bluuebunny/crossref_metadata_2025 huggingface dataset:
RsaM: a transcriptional regulator of Burkholderia spp. with novel fold
Authors: Michalska Karolina , Chhor Gekleng , Clancy Shonda , Jedrzejczak Robert , Babnigg Gyorgy , Winans Stephen C. , Joachimiak Andrzej
Published: June 2014

Burkholderia cepacia complex is a set of closely related bacterial species that are notorious pathogens of cystic fibrosis patients, responsible for life‐threatening lung infections. Expression of several virulence factors of Burkholderia cepacia complex is controlled by a mechanism known as quorum sensing (QS). QS is a means of bacterial communication used to coordinate gene expression in a cell‐density‐dependent manner. The system involves the production of diffusible signaling molecules (N‐acyl‐l‐homoserine lactones, AHLs), that bind to cognate transcriptional regulators and influence their ability to regulate gene expression. One such system that is highly conserved in Burkholderia cepacia complex consists of CepI and CepR. CepI is AHL synthase, whereas CepR is an AHL‐dependent transcription factor. In most members of the Burkholderia cepacia complex group, the cepI and cepR genes are divergently transcribed and separated by additional genes. One of them, bcam1869, encodes the BcRsaM protein, which was recently postulated to modulate the abundance or activity of CepI or CepR. Here, we show the crystal structure of BcRsaM from B. cenocepacia J2315. It is a single‐domain protein with unique topology and presents a novel fold. The protein is a dimer in the crystal and in solution. This regulator has no known DNA‐binding motifs and direct binding of BcRsaM to the cepI promoter could not be detected in in vitro assays. Therefore, we propose that the modulatory action of RsaM might result from interactions with other components of the QS machinery rather than from direct association with the DNA promoter.

Database

The atomic coordinates and structure factors have been deposited in the Protein Data Bank under entry 4O2H.

Structured digital abstract

BcRsaM and BcRsaM bind by x-ray crystallography (View interaction)

BcRsaM and BcRsaM bind by molecular sieving (View interaction)
Combining physiological threshold knowledge to species distribution models is key to improving forecasts of the future niche for macroalgae
Authors: Martínez Brezo , Arenas Francisco , Trilla Alba , Viejo Rosa M. , Carreño Francisco
Published: June 2014

Species distribution models (SDM) are a useful tool for predicting species range shifts in response to global warming. However, they do not explore the mechanisms underlying biological processes, making it difficult to predict shifts outside the environmental gradient where the model was trained. In this study, we combine correlative SDMs and knowledge on physiological limits to provide more robust predictions. The thermal thresholds obtained in growth and survival experiments were used as proxies of the fundamental niches of two foundational marine macrophytes. The geographic projections of these species’ distributions obtained using these thresholds and existing SDMs were similar in areas where the species are either absent‐rare or frequent and where their potential and realized niches match, reaching consensus predictions. The cold‐temperate foundational seaweed Himanthalia elongata was predicted to become extinct at its southern limit in northern Spain in response to global warming, whereas the occupancy of southern‐lusitanic Bifurcaria bifurcata was expected to increase. Combined approaches such as this one may also highlight geographic areas where models disagree potentially due to biotic factors. Physiological thresholds alone tended to over‐predict species prevalence, as they cannot identify absences in climatic conditions within the species’ range of physiological tolerance or at the optima. Although SDMs tended to have higher sensitivity than threshold models, they may include regressions that do not reflect causal mechanisms, constraining their predictive power. We present a simple example of how combining correlative and mechanistic knowledge provides a rapid way to gain insight into a species’ niche resulting in consistent predictions and highlighting potential sources of uncertainty in forecasted responses to climate change.
Transient Facial Nerve Palsy After Occipital Nerve Block: A Case Report
Authors: Strauss Lauren , Loder Elizabeth , Rizzoli Paul
Published: June 2014

Occipital nerve blocks are commonly performed to treat a variety of headache syndromes and are generally believed to be safe and well tolerated. We report the case of an otherwise healthy 24‐year‐old woman with left side‐locked occipital, parietal, and temporal pain who was diagnosed with probable occipital neuralgia. She developed complete left facial nerve palsy within minutes of blockade of the left greater and lesser occipital nerves with a solution of bupivicaine and triamcinolone. Magnetic resonance imaging of the brain with gadolinium contrast showed no abnormalities, and symptoms had completely resolved 4‐5 hours later. Unintended spread of the anesthetic solution along tissue planes seems the most likely explanation for this adverse event. An aberrant course of the facial nerve or connections between the facial and occipital nerves also might have played a role, along with the patient's prone position and the use of a relatively large injection volume of a potent anesthetic. Clinicians should be aware that temporary facial nerve palsy is a possible complication of occipital nerve block.
Dickkopf‐1 expression is down‐regulated during the colorectal adenoma–carcinoma sequence and correlates with reduced microvessel density and VEGF expression
Authors: Liu Zhiyong , Sun Baocun , Qi Lisha , Li Yixian , Zhao Xiulan , Zhang Danfang , Zhang Yanhui
Published: June 2014

Aims

Dickkopf‐1 (Dkk1), an antagonist of the Wnt–β‐catenin signalling pathway, has been reported to play a role in cancer progression. However, little is known about the role of Dkk1 during the colorectal adenoma–carcinoma sequence. This study aimed to elucidate the role of Dkk1 in tumorigenesis and angiogenesis in colorectal cancer.

