bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrovascular reactivity is associated with maximal aerobic capacity in healthy older adults
Authors: Barnes Jill N. , Taylor Jennifer L. , Kluck Breann N. , Johnson Christopher P. , Joyner Michael J.
Published: March 2013

Recently, several high-impact reviews suggest that regular aerobic exercise is beneficial for maintaining cognitive function in aging adults. Higher cerebral blood flow and/or cerebrovascular reactivity may explain the favorable effect of exercise on cognition. In addition, prostaglandin-mediated vasodilator responses may be influenced by regular exercise. Therefore, our purpose was to evaluate middle cerebral artery (MCA) vasodilator responses in healthy adults before and after cyclooxygenase inhibition. A total of 16 young (26 ± 6 yr; 8 males, 8 females) and 13 older (64 ± 6 yr; 7 males, 6 females) healthy adults participated in the study. Aerobic fitness was determined by maximal aerobic capacity (V̇o2max) on a cycle ergometer. MCA velocity (MCAv) was measured at baseline and during stepped hypercapnia (2%, 4%, and 6% FiCO2) before and after cyclooxygenase inhibition using indomethacin. To account for differences in blood pressure, cerebrovascular conductance index (CVCi) was calculated as MCAv/mean arterial pressure. Cerebrovascular reactivity slopes were calculated from the correlation between either MCAv or CVCi and end-tidal CO2. Young adults demonstrated greater MCAv reactivity (1.61 ± 0.17 vs. 1.06 ± 0.15 cm·s−1·mmHg−1; P < 0.05) and CVCi reactivity (0.015 ± 0.002 vs. 0.007 ± 0.002 cm·s−1·mmHg−1; P < 0.05) compared with the older adults. There was no association between cerebrovascular reactivity and V̇o2maxin the combined group of subjects; however, in older adults MCAv reactivity was correlated with maximal aerobic fitness ( r = 0.64; P < 0.05). Furthermore, the change in MCAv reactivity (between baseline and indomethacin trials) was also associated with V̇o2max( r = 0.59; P < 0.05) in older adults. Cerebral vasodilator responses to hypercapnia were associated with maximal aerobic capacity in healthy older adults. These results may explain the physiological link between regular aerobic exercise and improved cognitive function in aging adults.
Arterial blood gases, electrolytes, and metabolic indices associated with hemorrhagic shock: inter- and intrainbred rat strain variation
Authors: Rose Rajiv , Kheirabadi Bijan S. , Klemcke Harold G.
Published: March 2013

We have previously shown interstrain variation (indicating a genetic basis), and intrastrain variation in survival time after hemorrhage (STaH) among inbred rat strains. To assist in understanding physiological mechanisms associated with STaH, we analyzed various arterial blood measures (ABM; pH, Paco2, oxygen content, sodium, potassium, glucose, bicarbonate, base excess, total CO2, and ionized calcium) in inbred rats. Rats from five inbred strains ( n = 8–10/strain) were catheterized and, ∼24 h later, subjected to a conscious, controlled, 47% hemorrhage. ABM were measured at the start (initial) and end (final) of hemorrhage. Inter- and intrainbred strain variations of ABM were quantified and compared, and correlations of ABM with STaH were determined. All final ABM values and some initial ABM values were different among strains. Most ABM changed (Δ) during hemorrhage, and these changes differed among strains ( P < 0.03). Some strain-dependent correlations ( r ≥0.7; P ≤ 0.05) existed between ΔABM and STaH (e.g., BN/Mcwi, ΔK+, r = −0.84). Dark Agouti rats (longest STaH) had the smallest ΔPaco2, ΔHCO3−, and Δbase excess, and the highest final glucose. High coefficients of variation (CVs, >10%), strain-specific CVs, and low intraclass correlation coefficients ( rI< 0.5) defined the large intrastrain ABM variation that exceeded interstrain variation for most ABM. These results suggest that some ABM (K+, Paco2, glucose, oxygen content) could predict subsequent STaH in an inbred rat strain-dependent manner. We speculate that whereas genetic differences may be responsible for interstrain variation, individual-specific epigenetic processes (e.g., DNA methylation) may be partly responsible for both inter- and intrastrain ABM variation.
Comparison of neuromuscular adjustments associated with sustained isometric contractions of four different muscle groups
Authors: Neyroud Daria , Rüttimann Jennifer , Mannion Anne F. , Millet Guillaume Y. , Maffiuletti Nicola A. , Kayser Bengt , Place Nicolas
Published: March 2013

