bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone acetyltransferases in rice (Oryza sativaL.): phylogenetic analysis, subcellular localization and expression
Authors: Liu Xia , Luo Ming , Zhang Wei , Zhao Jinhui , Zhang Jianxia , Wu Keqiang , Tian Lining , Duan Jun
Published: August 2012

Background

Histone acetyltransferases (HATs) play an important role in eukaryotic transcription. Eight HATs identified in rice (OsHATs) can be organized into four families, namely the CBP (OsHAC701, OsHAC703, and OsHAC704), TAFII250 (OsHAF701), GNAT (OsHAG702, OsHAG703, and OsHAG704), and MYST (OsHAM701) families. The biological functions of HATs in rice remain unknown, so a comprehensive protein sequence analysis of the HAT families was conducted to investigate their potential functions. In addition, the subcellular localization and expression patterns of the eight OsHATs were analyzed.

Results

On the basis of a phylogenetic and domain analysis, monocotyledonous CBP family proteins can be subdivided into two groups, namely Group I and Group II. Similarly, dicotyledonous CBP family proteins can be divided into two groups, namely Group A and Group B. High similarities of protein sequences, conserved domains and three-dimensional models were identified among OsHATs and their homologs in Arabidopsis thaliana and maize. Subcellular localization predictions indicated that all OsHATs might localize in both the nucleus and cytosol. Transient expression in Arabidopsis protoplasts confirmed the nuclear and cytosolic localization of OsHAC701, OsHAG702, and OsHAG704. Real-time quantitative polymerase chain reaction analysis demonstrated that the eight OsHATs were expressed in all tissues examined with significant differences in transcript abundance, and their expression was modulated by abscisic acid and salicylic acid as well as abiotic factors such as salt, cold, and heat stresses.

Conclusions

Both monocotyledonous and dicotyledonous CBP family proteins can be divided into two distinct groups, which suggest the possibility of functional diversification. The high similarities of protein sequences, conserved domains and three-dimensional models among OsHATs and their homologs in Arabidopsis and maize suggested that OsHATs have multiple functions. OsHAC701, OsHAG702, and OsHAG704 were localized in both the nucleus and cytosol in transient expression analyses with Arabidopsis protoplasts. OsHATs were expressed constitutively in rice, and their expression was regulated by exogenous hormones and abiotic stresses, which suggested that OsHATs may play important roles in plant defense responses.
Identification and characterization of small non-coding RNAs from Chinese fir by high throughput sequencing
Authors: Wan Li-Chuan , Wang Feng , Guo Xiangqian , Lu Shanfa , Qiu Zongbo , Zhao Yuanyuan , Zhang Haiyan , Lin Jinxing
Published: August 2012

Background

Small non-coding RNAs (sRNAs) play key roles in plant development, growth and responses to biotic and abiotic stresses. At least four classes of sRNAs have been well characterized in plants, including repeat-associated siRNAs (rasiRNAs), microRNAs (miRNAs), trans-acting siRNAs (tasiRNAs) and natural antisense transcript-derived siRNAs. Chinese fir (Cunninghamia lanceolata) is one of the most important coniferous evergreen tree species in China. No sRNA from Chinese fir has been described to date.

Results

To obtain sRNAs in Chinese fir, we sequenced a sRNA library generated from seeds, seedlings, leaves, stems and calli, using Illumina high throughput sequencing technology. A comprehensive set of sRNAs were acquired, including conserved and novel miRNAs, rasiRNAs and tasiRNAs. With BLASTN and MIREAP we identified a total of 115 conserved miRNAs comprising 40 miRNA families and one novel miRNA with precursor sequence. The expressions of 16 conserved and one novel miRNAs and one tasiRNA were detected by RT-PCR. Utilizing real time RT-PCR, we revealed that four conserved and one novel miRNAs displayed developmental stage-specific expression patterns in Chinese fir. In addition, 209 unigenes were predicted to be targets of 30 Chinese fir miRNA families, of which five target genes were experimentally verified by 5' RACE, including a squamosa promoter-binding protein gene, a pentatricopeptide (PPR) repeat-containing protein gene, a BolA-like family protein gene, AGO1 and a gene of unknown function. We also demonstrated that the DCL3-dependent rasiRNA biogenesis pathway, which had been considered absent in conifers, existed in Chinese fir. Furthermore, the miR390-TAS3-ARF regulatory pathway was elucidated.

Conclusions

We unveiled a complex population of sRNAs in Chinese fir through high throughput sequencing. This provides an insight into the composition and function of sRNAs in Chinese fir and sheds new light on land plant sRNA evolution.
Human pancreatic adenocarcinoma contains a side population resistant to gemcitabine
Authors: Van den broeck Anke , Gremeaux Lies , Topal Baki , Vankelecom Hugo
Published: August 2012

Background

Therapy resistance remains one of the major challenges to improve the prognosis of patients with pancreatic cancer. Chemoresistant cells, which potentially also display cancer stem cell (CSC) characteristics, can be isolated using the side population (SP) technique. Our aim was to search for a SP in human pancreatic ductal adenocarcinoma (PDAC) and to examine its chemoresistance and CSC(−like) phenotype.

