bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre‐emptive epidural analgesia improves post‐operative pain and immune function in patients undergoing thoracotomy
Authors: Yang Chengzhi , Chang Hao , Zhang Tiewa , Liang Chao , Li Enyou
Published: July 2014

Background

Pre‐emptive analgesia may relieve post‐operative pain. However, its effects on immune function of patients undergoing thoracotomy are still unclear. Therefore, we investigated effects of pre‐emptive epidural analgesia on post‐operative pain and immune function in patients undergoing thoracotomy.

Methods

Ninety patients undergoing thoracotomy were randomized equally into three groups. Group A (control) only received patient‐controlled epidural analgesia (PCEA). Group B (routine) was given 0.125% ropivacaine 6 mL 30 min after surgery, then PCEA. Group C (pre‐emptive) received 0.125% ropivacaine 6 mL 30 min before skin incision and every 60 min during surgery, then PCEA. Visual analogue scale scores and cytokine levels were the main outcomes. Secondary outcomes included analgesic demands, side effects and hospital stays.

Results

Post‐operative visual analogue scale scores were decreased in group C compared with group B, and that of group B were lower than in group A (P < 0.05). Compared with group B, protein and mRNA expressions of tumour necrosis factor‐α, interleukin (IL)‐6 and IL‐8 were decreased, and that of IL‐4 were increased in group C (P = 0.002∼0.049). Both analgesic demands and the incidences of nausea/vomiting and hypotension were lower in group C compared with group B (P = 0.01∼0.037). Hospital stays were shorter in group C compared with group B (P = 0.045).

Conclusions

These findings suggest that pre‐emptive epidural analgesia can produce better analgesia effects, with less analgesic demands and side effects, and attenuate the surgery‐induced immune alterations, and improve the post‐operative recovery in patients undergoing thoracotomy.
Hemodialysis‐Specific Factors Associated With Salivary Flow Rates
Authors: Marques Paulo Leonardo Ponte , Libório Alexandre Braga , de Lima Saintrain Maria Vieira
Published: July 2014

The saliva is important to maintain the integrity of tissues and teeth, besides having microbial activity. Hemodialysis (HD) patients usually have reduced salivary flow rate (SFR) and are exposed to all its associated complications. The aim of the present study was to identify HD‐related factors associated with reduced SFR. A cross‐sectional study was performed with maintenance HD patients. Stimulated whole saliva was collected before and after HD. Xerostomia was assessed through the validated xerostomia inventory and thirst through the dialysis thirst inventory. Parameters of dental health status were obtained by the decayed, missed, and filled teeth index and community periodontal index. One hundred twenty‐eight patients (66 males) participated in this study. Stimulated SFR before HD was 0.38 ± 0.28 mL/min. In univariate analysis and after adjusting for several factors, serum urea before HD session, serum intact parathormone (iPTH), calcium‐phosphorus product (Ca×Pi), serum ferritin, and number of medications were negatively correlated with SFR in univariate analysis. Moreover, patients taking sevelamer had reduced SFR in comparison with those not receiving it (SFR 0.32 ± 0.19 vs. 0.44 ± 0.23 mL/min, P = 0.003). At multivariate analysis, including dialysis and nondialysis‐related factors, age, elevated pre‐HD serum urea, higher Ca×Pi product, higher iPTH, and sevelamer use remained as factors that were independently associated with a reduced SFR. After dialysis, there was a significant increment in SFR (0.39 ± 0.28 vs. 0.60 ± 0.34 mL/min, P < 0.001). Several HD‐related features were associated with reduced SFR, including serum urea, sevelamer use, and bone and mineral disorders markers.
Reduced activities of phospholipases A2 in platelets of drug‐naïve bipolar disorder patients
Authors: Ikenaga Eliza Hiromi , Talib Leda Leme , Ferreira Aline Siqueira , Machado‐Vieira Rodrigo , Forlenza Orestes Vicente , Gattaz Wagner F
Published: July 2014

Objective

Phospholipases A2 (PLA2) comprise a family of hydrolytic enzymes that cleave membrane phospholipids and play a key role in cellular homeostasis. Alterations in enzymatic activity have been hypothesized in bipolar disorder (BD). Recent studies suggest that PLA2 activity in platelets may reflect PLA2 activity in the brain. The aim of this study was to determine PLA2 activity in platelets of BD patients.

Methods

We determined the activity of PLA2 subtypes [extracellular, calcium‐dependent PLA2 (sPLA2), intracellular, calcium‐dependent PLA2 (cPLA2), and intracellular, calcium‐independent PLA2 (iPLA2)] by a radioenzymatic method in platelets from 20 patients with BD (15 drug‐naïve and five drug‐free) and from 16 age‐ and gender‐matched healthy controls.

Results

We found that iPLA2, cPLA2, and sPLA2 activities were lower in drug‐naïve patients with BD when compared to the control group (p = 0.017, p < 0.001, and p < 0.001, respectively).

