the male and female subjects can be considered moderate or poor. When compared to the European data heart rate of the subjects was 25-30% higher at submaximal levels of oxygen uptake, confirming earlier results. The low cardiorespiratory capacity of many Thai workers may be a limiting or even risk factor in physically demanding jobs.


The role of voice input for human-machine communication.
Optimism is growing that the near future will witness rapid growth in human-computer interaction using voice. System prototypes have recently been built that demonstrate speaker-independent real-time speech recognition, and understanding of naturally spoken utterances with vocabularies of 1000 to 2000 words, and larger. Already, computer manufacturers are building speech recognition subsystems into their new product lines. However, before this technology can be broadly useful, a substantial knowledge base is needed about human spoken language and performance during computer-based spoken interaction. This paper reviews application areas in which spoken interaction can play a significant role, assesses potential benefits of spoken interaction with machines, and compares voice with other modalities of human-computer interaction. It also discusses information that will be needed to build a firm empirical foundation for the design of future spoken and multimodal interfaces. Finally, it argues for a more systematic and scientific approach to investigating spoken input and performance with future language technology.


Incorporation of unnatural amino acids for synthetic biology.
The challenge of synthetic biology lies in the construction of artificial cellular systems. This requires the development of modular "parts" that can be integrated into living systems to elicit an artificial, yet programmed, response or function. The development of methods to engineer proteins bearing unnatural amino acids (UAAs) provides essential components that may address this challenge. Here we review the emerging strategies for incorporating UAAs into proteins with the endgame of engineering artificial cells and organisms.


Effect of Tooth-Whitening Procedures on Stained Composite Resins.
In this laboratory study, a composite resin was stained to a visibly discernible level using both coffee and red wine over 14 days (change was considered clinically noticeable and significant when ΔEab*≥2.7). Color change was measured at one, three, seven, and 14 days of staining. Although the nature of color change was different for the two staining solutions, the overall degree of staining (ΔEab*) rendered by either coffee or wine at each time interval was not significantly different ( p≥0.05). Four whitening protocols were applied to stained composites. Treatment included applications of distilled water (control), Crest Pro-Health [HD] toothpaste, Crest Whitestrips, Opalescence PF bleach (15%), and application of a fine pumice polishing (Preppies). HD toothpaste and Whitestrips were applied daily for 21 days, Opalescence was applied daily for 10 days, and polishing was applied once. Each of the whitening products, applied in a manner simulating at-home or in-office treatment, was effective in producing color improvements (lightening) over controls ( p<0.05), but none of the four treatments produced lightening that was significantly different from the other treatments ( p≥0.05). A comparison of final composite color with that measured at baseline showed that Opalescence returned composite color to an acceptable level following exposure to both staining solutions (ΔEab*<2.7), Whitestrips returned color close to baseline for wine-stained composites, and HD paste and polishing permitted residual stain to remain (ΔEab*≥2.7).


Evaluating Treatment Patterns, Relapses, Healthcare Resource Utilization, and Costs Associated with Disease-Modifying Treatments for Multiple Sclerosis in DMT-Naïve Patients.
Early diagnosis and treatment of multiple sclerosis (MS) with disease-modifying therapy (DMT) can reduce relapse number and severity, which has cost implications. We describe treatment patterns, healthcare utilization, and cost among MS patients newly initiating DMTs (index). DMT-naïve adults with 12 months' continuous enrollment pre- and post-index and ≥2 MS claims (2009‒2018) were identified from the Optum Clinformatics Data Mart database. Treatment adherence and persistence were measured as time on index DMT. Relapses were identified using a validated claims-based algorithm. All-cause and MS-related healthcare expenditures and utilization were captured pre- and post-index. Outcomes were stratified by route of administration. Multivariate analyses assessed differences in outcomes and costs. The analysis included 5906 MS patients (mean age, 46.6 years). The majority initiated injectable (63.5%) followed by oral (28.8%) and infusion (7.7%) DMTs. Post-index, 45.3% of patients were nonadherent and 39.4% were nonpersistent. Relapse rates decreased from pre- to post-index (oral: 24.3%‒16.1%; injectable: 25.0%‒17.1%; infusion: 29.3%‒15.5%). Post-index mean (SD) all-cause total costs were lowest with oral ($70,970 [$36,681]) vs injectable ($82,521 [$58,569]) and infusion ($80,871 [$49,627]) DMTs. MS-related total costs were lowest with oral ($65,149 [$65,133]) vs injectable ($76,197 [$60,204]) and infusion ($72,703 [$47,287]) DMTs. Multivariate analysis showed no differences between oral and injectable DMTs in adherence, persistence, or relapse rate; however, oral DMTs had significantly lower all-cause and MS-related costs. With similar outcomes across DMT administration routes, initiating the least costly DMT may be warranted for many patients. In newly treated MS patients, the need exists to improve adherence and persistence.


Pulmonary Arterial Hypertension-A Deadly Complication of Systemic Sclerosis.
Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Moreover, when PAH occurs in patients diagnosed with systemic sclerosis, worse outcomes are observed. The purpose of this review is to discuss the etiologies of PAH found in the systemic sclerosis patient, limitations of current medical therapies, and, finally, potential therapies for patients with this combination.


Linguistic diversity in Australia.
"This paper explores the changing patterns of language diversity in Australia, Sydney and Melbourne between 1991 and 1996. It shows that there has been a great increasing linguistic diversity, accompanied by an overall decline in the use of ¿older' community languages in favour of ¿newer' languages from Asia and the Middle East."


Long-term stability study of Prussian blue - a quality assessment of water content and thallium binding.
The purpose of this study is to assess the long-term stability of Prussian blue (PB) drug product (DP) and active pharmaceutical ingredient (API) under laboratory storage conditions by monitoring the loss in water content and the corresponding change of the in vitro thallium binding capacity that represents product performance. The bound water content and the in vitro thallium binding capacity of PB DPs and APIs were measured in 2003 and 2013, respectively. Water content, a critical quality attribute that directly correlates to the thallium (Tl) binding capacity was measured by thermal gravimetric analysis (TGA). The thallium binding study was conducted by testing PB in buffered solutions over the human gastrointestinal pH range with thallium concentrations ranging from 600 to 1,500 ppm. Samples were incubated at physiological temperature of 37°C in a shaking water bath to mimic gastric flux and intestinal transport. The binding equilibrium was reached at 24h. Following incubation, each sample was filtered and the free thallium was analyzed using a validated inductively coupled plasma spectroscopic method (ICP). The Langmuir isotherm was plotted to calculate maximum binding capacity (MBC). Compared with 2003, the water content of DP-1 decreased by about 14.1% (from 15.6 to 13.4 mol), and the MBC of DP-1 decreased by about 12.5% (from 714 to 625 mg/g) at pH 7.5. When low concentration of thallium (600 ppm) was used at pH 7.5, the Tl binding remained comparable for both API-1 (286 vs 276 mg/g) and DP-1 (286 vs 268 mg/g). Similarly, the Tl binding remained unchanged for both API-1 (237 vs 255 mg/g) and DP-1 (234 vs 236 mg/g) at pH 5.0. However, at pH 1.0 the binding was reduced 32.3% and 25.9% for API-1 and DP-1, respectively. Since the majority of binding takes place in the upper GI tract where pH around 5 can be expected, and therefore, the Tl binding capacity of PB should be comparable for new and aged samples. The findings that Tl binding changes with the water loss of PB and pH conditions are consistent with our previously published data. The study also represents the first quantitative assessment of the long-term stability of PB. Over last 10 years, PB DPs and APIs have lost about 20% water under ambient laboratory storage conditions which are consistent with a controlled warehouse environment. While the maximum binding capacity of PB to thallium was decreased after about 10 years of long-term storage, it is still very effective, suggesting that the shelf life of PB should be much longer than the manufacturer ascribed expiration date of 2008 under proper storage conditions.


High-throughput screening of low molecular weight NS3-NS4A protease inhibitors using a fluorescence resonance energy transfer substrate.
Hepatitis C virus (HCV) NS3-NS4A protease is an attractive target for anti-HCV agents because of its important role in replication. An optimized fluorescence resonance energy transfer (FRET) substrate for NS3-NS4A protease, based on the sequence of the NS5A-5B cleavage site, was designed and synthesized. High-throughput screening of in-house compound libraries was performed using a FRET substrate FS10 (MOCAcDKIVPC-SMSYK-Dnp) and MBP-NS3-NS4A fusion protein. Several hit compounds were found, including YZ-9577 (2-oxido-1,2,5-oxadiazole-3,4-diyl) bis (phenylmethanone) with potent inhibitory activity (IC50=1.6 microM) and good selectivity against other human serine proteases.


