bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of low molecular weight nuclear complexes containing integrase during the early stages of HIV-1 infection
Authors: Gérard Annabelle , Soler Nicolas , Ségéral Emmanuel , Belshan Michael , Emiliani Stéphane
Published: February 2013

Background

HIV-1 replication requires integration of its reverse transcribed viral cDNA into a host cell chromosome. The DNA cutting and joining reactions associated to this key step are catalyzed by the viral protein integrase (IN). In infected cells, IN binds the viral cDNA, together with viral and cellular proteins, to form large nucleoprotein complexes. However, the dynamics of IN complexes formation is still poorly understood.

Results

Here, we characterized IN complexes during the early stages of T-lymphocyte infection. We found that following viral entry into the host cell, IN was rapidly targeted to proteasome-mediated degradation. Interactions between IN and cellular cofactors LEDGF/p75 and TNPO3 were detected as early as 6 h post-infection. Size exclusion chromatography of infected cell extracts revealed distinct IN complexes in vivo. While at 2 h post-infection the majority of IN eluted within a high molecular weight complex competent for integration (IN complex I), IN was also detected in a low molecular weight complex devoid of full-length viral cDNA (IN complex II, ~440 KDa). At 6 h post-infection the relative proportion of IN complex II increased. Inhibition of reverse transcription or integration did not alter the elution profile of IN complex II in infected cells. However, in cells depleted for LEDGF/p75 IN complex II shifted to a lower molecular weight complex (IN complex III, ~150 KDa) containing multimers of IN. Notably, cell fractionation experiments indicated that both IN complex II and III were exclusively nuclear. Finally, IN complex II was not detected in cells infected with a virus harboring a mutated IN defective for LEDGF/p75 interaction and tetramerization.

Conclusions

Our findings indicate that, shortly after viral entry, a significant portion of DNA–free IN that is distinct from active pre-integration complexes accumulates in the nucleus.
Sero-epidemiological survey of human cytomegalovirus-infected children in Weifang (Eastern China) between 2009 and 2012
Authors: Sun Xiuning , Liu Zhijun , Wang Bin , Shi Lihong , Liang Ruiwen , Li Ling , Qian Dongmeng , Song Xuxia
Published: February 2013

Background

To understand the prevalence and characteristics of human cytomegalovirus (HCMV) infection in children in the Weifang area, and to provide information for its prevention and treatment.

Methods

A comprehensive survey was performed from 2009 to 2012 in 7582 children from birth to 6 years of age hospitalized in the Maternity and Child Health Hospital of Weifang. ELISA HCMV serology results and survey data were analyzed by age group and socio-economic level. The infection rates were based on IgG and IgM serology.

Results and conclusions

The overall infection rate from IgG and IgM in the Weifang area from 2009 to 2012 was 42.5% (3496/7582), among which 34.2% were HCMV-IgG positive, suggesting past infection. Overall, the probability of active HCMV infection showed no gender difference in any age group (P >0.05). Recent infections centered on the first 6 months of life, presumably due to breastfeeding. Among the 654 children hospitalized for active HCMV infection, 379 (57.9%) were from rural areas and 275 (42.1%) from urban areas, showing that active infection in the countryside was higher than that in the city (χ2 = 32.65, p <0.01).
The prevalence and risk factors of cytomegalovirus infection in inflammatory bowel disease in Wuhan, Central China
Authors: Yi Fengming , Zhao Jie , Luckheeram Rishi Vishal , Lei Yuan , Wang Changgao , Huang Sha , Song Lu , Wang Wei , Xia Bing
Published: February 2013

Background

The etiology of inflammatory bowel disease (IBD) is not clear and cytomegalovirus (CMV) infection is often associated with IBD patients. The etiologic link between IBD and CMV infection needs to be studied. The objective of the present study is to investigate the prevalence and risk factors of CMV in a cohort of IBD patients from Central China.

Methods

Two hundred and twenty six IBD patients (189 ulcerative colitis (UC) and 37 patients with Crohn’s disease (CD)), and 290 age and sex matched healthy controls were recruited. CMV DNA was detected by nested PCR, while serum anti-CMV IgG and anti-CMV IgM was determined by ELISAs. Colonoscopy/enteroscopy with biopsy of diseased tissues and subsequent H&E stain were then conducted in IBD patients with positive anti-CMV IgM. Finally, we analyzed the prevalence and clinical risk factors of CMV infection in IBD patients.

