bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Cryptococcus neoformans Rho1 GTPases in the PKC1 Signaling Pathway in Response to Thermal Stress
Authors: Lam Woei C. , Gerik Kimberly J. , Lodge Jennifer K.
Published: November 2012

To initiate and establish infection in mammals, the opportunistic fungal pathogen
Cryptococcus neoformans
must survive and thrive upon subjection to host temperature. Primary maintenance of cell integrity is controlled through the protein kinase C1 (PKC1) signaling pathway, which is regulated by a Rho1 GTPase in
Saccharomyces cerevisiae
. We identified three
C. neoformans
Rho GTPases, Rho1, Rho10, and Rho11, and have begun to elucidate their role in growth and activation of the PKC1 pathway in response to thermal stress. Western blot analysis revealed that heat shock of wild-type cells resulted in phosphorylation of Mpk1 mitogen-activated protein kinase (MAPK). Constitutive activation of Rho1 caused phosphorylation of Mpk1 independent of temperature, indicating its role in pathway regulation. A strain with a deletion of
RHO10
also displayed this constitutive Mpk1 phosphorylation phenotype, while one with a deletion of
RHO11
yielded phosphorylation similar to that of wild type. Surprisingly, like a
rho10
Δ strain, a strain with a deletion of both
RHO10
and
RHO11
displayed temperature sensitivity but mimicked wild-type phosphorylation, which suggests that Rho10 and Rho11 have coordinately regulated functions. Heat shock-induced Mpk1 phosphorylation also required the PKC1 pathway kinases Bck1 and Mkk2. However, Pkc1, thought to be the major regulatory kinase of the cell integrity pathway, was dispensable for this response. Together, our results argue that Rho proteins likely interact via downstream components of the PKC1 pathway or by alternative pathways to activate the cell integrity pathway in
C. neoformans
.
Chlorobaculum tepidum TLS Displays a Complex Transcriptional Response to Sulfide Addition
Authors: Eddie Brian J. , Hanson Thomas E.
Published: November 2012

Chlorobaculum tepidum
is a green sulfur bacterium (GSB) that is a model system for phototrophic sulfur oxidation. Despite over 2 decades of research, conspicuous gaps exist in our understanding of its electron donor metabolism and regulation. RNA sequencing (RNA-seq) was used to provide a global picture of the
C. tepidum
transcriptome during growth on thiosulfate as the sole electron donor and at time points following the addition of sulfide to such a culture. Following sulfide addition, 121 to 150 protein-coding genes displayed significant changes in expression depending upon the time point. These changes included a rapid decrease in expression of thiosulfate and elemental sulfur oxidation genes. Genes and gene loci with increased expression included CT1087, encoding a sulfide:quinone oxidoreductase required for growth in high sulfide concentrations; a polysulfide reductase-like complex operon,
psrABC
(CT0496 to CT0494); and, surprisingly, a large cluster of genes involved in iron acquisition. Finally, two genes that are conserved as a cassette in anaerobic bacteria and archaea, CT1276 and CT1277, displayed a strong increase in expression. The CT1277 gene product contains a DNA-binding domain, suggesting a role for it in sulfide-dependent gene expression changes.
Partial Complementation of Sinorhizobium meliloti bacA Mutant Phenotypes by the Mycobacterium tuberculosis BacA Protein
Authors: Arnold M. F. F. , Haag A. F. , Capewell S. , Boshoff H. I. , James E. K. , McDonald R. , Mair I. , Mitchell A. M. , Kerscher B. , Mitchell T. J. , Mergaert P. , Barry C. E. , Scocchi M. , Zanda M. , Campopiano D. J. , Ferguson G. P.
Published: November 2012

The
Sinorhizobium meliloti
BacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (
Medicago sativa
). The
Mycobacterium tuberculosis
BacA homolog was found to be important for the maintenance of chronic murine infections, yet its
in vivo
function is unknown. In the legume plant as well as in the mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We found that the
M. tuberculosis
BacA protein was able to partially complement the symbiotic defect of an
S. meliloti
BacA-deficient mutant on alfalfa plants and to protect this mutant
in vitro
from the antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant human β-defensin 2 (HBD2). This finding was also confirmed using an
M. tuberculosis
insertion mutant. Furthermore,
M. tuberculosis
BacA-mediated protection of the legume symbiont
S. meliloti
against legume defensins as well as HBD2 is dependent on its attached ATPase domain. In addition, we show that
M. tuberculosis
BacA mediates peptide uptake of the truncated bovine AMP, Bac7
1-16
. This process required a functional ATPase domain. We therefore suggest that
M. tuberculosis
BacA is important for the transport of peptides across the cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA-mediated protection against host AMPs might be important for the maintenance of latent infections.
Dermatofibrosarcoma: a rare neoplasm of skin
Authors: Aziz Rizwan , Jamil Anwer
Published: November 2012

A 25-year-old lady presented with a small pea-sized lesion on left side of her neck, anteriorly. There was no history of any other lesion on her body. She was medically fit otherwise. An excision was planned, after taking consent from her, which was performed under local anaesthesia as a day procedure. Her postoperative recovery was uneventful. Histopathology showed dermatofibrosarcoma protuberance which is an extremely rare skin tumour. She was further investigated for metastasis. Her CT scan of chest, abdomen and pelvis was performed which showed prominent thymus. Other than this finding, no other abnormality was found in CT scan.
Diabetes and intermediate hyperglycaemia in Kisantu, DR Congo: a cross-sectional prevalence study
Authors: Muyer Muel Telo , Muls Erik , Mapatano Mala Ali , Makulo Jean-Robert , Mvitu Moise , Kimenyembo Wivine , Mandja Bien-Aimé , Kimbondo Pierre , Bieleli Chris Bonketo , Kaimbo wa Kaimbo Dieudonné , Buntinx Frank
Published: November 2012

Objectives

To study the prevalence and risk markers of diabetes mellitus and intermediate hyperglycaemia (IH) in Kisantu, a semirural town in Bas-Congo province, The Democratic Republic of Congo.