Conclusions

Reduced PLA2 activity at the early stage of BD may disrupt brain function and increase the risk for the disease. Moreover, epidemiological studies show that patients with BD have a fivefold increased risk for developing Alzheimer's disease. Because patients with Alzheimer's disease also have reduced PLA2 activity, the present finding of reduced PLA2 in the BD group may be related to the risk factor for these individuals developing Alzheimer's disease in advanced age.
A novel canine model of immune thrombocytopenia: has immune thrombocytopenia (ITP) gone to the dogs?
Authors: LeVine Dana N. , Birkenheuer Adam J. , Brooks Marjory B. , Nordone Shila K. , Bellinger Dwight A. , Jones Sam L. , Fischer Thomas H. , Oglesbee Stephen E. , Frey Kahlina , Brinson Nicole S. , Peters Allison P. , Marr Henry S. , Motsinger‐Reif Alison , Gudbrandsdottir Sif , Bussel James B. , Key Nigel S.
Published: July 2014

Canine immune thrombocytopenia (ITP) is analogous to human ITP, with similar platelet counts and heterogeneity in bleeding phenotype among affected individuals. With a goal of ultimately investigating this bleeding heterogeneity, a canine model of antibody‐mediated ITP was developed. Infusion of healthy dogs with 2F9, a murine IgG2a monoclonal antibody to the canine platelet glycoprotein GPIIb (a common target of autoantibodies in ITP) resulted in profound, dose‐dependent thrombocytopenia. Model dogs developed variable bleeding phenotypes, e.g. petechiae and haematuria, despite similar degrees of thrombocytopenia. 2F9 infusion was not associated with systemic inflammation, consumptive coagulopathy, or impairment of platelet function. Unexpectedly however, evaluation of cytokine profiles led to the identification of platelets as a potential source of serum interleukin‐8 (IL8) in dogs. This finding was confirmed in humans with ITP, suggesting that platelet IL8 may be a previously unrecognized modulator of platelet‐neutrophil crosstalk. The utility of this model will allow future study of bleeding phenotypic heterogeneity including the role of neutrophils and endothelial cells in ITP.
Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma
Authors: Westin Jason R. , McLaughlin Peter , Romaguera Jorge , Hagemeister Fredrick B. , Pro Barbara , Dang Nam H. , Samaniego Felipe , Rodriguez Maria A. , Fayad Luis , Oki Yasuhiro , Fanale Michelle , Fowler Nathan , Nastoupil Loretta , Feng Lei , Loyer Evelyn , Younes Anas
Published: July 2014

Relapsed aggressive lymphomas are often treated with platinum‐based chemotherapy (PBC) followed by an autologous stem cell transplant (ASCT). Response rates to PBC in patients with relapsed aggressive lymphomas are c. 60%, and non‐responders have a dismal prognosis. Novel therapies for aggressive lymphomas, including those failing PBC, are needed. We performed a phase II study of paclitaxel, topotecan and rituximab (TTR) in patients with relapsed or refractory diffuse large B‐cell, follicular grade IIIB, or transformed lymphomas, including those who previously failed PBC. The median age of the 72 patients enrolled was 54 years. Responding patients were offered ASCT after two courses. The overall response rate was 69% for all patients (n = 49/71) and 45% for those who previously failed PBC (n = 9/20). With a median follow up of 125 months for the censored observations, the overall survival (OS) and progression‐free survival at 5 years was 39% and 27%, respectively. Responding patients who received ASCT had an OS of 63% at 5 years. Our results demonstrate that TTR is an effective salvage regimen for patients with relapsed aggressive B‐cell lymphomas, including those who previously failed PBC. Given the declining therapeutic outcomes of salvage PBC in the rituximab era, further evaluation of TTR is warranted.
Prenatal molecular diagnosis of X‐linked hydrocephalus via a silent C924T mutation in the L1CAM gene
Authors: Serikawa Takehiro , Nishiyama Kenichi , Tohyama Jun , Tazawa Ryushi , Goto Kiyoe , Kuriyama Yoko , Haino Kazufumi , Kanemura Yonehiro , Yamasaki Mami , Nakata Koh , Takakuwa Koichi , Enomoto Takayuki
Published: July 2014

We present a case of a patient whose L1CAM gene in X‐chromosome has a C924T transition. Her first son's ventriculomegaly was prenatally detected. A mature infant was born, his head circumference was large, and thumbs were bilaterally adducted. X‐linked hydrocephalus (XLH) was suspected. The DNA examination revealed that both her and boy's LICAM gene had a C924T transition. She became pregnant 5 years later and amniocentesis was performed. The results of cytogenetic analysis revealed that the fetus was female. She continued her pregnancy and delivered a healthy girl. She again became pregnant 3 years later. The chromosomal analysis revealed that the fetus was male. Fetal DNA analysis determined that the fetus had the inherited mutation. She chose to terminate the pregnancy. A C924T mutation can be disease causing for XLH, and the detection of this mutation would aid in genetic counseling for the prenatal diagnosis of XLH.
Dietary intake of high‐dose biotin inhibits spermatogenesis in young rats
Authors: Sawamura Hiromi , Ikeda Chieko , Shimada Ryoko , Yoshii Yui , Watanabe Toshiaki
Published: July 2014

To characterize a new function of the water‐soluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE‐2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair‐fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair‐fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose‐dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long‐term intake of high‐dose biotin inhibited spermatogenesis in young male rats.
Signaling regulating inner ear development: Cell fate determination, patterning, morphogenesis, and defects
Authors: Nakajima Yuji
Published: July 2014