Results

The prevalence of CMV DNA and anti-CMV IgG positive rate in IBD patients were 84.07% and 76.11%, respectively, higher than those in healthy controls (59.66% and 50.69%, respectively, P < 0.05), However, anti-CMV IgM positive rate was no different with healthy controls (1.77% vs 0.34%, P = 0.235). In univariate analysis of risk factors, the recent use of corticosteroid was associated with increase of CMV DNA and IgM positive rate in UC (P = 0.035 and P = 0.015, respectively), aminosalicylic acid drug therapy was correlated with positivity of CMV DNA and IgG in UC and CMV DNA in CD (P = 0.041, P < 0.001 and P = 0.014, respectively), the treatment of immunosuppresent was correlated with CMV IgM (P < 0.001). Furthermore, patients with severe UC were significantly associated with CMV DNA and IgM (P = 0.048 and P = 0.031, respectively). Malnutrition (albumin < 35 G/L) was also found to be related with CMV recent infection (P = 0.031). In multivariate analysis of risk factors in UC, pancolitis was significantly associated with CMV DNA positivity (P = 0.001). Severe UC and pancolitis seemed to be related with IgG positivity. For CD, there was just single factor associated with CMV positive in each group, multivariate analysis was unnecessary.

Conclusions

CMV positive rate in IBD patients was significantly higher, than in healthy controls. The use of aminosalicylic acid, corticosteroid, immunosuppressants, pancolitis and severe IBD patients seemed to be more susceptible to CMV infection in univariate analysis of risk factors. However, no risk factor was found to be significantly correlated with CMV infection in multivariate analysis of risk factors.
In-office bacteria test for a microbial monitoring during the conventional and self-ligating orthodontic treatment
Authors: Mummolo Stefano , Marchetti Enrico , Giuca Maria Rita , Gallusi Gianni , Tecco Simona , Gatto Roberto , Marzo Giuseppe
Published: February 2013

This study investigated the microbial level of Streptococcus mutans and Lactobacillus spp. during an orthodontic treatment, and compare the data with untreated control subjects.

Sixty young adult subjects were selected (average 20.5, DS 1.62), among which 40 underwent an orthodontic treatment (20 were treated with self-ligating brackets and 20 with conventional brackets) and 20 were controls. Plaque Index, salivary flow and buffering capacity of saliva were assessed before the beginning of the orthodontic treatment. Then the microbial counts were obtained by using an in-office bacteria test.

The plaque index (PI) increased over time in each group as well as salivary flow, mostly in subjects treated with self-ligating brackets, suggesting a difference between conventional and self-ligating brackets. S.mutans showed a different trend of colonization in the two treated groups, as for subjects treated with conventional brackets it showed the greater value at the early stage of treatment (T1), followed by a decrease at T2. Lactobacillus spp. showed significant increase over time in the two treated groups, respect to the control group. Linear regression analysis showed no significant predictor for the microbial count at T2.

The assortment of the various species of bacteria change over time during the orthodontic treatment, and seems to show different trends, depending on the type of orthodontic device. Consequently a periodical microbial monitoring using in-office bacteria tests, seems indicated.
Resection of a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn’s disease under infliximab treatment: a case report
Authors: Togashi Junichi , Sugawara Yasuhiko , Akamatsu Nobuhisa , Aoki Taku , Ijichi Masayoshi , Tanabe Mami , Kusaka Koji , Shibazaki Masayuki , Tadami Tokuma , Sakou Minako , Takazoe Masakazu , Bandai Yasutsugu , Kokudo Norihiro
Published: February 2013

Introduction

A liver abscess in Crohn’s disease is a rare but important entity that is associated with a poor prognosis and high mortality when treatment is delayed. We report a case of successful liver segmentectomy for a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn’s disease under infliximab treatment.

Case presentation

A 31-year-old Japanese man, who had been treated with infliximab infusions for Crohn’s disease, was referred to our hospital presenting with an abrupt onset of high fever and an elevated white blood cell count and serum C-reactive protein level. Computed tomography revealed a liver abscess occupying segment 8. The limited effect of percutaneous transhepatic abscess drainage and antibiotics led us to perform radical resection of the abscess. The patient recovered quickly after surgery and the postoperative course was uneventful.

Conclusion

The present case suggests that surgical removal of an abscess should be considered for patients under immunosuppression or refractory to conventional treatment.
A review of the foot function index and the foot function index – revised
Authors: Budiman‐Mak Elly , Conrad Kendon J , Mazza Jessica , Stuck Rodney M
Published: February 2013

Background

The Foot Function Index (FFI) is a self‐report, foot‐specific instrument measuring pain and disability and has been widely used to measure foot health for over twenty years. A revised FFI (FFI‐R) was developed in response to criticism of the FFI. The purpose of this review was to assess the uses of FFI and FFI‐R as were reported in medical and surgical literature and address the suggestions found in the literature to improve the metrics of FFI‐R.

Methods

A systematic literature search of PubMed/Medline and Embase databases from October 1991 through December 2010 comprised the main sources of literature. To enrich the bibliography, the search was extended to BioMedLib and Scopus search engines and manual search methods. Search terms included FFI, FFI scores, FFI‐R. Requirements included abstracts/full length articles, English‐language publications, and articles containing the term “foot complaints/problems.” Articles selected were scrutinized; EBM abstracted data from literature and collected into tables designed for this review. EBM analyzed tables, KJC, JM, RMS reviewed and confirmed table contents. KJC and JM reanalyzed the original database of FFI‐R to improve metrics.