The extent and characteristics of muscle fatigue of different muscle groups when subjected to a similar fatiguing task may differ. Thirteen healthy young men performed sustained contractions at 50% maximal voluntary contraction (MVC) force until task failure, with four different muscle groups, over two sessions. Per session, one upper limb and one lower limb muscle group were tested (knee extensors and thumb adductor, or plantar and elbow flexors). Changes in voluntary activation level and contractile properties were derived from doublet responses evoked during and after MVCs before and after exercise. Time to task failure differed ( P < 0.05) between muscle groups (220 ± 64 s for plantar flexors, 114 ± 27 s for thumb adductor, 77 ± 25 s for knee extensors, and 72 ± 14 s for elbow flexors). MVC force loss immediately after voluntary task failure was similar (−30 ± 11% for plantar flexors, −37 ± 13% for thumb adductor, −34 ± 15% for knee extensors, and −40 ± 12% for elbow flexors, P > 0.05). Voluntary activation was decreased for plantar flexors only (from 95 ± 5% to 82 ± 9%, P < 0.05). Potentiated evoked doublet amplitude was more depressed for upper limb muscles (−59.3 ± 14.7% for elbow flexors and −60.1 ± 24.1% for thumb adductor, P < 0.05) than for knee extensors (−28 ± 15%, P < 0.05); no reduction was found in plantar flexors (−7 ± 12%, P > 0.05). In conclusion, despite different times to task failure when sustaining an isometric contraction at 50% MVC force for as long as possible, diverse muscle groups present similar loss of MVC force after task failure. Thus the extent of muscle fatigue is not affected by time to task failure, whereas this latter determines the etiology of fatigue.
Vaccination for Invasive Canine Meningioma InducesIn SituProduction of Antibodies Capable of Antibody-Dependent Cell-Mediated Cytotoxicity
Authors: Andersen Brian M. , Pluhar G. Elizabeth , Seiler Charles E. , Goulart Michelle R. , SantaCruz Karen S. , Schutten Melissa M. , Meints Joyce P. , O'Sullivan M. Gerard , Bentley R. Timothy , Packer Rebecca A. , Thomovsky Stephanie A. , Chen Annie V. , Faissler Dominik , Chen Wei , Hunt Matthew A. , Olin Michael R. , Ohlfest John R.
Published: March 2013

Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. IFN-γ–elaborating T cells were detected in the peripheral blood of 2 cases, but vaccine-induced tumor-reactive antibody responses developed in all dogs. Antibody responses were polyclonal, recognizing both intracellular and cell surface antigens, and HSP60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, showing common antigens across breed and species. Histologic analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in posttreatment compared with pretreatment samples. Tumor-reactive antibodies were capable of inducing antibody-dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data show the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development toward human trials. Cancer Res; 73(10); 2987–97. ©2013 AACR.
Inhibition of Established Micrometastases by Targeted Drug Delivery via Cell Surface–Associated GRP78
Authors: Miao Yu Rebecca , Eckhardt Bedrich L. , Cao Yuan , Pasqualini Renata , Argani Pedram , Arap Wadih , Ramsay Robert G. , Anderson Robin L.
Published: March 2013

Purpose: The major cause of morbidity in breast cancer is development of metastatic disease, for which few effective therapies exist. Because tumor cell dissemination is often an early event in breast cancer progression and can occur before diagnosis, new therapies need to focus on targeting established metastatic disease in secondary organs. We report an effective therapy based on targeting cell surface–localized glucose-regulated protein 78 (GRP78). GRP78 is expressed normally in the endoplasmic reticulum, but many tumors and disseminated tumor cells are subjected to environmental stresses and exhibit elevated levels of GRP78, some of which are localized at the plasma membrane.