The membranous labyrinth of the inner ear is a highly complex organ that detects sound and balance. Developmental defects in the inner ear cause congenital hearing loss and balance disorders. The membranous labyrinth consists of three semicircular ducts, the utricle, saccule, and endolymphatic ducts, and the cochlear duct. These complex structures develop from the simple otic placode, which is established in the cranial ectoderm adjacent to the neural crest at the level of the hindbrain at the early neurula stage. During development, the otic placode invaginates to form the otic vesicle, which subsequently gives rise to neurons for the vestibulocochlear ganglion, the non‐sensory and sensory epithelia of the membranous labyrinth that includes three ampullary crests, two maculae, and the organ of Corti. Combined paracrine and autocrine signals including fibroblast growth factor, Wnt, retinoic acid, hedgehog, and bone morphogenetic protein regulate fate determination, axis formation, and morphogenesis in the developing inner ear. Juxtacrine signals mediated by Notch pathways play a role in establishing the sensory epithelium, which consists of mechanosensory hair cells and supporting cells. The highly differentiated organ of Corti, which consists of uniformly oriented inner/outer hair cells and specific supporting cells, develops during fetal development. Developmental alterations/arrest causes congenital malformations in the inner ear in a spatiotemporal‐restricted manner. A clearer understanding of the mechanisms underlying inner ear development is important not only for the management of patients with congenital inner ear malformations, but also for the development of regenerative therapy for impaired function.
In vitro assessment of artifacts induced by titanium, titanium–zirconium and zirconium dioxide implants in cone‐beam computed tomography
Authors: Sancho‐Puchades Manuel , Hämmerle Christoph H. F. , Benic Goran I.
Published: July 2014

Aim

The aim of this study was to test whether or not the intensity of artifacts around implants in cone‐beam computed tomography (CBCT) differs between titanium, titanium–zirconium and zirconium dioxide implants.

Materials and methods

Twenty models of a human mandible, each containing one implant in the single‐tooth gap position 45, were cast in dental stone. Five test models were produced for each of the following implant types: titanium 4.1 mm diameter (Ti4.1), titanium 3.3 mm diameter (Ti3.3), titanium–zirconium 3.3 mm diameter (TiZr3.3) and zirconium dioxide 3.5–4.5 mm diameter (ZrO3.5–4.5) implants. For control purposes, three models without implants were produced. Each model was scanned using a CBCT device. Gray values (GV) were recorded at eight circumferential positions around the implants at 0.5 mm, 1 mm and 2 mm from the implant surface (GVTest). GV were assessed in the corresponding volumes of interest (VOI) in the control models without implants (GVControl). Differences of gray values (ΔGV) between GVTest and GVControl were calculated as percentages. One‐way ANOVA and post hoc tests were applied to detect differences between implant types.

Results

Mean ΔGV for ZrO3.5–4.5 presented the highest absolute values, generally followed by TiZr3.3, Ti4.1 and Ti3.3 implants. The differences of ΔGV between ZrO3.5–4.5 and the remaining groups were statistically significant in the majority of the VOI (P ≤ 0.0167). ΔGV for TiZr3.3, Ti4.1 and Ti3.3 implants did not differ significantly in the most VOI. For all implant types, ΔGV showed positive values buccally, mesio‐buccally, lingually and disto‐lingually, whereas negative values were detected mesially and distally.

Conclusions

Zirconium dioxide implants generate significantly more artifacts as compared to titanium and titanium–zirconium implants. The intensity of artifacts around zirconium dioxide implants exhibited in average the threefold in comparison with titanium implants.
Comparable cytological features between cells processed as either wet mount or conventional cytospins
Authors: Mojica W. D. , Chen F.
Published: July 2014

Objective

Microfluidics represents a novel approach for the processing of pathological biopsy specimens. It represents an enabling platform between traditional morphology‐driven pathology diagnostics and future sequencing technologies. Microfluidics requires the dissociation of cells from tissue, but the evaluation of these cells still lies within the domain of pathology, specifically cytopathology. The dissociated cells, however, require supravital staining and examination under wet mount conditions as part of their processing in a microfluidic platform. These conditions are vastly different from current approaches for cytopathological specimen preparation. No studies to date have compared the cytological characteristics of cells between these two different conditions.

Methods

Slivers of different types of unfixed tissue were procured and the cells were dissociated. The cells were recovered and separated for processing either by staining with a supravital dye and examination under wet mount conditions or by conventional preparatory methods and staining by the Papanicolaou method.

Results

Obvious differences existed in the tinctorial hue between similar cells stained by the two different methods; however, there were no significant differences in the features between the matched cells. Some cells in the wet mount preparations existed in three‐dimensional balls, reducing the quality of the images relative to cells flattened to the slide by the cytospin method.

Conclusions

Cells stained with a supravital stain and examined in a wet mount environment appear to be cytologically similar to cells prepared by conventional methods. Long‐established criteria for the evaluation of cells prepared by established protocols can therefore be extended and applied to cells viewed within a microfluidic platform.
Dipyridamole‐induced headache and lower recurrence risk in secondary prevention of ischaemic stroke: a post hoc analysis
Authors: Davidai G. , Cotton D. , Gorelick P. , Bath P. M. W. , Lipton R. B. , Sacco R. , Diener H.‐C.
Published: July 2014

Background and purpose

Our objective was to investigate the association between recurrent stroke risk and headache induced by extended‐release dipyridamole (ER‐DP) when administered alone or with low‐dose aspirin (ASA+ER‐DP).

Methods

This was a post hoc analysis of prospectively collected data on recurrent stroke risk and headache as an adverse event or reason for treatment discontinuation from the PRoFESS (N = 20 332) and ESPS2 (N = 6602) trials. Hazard ratios (HRs) for recurrent stroke were calculated using the Cox model.