Methods

Human PDAC samples were expanded in immunodeficient mice and first-generation xenografts analyzed for the presence of a Hoechst dye-effluxing SP using flow cytometry (FACS). To investigate chemoresistance of the SP, mice bearing PDAC xenografts were treated with gemcitabine and SP proportion determined. In addition, the SP and the main tumour cell population (MP) were sorted by FACS for RNA extraction to profile gene expression, and for culturing under sphere-forming conditions.

Results

A SP was identified in all PDAC samples, analyzed. This SP was more resistant to gemcitabine than the other tumour cells as examinedin vivo. Whole-genome expression profiling of the SP revealed upregulation of genes related to therapy resistance, apoptotic regulation and epithelial-mesenchymal transition. In addition, the SP displayed higher tumourigenic (CSC) activity than the MP as analyzedin vitroby sphere-forming capacity.

Conclusion

We identified a SP in human PDAC and uncovered a chemoresistant and CSC-associated phenotype. This SP may represent a new therapeutic target in pancreatic cancer.

Trial registration

Clinicaltrials.gov NCT00936104
Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial
Authors: Ghoreishi Zohreh , Esfahani Ali , Djazayeri Abolghasem , Djalali Mahmoud , Golestan Banafsheh , Ayromlou Hormoz , Hashemzade Shahriar , Asghari Jafarabadi Mohammad , Montazeri Vahid , Keshavarz Seyed Ali , Darabi Masoud
Published: August 2012

Background

Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy.

Methods

This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score".

Results

Twenty one patients (70%) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7%( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (−2.06 -0.02), p = 0.054).

Conclusions

Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients’ quality of life.

Trial registration

This trial was registered at ClinicalTrials.gov (NCT01049295)
Visual acuity improvements after implantation of toric intraocular lenses in cataract patients with astigmatism: a systematic review
Authors: Agresta Blaise , Knorz Michael C , Donatti Christina , Jackson Daniel
Published: August 2012

Background

Cataracts are a common and significant cause of visual impairment globally. We aimed to evaluate uncorrected distance visual acuity (UDVA) as an outcome in treating astigmatic cataract patients to assist clinicians or ophthalmologists in their decision making process regarding available interventions.

Methods

Medline, Embase and Evidence Based Reviews were systematically reviewed to identify relevant studies reporting changes in UDVA, UIVA and UNVA after cataract surgery in presbyopic patients. Strict inclusion/exclusion criteria were used to exclude any non-relevant studies. Relevant outcomes (UDVA, UIVA and UNVA) were identified from the studies retrieved through the systematic review process.

Results

The systematic review identified 11 studies which reported UCVA. All 11 studies reported UDVA. Four brands of toric intraocular lenses (IOLs) were reported in these studies. All studies identified in the literature search reported improvements in UDVA following surgical implant of a toric IOL. The largest improvements in VA were reported using the Human Optics MicroSil toric IOL (0.74 LogMAR, UDVA) and the smallest improvements were also reported using the Human Optics MicroSil toric IOL (0.23 LogMAR, UDVA) in a different study.

Conclusions

The results of this systematic review showed the aggregate of studies reporting a beneficial increase in UDVA with the use of toric IOLs in cataract patients with astigmatism.
Risk factors for criminal recidivism – a prospective follow-up study in prisoners with substance abuse
Authors: Håkansson Anders , Berglund Mats
Published: August 2012

Background

Substance use in general has been shown to predict criminal recidivism. The present study aimed to examine potential predictors of criminal recidivism, including substance-specific substance use patterns, in prisoners with substance use.

Methods

A cohort of prisoners with substance use problems (N = 4,152) were assessed with the Addiction Severity Index (ASI) in the Swedish criminal justice system. Clients were followed for an average of 2.7 years. Criminal recidivism was defined as any return to the criminal justice system.

Results

During follow-up, 69 percent (n = 2,862) returned to the criminal justice system. Recidivism was associated with amphetamine and heroin use, with an additive risk for injectors, and with polysubstance use. Also, recidivism was negatively associated with alcohol, other opioids than heroin/methadone and with hallucinogenic drugs, and positively associated with previous psychiatric in-patient treatment, violent behaviour, and with a shorter index sentence. Associations remained when controlling for type of crime.

Conclusions

Even when controlling for type and severity of crime, and for psychiatric problems, risk of criminal relapse was increased by substance use variables, including amphetamine, heroin and polysubstance use, and an additional risk was shown for injection drug users. These findings have implications for the need for substance abuse treatment after release from prison.
Explaining the disability paradox: a cross-sectional analysis of the Swiss general population
Authors: Fellinghauer Bernd , Reinhardt Jan D , Stucki Gerold , Bickenbach Jerome
Published: August 2012

Background

Disability can be broken down into difficulties in different components of functioning such as impairments and limitations in activities and participation (A&P). Previous studies have produced the seemingly surprising result that persons with severe impairments tend to report high quality of life (QoL) including perceived health regardless of their condition; the so-called “disability paradox”. We aim to study the role of contextual factors (i.e. the personal and environmental situation) in explaining the disability paradox.