Methods and results

We examined Dkk1 expression immunohistochemically in 476 colorectal tissue samples, including 46 sets of matched specimens. Dkk1 expression was down‐regulated during the colorectal adenoma–carcinoma sequence, both among the 476 samples and in the 46 sets of matched specimens. Dkk1 expression was correlated with decreased microvessel density (P < 0.05) and VEGF expression. In‐vitro 3D coculture experiments showed that Dkk1 overexpression in HCT116 cells inhibited tube‐like structure formation and down‐regulated VEGF expression in human umbilical vein endothelial cells. Xenografts of Dkk1‐overexpressing colorectal cancer cells were smaller, and showed lower microvessel density and VEGF expression levels, than those of control cells.

Conclusions

This study is the first to show the roles of Dkk1 during the colorectal adenoma–carcinoma sequence, which may involve suppression of the tumorigenesis and angiogenesis of CRC. Dkk1 could therefore serve as a potential target for tumour therapy.
Association of PTPN22+1858C/T polymorphism with Type 1 diabetes in the North Indian population
Authors: Kumar N. , Kaur G. , Kanga U. , Tandon N. , Caillat‐Zucman S. , Mehra N. K.
Published: June 2014

A nonsynonymous SNP +1858C/T (rs2476601) in the protein tyrosine phosphatase, nonreceptor type 22(PTPN22) gene leading to Arg 620 Trp substitution is known to be associated with susceptibility to type 1 diabetes (T1D) and several other autoimmune diseases. We studied this polymorphism in 145 T1D patients and 210 healthy controls from North India. The minor allele +1858T was observed to be significantly increased among patients as compared to healthy controls (2.76% vs 0.5%, P = 0.027, OR = 5.93; 95% CI = 1.4–24.8). The association was also observed at the level of heterozygous C/T genotype (5.5% vs 0.95%, P = 0.026, OR = 6.07; 95% CI = 1.43–25.6). The T allele and C/T genotype were predominantly found among patients who were positive for both glutamic acid decarboxylase 65 (GAD65) and insulin antigen 2 (IA2) autoantibodies and showed significantly increased frequencies (10%, P = 0.034, OR = 11.67; 95% CI = 1.58–84.1 and 20%, P = 0.031, OR = 13.0; 95% CI = 1.66–97.5, respectively) as compared to patients negative for these autoantibodies (0.95% and 1.9%, respectively). The results suggest that the PTPN22+1858T allele is positively associated with T1D in the North Indian population.
Trajectories of Depressive Symptoms in Women Prior to and for 6 Months After Breast Cancer Surgery
Authors: Kyranou Marianna , Puntillo Kathleen , Aouizerat Bradley E. , Paul Steven M. , Cooper Bruce A. , West Claudia , Dodd Marylin , Miaskowski Christine , Dunn Laura B. , Elboim Charles
Published: June 2014

Depressive symptoms are common in women with breast cancer. This study evaluated how ratings of depressive symptoms changed from the time of the preoperative assessment to 6 months after surgery and investigated whether specific demographic, clinical, and symptom characteristics predicted preoperative levels of and/or characteristics of the trajectories of depressive symptoms. Characteristics that predicted higher preoperative levels of depressive symptoms included being married/partnered; receipt of adjuvant chemotherapy; more fear of metastasis; higher levels of trait anxiety, state anxiety, sleep disturbance, problems with changes in appetite; more hours per day in pain; and lower levels of attentional function. Future studies need to evaluate associations between anxiety, fears of recurrence, and uncertainty, as well as personality characteristics and depressive symptoms.
Examining Psychobiological Responses to an Anticipatory Body Image Threat in Women
Authors: Lamarche Larkin , Gammage Kimberley L. , Klentrou Panagiota , Kerr Gretchen , Faulkner Guy
Published: June 2014

The present study extended the applicability of social self‐preservation theory (SSPT) to an anticipatory body image threat. Women (n = 80) were randomized into either a control or threat group (anticipating having a body composition assessment). Participants completed measures of body shame and social physique anxiety (self‐conscious outcomes), and body dissatisfaction (a non‐self‐conscious outcome), and provided a sample of saliva (to assess cortisol levels) at baseline and immediately following their condition. Findings showed that for the threat condition, body image variables were significantly more negative pre‐ to post‐condition. Findings also showed that self‐conscious outcomes were more sensitive than the non‐self‐conscious outcome. There was not a significant group‐by‐time interaction for cortisol. Findings support SSPT's applicability to the anticipation of a social‐evaluative body‐related threat.
Relevance of Osmotic and Frost Protecting Compounds for the Winter Hardiness of Autumn Sown Sugar Beet
Authors: Loel J. , Hoffmann C. M.
Published: June 2014

The cultivation of autumn sown sugar beet (winter beet) is supposed to result in a marked yield increase compared with spring sown sugar beet. Although the importance of the growth stage reached before winter for the survival of autumn sown sugar beet has already been shown, it is not clear to which extent osmotic and potentially frost protecting compounds may contribute to winter hardiness. The study thus aimed to analyse the acclimatization process of sugar beet to low temperatures and to identify compounds which are important for survival of frost. Field trials with autumn sown sugar beet were conducted at eleven environments in Germany from 2009/10 to 2012/13, which were accompanied by greenhouse experiments with controlled temperature regimes. In the field trials, the survival rates after winter varied from 0 % to 99 %, but only in four environments differences between the five genotypes occurred. During acclimatization, betaine, glutamine, proline and raffinose were markedly accumulated and osmolality was enhanced. In particular betaine, amino acids and osmolality showed a positive correlation to the survival rate and were thus identified as potentially frost protecting substances for sugar beet. In contrast, raffinose and proline seem to act rather as stress indicators as they were negatively related to survival. Possible frost protecting substances were identified which can be used in breeding to improve the winter hardiness of sugar beet.
Physiological and Growth Responses of Sugarcane Genotypes to Nitrogen Rate on a Sand Soil
Authors: Zhao D. , Glaz B. , Comstock J. C.
Published: June 2014

