bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional characterization of the hGRαT556I causing Chrousos syndrome
Authors: Nicolaides Nicolas C. , Skyrla Eirini , Vlachakis Dimitrios , Psarra Anna‐Maria G. , Moutsatsou Paraskevi , Sertedaki Amalia , Kossida Sophia , Charmandari Evangelia
Published: November 2015

Background

Chrousos syndrome is a rare pathologic condition characterized by generalized, partial resistance of target tissues to glucocorticoids and caused by inactivating mutations of the human glucocorticoid receptor (hGR) gene. A novel case of Chrousos syndrome has been reported in a patient with adrenal incidentaloma, who harboured a heterozygous point mutation in the hGR gene, which resulted in threonine (T) to isoleucine (I) substitution at amino acid position 556 in the ligand‐binding domain of the receptor.

Objective

To delineate the molecular mechanisms through which the mutant receptor hGRαT556I causes Chrousos syndrome.

Design and Results

Compared with the wild‐type receptor, the mutant receptor hGRαT556I demonstrated 50% reduction in its ability to transactivate glucocorticoid‐responsive genes and in the affinity for the ligand, 30% increase in the ability to transrepress the nuclear factor‐κB‐target genes and a 3,4‐fold delay in the cytoplasmic‐to‐nuclear translocation. The mutant receptor hGRαT556I did not exert a dominant negative effect upon the hGRα‐mediated transcriptional activity; it preserved its ability to bind to DNA and interacted with the glucocorticoid receptor‐interacting protein 1 coactivator mostly through its activation function‐1 domain. Structural biology studies revealed that the T556I mutation caused disruption of the hydrogen bond formed by the T556 with the =O group of P637 backbone, which resulted in a significant relocation of the P637‐bearing loop. This conformational alteration affected the local 3D arrangement of the receptor and hence the electrostatic surface of the region.

Conclusions

The hGRαT556I causes Chrousos syndrome by impairing multiple steps of the glucocorticoid signal transduction pathway.
Ambulatory blood pressure monitoring in daily clinical practice – the Spanish ABPM Registry experience
Authors: Gorostidi Manuel , Banegas José R. , de la Sierra Alejandro , Vinyoles Ernest , Segura Julián , Ruilope Luis M.
Published: November 2015

Many patients are hypertensive at the medical settings but show normal blood pressure out of the doctor's office, and are classified as white‐coat hypertensives. On the other hand, many patients with controlled hypertension at the clinic show ambulatory blood pressure levels above the thresholds considered for an adequate blood pressure control, known as having masked hypertension. Using data from the Spanish Ambulatory Blood Pressure Monitoring Registry (Spanish ABPM Registry), a national program developed to promote the use of the ambulatory technique for hypertension management in daily practice, we have reviewed the main strengths of this approach, that is the ability to detect discrepancies of blood pressure status with respect to office blood pressure measurement, and to better assess accurate rates of hypertension control. White‐coat hypertension within patients with elevated office blood pressure, and masked hypertension within office‐controlled patients affected one of three patients in each office status. On the other hand, rates of ambulatory blood pressure control (50%) doubled those of office blood pressure control (25%), still remaining half the patients uncontrolled. We think that a systematic use of ambulatory blood pressure monitoring, and strategies to improve blood pressure control constitute key priorities in hypertension management.
The influence of number of line pairs in digital intra‐oral radiography on the detection accuracy of horizontal root fractures
Authors: Nejaim Yuri , Gomes Amanda Farias , Silva Emmanuel João Nogueira Leal da , Groppo Francisco Carlos , Haiter Neto Francisco
Published: November 2015

Aim

Line pairs are the unit for measurement of resolution and are related to the spatial quality of the system. Thus, the objective of this study was to evaluate the influence of number of line pairs in digital intra‐oral radiography on the detection accuracy of horizontal root fractures.

Materials and Methods

Sixty‐four extracted single‐root human teeth were used. Thirty‐two had horizontal root fractures created and were mounted in dry human mandibles. The teeth were radiographed with two digital receptors: the Digora Optime (14.3 lp mm‐1) and the Digora Toto (26.3 lp mm‐1). Images were viewed under standardized conditions by 3 calibrated examiners using the respective dedicated software (Digora for Windows 2.6® and Scanora®). Digora Toto® images were also evaluated through the Digora for Windows 2.6® software. The results were statistically analyzed based on the area under the ROC curve for each examiner.

Results

Pairing Digora Toto® with Scanora® allowed for greater accuracy in horizontal root fractures diagnosis, while images acquired with that same system seem to lose accuracy when visualized with Digora for Windows 2.6®. Pairing Digora Optime® with Digora for Windows 2.6® resulted in the lowest accuracy for horizontal root fractures diagnosis.

