A Study of the Binding of Estradiol and 8-Isoestradiol to the Estrogen α-Receptor by Molecular Modeling

The complexes of the estrogen -receptor with estradiol and 8-isoestradiol were comparatively analyzed. The computations of ligand–receptor complexes, carried out using the FLEXX program, allowed us to propose a model for the binding of the analogues of 8-isoestradiol. It was found that rings Cand D of estradiol and 8-isoestradiol are similarly arranged in the ligand-binding pocket and coincide upon the superposition of the corresponding ligand–receptor complexes, whereas rings A and B do not coincide. The oxygen functions in position 17 of the estradiol analogues of both series coincide upon superposition, whereas the phenol 3-hydroxyl groups are 0.05 Å apart. A comparison of the predicted biological properties of modified estradiol analogues of the natural and 8-iso-series with the available experimental data revealed their similarity. Synthetic 2-acetyl analogues of 8-isoestrogens were found to have no uterotropic activity, which is also consistent with the proposed model.     

Variables Related to Working Capability among Swiss Patients with Multiple Sclerosis—A Cohort Study

Introduction

Reduced working capability is one of the most devastating consequences of multiple sclerosis (MS). We aimed to study working capability and related variables in Swiss MS patients.

Materials and Methods

A cross-sectional analysis of employment status and risk factors for reduced working capability among MS patients treated at our outpatient clinic. A questionnaire was mailed to 644 MS patients and returned by 69.7%. 405 patients (66% female, mean age 44.2 years (SD±10.2), median EDSS 3.0 (SD±1.8)) were eligible for subsequent analysis.

Results

After a mean disease duration of 12.3 years (SD±8.25), full or part time employment was declared by 26.7% and 25.7%, respectively. Incapacity to work was reported by 27.1%. A total of 52.8% specified MS as the cause for altered working capability, whereas 20.5% cited reasons unrelated to the disorder. Even with minimal disability (EDSS<3) a significant proportion of patients (24%) reported reduced working capability. Among the MS-specific restricting factors were fatigue (47.6%), sensorimotor deficits (31.1%), impaired vision (3.3%) and pain (2.8%).

Conclusion

MS continues to takes its toll on the professional life of the patients early in the course. While complete incapacity becomes relevant with moderate to severe disability, many patients scale down to part-time even with minimal impairment.     

Environmental Pathway and Risk Assessment Studies of the Musi River's Heavy Metal Contamination—A Case Study

The Musi River, in Hyderabad, the capital city of Andhra Pradesh state in India, is relatively dry for most of the year except for the four monsoon months when 700–800 mm of rain falls. Throughout the year, sewage, industrial, and hospital waste is released into the river. In the present work the Musi River from Amberpet Bridge to Nallacheruvu (8 km stretch) was assessed and monitored for heavy metal contamination attributable to sewage and industrial effluents. Twelve locations were assessed for Zn, Cr, Cu, Ni, Co, As, Hg, Cd, and Pb in soils, waters, forage grass, milk, and vegetables. A sequential extraction scheme revealed that high levels of Zn, Cr, and Cu were associated with labile fractions, making them more mobile and phytoavailable. Human risk was assessed in people exposed to pollution by analyzing metals concentrations in venous blood and urine. Results showed high amounts of Pb, Zn, Cr, and Ni compared to permissible limits, attributable to the consumption of contaminated food. Metals concentrations were monitored systematically to assess risks and support management decisions to help curtail the possible entry of metals into human food chains. An assessment was also made of a possible analysis of a remediation technology for lead-contaminated soils and water.     

Indigenous Research: A Commitment to Walking the Talk. The Gudaga Study—an Australian Case Study

Increasingly, the role of health research in improving the discrepancies in health outcomes between Indigenous and non-Indigenous populations in developed countries is being recognised. Along with this comes the recognition that health research must be conducted in a manner that is culturally appropriate and ethically sound. Two key documents have been produced in Australia, known as The Road Map and The Guidelines, to provide theoretical and philosophical direction to the ethics of Indigenous health research. These documents identify research themes considered critical to improving the health of the nation’s Indigenous peoples. They also provide values that, from an Indigenous perspective, are foundational to an ethical research process. This paper examines these research themes and values within the context of a current longitudinal birth cohort study of Indigenous infants and children in south-west Sydney: the Gudaga Study. Considerable time and effort have been invested in being true to the values stated in these documents: reciprocity; respect; equality; responsibility; survival and protection; and spirit and integrity. We have learnt that it is vital to be true to these values when conducting Indigenous health research—to quite literally “walk the talk”.     