Respiratory Syncytial Virus Bronchiolitis in Infancy: The Acute Hospitalization Cost.
Introduction: Respiratory syncytial virus (RSV) bronchiolitis is among the leading causes of hospitalization in infants. Prophylaxis with palivizumab may reduce RSV infection, but its prescription is restricted to high-risk groups. The aim of the study is to retrospectively determine acute hospitalization costs of bronchiolitis. Materials and methods: Infants aged 1 month-1 year, admitted to Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of bronchiolitis from January 1 till December 31, 2017, were included in the study. Results: A total of 531 patients were enrolled in the study, and the mean age was 78.75 days. The main etiologic agent causing bronchiolitis was RSV, accounting for 58.38% of infections. The total cost of bronchiolitis hospitalization was 2,958,786 euros. The mean cost per patient was significantly higher in the case of RSV (5,753.43 ± 2,041.62 euros) compared to other etiology (5,395.15 ± 2,040.87 euros) (p = 0.04). Discussion: The study confirms the high hospitalization cost associated with bronchiolitis. In detail, in the case of RSV etiology, the cost was higher compared to other etiology, which is likely due to the longer hospitalization and the more frequent admission to the intensive cure department. Conclusion: This study highlights that bronchiolitis is an important cost item even in a tertiary hospital and that cost-effective interventions targeting RSV are increasingly urgent.


Evaluation of platelet distribution width as a diagnostic and prognostic biomarker in bladder neoplasm.
Aim: To evaluate the role of preoperative platelet distribution width (PDW) as a potential biomarker for distinguishing malignancy and tumor advantage of bladder neoplasm. Methods: The study included 210 subjects with bladder cancer, 76 subjects with urothelial papilloma and 132 healthy control subjects. Preoperative PDW along with other blood indices was evaluated. Results: PDW was higher in urothelial papilloma patients than that in bladder cancer patients (p < 0.001). Bladder cancer patients with advanced-stage disease exhibited lower PDW levels compared with patients with early stage disease. Conclusion: Reduced preoperative PDW level is an indicator of malignancy and advanced bladder cancer stages, suggesting it as a potential biomarker in bladder cancer diagnosis and prognosis.


An impairment index of brain functions in children.
An impairment index of brain functions in children, based on the 1979 Rules System by Selz and Reitan, was developed to summarize the performance on the Halstead-Reitan Neuropsychological Test Battery for older children comparing groups of 25 normal, learning-disabled, and brain-damaged children aged 9 through 14 yr. Analysis of variance indicated a significant difference between all pairs of groups. A cut-off Impairment Index between .17 and .18 correctly differentiated 78% of the brain-damaged and control subjects. The findings suggested that the Impairment Index for Children may be a valid and objective indicator of brain functions in older children, although cross-validation is necessary.


Associations of Left Atrial Function and Structure With Supraventricular Ectopy: The Multi-Ethnic Study of Atherosclerosis.
Background High levels of supraventricular ectopy are associated with greater risk of atrial fibrillation, stroke, and death. Little information is available about differences by race/ethnicity in the extent of supraventricular ectopy, or about whether high levels of supraventricular ectopy are associated with impaired left atrial (LA) function and LA enlargement. Methods and Results In the MESA (Multi-Ethnic Study of Atherosclerosis), 1148 participants (47% men; mean age, 67 years) had cardiovascular magnetic resonance imaging in 2010 to 2012, followed by 14-day ambulatory electrocardiographic monitoring in 2016 to 2018. We analyzed participant characteristics and cardiovascular magnetic resonance measures of LA function and structure in relation to average count of premature atrial contractions (PACs) per hour and average number of runs per day of supraventricular tachycardia. In adjusted regression analyses, older age, male sex, White race, elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide), and a history of clinically detected atrial fibrillation were associated with more PACs/hour. Chinese and Hispanic participants had on average fewer PACs/hour than White participants (Chinese participants, 31% less [95% CI, 8%-49%]; Hispanic participants, 38% less [95% CI, 19%-52%]). Greater LA total emptying fraction was associated with fewer PACs/hour (per SD, 16% fewer PACs/hour [95% CI, 7%-25% fewer PACs/hour]). Larger LA minimum volume was associated with more PACs/hour (per SD, 7% more PACs/hour [95% CI, 2%-13% more PACs/hour]). Associations of LA volumes with runs of supraventricular tachycardia/day were similar in direction but were weaker. Conclusions Impaired LA function and LA enlargement were associated with more PACs/hour on extended ambulatory electrocardiographic monitoring. Measurement of supraventricular ectopy may provide information about the extent of atrial myopathy.


Radical dose escalation by high-dose-rate brachytherapy for localized prostate cancer-Significance of prostate-specific antigen nadir level within 18 months as correlation for long-term biochemical control.
High-dose-rate brachytherapy (HDR-BT) for dose escalation in localized prostate cancer has been established as one standard treatment option. However, long-term results at followup (FU) ≥5 years are usually needed to ensure robustness of reported outcomes. Potential benefit of salvage therapy is, nevertheless, higher when relapse is diagnosed early. This study aimed to solve this dilemma by evaluating the prostate-specific antigen (PSA) nadir for early prediction of long-term biochemical control. Combined pelvis-external beam radiation/HDR-BT boost to EQD2 >100 Gy (α/β = 3) was performed in 459 consecutively treated patients. These patients with an FU ≥ 24 months were analyzed and stratified in PSA nadir (nPSA)-groups by PSA nadir within 18 months after radiotherapy (nPSA18). Kaplan-Meier/log-rank tests and Cox-regression models were used to compare the study endpoints. The mean FU was 77 months. A PSA nadir within 18 months (nPSA18) <0.5 ng/mL was achieved in 222 patients with median time to reach nPSA18 of 7 months. The 5-year American Society of Therapeutic Radiology and Oncology (ASTRO) biochemical control (prostate-specific antigen disease-free survival) for the nPSA18 group <0.5 ng/mL was 89% and for the group ≥ 0.5 ng/mL, it was 78.6% (p = 0.011). nPSA18 was an independent predictor of cancer-specific survival, distant metastasis-free survival, and biochemical control (ASTRO) (p = 0.026, p = 0.020, and p = 0.01, respectively). The present results suggest that the PSA nadir level within 18 months after radiotherapy may serve as an early parameter for long-term biochemical control according to ASTRO definitions following radical dose escalation by HDR-BT for prostate cancer. Excellent outcomes were associated with nPSA18 < 0.5 ng/mL.


Novel methods for generating fractional epidermal micrografts.
Epidermal suction blister grafts are an effective treatment for chronic wounds or vitiligo, but this treatment is time consuming and limited to small areas. To compare two novel strategies to create fractional epidermal grafts. Epidermal blisters were raised from fresh human skin ex vivo at 38-40 °C, with suction of 380-510 mmHg. In Strategy 1, a 1-cm blister was micromeshed into approximately 500 pieces, transferred to elastic adhesive dressing, then pneumatically expanded to approximately nine times the original blister area. In Strategy 2, a 25-cm(2) array of 100 small blisters was raised, simultaneously harvested and captured directly onto an adhesive dressing. Measurements were taken for the pneumatic expansion limit, the release of microblisters upon hydration of the dressing adhesive, light microscopy, epidermal cell viability and positive L-3,4 dihydroxyphenylalanine melanocyte presence in blisters. Both strategies yielded viable fractional epidermal microblister arrays, carried on a dressing for transfer to graft recipient sites. The microblisters were gradually released upon hydration of the dressing adhesive. Strategy 2 has major advantages as only small blisters are made at the donor site, skilful dissection and physical expansion are not required and the strategy can be scaled to create large-area grafts. Strategy 2 is the more practical method for fractional epidermal micrografting to treat larger lesions with less donor-site trauma and has recently been commercialized.


Variation of expression levels of seven housekeeping genes at different life-history stages in Porphyra yezoensis.
In order to identify the optimal internal control for relative real-time PCR when studying target gene expression in the red alga Porphyra yezoensis, we quantified the expression of seven housekeeping genes (18S ribosomal RNA, 30S ribosomal protein S8, Polyubiquitin-2, Glyceraldehyde-3-phosphate dehydrogenase, Elongation factor 1-alpha, Beta-tubulin and Actin 3) at different life-history stages. Absolute quantification was done by normalization to total RNA quantity and by normalization to genomic DNA quantity. We used these two normalization approaches, comparing the differences of expression levels of all candidate housekeeping genes between any two generations and across three life-history stages (filamentous sporophytes, leafy gametophytes and conchospores). We found GAPDH had the best stability in all cases and we recommend that GAPDH be considered as a potential internal control for gene expression studies at different life-history stages in P. yezoensis.