Methods

The Swiss Health Survey provides information on the perceived health of 18,760 participants from the general population. We construct a conditional independence graph applying random forests and stability selection in order to represent the structure of impairment, A&P limitation, contextual factors, and perceived health.

Results

We find that impairment and A&P limitations are not directly related but only via a cluster of contextual factors. Similarly, impairment and perceived health are not directly related. On the other hand, perceived health is directly connected with A&P limitations. We hypothesize that contextual factors have a moderating and/or mediating effect on the relationship of impairment, A&P limitations, and perceived health.

Conclusion

The disability paradox seems to dissolve when contextual factors are put into consideration. Contextual factors may be responsible for some persons with impairments developing A&P limitations and others not. In turn, persons with impairments may only then perceive bad health when they experience A&P limitation. Political interventions at the level of the environment may reduce the number of persons who perceive bad health.
Care-seeking patterns for fatal non-communicable diseases among women of reproductive age in rural northwest Bangladesh
Authors: Sikder Shegufta S , Labrique Alain B , Ullah Barkat , Mehra Sucheta , Rashid Mahbubur , Ali Hasmot , Jahan Nusrat , Shamim Abu A , West Keith P , Christian Parul
Published: August 2012

Background

Though non-communicable diseases contribute to an increasing share of the disease burden in South Asia, health systems in most rural communities are ill-equipped to deal with chronic illness. This analysis seeks to describe care-seeking behavior among women of reproductive age who died from fatal non-communicable diseases as recorded in northwest rural Bangladesh between 2001 and 2007.

Methods

This analysis utilized data from a large population-based cohort trial in northwest rural Bangladesh. To conduct verbal autopsies of women who died while under study surveillance, physicians interviewed family members to elicit the biomedical symptoms that the women experienced as well as a narrative of the events leading to deaths. We performed qualitative textual analysis of verbal autopsy narratives for 250 women of reproductive age who died from non-communicable diseases between 2001 and 2007.

Results

The majority of women (94%) sought at least one provider for their illnesses. Approximately 71% of women first visited non-certified providers such as village doctors and traditional healers, while 23% first sought care from medically certified providers. After the first point of care, women appeared to switch to medically certified practitioners when treatment from non-certified providers failed to resolve their illness.

Conclusions

This study suggests that treatment seeking patterns for non-communicable diseases are affected by many of the sociocultural factors that influence care seeking for pregnancy-related illnesses. Families in northwest rural Bangladesh typically delayed seeking treatment from medically certified providers for NCDs due to the cost of services, distance to facilities, established relationships with non-certified providers, and lack of recognition of the severity of illnesses. Most women did not realize initially that they were suffering from a chronic illness. Since women typically reached medically certified providers in advanced stages of disease, they were usually told that treatment was not possible or were referred to higher-level facilities that they could not afford to visit. Women suffering from non-communicable disease in these rural communities need feasible and practical treatment options. Further research and investment in adequate, appropriate care seeking and referral is needed for women of reproductive age suffering from fatal non-communicable diseases in resource-poor settings.
Effects of proactive population-based nephrologist oversight on progression of chronic kidney disease: a retrospective control analysis
Authors: Lee Brian , Turley Marianne , Meng Di , Zhou Yvonne , Garrido Terhilda , Lau Alan , Radler Linda
Published: August 2012

Background

Benefits of early nephrology care are well-established, but as many as 40% of U.S. patients with end-stage renal disease (ESRD) do not see a nephrologist before its onset. Our objective was to evaluate the effect of proactive, population-based nephrologist oversight (PPNO) on chronic kidney disease (CKD) progression.

Methods

Retrospective control analysis of Kaiser Permanente Hawaii members with CKD using propensity score matching methods. We matched 2,938 control and case pairs of individuals with stage 3a CKD for the pre-PPNO period (2001–2004) and post-PPNO period (2005–2008) that were similar in other characteristics: age, gender, and the presence of diabetes and hypertension. After three years, we classified the stage outcomes for all individuals. We assessed the PPNO effect across all stages of progression with a χ
2- test. We used the z-score test to assess the proportional differences in progression within a stage.

Results

The progression within the post-PPNO period was less severe and significantly different from the pre-PPNO period (p = 0.027). Within the stages, there were 2.6% more individuals remaining in 3a in the post-period (95% confidence interval [CI], 1.5% to 3.8%; P value < 0.00001). Progression from 3a to 3b was 2.2% less in the post-period (95% [CI], 0.7% to 3.6%; P value = 0.0017), 3a to 4/5 was 0.2% less (95% CI, 0.0% to 0.87%; P value = 0.26), and 3a to ESRD was 0.24% less (95% CI, 0.0% to 0.66%, P value = 0.10).