Results

Seventy‐eight articles qualified for this review, abstracts were compiled into 12 tables. FFI and FFI‐R were used in studies of foot and ankle disorders in 4700 people worldwide. FFI Full scale or the Subscales and FFI‐R were used as outcome measures in various studies; new instruments were developed based on FFI subscales. FFI Full scale was adapted/translated into other cultures. FFI and FFI‐R psychometric properties are reported in this review. Reanalysis of FFI‐R subscales’ confirmed unidimensionality, and the FFI‐R questionnaires’ response categories were edited into four responses for ease of use.

Conclusion

This review was limited to articles published in English in the past twenty years. FFI is used extensively worldwide; this instrument pioneered a quantifiable measure of foot health, and thus has shifted the paradigm of outcome measure to subjective, patient‐centered, valid, reliable and responsive hard data endpoints. Edited FFI‐R into four response categories will enhance its user friendliness for measuring foot health.
Conserved structure and inferred evolutionary history of long terminal repeats (LTRs)
Authors: Benachenhou Farid , Sperber Göran O , Bongcam-Rudloff Erik , Andersson Göran , Boeke Jef D , Blomberg Jonas
Published: February 2013

Background

Long terminal repeats (LTRs, consisting of U3-R-U5 portions) are important elements of retroviruses and related retrotransposons. They are difficult to analyse due to their variability.

The aim was to obtain a more comprehensive view of structure, diversity and phylogeny of LTRs than hitherto possible.

Results

Hidden Markov models (HMM) were created for 11 clades of LTRs belonging to Retroviridae (class III retroviruses), animal Metaviridae (Gypsy/Ty3) elements and plant Pseudoviridae (Copia/Ty1) elements, complementing our work with Orthoretrovirus HMMs. The great variation in LTR length of plant Metaviridae and the few divergent animal Pseudoviridae prevented building HMMs from both of these groups.

Animal Metaviridae LTRs had the same conserved motifs as retroviral LTRs, confirming that the two groups are closely related. The conserved motifs were the short inverted repeats (SIRs), integrase recognition signals (5´TGTTRNR…YNYAACA 3´); the polyadenylation signal or AATAAA motif; a GT-rich stretch downstream of the polyadenylation signal; and a less conserved AT-rich stretch corresponding to the core promoter element, the TATA box. Plant Pseudoviridae LTRs differed slightly in having a conserved TATA-box, TATATA, but no conserved polyadenylation signal, plus a much shorter R region.

The sensitivity of the HMMs for detection in genomic sequences was around 50% for most models, at a relatively high specificity, suitable for genome screening.

The HMMs yielded consensus sequences, which were aligned by creating an HMM model (a ‘Superviterbi’ alignment). This yielded a phylogenetic tree that was compared with a Pol-based tree. Both LTR and Pol trees supported monophyly of retroviruses. In both, Pseudoviridae was ancestral to all other LTR retrotransposons. However, the LTR trees showed the chromovirus portion of Metaviridae clustering together with Pseudoviridae, dividing Metaviridae into two portions with distinct phylogeny.

Conclusion

The HMMs clearly demonstrated a unitary conserved structure of LTRs, supporting that they arose once during evolution. We attempted to follow the evolution of LTRs by tracing their functional foundations, that is, acquisition of RNAse H, a combined promoter/ polyadenylation site, integrase, hairpin priming and the primer binding site (PBS). Available information did not support a simple evolutionary chain of events.
Reviewer acknowledgement 2012
Authors: Grattan Clive
Published: February 2013

Contributing reviewers

The editors of Clinical and Translational Allergy would like to thank all of our reviewers who have contributed to the journal in Volume 2 (2012).
Bacterial diversity of the rock-water interface in an East Antarctic freshwater ecosystem, Lake Tawani(P)†
Authors: Huang Jonathan P , Swain Ashit K , Thacker Robert W , Ravindra Rasik , Andersen Dale T , Bej Asim K
Published: February 2013

Schirmacher Oasis is one of the few ice-free plateaus in East Antarctica that maintains a unique distribution of over 120 microbial-rich, dynamic freshwater lakes, most of which are unexplored. In this study, we describe the bacterial diversity of the rock-water interface in Lake Tawani(P) using culture-independent Bacterial Tag Encoded FLX Amplicon Pyrosequencing (bTEFAP), clone library construction, and culture-based analysis targeting the eubacterial 16S rRNA gene. Lake Tawani(P)was formed in a fossil valley by the accumulation of snow and glacial melt through surface channels into a low-catchment depression. Overall this lake exhibited thirteen bacterial phyla and one-hundred and twelve genera. The Qiime bioinformatics analysis on the bTEFAP alone exhibited higher coverage of the bacterial composition in Lake Tawani(P) than the clone library construction or culture-based methodology. Particularly due to the higher sensitivity of the bTEFAP approach, we detected and differentiated members of the phyla: Chloroflexi, Gemmatimonadetes, Planctomycetes, Nitrospira, and Candidate Division TM7 that other methods were unable to reveal. Nevertheless we found that the use of multiple approaches identified a more complete bacterial community than by using any single approach. Investigating the bacterial diversity of the Schirmacher Oasis lakes, especially those connected through surface channels and encompassed by valleys, will help unravel the dynamic nature of these unique seasonal, freshwater lakes, which potentially harbors highly adapted bacterial taxa with defined ecological functions.
Leflunomide inhibits the apoptosis of human embryonic lung fibroblasts infected by human cytomegalovirus
Authors: Qi Ren , Hua-Song Zeng , Xiao-Feng Zeng
Published: February 2013