Chloramphenicol Mitigates Oxidative Stress by Inhibiting Translation of Mitochondrial Complex I in Dopaminergic Neurons of Toxin-Induced Parkinson's Disease Model.
Paraquat (PQ), an herbicide considered an environmental contributor to the development of Parkinson's disease (PD), induces dopaminergic neuronal loss through reactive oxygen species (ROS) production and oxidative stress by mitochondrial complex I. Most patients with PQ-induced PD are affected by chronic exposure and require a preventive strategy for modulation of disease progression. To identify drugs that are effective in preventing PD, we screened more than 1000 drugs that are currently used in clinics and in studies employing PQ-treated cells. Of these, chloramphenicol (CP) showed the most powerful inhibitory effect. Pretreatment with CP increased the viability of PQ-treated SN4741 dopaminergic neuronal cells and rat primary cultured dopaminergic neurons compared with control cells treated with PQ only. CP pretreatment also reduced PQ-induced ROS production, implying that mitochondrial complex I is a target of CP. This effect of CP reflected downregulation of the mitochondrial complex I subunit ND1 and diminished PQ recycling, a major mechanism of ROS production, and resulted in the prevention of cell loss. Notably, these effects of CP were not observed in rotenone-pretreated SN4741 cells and Rho-negative cells, in which mitochondrial function is defective. Consistent with these results, CP pretreatment of MPTP-treated PD model mice also ameliorated dopaminergic neuronal cell loss. Our findings indicate that the inhibition of mitochondrial complex I with CP protects dopaminergic neurons and may provide a strategy for preventing neurotoxin-induced PD.


[PET/CT in radiotherapy].
Combining positron emission tomography (PET) and X-ray computed tomography (CT) with simultaneous acquisition may improve diagnostic accuracy in oncology. Moreover this combination holds considerable promise in radiotherapy. Metabolic information may be used in decision making in radiotherapy and in planning target volumes. Furthermore early evaluation of treatment efficacy becomes possible. New tracers for the assessment of tumour hypoxia or apoptosis in clinical routine are currently being developed. These tracers may yield high relevance in radiotherapy. Hybrid scanners facilitate patient handling and shorten the duration of acquisition. Furthermore fusion accuracy is optimal. Prospective studies have to be conducted to show that the new technology improves patient care in terms of efficiency and quality.


Tissue distribution and deposition of clofazimine in rat following subchronic treatment with or without rifampicin.
Tissue distribution and deposition characteristics of clofazimine (CAS 2030-63-9), an antileprotic drug in rats have been investigated following controlled sub-chronic administration (p.o.) for a period of 1-2 months. The drug was administered alone at a dose of 20 mg/kg body weight and in combination with rifampicin (CAS 13292-46-1) (20 mg/kg p.o.). Various tissues (liver, lung, spleen, small intestine, brain, heart, kidney, skin, stomach and subcutaneous fat) were analyzed for clofazimine in all the treated groups. High levels (range 0.9-3.6 mg/g of wet tissue) were observed in tissues having reticuloendothelial components. In other tissues the levels were relatively lower (range 3-114 micrograms/g of wet tissue). Histopathological studies revealed that clofazimine is deposited in many tissues in the form of reddish-orange crystals. Concomitant treatment with rifampicin did not significantly alter tissue distribution or deposition profile of clofazimine nor did it influence the histopathology.


Biofilms in an urban water distribution system: measurement of biofilm biomass, pathogens and pathogen persistence within the Greater Stockholm Area, Sweden.
Distribution pipe biofilms can provide sites for the concentration of a wide range of microbial pathogens, thereby acting as a potential source of continual microbial exposure and furthermore can affect the aesthetic quality of water. In a joint project between Stockholm Water, the MISTRA "Sustainable Urban Water" program, the Swedish Institute for Infectious Disease Control and the Royal Technical University, Stockholm, the aim of the current study was to investigate biofilms formed in an urban water distribution system, and quantify the impact of such biofilms on potential pathogen accumulation and persistence within the Greater Stockholm Area, Sweden. When used for primary disinfection, ultra-violet (UV) treatment had no measurable influence on biofilm formation within the distribution system when compared to conventional chlorination. Biofilms produced within a model pilot-plant were found to be representative to those that had formed within the larger municipal water distribution system, demonstrating the applicability of the novel pilot-plant for future studies. Polystyrene microspheres (1.0 microm) and Salmonella bacteriophages demonstrated their ability to accumulate and persist within the model pilot-plant system, where the means of primary disinfection (UV-treatment, chlorination) had no influence on such phenomena. With the exception of aeromonads, potential pathogens and faecal indicators could not be detected within biofilms from the Stockholm water distribution system. Results from this investigation may provide information for water treatment and distribution management strategies, and fill key data gaps that presently hinder the refinement of microbial risk models.


Validation and standardization of the Childhood Trauma Screener (CTS) in the general population.
A valid, quick and widely applicable retrospective screening tool for child maltreatment is of great importance to better adapt interventions and treatments. The Childhood Trauma Screener (CTS), derived from the Childhood Trauma Questionnaire (CTQ), is one such instrument that aims to increase the likelihood of detecting mental and physical disorders that have manifested in adulthood as a result of traumatic experiences and maltreatment in childhood and adolescence. The present study aimed to investigate the psychometric properties of the CTS and generate normative data. Data from two representative surveys were combined. Both surveys used identical methods. The CTS, consisting of five items, other self-report instruments, and demographic characteristics were used. Construct validity was examined using confirmatory factor analysis (CFA). A subsample was used to examine convergent validity with the Adverse Childhood Experiences Questionnaire (ACE). Normative data are reported for age groups and gender. A total of 5039 study participants provided valid responses to the 5-items questionnaire (54.3% female, response rate = 78.9%). CFA showed good fit indices for a 2-factor solution. Convergent validity was generally supported by moderate intercorrelations with the ACE. The results confirm the solid psychometric properties of the CTS as an easy-to-use, ultra-short retrospective measure of child maltreatment. The data can be used to compare sample or individual results with reference data provided.


Novel approach to the zaragozic acids. Enantioselective total synthesis of 6,7-dideoxysqualestatin H5.
The total synthesis of 6,7-dideoxysqualestatin H5 (3) has been completed by a concise approach that features the stereoselective intramolecular vinylogous aldol reaction of the furoic ester 25a to give 30 or its trimethylsilyl ether derivative 34, which possess the requisite absolute stereochemistry at C(3)-C(5) of 3. Compound 34 was reduced to the saturated bislactone 39, and the C(1) side chain subunit 47 was introduced leading to a mixture of the hemiacetals 48 and the corresponding ketone 49. When this mixture was stirred with methanolic acid, transketalization occurred to give a mixture of 50 and the spirocyclic methyl acetals 51a,b. Oxidation of the primary alcohol group in 50 followed by saponification of the two remaining ester groups gave 3. The longest linear sequence in the synthesis commences with commercially available erythronolactone (26) and requires 17 chemical steps with only 10 isolated intermediates.


Population declines in the snowshoe hare and the role of stress.
Every 10 years snowshoe hare populations across the boreal forest of North America go through a population cycle, culminating in a decline lasting 4 or more years. We tested the hypothesis that snowshoe hares during the decline are in poor condition and less able to respond to challenges in their environment by examining the stress response of male hares. Three groups from February and May, 1991 (the second year of the hare decline in the Yukon), were compared: baseline hares were collected to obtain resting hormone levels; control hares were wild animals caught at randomly placed sites; and fed hares were wild animals caught on supplementary fed areas. The latter two groups were sequentially bled to examine their response to dexamethasone (DEX) followed by adrenocorticotropic hormone (ACTH). Trapping and handling were stressful to the experimental hares as the initial blood levels of total and free cortisol levels were higher (especially in controls), testosterone levels were lower, and glucose levels were higher in experimental hares than in baseline hares. Control and fed hares showed similar total and free cortisol responses, falling to low levels after the DEX injection and increasing rapidly in response to the ACTH injection. However, control hares were in worse condition than fed hares as indicated by the higher free cortisol levels and lower maximum corticosteroid-binding capacity (MCBC) in control hares. In addition, though testosterone levels fell in both groups in response to DEX, only the fed hares showed a large, transitory increase 30 min after the ACTH injection. An unexpected finding was a dramatic increase in MCBC levels 30 min after the ACTH injection in both experimental groups, but it was more pronounced in the fed group. We conclude that the pituitary-adrenocortical feedback system in hares from declining populations is operating normally and that they should be able to cope with acute, short-term stressors, but that they are in poor condition and are exposed to higher levels of free cortisol than fed hares in good condition.