Design

A cross-sectional population-based survey.

Settings

A modified WHO STEPwise strategy was used. Capillary glycaemia was measured for fasting plasma glucose and 2-h-postload glucose. Both WHO/IDF (International Diabetes Federation) 2006 and American Diabetes Association (ADA) 2003 diagnostic criteria for diabetes and IH were used.

Participants

1898 subjects aged ⩾ 20 years.

Results

Response rate was 93.7%. Complete data were available for 1759 subjects (86.9%). Crude and standardised (for Doll and UN population) prevalence of diabetes were 4.8% and 4.0–4.2%. Crude IH prevalence was 5.8% (WHO/IDF) and 14.2% (ADA). Independent risk markers for diabetes (p<0.01) were male (OR 2.5), age 50–69 years (OR 2.6), family history (OR 3.5), waist (OR 4.1) and alcohol consumption (OR 0.36). In receiver operating characteristic (ROC) analysis, prediction of diabetes was slightly better by waist than body mass index (BMI). IH defined according to WHO/IDF was associated with BMI (OR 2.6, p<0.001). IH defined according to ADA was associated (p<0.05) with waist (OR 1.4), education level (OR 1.6), BMI (OR 2.4) and physical activity (OR 0.7).

Conclusions

Current prevalence of diabetes in DR Congo exceeds IDF projections for 2030. The lower glucose threshold used by ADA almost triples impaired fasting glucose prevalence compared to WHO/IDF criteria. The high proportion of disorders of glycaemia made up by IH suggests the early stages of a diabetes epidemic.
Success rates and procedure times of oesophageal temperature probe insertion for therapeutic hypothermia treatment of cardiac arrest according to insertion methods in the emergency department
Authors: Paik Uh-Hyun , Lee Tae Rim , Kang Mun Ju , Shin Tae Gun , Sim Min Seob , Jo Ik Joon , Song Keun Jeong , Jeong Yeon Kwon
Published: November 2012

Purpose

Therapeutic hypothermia has become the standard treatment for unconscious patients in cardiac arrest. Although various body parts, including the oesophagus, rectum, bladder and tympanum, can be used for measurement of the core temperature, the oesophageal temperature is preferred because of its accuracy and stability. We first investigated the success rate and procedure time of oesophageal temperature probe (ETP) insertion according to the insertion method.

Methods

The conventional method involved blind insertion through nasal orifices. The alternative method was insertion with Magill's forceps or long forceps under visualisation using a direct laryngoscope. The new method was performed as follows: (1) insertion of another endotracheal tube (ETT) orally into the oesophagus; (2) insertion of a temperature probe into the hole of the ETT; (3) removal of the ETT. To compare the success rates and procedure times according to the insertion method, we collected data retrospectively from the prospective Samsung Medical Centre hypothermia database and medical records.

Results

A total of 91 cases were examined. Insertion was performed using the conventional method in 36 cases, the alternative method in 26, and the new method in 29. Rates of success on the first attempt were 63.9%, 65.4% and 100%, and procedure times were 33.2±13.6, 33.3±17.8 and 27.0±7.9 min, for the conventional, alternative and new methods, respectively. The initial success rates and procedure times were significantly different among the three groups (p<0.01).

Conclusions

The new ETP insertion method had a better first attempt success rate than the conventional method and the alternative method.
Haemostatic dressings in prehospital care
Authors: Smith Adam Hewitt , Laird Colville , Porter Keith , Bloch Mark
Published: November 2012

Massive haemorrhage still accounts for up to 40% of mortality after traumatic injury. The importance of limiting blood loss after injury in order to prevent its associated complications has led to rapid advances in the development of dressings for haemostatic control. Driven by recent military conflicts, there is increasing evidence to support their role in the civilian prehospital care environment. This review aims to summarise the key characteristics of the haemostatic dressings currently available on the market and provide an educational review of the published literature that supports their use. Medline and Embase were searched from start to January 2012. Other sources included both manufacturer and military publications. Agents not designed for use in prehospital care or that have been removed from the market due to significant safety concerns were excluded. The dressings reviewed have differing mechanisms of action. Mineral based dressings are potent activators of the intrinsic clotting cascade resulting in clot formation. Chitosan based dressings achieve haemostasis by adhering to damaged tissues and creating a physical barrier to further bleeding. Acetylated glucosamine dressings work via a combination of platelet and clotting cascade activation, agglutination of red blood cells and local vasoconstriction. Anecdotal reports strongly support the use of haemostatic dressings when bleeding cannot be controlled using pressure dressings alone; however, current research focuses on studies conducted using animal models. There is a paucity of published clinical literature that provides an evidence base for the use of one type of haemostatic dressing over another in humans.
Over-expression of phosphorylated mammalian target of rapamycin is associated with poor survival in oesophageal adenocarcinoma: a tissue microarray study
Authors: Prins Margriet J D , Verhage Roy J J , Ruurda Jelle P , ten Kate Fiebo J W , van Hillegersberg Richard
Published: November 2012

Background

Protein kinase mammalian target of rapamycin (mTOR) is an important downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway. In several tumour types, phosphorylated mTOR (p-mTOR) over-expression is an independent prognostic marker for poor survival. However, p-mTOR expression has not been assessed in oesophageal adenocarcinoma (OAC).