Yields of sugarcane (a complex hybrid of Saccharum spp.) in FL, USA, are lower on sand soils than on organic (muck) soils. Nitrogen (N) supply may limit sugarcane growth and yields on these sand soils. A 2‐year pot study was conducted to determine sugarcane genotypic variation in response to N rate on a sand soil. Treatments included four N rates (0, 75, 150 and 225 kg ha−1) and three sugarcane genotypes (CP 80‐1743, CP 01‐2390 and TCP 87‐3388). Nitrogen fertilizer was equally split and applied at about 55 and 125 days after planting (DAP) for each treatment. During the experiment, the number of nodes and length of the primary stalks and tillers were recorded. Leaf relative chlorophyll (soil plant analysis development (SPAD)) and net photosynthetic rate (Pn) were measured biweekly. All plants were harvested at 183 DAP to measure green leaf area (GLA), shoot biomass accumulation and partitioning, and fertilizer N use efficiency (NUE). Genotypes differed significantly in leaf SPAD, Pn, GLA, and shoot biomass accumulation and partitioning. CP 01‐2390 had the highest leaf Pn and shoot biomass, and CP 80‐1743 had the lowest GLA, shoot biomass and NUE among genotypes. Nitrogen rate affected leaf SPAD, GLA, shoot biomass and NUE, but had much less effect on leaf Pn. Green leaf area and biomass increased with increasing N rates. Our results suggest that a two‐pronged approach, selection of genotypes with high NUE while working to optimize N rates and delivery can improve sugarcane yields on sand soils.
Internalization of isolated functional mitochondria: involvement of macropinocytosis
Authors: Kitani Tomoya , Kami Daisuke , Matoba Satoaki , Gojo Satoshi
Published: June 2014

In eukaryotic cells, mitochondrial dysfunction is associated with a variety of human diseases. Delivery of exogenous functional mitochondria into damaged cells has been proposed as a mechanism of cell transplant and physiological repair for damaged tissue. We here demonstrated that isolated mitochondria can be transferred into homogeneic and xenogeneic cells by simple co‐incubation using genetically labelled mitochondria, and elucidated the mechanism and the effect of direct mitochondrial transfer. Intracellular localization of exogenous mitochondria was confirmed by PCR, real‐time PCR, live fluorescence imaging, three‐dimensional reconstruction imaging, continuous time‐lapse microscopic observation, flow cytometric analysis and immunoelectron microscopy. Isolated homogeneic mitochondria were transferred into human uterine endometrial gland‐derived mesenchymal cells in a dose‐dependent manner. Moreover, mitochondrial transfer rescued the mitochondrial respiratory function and improved the cellular viability in mitochondrial DNA‐depleted cells and these effects lasted several days. Finally, we discovered that mitochondrial internalization involves macropinocytosis. In conclusion, these data support direct transfer of exogenous mitochondria as a promising approach for the treatment of various diseases.
Proteomics‐based discovery of biomarkers for paediatric acute lymphoblastic leukaemia: challenges and opportunities
Authors: López Villar Elena , Wu Duojiao , Cho William C. , Madero Luis , Wang Xiangdong
Published: June 2014

There are important breakthroughs in the treatment of paediatric acute lymphoblastic leukaemia (ALL) since 1950, by which the prognosis of the child majority suffered from ALL has been improved. However, there are urgent needs to have disease‐specific biomarkers to monitor the therapeutic efficacy and predict the patient prognosis. The present study overviewed proteomics‐based research on paediatric ALL to discuss important advances to combat cancer cells and search novel and real protein biomarkers of resistance or sensitivity to drugs which target the signalling networks. We highlighted the importance and significance of a proper phospho‐quantitative design and strategy for paediatric ALL between relapse and remission, when human body fluids from cerebrospinal, peripheral blood, or bone‐marrow were applied. The present article also assessed the schedule for the analysis of body fluids from patients at different states, importance of proteomics‐based tools to discover ALL‐specific and sensitive biomarkers, to stimulate paediatric ALL research via proteomics to ‘build’ the reference map of the signalling networks from leukemic cells at relapse, and to monitor significant clinical therapies for ALL‐relapse.
Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF‐β signalling
Authors: Yan Wenji , Wu Kongming , Herman James G. , Brock Malcolm V. , Zhou Yusen , Lu Youyong , Zhang Zhiqian , Yang Yunsheng , Guo Mingzhou
Published: June 2014