Background

The immunomodulatory drug leflunomide (LEF) is frequently used for treating human cytomegalovirus (HCMV), but its antiviral mechanism is still unclear. In this study,we therefore investigated the effects of the active LEF metabolite A771726 on the HCMV lifecycle in human embryonic lung fibroblasts. We clarified the mechanism of LEF antiviral infection, and provide a new way to treat immune dysfunction patients with HCMV infection.

Methods

The experiment was divided into four groups: the control group, the HCMV group, the ganciclovir + HCMV group as well as the LEF + HCMV group. MTT was usedfor assessment of the cell inhibitory rate. Apoptosis was measured by staining with fluorescein isothiocyanate Annexin V and propidium iodide. Statistical significance was determined by paired t- test using SPSS software.

Results

The results of the study showed that cell proliferation was significantly inhibited by HCMV at 24 hours and 48 hours. With increasing HCMV concentration, the value-added inhibition of the cells was significantly decreased compared with the control group, and was statistically significant (P <0.01). Ganciclovir can increase proliferation of cellsinfected with HCMV; compared with the control group it was statistically significant (P <0.05). Meanwhile, with LEF treatment cell proliferation was significantly improved at 24 hours and 48 hours, with statistical significance (P <0.05). The apoptosis rate of human embryonic lung fibroblasts infected with HCMV increased significantly at 24 hours, 48 hours and 72 hours, and as time goes on the apoptosis rate increases statistically significantly (P <0.01) compared with the control group The apoptosis rate of theHCMV infection group decreased by adding LEF,and was statistically significant (P <0.05).

Conclusions

In this studywe show that LEF is an exciting new drug for cytomegalovirus infection. LEF significantly inhibited HCMV infection-induced apoptosis and proliferation, playing an important role in the treatment of patients infected by HCMV. In this study we explored the potential usefulness of LEF for cytomegalovirus infection and found it to be a cost-effective new treatment for cytomegalovirus infection that deserves further study.
Rilonacept in the treatment of acute gouty arthritis: a randomized, controlled clinical trial using indomethacin as the active comparator
Authors: Terkeltaub Robert A , Schumacher H Ralph , Carter John D , Baraf Herbert SB , Evans Robert R , Wang Jian , King-Davis Shirletta , Weinstein Steven P
Published: February 2013

Introduction

In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares.

Methods

Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (n = 74); SC placebo at baseline plus oral indomethacin as above (n = 76); or SC rilonacept 320 mg at baseline plus oral placebo (n = 75). The primary efficacy endpoint was change in pain in the index joint (patient-reported using a Likert scale (0 = none; 4 = extreme)) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments.

Results

Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean ± SD age of 50.3 ± 10.6 years. All treatment groups reported within-group pain reductions from baseline (P < 0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55 ± 0.92) relative to indomethacin alone (-1.40 ± 0.96), the difference was not statistically significant (P = 0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69 ± 0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness.

Conclusions

Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.

Trial registration

ClinicalTrials.gov registration number NCT00855920.
Serum adipocyte fatty acid-binding protein levels in patients with critical illness are associated with insulin resistance and predict mortality
Authors: Huang Chi-Lun , Wu Yen-Wen , Hsieh Ai-Ru , Hung Yu-Hsuan , Chen Wen-Jone , Yang Wei-Shiung
Published: February 2013

Introduction

Hyperglycemia and insulin resistance are commonplace in critical illness, especially in patients with sepsis. Recently, several hormones secreted by adipose tissue have been determined to be involved in overall insulin sensitivity in metabolic syndrome-related conditions, including adipocyte fatty-acid binding protein (A-FABP). However, little is known about their roles in critical illness. On the other hand, there is evidence that several adipose tissue gene expressions change in critically ill patients.

Methods

A total of 120 patients (72 with sepsis, 48 without sepsis) were studied prospectively on admission to a medical ICU and compared with 45 healthy volunteers as controls. Various laboratory parameters and metabolic and inflammatory profiles were assessed within 48 hours after admission. Clinical data were collected from medical records.

Results

Compared with healthy controls, serum A-FABP concentrations were higher in all critically ill patients, and there was a trend of higher A-FABP in patients with sepsis. In multivariate correlation analysis in all critically ill patients, the serum A-FABP concentrations were independently related to serum creatinine, fasting plasma glucose, total cholesterol, TNF-alpha, albumin, and the Acute Physiology and Chronic Health Evaluation II scores. In survival analysis, higher A-FABP levels (> 40 ng/ml) were associated with an unfavorable overall survival outcome, especially in sepsis patients.