Materials and methods

Tumour cores of 154 patients with OAC were included in a tissue microarray (TMA). Scoring criteria were based on p-mTOR staining intensity.

Results

147 (95.5%) patients were available for immunohistochemical evaluation. Over-expression of p-mTOR was detected in 29 (19.7%) tumours, whereas 118 (80.3%) patients showed negative expression. Over-expression was significantly associated with poor overall survival in univariate analysis (HR 1.648; 95% CI 1.019 to 2.664; p=0.042). Median survival was 21.2 months in patients with p-mTOR over-expression and 29.0 in the negative p-mTOR group (p=0.040). In addition, a trend towards p-mTOR over-expression and vasoinvasive growth was seen (p=0.057). In multivariate analysis, including clinical and pathological variables (p<0.10), only T-stage (HR 2.795; 95% CI 1.343 to 5.813; p=0.006) and differentiation grade (HR 2.198; 95% CI 1.353 to 3.570; p=0.001) were independent prognostic markers of poor survival.

Conclusion

p-mTOR over-expression was detected in 19.7% of patients with OAC and was associated with poor overall survival.
Anatomical basis and histopathological changes resulting from selective internal radiotherapy for liver metastases
Authors: Wang Lai Mun , Jani Anant R , Hill Esme J , Sharma Ricky A
Published: November 2012

Background

Knowledge that liver tumours preferentially take their blood supply from the arterial blood supply rather than the portal venous system can be used for local delivery of treatment or for embolisation to cut off the blood supply to tumours.

Aims

To present histological evaluation of malignant and non-malignant hepatic tissue of one such therapy, selective internal radiation therapy (SIRT) with yttrium-90 microspheres, to decipher its principal mechanism of action.

Methods

The H&E stained sections of hepatic resection specimens from three patients with liver metastases from colorectal (CRC) cancer, who underwent hepatic surgery 4–9 months following SIRT, were examined and the pathological changes documented.

Results

Resin microspheres were identified in the vascular tumour bed and vessels within the portal tracts of the background liver parenchyma. Microspheres were usually associated with giant cell reaction or histiocytes. In the tumour bed, tumour necrosis, mucinous alteration, collections of foamy histiocytes, ectatic vessels, calcification and fibrosis were observed. There was minimal cellular inflammatory response observed, suggestive of direct radiation injury as a non-immune mediated process.

Conclusions

We describe in detail the spectrum of histopathological changes in malignant tissue and liver parenchyma in patients with metastatic CRC treated with SIRT. Our findings are consistent with the hypothesis that the principal mechanism of action of SIRT appears to be via arterially directed delivery of highly radioactive microspheres in and around the vascular tumour bed rather than by micro-arterial embolisation.
Endovascular treatment of very small ruptured intracranial aneurysms: complications, occlusion rates and prediction of outcome
Authors: Starke Robert M , Chalouhi Nohra , Ali Muhammad S , Penn David L , Tjoumakaris Stavropoula I , Jabbour Pascal M , Gonzalez L Fernando , Rosenwasser Robert H , Dumont Aaron S
Published: November 2012

Objective

To assess predictors of outcome following endovascular treatment of small ruptured intracranial aneurysms (SRA).

Methods

Between 2004 and 2011, 91 patients with SRA (≤3 mm) were treated at our institution. Multivariate analysis was carried out to assess predictors of endovascular-related complications, aneurysm obliteration (>95%), recanalization and favorable outcome (Glasgow Outcome Scale 3–5).

Results

Endovascular treatment was aborted in nine of 91 patients (9.9%). Procedure-related complications occurred in eight of 82 patients (9.8%) of which five were transient and three were permanent. Three patients (3.7%) undergoing endovascular treatment experienced an intraprocedural aneurysm rupture. Three of nine patients (33.3%) treated with stent- or balloon-assisted coiling experienced periprocedural complications compared with five of 73 patients (6.8%) receiving only coils or Onyx (p=0.039). There were no procedural deaths or rehemorrhages. Rates of recanalization and retreatment were 18.2% and 12.7%, respectively. No factors predicted initial occlusion or recanalization. In multivariate analysis, pretreatment factors predictive of a favorable outcome included younger age (OR 0.94; 95% CI 0.91 to 0.99, p=0.017), larger aneurysm size (OR 3.4; 95% CI 1.02 to 11.11, p=0.045), Hunt and Hess grade (OR 0.38; 95% CI 0.19 to 0.75, p=0.005) and location (OR 5.12; 95% CI 1.29 to 20.25, p=0.02). When assessing treatment and post-treatment variables, vasospasm was the only additional covariate predictive of a poor outcome (OR 5.90; 95% CI 1.34 to 25.93,p=0.019).