Does Forest Scarcity Affect the Collection and Use of Firewood by Rural Communities? A Case Study in the Atlantic Forest of Northeastern Brazil

Many rural communities no longer have abundant forest areas for firewood collection. Based on this scenario, we evaluated how the scarcity of forest environments influences the collection and use of this resource in rural areas. A community located in the Atlantic Forest region of northeastern Brazil, which already lacks forest areas for firewood, was selected for field research. We observed that despite this context of forest scarcity, firewood remains the main source of fuel energy in the community. In total, 27 species of wood were cited, with an emphasis on exotic species in terms of number of citations. The perceived wood quality explained the frequency of plant use, but not the number of consumers. This can be explained by the difficulty of access to some species considered of better quality, because in the studied region, the plants are usually collected in private areas. Efforts in conservation strategies are recommended to encourage an increase in the frequency of use of the available exotic species in order to safeguard the native ones.     

A Microarray Based Genomic Hybridization Method for Identification of New Genes in Plants：Case Analyses of Arabidopsis and Oryza

To systematically estimate the gene duplication events In closely related species, we have to use comparative genomlc approaches, either through genomlc sequence comparison or comparative genomlc hybridization （CGH）. Given the scarcity of complete genomlc sequences of plant species, in the present study we adopted an array based CGH to Investigate gene duplications In the genus Arabldopsls. Fragment genomlc DNA from four species, namely Arabidopsls thallana, A. lyrata subsp, lyrata, A. lyrata subsp, petraea, and A. halleri, was hybridized to Affymetrlx （Santa Clara, CA, USA） tiling arrays that are designed from the genomlc sequences of A. thallana. Pairwlse comparisons of signal intensity were made to infer the potential duplicated candidates along each phylogenetic branch. Ninety-four potential candidates of gene duplication along the genus were Identified. Among them, the majority （69 of 94） were A. thallana lineage specific. This result indicates that the array based CGH approach may be used to Identify candidates of duplication In other plant genera containing closely related species, such as Oryza, particularly for the AA genome species. We compared the degree of gene duplication through retrotransposon between O. satlva and A. thallana and found a strikingly higher number of chimera retroposed genes In rice. The higher rate of gene duplication through retroposltlon and other mechanisms may Indicate that the grass species Is able to adapt to more diverse environments.     

A New Solid Phase Method for the Synthesis of Oligonucleotides with Terminal -3′-Phosphate

Abstract

A novel method for the synthesis of oligonucleotides with terminal-3′-phosphate using universal CPG polymer support is described.     

Concerns Expressed by Parents of Children with Pervasive Developmental Disorders for Different Time Periods of the Day: A Case–Control Study

Background/Aim

The Questionnaire: Children with Difficulties (QCD) is a parent-assessed questionnaire designed to evaluate child’s difficulties in functioning during specific periods of the day. This study aimed to evaluate difficulties in daily functioning of children and adolescents with pervasive developmental disorder (PDD) using the QCD. Results were compared with those for a community sample.

Methods

A case–control design was used. The cases comprised elementary school students (182 males, 51 females) and junior high school students (100 males, 39 females) with PDD, whereas a community sample of elementary school students (568 males, 579 females) and junior high school students (180 males, 183 females) was enrolled as controls. Their behavior was assessed using the QCD, the Tokyo Autistic Behavior Scale (TABS), the ADHD-rating scale (ADHD-RS), and the Oppositional Defiant Behavior Inventory (ODBI) for elementary and junior high school students, respectively. Effects of gender and diagnosis on the QCD scores were analyzed. Correlation coefficients between QCD and TABS, ADHD-RS, and ODBI scores were analyzed.

Results

The QCD scores for the children with PDD were significantly lower compared with those from the community sample (P < 0.001). Significantly strong correlations were observed in more areas of the ADHD-RS and ODBI scores compared with the TABS scores.

Conclusions

Children with PDD experienced greater difficulties in completing basic daily activities; moreover, their QCD scores revealed stronger associations with their ADHD-RS and ODBI scores in comparison with their TABS scores. The difficulties of PDD, ADHD and OBDI symptoms combined in children makes it necessary to assess all diagnoses before any therapy for PDD is initiated in order to be able to evaluate its results properly.     

The Postnatal Development of the Cerebellum— A fMRI and Silver Study

Summary The aim of this study was to evaluate the postnatal development of the cerebella of the pig and to compare this with the activation of the fMRI. The cells in the cerebella were studied by silver technique and the activation of the fMRI in the cerebella was initiated by flexion and extension of the hind paw. Our results showed an increase of the branching of the cells of the cerebellar cortex postnatally, coordinated with registration of fMRI active sites in the cerebella at 6-month postnatal. We concluded that the full maturation of the cerebella was around 6-month postnatal in the pig.     