Mathematical model of thermal shields for long-term stability optical resonators.
Modern experiments aiming at tests of fundamental physics, like measuring gravitational waves or testing Lorentz Invariance with unprecedented accuracy, require thermal environments that are highly stable over long times. To achieve such a stability, the experiment including typically an optical resonator is nested in a thermal enclosure, which passively attenuates external temperature fluctuations to acceptable levels. These thermal shields are usually designed using tedious numerical simulations or with simple analytical models. In this paper, we propose an accurate analytical method to estimate the performance of passive thermal shields in the frequency domain, which allows for fast evaluation and optimization. The model analysis has also unveiled interesting properties of the shields, such as dips in the transfer function for some frequencies under certain combinations of materials and geometries. We validate the results by comparing them to numerical simulations performed with commercial software based on finite element methods.


Mitochondrial antioxidant defence in radio-resistant Lepidopteran insect cells.
Cells isolated from Lepidopteran insects (butterfly and moths) display very high radioresistance as compared to mammals and other insect species. Since free radical induced mitochondrial damage under stress conditions is very crucial for cellular fate determination, antioxidant system is the major protective modality required to minimize stress-induced damage and to modulate cellular sensitivity. In this study, we predict the mitochondrial localization potential and co-existence of important antioxidant enzymes in insect cells and compare with other radiosensitive (mammals, Dipteran insects) and radioresistant (nematodes) species. Our study clearly demonstrates the inter-species variation in then localization potential of various antioxidant enzymes. A higher mitochondrial localization potential as a function of mitoprot score was evident for all important antioxidant enzymes in the lepidopteran insect Bombyx mori (Mn-SOD, 0.694; GPx, 0.862; TRPx, 0.997; TR, 0.9), besides an unusual mitochondrial localization prediction for catalase (0.453). We further found coexistence of glutathione and thioredoxin system in the mitochondria of lepidopteran insects as also reported in various plant species. On the basis of above observations, we hypothesize that a strong mitochondrial antioxidant enzyme system including the unusual coexistence of catalase, glutathione and thioredoxin system may help minimize the free radical mediated damage to mitochondria and can contribute to the intrinsic radioresistance of lepidopteran insects.


Exploring referral systems for injured patients in low-income countries: a case study from Cambodia.
Injury is a growing public health concern worldwide. Since severe injuries require urgent treatment, involving smooth, timely patient referral between facilities, strengthening of the referral system would reduce injury mortality. Smooth referral consists of identification of severe cases, organization of transportation, communication between facilities and prompt care at the receiving facility. This study examined these components of referral of injured patients in a representative sample of health centres (HCs) and referral hospitals (RHs) in Cambodia. We analysed data from a survey carried out in 80 HCs and 17 RHs by interview or mailed questionnaire from December 2006 to April 2007. Collected information on referral included the presence of referral guidelines for injured patients, distance of referral, commonly used transportation and its cost, communication with receiving facilities, and fast-tracking at receiving facilities. Formal referral systems were not functioning well in some areas (insufficient communication and underutilization of ambulances), and informal systems were frequently involved (patient transfer by taxi or referral by community volunteers, and treatment by traditional healers) but were not fully integrated into the referral network (traditional healers seldom referred patients to public facilities). The referral distance was long for most of the surveyed facilities and transportation costs were high when transferring from remote areas, even by ambulance. This study identified the weaknesses and strengths of the emergency referral system in Cambodia. Streamlining referral mechanisms will require organization of each component of the referral mechanism by strengthening the existing system and mobilizing local resources, which would allow Cambodia to develop an efficient system at reasonable cost, though it may differ from Western models. Guidelines including these components along with training and supervision, and expansion of the system to cover other disease conditions, would strengthen the health care system as a whole in this country.


SNHG1 functions as an oncogenic lncRNA and promotes osteosarcoma progression by up-regulating S100A6 via miR-493-5p.
The mechanism behind the aberrant expression of S100A6 in osteosarcoma is seldom reported so far. This study sought to explore the regulatory axis targeting S100A6 involved in osteosarcoma progression. Clinical samples collected from osteosarcoma patients were used to detect the expressions of SNHG1, miR-493-5p, and S100A6 by western bolt analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of S100A6 on proliferation and osteogenic differentiation were investigated by the CCK-8 assay, colony formation assay, Ethynyl deoxyuridine staining, matrix mineralization assay, and alkaline phosphatase assay. The potential of lncRNAs/miRNAs targeting S100A6 was identified by the bioinformatics approach, and the results were verified by the dual luciferase assay and RNA immunoprecipitation assay. Both and rescue experiments were performed to investigate the regulatory relationship between the identified lncRNAs and S100A6. The results showed that S100A6 is highly expressed in osteosarcoma. S100A6 overexpression not only increases the proliferation but also reduces the osteogenic differentiation of osteosarcoma cells, while S1006A silence exerts the opposite effects. Then, SNHG1 is identified to directly interact with miR-493-5p to attenuate miR-493-5p binding to the 3'-untranslated region of S100A6. Notably, S100A6 silence partially rescues the effect of SNHG1 overexpression on proliferation and osteogenic differentiation of osteosarcoma cells. Furthermore, the suppressive role of SNHG1 silence in the growth of osteosarcoma xenograft tumors is countered by S100A6 overexpression. Collectively, this study reveals that S100A6 plays an important role in osteosarcoma progression, and SNHG1 promotes S100A6 expression by competitively sponging miR-493-5p.


Peripheral neuropathy associated with anti-myelin basic protein antibodies in a woman vaccinated with rubella virus vaccine.
Active immunisation with rubella vaccine has not been commonly associated with neurological complications. We report the case of a 23-year-old woman who developed a mild, distal demyelinating neuropathy after immunisation with the live attenuated RA 27/3 rubella strain. Post-immunisation immunologic studies carried over 24 months showed the presence of antibodies to the RV proteins, particularly to the capsid antigen, and to the myelin basic protein (MBP). A similarity between a C antigen motif and a sequence of the MBP was found by computer analysis. The cross-reactivity was confirmed by immunising mice with a synthetic peptide derived from the MBP, which developed a strong humoral response to RV and MBP. This finding raises the possibility that a virus-induced immune response could lead to an autoaggressive reaction responsible for demyelination.


Influence of cooking methods on antioxidant activity of vegetables.
The influence of home cooking methods (boiling, microwaving, pressure-cooking, griddling, frying, and baking) on the antioxidant activity of vegetables has been evaluated in 20 vegetables, using different antioxidant activity assays (lipoperoxyl and hydroxyl radicals scavenging and TEAC). Artichoke was the only vegetable that kept its very high scavenging-lipoperoxyl radical capacity in all the cooking methods. The highest losses of LOO. scavenging capacity were observed in cauliflower after boiling and microwaving, pea after boiling, and zucchini after boiling and frying. Beetroot, green bean, and garlic kept their antioxidant activity after most cooking treatments. Swiss chard and pepper lost OH. scavenging capacity in all the processes. Celery increased its antioxidant capacity in all the cooking methods, except boiling when it lost 14%. Analysis of the ABTS radical scavenging capacity of the different vegetables showed that the highest losses occurred in garlic with all the methods, except microwaving. Among the vegetables that increased their TEAC values were green bean, celery, and carrot after all cooking methods (except green bean after boiling). These 3 types of vegetables showed a low ABTS radical scavenging capacity. According to the method of analysis chosen, griddling, microwave cooking, and baking alternately produce the lowest losses, while pressure-cooking and boiling lead to the greatest losses; frying occupies an intermediate position. In short, water is not the cook's best friend when it comes to preparing vegetables.


Cell wall invertase activity regulates the expression of the transfer cell-specific transcription factor ZmMRP-1.
Studies in cell wall bound invertase mutants indicate that the promoter of the transfer cell-specific transcription factor, ZmMRP - 1 , is modulated by the carbohydrate balance. Transfer cells are highly specialized plant cells located at the surfaces that need to support an intensive exchange of nutrients, such as the entrance of fruits, seeds and nodules or the young branching points along the stem. ZmMRP-1 is a one-domain MYB-related transcription factor specifically expressed at the transfer cell layer of the maize endosperm. Previous studies demonstrated that this factor regulates the expression of a large number of transfer cell-specific genes, and suggested that ZmMRP-1 is a key regulator of the differentiation of this tissue. The expression of this gene is largely dominated by positional cues, but within the ZmMRP-1 expressing cells the promoter appears to be modulated by sugars. Here we have investigated in vivo this modulation. Using maize and Arabidopsis mutants for cell wall invertase genes, we found that the absence of cell wall invertase activity is a major inductive signal of the ZmMRP-1 expression.