Conclusions

The higher number of line pairs and the consequent higher image resolution provided by the Digora Toto® system and its dedicated software seem to enhance the accuracy of horizontal root fractures diagnostic imaging.
Effects of plateau pika activities on seasonal plant biomass and soil properties in the alpine meadow ecosystems of the Tibetan Plateau
Authors: Sun Feida , Chen Wenye , Liu Lin , Liu Wei , Cai Yimin , Smith Pete
Published: November 2015

The foraging and burrowing activities of small mammalian herbivores may have either detrimental or beneficial effects on grassland ecosystems; the direction of the effect is determined by the species, population abundances and fluctuations. Twelve survey sites with active burrow of plateau pika were classified into four degrees of density: approximately zero‐density, low‐density, medium‐density and high‐density, to evaluate the impact of different pika densities on vegetation, plant biomass, soil organic carbon and nutrients in a whole growing season. We show that pika as a main supplement to livestock activities contributed to a decrease in the number of plant species, vegetation cover, plant height and seasonal mean biomass, while values at medium‐density site except above‐ground biomass were the lowest. With the exception of available potassium, soil organic carbon, nitrogen, total phosphorus and soil water content, zero‐density areas were significantly higher than those of pika occupied areas. However, there were slight or no differences in vegetation characteristics and soil properties between medium‐and high‐density sites. Our study suggests pika activities with high‐density made palatable forage less and soil carbon and nitrogen more than low‐density, moreover, plateau pika had greater impacts on above‐ground vegetation than on root system.
Manganese‐Doped BiFeO3–BaTiO3 High‐Temperature Piezoelectric Ceramics: Phase Structures and Defect Mechanism
Authors: Yao Zhonghua , Xu Chaobing , Hao Hua , Xu Qi , Hu Wei , Cao Minghe , Liu Hanxing
Published: November 2015

The bulk BiFeO3–BaTiO3 system has been studied as a potential lead‐free high‐temperature piezoelectric material. It is found that the multivalency manganese‐doped 0.8BiFeO3–0.2BaTiO3 ceramics exhibit the coexistence of tetragonal and rhombohedral phases, whereas Mn doping improves the resistivity and exhibits hard characteristic. The optimal properties were obtained at 0.12 wt% Mn addition exhibiting Tc ˜ 637°C. The increase of Tc in Mn‐modified compositions can be ascribed to the appearance of internal electric bias field by acceptor doping. The combination of good electrical properties and high Tc makes these ceramics suitable for elevated temperature piezoelectric devices.
Enhanced Optical Properties of Bredigite‐Structure Ca13.7Eu0.3Mg2[SiO4]8 Phosphor: Effective Eu Reduction by La Co‐Doping
Authors: Kim Seung Jun , Jang Ho Seong , Unithrattil Sanjith , Kim Yoon Hwa , Im Won Bin
Published: November 2015

A green phosphor, La0.4Ca13.3Eu0.3Mg2Si8O31.6+δN0.4−δ (LaCMSN:Eu2+), was prepared by a solid‐state reaction and an efficient green emission was observed at 506 nm under near‐ultraviolet (NUV) excitation. The structural and optical properties of LaCMSN:Eu2+ phosphors as well as their thermal quenching were investigated. The partial substitution of La3+ and N3− in Ca13.7Eu0.3Mg2Si8O32 led to a considerable enhancement in the peak emission intensity by as much as 194%. This demonstrates not only that the total number of Eu2+ activators increased, but also that the probability of a nonradiative transition between Eu2+ and Eu3+ could be reduced as the increase in concentration of the former is at the expense of the later. The white light‐emitting diode (LED) was fabricated using phosphor with a NUV LED chip. The LED showed warm white light with an excellent color rendering index of 91. The LaCMSN:Eu2+ is thus a potential green‐emitting phosphor for white LEDs.
Nursing performance under high workload: a diary study on the moderating role of selection, optimization and compensation strategies
Authors: Baethge Anja , Müller Andreas , Rigotti Thomas
Published: November 2015

Aims

The aim of this study was to investigate whether selective optimization with compensation constitutes an individualized action strategy for nurses wanting to maintain job performance under high workload.

Background

High workload is a major threat to healthcare quality and performance. Selective optimization with compensation is considered to enhance the efficient use of intra‐individual resources and, therefore, is expected to act as a buffer against the negative effects of high workload.

Design

The study applied a diary design. Over five consecutive workday shifts, self‐report data on workload was collected at three randomized occasions during each shift. Self‐reported job performance was assessed in the evening. Self‐reported selective optimization with compensation was assessed prior to the diary reporting.

Methods

Data were collected in 2010. Overall, 136 nurses from 10 German hospitals participated. Selective optimization with compensation was assessed with a nine‐item scale that was specifically developed for nursing. The NASA‐TLX scale indicating the pace of task accomplishment was used to measure workload. Job performance was assessed with one item each concerning performance quality and forgetting of intentions.

Results

There was a weaker negative association between workload and both indicators of job performance in nurses with a high level of selective optimization with compensation, compared with nurses with a low level. Considering the separate strategies, selection and compensation turned out to be effective.

Conclusion

The use of selective optimization with compensation is conducive to nurses’ job performance under high workload levels. This finding is in line with calls to empower nurses’ individual decision‐making.
Morning Blood Pressure Surge as a Predictor of Development of Chronic Kidney Disease
Authors: Turak Osman , Afsar Baris , Siriopol Dimitrie , Ozcan Firat , Cagli Kumral , Yayla Cagri , Oksuz Fatih , Mendi Mehmet Ali , Kario Kazuomi , Covic Adrian , Kanbay Mehmet
Published: November 2015