Experimental Design and Results: Here, we show that matched primary tumors and metastases from patients who died from advanced breast cancer also express high levels of GRP78. We used a peptidomimetic targeting strategy that uses a known GRP78-binding peptide fused to a proapoptotic moiety [designated bone metastasis targeting peptide 78 (BMTP78)] and show that it can selectively kill breast cancer cells that express surface-localized GRP78. Furthermore, in preclinical metastasis models, we show that administration of BMTP78 can inhibit primary tumor growth as well as prolong overall survival by reducing the extent of outgrowth of established lung and bone micrometastases.

Conclusions: The data presented here provide strong evidence that it is possible to induce cell death in established micrometastases by peptide-mediated targeting of cell surface–localized GRP in advanced breast cancers. The significance to patients with advanced breast cancer of a therapy that can reduce established metastatic disease should not be underestimated. Clin Cancer Res; 19(8); 2107–16. ©2013 AACR.
Development and Validation of a Clinical Risk Score Predicting the No-Reflow Phenomenon in Patients Treated with Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction
Authors: Wang Jin-Wen , Chen Yun-Dai , Wang Chang-Hua , Yang Xin-Chun , Zhu Xiao-Ling , Zhou Zi-Qiang
Published: March 2013

Objective: The ‘no-reflow' phenomenon after a primary percutaneous coronary intervention (pPCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) is a strong predictor of both short- and long-term mortality. We therefore developed and prospectively validated a risk score system in order to identify STEMI patients at high risk in terms of no-reflow after primary PCI. Methods: The first part of our study used data from 1,615 STEMI patients who underwent primary PCI within 12 h from symptom onset. Using logistic regression, we derived a risk score to predict angiographic no-reflow using baseline clinical variables. From this score, we developed a simplified fast-track screen that can be used before reperfusion. In the second part of our study, we prospectively validated the score system using receiver-operating characteristic (ROC) curves with data from 692 STEMI patients. Results: The model included six clinical items: age, neutrophil count, admission plasma glucose, β-blocker treatment, time-to-hospital admission and Killip classes. The risk score system demonstrated a good risk prediction with a c-statistic of 0.757 (95% CI 0.732-0.781) based on ROC analysis. Conclusion: A simple risk score system based on clinical variables is useful to predict the risk of developing no-reflow after pPCI in patients with STEMI.
Möglichkeiten und Grenzen einer Zusammenarbeit mit Heilpraktikern aus ärztlicher Sicht
Authors: Thanner Mirjam , Nagel Eckhard , Loss Julika
Published: March 2013