Customizing anaphylaxis guidelines for emergency medicine.
Most episodes of anaphylaxis are managed in emergency medical settings, where the cardinal signs and symptoms often differ from those observed in the allergy clinic. Data suggest that low recognition of anaphylaxis in the emergency setting may relate to inaccurate coding and lack of a standard, practical definition. Develop a simple, consistent definition of anaphylaxis for emergency medicine providers, supported by clinically relevant consensus statements. Definitions of anaphylaxis and criteria for diagnosis from current anaphylaxis guidelines were reviewed with regard to their utilization in emergency medical settings. The agreed-upon working definition is: Anaphylaxis is a serious reaction causing a combination of characteristic findings, and which is rapid in onset and may cause death. It is usually due to an allergic reaction but can be non-allergic. The definition is supported by Consensus Statements, each with referenced discussion. For a positive outcome, quick diagnosis and treatment of anaphylaxis are critical. However, even in the emergency setting, the patient may not present with life-threatening symptoms. Because mild initial symptoms can quickly progress to a severe, even fatal, reaction, the first-line treatment for any anaphylaxis episode--regardless of severity--is intramuscular injection of epinephrine into the anterolateral thigh; delaying its administration increases the potential for morbidity and mortality. When a reaction appears as "possible anaphylaxis," it is generally better to err on the side of caution and administer epinephrine. We believe that this working definition and the supporting Consensus Statements are a first step to better management of anaphylaxis in the emergency medical setting.


Chocolate eating in healthy men during experimentally induced sadness and joy.
The study compared influences of qualitatively different emotions on eating. Motivation to eat, affective responses to chocolate and chewing of chocolate were investigated in healthy normal weight males during experimentally induced emotions. Subjects abstained from eating 2 h (n = 24) or 8 h (n = 24) before testing. They received pieces of chocolate after viewing film clips presented to induce anger, fear, sadness and joy. Motivation to eat and most affective responses to eating chocolate were higher after 8 h than after 2 h of deprivation. Sadness and joy affected motivation to eat in opposite directions: joy increased and sadness decreased appetite (p < 0.001). In joy, a higher tendency to eat more chocolate was reported (p < 0.001), and chocolate tasted more pleasant (p < 0.001) and was experienced as more "stimulating" than in sadness (p < 0.01). No effects of deprivation could be found for chewing time and number of chews. Results indicate that the quality of emotions can affect motivation to eat and affective responses to eating chocolate. Our findings on decreased eating responses to sadness in healthy males and the contradictory increased eating responses to sadness reported by others supports two types of emotion-induced changes of eating: emotion-congruent modulation of eating and eating to regulate emotions.


Effects of upper airway anaesthesia on respiratory-related evoked potentials in humans.
Cortical potentials evoked by mid-inspiratory occlusion arise from numerous receptors, many of which are probably within the upper airway. Their precise nature is not known. The aim of the current study was to improve knowledge of this by studying the effects of topical upper airway anaesthesia on respiratory-related evoked potentials. Respiratory-related evoked potentials were described through the averaging of electroencephalogram (EEG) epochs following mid-inspiratory occlusions (C3-CZ; C4-CZ). A total of 21 healthy volunteers (13 male, aged 22-52 yrs) were studied during mouth breathing, before and after topical upper airway anaesthesia (lidocaine). Moreover, 15 subjects were studied during nose breathing with and without anaesthesia. Six subjects were studied whilst inhaling L-menthol. Typical potentials were present in all the subjects, their components featuring normal amplitudes and latencies. The route of breathing and upper airway anaesthesia did not modify the EEG responses to inspiratory occlusions, qualitatively or quantitatively, during mouth or nose breathing. L-menthol had no effect. Upper airway receptors sensitive to topical anaesthesia are unlikely to contribute significantly to mid-inspiratory occlusion-evoked potentials. On the contrary, deeper receptors, such as joint and muscle receptors, could contribute dominantly to these potentials.


Human alpha-fetoprotein contains potential heterodimerization motifs capable of interaction with nuclear receptors and transcription/growth factors.
Alpha-fetoprotein (AFP) serum levels in man have long been utilized as a tumor marker and as a birth defect screening agent in the clinical laboratory. Although the physiological role of AFP has remained obscure, the stereotypic carrier/transport function of a fetal counterpart to albumin has been attributed to this oncofetal protein. However, reports from a multitude of investigators in the last decade have provided a rationale to reconsider and extend the biological role of AFP to include cell growth modulation during development. Previously, a leucine zipper-like (heptad) motif, which mimicked that found in the steroid/thyroid receptor superfamily, was postulated for portions of the third domain of AFP. The present report proposes the presence of additional potential heterodimerization sites for the nuclear receptor superfamily members and other growth factors in the second and third domains of human AFP.


Role of physicochemical properties in the estimation of skin permeability: in vitro data assessment by Partial Least-Squares Regression.
Skin provides passage for the delivery of drugs. The in vitro and in vivo testing of chemicals for estimation of dermal absorption is very time consuming, costly and has many ethical difficulties related to human and animal testing. The solution to the problem is Quantitative structure-permeability relationships. This method relates dermal penetration properties of a range of chemical compounds to their physicochemical parameters. In the present study, an effort has been made to develop models for the accurate prediction of skin permeability using a large, diverse dataset through the combination of various regression methods coupled with the Genetic Algorithm (GA)/Interval Partial Least-Squares Algorithm (iPLS). The descriptors were calculated using e-DRAGON and ADME Pharma Algorithms-Abrahams descriptors. The original dataset was divided into a training set and a testing set using the Kennard-Stone Algorithm. The selection of descriptors was made by the GA and iPLS. The model applicability domain was determined. The results showed that a three-parameter model built through Partial Least-squares Regression was most accurate with r(2) of 0.936.


Transplant of bone marrow and muscle-derived connective tissue cultures in diffusion chambers for bioassay of bone morphogenetic protein.
To promote a high concentration gradient, syngeneic bone marrow and muscle connective tissue cell cultures and subcultures were exposed to bone morphogenetic protein and associated noncollagenous bone matrix proteins (BMP/NCP) in vitro, transferred to diffusion chambers, and then transplanted into the anterior abdominal wall of isogeneic rats. Both muscle- and marrow-derived cells differentiated into cartilage and chondroosteoid on the inside of diffusion chambers. New bone developed on the vascularized outside surfaces in juxtaposition to avascular tissue on the inside. Levels of glycosaminoglycans (GAGs) and DNA synthesis in tissues inside the chambers were sharply elevated. These data, correlated with histologic observations, demonstrate that the BMP/NCP recruits mesenchymal-type cells for a skeletal tissue pathway of development. Muscle-derived cells, as distinguished from marrow-derived cells, originate in a nonosseous environment but differentiate into osteoprogenitor (osteogenic stem) cells and display levels of DNA synthesis almost as high as marrow stroma-derived cells. The rise in DNA synthesis was maximal in the interval from two to three weeks after transplantation. Whether the bone marrow stroma mesenchymal cell target for BMP is only the osteogenic stem cell population or also includes colony-forming units fibroblasts (CFU-F) remains to be investigated by experiments on established cell lines.


Meningococcal disease in children: case studies and discussion.
This article is based on two case studies in which children with suspected meningococcal disease were brought to the author's emergency department. It examines the signs and symptoms of the disease, and discusses its management. Emergency practitioners should understand and recognise the signs and symptoms of serious meningococcal disease and refer children to paediatric services immediately.


Smoking and wound healing: a review.
It is now generally accepted that smoking impairs wound healing. This article briefly reviews wound healing and a number of local and systemic responses to smoking which may have deleterious effects on wound healing. It is important that dentists fully understand the deleterious effects of smoking on wound healing and that they fully explain to their patients who smoke the compromised tissue response and surgical results that can be anticipated.


High resolution luminescence spectrometer. 1: simultaneous recording of total luminescence and phosphorescence.
A luminescence spectrometer is described that has the particular advantage of allowing the simultaneous recording of total luminescence and phosphorescence spectra. The basic design is straightforward and uses commercially available components. The measuring and recording system is completely digital. The technique of single-photon counting is employed, and the data are recorded digitally in the form of listings and punched paper tapes. This output is suitable for further data analysis on a computer. An additional analog recording system allows an instant examination of the quality of the incoming data.


Dose-dependent cardiovascular, renal, and endocrine effects of furosemide in conscious lambs.
In recent experiments in conscious lambs, we showed that in addition to its well-known natriuretic and diuretic effects, i.v. injection of 2 mg/kg of furosemide resulted in a sustained increase in heart rate and an age-dependent increase in plasma renin activity. To determine whether these responses were dose dependent, we measured various parameters of cardiovascular, renal, and endocrine function in six chronically instrumented lambs. Three of seven doses of furosemide were tested at 48-h intervals; the range of doses was 0 to 7.5 mg/kg. A dose-dependent transient pressor response occurred within 20 min of furosemide administration; the duration of this response increased with increasing doses. Heart rate increased 40 min after doses of furosemide > or = 0.25 mg/kg; this response was not dose dependent. Renin increased following all doses; the peak and the duration of the renin response were dose dependent. These data provide new information on the dose-dependent cardiovascular, renal, and endocrine responses to furosemide in conscious newborn lambs.