Blood pressure (BP) usually increases upon awakening––a physiological mechanism called morning BP surge (MBPS). BP values above the MBPS threshold are associated with target organ damage, including left ventricular hypertrophy and proteinuria. Despite these data, there have been no studies that have investigated the association between elevated MBPS and the development of incident chronic kidney disease (CKD). In this study, patients with essential hypertension were included and underwent ambulatory BP measurements and MBPS. Patients were followed for a median of 3.33 years. In total, 622 patients were enrolled. The mean age of patients was 57.6±12.4 years, 54.0% were men, 16.7% had diabetes, and 10.6% had prevalent cardiovascular disease. During follow‐up, 32 patients developed CKD. Higher MBPS, analyzed both as continuous and categorical variables, was associated with incident CKD in all models. Elevated MBPS is associated with kidney function deterioration and the development of CKD. Studies are needed to further examine underlying mechanisms regarding MBPS and these renal outcomes.
Automated Outreach for Cardiovascular‐Related Medication Refill Reminders
Authors: Harrison Teresa N. , Green Kelley R. , Liu In‐Lu Amy , Vansomphone Southida S. , Handler Joel , Scott Ronald D. , Cheetham T. Craig , Reynolds Kristi
Published: November 2015

The objective of this study was to evaluate the effectiveness of an automated telephone system reminding patients with hypertension and/or cardiovascular disease to obtain overdue medication refills. The authors compared the intervention with usual care among patients with an overdue prescription for a statin or lisinopril‐hydrochlorothiazide (lisinopril‐HCTZ). The primary outcome was refill rate at 2 weeks. Secondary outcomes included time to refill and change in low‐density lipoprotein cholesterol and blood pressure. Significantly more patients who received a reminder call refilled their prescription compared with the usual‐care group (statin cohort: 30.3% vs 24.9% [P<.0001]; lisinopril‐HCTZ cohort: 30.7% vs 24.2% [P<.0001]). The median time to refill was shorter in patients receiving the reminder call (statin cohort: 29 vs 36 days [P<.0001]; lisinopril‐HCTZ cohort: 24 vs 31 days [P<.0001]). There were no statistically significant differences in mean low‐density lipoprotein cholesterol and blood pressure. These findings suggest the need for interventions that have a longer‐term impact.
Epigenetic‐Imprinting Changes Caused by Neonatal Fasting Stress Protect From Future Fasting Stress
Authors: Jiang Y. , Denbow C. , Meiri N. , Denbow D. M.
Published: November 2015

Unfavourable nutritional conditions during the neonatal critical period can cause both acute metabolic disorders and severe metabolic syndromes in later life. These phenomena have been tightly related to the epigenetic modification controlling the balance between satiety and hunger in the hypothalamus. In the present study, we investigated epigenetic modification associated with both the fasting stress effects and the short‐term resilience to fasting stress in the hypothalamic paraventricular nucleus (PVN) of chicks. Fasting for 24 h at 3 days of age (D) (i.e. D3) significantly increased global methylation at lysine 27 of histone 3 (H3K27) and its specific histone methyltransferase (HMT) expression level in the PVN. Because global methylation could not fully reveal the changes at specific genes, the regulation of the gene for brain‐derived neurotrophic factor (Bdnf), which was recently also found to have an anorexigenic effect, was evaluated as a potential target. Chromatin immunoprecipitation assay analysis revealed that tri‐ (me3) and di‐methylated (me2) H3K27 exhibited an instant (on D4 only) and latent increase (on both D11 and D41), respectively, at the putative promoter of Bdnf after 24 h of fasting on D3. This indicated that fasting could regulate energy‐expenditure‐related genes via modifying methylation at H3K27, which we suspected might be a protective mechanism for keeping the inner environment homeostatic. To test this hypothesis, a short‐term repetitive fasting stress was applied to chickens, which were fasted for 24 h either on D10 only or on both D3 and D10. It was found that pre‐existing fasting on D3 could induce a short‐term fasting resilience, which rescued the reduction of Bdnf expression from future fasting on D10. We call this phenomenon the ‘molecular memory’, which was mainly conducted by HMTs and H3K27me2/me3 in the PVN. In conclusion, chicks respond to fasting with dynamic methylation at H3K27 in the PVN during the neonatal critical period. This allows the PVN to form a ‘molecular memory’, which keeps the individual inner environment homeostatic and resilient to future fasting over the short term.
A Placebo‐Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation
Authors: Olby N.J. , Muguet‐Chanoit A.C. , Lim J.‐H. , Davidian M. , Mariani C.L. , Freeman A.C. , Platt S.R. , Humphrey J. , Kent M. , Giovanella C. , Longshore R. , Early P.J. , Muñana K.R.
Published: November 2015

Background

Acute intervertebral disk herniation (IVDH) is a common cause of spinal cord injury in dogs and currently there is no proven medical treatment to counter secondary injury effects. Use of methylprednisolone sodium succinate (MPSS) or polyethylene glycol (PEG) as neuroprotectants is advocated but controversial because neither treatment has been tested in placebo‐controlled, randomized, blinded trials in dogs.

Hypothesis

Polyethylene glycol will improve the outcome of severe spinal cord injury caused byIVDHcompared toMPSSor placebo.

Animals

Client‐owned dogs with acute onset of thoracolumbarIVDHcausing paralysis and loss of nociception for <24 hours.

Methods

Dogs were randomized to receiveMPSS,PEG, or placebo; drugs appeared identical and group allocation was masked. Drug administration was initiated once the diagnosis ofIVDHwas confirmed and all dogs underwent hemilaminectomy. Neurologic function was assessed 2, 4, 8, and 12 weeks postoperatively using an open field gait score (OFS) as the primary outcome measure. Outcomes were compared by the Wilcoxon rank sum test.

Results

Sixty‐three dogs were recruited and 47.6% recovered ambulation. 17.5% developed progressive myelomalacia but there was no association with group. There was no difference inOFSamong groups. Although full study power was not reached, conditional power analyses indicated the futility of continued case recruitment.