Conclusions

Critically ill patients have higher serum A-FABP concentrations. Moreover, A-FABP may potentially serve as a prognostic biomarker in critically ill patients with sepsis.
MT and reflection seismics in northwestern Skellefte Ore District, Sweden
Authors: García Juanatey María de los Ángeles , Tryggvason Ari , Juhlin Christopher , Bergström Ulf , Hübert Juliane , Pedersen Laust B.
Published: February 2013

A seismic reflection and MT survey was carried out along a 27-km long transect in northwestern Skellefte District, as part of a bigger 3D modeling project. The main motivation for the data acquisition is to elucidate the geologic relationship between the known mineralizations in the Adak mining camp to the north and in the well studied Kristineberg area south of the transect. The seismic reflection data were acquired with a VIBSIST system, and show reflectivity down to 3 s. Apart from the conventional processing for crystalline environments, the seismic data was also subject to an azimuthal binning procedure and cross-dip analysis, allowing the orientation of planar reflectors in 3D. Regarding the MT data, it is primarily of good quality along the 17 installed sites. The inversion of the determinant of the impedance tensor yielded a stable 2D resistivity model, dominated by resistors corresponding to the postorogenic intrusions along the transect. Adding the location of the analyzed seismic reflectors in the MT inversion rendered an integrated model that facilitated a preliminary joint interpretation of the data sets. Overall, the results are in good agreement with surface observations and reveal a crude configuration of the geologic units below the transect. The most prominent outcomes are the lateral and depth extent of the large postorogenic intrusions in the area reaching to 5- or 6-km depth, the dimensions of the nearly vertical Brännäs gabbro extending to 6-km depth, and the presence of enhanced conductivities along the transect at about 10 km depth. The latter is probably related to the deep conductor previously identified in the district.
Time-lapse wave-equation migration velocity analysis
Authors: Shragge Jeffrey , Lumley David
Published: February 2013

Time-lapse (4D) analysis of seismic data acquired at different stages of hydrocarbon production or gas/fluid injection has been very successful at imaging detailed reservoir changes. Conventional time-domain analysis of 4D data sets usually assumes a linear perturbation about a reference baseline earth model. However, this assumption is violated when production/injection significantly alters the subsurface generating large 4D velocity changes, time shifts, and complicated 4D wavefield coda, necessitating a more robust 4D analysis involving prestack wave-equation depth migration and velocity analysis. We address these situations by extending conventional 3D wave-equation migration velocity analysis (WEMVA) based on one-way wave-equations and single-scattering theory to 4D velocity estimation using a “parallel” inversion approach involving parallel solution of two separate inversion problems. Recognizing that the 4D WEMVA strategy requires precomputed baseline/monitor image-difference volumes, we develop an approximate 4D WEMVA technique that replaces these differences with a single weight function derived from the smooth background time-lapse image difference. We demonstrate the usefulness of the parallel and an approximate 4D WEMVA approach using a synthetic time-lapse [Formula: see text] geosequestration experiment that requires inverting for a thin-layer velocity change derived from [Formula: see text] injection in an analogue North Sea reservoir. The parallel 4D WEMVA solutions generate an excellent high-resolution velocity estimates, whereas the approximate methods recover lower-resolution estimates with magnitudes that must be rescaled through a post-inversion gradient line-search.
Socioeconomic disadvantage and psychotherapy
Authors: Meadows Graham N. , Tylee Andre T.
Published: February 2013

In this edition of the Journal, findings presented by Jokela and colleagues suggest some improvements in the equity of service provision of psychotherapies in the UK. This is encouraging, however, further work would be necessary to exclude other forms of inequity. For instance, people with equivalent need in different areas might find their needs are responded to with different durations of treatment.
Vitamin D deficiency and depression in adults: systematic review and meta-analysis
Authors: Anglin Rebecca E. S. , Samaan Zainab , Walter Stephen D. , McDonald Sarah D.
Published: February 2013

Background

There is conflicting evidence about the relationship between vitamin D deficiency and depression, and a systematic assessment of the literature has not been available.

Aims

To determine the relationship, if any, between vitamin D deficiency and depression.

Method

A systematic review and meta-analysis of observational studies and randomised controlled trials was conducted.

Results

One case-control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60,95% Cl 0.23–0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0–1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR=2.21, 95% CI 1.40–3.49).

Conclusions

Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal.
Prevalence of experiences of domestic violence among psychiatric patients: systematic review
Authors: Oram S. , Trevillion K. , Feder G. , Howard L. M.
Published: February 2013

Background

Domestic violence has been linked with many mental disorders, including anxiety, depression, post-traumatic stress disorder, eating disorders and psychosis.

Aims

To estimate the prevalence (adult lifetime and past year) of different types of domestic violence experienced by men and women receiving psychiatric treatment.

Method

In a systematic review, a search of 18 electronic databases was supplemented by hand searching, citation tracking and updating a recent systematic review of criminal victimisation in psychiatric populations. Two reviewers independently extracted data and appraised study quality.