Conclusions

Most patients with SRA can be treated with endovascular therapy and have limited complications. Overall predictors of outcome for patients undergoing endovascular treatment of SRA include age, aneurysm size, Hunt and Hess grade, location and post-treatment vasospasm.
Obstructive sleep apnoea in adults
Authors: Usmani Zafar Ahmad , Chai-Coetzer Ching Li , Antic Nick A , McEvoy R Doug
Published: November 2012

Obstructive sleep apnoea (OSA) is characterised by repetitive closure of the upper airway, repetitive oxygen desaturations and sleep fragmentation. The prevalence of adult OSA is increasing because of a worldwide increase in obesity and the ageing of populations. OSA presents with a variety of symptoms the most prominent of which are snoring and daytime tiredness. Interestingly though, a significant proportion of OSA sufferers report little or no daytime symptoms. OSA has been associated with an increased risk of cardiovascular disease, cognitive abnormalities and mental health problems. Randomised controlled trial evidence is awaited to confirm a causal relationship between OSA and these various disorders. The gold standard diagnostic investigation for OSA is overnight laboratory-based polysomnography (sleep study), however, ambulatory models of care incorporating screening questionnaires and home sleep studies have been recently evaluated and are now being incorporated into routine clinical practice. Patients with OSA are very often obese and exhibit a range of comorbidities, such as hypertension, depression and diabetes. Management, therefore, needs to be based on a multidisciplinary and holistic approach which includes lifestyle modifications. Continuous positive airway pressure (CPAP) is the first-line therapy for severe OSA. Oral appliances should be considered in patients with mild or moderate disease, or in those unable to tolerate CPAP. New, minimally invasive surgical techniques are currently being developed to achieve better patient outcomes and reduce surgical morbidity. Successful long-term management of OSA requires careful patient education, enlistment of the family's support and the adoption of self-management and patient goal-setting principles.
Saccharomyces boulardii viability and efficacy in horses with antimicrobial‐induced diarrhoea
Authors: Boyle A. G. , Magdesian K. G. , Gallop R. , Sigdel S. , Durando M. M.
Published: November 2012

Saccharomyces boulardii has been successfully used in the prevention and treatment of antimicrobial‐associated diarrhoea in humans. We hypothesised that a viable, dried lyophilised preparation of S boulardii would survive in the gastrointestinal tract of horses with antimicrobial‐associated enterocolitis, and significantly decrease the duration of diarrhoea. Twenty‐one horses, over one year of age, with antimicrobial‐associated diarrhoea of up to 72 hours duration, were consecutively randomised in a controlled prospective study. The treatment group received S boulardii (25 g, orally, every 12 hours) until the cessation of clinical signs. S boulardii was successfully cultured in 58.3 per cent of treatment horses on day 3. No statistically significant differences were found in days to return to normal faecal consistency; resolution of watery diarrhoea; return to normal heart rate, respiratory rate and temperature; resolution of leucopaenia; attitude improvement; appetite improvement; and survival at discharge. This is the first study to demonstrate survival of S boulardii in horses with gastrointestinal illness. Further study of the efficacy and safety of S boulardii in horses with antimicrobial‐associated diarrhoea in a larger group is warranted.
MULTISCALE ENTROPY ANALYSIS OF TRAFFIC TIME SERIES
Authors: WANG JING , SHANG PENGJIAN , ZHAO XIAOJUN , XIA JIANAN
Published: November 2012

There has been considerable interest in quantifying the complexity of different time series, such as physiologic time series, traffic time series. However, these traditional approaches fail to account for the multiple time scales inherent in time series, which have yielded contradictory findings when applied to real-world datasets. Then multi-scale entropy analysis (MSE) is introduced to solve this problem which has been widely used for physiologic time series. In this paper, we first apply the MSE method to different correlated series and obtain an interesting relationship between complexity and Hurst exponent. A modified MSE method called multiscale permutation entropy analysis (MSPE) is then introduced, which replaces the sample entropy (SampEn) with permutation entropy (PE) when measuring entropy for coarse-grained series. We employ the traditional MSE method and MSPE method to investigate complexities of different traffic series, and obtain that the complexity of weekend traffic time series differs from that of the workday time series, which helps to classify the series when making predictions.
REMOVAL OF CATIONIC DYES FROM AQUEOUS SOLUTION USING CARBON-ENCAPSULATED SUPERPARAMAGNETIC COLLOIDAL NANOPARTICLES AS ADSORBENT
Authors: WANG HUI , ZHOU XUHUI , CHEN QIANWANG
Published: November 2012

This paper demonstrates the application of negative charge-functionalized carbon-encapsulated superparamagnetic colloidal nanoparticles being as nanoadsorbents for the removal of cationic dyes from aqueous solutions. Adsorption characteristics of the magnetic nanoadsorbents were examined using methylene blue as adsorbates, exhibiting excellent ability to remove cationic dyes from aqueous solutions. In addition, the influences of uptake time, concentration of nanoadsorbents and pH values of aqueous solution on the removal of cationic dyes have been discussed. Results show that the removal efficiency can be up to 90% at a dye concentration of 100 mg L-1 when the uptake time is 1 min, which indicates rapidly removal ability of the magnetic nanoadsorbents. Furthermore, other cationic dyes including rhodamine B and methyl violet were used to examine the universality of nanoadsorbents.
Integrated stratigraphy (magneto-, bio- and chronostratigraphy) and geochronology of the Palaeogene pelagic succession of the Umbria–Marche Basin (central Italy)
Authors: Coccioni Rodolfo , Sideri Marianna , Bancalà Giuseppe , Catanzariti Rita , Frontalini Fabrizio , Jovane Luigi , Montanari Alessandro , Savian Jairo
Published: November 2012