Conclusions

This clinical trial did not show a benefit of eitherMPSSorPEGin the treatment of acute, severe thoracolumbarIVDHwhen used as adjunctive medical treatment administered to dogs presenting within 24 hours of onset of paralysis.
Preventing environmental enteric dysfunction through improved water, sanitation and hygiene: an opportunity for stunting reduction in developing countries
Authors: Mbuya Mduduzi N. N. , Humphrey Jean H.
Published: November 2015

In 2011, one in every four (26%) children under 5 years of age worldwide was stunted. The realization that most stunting cannot be explained by poor diet or by diarrhoea, nor completely reversed by optimized diet and reduced diarrhoea has led to the hypothesis that a primary underlying cause of stunting is subclinical gut disease. Essentially, ingested microbes set in motion two overlapping and interacting pathways that result in linear growth impairment. Firstly, partial villous atrophy results in a reduced absorptive surface area and loss of digestive enzymes. This in turn results in maldigestion and malabsorption of much needed nutrients. Secondly, microbes and their products make the gut leaky, allowing luminal contents to translocate into systemic circulation. This creates a condition of chronic immune activation, which (i) diverts nutrient resources towards the metabolically expensive business of infection fighting rather than growth; (ii) suppresses the growth hormone‐IGF axis and inhibits bone growth, leading to growth impairment; and (iii) causes further damage to the intestinal mucosa thereby exacerbating the problem. As such, the unhygienic environments in which infants and young children live and grow must contribute to, if not be the overriding cause of, this environmental enteric dysfunction. We suggest that a package of baby‐WASH interventions (sanitation and water improvement, handwashing with soap, ensuring a clean play and infant feeding environment and food hygiene) that interrupt specific pathways through which feco‐oral transmission occurs in the first two years of a child's life may be central to global stunting reduction efforts.
Role of Laser Doppler for the Evaluation of Pedal Microcirculatory Function in Diabetic Neuropathy Patients
Authors: Park Hyung Sub , Yun Han Mi , Jung In Mok , Lee Taeseung
Published: November 2015

Objective

We evaluated whetherLDcan detect alterations in skin microcirculatory flow in type II diabetic neuropathy patients and determined which parameters were most predictive.

Methods

A prospective analysis was performed for three groups with presumed varying degrees of microvascular dysfunction: diabetics with neuropathy (DMN,n = 20), diabetics without microangiopathic complications (DM,n = 20), and healthy controls (n = 16).LDwas performed under strictly controlled protocols with provocation, consisting of vasoconstrictive (valsalva, postural) and vasodilative tests (PORH,LTH).

Results

There was an overall decrease inLDvalues in response to both vasoconstrictive and vasodilative provocations inDMNpatients compared toDMand control groups. Statistically significant parameters were as follows: valsalva,PORHandLTHbetweenDMNand control; valsalva only betweenDMNandDM; andPORHandLTHbetweenDMand control. ROC curve analysis showed that Valsalva was the most accurate parameter inDMNpatients.

Conclusions

LDcould consistently detect differences in microcirculatory flow between the three study groups consisting of gradually more severe microvascular dysfunction. The Valsalva parameter was the most accurate in detecting established microvascular dysfunction, whereasPORHandLTHmay have a possible role for detection of early microvascular impairment.
Endothelium‐Derived Hyperpolarization and Coronary Vasodilation: Diverse and Integrated Roles of Epoxyeicosatrienoic Acids, Hydrogen Peroxide, and Gap Junctions
Authors: Ellinsworth David C. , Sandow Shaun L. , Shukla Nilima , Liu Yanping , Jeremy Jamie Y. , Gutterman David D.
Published: November 2015

Myocardial perfusion and coronary vascular resistance are regulated by signaling metabolites released from the local myocardium that act either directly on the VSMC or indirectly via stimulation of the endothelium. A prominent mechanism of vasodilation is EDH of the arteriolar smooth muscle, with EETs and H2O2 playing important roles in EDH in the coronary microcirculation. In some cases, EETs and H2O2 are released as transferable hyperpolarizing factors (EDHFs) that act directly on the VSMCs. By contrast, EETs and H2O2 can also promote endothelial KCa activity secondary to the amplification of extracellular Ca2+ influx and Ca2+ mobilization from intracellular stores, respectively. The resulting endothelial hyperpolarization may subsequently conduct to the media via myoendothelial gap junctions or potentially lead to the release of a chemically distinct factor(s). Furthermore, in human isolated coronary arterioles dilator signaling involving EETs and H2O2 may be integrated, being either complimentary or inhibitory depending on the stimulus. With an emphasis on the human coronary microcirculation, this review addresses the diverse and integrated mechanisms by which EETs and H2O2 regulate vessel tone and also examines the hypothesis that myoendothelial microdomain signaling facilitates EDH activity in the human heart.
Histopathologic patterns among achalasia subtypes
Authors: Sodikoff J. B. , Lo A. A. , Shetuni B. B. , Kahrilas P. J. , Yang G.‐Y. , Pandolfino J. E.
Published: November 2015

Background

Achalasia has three distinct manometric phenotypes. This study aimed to determine if there were corresponding histopathologic patterns.