Results

In PRoFESS, the 2.5‐year recurrent stroke risk in patients receiving ASA+ER‐DP was 8.2% in those with headache within 7 days of starting treatment and 9.4% in those without [HR 0.85, 95% confidence interval (CI) 0.73–0.98; P = 0.03]. Recurrent stroke risk was 5.0% in patients who discontinued ASA+ER‐DP due to headache by day 90 versus 9.2% in those who did not (HR 0.52, 95% CI 0.35–0.77; P = 0.001). No such difference was observed in clopidogrel‐treated patients. In ESPS2, risk of recurrent stroke was 6.2% in patients who discontinued ASA+ER‐DP due to headache by day 90 versus 9.8% in patients who did not (HR 0.62, 95% CI 0.31–1.27; P = 0.19) and 7.3% in patients who discontinued ER‐DP due to headache by day 90 versus 13.2% in those who did not (HR 0.53, 95% CI 0.27–1.04; P = 0.06).

Conclusions

Patients taking ASA+ER‐DP in PRoFESS who developed headache had significantly reduced stroke recurrence risk versus those without headache. Similar (non‐significant) findings for ASA+ER‐DP and ER‐DP in ESPS2 suggest that dipyridamole‐induced headache may reflect better cerebrovascular function.
The effects of caffeine on wound healing
Authors: Ojeh Nkemcho , Stojadinovic Olivera , Pastar Irena , Sawaya Andrew , Yin Natalie , Tomic‐Canic Marjana
Published: July 2014

The purine alkaloid caffeine is a major component of many beverages such as coffee and tea. Caffeine and its metabolites theobromine and xanthine have been shown to have antioxidant properties. Caffeine can also act as adenosine‐receptor antagonist. Although it has been shown that adenosine and antioxidants promote wound healing, the effect of caffeine on wound healing is currently unknown. To investigate the effects of caffeine on processes involved in epithelialisation, we used primary human keratinocytes, HaCaT cell line and ex vivo model of human skin. First, we tested the effects of caffeine on cell proliferation, differentiation, adhesion and migration, processes essential for normal wound epithelialisation and closure. We used 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) proliferation assay to test the effects of seven different caffeine doses ranging from 0·1 to 5 mM. We found that caffeine restricted cell proliferation of keratinocytes in a dose‐dependent manner. Furthermore, scratch wound assays performed on keratinocyte monolayers indicated dose‐dependent delays in cell migration. Interestingly, adhesion and differentiation remained unaffected in monolayer cultures treated with various doses of caffeine. Using a human ex vivo wound healing model, we tested topical application of caffeine and found that it impedes epithelialisation, confirming in vitro data. We conclude that caffeine, which is known to have antioxidant properties, impedes keratinocyte proliferation and migration, suggesting that it may have an inhibitory effect on wound healing and epithelialisation. Therefore, our findings are more in support of a role for caffeine as adenosine‐receptor antagonist that would negate the effect of adenosine in promoting wound healing.
Medical Infrared Imaging (Thermography) of Type I Thoracolumbar Disk Disease in Chondrodystrophic Dogs
Authors: Grossbard Brian P. , Loughin Catherine A. , Marino Dominic J. , Marino Leonard J. , Sackman Joseph , Umbaugh Scott E. , Solt Patrick S. , Afruz Jakia , Leando Peter , Lesser Martin L. , Akerman Meredith
Published: July 2014

Objective

To: (1) determine the success of medical infrared imaging (MII) in identifying dogs with TLIVDD, (2) compare MII localization with magnetic resonance imaging (MRI) results and surgical findings, and (3) determine if the MII pattern returns to that of normal dogs 10 weeks after decompression surgery.

Study Design

Prospective case series.

Animals

Chondrodystrophic dogs (n = 58) with Type I TLIVDD and 14 chondrodystrophic dogs with no evidence of TLIVDD.

Methods

Complete neurologic examination, MII, and MRI studies were performed on all dogs. Dogs with type I TLIVDD had decompressive surgery and follow‐up MII was performed at 10 weeks. Pattern analysis software was used to differentiate between clinical and control dogs, and statistical analysis using anatomic regions of interest on the dorsal views were used to determine lesion location. Recheck MII results were compared with control and pre‐surgical images.

Results

Computer recognition pattern analysis was 90% successful in differentiating normal dogs from dogs affected by TLIVDD and 97% successful in identifying the abnormal intervertebral disc space in dogs with TLIVDD. Statistical comparisons of the ROI mean temperature were unable to determine the location of the disc herniation. Recheck MII patterns did not normalize and more closely resembled the clinical group.

Conclusions

MII was 90% successful differentiating between normal dogs and 97% successful in identifying the abnormal intervertebral disc space in dogs with TLIVDD. Abnormal intervertebral disc space localization using ROI mean temperature analysis was not successful. MII patterns 10 weeks after surgery do not normalize.
Low testosterone syndrome protects subjects with high cardiovascular risk burden from major adverse cardiovascular events
Authors: Corona G. , Rastrelli G. , Maseroli E. , Fralassi N. , Sforza A. , Forti G. , Mannucci E. , Maggi M.
Published: July 2014