Conclusions

Proactive, population-based nephrologist oversight was associated with a statistically significant decrease in progression. With enabling health information technology, risk stratification and targeted intervention by collaborative primary and specialty care achieves population-level care improvements. This model may be applicable to other chronic conditions.
Kinetic study of Pt nanocrystal deposition on Ag nanowires with clean surfaces via galvanic replacement
Authors: Shen Yu-Lin , Chen Shih-Yun , Song Jenn-Ming , Chen In-Gann
Published: August 2012

Without using any templates or surfactants, this study develops a high-yield process to prepare vertical Ag-Pt core-shell nanowires (NWs) by thermally assisted photoreduction of Ag NWs and successive galvanic replacement between Ag and Pt ions. The clean surface of Ag nanowires allows Pt ions to reduce and deposit on it and forms a compact sheath comprising Pt nanocrystals. The core-shell structural feature of the NWs thus produced has been demonstrated via transmission electron microscopy observation and Auger electron spectroscopy elemental analysis. Kinetic analysis suggests that the deposition of Pt is an interface-controlled reaction and is dominated by the oxidative dissolution of Ag atoms. The boundaries in between Pt nanocrystals may act as microchannels for the transport of Ag ions during galvanic replacement reactions.
Liposomal clodronate selectively eliminates microglia from primary astrocyte cultures
Authors: Kumamaru Hiromi , Saiwai Hirokazu , Kobayakawa Kazu , Kubota Kensuke , van Rooijen Nico , Inoue Kazuhide , Iwamoto Yukihide , Okada Seiji
Published: August 2012

Background

There is increasing interest in astrocyte biology because astrocytes have been demonstrated to play prominent roles in physiological and pathological conditions of the central nervous system, including neuroinflammation. To understand astrocyte biology, primary astrocyte cultures are most commonly used because of the direct accessibility of astrocytes in this system. However, this advantage can be hindered by microglial contamination. Although several authors have warned regarding microglial contamination in this system, complete microglial elimination has never been achieved.

Methods

The number and proliferative potential of contaminating microglia in primary astrocyte cultures were quantitatively assessed by immunocytologic and flow cytometric analyses. To examine the utility of clodronate for microglial elimination, primary astrocyte cultures or MG-5 cells were exposed to liposomal or free clodronate, and then immunocytologic, flow cytometric, and gene expression analyses were performed. The gene expression profiles of microglia-eliminated and microglia-contaminated cultures were compared after interleukin-6 (IL-6) stimulation.

Results

The percentage of contaminating microglia exceeded 15% and continued to increase because of their high proliferative activity in conventional primary astrocyte cultures. These contaminating microglia were selectively eliminated low concentration of liposomal clodronate. Although primary microglia and MG-5 cells were killed by both liposomal and free clodronate, free clodronate significantly affected the viability of astrocytes. In contrast, liposomal clodronate selectively eliminated microglia without affecting the viability, proliferation or activation of astrocytes. The efficacy of liposomal clodronate was much higher than that of previously reported methods used for decreasing microglial contamination. Furthermore, we observed rapid tumor necrosis factor-α and IL-1b gene induction in conventional primary astrocyte cultures after IL-6 stimulation, which was due to the activation of the Janus kinase/signal transducer and activator of the transcription pathway in contaminating microglia.

Conclusions

Because contaminating microglia could result in erroneous data regarding the pro-inflammatory properties of astrocytes, astrocyte biology should be studied in the absence of microglial contamination. Our simple method will be widely applicable to experimental studies of astrocyte biology and provide clues for understanding the role of astrocytes in neural development, function and disease.
Salmonella aortitis treated with endovascular aortic repair: a case report
Authors: Strahm Carol , Lederer Heidi , Schwarz Esther I , Bachli Esther B
Published: August 2012

Introduction

Salmonella is a typical cause of aortitis, which is associated with high morbidity and mortality. In infrarenal disease, besides open surgery, endovascular aortic repair as an alternative treatment has been reported. To the best of our knowledge, we report the first successful endovascular aortic repair documented by necropsy to date.

Case presentation

A 67-year-old Caucasian man presented with low back pain, fever and positive blood cultures for Salmonella Enteritidis. A computed tomography scan showed an enlargement and intramural hematoma of the infrarenal aortic wall; a Salmonella aortitis was suspected and antimicrobial therapy initiated. Because of substantial comorbidities, endovascular aortic repair was favored over open surgery; postoperatively the antibiotic treatment was continued for 12 months. Post-mortem there were neither macroscopic nor microscopic signs of aortitis or graft infection.

Conclusions

We could demonstrate by necropsy that endovascular aortic repair of infrarenal aortitis with prolonged pre- and postinterventional antibiotic therapy for 12 months was a minimally invasive alternative and should be considered in selected clinically stable patients with substantial co-morbidities.
Identification and profiling of circulating antigens by screening with the sera from schistosomiasis japonica patients
Authors: Lu Yan , Xu Bin , Ju Chuan , Mo Xiaojin , Chen Shenbo , Feng Zheng , Wang Xiaoning , Hu Wei
Published: August 2012

Background

Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma. The disease remains a serious public health problem in endemic countries and affects at least 207 million people worldwide. A definite diagnosis of the disease plays a key role in the control of schistosomiasis. The detection of schistosome circulating antigens (CAs) is an effective approach to discriminate between previous exposure and current infection. Different methods have been investigated for detecting the CAs. However, the components of the schistosome CAs remain unclear. In this study, we analyzed the CAs in sera of patients infected with Schistosoma japonicum.