Methods

We retrospectively examined surgical muscularis propria biopsies obtained from 46 patients during laparoscopic esophagomyotomy. Pre‐operative (conventional) manometry tracings were reviewed by two expert gastroenterologists who categorized patients into Chicago Classification subtypes. Pathology specimens were graded on degree of neuronal loss, inflammation, fibrosis, and muscle changes.

Key Results

Manometry studies were categorized as follows: type I (n = 20), type II (n = 20), type III (n = 3), and esophagogastric junction outflow obstruction (EGJOO) (n = 3). On histopathology, complete ganglion cell loss occurred in 74% of specimens, inflammation in 17%, fibrosis in 11%, and muscle atrophy in 2%. Comparing type I and type II specimens, there was a statistically significant greater proportion of type I specimens with aganglionosis (19/20 vs 13/20, p = 0.044) and a statistically significant greater degree of ganglion cell loss in type I specimens (Wilcoxon Rank‐Sum, p = 0.016). CD3+/CD8+ cytotoxic T cells represented the predominant inflammatory infiltrate on immunohistochemistry. Three patients had completely normal appearing tissue (1 each in type II, type III, EGJOO).

Conclusions & Inferences

The greater degree, but similar pattern, of ganglion cell loss observed in type I compared to type II achalasia specimens suggests that type I achalasia represents a progression from type II achalasia. The spectrum of histopathologic findings – from complete neuronal loss to lymphocytic inflammation to apparently normal histopathology – emphasizes that ‘achalasia’ represents a pathogenically heterogeneous patient group with the commonality being EGJ outflow obstruction.
Differentially expressed small RNAs in Arabidopsis galls formed by Meloidogyne javanica: a functional role for miR390 and its TAS3‐derived tasiRNAs
Authors: Cabrera Javier , Barcala Marta , García Alejandra , Rio‐Machín Ana , Medina Clémence , Jaubert‐Possamai Stephanie , Favery Bruno , Maizel Alexis , Ruiz‐Ferrer Virginia , Fenoll Carmen , Escobar Carolina
Published: November 2015

Root‐knot nematodes (RKNs) induce inside the vascular cylinder the giant cells (GCs) embedded in the galls. The distinctive gene repression in early‐developing GCs could be facilitated by small RNAs (sRNA) such as miRNAs, and/or epigenetic mechanisms mediated by 24nt‐sRNAs, rasiRNAs and 21‐22nt‐sRNAs. Therefore, the sRNA‐population together with the role of the miR390/TAS3/ARFs module were studied during early gall/GC formation.

Three sRNA libraries from 3‐d‐post‐inoculation (dpi) galls induced by Meloidogyne javanica in Arabidopsis and three from uninfected root segments were sequenced following Illumina‐Solexa technology. pMIR390a::GUS and pTAS3::GUS lines were assayed for nematode‐dependent promoter activation. A sensor line indicative of TAS3‐derived tasiRNAs binding to the ARF3 sequence (pARF3:ARF3‐GUS) together with a tasiRNA‐resistant ARF3 line (pARF3:ARF3m‐GUS) were used for functional analysis.

The sRNA population showed significant differences between galls and controls, with high validation rate and correspondence with their target expression: 21‐nt sRNAs corresponding mainly to miRNAs were downregulated, whilst 24‐nt‐sRNAs from the rasiRNA family were mostly upregulated in galls. The promoters of MIR390a and TAS3, active in galls, and the pARF3:ARF3‐GUS line, indicated a role of TAS3‐derived‐tasiRNAs in galls.

The regulatory module miR390/TAS3 is necessary for proper gall formation possibly through auxin‐responsive factors, and the abundance of 24‐nt sRNAs (mostly rasiRNAs) constitutes a gall hallmark.
A systematic review of methodology applied during preclinical anesthetic neurotoxicity studies: important issues and lessons relevant to the design of future clinical research
Authors: Disma Nicola , Mondardini Maria C. , Terrando Niccolò , Absalom Anthony R. , Bilotta Federico
Published: November 2015

Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long‐term neurocognitive impairments. It is not clear if these findings apply to humans, and retrospective epidemiological studies thus far have failed to show definitive evidence that anesthetic agents are harmful to the developing human brain.

Aim

The aim of this systematic review was to summarize the preclinical studies published over the past decade, with a focus on methodological issues, to facilitate the comparison between different preclinical studies and inform better design of future trials.

Method

The literature search identified 941 articles related to the topic of neurotoxicity. As the primary aim of this systematic review was to compare methodologies applied in animal studies to inform future trials, we excluded a priori all articles focused on putative mechanism of neurotoxicity and the neuroprotective agents. Forty‐seven preclinical studies were finally included in this review.

Results

Methods used in these studies were highly heterogeneous—animals were exposed to anesthetic agents at different developmental stages, in various doses and in various combinations with other drugs, and overall showed diverse toxicity profiles. Physiological monitoring and maintenance of physiological homeostasis was variable and the use of cognitive tests was generally limited to assessment of specific brain areas, with restricted translational relevance to humans.

Conclusion

Comparison between studies is thus complicated by this heterogeneous methodology and the relevance of the combined body of literature to humans remains uncertain. Future preclinical studies should use better standardized methodologies to facilitate transferability of findings from preclinical into clinical science.
Continuous chloroprocaine infusion for thoracic and caudal epidurals as a postoperative analgesia modality in neonates, infants, and children
Authors: Veneziano Giorgio , Iliev Peter , Tripi Jennifer , Martin David , Aldrink Jennifer , Bhalla Tarun , Tobias Joseph
Published: November 2015

Background

Neonates and infants have decreased metabolic capacity for amide local anesthetics and increased risk of local anesthetic toxicity compared to the general population. Chloroprocaine is an ester local anesthetic that has an extremely short plasma half‐life in infants as well as adults. Existing reports support the safety and efficacy of continuous chloroprocaine epidural infusions in neonates and young infants during the intraoperative period. Despite this, continuous chloroprocaine epidural infusion may be an under‐utilized method of postoperative analgesia for this patient population. In particular, it may improve pain control in neonates and infants with incisions stretching many dermatomes or those with hepatic impairment.