Extensive outcrops in the Umbria–Marche Basin of central Italy include some of the most complete successions of Palaeogene sediments known from the Tethyan Realm. Owing to the continuous deposition in a pelagic setting, a rather modest tectonic overprint, the availability of excellent age control through magneto-, bio-, chemo- and tephrostratigraphy, and direct radioisotopic dates from interbedded volcaniclastic layers, these sediments have played a prominent role in the establishment of standard Palaeogene time scales. We present here a complete and well-preserved Palaeogene pelagic composite succession of the Umbria–Marche Basin, which provides the means for an accurate and precise calibration of the Palaeogene time scale. As a necessary step towards the compilation of a more robust database on a wide scale so as to improve the magneto-, bio- and chronostratigraphic framework of the classical southern Tethyan zonations, enabling regional and supraregional correlations, we have constructed a record of reliable Palaeogene planktonic foraminifera, calcareous nannofossil and dinocyst biohorizons commonly used in tropical to subtropical Cenozoic zonations. In addition, an age model is provided for the Palaeogene pelagic composite succession based on magnetostratigraphy, planktonic foraminifera and calcareous nannofossils, which contributes to an integrated chronology for the Palaeogene Tethyan sediments from
c.
65.5 to 23 Ma.

Supplementary material:

Tables 1 to 13 which provide further details of the Palaeogene pelagic succession of the Umbria–Marche Basin (central Italy) are available at
http://www.geolsoc.org.uk/SUP18539
Neogene rotations in the Jiuquan Basin, Hexi Corridor, China
Authors: Yan Maodu , Fang Xiaomin , Van Der Voo Rob , Song Chunhui , Li Jijun
Published: November 2012

Vertical-axis rotations of blocks in/around the Tibetan Plateau can be attributed to the India–Asia collision. Study of the vertical-axis rotations of these blocks will increase our understanding of the mechanisms and kinematics of continent–continent collisions. We report here a new palaeomagnetic study of rotations using data from four localities (five magnetostratigraphy sections) in the Jiuquan Basin. Our study indicates that the mean declinations of each section are different from each other, similar to what has been observed in the other localities in the NE Tibetan Plateau. However, using the mean directions of every 100 m of section, we observe that the four localities have similar sequential patterns of rotations during the last 13 Ma: significant continuous counterclockwise before
c.
8.0 Ma, insignificant rotations between 8.0–4.0 Ma, and slight clockwise rotation after 4.0 Ma. This indicates that, rather than being a record of spatially varying declinations, it is a temporal variation in the occurrence of regional rotations. Combined with other geological evidence, the rotation patterns may suggest two major tectonic activity phases of the northeastern Tibetan Plateau during the last 13 Ma: an eastward extrusion and strike-slip dominant phase before 8.0 Ma, a significant shortening and a rapid uplift dominant phase after 8.0 Ma.

Supplementary material:

Magnetostratigraphic results of the Hongshuiba and Wenshushan sections are available at:
http://www.geolsoc.org.uk/SUP18540
.
Independent trafficking of the KCNQ1 K+channel and H+-K+-ATPase in gastric parietal cells from mice
Authors: Nguyen Nhung , Kozer-Gorevich Noga , Gliddon Briony L. , Smolka Adam J. , Clayton Andrew H. , Gleeson Paul A. , van Driel Ian R.
Published: November 2012

Gastric acid secretion by the H+-K+-ATPase at the apical surface of activated parietal cells requires luminal K+provided by the KCNQ1/KCNE2 K+channel. However, little is known about the trafficking and relative spatial distribution of KCNQ1 and H+-K+-ATPase in resting and activated parietal cells and the capacity of KCNQ1 to control acid secretion. Here we show that inhibition of KCNQ1 activity quickly curtails gastric acid secretion in vivo, even when the H+-K+-ATPase is permanently anchored in the apical membrane, demonstrating a key role of the K+channel in controlling acid secretion. Three-dimensional imaging analysis of isolated mouse gastric units revealed that the majority of KCNQ1 resides in an intracytoplasmic, Rab11-positive compartment in resting parietal cells, distinct from H+-K+-ATPase-enriched tubulovesicles. Upon activation, there was a significant redistribution of H+-K+-ATPase and KCNQ1 from intracytoplasmic compartments to the apical secretory canaliculi. Significantly, high Förster resonance energy transfer was detected between H+-K+-ATPase and KCNQ1 in activated, but not resting, parietal cells. These findings demonstrate that H+-K+-ATPase and KCNQ1 reside in independent intracytoplasmic membrane compartments, or membrane domains, and upon activation of parietal cells, both membrane proteins are transported, possibly via Rab11-positive recycling endosomes, to apical membranes, where the two molecules are closely physically opposed. In addition, these studies indicate that acid secretion is regulated by independent trafficking of KCNQ1 and H+-K+-ATPase.
Cardiomyocyte architectural plasticity in fetal, neonatal, and adult pig hearts delineated with diffusion tensor MRI
Authors: Zhang Lei , Allen John , Hu Lingzhi , Caruthers Shelton D. , Wickline Samuel A. , Chen Junjie
Published: November 2012