Results

Forty-two studies were included. The median prevalence of lifetime partner violence reported in high-quality papers was 30% (interquartile range (IQR) 26–39) among female in-patients and 33% (IQR 21–53) among female out-patients. Among male patients, one high-quality study reported a lifetime prevalence of 32% across mixed psychiatric settings. No study included a control group.

Conclusions

Psychiatric patients experience a high prevalence of domestic violence but there is limited information on family (non-partner) domestic violence, the prevalence of emotional abuse and the extent of risk compared with non-psychiatric controls.
A call for a new positive psychiatry of ageing
Authors: Jeste Dilip V. , Palmer Barton W.
Published: February 2013

We propose a new model for geriatric psychiatry to help meet the needs of a rapidly growing population of older adults. This positive old age psychiatry would focus on recovery, promotion of successful ageing, neuroplasticity, prevention, and interventions to enhance positive psychological traits such as resilience, social engagement and wisdom.
Parental depression and the challenge of preventing mental illness in children
Authors: Ramchandani Paul G. , Murphy Susannah E.
Published: February 2013

Parental depression is a risk factor for psychiatric problems in children and adolescents. Exciting scientific developments have elucidated potential early mechanisms of intergenerational risk transmission and new models of intervention may help to prevent some childhood problems. However, caution is needed in interpreting such associations as causal and in targeting interventions appropriately.
Community treatment orders: current practice and a framework to aid clinicians
Authors: Lepping Peter , Malik Masood
Published: February 2013

Aims and method

Community treatment orders (CTOs) have been used more than anticipated. We report data from the North Wales audit about their current use and explain how a SMART framework can be used to potentially improve their effectiveness.

Results

Findings from this audit confirm those from other studies, with the reasons for use of CTOs extending beyond that of medication adherence to risk management. The combined recall and voluntary admission rate was 40%, which raises questions about the effectiveness of CTOs.

Clinical implications

More research is needed as it remains to be seen whether CTOs are able to achieve their intended aims. The SMART framework can be used to aid clinicians in ensuring that conditions placed on patients have a specific purpose and are clinically meaningful.
Prevalence study of head shop drug usage in mental health services
Authors: Lally John , Higaya Emam-El , Nisar Zafar , Bainbridge Emma , Hallahan Brian
Published: February 2013

Aims and method

To examine the prevalence of head shop drug usage in individuals attending a range of adult mental health services. We examined the effect of head shop drug usage on the mental state of individuals with a range of mental health disorders. Clinical data were obtained from 608 consecutively reviewed individuals attending adult mental health services in relation to their use of head shop and psychoactive drugs and the putative effects of head shop drugs on their mental state.

Results

The prevalence of head shop drug use was 13% (n= 78), with a higher prevalence of usage noted in individuals younger than 35 years of age (25%). A large proportion of individuals (n= 41, 54%) reported adverse effects of these agents on their mental state, with psychotic symptoms being the most prevalent.

Clinical implications

Head shop drug usage was associated with a reported deleterious effect on mental state, which was particularly evident for individuals with a history of psychosis.
Manganese Supplementation Protects Against Diet-Induced Diabetes in Wild Type Mice by Enhancing Insulin Secretion
Authors: Lee Soh-Hyun , Jouihan Hani A. , Cooksey Robert C. , Jones Deborah , Kim Hyung J. , Winge Dennis R. , McClain Donald A.
Published: February 2013

Mitochondrial dysfunction is both a contributing mechanism and complication of diabetes, and oxidative stress contributes to that dysfunction. Mitochondrial manganese-superoxide dismutase (MnSOD) is a metalloenzyme that provides antioxidant protection. We have previously shown in a mouse model of hereditary iron overload that cytosolic iron levels affected mitochondrial manganese availability, MnSOD activity, and insulin secretion. We therefore sought to determine the metallation status of MnSOD in wild-type mice and whether altering that status affected β-cell function. 129/SvEVTac mice given supplemental manganese exhibited a 73% increase in hepatic MnSOD activity and increased metallation of MnSOD. To determine whether manganese supplementation offered glucose homeostasis under a situation of β-cell stress, we challenged C57BL/6J mice, which are more susceptible to diet-induced diabetes, with a high-fat diet for 12 weeks. Manganese was supplemented or not for the final 8 weeks on that diet, after which we examined glucose tolerance and the function of isolated islets. Liver mitochondria from manganese-injected C57BL/6J mice had similar increases in MnSOD activity (81%) and metallation as were seen in 129/SvEVTac mice. The manganese-treated group fed high fat had improved glucose tolerance (24% decrease in fasting glucose and 41% decrease in area under the glucose curve), comparable with mice on normal chow and increased serum insulin levels. Isolated islets from the manganese-treated group exhibited improved insulin secretion, decreased lipid peroxidation, and improved mitochondrial function. In conclusion, MnSOD metallation and activity can be augmented with manganese supplementation in normal mice on normal chow, and manganese treatment can increase insulin secretion to improve glucose tolerance under conditions of dietary stress.
Impact of Clinically Relevant Mutations on the Pharmacoregulation and Signaling Bias of the Calcium-Sensing Receptor by Positive and Negative Allosteric Modulators
Authors: Leach Katie , Wen Adriel , Cook Anna E. , Sexton Patrick M. , Conigrave Arthur D. , Christopoulos Arthur
Published: February 2013