Methods

We retrospectively reviewed our experience over 4 years with continuous chloroprocaine epidural infusions in neonates, infants, and children with a focus on the postoperative management of pain.

Results

Twenty‐one pediatric patients received continuous 2‐chloroprocaine epidural infusions for postoperative pain management from January 2010 to April 2014 for thoracic, abdominal, and limb procedures. The epidural infusion consisted of 1.5% chloroprocaine or 1.5% chloroprocaine with fentanyl. Tabulating the morphine and hydromorphone used for rescue analgesia, the median (interquartile range) opioid consumption (mg·kg−1·day−1 of intravenous morphine equivalents) for the first, second, and third 24‐h postoperative periods were 0.02 (0–0.48), 0.30 (0–0.44), and 0.14 (0–0.29), respectively. Examining the total fentanyl usage, the median (interquartile range) fentanyl consumption (μg·kg−1·day−1) for first, second, and third 24‐h postoperative periods were 3.89 (0.41–7.24), 0 (0.00–4.06), and 0 (0.00–0.51), respectively. The median N‐PASS score assessed every 6 h from 0 to 72 h postoperatively was 0, 1, 2, 0, 0, 1, 0, 0, 0, 0, 1, 0, and 0, respectively. The median FLACC score assessed every 6 h from 0 to 72 h postoperatively was 0, 0, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, and 0, respectively.

Conclusion

The results suggest that chloroprocaine offers an efficacious alternative to the amide local anesthetics for postoperative epidural analgesia in the pediatric population.
Complete bone regeneration in hemophilic pseudotumor of the mandible
Authors: Otsuka Hiroki , Ozeki Michio , Kanda Kaori , Hori Tomohiro , Kawamoto Norio , Saigo Chiemi , Kato Hiroki , Makita Hiroki , Shibata Toshiyuki , Fukao Toshiyuki
Published: November 2015

Hemophilic pseudotumor (HP) is rare, seen in 1–2% of patients with hemophilia, and is extremely uncommon in the mandible. A 6‐year‐old boy with moderate hemophilia A presented to our hospital with left mandibular swelling. Based on clinical and radiological findings, a tentative diagnosis of HP was made. After factor VIII administration, the lesion was curetted and HP was confirmed on histopathology. The patient was treated with twice‐weekly factor VIII until the lesion had completely resolved and bone had regenerated at 1 year. The best treatment for HP is not established; however, appropriate initial treatment and postoperative prophylaxis are effective.
Optimised Experimental Characterisation of Polymeric Foam Material Using DIC and the Virtual Fields Method
Authors: Wang P. , Pierron F. , Rossi M. , Lava P. , Thomsen O. T.
Published: November 2015

This article presents a methodology to optimise the design of a realistic mechanical test to characterise the material elastic stiffness parameters of an orthotropic PVC foam material in one single test. Two main experimental techniques were used in this study: Digital Image Correlation (DIC) and the Virtual Fields Method (VFM). The actual image recording process was mimicked by numerically generating a series of deformed synthetic images. Subsequent to this, the entire measurement and data processing procedure was simulated by processing the synthetic images using DIC and VFM algorithms. This procedure was used to estimate the uncertainty of the measurements (systematic and random errors) by including the most significant parameters of actual experiments, e.g. the geometric test configuration, the parameters of the DIC process and the noise. By using these parameters as design variables and by defining different error functions as object functions, an optimisation study was performed to minimise the uncertainty of the material parameter identification and to select the optimal test parameters. The confidence intervals of the identified parameters were predicted based on systematic and random errors obtained from the simulations. The simulated experimental results have shown that averaging multiple images can lead to a significant reduction of the random error. An experimental determination of the elastic coefficient of a PVC foam material was conducted using the optimised test parameters obtained from the numerical study. The identified stiffness values matched well with data from previous tests, but even more interesting was the fact that the experimental uncertainty intervals matched reasonably well with the predictions of the simulations, which is a highly original result and probably the main outcome of the present paper.
Increasing nondonors’ intention to give blood: addressing common barriers
Authors: Balegh Saharnaz , Marcus Natania , Dubuc Sophie , Godin Gaston , France Christopher R. , Ditto Blaine
Published: November 2015

BACKGROUND

Recruiting new donors is a challenging experience for most blood collection agencies. A modest proportion of the population is eligible to give blood and few of these individuals volunteer. The goal of this study was to examine the effects of brief behavioral interventions on nondonors’ intention to give blood, by addressing some commonly reported obstacles.

STUDY DESIGN AND METHODS

A total of 244 young adults who were eligible to give blood but had never done so participated in the study. They were assigned randomly to an applied tension (AT) instruction condition, a relaxation instruction condition, a Web browsing condition, or a no‐treatment control condition. After the 20‐minute experimental intervention, half watched three short injection and blood draw videos and the others sat quietly. Intention to give blood and different cognitive constructs associated with blood donation were measured using a Theory of Planned Behavior questionnaire.