Cardiomyocyte organization is a critical determinant of coordinated cardiac contractile function. Because of the acute opening of the pulmonary circulation, the relative workload of the left ventricle (LV) and right ventricle (RV) changes substantially immediately after birth. We hypothesized that three-dimensional cardiomyocyte architecture might be required to adapt rapidly to accommodate programmed perinatal changes of cardiac function. Isolated fixed hearts from pig fetuses or pigs at midgestation, preborn, postnatal day 1 (P1), postnatal day 5, postnatal day 14 (P14), and adulthood ( n = 5 for each group) were acquired for diffusion-weighted magnetic resonance imaging. Cardiomyocyte architecture was visualized by three-dimensional fiber tracking and was quantitatively evaluated by the measured helix angle (αh). Upon the completion of MRI, hearts were sectioned and stained with hematoxylin/eosin (H&E) to evaluate cardiomyocyte alignment, with picrosirius red to evaluate collagen content, and with anti-Ki67 to evaluate postnatal cell proliferation. The helical architecture of cardiomyocyte was observed as early as the midgestational period. Postnatal changes of cardiomyocyte architecture were observed from P1 to P14, which primary occurred in the septum and RV free wall (RVFW). In the septum, the volume ratio of LV- vs. RV-associated cardiomyocytes rapidly changed from RV-LV balanced pattern at birth to LV dominant pattern by P14. In the RVFW, subendocardial αh decreased by ∼30° from P1 to P14. These findings indicate that the helical architecture of cardiomyocyte is developed as early as the midgestation period. Substantial and rapid adaptive changes in cardiac microarchitecture suggested considerable developmental plasticity of cardiomyocyte form and function in the postnatal period in response to altered cardiac mechanical function.
Cardiomyocyte-specific overexpression of an active form of Rac predisposes the heart to increased myocardial stunning and ischemia-reperfusion injury
Authors: Talukder M. A. Hassan , Elnakish Mohammad T. , Yang Fuchun , Nishijima Yoshinori , Alhaj Mazin A. , Velayutham Murugesan , Hassanain Hamdy H. , Zweier Jay L.
Published: November 2012

The GTP-binding protein Rac regulates diverse cellular functions including activation of NADPH oxidase, a major source of superoxide production (O2·−). Rac1-mediated NADPH oxidase activation is increased after myocardial infarction (MI) and heart failure both in animals and humans; however, the impact of increased myocardial Rac on impending ischemia-reperfusion (I/R) is unknown. A novel transgenic mouse model with cardiac-specific overexpression of constitutively active mutant form of Zea maize Rac D (ZmRacD) gene has been reported with increased myocardial Rac-GTPase activity and O2·−generation. The goal of the present study was to determine signaling pathways related to increased myocardial ZmRacD and to what extent hearts with increased ZmRacD proteins are susceptible to I/R injury. The effect of myocardial I/R was examined in young adult wild-type (WT) and ZmRacD transgenic (TG) mice. In vitro reversible myocardial I/R for postischemic cardiac function and in vivo regional myocardial I/R for MI were performed. Following 20-min global ischemia and 45-min reperfusion, postischemic cardiac contractile function and heart rate were significantly reduced in TG hearts compared with WT hearts. Importantly, acute regional myocardial I/R (30-min ischemia and 24-h reperfusion) caused significantly larger MI in TG mice compared with WT mice. Western blot analysis of cardiac homogenates revealed that increased myocardial ZmRacD gene expression is associated with concomitant increased levels of NADPH oxidase subunit gp91phox, O2·−, and P21-activated kinase. Thus these findings provide direct evidence that increased levels of active myocardial Rac renders the heart susceptible to increased postischemic contractile dysfunction and MI following acute I/R.
The Anrep effect: 100 years later
Authors: Cingolani Horacio E. , Pérez Néstor G. , Cingolani Oscar H. , Ennis Irene L.
Published: November 2012

Myocardial stretch elicits a rapid increase in developed force, which is mainly caused by an increase in myofilament calcium sensitivity (Frank-Starling mechanism). Over the ensuing 10–15 min, a second gradual increase in force takes place. This slow force response to stretch is known to be the result of an increase in the calcium transient amplitude and constitutes the in vitro equivalent of the Anrep effect described 100 years ago in the intact heart. In the present review, we will update and discuss what is known about the Anrep effect as the mechanical counterpart of autocrine/paracrine mechanisms involved in its genesis. The chain of events triggered by myocardial stretch comprises 1) release of angiotensin II, 2) release of endothelin, 3) activation of the mineralocorticoid receptor, 4) transactivation of the epidermal growth factor receptor, 5) increased formation of mitochondria reactive oxygen species, 6) activation of redox-sensitive kinases upstream myocardial Na+/H+ exchanger (NHE1), 7) NHE1 activation, 8) increase in intracellular Na+ concentration, and 9) increase in Ca2+ transient amplitude through the Na+/Ca2+ exchanger. We will present the experimental evidence supporting each of the signaling steps leading to the Anrep effect and its blunting by silencing NHE1 expression with a specific small hairpin interference RNA injected into the ventricular wall.
Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats
Authors: Veitenheimer Britta , Osborn John W.
Published: November 2012