The role of testosterone (T) in the cardiovascular (CV) health of men is controversial. Some data suggest that hypogonadism is associated with CV mortality but not morbidity, however, recent evidence shows that hypogonadal subjects treated with T replacement therapy have a higher incidence of new CV events. The aim of this study is to analyse whether gonadal status might predict new CV event incidence according to a patient's previous history of CV events, in a cohort of subjects complaining of sexual dysfunction. A consecutive series of 1687 patients was followed‐up for a mean time of 4.3 ± 2.6 years for new occurrence of CV events, detecting 139 events. Hypogonadism (total T < 12 nmol/L) was not associated with an increased incidence of new CV events in the entire cohort. However, when considering patients with a previous history of CV events, hypogonadism was associated with a reduced risk of new CV events, even after adjusting for confounders (hazard ratios – HR = 0.498 [0.240; 0.996]; p = 0.049), whereas no relationship was observed in subjects free of previous CV events. Similar results were observed when reduced testis volume (TV) was considered as a predictor of new CV events in subjects with previous CV events (HR = 0.486 [0.257; 0.920]; p = 0.027). In patients with a history of previous CV events, but not in those without previous CV events, having both low T and low TV was associated with a lower incidence of new CV events as compared with subjects with only one or none of these conditions, even after adjusting for confounders (HR = 0.514 [0.306; 0.864]; p for trend < 0.02). Notably, CV risk estimated with risk engines based on traditional risk factors was not different between hypogonadal and eugonadal subjects. In conclusion, hypogonadism could be interpreted as a protective mechanism in unhealthy conditions, such as previous CV events, to avoid fatherhood and spare energy.
Synthesis and Photoluminescence of a Novel Green‐Emitting La5Si3O12N:Eu2+ Phosphor
Authors: Lu Fa‐Chun , Bai Li‐Jing
Published: July 2014

A novel green‐emitting La5Si3O12N:Eu2+ phosphor has been synthesized with the solid‐state reaction method under the high temperature, high pressure, and reducing atmosphere. This phosphor shows stable Eu2+ photoluminescence spectra. No Eu3+ line spectra have been found. For the emission band, an abnormal blue shift has been found. Concentration quenching occurs at Eu2+ concentration of 4 mol%. The photoluminescence property at high temperature was investigated. The physical mechanisms for blue shift, concentration quenching and thermal quenching were investigated and discussed. The proposed synthesis process could be a suitable method to acquire the stable Eu2+ photoluminescence in the trivalent metal cation compounds.
Glycosylated Hemoglobin Level Is Associated with Hearing Impairment in Older Japanese: The Kurabuchi Study
Authors: Michikawa Takehiro , Mizutari Kunio , Saito Hideyuki , Takebayashi Toru , Nishiwaki Yuji
Published: July 2014

Objectives

To examine the association between glycemic levels (glycosylated hemoglobin (HbA1c)) and hearing impairment in a general older population.

Design

Community‐based prospective longitudinal cohort study.

Setting

Kurabuchi Town, Gunma Prefecture, Japan.

Participants

Residents (N = 831; 350 men, 481 women) aged 65 and older were examined in 2005 and 2006 and analyzed in a cross‐sectional study. Residents without hearing impairment at baseline who participated in audiometric re‐examinations 4 years later were analyzed (n = 338).

Measurements

Hearing impairment was defined as failure to hear a 30‐dB signal at 1 kHz and a 40‐dB signal at 4 kHz in the better ear in pure‐tone audiometric tests.

Results

Mean HbA1c level (National Glycohemoglobin Standardization Program) was 5.8 ± 0.8% (40 mmol/mol). Odds ratios (ORs) and 95% confidence intervals (CIs) of hearing impairment associated with HbA1c were estimated using a logistic regression model. In the cross‐sectional analysis, HbA1c levels were positively associated with hearing impairment (OR per 1.0% increase in HbA1c = 1.30, 95% CI = 1.00−1.68). This association persisted even after excluding 58 participants with a self‐reported history of diagnosed diabetes mellitus. Longitudinal analysis revealed the temporality of the discussed association (OR = 1.52, 95% CI = 1.03−2.23).

Conclusion

The present study provides supportive evidence for a causal link between hyperglycemia and age‐related hearing loss.
The regulatory network mediated by circadian clock genes is related to heterosis in rice
Authors: Shen Guojing , Hu Wei , Zhang Bo , Xing Yongzhong
Published: July 2014

Exploitation of heterosis in rice (Oryza sativa L.) has contributed greatly to global food security. In this study, we generated three sets of reciprocal F1 hybrids of indica and japonica subspecies to evaluate the relationship between yield heterosis and the circadian clock. There were no differences in trait performance or heterosis between the reciprocal hybrids, indicating no maternal effects on heterosis. The indica‐indica and indica‐japonica reciprocal F1 hybrids exhibited pronounced heterosis for chlorophyll and starch content in leaves and for grain yield/biomass. In contrast, the japonica‐japonica F1 hybrids showed low heterosis. The three circadian clock genes investigated expressed in an above‐high‐parent pattern (AHP) at seedling stage in all the hybrids. The five genes downstream of the circadian clock, and involved in chlorophyll and starch metabolic pathways, were expressed in AHP in hybrids with strong better‐parent heterosis (BPH). Similarly, three of these five genes in the japonica‐japonica F1 hybrids showing low BPH were expressed in positive overdominance, but the other two genes were expressed in additive or negative overdominance. These results indicated that the expression patterns of circadian clock genes and their downstream genes are associated with heterosis, which suggests that the circadian rhythm pathway may be related to heterosis in rice.
Impacts of dietary fat level and saturation when feeding distillers grains to high producing dairy cows
Authors: Havlin J. M. , Robinson P. H. , Karges K.
Published: July 2014