Hintergrund: Deutschland weist gegenüber zahlreichen anderen Staaten die Besonderheit auf, dass neben Ärzten auch Heilpraktiker eine staatliche Zulassung zur Ausübung der Heilkunde erlangen können. Das Verhältnis der beiden Berufsgruppen zueinander gilt als schwierig - unabhängig von berufsrechtlichen Hindernissen. Ziel der Untersuchung war es zu klären, inwieweit bei niedergelassenen Ärzten eine Bereitschaft zur Zusammenarbeit mit Heilpraktikern besteht. Gleichzeitig sollten Bedingungen, Chancen sowie Hindernisse einer Kooperation aufgezeigt werden. Methoden: Um die ärztliche Bereitschaft zur Zusammen arbeit mit Heilpraktikern zu evaluieren, wurden mit 15 niedergelassenen Ärzten und Zahnärzten semi-strukturierte Interviews geführt. Die Fragen thematisierten Bedingungen, Chancen sowie Barrieren einer Kooperation. Im Anschluss wurden die Interviews wörtlich transkribiert und mithilfe der thematischen Inhaltsanalyse ausgewertet. Ergebnisse: Einer Zusammenarbeit gegenüber aufgeschlossene Ärzte sehen Heilpraktiker als ergänzende Therapeuten bei leichteren oder psychisch beeinflussten Erkrankungen. Dafür bestehen allerdings klare Bedingungen: Heilpraktiker müssten die Grenzen ihrer Behandlungsfähigkeit erkennen. Voraussetzungen seien auch transparente Regelungen der Kostenerstattung durch Krankenkassen, insbesondere dürften ärztliche Leistungen im Bereich der Komplementär- und Alternativmedizin nicht diskriminiert werden. Neben dem mangelnden Vertrauen der befragten Ärzte in die Heilpraktikerausbildung erweist es sich als hinderlich, wenn Heilpraktiker störend auf die bestehende Arzt-Patienten-Beziehung einwirken bzw. den Abbruch einer schulmedizinischen Therapie veranlassen. Gleichzeitig wird die bestehende Patientenversorgung bereits als zu komplex für eine Kooperation eingeschätzt. Schlussfolgerungen: Um zu reproduzierbaren Ergebnissen zu gelangen, sind Untersuchungen mit quantitativem Forschungsdesign nötig. Auch sollte geklärt werden, inwieweit aus Sicht der Heilpraktiker eine Zusammenarbeit mit Ärzten wünschenswert ist. Der Abbau von Kommunikationsbarrieren ist nötig, damit Patienten offen mit ihrem Arzt über Heilpraktiker besuche sprechen kön-nen. Das Wissen über Unterschiede in Ausbildung und Zulassung zum Arzt oder Heilpraktiker ist Grundvoraussetzung für eine informierte Entscheidung der Patienten.
Tanztherapie in der stationären onkologischen Rehabilitation
Authors: Mannheim Elana G. , Helmes Almut , Weis Joachim
Published: March 2013

Hintergrund: Die Tanztherapie ist ein Verfahren der künstlerischen Therapie, welches den unmittelbaren Körperbezug im individuellen Tanz zur Erfahrung und zum Ausdruck emotionaler und kognitiver Themen einsetzt. Sie stellt für Krebspatienten eine wichtige Hilfe zur Krankheitsverarbeitung dar. Bislang liegen nur wenige wissenschaftliche Studien zur Tanztherapie bei Krebspatienten vor. Methodik: In der vorliegenden explorativen Studie wurden Wirkmechanismen der Tanztherapie bei Krebspatientinnen (n = 115) im Setting der onkologischen Rehabilitation auf der Basis eines Ein-Gruppen-prä-post-Designs einschließlich einer 3-monatigen Katamnese untersucht. Hierbei wurden Lebensqualität, Angst und Depression sowie Fragen zum Selbstkonzept mit standardisierten Messinstrumenten erhoben (EORTC QLQ-C30, HADS, FSKN). Außerdem konnten die Studienteilnehmerinnen den Therapieerfolg durch subjektive Einschätzung des Nutzens und des Erfolgs der Tanztherapie bewerten. Die folgende Darstellung fokussiert die Ergebnisse der Prä-post-Messung. Ergebnisse: Als Wirkfaktoren der Tanztherapie konnten emotionale Ausdrucksfähigkeit, Stärkung des Selbstwerts/Selbstbewusstseins, Persönlichkeitsentwicklung, Vitalität, allgemeine Ausgeglichenheit sowie Herstellung eines Bezugs zum eigenen Körper identifiziert werden. In Bezug auf die Lebensqualität und psychische Befindlichkeit konnten mittlere bis große Effektstärken festgestellt werden. Schlussfolgerungen: Wenngleich die dargestellten Effektstärken aufgrund des Studiendesigns nicht als Wirksamkeitsnachweis interpretiert werden können, gibt die Untersuchung wichtige Aufschlüsse über Wirkprinzipien und Therapieprozesse des fokussierten kurzzeit-tanztherapeutischen Vorgehens im Rahmen der stationären Rehabilitation.
Zur Lage der Komplementärmedizin in Deutschland
Authors: Albrecht Henning
Published: March 2013