Increased plasma osmolality elevates mean arterial pressure (MAP) through activation of the sympathetic nervous system, but the neurotransmitters released in the spinal cord to regulate MAP during osmotic stress remain unresolved. Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic preganglionic neurons in the spinal cord and are likely activated during conditions of osmotic stress; however, this has not been examined in conscious rats. This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ∼15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5-phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared with normotensive controls. Our results suggest that spinally released glutamate mediates increased MAP during 48-h WD and DOCA-salt hypertension.
Elongated Photonic Nanojet from Truncated Cylindrical Zone Plate
Authors: Stafeev Sergey S. , Kotlyar Victor V.
Published: November 2012

Previously (Chen et al., 2004), it was shown that dielectric cylinder can form focal spots with small diameters and long depth. This type of focal spot was called photonic nanojet. In this paper, it was shown that dielectric cylinder of radius 595 nm (1.12 of wavelength) forms near the surface a photonic nanojet with diameter equal to 0.31 of wavelength and depth of focus equal to 0.57 of wavelength. Adding truncated concentric rings with radiuses equal to radiuses of zone plate to the cylinder increases the depth of focus to 1.18 of the wavelength. The diameter and intensity of focal spot near the cylinder surface remain unchanged.
Antioxidant, Antinociceptive, and Anti-Inflammatory Activities fromActinidia callosavar.callosa In VitroandIn Vivo
Authors: Liao Jung-Chun , Deng Jeng-Shyan , Lin Ying-Chih , Lee Chao-Ying , Lee Min-Min , Hou Wen-Chi , Huang Shyh-Shyun , Huang Guan-Jhong
Published: November 2012

Actinidia callosavar.callosahas been widely used to treat antipyretic, analgesic, anti-inflammation, abdominal pain, and fever in Taiwan. The aim of this study was to evaluate the antioxidant, antinociceptive, and anti-inflammatory lipopolysaccharide-(LPS-)induced nitric oxide (NO) production in RAW264.7 macrophages and pawedema induced byλ-carrageenan activities of the methanol extract fromA. callosa. In HPLC analysis, the fingerprint chromatogram of ethyl-acetate fraction ofA. callosa(EAAC) was established. EAAC showed the highest TEAC and DPPH radical scavenging activities, respectively. We evaluated that EAAC and the reference compound of catechin and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Treatment of male ICR mice with EAAC significantly inhibited the numbers of acetic acid-induced writhing response and the formalin-induced pain in the late phase. Administration of EAAC showed a concentration-dependent inhibition on paw edema development after Carr treatment in mice. Anti-inflammatory mechanisms of EAAC might be correlated to the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1)in vitroandin vivo. Overall, the results showed that EAAC demonstrated antioxidant, antinociceptive, and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain.
Observation of Pain-Sensitive Points along the Meridians in Patients with Gastric Ulcer or Gastritis
Authors: Ben Hui , Li Liang , Rong Pei-Jing , Jin Zhi-Gao , Zhang Jian-Liang , Li Yan-Hua , Li Xia
Published: November 2012

This study aims to investigate the sensitization of human skin points along certain meridians related to visceral disease by using the pressure-pain threshold (PPT) as an indicator. We detected and compared the PPTs of people with and without gastric ulcer or gastritis on the related acupoints, abdomen area, and back area with von Frey detector and observed the similarities and differences under their respective physiological and pathological states. The results showed that (1) the PPTs of patients with gastric ulcer on related acupoints decreased significantly compared with the control group; (2) there was no significant difference in PPT between the chosen points of the measured meridian and the adjacent nonacupoints; (3) there was an apparent distribution of tender points on the relevant abdomen and back regions of patients with gastric ulcer or gastritis, but none was found on the control group; (4) the pain-sensitive points of gastric ulcer and gastritis patients were BURONG (ST19), LIANGMEN (ST21), and HUAROUMEN (ST24) of the stomach meridian on the abdominal region and PISHU (BL20), WEISHU (BL21), and WEICANG (BL50) on the back, among others The results suggest that the practical significance of acupoints may lie in its role as a relatively sensitive functional area. In a pathological state, the reflex points on the skin which are related to certain visceral organs become sensitive and functionally intensify.
Human Leukocyte Antigen Profiles of Latin American Populations: Differential Admixture and Its Potential Impact on Hematopoietic Stem Cell Transplantation
Authors: Arrieta-Bolaños Esteban , Madrigal J. Alejandro , Shaw Bronwen E.
Published: November 2012

The outcome of hematopoietic stem cell transplantation (HSCT) is shaped by both clinical and genetic factors that determine its success. Genetic factors including human leukocyte antigen (HLA) and non-HLA genetic variants are believed to influence the risk of potentially fatal complications after the transplant. Moreover, ethnicity has been proposed as a factor modifying the risk of graft-versus-host disease. The populations of Latin America are a complex array of different admixture processes with varying degrees of ancestral population proportions that came in different migration waves. This complexity makes the study of genetic risks in this region complicated unless the extent of this variation is thoroughly characterized. In this study we compared the HLA-A and HLA-B allele group profiles for 31 Latin American populations and 61 ancestral populations from Iberia, Italy, Sub-Saharan Africa, and America. Results from population genetics comparisons show a wide variation in the HLA profiles from the Latin American populations that correlate with different admixture proportions. Populations in Latin America seem to be organized in at least three groups with (1) strong Amerindian admixture, (2) strong Caucasian component, and (3) a Caucasian-African gradient. These results imply that genetic risk assessment for HSCT in Latin America has to be adapted for different population subgroups rather than as a pan-Hispanic/Latino analysis.
Bleeding in Hepatic Surgery: Sorting through Methods to Prevent It
Authors: Romano Fabrizio , Garancini Mattia , Uggeri Fabio , Degrate Luca , Nespoli Luca , Gianotti Luca , Nespoli Angelo , Uggeri Franco
Published: November 2012