Cinacalcet is predominantly used to treat secondary hyperparathyroidism due to end-stage renal failure, but, more recently, its potential clinical efficacy in treating patients with loss-of-function mutations in the calcium-sensing receptor (CaSR) has been recognized. Many clinically relevant CaSR mutations are located in the heptahelical membrane spanning and extracellular loop regions of the receptor, where allosteric modulators are predicted to bind. The aim of the present study was to investigate the impact of such mutations on the pharmacoregulation of the CaSR by the positive and negative allosteric modulators, cinacalcet and NPS-2143, respectively. Both cinacalcet and NPS-2143 effectively rescued mutants whose cell surface expression was substantially impaired, suggesting that both classes of drug can stabilize a receptor conformation that is trafficked more effectively to the cell surface. In addition, functional impairments in almost all mutant CaSRs were rescued by either cinacalcet or NPS-2143 via restoration of intracellular signaling. There was a significantly greater ability of both compounds to modulate agonist-stimulated intracellular Ca2+ mobilization than ERK1/2 phosphorylation, indicating that the allosteric modulators engender bias in agonist-stimulated CaSR signaling to different pathways. Three mutations (G670R, P748R, and L773R) altered the binding affinity of allosteric modulators to the CaSR, and 3 mutations (V817I, L773R, and E767K) altered the cooperativity between the allosteric modulator and Ca2+o. These findings have important implications for the treatment of diseases associated with CaSR mutations using allosteric CaSR modulators and for analyzing the effects of mutations on the function and pharmacoregulation of the CaSR.
B-Raf and CRHR1 Internalization Mediate Biphasic ERK1/2 Activation by CRH in Hippocampal HT22 Cells
Authors: Bonfiglio Juan J. , Inda Carolina , Senin Sergio , Maccarrone Giuseppina , Refojo Damián , Giacomini Damiana , Turck Christoph W. , Holsboer Florian , Arzt Eduardo , Silberstein Susana
Published: February 2013

CRH is a key regulator of neuroendocrine, autonomic, and behavioral response to stress. CRH-stimulated CRH receptor 1 (CRHR1) activates ERK1/2 depending on intracellular context. In a previous work, we demonstrated that CRH activates ERK1/2 in limbic areas of the mouse brain (hippocampus and basolateral amygdala). ERK1/2 is an essential mediator of hippocampal physiological processes including emotional behavior, synaptic plasticity, learning, and memory. To elucidate the molecular mechanisms by which CRH activates ERK1/2 in hippocampal neurons, we used the mouse hippocampal cell line HT22. We document for the first time that ERK1/2 activation in response to CRH is biphasic, involving a first cAMP- and B-Raf–dependent early phase and a second phase that critically depends on CRHR1 internalization and β-arrestin2. By means of mass-spectrometry–based screening, we identified B-Raf–associated proteins that coimmunoprecipitate with endogenous B-Raf after CRHR1 activation. Using molecular and pharmacological tools, the functional impact of selected B-Raf partners in CRH-dependent ERK1/2 activation was dissected. These results indicate that 14-3-3 proteins, protein kinase A, and Rap1, are essential for early CRH-induced ERK1/2 activation, whereas dynamin and vimentin are required for the CRHR1 internalization-dependent phase. Both phases of ERK1/2 activation depend on calcium influx and are affected by calcium/calmodulin-dependent protein kinase II inactivation. Thus, this report describes the dynamics and biphasic nature of ERK1/2 activation downstream neuronal CRHR1 and identifies several new critical components of the CRHR1 signaling machinery that selectively controls the early and late phases of ERK1/2 activation, thus providing new potential therapeutic targets for stress-related disorders.
Life in the balance – a mechanistic view of the crosstalk between autophagy and apoptosis
Authors: Rubinstein Assaf D. , Kimchi Adi
Published: February 2013

Cellular stress triggers a fascinating decision-making process in cells; they can either attempt to survive until the stress is resolved through the activation of cytoprotective pathways, such as autophagy, or can commit suicide by apoptosis in order to prevent further damage to surrounding healthy cells. Although autophagy and apoptosis constitute distinct cellular processes with often opposing outcomes, their signalling pathways are extensively interconnected through various mechanisms of crosstalk. The physiological relevance of the autophagy–apoptosis crosstalk is not well understood, but it is presumed to facilitate a controlled and well-balanced cellular response to a given stress signal. In this Commentary, we explore the various mechanisms by which autophagy and apoptosis regulate each other, and define general paradigms of crosstalk on the basis of mechanistic features. One paradigm relates to physical and functional interactions between pairs of specific apoptotic and autophagic proteins. In a second mechanistic paradigm, the apoptosis or autophagy processes (as opposed to individual proteins) regulate each other through induced caspase and autolysosomal activity, respectively. In a third paradigm unique to autophagy, caspases are recruited and activated on autophagosomal membranes. These mechanistic paradigms are discernible experimentally, and can therefore be used as a practical guide for the interpretation of experimental data.
Stem cells and orthopaedic surgery
Authors: Khan M. , Roberts S. , Richardson J. B. , McCaskie A.
Published: February 2013