Mit der Novellierung des Arzneimittelgesetzes von 1976 und der Aufnahme der Fächer Naturheilverfahren und Homöopathie in die Approbationsordnung für Ärzte (ÄAppO) von 1988 wurden verhältnismäßig günstige politische Rahmenbedingungen für die Komplementärmedizin in Deutschland geschaffen. Eine umfassende Integration in den akademischen Betrieb erfolgte jedoch nicht. Denn die Universitäten und der Gesetzgeber zeigten augenscheinlich nur wenig Interesse an komplementärmedizinischen Themen, sodass komplementärmedizinische Forschungsvorhaben und Professuren immer noch nahezu vollständig aus Drittmitteln finanziert werden müssen.Trotz des Erfolgs vieler von privater Hand geförderter Projekte, können diese kaum eine nachhaltige Entwicklung in Gang setzen: Mit den Protagonisten und der Drittmittelfinanzierung verschwinden zumeist auch die geschaffenen institutionellen Strukturen. Obwohl die Nachfrage seitens der Bevölkerung groß ist, strich die Bundesregierung 2002 die Homöopathie als Pflichtfach aus der ÄAppO und schränkte im Zuge der Gesundheitsreform 2004 die Erstattungsfähigkeit von Naturheilmitteln durch die gesetzliche Krankenversicherung stark ein. Zudem etablierte sich in der deutschen Medienlandschaft zunehmend der Trend, unsauber recherchierte, reißerische Artikel gegen die Komplementärmedizin zu publizieren. Beklagenswert erscheint auch die mangelnde Einigkeit der komplementärmedizinischen Szene sowie die Unfähigkeit, basale Datensammlung im klinischen Alltag zu betreiben, um Zahlen vorzulegen, die gegenüber der Politik und der akademischen Welt weitergehende Bemühungen rechtfertigen könnten. Positiv ist hervorzuheben, dass der wissenschaftliche Standard in der komplementärmedizinischen Forschung fast durchgängig hoch ist und dass die aus Drittmitteln geförderten Projekte überzeugende Ergebnisse zeitigen.
Everolimus in Metastatic Renal Cell Carcinoma after Failure of Initial Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor (VEGFr-TKI) Therapy: Results of an Interim Analysis of a Non-Interventional Study
Authors: Bergmann Lothar , Goebell Peter J. , Kube Ulrich , Kindler Manfred , Herrmann Edwin , Janssen Jan , Schmitz Joerg , Weikert Steffen , Steiner Gabriel , Jakob Andreas , Staehler Michael D. , Steiner Thomas , Overkamp Friedrich , Albrecht Michael , Guderian Gernot , Doehn Christian
Published: March 2013

Background: Everolimus is approved for treatment of anti-vascular endothelial growth factor (VEGF)-refractory patients with metastatic renal cell carcinoma (mRCC). Clinical trials rarely mirror treatment reality. Thus, a broader evaluation of everolimus is valuable for routine use. Patients and Methods: A German multicenter non-interventional study documented mRCC patients starting everolimus after failure of initial VEGF-targeted therapy. Primary endpoint was effectiveness, defined as time to progression (TTP) according to investigator assessment (time from first dose to progression). Results: Of 382 documented patients, 196 were included in this interim analysis. In the efficacy population (n = 165), median TTP was 7.0 months (95% confidence interval (CI) 5.1-9.0). Among patients with < or ≥ 6 months of previous VEGF-targeted therapy, median TTP was 6.6 months (95% CI 3.8-not estimable) and 7.4 months (95% CI 4.6-9.6), respectively. Most common adverse events were anemia (13%) and dyspnea (14%). Physicians assessed high tolerance and documented high adherence to everolimus therapy (approximately 97%). Conclusion: In routine clinical practice, everolimus is effective, as measured by median TTP (longer than median progression-free survival in RECORD-1 trial), and well tolerated. Our results support everolimus use in anti-VEGF-refractory patients with mRCC.
A Rare Case of Crowned Dens Syndrome Mimicking Aseptic Meningitis
Authors: Takahashi Teruyuki , Minakata Yugo , Tamura Masato , Takasu Toshiaki , Murakami Marohito
Published: March 2013