Gastric cancer (GC) is the fourth most common malignancy in males and the fifth most common malignancy in females worldwide. DACH1 is frequently methylated in hepatic and colorectal cancer. To further understand the regulation and mechanism of DACH1 in GC, eight GC cell lines, eight cases of normal gastric mucosa, 98 cases of primary GC and 50 cases of adjacent non‐tumour tissues were examined. Methylation‐specific PCR, western blot, transwell assay and xenograft mice were used in this study. Loss of DACH1 expression correlated with promoter region methylation in GC cells, and re‐expression was induced by 5‐Aza‐2′‐deoxyazacytidine. DACH1 is methylated in 63.3% (62/98) of primary GC and 38% (19/50) of adjacent non‐tumour tissues, while no methylation was found in normal gastric mucosa. Methylation of DACH1 correlated with reduced expression of DACH1 (P < 0.01), late tumour stage (stage III/IV) (P < 0.01) and lymph node metastasis (P < 0.05). DACH1 expression inhibited epithelial–mesenchymal transition and metastasis by inhibiting transforming growth factor (TGF)‐β signalling and suppressed GC cell proliferation through inducing G2/M phase arrest. The tumour size is smaller in DACH1‐expressed BGC823 cell xenograft mice than in unexpressed group (P < 0.01). Restoration of DACH1 expression also sensitized GC cells to docetaxel. These studies suggest that DACH1 is frequently methylated in human GC and expression of DACH1 was controlled by promoter region methylation. DACH1 suppresses GC proliferation, invasion and metastasis by inhibiting TGF‐β signalling pathways both in vitro and in vivo. Epigenetic silencing DACH1 may induce GC cells' resistance to docetaxel.
Altered β1,6‐GlcNAc branched N‐glycans impair TGF‐β‐mediated Epithelial‐to‐Mesenchymal Transition through Smad signalling pathway in human lung cancer
Authors: Li Na , Xu Haineng , Fan Kun , Liu Xijun , Qi Jingjing , Zhao Chao , Yin Peng , Wang Liying , Li Zengxia , Zha Xiliang
Published: June 2014

The change of oligosaccharide structure has been revealed to be crucial for glycoproteins' biological functions and cell biological characteristics. N‐acetylglucosaminy transferase V (GnT‐V), a key enzyme catalysing the reaction of adding β1, 6‐N‐acetylglucosamine (GlcNAc) on asparagine‐linked oligosaccharides of cell proteins, has been implicated to a metastastic‐promoting oncoprotein in some carcinomas. However, this correlation might not be subjected to all types of cancers, for example, in non‐small cell lung cancers, low level of GnT‐V expression is associated with relatively short survival time and poor prognosis. To explain the role of GnT‐V in lung cancer progression, we studied the association of GnT‐V expression with lung cancer EMT behaviour. We found that GnT‐V expression was correlated with epithelial marker positively and mesenchymal marker negatively. GnT‐V levels, as well as β1,6‐GlcNAc branched N‐glycans, were strongly reduced in TGF‐β1‐induced EMT of human lung adenocarcinoma A549 cells. Further studies showed that suppression of β1,6‐GlcNAc branched N‐glycans by inhibitor or GnT‐V silencing in A549 cells could promote TGF‐β1‐induced EMT‐like changes, cell migration and invasion. Meanwhile, overexpression of GnT‐V impaired TGF‐β1‐induced EMT, migration and invasion. It suggests that GnT‐V suppresses the EMT process of lung cancer cells through inhibiting the TGF‐β/Smad signalling and its downstream transcription factors in a GnT‐V catalytic activity–dependent manner. Taken together, the present study reveals a novel mechanism of GnT‐V as a suppressor of both EMT and invasion in human lung cancer cells, which may be useful for fully understanding N‐glycan's biological roles in lung cancer progression.
Ultrasound analysis of gray‐scale median value of carotid plaques is a useful reference index for cerebro‐cardiovascular events in patients with type 2 diabetes
Authors: Ariyoshi Kyoko , Okuya Shigeru , Kunitsugu Ichiro , Matsunaga Kimie , Nagao Yuko , Nomiyama Ryuta , Takeda Komei , Tanizawa Yukio
Published: June 2014

Aims/Introduction

Measurements of plaque echogenicity, the gray‐scale median (GSM), were shown to correlate inversely with risk factors for cerebro‐cardiovascular disease (CVD). The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is a potential predictor of CVD risk. In the present study, we assessed the usefulness of carotid plaque GSM values and EPA/AA ratios in atherosclerotic diabetics.

Materials and Methods

A total of 84 type 2 diabetics with carotid artery plaques were enrolled. On admission, platelet aggregation and lipid profiles, including EPA and AA, were examined. Using ultrasound, mean intima media thickness and plaque score were measured in carotid arteries. Plaque echogenicity was evaluated using computer‐assisted quantification of GSM. The patients were then further observed for approximately 3 years.

Results

Gray‐scale median was found to be a good marker of CVD events. On multivariate logistic regression analysis, GSM <32 and plaque score ≥5 were significantly associated with past history and onset of CVD during the follow‐up period, the odds ratios being 7.730 (P = 0.014) and 4.601 (P = 0.046), respectively. EPA/AA showed a significant correlation with GSM (P = 0.012) and high‐density lipoprotein cholesterol (P = 0.039), and an inverse correlation with platelet aggregation (P = 0.046) and triglyceride (P = 0.020). Although most patients with CVD had both low GSM and low EPA/AA values, an association of EPA/AA with CVD events could not be statistically confirmed.