Methods

The parasites were collected from the infected rabbits for preparing the adult worm antigen (AWA). The hyline hens were immunized subcutaneously with AWA to produce anti-AWA IgY. The IgY was purified by water-dilution and ammonium sulfate precipitation method and identified by ELISA and Western blotting. After purification and characterization, IgY was immobilized onto the resin as a capture antibody. The circulating antigens were immune-precipitated from patients′ serum samples by direct immunoprecipitation. The precipitated proteins were separated by one-dimensional electrophoresis and analyzed by LC-MS/MS.

Results

Firstly, the IgY against AWA was produced from the eggs of immunized hens by AWA, which gave a titer of 1:12800. The purified IgY was used as the capture antibody to enrich the CAs in sera of S. japonicum infected patients through immunoprecipitation. The CAs were determined by LC-MS/MS. There were four proteins, including protein BUD31 homolog, ribonuclease, SJCHGC06971 protein and SJCHGC04754 protein, which were identified among the CAs.

Conclusions

We developed a novel method based on IgY for identification and profiling CAs in sera of S. japonicum infected patients. Four new CAs were identified and have potential value for further development of an antigen assay.
Comparison of variations between percentage of body fat, body mass index and daily physical activity among young Japanese and Thai female students
Authors: Morinaka Tomoko , Limtrakul Porn-ngarm , Makonkawkeyoon Luksana , Sone Yoshiaki
Published: August 2012

Background

In our series of investigations concerning the causes of seasonal change in fat accumulation in young university students, we could not find any contribution of seasonal variation in the ratio of carbohydrate and fat metabolism to that of body fat percentage in Japanese and Thai participants. After our previous study, we examined the effect of daily physical activity on body fat percentage to look for the major causes of seasonal change in fat accumulation in young university students.

Findings

In this study, we measured participants’ (young Japanese and Thai university students) daily physical activity by a uniaxial accelerometer in addition to the measurements of body fat percentage and body mass index by a bioelectrical impedance meter. We found that there was significant and moderate negative correlation between body fat percentage and daily step counts among Japanese but not Thai participants. We observed significant, moderate and positive correlations between the percentage of body fat and body mass index among Japanese and Thai participants.

Conclusions

Daily physical activity plays an important role in the seasonal variation of body fat percentage of Japanese female students. Our present study also confirmed the importance of daily physical activity for controlling body mass index and for the prevention of obesity.
Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study
Authors: Mongardon Nicolas , Max Adeline , Bouglé Adrien , Pène Frédéric , Lemiale Virginie , Charpentier Julien , Cariou Alain , Chiche Jean-Daniel , Bedos Jean-Pierre , Mira Jean-Paul
Published: August 2012

Introduction

Community-acquired pneumonia (CAP) account for a high proportion of ICU admissions, with Streptococcus pneumoniae being the main pathogen responsible for these infections. However, little is known on the clinical features and outcomes of ICU patients with pneumococcal pneumonia. The aims of this study were to provide epidemiological data and to determine risk factors of mortality in patients admitted to ICU for severe S. pneumoniae CAP.

Methods

We performed a retrospective review of two prospectively-acquired multicentre ICU databases (2001-2008). Patients admitted for management of severe pneumococcal CAP were enrolled if they met the 2001 American Thoracic Society criteria for severe pneumonia, had life-threatening organ failure and had a positive microbiological sample for S. pneumoniae. Patients with bronchitis, aspiration pneumonia or with non-pulmonary pneumococcal infections were excluded.

Results

Two hundred and twenty two patients were included, with a median SAPS II score reaching 47 [36-64]. Acute respiratory failure (n = 154) and septic shock (n = 54) were their most frequent causes of ICU admission. Septic shock occurred in 170 patients (77%) and mechanical ventilation was required in 186 patients (84%); renal replacement therapy was initiated in 70 patients (32%). Bacteraemia was diagnosed in 101 patients. The prevalence of S. pneumoniae strains with decreased susceptibility to penicillin was 39.7%. Although antibiotherapy was adequate in 92.3% of cases, hospital mortality reached 28.8%. In multivariate analysis, independent risk factors for mortality were age (OR 1.05 (95% CI: 1.02-1.08)), male sex (OR 2.83 (95% CI: 1.16-6.91)) and renal replacement therapy (OR 3.78 (95% CI: 1.71-8.36)). Co-morbidities, macrolide administration, concomitant bacteremia or penicillin susceptibility did not influence outcome.