Imprinting, the X-chromosome, and the male brain: explaining sex differences in the liability to autism.
Males are at least four times more likely to develop autism than females. Among relatives with a broader autistic phenotype, males predominate too. Autism is a highly heritable disorder, yet genome scans have not revealed any predisposing loci on the sex chromosomes. A nongenetic explanation for male vulnerability, such as exposure to prenatal androgens, is unlikely for a variety of reasons. A novel genetic mechanism that resolves many of the outstanding difficulties is outlined here. The imprinted-X liability threshold model hypothesizes that the threshold for phenotypic expression of many autistic characteristics is influenced by an imprinted X-linked gene(s) that is protective in nature. Imprinted genes are known to play an important role in normal fetal and behavioral development. The gene is expressed only on the X-chromosome that is inherited from the father and raises the threshold for phenotypic expression. It is normally silenced when transmitted maternally. Because only females have a paternal X-chromosome, the threshold for phenotypic expression is higher in them than in males. Evidence for the existence of the genetic locus was found in a study of females with X-monosomy (Turner's syndrome) in which females had either a single paternal or maternal X-chromosome. Identifying the sites of action of this X-linked gene could lead to the discovery of autosomal loci that confer more directly a predisposition to autism.


Myopericytoma of the tongue: a case report.
Myopericytoma is a rare benign tumour composed of pericytic cells that show myoid differentiation and have a tendency for concentric perivascular growth. It belongs to a spectrum ofperivascular myoid cell neoplasms. To date, only a small number of cases of myopericytoma involving the oral cavity have been reported. We describe a case of myopericytoma presenting as a slowly growing tongue nodule in a 61-year-old woman. A diagnosis of myopericytoma was established with the histopathological findings combined with immunohistochemical staining. Myopericytoma should be included in the differential diagnosis of well-circumscribed, slow-growing lesions of the oral cavity.


[Fertility behavior in Quebec, family allowances, and taxes: results and simulations with a discrete choice model for the years 1975-1987].
"We suppose that women (couples), who are less than 40 years old, are faced with three types of sequential decisions: the fertility decision, the decision relative to the number of children to have and the decision concerning labour force participation.... We use a nested polychotomous discrete choice model to estimate the responsiveness of the behaviour of 'married' women in Quebec to variations in the expected flow of revenue resulting from changes in the parameters of the personal income tax and in the level of public monetary transfers conditional on the number of children. The model is estimated with micro-data from 9 repeated cross-sections for the years 1975 to 1987 with a full information maximum likelihood method.... This empirical setting is used to simulate the effects of changes made to the fiscal and transfer policies in favor of families with dependent children on fertility, [women's] labor force participation and the importance of spending costs for the two levels of government." (SUMMARY IN ENG)


Classification of health webpages as expert and non expert with a reduced set of cross-language features.
Making the distinction between expert and non expert health documents can help users to select the information which is more suitable for them, according to whether they are familiar or not with medical terminology. This issue is particularly important for the information retrieval area. In our work we address this purpose through stylistic corpus analysis and the application of machine learning algorithms. Our hypothesis is that this distinction can be performed on the basis of a small number of features and that such features can be language and domain independent. The used features were acquired in source corpus (Russian language, diabetes topic) and then tested on target (French language, pneumology topic) and source corpora. These cross-language features show 90% precision and 93% recall with non expert documents in source language; and 85% precision and 74% recall with expert documents in target language.


Physical aspects of cardiac scanning with a block detector positron tomograph.
Physical aspects relating to cardiac scanning are described for an eight ring (15 plane) positron tomograph consisting of BGO block detectors (CTI/Siemens 931-08/12). Performance parameters were derived from a cylindrical heart phantom having a "myocardial" wall of thickness varying from 3 mm to 27 mm. This phantom was inserted into a chest phantom consisting of simulated chest wall, lungs, and arms. Recovery coefficients for myocardial thicknesses of 10 mm and 15 mm were 0.75 and 0.9, respectively. Division by the transmission minus "blood pool" (extravascular density) image was found to give a variation of corrected myocardial counts within +/- 5% when transmission data were smoothed. The on-line dead time correction algorithm was found to be accurate to within 5% up to 20 mCi (740 MBq) in the axial field of view (FOV) (10.8 cm) in the central chamber of the heart phantom. However, the correction factor at this rate is approximately 3, which would imply poor use of administered dose. Counts in the image due to scatter are approximately 2% in the (cold) central cavity of the heart phantom relative to counts/pixel in the active myocardium. The presence of phantom arms in the FOV was found to have only a small effect on mean pixel counts and noise in the heart phantom image, as did movement of the arms within a reasonable range.


Direct pulp capping with a dentinal adhesive resin system: a pilot study.
The clinical and histological responses of exposed pulpal tissue after direct capping appear to be more closely related to bacterial infiltration than to direct material toxicity. Dentinal bonding agents have been suggested as a replacement for calcium hydroxide for pulpal protection. In this pilot study, direct pulp capping with a glutaraldehyde-containing dentinal adhesive was performed on eight permanent premolars and molars. The teeth were immediately restored with a resin composite restoration. The clinical technique included the use of a calcium hydroxide paste to cover the exposure site during completion of the preparation. Enamel and dentin were etched with phosphoric acid. All teeth remained vital and without symptoms during the initial observation period of 2 to 6 months.


Daily rumination about stress, sleep, and diurnal cortisol activity.
Rumination is an involuntary cognitive process theorized to prolong arousal and inhibit proper emotion regulation. Most available research has examined individual differences in cognitive dispositions to ruminate about stress as a risk marker for psychopathology and other health problems. This intensive longitudinal study extended previous research by examining day-to-day associations of rumination about stress with objectively-measured actigraph-based sleep and diurnal salivary cortisol activity. Sixty-one healthy participants (Mage = 20.91) completed up to five ecological momentary assessments (EMA) each day and wore actigraph wristwatches for eight days (N = 488). On three of these days, participants provided five saliva samples assayed for cortisol (N = 910). On average, greater daily stress levels were associated with shorter sleep duration and higher waking cortisol levels. In day-to-day analyses, greater daily stress levels, when combined with ruminating about daily stress more than usual, was associated with higher waking cortisol levels the following morning. Ruminating more than usual about daily stress, in the context of low-stress days, was also associated with flatter diurnal cortisol slopes the next day. These findings highlight the potential influences of daily stress, and rumination about stress, on sleep and diurnal cortisol activity - two important markers of health and well-being.


Skin irritation potential of copper compounds.
Data on the dermal irritation by copper and its compounds is scant, and its irritancy has not been determined, e.g., in terms of an irritant dose ID50. Irritancy of copper can only be comparatively characterized in relation to other metal salts. A rank order for the irritancy of metal compounds can be inferred from the patch test concentrations recommended as non-irritating for the purpose of cutaneous allergy testing: potassium dichromate 0.5% in petrolatum; copper sulfate, cobalt chloride and palladium chloride ex equo: 1% in aqueous solution, and nickel sulfate: 5% in petrolatum.


[An economic analysis of ambulatory surgery of inguinal hernias].
A cost-analysis study has been carried out on ambulatory surgery of inguinal hernias, in 1991, at Béziers hospital, in France. Analytical book-keeping allows to approach real costs, that is to say 3,061 FF for all medical care spending, and 2,100 FF for the hospital stay. The overall profitability of this surgery questions the urgency of its spreading within the French health care system.


Imaging in assessing lymph node status in gastric cancer.
Accurate assessment of lymph node status is of crucial importance for appropriate treatment planning and determining prognosis in patients with gastric cancer. The aim of this study was to systematically review the current role of imaging in assessing lymph node (LN) status in gastric cancer. A systematic literature search was performed in the PubMed/MEDLINE and Embase databases. The methodological quality and diagnostic performance of the included studies was assessed. Six abdominal ultrasonography (AUS) studies, 30 endoscopic ultrasonography (EUS) studies, 10 multidetectorrow computed tomography (MDCT) studies, 3 conventional magnetic resonance imaging (MRI) studies, 4 (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) studies, and 1 FDG-PET/CT fusion study were included. In general, the included studies had moderate methodological quality. The sensitivity and specificity of AUS varied between 12.2% and 80.0% (median, 39.9%) and 56.3% and 100% (median, 81.8%). The sensitivity and specificity of EUS varied between 16.7% and 95.3% (median, 70.8%) and 48.4% and 100% (median, 84.6%). The sensitivity and specificity of MDCT varied between 62.5% and 91.9% (median, 80.0%) and 50.0% and 87.9% (median, 77.8%). The sensitivity and specificity of MRI varied between 54.6% and 85.3% (median, 68.8%) and 50.0% and 100% (median, 75.0%). The sensitivity and specificity of FDG-PET varied between 33.3% and 64.6% (median, 34.3%) and 85.7% and 97.0% (median, 93.2%). The sensitivity and specificity of the FDG-PET/CT fusion study were 54.7% and 92.2%. For all the imaging modalities, there were no significant differences between the mean sensitivities and specificities of high- and low-quality studies. AUS, EUS, MDCT, conventional MRI, and FDG-PET cannot reliably be used to confirm or exclude the presence of LN metastasis. The performance of highresolution PET/CT fusion and functional MRI techniques still has to be determined.