Conclusions

The present results suggest the GSM value to be useful as a reference index for CVD events in high‐risk atherosclerotic diabetics. Associations of the EPA/AA ratio with known CVD risk factors warrant a larger and more extensive study to show the usefulness of this parameter.
Improving phenological forecasting models for rape stem weevil,Ceutorhynchus napiGyll., based on long‐term multisite datasets
Authors: Eickermann M. , Ulber B. , Hoffmann L. , Junk J.
Published: June 2014

New threshold‐based models to predict the start of invasion by the stem‐boring pest, the rape stem weevil (Ceutorhynchus napiGyll.) of winter oilseed rape (Brassica napusL.), were developed and compared to published models using long‐term datasets on weather and weevil phenology from experimental locations in Germany and Luxembourg. Threshold values for daily records of maximum air temperature, mean soil temperature, sunshine duration and total precipitation were adjusted to local conditions on the date of first weevil migration in spring. Mean error and the root mean squared error were used to assess model quality, where the error is defined as the number of days between predicted and observed arrival of weevils on the crop (regardless of sign). Best model results predicted first crop invasion by rape stem weevil when the thresholds of daily maximum air temperature ≥7.8°C, mean soil temperature ≥6.6°C, daily total precipitation ≤1.0 mm and sunshine duration ≥1 h were matched. This model takes into account meteorological variables likely to influence conditions at the overwintering site of the weevils in the soil, as well as variables that may limit weevil flight. Adjusted air temperature threshold values were consistently lower for Luxembourg sites than for those optimized for Germany. A simple model relating the date of first weevil invasion to accumulated daily maximum air temperature above 0°C (from 1 January) was also evaluated. This proved less suitable for forecasting crop invasion byC. napi. We suggest that phenological models using locally adjusted meteorological‐based thresholds have the potential to offer sufficiently accurate forecasts of first immigration flights byC. napifor appropriate timing of insecticide application. In addition, the developed models are suitable tools to be used in climate change impact studies.
Capacity of Japanese Asobara species (Hymenoptera; Braconidae) to parasitize a fruit pest Drosophila suzukii (Diptera; Drosophilidae)
Authors: Nomano F. Y. , Mitsui H. , Kimura M. T.
Published: June 2014

Drosophila suzukii is a pest of soft fruit such as cherry, strawberry or blueberry and recently colonized North America and Europe from Asia. In this study, we assessed the utility of Japanese Asobara species as agents for the biological control of this pest species by examining their host use in nature and their capacity to parasitize this pest species. From Japan, eight Asobara species including putative three undescribed species were found; Asobara japonica was recorded from all over Japan, Asobara tabida from high altitude areas in central and northern Japan, Asobara rossica and Asobara rufescens from central to northern Japan, three undescribed species from central to western or southern Japan and Asobara pleuralis from a subtropical island of Japan. Among them, an undescribed species Asobara sp. TK1 may be useful as an agent for the biological control because it was recorded only from D. suzukii. All of the remaining seven species were generalists mainly using drosophilid species associated with fermenting fruits, and four of them had no or very low abilities to parasitize D. suzukii, indicating that these seven species are not or less appropriate as agents for biological control.
Structured Pharmaceutical Analysis of the Systematic Tool to Reduce Inappropriate Prescribing Is an Effective Method for Final‐Year Medical Students to Improve Polypharmacy Skills: A Randomized Controlled Trial
Authors: Keijsers Carolina J. P. W. , van Doorn Adriaan B. D. , van Kalles Anouk , de Wildt Dick J. , Brouwers Jacobus R. B. J. , van de Kamp Henrieke J. , Jansen Paul A. F.
Published: June 2014

Medical students may not be adequately trained to prescribe appropriately to older adults with polypharmacy. This study addressed how to teach students to minimize inappropriate polypharmacy. Final‐year medical students (N = 106) from two Dutch schools of medicine participated in this randomized controlled trial with a pre/posttest design. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) was used as the intervention. This medication review tool consists of five steps and is part of the Dutch multidisciplinary guideline on polypharmacy. Step two is a structured pharmaceutical analysis of drug use, assessed using six questions regarding undertreatment, ineffective treatment, overtreatment, potential adverse effects, contraindications or interactions, and dose adjustments. It is used in combination with the Screening Tool to Alert doctors to Right Treatment and the Screening Tool of Older Person's Prescriptions checklists. Students were asked to optimize the medication lists of real people, making use, or not, of the STRIP. The number of correct or potentially harmful decisions that the students made when revising the lists was determined by comparison with expert consensus. Students who used the STRIP had better scores than control students; they made more correct decisions (9.3 vs 7.0, 34%; P < .001, correlation coefficient (r) = 0.365) and fewer potentially harmful decisions (3.9 vs 5.6, −30%; P < .001, r = 0.386). E‐learning did not have a different effect from that of non‐E‐learning methods. Students were satisfied with the method. The STRIP method is effective in helping final‐year medical students improve their prescribing skills.
Randomized Controlled Trial of a Prehospital Decision System by Emergency Medical Services to Ensure Optimal Treatment for Older Adults in Sweden
Authors: Vicente Veronica , Svensson Leif , Wireklint Sundström Birgitta , Sjöstrand Fredrik , Castren Maaret
Published: June 2014

Objectives

To evaluate the feasibility and appropriateness of a prehospital system allowing ambulance nurses to transport older adults directly to geriatric care at a community‐based hospital (CH) or to an emergency department (ED).

Design

Randomized controlled trial.

Setting

Emergency medical services in Stockholm, Sweden.

Participants

Older adults who called the emergency number were randomized to an intervention group (n = 410) or a control group (n = 396).