RESULTS

Participants in all three active conditions had significantly greater increases in intention to donate blood compared to controls, although those who learned AT had greater increases than Web browsing. Bootstrapping tests of mediation indicated particular importance of increased perceived behavioral control in AT and relaxation treatment effects. Follow‐up analyses revealed a significant association between degree of within‐session increase in intention and subsequent blood clinic attendance.

CONCLUSION

These results suggest that simple interventions can be effective in increasing nondonors’ intention to donate blood and, perhaps, actual attendance. The mediational analyses suggest that interventions can selectively target different barriers associated with blood donation.
Simplified analytical model for sound level prediction at shielded urban locations involving multiple diffraction and reflections
Authors: Wei Weigang , Van Renterghem Timothy , Botteldooren Dick
Published: November 2015

Accurate and efficient prediction of the sound field in shadow zones behind obstacles is a challenging task but essential to produce urban noise maps. A simplified method is presented to predict sound levels at shielded urban locations, including multi-edge diffraction over successive buildings and multiple reflections between parallel façades. The model is essentially based on Pierce's diffraction theory, where the Fresnel Integral is approximated by trigonometric functions for efficient evaluation, and parameterized for urban environments. The model has been validated for idealized urban configurations by comparing to the results of Pierce's theory and a full-wave numerical method. In case of multi-edge diffraction over buildings in absence of a source or receiver canyon, deviations from the full-wave simulations are smaller than 2 dB for the octave bands with central frequencies ranging from 125 to 1000 Hz. However, larger errors are made when receivers are close to the extension line from the diffraction edge closest to the receiver. In case of combining the simplified multi-edge diffraction model with an efficient approach for including the series of mirror sources and mirror receivers, based on the Hurwitz-Lerch transcendent, this same accuracy is obtained.
Vitamin C selectively kills
KRAS
and
BRAF
mutant colorectal cancer cells by targeting GAPDH
Authors: Yun Jihye , Mullarky Edouard , Lu Changyuan , Bosch Kaitlyn N. , Kavalier Adam , Rivera Keith , Roper Jatin , Chio Iok In Christine , Giannopoulou Eugenia G. , Rago Carlo , Muley Ashlesha , Asara John M. , Paik Jihye , Elemento Olivier , Chen Zhengming , Pappin Darryl J. , Dow Lukas E. , Papadopoulos Nickolas , Gross Steven S. , Cantley Lewis C.
Published: November 2015

Getting all stressed out by vitamin C

Few experimental cancer therapies have incited as much debate as vitamin C. Yet the mechanistic effect of vitamin C on cancer cells is still poorly understood. Yun
et al.
studied human colorectal cancer cells with KRAS or BRAF mutations and found that they “handle” vitamin C in a different way than other cells, ultimately to their detriment (see the Perspective by Reczek and Chandel). Because a certain receptor is up-regulated in the mutant cells, they take up the oxidized form of vitamin C (dehydroascorbate). This leads to oxidative stress, inactivation of a glycolytic enzyme required by the mutant cells for growth, and finally cell death. Whether the selective toxicity of vitamin C to these mutant cells can be exploited therapeutically remains unclear.

Science
, this issue p.
1391
; see also p.
1317
Three-dimensional charge density wave order in YBa
2
Cu
3
O
6.67
at high magnetic fields
Authors: Gerber S. , Jang H. , Nojiri H. , Matsuzawa S. , Yasumura H. , Bonn D. A. , Liang R. , Hardy W. N. , Islam Z. , Mehta A. , Song S. , Sikorski M. , Stefanescu D. , Feng Y. , Kivelson S. A. , Devereaux T. P. , Shen Z.-X. , Kao C.-C. , Lee W.-S. , Zhu D. , Lee J.-S.
Published: November 2015

Discerning charge patterns in a cuprate

Copper oxides are well known to be able to achieve the order required for superconductivity. They can also achieve another order—one that produces patterns in their charge density. Experiments using nuclear magnetic resonanceand resonant x-ray scattering have both detected this so-called charge density wave (CDW) in yttrium-based cuprates. However, the nature of the CDW appeared to be different in the two types of measurement. Gerber
et al.
used pulsed magnetic fields of up to 28 T, combined with scattering, to bridge the gap (see the Perspective by Julien). As the magnetic field increased, a two-dimensional CDW gave way to a three-dimensional one.

Science
, this issue p.
949
; see also p.
914
Complete Genome Sequence of Multidrug-Resistant Clinical Isolate Mycobacterium tuberculosis 187.0, Used To Study the Effect of Drug Susceptibility Reversion by the New Medicinal Drug FS-1
Authors: Ilin Aleksandr I. , Kulmanov Murat E. , Korotetskiy Ilya S. , Akhmetova Gulshara K. , Lankina Marina V. , Shvidko Sergey V. , Reva Oleg N.
Published: November 2015

Complete genome sequence of the multidrug-resistant clinical isolate
Mycobacterium tuberculosis
SCAID 187.0 containing several drug-resistance mutations is presented. This strain is used in experiments to study genomic and population changes leading to reversion of susceptibility to the 1st line anti-tuberculosis (TB) drugs under the influence of a new medicinal drug FS-1.
Genome Assembly of Chryseobacterium polytrichastri ERMR1:04, a Psychrotolerant Bacterium with Cold Active Proteases, Isolated from East Rathong Glacier in India
Authors: Kumar Rakshak , Singh Dharam , Swarnkar Mohit Kumar , Singh Anil Kumar , Kumar Sanjay
Published: November 2015