Needle aspiration of the lung in complex pneumonias.
In 39 patients with treated unresponsive pneumonia complicated by life-threatening underlying disease, direct needle aspiration of the lung was performed to establish a cause. An infectious agent was detected in 18 patients (46 percent), a nonbacterial cause was found in one, and cure of a recent infection was substantiated in six patients. An incorrect diagnosis was made in seven patients (one false-positive and six false-negative), and an indeterminant answer was obtained by needle aspiration in seven. Serious complications occurred in 11 patients, most commonly in those who had hypoxia or thrombocytopenia, but no morbidity occurred in 22 patients. The diagnostic yield allowed effective rational therapy to be selected for multiple potential pathogens in 12 patients and detected pathogens not suspected in six instances. The technique compares favorably to other invasive techniques for establishing definitive information in this group of seriously ill patients.


Can Nicotine Replacement Therapy Decrease Complications in Plastic Surgery?
Cigarette smoking has been well demonstrated to be associated with adverse outcomes and increased complications in surgical patients in the operative and postoperative periods. There is general agreement that smoking cessation decreases such risks; however, much debate still exists regarding the most effective modalities for risk mitigation, especially concerning modalities involving nicotine replacement in some form. This article reviews the discussion regarding smoking cessation therapies, in particular those involving nicotine replacement, in the context of mitigating risk in plastic surgery procedures. The recent rise in popularity of electronic cigarettes poses further challenges for clinicians in minimizing risk and optimizing outcomes for patients. Prospective studies including high-level evidence such as randomized controlled clinical trials will be required to help plastic surgeons develop guidelines that will enable optimization of patient safety and clinical outcomes.


Comparing welfare estimates from payment card contingent valuation and discrete choice experiments.
This study presents the first comparison of willingness to pay estimates derived from the payment card (PC) contingent valuation and discrete choice experiment (DCE) methods. A within-sample experiment was used to elicit women's preferences for Chlamydia screening. The willingness to pay estimate derived from the DCE was larger than that derived from the PC. To investigate why the willingness to pay estimates were different, a range of validity tests were conducted. Both methods produced theoretically valid results, and there was no difference in the reported difficulty of completing the tasks. Evidence of a prominence effect was found in the PC responses. Responses to the DCE satisfied tests of non-satiation. Responses to both methods were compared with revealed preference data. There were significant differences between stated screening intention in both methods and actual screening uptake. Future work should address the external validity of stated preference methods.


A physician's guide to early detection of oral cancer.
Oral cancer is a disease of the elderly that is more prevalent in patients who drink alcohol, smoke, or are chronically exposed to the sun. An oral examination is recommended annually for all elderly patients and more often for patients with these risk factors. The key to diagnosis and long-term patient survival is recognition of early lesions, which are often asymptomatic. Cancerous lesions occur more frequently at specific oral sites and may be difficult to differentiate from lesions caused by such benign conditions as denture irritation and herpetic ulcers.


[The cellular immunologic status of the laryngeal cancer patients].
To observe the cellular immunologic status of the laryngeal cancer patients 70 laryngeal cancer patients were examined with immunohistochemical method. The peripheral blood T lymphocyte subsets were detected and local tumor infiltrative T lymphocytes were observed. The results showed that the cellular immunologic function of laryngeal cancer patients was lower than that of the healthy persons and the function of late staged patients was lower than that of the early staged patients. The pattern of changes of these two observations was of the same trend. The clinical significance of the examinations was discussed.


Biochemical and biophysical characterization of four EphB kinase domains reveals contrasting thermodynamic, kinetic and inhibition profiles.
The Eph (erythropoietin-producing hepatocellular carcinoma) B receptors are important in a variety of cellular processes through their roles in cell-to-cell contact and signalling; their up-regulation and down-regulation has been shown to have implications in a variety of cancers. A greater understanding of the similarities and differences within this small, highly conserved family of tyrosine kinases will be essential to the identification of effective therapeutic opportunities for disease intervention. In this study, we have developed a route to production of multi-milligram quantities of highly purified, homogeneous, recombinant protein for the kinase domain of these human receptors in Escherichia coli. Analyses of these isolated catalytic fragments have revealed stark contrasts in their amenability to recombinant expression and their physical properties: e.g., a >16°C variance in thermal stability, a 3-fold difference in catalytic activity and disparities in their inhibitor binding profiles. We find EphB3 to be an outlier in terms of both its intrinsic stability, and more importantly its ligand-binding properties. Our findings have led us to speculate about both their biological significance and potential routes for generating EphB isozyme-selective small-molecule inhibitors. Our comprehensive methodologies provide a template for similar in-depth studies of other kinase superfamily members.


Is duct excision still necessary for all cases of suspicious nipple discharge?
Despite the low likelihood of malignancy, it is recommended that all women with pathologic nipple discharge undergo duct excision based on the inadequate sensitivity of diagnostic modalities. However, these data originates prior to recent improvements in breast imaging. We performed a retrospective review of patients evaluated in the setting of modern diagnostic breast imaging. Of 175 women referred to our breast clinic with a primary complaint of nipple discharge, 142 (81%) had suspicious discharge. Of the 23 patients who opted for observation over duct excision, with a mean follow-up of 3.3 years, none have been diagnosed with cancer. Among patients who proceeded with surgery, cancer was diagnosed in seven patients (5%). Six of the seven patients had either an abnormal mammogram or ultrasound. Among 46 patients with suspicious nipple discharge, a normal physical exam and normal diagnostic mammogram/ultrasound, only one malignancy (2%) was identified in a 79-year-old patient with a personal history of breast cancer. In selected patients with suspicious nipple discharge, but normal physical exam and diagnostic imaging, short-term observation with repeat evaluation seems reasonable for patients who do not desire duct excision.


Hydrocortisone reduces restenosis after stenting of small coronary arteries.
Stenting of small coronary arteries has been limited by high rates of restenosis, and restenosis after stenting has chiefly been attributed to inflammatory reactions resulting in cell proliferation and intimal hyperplasia. In order to suppress this inflammatory process, we examined the effects of hydrocortisone, an antiinflammatory agent, on restenosis after stenting in a nonrandomized retrospective registry. The study population consisted of 193 patients treated at two hospitals, who underwent stent implantations in coronary arteries of reference diameter <3 mm between February 1999 and September 2001. Target lesions included complex, restenotic, diabetic, or chronic total lesions and types of implanted stents were Multi-Link, S-series, and gfx stents. Effect of intravenous administration of hydrocortisone (200 mg) before stenting was compared to control patients who did not receive this treatment. There was no significant difference of early outcomes between the hydrocortisone group and the control group. On angiographic follow-up at 6 months after stenting, the rate of restenosis was significantly lower in patients treated with hydrocortisone as compared with control group (22.8% vs 37%, respectively; P < 0.05). The revascularization rate of target lesion at 6 months was also significantly lower in the treated group (16.5% vs 29%, respectively; P < 0.05). These results suggest that preprocedural intravenous administration of hydrocortisone reduces restenosis after stenting of small coronary arteries. Prospectively controlled trials will be necessary to confirm this preventive effect of hydrocortisone on coronary in-stent restenosis.


Study on DNA damaging effects of 4-nonylphenol using erythrocytes from peripheral circulation, gill and kidney of fish Channapunctatus.
The present study aimed to evaluate the genotoxic effect of 4-nonylphenol (NP) on blood cells of fish Channapunctatus. Fish were exposed to three sublethal concentrations (0.15 mg l⁻¹; 0.31 mg l⁻¹ and 0.63 mg l⁻¹) of 4-NP for 24, 48, 72 and 96 hrs. Blood cells from kidney, gills and peripheral circulation were analyzed for the presence of micronuclei and other changes in the erythrocytes. Significant changes were observed in all the experimental groups tested when compared with control. Highest genotoxicity was observed in blood cells obtained from gills (MN-2.92%, aberrant cell- 70.64%), followed by kidney (MN-1.34%, aberrant cells-64.94%), were least effect was observed in blood cells obtained from peripheral circulation (MN-0.88%, aberrant cells-46.27%).Therefore, micronucleus test performed on blood cells obtained from different sources showed that gills were more sensitive as compared to peripheral blood and kidney revealing genotoxic effect of 4-NP on fish C. punctatus.