Conclusions

In ICU, mortality of pneumococcal CAP remains high despite adequate antimicrobial treatment. Baseline demographic data and renal replacement therapy have a major impact on adverse outcome.
A delayed diagnosis of acute myocarditis: diagnostic value of cardiovascular magnetic resonance imaging
Authors: Lee P T , Japp A , Payne J R
Published: August 2012

Acute myocarditis is an inflammatory disorder of the myocardium associated with cardiac dysfunction. The definition of myocarditis varies, but the Dallas criteria for myocarditis requires an inflammatory infiltrate and associated myocyte necrosis or damage not characteristic of an ischaemic event. Here we present a case of acute myocarditis in a 48-year-old woman masquerading as acute coronary syndrome. Patients with myocarditis usually have normal coronary arteries and we discuss diagnostic difficulties when it presents with ‘true’ acute coronary syndrome. In this case, cardiovascular magnetic resonance played an important role in the diagnosis of our patient and follow-up.
Ribosomal proteins L7 and L8 function in concert with six A3 assembly factors to propagate assembly of domains I and II of 25S rRNA in yeast 60S ribosomal subunits
Authors: Jakovljevic Jelena , Ohmayer Uli , Gamalinda Michael , Talkish Jason , Alexander Lisa , Linnemann Jan , Milkereit Philipp , Woolford John L.
Published: August 2012

Ribosome biogenesis is a complex multistep process that involves alternating steps of folding and processing of pre-rRNAs in concert with assembly of ribosomal proteins. Recently, there has been increased interest in the roles of ribosomal proteins in eukaryotic ribosome biogenesis in vivo, focusing primarily on their function in pre-rRNA processing. However, much less is known about participation of ribosomal proteins in the formation and rearrangement of preribosomal particles as they mature to functional subunits. We have studied ribosomal proteins L7 and L8, which are required for the same early steps in pre-rRNA processing during assembly of 60S subunits but are located in different domains within ribosomes. Depletion of either leads to defects in processing of 27SA3 to 27SB pre-rRNA and turnover of pre-rRNAs destined for large ribosomal subunits. A specific subset of proteins is diminished from these residual assembly intermediates: six assembly factors required for processing of 27SA3 pre-rRNA and four ribosomal proteins bound to domain I of 25S and 5.8S rRNAs surrounding the polypeptide exit tunnel. In addition, specific sets of ribosomal proteins are affected in each mutant: In the absence of L7, proteins bound to domain II, L6, L14, L20, and L33 are greatly diminished, while proteins L13, L15, and L36 that bind to domain I are affected in the absence of L8. Thus, L7 and L8 might establish RNP structures within assembling ribosomes necessary for the stable association and function of the A3 assembly factors and for proper assembly of the neighborhoods containing domains I and II.
Planning a Pharmacy-Led Medical Mission Trip, Part 4: An Exploratory Study of Student Experiences
Authors: Brown Dana A , Fairclough Jamie L , Ferrill Mary J
Published: August 2012

This article is an evaluation of data collected from both Advanced Pharmacy Practice Experience (APPE) and non-APPE student participants on Gregory School of Pharmacy mission trips during the summer of 2011. Specifically, it examines the issue of professionalism and the personal impact that mission trips may have on pharmacy students. It is the fourth in a 4-part series on pharmacist-led medical mission trips.

BACKGROUND:

At the Gregory School of Pharmacy (GSOP), pharmacy students routinely participate in domestic and international medical mission trips. Participation can be for academic credit as part of final-year Advanced Pharmacy Practice Experiences (APPEs) or as required community service hours. These mission experiences could potentially result in both professional and personal transformations for participating students.

OBJECTIVE:

To evaluate data collected from GSOP pharmacy students regarding their experiences on the medical mission field in 2011 and how that participation has impacted the students professionally and personally.

METHODS:

GSOP students participating in an international or domestic medical mission trip in the summer of 2011 were asked to voluntarily complete pre- and posttrip surveys.

RESULTS:

Of the 68 final-year APPE students and student volunteers who participated in a summer 2011 GSOP medical mission trip, 36 (53%) completed pre- and posttrip surveys. The mission trips significantly impacted students' beliefs regarding better preparation to care for the medical needs of patients, identification of others' needs, understanding team dynamics, perceptions about the value of patient care, and comfort level with the provision of medical and pharmaceutical care in a foreign country. However, there were no statistically significant improvements in students' perceptions of their ability to care for the emotional needs of patients, the importance of team unity, and their level of respect for team members; their ability to lead or participate in future trips; and their belief that participating preceptors and faculty serve as effective role models of servant leaders.

CONCLUSIONS:

Based on the findings from this exploratory study, participation in a domestic or international medical mission trip as a student volunteer or APPE student appears to have a positive impact on some of the beliefs and perceptions of GSOP students. By continuing to follow these particular students and similar cohorts of students in the future, further insight may be gained regarding the long-term impact of medical mission experiences during pharmacy school training.
1,4:3,6-Dianhydrohexitols: Original platform for the design of biobased polymers using robust, efficient, and orthogonal chemistry
Authors: Raytchev Pascal Dimitrov , Besset Céline , Fleury Etienne , Pascault Jean-Pierre , Bernard Julien , Drockenmuller Eric
Published: August 2012