Background: Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Microcrystal-line deposition most often consists of calcium pyrophosphate dehydrate crystals and/or hydroxyapatite crystals. Case Presentation: This report describes the case of an 89-year-old woman who presented with sudden onset, high fever, severe occipital headache, and neck stiffness. A laboratory examination revealed a markedly elevated white blood cell count (11,100/µl) and C-reactive protein level (23.8 mg/dl). These clinical findings suggested severe infection such as meningitis with sepsis. However, the results of blood culture, serum endotoxin, and procalcitonin were all negative, and cerebrospinal fluid studies revealed only a slight abnormality. The patient was first diagnosed with meningitis and treated with antiviral and antibiotic agents as well as non-steroidal anti-inflammatory drugs, but they only had limited effects. A cervical plain computed tomography (CT) scan and its three-dimensional (3D) reconstruction detected a remarkable crown-like calcification surrounding the odontoid process. On the basis of the CT findings, the patient was diagnosed as a severe case of CDS and was immediately treated with corticosteroids. The patient's condition drastically improved within a week after one course of corticosteroid therapy. Conclusion: Some atypical symptoms of CDS are misleading and may be misdiagnosed as meningitis, as happened in our case. A CT scan, especially a 3D-CT scan, is necessary and useful for a definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for fever, headache, and cervical pain of unknown origin.
Novel Role of Enteral Monosaccharides in Intestinal Lipoprotein Production in Healthy Humans
Authors: Xiao Changting , Dash Satya , Morgantini Cecilia , Lewis Gary F.
Published: March 2013

Objective—

Overproduction of triglyceride-rich lipoproteins (TRLs) by liver and intestine contributes to hypertriglyceridemia and may increase cardiovascular risk. Dietary carbohydrates, especially fructose, have been shown to amplify postprandial lipemia but little is known about its effect on intestinal TRL particle production. Here, we examined intestinal and hepatic TRL particle production in response to enteral glucose or fructose in the presence of enteral lipid.

Approach and Results—

In 2 randomized studies, 4 to 6 weeks apart, 7 healthy male subjects received intraduodenal infusion of Intralipid plus saline or glucose. TRL-apolipoprotein (apo) B48 and apoB100 kinetics were assessed under pancreatic clamp conditions. In a separate study of another 7 subjects under similar conditions, glucose was replaced by fructose. When coinfused with Intralipid into the duodenum, glucose markedly stimulated TRL-apoB48 production (
P
<0.01), with a concomitant moderate increase in fractional clearance (
P
<0.05), resulting in net elevation of TRL-apoB48 concentration. TRL-apoB100 concentration, fractional clearance, and production were not significantly affected by glucose. When glucose was replaced by fructose, both TRL-apoB100 and apoB48 production (
P
<0.05), but not fractional clearance, were enhanced compared with Intralipid alone.

Conclusions—

These results reveal a novel role of monosaccharides in acutely enhancing intestinal lipoprotein particle production, thereby aggravating hyperlipidemia.
Ezetimibe Inhibits Hepatic Niemann-Pick C1-Like 1 to Facilitate Macrophage Reverse Cholesterol Transport in Mice
Authors: Xie Ping , Jia Lin , Ma Yinyan , Ou Juanjuan , Miao Hongming , Wang Nanping , Guo Feng , Yazdanyar Amirfarbod , Jiang Xian-Cheng , Yu Liqing
Published: March 2013

Objective—

Controversies have arisen from recent mouse studies about the essential role of biliary sterol secretion in reverse cholesterol transport (RCT). The objective of this study was to examine the role of biliary cholesterol secretion in modulating macrophage RCT in Niemann-Pick C1-Like 1 (NPC1L1) liver only (L1
LivOnly
) mice, an animal model that is defective in both biliary sterol secretion and intestinal sterol absorption, and determine whether NPC1L1 inhibitor ezetimibe facilitates macrophage RCT by inhibiting hepatic NPC1L1.