Intervention

The dispatcher randomized the individuals. Those randomized to the intervention group were transported to several alternative destinations decided by a trained nurse performing a comprehensive assessment, using the new prehospital system. Those randomized to the control group were transported to the ED.

Measurements

Primary endpoint: number of individuals triaged directly to a CH (feasibility). Secondary endpoint: number of subsequent transfers (appropriateness) from CH to ED within 24 hours after initial admission.

Results

After exclusion and crossover, the control group consisted of 217 and the intervention group of 449 older adults. The nurse sent 20% of the intervention group (90/449) (95% confidence interval (CI) = 16.6–24.0) directly to the CH when using the prehospital system. Six of those individuals (6.7%) (95% CI = 3.1–13.8) were subsequently transferred from the CH to the ED. Overall, the nurse appropriately triaged 93.3% of the participants (84/90) and transferred them to the CH, avoiding an ED visit.

Conclusion

Ambulance nurses are able to send older adults to an alternative healthcare facility with the help of a prehospital decision support system. In this geographical setting, this appears to be a promising method to optimize resources and improve emergency care of elderly adults.
Morphometric analysis of variation in the ribs with age and sex
Authors: Weaver Ashley A. , Schoell Samantha L. , Stitzel Joel D.
Published: June 2014

Rib cage morphology changes with age and sex are expected to affect thoracic injury mechanisms and tolerance, particularly for vulnerable populations such as pediatrics and the elderly. The size and shape variation of the external geometry of the ribs was characterized for males and females aged 0–100 years. Computed tomography (CT) scans from 339 subjects were analyzed to collect between 2700 and 10 400 homologous landmarks from each rib. Rib landmarks were analyzed using the geometric morphometric technique known as Procrustes superimposition. Age‐ and sex‐specific functions of 3D rib morphology were produced representing the combined size and shape variation and the isolated shape variation. Statistically significant changes in the size and shape variation (P < 0.0001) and shape variation (P < 0.0053) of all 24 ribs were found to occur with age in males and females. Rib geometry, location, and orientation varied according to the rib level. From birth through adolescence, the rib cage experienced an increase in size, a decrease in thoracic kyphosis, and inferior rotation of the ribs relative to the spine within the sagittal plane. From young adulthood into elderly age, the rib cage experienced increased thoracic kyphosis and superior rotation of the ribs relative to the spine within the sagittal plane. The increased roundedness of the rib cage and horizontal angling of the ribs relative to the spine with age influences the biomechanical response of the thorax. With the plane of the rib oriented more horizontally, loading applied in the anterior‐posterior direction will result in increased deformation within the plane of the rib and an increased risk for rib fractures. Thus, morphological changes may be a contributing factor to the increased incidence of rib fractures in the elderly. The morphological functions derived in this study capture substantially more information on thoracic skeleton morphology variation with age and sex than is currently available in the literature. The developed models of rib cage anatomy can be used to study age and sex variations in thoracic injury patterns due to motor vehicle crashes or falls, and clinically relevant changes due to chronic obstructive pulmonary disease or other diseases evidenced by structural and anatomic changes to the chest.
The cubital tunnel: a radiologic and histotopographic study
Authors: Macchi Veronica , Tiengo Cesare , Porzionato Andrea , Stecco Carla , Sarasin Gloria , Tubbs Shane , Maffulli Nicola , De Caro Raffaele
Published: June 2014

Entrapment of the ulnar nerve at the elbow is the second most common compression neuropathy in the upper limb. The present study evaluates the anatomy of the cubital tunnel. Eighteen upper limbs were analysed in unembalmed cadavers using ultrasound examination in all cases, dissection in nine cases, and microscopic study in nine cases. In all cases, thickening of the fascia at the level of the tunnel was found at dissection. From the microscopic point of view, the ulnar nerve is a multifascicular trunk (mean area of 6.0 ± 1.5 mm2). The roof of the cubital tunnel showed the presence of superimposed layers, corresponding to fascial, tendineous and muscular layers, giving rise to a tri‐laminar structure (mean thickness 523 ± 235 μm). This multilayered tissue was hyperechoic (mean thickness 0.9 ± 0.3 mm) on ultrasound imaging. The roof of the cubital tunnel is elastic, formed by a myofascial trilaminar retinaculum. The pathological fusion of these three layers reduces gliding of the ulnar nerve during movements of the elbow joint. This may play a role in producing the symptoms typical of cubital tunnel syndrome. Independent from the surgical technique, decompression should span the ulnar nerve from the triceps brachii muscle to the flexor carpi ulnaris fascia.
Assessment of occlusion after placement of stainless steel crowns in children – a pilot study
Authors: Gallagher S. , O'Connell B. C. , O'Connell A. C.
Published: June 2014