1,4:3,6-Dianhydrohexitols (DAHs) are nontoxic and sustainable diols that have been extensively applied as monomers for the preparation of polymer materials by step-growth polymerization processes. The presence of two reactive alcohol groups was exploited to design a library of symmetric and asymmetric stereocontrolled alkyne- and/or azide-functionalized AA/BB and AB monomers suitable for thermal or copper(I)-catalyzed azide-alkyne cycloaddition (TAAC and CuAAC). Step-growth polymerization of these monomers yielded a series of linear polytriazoles as well as partially biosourced networks using a combination of AB + A2B2 derivatives. Characterization of the resulting materials allowed for the establishment of a thorough structure–property relationship emphasizing the impact of monomer stereochemistry and cycloaddition regioselectivity on materials properties.
Noninvasive Prenatal Diagnosis of Monogenic Diseases by Targeted Massively Parallel Sequencing of Maternal Plasma: Application to β-Thalassemia
Authors: Lam Kwan-Wood G , Jiang Peiyong , Liao Gary J W , Chan K C Allen , Leung Tak Y , Chiu Rossa W K , Lo Y M Dennis
Published: August 2012

BACKGROUND

A genomewide genetic and mutational profile of a fetus was recently determined via deep sequencing of maternal plasma DNA. This technology could have important applications for noninvasive prenatal diagnosis (NIPD) of many monogenic diseases. Relative haplotype dosage (RHDO) analysis, a core step of this procedure, would allow one to elucidate the maternally inherited half of the fetal genome. For clinical applications, the cost and complexity of data analysis might be reduced via targeted application of this approach to selected genomic regions containing disease-causing genes. There is thus a need to explore the feasibility of performing RHDO analysis in a targeted manner.

METHODS

We performed target enrichment by using solution-phase hybridization followed by massively parallel sequencing of the β-globin gene region in 2 families undergoing prenatal diagnosis for β-thalassemia. We used digital PCR strategies to physically deduce parental haplotypes. Finally, we performed RHDO analysis with target-enriched sequencing data and parental haplotypes to reveal the β-thalassemic status for the fetuses.

RESULTS

A mean sequencing depth of 206-fold was achieved in the β-globin gene region by targeted sequencing of maternal plasma DNA. RHDO analysis was successful for the sequencing data obtained from the target-enriched samples, including a region in one of the families in which the parents had similar haplotype structures. Data analysis revealed that both fetuses were heterozygous carriers of β-thalassemia.

CONCLUSIONS

Targeted sequencing of maternal plasma DNA for NIPD of monogenic diseases is feasible.
Response Properties of Local Field Potentials and Neighboring Single Neurons in Awake Primary Visual Cortex
Authors: Lashgari Reza , Li Xiaobing , Chen Yao , Kremkow Jens , Bereshpolova Yulia , Swadlow Harvey A. , Alonso Jose-Manuel
Published: August 2012

Recordings from local field potentials (LFPs) are becoming increasingly common in research and clinical applications, but we still have a poor understanding of how LFP stimulus selectivity originates from the combined activity of single neurons. Here, we systematically compared the stimulus selectivity of LFP and neighboring single-unit activity (SUA) recorded in area primary visual cortex (V1) of awake primates. We demonstrate that LFP and SUA have similar stimulus preferences for orientation, direction of motion, contrast, size, temporal frequency, and even spatial phase. However, the average SUA had 50 times better signal-to-noise, 20% higher contrast sensitivity, 45% higher direction selectivity, and 15% more tuning depth than the average LFP. Low LFP frequencies (<30 Hz) were most strongly correlated with the spiking frequencies of neurons with nonlinear spatial summation and poor orientation/direction selectivity that were located near cortical current sinks (negative LFPs). In contrast, LFP gamma frequencies (>30 Hz) were correlated with a more diverse group of neurons located near cortical sources (positive LFPs). In summary, our results indicate that low- and high-frequency LFP pool signals from V1 neurons with similar stimulus preferences but different response properties and cortical depths.
TMEM106B, the Risk Gene for Frontotemporal Dementia, Is Regulated by the microRNA-132/212 Cluster and Affects Progranulin Pathways
Authors: Chen-Plotkin Alice S. , Unger Travis L. , Gallagher Michael D. , Bill Emily , Kwong Linda K. , Volpicelli-Daley Laura , Busch Johanna I. , Akle Sebastian , Grossman Murray , Van Deerlin Vivianna , Trojanowski John Q. , Lee Virginia M.-Y.
Published: August 2012

Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is a fatal neurodegenerative disease with no available treatments. Mutations in the progranulin gene (GRN) causing impaired production or secretion of progranulin are a common Mendelian cause of FTLD-TDP; additionally, common variants at chromosome 7p21 in the uncharacterized geneTMEM106Bwere recently linked by genome-wide association to FTLD-TDP with and withoutGRNmutations. Here we show thatTMEM106Bis neuronally expressed in postmortem human brain tissue, and that expression levels are increased in FTLD-TDP brain. Furthermore, using an unbiased, microarray-based screen of >800 microRNAs (miRs), we identify microRNA-132 as the top microRNA differentiating FTLD-TDP and control brains, with <50% normal expression levels of three members of the microRNA-132 cluster (microRNA-132, microRNA-132*, and microRNA-212) in disease. Computational analyses, corroborated empirically, demonstrate that the top mRNA target of both microRNA-132 and microRNA-212 isTMEM106B; both microRNAs repress TMEM106B expression through shared microRNA-132/212 binding sites in theTMEM106B3′UTR. Increasing TMEM106B expression to model disease results in enlargement and poor acidification of endo-lysosomes, as well as impairment of mannose-6-phosphate-receptor trafficking. Finally, endogenous neuronal TMEM106B colocalizes with progranulin in late endo-lysosomes, and TMEM106B overexpression increases intracellular levels of progranulin. Thus,TMEM106Bis an FTLD-TDP risk gene, with microRNA-132/212 depression as an event which can lead to aberrant overexpression of TMEM106B, which in turn alters progranulin pathways. Evidence for this pathogenic cascade includes the striking convergence of two independent, genomic-scale screens on a microRNA:mRNA regulatory pair. Our findings open novel directions for elucidating miR-based therapies in FTLD-TDP.
Post-Translational Oxidative Modification and Inactivation of Mitochondrial Complex I in Epileptogenesis
Authors: Ryan Kristen , Backos Donald S. , Reigan Philip , Patel Manisha
Published: August 2012

Mitochondrial oxidative stress and damage have been implicated in the etiology of temporal lobe epilepsy, but whether or not they have a functional impact on mitochondrial processes during epilepsy development (epileptogenesis) is unknown. One consequence of increased steady-state mitochondrial reactive oxygen species levels is protein post-translational modification (PTM). We hypothesize that complex I (CI), a protein complex of the mitochondrial electron transport chain, is a target for oxidant-induced PTMs, such as carbonylation, leading to impaired function during epileptogenesis. The goal of this study was to determine whether oxidative modifications occur and what impact they have on CI enzymatic activity in the rat hippocampus in response to kainate (KA)-induced epileptogenesis. Rats were injected with a single high dose of KA or vehicle and evidence for CI modifications was measured during the acute, latent, and chronic stages of epilepsy. Mitochondrial-specific carbonylation was increased acutely (48 h) and chronically (6 week), coincident with decreased CI activity. Mass spectrometry analysis of immunocaptured CI identified specific metal catalyzed carbonylation to Arg76 within the 75 kDa subunit concomitant with inhibition of CI activity during epileptogenesis. Computational-based molecular modeling studies revealed that Arg76 is in close proximity to the active site of CI and carbonylation of the residue is predicted to induce substantial structural alterations to the protein complex. These data provide evidence for the occurrence of a specific and irreversible oxidative modification of an important mitochondrial enzyme complex critical for cellular bioenergetics during the process of epileptogenesis.
State-Dependent Modulation of Breathing in Urethane-Anesthetized Rats
Authors: Pagliardini Silvia , Greer John J. , Funk Gregory D. , Dickson Clayton T.
Published: August 2012

Respiratory activity is most fragile during sleep, in particular during paradoxical [or rapid eye movement (REM)] sleep and sleep state transitions. Rats are commonly used to study respiratory neuromodulation, but rodent sleep is characterized by a highly fragmented sleep pattern, thus making it very challenging to examine different sleep states and potential pharmacological manipulations within them. Sleep-like brain-state alternations occur in rats under urethane anesthesia and may be an effective and efficient model for sleep itself. The present study assessed state-dependent changes in breathing and respiratory muscle modulation under urethane anesthesia to determine their similarity to those occurring during natural sleep. Rats were anesthetized with urethane and respiratory airflow, as well as electromyographic activity in respiratory muscles were recorded in combination with local field potentials in neocortex and hippocampus to determine how breathing pattern and muscle activity are modulated with brain state. Measurements were made in normoxic, hypoxic, and hypercapnic conditions. Results were compared with recordings made from rats during natural sleep. Brain-state alternations under urethane anesthesia were closely correlated with changes in breathing rate and variability and with modulation of respiratory muscle tone. These changes closely mimicked those observed in natural sleep. Of great interest was that, during both REM and REM-like states, genioglossus muscle activity was strongly depressed and abdominal muscle activity showed potent expiratory modulation. We demonstrate that, in urethane-anesthetized rats, respiratory airflow and muscle activity are closely correlated with brain-state transitions and parallel those shown in natural sleep, providing a useful model to systematically study sleep-related changes in respiratory control.
Spontaneous Brain Activity Relates to Autonomic Arousal
Authors: Fan Jin , Xu Pengfei , Van Dam Nicholas T. , Eilam-Stock Tehila , Gu Xiaosi , Luo Yue-jia , Hof Patrick R.
Published: August 2012

Although possible sources and functions of the resting-state networks (RSNs) of the brain have been proposed, most evidence relies on circular logic and reverse inference. We propose that autonomic arousal provides an objective index of psychophysiological states during rest that may also function as a driving source of the activity and connectivity of RSNs. Recording blood oxygenation level-dependent (BOLD) signal using functional magnetic resonance imaging and skin conductance simultaneously during rest in human subjects, we found that the spontaneous fluctuations of BOLD signals in key nodes of RSNs are associated with changes in nonspecific skin conductance response, a sensitive psychophysiological index of autonomic arousal. Our findings provide evidence of an important role for the autonomic nervous system to the spontaneous activity of the brain during “rest.”