This experiment was conducted to determine whether increasing the net energy (NEL) of a total mixed ration (TMR) with mainly unsaturated fat from corn distillers dried grains with solubles (DDGS) vs. rumen inert (RI)‐saturated fat has similar impacts on animal performance. The experiment was an incomplete Youden square with three treatments and four 28‐days periods, completed on a large commercial dairy using three early lactation pens each with approximately 380 multiparity cows. The TMR for all treatments was the same, except for 150 g/kg dry matter (DM) of each TMR which contained 90 g/kg high‐protein DDGS (HPDDGS) and 60 g/kg beet pulp (i.e. low‐fat control diet; LFC); 150 g/kg DDGS (i.e. high‐fat diet with unsaturated fat; HFU); or 111 g/kg HPDDGS, 20 g/kg beet pulp and 19 g/kg RI fat (i.e. high‐fat diet with saturated fat; HFS). The DM intake was highest (p < 0.05) for HFU‐fed cows. Milk, fat and true protein yields, as well as milk energy output, were higher (p < 0.01) when cows were fed HFS vs. HFU and LFC diets. Milk true protein concentration was lowest (p < 0.01) for HFS‐fed cows, but milk fat % was lowest (p < 0.01) for HFU and highest (p < 0.01) for HFS‐fed cows. There were numerous differences (p < 0.01) in milk fatty acid levels amongst diets. The increase in body condition score was lowest (p < 0.01) for LFC. Whole tract digestibility of acid detergent fibre was lower (p < 0.01) for LFC vs. HFS cows, and fat digestion was lowest (p < 0.01) for LFC‐fed cows. This DDGS, high in unsaturated fatty acids, was fed at high levels (i.e. 152 g/kg DM) with little impact on animal performance vs. a lower fat control diet, although addition of an RI‐saturated fat to create a diet with a similarly higher fat level resulted in higher animal productivity.
Metamorphism in the Martian crust
Authors: McSween Harry Y. , Labotka Theodore C. , Viviano‐Beck Christina E.
Published: July 2014

Compositions of basaltic and ultramafic rocks analyzed by Mars rovers and occurring as Martian meteorites allow predictions of metamorphic mineral assemblages that would form under various thermophysical conditions. Key minerals identified by remote sensing roughly constrain temperatures and pressures in the Martian crust. We use a traditional metamorphic approach (phase diagrams) to assess low‐grade/hydrothermal equilibrium assemblages. Basaltic rocks should produce chlorite + actinolite + albite + silica, accompanied by laumontite, pumpellyite, prehnite, or serpentine/talc. Only prehnite‐bearing assemblages have been spectrally identified on Mars, although laumontite and pumpellyite have spectra similar to other uncharacterized zeolites and phyllosilicates. Ultramafic rocks are predicted to produce serpentine, talc, and magnesite, all of which have been detected spectrally on Mars. Mineral assemblages in both basaltic and ultramafic rocks constrain fluid compositions to be H2O‐rich and CO2‐poor. We confirm the hypothesis that low‐grade/hydrothermal metamorphism affected the Noachian crust on Mars, which has been excavated in large craters. We estimate the geothermal gradient (>20 °C km−1) required to produce the observed assemblages. This gradient is higher than that estimated from radiogenic heat‐producing elements in the crust, suggesting extra heating by regional hydrothermal activity.
Region‐specific regulation of the serotonin 2A receptor expression in development and ageing in post mortem human brain
Authors: Marinova Zoya , Monoranu Camelia‐Maria , Fetz Sonja , Walitza Susanne , Grünblatt Edna
Published: July 2014

Aims

The serotonin 2A receptor (HTR2A) is widely expressed in the brain and involved in the modulation of fear, mood, anxiety and other symptoms. HTR2A and HTR2A gene variations are implicated in depression, schizophrenia, anxiety and obsessive‐compulsive disorder. To understand HTR2A signalling changes in psychiatric or neurodegenerative disorders, its normal pattern of brain expression and region specificity during development and ageing needs to be clarified. The aim of the present study was to assess HTR2A expression through developmental and ageing stages in six brain regions in post mortem human brain samples from individuals with no clinical or neuropathological evidence of neuropsychiatric disorders and to investigate the interaction with the rs6311 HTR2A promoter polymorphism.

Methods

DNA, RNA and protein were isolated from post mortem brain samples including six regions (frontal cortex, striatum, amygdala, thalamus, brain stem and cerebellum) from 55 individuals. HTR2A mRNA levels were assessed using quantitative real‐time RT‐PCR and HTR2A protein levels – with Western blot. The rs6311 HTR2A polymorphism was analysed with genotyping.

Results

We found that HTR2A mRNA and protein levels are differentially regulated with age in different brain regions studied, but are not affected by gender. Significant changes in HTR2A expression with age were found in frontal cortex, amygdala, thalamus, brain stem and cerebellum.

Conclusions

Our results show plasticity and region specificity of HTR2A expression regulation in human brain with age, which may be important for the interaction with other neurotransmitter systems and for the occurrence of developmental periods with increased vulnerability to neuropsychiatric or neurodegenerative disorders.
Random placement models predict species–area relationships in duck communities despite species aggregation
Authors: Bidwell Mark T. , Green Andy J. , Clark Robert G.
Published: July 2014