We report here the genome assembly of a psychrotolerant bacterium,Chryseobacterium polytrichastriERMR1:04, which secretes cold-active proteases. The bacterium was isolated from a pristine location, the East Rathong Glacier in the Sikkim Himalaya. The 5.53-Mb genome provides insight into the cold-active industrial enzyme and adaptation in the cold environment.
Silica Gel for Enhanced Activity and Hypochlorite Protection of Cyanuric Acid Hydrolase in Recombinant Escherichia coli
Authors: Radian Adi , Aukema Kelly G. , Aksan Alptekin , Wackett Lawrence P.
Published: November 2015

Chlorinated isocyanuric acids are widely used water disinfectants that generate hypochlorite, but with repeated application, they build up cyanuric acid (CYA) that must be removed to maintain disinfection. 3-Aminopropyltriethoxysilane (APTES)-treated
Escherichia coli
cells expressing cyanuric acid hydrolase (CAH) from
Moorella thermoacetica
exhibited significantly high CYA degradation rates and provided protection against enzyme inactivation by hypochlorite (chlorine). APTES coating or encapsulation of cells had two benefits: (i) overcoming diffusion limitations imposed by the cell wall and (ii) protecting against hypochlorite inactivation of CAH activity. Cells encapsulated in APTES gels degraded CYA three times faster than nonfunctionalized tetraethoxysilane (TEOS) gels, and cells coated with APTES degraded CYA at a rate of 29 µmol/min per mg of CAH protein, similar to the rate with purified enzyme. UV spectroscopy, fluorescence spectroscopy, and scanning electron microscopy showed that the higher rates were due to APTES increasing membrane permeability and enhancing cyanuric acid diffusion into the cytoplasm to reach the CAH enzyme. Purified CAH enzyme was shown to be rapidly inactivated by hypochlorite. APTES aggregates surrounding cells protected via the amine groups reacting with hypochlorite as shown by pH changes, zeta potential measurements, and infrared spectroscopy. APTES-encapsulated
E. coli
cells expressing CAH degraded cyanuric acid at high rates in the presence of 1 to 10 ppm hypochlorite, showing effectiveness under swimming pool conditions. In contrast, CAH activity in TEOS gels or free cells was completely inactivated by hypochlorite. These studies show that commercially available silica materials can selectively enhance, protect, and immobilize whole-cell biocatalysts for specialized applications.

IMPORTANCE
Hypochlorite is used in vast quantities for water disinfection, killing bacteria on surfaces, and washing and whitening. In pools, spas, and other waters, hypochlorite is frequently delivered as chlorinated isocyanuric acids that release hypochlorite and cyanuric acid. Over time, cyanuric acid accumulates and impairs disinfection and must be removed. The microbial enzyme cyanuric acid hydrolase can potentially remove cyanuric acid to restore disinfection and protect swimmers. Whole bacterial cells expressing cyanuric acid hydrolase were encapsulated in an inert silica matrix containing an amine group. The amine group serves to permeabilize the cell membrane and accelerate cyanuric acid degradation, and it also reacts with hypochlorite to protect against inactivation of cyanuric acid hydrolase. Methods for promoting whole-cell biocatalysis are important in biotechnology, and the present work illustrates approaches to enhance rates and protect against an inhibitory substance.
Unusual presentation of a retained foreign body in a child
Authors: Almuallem Sultan , Yousef Yasmin A M , Suhail Abdulmalik
Published: November 2015

A 4-year-old boy, not known to have any medical illness, presented to several medical facilities reporting right upper quadrant and right flank pain, intermittent fever and chills for 3 months. A CT of the abdomen showed that a swallowed ‘bobby pin’ had pierced through the right kidney. This finding explained the boy's symptoms. The pin was removed by laparotomy without any subsequent complication. The patient had an uneventful postoperative recovery.
Identifying patient safety problems associated with information technology in general practice: an analysis of incident reports
Authors: Magrabi Farah , Liaw Siaw Teng , Arachi Diana , Runciman William , Coiera Enrico , Kidd Michael R
Published: November 2015

Objective

To identify the categories of problems with information technology (IT), which affect patient safety in general practice.

Design

General practitioners (GPs) reported incidents online or by telephone between May 2012 and November 2013. Incidents were reviewed against an existing classification for problems associated with IT and the clinical process impacted.

Participants and setting

87 GPs across Australia.

Main outcome measure

Types of problems, consequences and clinical processes.

Results

GPs reported 90 incidents involving IT which had an observable impact on the delivery of care, including actual patient harm as well as near miss events. Practice systems and medications were the most affected clinical processes. Problems with IT disrupted clinical workflow, wasted time and caused frustration. Issues with user interfaces, routine updates to software packages and drug databases, and the migration of records from one package to another generated clinical errors that were unique to IT; some could affect many patients at once. Human factors issues gave rise to some errors that have always existed with paper records but are more likely to occur and cause harm with IT. Such errors were linked to slips in concentration, multitasking, distractions and interruptions. Problems with patient identification and hybrid records generated errors that were in principle no different to paper records.

Conclusions

Problems associated with IT include perennial risks with paper records, but additional disruptions in workflow and hazards for patients unique to IT, occasionally affecting multiple patients. Surveillance for such hazards may have general utility, but particularly in the context of migrating historical records to new systems and software updates to existing systems.