Leprosy New Case Detection Trends and the Future Effect of Preventive Interventions in Pará State,Brazil: A Modelling Study

BackgroundLeprosy remains a public health problem in Brazil. Although the overall number of new cases is declining, there are still areas with a high disease burden, such as Pará State in the north of the country. We aim to predict future trends in new case detection rate (NCDR) and explore the potential impact of contact tracing and chemoprophylaxis on NCDR in Pará State.MethodsWe used SIMCOLEP, an existing individual-based model for the transmission and control of M. leprae, in a population structured by households. The model was quantified to simulate the population and observed NCDR of leprosy in Pará State for the period 1990 to 2014. The baseline scenario was the current control program, consisting of multidrug therapy, passive case detection, and active case detection from 2003 onwards. Future projections of the NCDR were made until 2050 given the continuation of the current control program (i.e. baseline). We further investigated the potential impact of two scenarios for future control of leprosy: 1) discontinuation of contact tracing; and 2) continuation of current control in combination with chemoprophylaxis. Both scenarios started in 2015 and were projected until 2050.ResultsThe modelled NCDR in Pará State after 2014 shows a continuous downward trend, reaching the official elimination target of 10 cases per 100,000 population by 2030. The cessation of systematic contact tracing would not result in a higher NCDR in the long run. Systematic contact tracing in combination with chemoprophylaxis for contacts would reduce the NCDR by 40% and bring attainment of the elimination target two years forward to 2028.ConclusionThe NCDR of leprosy continues to decrease in Pará State. Elimination of leprosy as a public health problem could possibly be achieved around 2030, if the current control program is maintained. Providing chemoprophylaxis would decrease the NCDR further and would bring elimination forward by two years.     

Coming to Terms with the Concept of Moving Species Threatened by Climate Change – A Systematic Review of the Terminology and Definitions

Intentional moving of species threatened by climate change is actively being discussed as a conservation approach. The debate, empirical studies, and policy development, however, are impeded by an inconsistent articulation of the idea. The discrepancy is demonstrated by the varying use of terms, such as assisted migration, assisted colonisation, or managed relocation, and their multiple definitions. Since this conservation approach is novel, and may for instance lead to legislative changes, it is important to aim for terminological consistency. The objective of this study is to analyse the suitability of terms and definitions used when discussing the moving of organisms as a response to climate change. An extensive literature search and review of the material (868 scientific publications) was conducted for finding hitherto used terms (N = 40) and definitions (N = 75), and these were analysed for their suitability. Based on the findings, it is argued that an appropriate term for a conservation approach relating to aiding the movement of organisms harmed by climate change is assisted migration defined as follows: Assisted migration means safeguarding biological diversity through the translocation of representatives of a species or population harmed by climate change to an area outside the indigenous range of that unit where it would be predicted to move as climate changes, were it not for anthropogenic dispersal barriers or lack of time. The differences between assisted migration and other conservation translocations are also discussed. A wide adoption of the clear and distinctive term and definition provided would allow more focused research on the topic and enable consistent implementation as practitioners could have the same understanding of the concept.     

PSYCHOSIS AND SYSTEMIC LUPUS ERYTHEMATOSUS—A Review of the Literature and Case Reports

In a review of the literature of the last 60 years concerning the association between psychosis and systemic lupus erythematosus, reports of 227 cases of this association were found. The average incidence of psychosis in the various series of systemic lupus erythematosus that were reviewed was 22 per cent. In only 25 per cent of the cases in which the information was given was the psychosis associated with steroid therapy.The psychiatric manifestations are variable and may be associated with a neurological disorder. Psychosis may antedate by many years other features of lupus. The psychosis due to lupus may respond to steroid therapy. Since systemic lupus erythematosus sometimes may be an important differential diagnosis of functional psychosis, appropriate diagnostic studies should be carried out in psychotic patients who have an accelerated sedimentation rate or positive serological test for syphilis without apparent reason.     

Residential Exposure to Traffic Noise and Health-Related Quality of Life—A Population-Based Study

Background

Few studies have investigated the association between objectively measured traffic noise and health-related quality of life. However, as traffic noise has been associated with both cardiovascular disease and diabetes, and health-issues including sleeping problems, annoyance, and stress, it seems plausible that traffic noise is associated with health-related quality of life.

Methods

Between 1999 and 2002, a cohort of 38,964 Danes filled in the short form-36 (SF-36) questionnaire. Residential exposure to road traffic and railway noise was calculated for all historical addresses for 10 years preceding the SF-36, using the Nordic prediction method. Associations between noise exposure and SF-36 summary scales and the eight sub-scales were calculated using general linear models, adjusted for age, sex, socioeconomic status, and lifestyle.

Results

Models adjusted for age, sex and socioeconomic factors showed that a 10 dB higher road traffic noise 1 year preceding SF-36 assessment was associated with a 0.14 lower mental component summary (MCS) score (95% confidence interval (CI) -0.26, -0.01). However, further adjustment for lifestyle factors (smoking, alcohol, and waist circumference) attenuated the association: (-0.08 (95% CI: -0.20, 0.04)). Exposure to more than 55 dB of railway noise in the same time period was borderline significantly associated with lower MCS. The physical component summary was not associated with traffic noise.

Conclusion

The present study suggests a weak association between traffic noise exposure and the mental health component score of SF-36, which may operate through lifestyle. The magnitude of effect was, however, not clinically relevant.