Species–area relationships are the product of many ecological processes and their interactions. Explanations for the species–area relationship (SAR) have focused on separating putative niche‐based mechanisms that correlate with area from sampling effects caused by patches with more individuals containing more species than patches with fewer individuals. We tested the hypothesis that SARs in breeding waterfowl communities are caused by sampling effects (i.e. random placement from the regional species pool). First, we described observed SARs and patterns of species associations for fourteen species of ducks on ponds in prairie Canada. Second, we used null models, which randomly allocated ducks to ponds, to test if observed SARs and patterns of species associations differed from those expected by chance. Consistent with the sampling effects hypothesis, observed SARs were accurately predicted by null models in three different years and for diving and dabbling duck guilds. This is the first demonstration that null models can predict SARs in waterbirds or any other aquatic organisms. Observed patterns of species association, however, were not well predicted by null models as in all years there was less observed segregation among species (i.e. more aggregation) than under the random expectation, suggesting that intraspecific competition could play a role in structuring duck communities. Taken together, our results indicate that when emergent properties of ecological communities such as the SAR appear to be caused by random processes, analyses of species associations can be critical in revealing the importance of niche‐based processes (e.g. competition) in structuring ecological communities.
The role of Porphyromonas gingivalis gingipains in platelet activation and innate immune modulation
Authors: Klarström Engström K. , Khalaf H. , Kälvegren H. , Bengtsson T.
Published: July 2014

Platelets are considered to have important functions in inflammatory processes and as actors in the innate immunity. Several studies have shown associations between cardiovascular disease and periodontitis, where the oral anaerobic pathogen Porphyromonas gingivalis has a prominent role in modulating the immune response. Porphyromonas gingivalis has been found in atherosclerotic plaques, indicating spreading of the pathogen via the circulation, with an ability to interact with and activate platelets via e.g. Toll‐like receptors (TLR) and protease‐activated receptors. We aimed to evaluate how the cysteine proteases, gingipains, of P. gingivalis affect platelets in terms of activation and chemokine secretion, and to further investigate the mechanisms of platelet–bacteria interaction. This study shows that primary features of platelet activation, i.e. changes in intracellular free calcium and aggregation, are affected by P. gingivalis and that arg‐gingipains are of great importance for the ability of the bacterium to activate platelets. The P. gingivalis induced a release of the chemokine RANTES, however, to a much lower extent compared with the TLR2/1‐agonist Pam3CSK4, which evoked a time‐dependent release of the chemokine. Interestingly, the TLR2/1‐evoked response was abolished by a following addition of viable P. gingivalis wild‐types and gingipain mutants, showing that both Rgp and Kgp cleave the secreted chemokine. We also demonstrate that Pam3CSK4‐stimulated platelets release migration inhibitory factor and plasminogen activator inhibitor‐1, and that also these responses were antagonized by P. gingivalis. These results supports immune‐modulatory activities of P. gingivalis and further clarify platelets as active players in innate immunity and in sensing bacterial infections, and as target cells in inflammatory reactions induced by P. gingivalis infection.
In comparison with nitrate nutrition, ammonium nutrition increases growth of the frostbite1 Arabidopsis mutant
Authors: PODGÓRSKA ANNA , OSTASZEWSKA MONIKA , GARDESTRÖM PER , RASMUSSON ALLAN G. , SZAL BOŻENA
Published: July 2014

Ammonium nutrition inhibits the growth of many plant species, including Arabidopsis thaliana. The toxicity of ammonium is associated with changes in the cellular redox state. The cellular oxidant/antioxidant balance is controlled by mitochondrial electron transport chain. In this study, we analysed the redox metabolism of frostbite1 (fro1) plants, which lack mitochondrial respiratory chain complex I. Surprisingly, the growth of fro1 plants increased under ammonium nutrition. Ammonium nutrition increased the reduction level of pyridine nucleotides in the leaves of wild‐type plants, but not in the leaves of fro1 mutant plants. The observed higher activities of type II NADH dehydrogenases and cytochrome c oxidase in the mitochondrial electron transport chain may improve the energy metabolism of fro1 plants grown on ammonium. Additionally, the observed changes in reactive oxygen species (ROS) metabolism in the apoplast may be important for determining the growth of fro1 under ammonium nutrition. Moreover, bioinformatic analyses showed that the gene expression changes in fro1 plants significantly overlap with the changes previously observed in plants with a modified apoplastic pH. Overall, the results suggest a pronounced connection between the mitochondrial redox system and the apoplastic pH and ROS levels, which may modify cell wall plasticity and influence growth.
Fasciola hepatica tegumental antigens indirectly induce an M2 macrophage‐like phenotype in vivo
Authors: Adams P. N. , Aldridge A. , Vukman K. V. , Donnelly S. , O'Neill S. M.
Published: July 2014

The M2 subset of macrophages has a critical role to play in host tissue repair, tissue fibrosis and modulation of adaptive immunity during helminth infection. Infection with the helminth, Fasciola hepatica, is associated with M2 macrophages in its mammalian host, and this response is mimicked by its excretory‐secretory products (FhES). The tegumental coat of F. hepatica (FhTeg) is another major source of immune‐modulatory molecules; we have previously shown that FhTeg can modulate the activity of both dendritic cells and mast cells inhibiting their ability to prime a Th1 immune response. Here, we report that FhTeg does not induce Th2 immune responses but can induce M2‐like phenotype in vivo that modulates cytokine production from CD4+ cells in response to anti‐CD3 stimulation. FhTeg induces a RELMα expressing macrophage population in vitro, while in vivo, the expression of Arg1 and Ym‐1/2 but not RELMα in FhTeg‐stimulated macrophages was STAT6 dependent. To support this finding, FhTeg induces RELMα expression in vivo prior to the induction of IL‐13. FhTeg can induce IL‐13‐producing peritoneal macrophages following intraperitoneal injection This study highlights the important role of FhTeg as an immune‐modulatory source during F. hepatica infection and sheds further light on helminth–macrophage interactions.
High‐resolution time‐resolved imaging of in vitro Arabidopsis rosette growth
Authors: Dhondt Stijn , Gonzalez Nathalie , Blomme Jonas , De Milde Liesbeth , Van Daele Twiggy , Van Akoleyen Dirk , Storme Veronique , Coppens Frederik , T.S. Beemster Gerrit , Inzé Dirk
Published: July 2014