Many stainless steel crowns (SSCs) disrupt the occlusion in children, but stabilisation appears to occur within a short period post‐placement. The extent and mechanism of these short‐term occlusal changes in children are unknown. This study sought to determine whether placement of a SSC changes the maximum intercuspation position (MIP) in children, whether the MIP returns to normal within 4 weeks and whether local anaesthesia had an effect on the child's ability to achieve MIP. The T‐Scan® III was used for the measurement of occlusal contacts. Reliability and reproducibility of the system was determined using a calibration exercise where MIP recordings were taken of eleven children not undergoing any dental treatment. For the main study, the percentage of total occlusal force on each tooth was recorded in 20 children preoperatively, after local anaesthesia, after SSC placement and 4 weeks postoperatively. There was no significant difference in MIP (P = 0·435) preoperatively and post‐administration of local anaesthesia. There was a significant difference between the preoperative force on a tooth and the reading after crown placement (P = 0·0013, Wilcoxon test). By 4 weeks, there was no significant difference overall between post‐SSC placement and the preoperative value for the tooth (P = 0·3). Administration of local anaesthesia did not affect the ability of a child to attain MIP. Maximum intercuspation position was disturbed by the placement of a SSC in seven of 20 cases. When MIP was disturbed, in most cases, it returned to preoperative status within 4 weeks of crown placement.
Holocene fire regimes, vegetation and biogeochemistry of an ecotone site in the Great Lakes Region of North America
Authors: Morris Jesse L. , Mueller Joshua R. , Nurse Andrea , Long Colin J. , McLauchlan Kendra K.
Published: June 2014

Question

As anthropogenic change pushes ecosystems towards historically novel states, understanding how landscape disturbances interact with climate variability becomes increasingly important. We reconstructed the Holocene vegetation and fire history of a small watershed to investigate the linkages among disturbance regimes, biogeochemical cycling and ecosystem structure. Specifically we asked: (i) how do compositional and structural changes in forest ecosystems modify fire regimes; and (ii) how do changes in fuel type and fire regimes impact biogeochemical cycling?

Location

Comstock Lake, Wisconsin, USA, a small kettle lake at the modern prairie–forest ecotone in the Great Lakes Region of North America.

Methods

We analysed a lacustrine sediment core from Comstock Lake, Wisconsin, for paleoecological proxies including charcoal quantity and morphotype, pollen composition, magnetic susceptibility, organic matter concentration and stable carbon and nitrogen isotopes. These paleoecological variables were used to reconstruct climate‐mediated shifts in vegetation, fire disturbance and biogeochemical cycling during the last 13 200 calendar years before present (cal yr BP).

Results

Forest composition in the landscape surrounding Comstock Lake varied among coniferous forest, deciduous forest and savanna over the Holocene. Independent of the vegetation changes, five distinct fire regimes were identified, ranging from frequent, low‐intensity surface fires to infrequent, high‐intensity crown fires. The main feature of our vegetation reconstruction is a shift from Pinus to Quercus forest that occurred between 10 000 and 11 000 cal yr BP. However, changes in fuel source and forest structure were apparently more important than shifts of species composition in determining fire regimes. We observed an inverse relationship between non‐arboreal fuel sources and biomass burning throughout all five fire regimes. The biogeochemical consequences of fires were apparent during some, but not all regime transitions. Generally, the sediments were composed of relatively small clastic inputs from the catchment and mostly autochthonous organic sources.

Conclusion

The location of Comstock Lake on the prairie–forest boundary meant that regional climate signals during the Holocene were filtered through vegetation. Both compositional changes in dominant tree taxa and structural changes in canopy openness influenced fire regimes.
Grazing effects on biological soil crusts and their interaction with shrubs and grasses in an arid rangeland
Authors: Tabeni Solana , Garibotti Irene A. , Pissolito Clara , Aranibar Julieta N.
Published: June 2014

Question

Biological soil crust (BSC) communities can be used in the identification and monitoring of degradation. A key question is how landscape‐scale livestock disturbance and other local‐scale factors influence BSC communities. We hypothesize that at the landscape scale, increased grazing pressure would lead to decreasing cover of BSC, but at the local scale biotic interactions between BSC and vascular plants would modulate the influence of grazing on BSC.

Methods

Spatially explicit sampling of vegetation composition and cover was conducted using point‐sampling methods in digital images along two disturbance gradients in the central Monte Desert in Argentina.

Results

The grazing gradient is the major determinant of changes in the structure of plant communities at the landscape scale. Approximately 1500 to 2000 m from a watering point, there is a threshold in vegetation structure associated with a nonlinear trend of the BSC, herb, grass and shrub cover. Bivariate spatial patterns show attraction between BSC and shrubs in the vicinity of settlements, and repulsion between BSC and both grasses and litter in less disturbed sites.

Conclusion

Grazing affects BSC directly through trampling and indirectly by altering vascular plant communities that interact with the BSC communities. Both these effects vary according to the spatial scale being considered. The results evidence that understanding of livestock impact in structuring arid ecosystems requires an integrated analysis of BSC and vascular plant communities at different spatial scales.
Expression of vasoactive proteins in gastric antral mucosa reflects vascular dysfunction in patients with cirrhosis and portal hypertension
Authors: Trebicka Jonel , Wix Cyrus , von Heydebrand Matthias , Hittatiya Kanishka , Reiberger Thomas , Klein Sabine , Schierwagen Robert , Kristiansen Glen , Peck‐Radosavljevic Markus , Fischer Hans‐Peter , Møller Søren , Bendtsen Flemming , Krag Aleksander , Sauerbruch Tilman
Published: June 2014

Background & Aims

Patients with cirrhosis display hypocontractility of splanchnic vessels because of dysregulation of vasoactive proteins, such as decreased effect of RhoA/ROCK and increased activity of β‐Arrestin‐2 and eNOS. However, it is unknown whether the dysregulation of vasoactive proteins is displayed in other vessels. We investigated whether expression of vasoactive proteins can be evaluated in gastric mucosa vessels.