Maximum feasibility guideline in the design and analysis of protein folding potentials.
Protein folding potentials are expected to have the lowest energy for the native shape. The Linear Programming (LP) approach achieves exactly that goal for a training set, or indicates that this goal is impossible to obtain. If a solution cannot be found (i.e., the problem is infeasible) two possible routes are possible: (a) choosing a new functional form for the potential, (b) finding the best potential with a feasible subset of the data, and (or) detecting inconsistent subset of the data in the training set. Here, we explore option (b). A simple heuristic for finding an approximate solution to an infeasible set of linear inequalities is outlined. An approximately feasible solution is obtained iteratively, starting from a certain initial guess, by computing a series of analytic centers of the polyhedra defined by all the inequalities satisfied at the subsequent iterations. Standard interior point algorithms for Linear Programming can be used to compute efficiently the analytic center of a polyhedron. We demonstrate how this procedure can be used for the design of folding potentials that are linear in their parameters. The procedure shows an improvement in the quality of the potentials and sometimes points to flaws in the original data.


Lipid membranes with an edge.
Consider an open lipid membrane with a free exposed edge. The energy describing this membrane is quadratic in the extrinsic curvature; that describing the edge is proportional to its length. We determine the boundary conditions satisfied by the equilibria of the membrane on this edge. The derivation is free of any assumptions on the symmetry of the membrane geometry. With respect to the axially symmetric case, there is an additional boundary condition that is identically satisfied in that limit. By considering the balance of the forces operating at the edge, a physical interpretation for the boundary conditions is provided. The effect of the addition of a Gaussian rigidity term for the membrane is also considered.


Three-Dimensional Chipless RFID Tags: Fabrication through Additive Manufacturing.
A new class of Radio Frequency IDentification (RFID) tags, namely the three-dimensional (3D)-printed chipless RFID one, is proposed, and their performance is assessed. These tags can be realized by low-cost materials, inexpensive manufacturing processes and can be mounted on metallic surfaces. The tag consists of a solid dielectric cylinder, which externally appears as homogeneous. However, the information is hidden in the inner structure of the object, where voids are created to encrypt information in the object. The proposed chipless tag represents a promising solution for anti-counterfeiting or security applications, since it avoids an unwanted eavesdropping during the reading process or information retrieval from a visual inspection that may affect other chipless systems. The adopted data-encoding algorithm does not rely on On-Off or amplitude schemes that are commonly adopted in the chipless RFID implementations but it is based on the maximization of available states or the maximization of non-overlapping regions of uncertainty. The performance of such class of chipless RFID tags are finally assessed by measurements on real prototypes.


The role of IVIg treatment in severe pemphigus vulgaris.
High-dose intravenous immunoglobulin (IVIg) has become a part of the treatment armentarium in pemphigus vulgaris (PV). Some consider IVIg as an adjuvant steroid sparing agent in PV, while others as disease modifying that can be used as monotherapy. We report our experience with a series of 12 PV patients with severe disease treated with IVIg as an adjuvant therapy. Ten of 12 patients (83%) showed response to six cycles of IVIg, six (50%) having complete remission and four (33%) having a partial response. This response rate is concordant with previous reports. The therapy was well tolerated. In all 12 patients, treatment with IVIg allowed a gradual reduction of prednisone dose compared with baseline levels. IVIg treatment was beneficial as a steroid sparing agent in our series of patients with severe PV.


Silencing of the expression of the immunoglobulin kappa gene in non-B cells.
Although the activating factor NF-kappa B can be present in the nucleus of many cell types, transcription and rearrangement of the immunoglobulin kappa chain gene is restricted to cells of the B lineage. Part of this specificity is determined by sequences within the major intron of the kappa gene that specifically silence gene expression in non-B cells (T cells and HeLa cells). These sequences are found in a 232-bp fragment located 5' of the NF-kappa B binding sequence of the enhancer. When this fragment is added back upstream of an active NF-kappa B site, it specifically decreases the expression of a linked gene by more than 10-fold in activated T cells but it has no effect on expression in B cells. The kappa silencer region acts in an orientation- and distance-independent manner and appears to be composed of multiple negative elements. The kappa silencer may act to restrict transcription and rearrangement of the C kappa locus to cells of the B lineage.


Conformational stability of apoflavodoxin.
Flavodoxins are alpha/beta proteins that mediate electron transfer reactions. The conformational stability of apoflavodoxin from Anaboena PCC 7119 has been studied by calorimetry and urea denaturation as a function of pH and ionic strength. At pH > 12, the protein is unfolded. Between pH 11 and pH 6, the apoprotein is folded properly as judged from near-ultraviolet (UV) circular dichroism (CD) and high-field 1H NMR spectra. In this pH interval, apoflavodoxin is a monomer and its unfolding by urea or temperature follows a simple two-state mechanism. The specific heat capacity of unfolding for this native conformation is unusually low. Near its isoelectric point (3.9), the protein is highly insoluble. At lower pH values (pH 3.5-2.0), apoflavodoxin adopts a conformation with the properties of a molten globule. Although apoflavodoxin at pH 2 unfolds cooperatively with urea in a reversible fashion and the fluorescence and far-UV CD unfolding curves coincide, the transition midpoint depends on the concentration of protein, ruling out a simple two-state process at acidic pH. Apoflavodoxin constitutes a promising system for the analysis of the stability and folding of alpha/beta proteins and for the study of the interaction between apoflavoproteins and their corresponding redox cofactors.


Ginseng inhibits cardiomyocyte hypertrophy and heart failure via NHE-1 inhibition and attenuation of calcineurin activation.
Ginseng is a medicinal plant used widely in Asia that has gained popularity in the West during the past decade. Increasing evidence suggests a therapeutic role for ginseng in the cardiovascular system. The pharmacological properties of ginseng are mainly attributed to ginsenosides, the principal bioactive constituents in ginseng. The present study was carried out to determine whether ginseng exerts a direct antihypertrophic effect in cultured cardiomyocytes and whether it modifies the heart failure process in vivo. Moreover, we determined the potential underlying mechanisms for these actions. Experiments were performed on cultured neonatal rat ventricular myocytes as well as adult rats subjected to coronary artery ligation (CAL). Treatment of cardiomyocytes with the α(1) adrenoceptor agonist phenylephrine (PE) for 24 hours produced a marked hypertrophic effect as evidenced by significantly increased cell surface area and ANP gene expression. These effects were attenuated by ginseng in a concentration-dependent manner with a complete inhibition of hypertrophy at a concentration of 10 μg/mL. Phenylephrine-induced hypertrophy was associated with increased gene and protein expression of the Na(+)-H(+) exchanger 1 (NHE-1), increased NHE-1 activity, increased intracellular concentrations of Na(+) and Ca(2+), enhanced calcineurin activity, increased translocation of NFAT3 into nuclei, and GATA-4 activation, all of which were significantly inhibited by ginseng. Upregulation of these systems was also evident in rats subjected to 4 weeks of CAL. However, animals treated with ginseng demonstrated markedly reduced hemodynamic and hypertrophic responses, which were accompanied by attenuation of upregulation of NHE-1 and calcineurin activity. Taken together, our results demonstrate a robust antihypertrophic and antiremodeling effect of ginseng, which is mediated by inhibition of NHE-1-dependent calcineurin activation.


Pattern and cause of fractures in patients who abuse alcohol: what should we do about it?
Alcohol abuse is increasing in the UK and contributes significantly to the rising number of acute hospital admissions. The effects are increasingly seen among younger people who binge drink. The effects of excess alcohol on the skeleton have attracted far less attention than those on other organs, but the risk of fractures at important sites, such as the hips and vertebrae, is greatly increased in alcoholics. This is partly owing to reductions in bone mineral density, but other factors such as an increased rate of falls play an important part. The contribution of excess alcohol consumption to the risk of fractures is recognised in the widely available fracture assessment tool (FRAX). The mechanisms of fracture in alcohol abusers are complex and involve direct effects on bone cells, and indirect effects, mediated by alcohol, on the endocrine system, pancreas and cytokine system. Poor nutrition, with a reduction in body mass index and vitamin D levels, often contributes significantly. Prevention and treatment of fractures in alcohol abusers has received limited attention, and there are surprisingly few therapeutic trials to guide clinical intervention. Abstinence has been shown to improve markers of bone turnover within 2 months. However, compliance with oral therapeutic agents is often poor, and bisphosphonates may be contraindicated in patients with alcoholic liver disease and varices. The emergence of newer therapeutic options may facilitate controlled prospective studies of the role of parenteral agents in providing protection against both primary and secondary osteoporotic fractures among patients with alcohol abuse.