Stem cells are a key component of regenerative medicine strategies. Particular areas of musculoskeletal application include cartilage and bone regeneration in arthritis and trauma. There are several types of stem cell and this article will focus on the adult derived cells. The review includes current issues and future developments.
Semifields from skew polynomial rings
Authors: Lavrauw Michel , Sheekey John
Published: February 2013

Skew polynomial rings are used to construct finite semifields, following from a construction of Ore and Jacobson of associative division algebras. Johnson and Jha [10] constructed the so-called cyclic semifields, obtained using irreducible semilinear transformations. In this work we show that these two constructions in fact lead to isotopic semifields, show how the skew polynomial construction can be used to calculate the nuclei more easily, and provide an upper bound for the number of isotopism classes, improving the bounds obtained by Kantor and Liebler in [13] and implicitly by Dempwolff in [2].
Real hypersurfaces of complex and quaternionic hyperbolic spaces
Authors: Murphy Thomas
Published: February 2013

We introduce curvature-adapted foliations of complex hyperbolic space and study some of their properties. Generalized pseudo-Einstein hypersurfaces of complex hyperbolic space are classified. Analogous results for curvature-adapted foliations of quaternionic hyperbolic space are also discussed.
A note on CR quaternionic maps
Authors: Marchiafava S. , Pantilie R.
Published: February 2013

We introduce the notion of CR quaternionic map and we prove that any such realanalytic map, between CR quaternionic manifolds, is the restriction of a quaternionic map between quaternionic manifolds. As an application, we prove, for example, that for any submanifold M of dimension 4k-1 of a quaternionic manifold N such that TM generates a quaternionic subbundle of TN|M of (real) rank 4k, there exists, locally, a quaternionic submanifold of N containing M as a hypersurface.
Some remarks on Nijenhuis brackets, formality, and Kähler manifolds
Authors: Bartolomeis Paolo de , Matveev Vladimir S.
Published: February 2013

In order to detect formality of the DeRham algebra of a smooth manifold, we determine conditions that ensure that a general dδ-lemma holds; then, as an application of the previous constructions, we obtain a new characterization of Kähler structures.
A new prime-focus corrector for paraboloid mirrors
Authors: Rakich Andrew , Rumsey Norman J.
Published: February 2013

A new form of field corrector for astronomical telescopes with paraboloid primary mirrors is described. Like an earlier design by Wynne, it consists of four spaced lens elements with spherical surfaces only. In commonly occurring circumstances, the new design gives better image sharpness than does Wynne’s. The new system outperforms Wynne’s system for any probable wavelength range, when the field of view exceeds ~50 arc-minutes. Wynne’s original system tends to work better for narrower fields of view with a larger wavelength range. Also, the new system is closer to being telecentric than Wynne’s, which is of interest to the developers of multifiber-fed systems. Further, the geometry of the new system should yield a modestly reduced manufacturing cost.
Lefschetz trace formula for open adic spaces
Authors: Mieda Yoichi
Published: February 2013

In this article, we discuss the Lefschetz trace formula for an adic space
which is separated smooth of finite type but not necessarily proper over an algebraically closed
non-archimedean field. Under the condition that there is no set-theoretical fixed point on the boundary,
we obtain a fixed point formula. As an application, we can establish a trace formula for some formal schemes,
which is applicable to some Rapoport–Zink towers. A partial generalization of Fujiwara's trace formula for contracting morphisms is also given.
Expression and translation of the COX-1b gene in human cells – no evidence of generation of COX-1b protein
Authors: Reinauer Christina , Censarek Petra , Kaber Gernot , Weber Artur-Aron , Steger Gerhard , Klamp Thorsten , Schrör Karsten
Published: February 2013

Cyclooxygenase 1b (COX-1b) is a splice variant of COX-1, containing a retained intron 1 within the signal peptide sequence. COX-1b mRNA is found in many species, but the existence of a functionally active protein, which is possibly related to different species-dependent lengths of intron 1, is controversially discussed. The human intron 1 comprises 94 bp, and the resulting frameshift at the intron 1-exon 2 junction creates a premature stop codon. Nevertheless, full-length human COX-1b protein expression, including translated intron 1 and the signal peptide, has been reported and was explained by a frameshift repair. In this study, the fate of COX-1b mRNA in a human overexpression system is analyzed. Independent of the hypothetical frameshift repair mechanism, the splicing of the COX-1b intron 1, resulting in COX-1 mRNA and removal of the signal peptide during protein maturation, with subsequent generation of a COX-1 protein is demonstrated.