Liver resections are demanding operations which can have life threatening complications although they are performed by experienced liver surgeons. The parameter “Blood Loss” has a central role in liver surgery, and different strategies to minimize it are a key to improve results. Moreover, recently, new technologies are applied in the field of liver surgery, having one goal: safer and easier liver operations. The aim of this paper is to review the different principal solutions to the problem of blood loss in hepatic surgery, focusing on technical aspects of new devices.
Wind Velocity Vertical Extrapolation by Extended Power Law
Authors: Şen Zekai , Altunkaynak Abdüsselam , Erdik Tarkan
Published: November 2012

Wind energy gains more attention day by day as one of the clean renewable energy resources. We predicted wind speed vertical extrapolation by using extended power law. In this study, an extended vertical wind velocity extrapolation formulation is derived on the basis of perturbation theory by considering power law and Weibull wind speed probability distribution function. In the proposed methodology not only the mean values of the wind speeds at different elevations but also their standard deviations and the cross-correlation coefficient between different elevations are taken into consideration. The application of the presented methodology is performed for wind speed measurements at Karaburun/Istanbul, Turkey. At this location, hourly wind speed measurements are available for three different heights above the earth surface.
Posttraumatic Atlantoaxial Rotatory Dislocation in a Healthy Adult Patient: A Case Report and Review of the Literature
Authors: Maida Giuseppe , Marcati Eleonora , Sarubbo Silvio
Published: November 2012

Atlantoaxial rotatory dislocation (AARD) is a rare complication in adults usually leading to pain, spinal cord injury, or death. Clinical and radiological diagnosis is difficult and often delayed. We report a rare case of posttraumatic AARD in a neurological intact 27-year-old male in which initial radiographic evaluation was negative. A computed tomography (CT) scan was promptly done because the patient showed a severe torticollis. Therefore, early diagnosis, immobilisation, and surgical fusion and arthrodesis were performed. After surgery, cervical pain and torticollis were resolved and the patient remained neurologically intact with a CT scan documentation of fusion at the 3-year followup.
Monitoring Heart Disease and Diabetes with Mobile Internet Communications
Authors: Mulvaney David , Woodward Bryan , Datta Sekharjit , Harvey Paul , Vyas Anoop , Thakker Bhaskar , Farooq Omar , Istepanian Robert
Published: November 2012

A telemedicine system is described for monitoring vital signs and general health indicators of patients with cardiac and diabetic conditions. Telemetry from wireless sensors and readings from other instruments are combined into a comprehensive set of measured patient parameters. Using a combination of mobile device applications and web browser, the data can be stored, accessed, and displayed using mobile internet communications to the central server. As an extra layer of security in the data transmission, information embedded in the data is used in its verification. The paper highlights features that could be enhanced from previous systems by using alternative components or methods.
Dyarrheal Syndrome in a Patient Co-Infected withLeishmania infantumandSchistosoma mansoni
Authors: Cota Gláucia Fernandes , Gomes Luciana Inácia , Pinto Bruna Fernandes , Santos-Oliveira Joanna R. , Da-Cruz Alda Maria , Pedrosa Moisés Salgado , Tafuri Wagner Luiz , Rabello Ana
Published: November 2012

This case report describes an atypical clinical presentation of visceral leishmaniasis affecting the digestive tract and causing malabsorption syndrome in a patient without recognized immunosuppressive condition. After appropriate treatment for the classical visceral form of the disease, diarrhea persisted as the main symptom and massive infection byLeishmaniawas detected by histopathology analysis of the duodenal mucosa.Schistosoma mansonicoinfection was also confirmed and treated without impact on diarrhea. New course of amphotericin B finally led to complete improvement of diarrhea. Atypical visceral leishmaniasis involving the gastrointestinal tract is well recognized in HIV coinfection but very rare in immunocompetent patients. The factors determining the control or evolution of theLeishmaniainfection have not been completely identified. This case stresses the importance of atypical symptoms and the unusual location of visceral leishmaniasis, not only in immunodepressed patients, and raises the possible influence of chronic infection byS. mansonireducing the immune response toLeishmania.
Laryngeal Involvement of Multiple Myeloma
Authors: Grobman Ariel B. , Vivero Richard J. , Campuzano-Zuluaga German , Ganjei-Azar Parvin , Rosow David E.
Published: November 2012

The objectives of this paper are to discuss a rare cause of laryngeal multiple myeloma, to review unique pathologic findings associated with plasma cell neoplasms, to discuss epidemiology, differential diagnosis, and treatment options for plasma cell neoplasms of the larynx. Laryngeal multiple myeloma, also noted in the literature as “metastatic” multiple myeloma, presenting as a de novo laryngeal mass is extremely rare with few reported cases. Laryngeal involvement of extramedullary tumors is reported to be between 6% and 18% with the epiglottis, glottis, false vocal folds, aryepiglottic folds, and subglottis involved in decreasing the order of frequency. We present the case of a 58-year-old male with a history of IgA smoldering myeloma who presented to a tertiary care laryngological practice with a two-month history of dysphonia, which was found to be laryngeal involvement of multiple myeloma. We review the classification of and differentiation between different plasma cell neoplasms, disease workups, pathologic findings, and treatment options.