Although quantitative characterization of growth phenotypes is of key importance for the understanding of essential networks driving plant growth, the majority of growth‐related genes are still being identified based on qualitative visual observations and/or single‐endpoint quantitative measurements. We developed an in vitro growth imaging system (IGIS) to perform time‐resolved analysis of rosette growth. In this system, Arabidopsis plants are grown in Petri dishes mounted on a rotating disk, and images of each plate are taken on an hourly basis. Automated image analysis was developed in order to obtain several growth‐related parameters, such as projected rosette area, rosette relative growth rate, compactness and stockiness, over time. To illustrate the use of the platform and the resulting data, we present the results for the growth response of Col–0 plants subjected to three mild stress conditions. Although the reduction in rosette area was relatively similar at 19 days after stratification, the time‐lapse analysis demonstrated that plants react differently to salt, osmotic and oxidative stress. The rosette area was altered at various time points during development, and leaf movement and shape parameters were also affected differently. We also used the IGIS to analyze in detail the growth behavior of mutants with enhanced leaf size. Analysis of several growth‐related parameters over time in these mutants revealed several specificities in growth behavior, underlining the high complexity of leaf growth coordination. These results demonstrate that time‐resolved imaging of in vitro rosette growth generates a better understanding of growth phenotypes than endpoint measurements.
Analysis of an Arabidopsis heat‐sensitive mutant reveals that chlorophyll synthase is involved in reutilization of chlorophyllide during chlorophyll turnover
Authors: Lin Yao‐Pin , Lee Tsung‐yuan , Tanaka Ayumi , Charng Yee‐yung
Published: July 2014

Chlorophylls, the most abundant pigments in the photosynthetic apparatus, are constantly turned over as a result of the degradation and replacement of the damage‐prone reaction center D1 protein of photosystem II. Results from isotope labeling experiments suggest that chlorophylls are recycled by reutilization of chlorophyllide and phytol, but the underlying mechanism is unclear. In this study, by characterization of a heat‐sensitive Arabidopsis mutant we provide evidence of a salvage pathway for chlorophyllide a. A missense mutation in CHLOROPHYLL SYNTHASE (CHLG) was identified and confirmed to be responsible for a light‐dependent, heat‐induced cotyledon bleaching phenotype. Following heat treatment, mutant (chlg‐1) but not wild‐type seedlings accumulated a substantial level of chlorophyllide a, which resulted in a surge of phototoxic singlet oxygen. Immunoblot analysis suggested that the mutation destabilized the chlorophyll synthase proteins and caused a conditional blockage of esterification of chlorophyllide a after heat stress. Accumulation of chlorophyllide a after heat treatment occurred during recovery in the dark in the light‐grown but not the etiolated seedlings, suggesting that the accumulated chlorophyllides were not derived from de novo biosynthesis but from de‐esterification of the existing chlorophylls. Further analysis of the triple mutant harboring the CHLG mutant allele and null mutations of CHLOROPHYLLASE1 (CLH1) and CLH2 indicated that the known chlorophyllases are not responsible for the accumulation of chlorophyllide a in chlg‐1. Taken together, our results show that chlorophyll synthase acts in a salvage pathway for chlorophyll biosynthesis by re‐esterifying the chlorophyllide a produced during chlorophyll turnover.
Arabidopsis CPL4 is an essential C‐terminal domain phosphatase that suppresses xenobiotic stress responses
Authors: Fukudome Akihito , Aksoy Emre , Wu Xiaoqiang , Kumar Krishna , Jeong In Sil , May Kimberly , Russell William K. , Koiwa Hisashi
Published: July 2014

Eukaryotic gene expression is both promoted and inhibited by the reversible phosphorylation of the C‐terminal domain of RNA polymerase II (pol II CTD). More than 20 Arabidopsis genes encode CTD phosphatase homologs, including four CTD phosphatase‐like (CPL) family members. Although in vitro CTD phosphatase activity has been established for some CPLs, none have been shown to be involved in the phosphoregulation of pol II in vivo. Here we report that CPL4 is a CTD phosphatase essential for the viability of Arabidopsis thaliana. Mass spectrometry analysis identified the pol II subunits RPB1, RPB2 and RPB3 in the affinity‐purified CPL4 complex. CPL4 dephosphorylates both Ser2‐ and Ser5‐PO4 of the CTD in vitro, with a preference for Ser2‐PO4. Arabidopsis plants overexpressing CPL4 accumulated hypophosphorylated pol II, whereas RNA interference‐mediated silencing of CPL4 promoted hyperphosphorylation of pol II. A D128A mutation in the conserved DXDXT motif of the CPL4 catalytic domain resulted in a dominant negative form of CPL4, the overexpression of which inhibited transgene expression in transient assays. Inhibition was abolished by truncation of the phosphoprotein‐binding Breast Cancer 1 C‐terminal domain of CPL4, suggesting that both catalytic function and protein–protein interaction are essential for CPL4‐mediated regulation of gene expression. We were unable to recover a homozygous cpl4 mutant, probably due to the zygotic lethality of this mutation. The reduction in CPL4 levels in CPL4RNAi plants increased transcript levels of a suite of herbicide/xenobiotic‐responsive genes and improved herbicide tolerance, thus suggesting an additional role for CPL4 as a negative regulator of the xenobiotic detoxification pathway.