Methods

Biopsies from the gastric mucosa of 111 patients with cirrhosis were collected at three different centres and from 13 controls. Forty‐nine patients had received TIPS. Portal pressure gradient was measured in 49 patients with TIPS and in 16 patients without TIPS. Biopsies from the antrum were conserved in formaldehyde for immunohistochemistry or shock‐frozen for PCR and Western blot.

Results

The mucosal transcription of vascular markers (αSMA, CD31) was higher in cirrhotic patients than controls, which was confirmed by immunohistochemistry. On average, relative mucosal levels of RhoA and ROCK were lower, while β‐Arrestin‐2 levels were higher in cirrhotic patients compared to controls. Transcriptional levels of eNOS increased with presence of ascites and grade of oesophageal varices. Patients with TIPS showed less pronounced markers of vascular dysfunction in gastric mucosa.

Conclusion

This is the first evidence that the expression of vasoactive proteins in mucosa from the gastric antrum of patients with cirrhosis reflects their vascular dysfunction and possibly changes after therapeutic interventions.
An alternative, arginase‐independent pathway for arginine metabolism in Kluyveromyces lactis involves guanidinobutyrase as a key enzyme
Authors: Romagnoli G. , Verhoeven M. D. , Mans R. , Fleury Rey Y. , Bel‐Rhlid R. , van den Broek M. , Maleki Seifar R. , Ten Pierick A. , Thompson M. , Müller V. , Wahl S. A. , Pronk J. T. , Daran J. M.
Published: June 2014

Most available knowledge on fungal arginine metabolism is derived from studies on Saccharomyces cerevisiae, in which arginine catabolism is initiated by releasing urea via the arginase reaction. Orthologues of the S. cerevisiae genes encoding the first three enzymes in the arginase pathway were cloned from Kluyveromyces lactis and shown to functionally complement the corresponding deletion in S. cerevisiae. Surprisingly, deletion of the single K. lactis arginase gene KlCAR1 did not completely abolish growth on arginine as nitrogen source. Growth rate of the deletion mutant strongly increased during serial transfer in shake‐flask cultures. A combination of RNAseq‐based transcriptome analysis and 13C‐15N‐based flux analysis was used to elucidate the arginase‐independent pathway. Isotopic 13C15N‐enrichment in γ‐aminobutyrate revealed succinate as the entry point in the TCA cycle of the alternative pathway. Transcript analysis combined with enzyme activity measurements indicated increased expression in the Klcar1Δ mutant of a guanidinobutyrase (EC.3.5.3.7), a key enzyme in a new pathway for arginine degradation. Expression of the K. lactis KLLA0F27995g (renamed KlGBU1) encoding guanidinobutyrase enabled S. cerevisiae to use guanidinobutyrate as sole nitrogen source and its deletion in K. lactis almost completely abolish growth on this nitrogen source. Phylogenetic analysis suggests that this enzyme activity is widespread in fungi.
Obesity and mortality: are the risks declining? Evidence from multiple prospective studies in the United States
Authors: Mehta T. , Fontaine K. R. , Keith S. W. , Bangalore S. S. , de los Campos G. , Bartolucci A. , Pajewski N. M. , Allison D. B.
Published: June 2014

We evaluated whether the obesity‐associated years of life lost (YLL) have decreased over calendar time. We implemented a meta‐analysis including only studies with two or more serial body mass index (BMI) assessments at different calendar years. For each BMI category (normal weight: BMI 18.5 to <25 [reference]; overweight: BMI 25 to <30; grade 1 obesity: BMI 30 to <35; and grade 2–3 obesity: BMI ≥ 35), we estimated the YLL change between 1970 and 1990. Because of low sample sizes for African–American, results are reported on Caucasian. Among men aged ≤60 years YLL for grade 1 obesity increased by 0.72 years (P < 0.001) and by 1.02 years (P = 0.01) for grade 2–3 obesity. For men aged >60, YLL for grade 1 obesity decreased by 1.02 years (P < 0.001) and increased by 0.63 years for grade 2–3 obesity (P = 0.63). Among women aged ≤60, YLL for grade 1 obesity decreased by 4.21 years (P < 0.001) and by 4.97 years (P < 0.001) for grade 2–3 obesity. In women aged >60, YLL for grade 1 obesity decreased by 3.98 years (P < 0.001) and by 2.64 years (P = 0.001) for grade 2–3 obesity. Grade 1 obesity's association with decreased longevity has reduced for older Caucasian men. For Caucasian women, there is evidence of a decline in the obesity YLL association across all ages.
The mutational burden of acral melanoma revealed by whole‐genome sequencing and comparative analysis
Authors: Furney Simon J. , Turajlic Samra , Stamp Gordon , Thomas J. Meirion , Hayes Andrew , Strauss Dirk , Gavrielides Mike , Xing Wei , Gore Martin , Larkin James , Marais Richard
Published: June 2014

Acral melanoma is a subtype of melanoma with distinct epidemiological, clinical and mutational profiles. To define the genomic alterations in acral melanoma, we conducted whole‐genome sequencing and SNP array analysis of five metastatic tumours and their matched normal genomes. We identified the somatic mutations, copy number alterations and structural variants in these tumours and combined our data with published studies to identify recurrently mutated genes likely to be the drivers of acral melanomagenesis. We compared and contrasted the genomic landscapes of acral, mucosal, uveal and common cutaneous melanoma to reveal the distinctive mutational characteristics of each subtype.