Approach and Results—

L1
LivOnly
mice were generated by crossing NPC1L1 knockout (L1-KO) mice with transgenic mice overexpressing human NPC1L1 specifically in liver. Macrophage-to-feces RCT was assayed in L1-KO and L1
LivOnly
mice injected intraperitoneally with [
3
H]-cholesterol–labeled peritoneal macrophages isolated from C57BL/6 mice. Inhibition of biliary sterol secretion by hepatic overexpression of NPC1L1 substantially reduced transport of [
3
H]-cholesterol from primary peritoneal macrophages to the neutral sterol fraction in bile and feces in L1
LivOnly
mice without affecting tracer excretion in the bile acid fraction. Ezetimibe treatment for 2 weeks completely restored both biliary and fecal excretion of [
3
H]-tracer in the neutral sterol fraction in L1
LivOnly
mice. High-density lipoprotein kinetic studies showed that L1
LivOnly
mice compared with L1-KO mice had a significantly reduced fractional catabolic rate without altered hepatic and intestinal uptake of high-density lipoprotein–cholesterol ether.

Conclusions—

In mice lacking intestinal cholesterol absorption, macrophage-to-feces RCT depends on efficient biliary sterol secretion, and ezetimibe promotes macrophage RCT by inhibiting hepatic NPC1L1 function.
Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Repeat Doses of GSK249320 in Patients With Stroke
Authors: Cramer Steven C. , Abila Bams , Scott Nicola E. , Simeoni Monica , Enney Lori A.
Published: March 2013

Background and Purpose—

Restorative therapies have the potential to improve function and reduce disability after stroke with a wide therapeutic window. The current study evaluated GSK249320, a monoclonal antibody that blocks the axon outgrowth inhibition molecule myelin-associated glycoprotein and also protects oligodendrocytes.

Methods—

Patients with mild-moderate stroke were randomized to intravenous GSK249320 (1, 5, or 15 mg/kg per infusion, in escalating cohorts of 8–9 subjects) versus placebo (n=17). Infusion 1 was 24 to 72 hours after stroke; infusion 2 was 9±1 days later. The primary objective evaluated safety and tolerability, and the secondary objectives evaluated immunogenicity, pharmacokinetics, biomarkers, neurophysiology, and motor function.

Results—

Baseline (n=42) characteristics were similar across treatment groups. No safety concerns were found based on adverse events, examination, vital signs, ECG, nerve conduction tests, brain imaging, motor function testing, and laboratory studies. Two of the 25 subjects dosed with GSK249320 developed transient antidrug antibodies after infusion 1. The pharmacokinetics profile was as expected for an IgG1 type monoclonal antibody. Serum levels of the biomarker S100β did not differ between groups. Global outcome measures were similar across groups. Modality-specific end points could be consistently measured in the first few days after stroke, and one of these, gait velocity, demonstrated a trend toward improvement with GSK249320 compared with placebo.

Conclusions—

GSK249320 was generally well tolerated. No major safety issues were identified in this first study of a monoclonal antibody to modulate the neurobiology of brain repair after stroke. Future studies might explore the efficacy of GSK249320 as a restorative therapy for stroke.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique Identifier: NCT00833989.
God Willing: Im Yirẓeh Hashem—In Sha Allah
Authors: Jospe Raphael , Milo Yonatan
Published: March 2013

Abstract

Except for three passages in the New Testament, the earliest usage in Jewish literature of the phrase “God willing” (or: “if God wills”) dates from the Islamic period. The Hebrew im yirẓeh Hashem reflects the Arabic in sha Allah, but without the underlying Islamic occasionalist denial of natural causality and emphasis on divine omnipotence and decree (al-qadar) propounded by Al-Ghazali and Ash’arite Kalam. The Hebrew term merely reflects belief in divine providence and not occasionalism.
Easing Into Norman: Ed Kessler on the Origins and Growth of the National Severe Storms Laboratory
Authors: Kessler Edwin , Cohen Ariel E. , Corfidi Stephen F. , Corfidi Sarah J.
Published: March 2013

The following essay is excerpted from conversations with Edwin Kessler, founding director of NOAA's National Severe Storms Laboratory in Norman, Oklahoma, conducted by Ariel Cohen and Stephen and Sarah Corfidi of the National Weather Service's Storm Prediction Center. Cohen and the Corfidis based the discussion in part on Kessler's speech at the 50th anniversary of the School of Meteorology at the University of Oklahoma in October 2010, and Cohen converted this discussion to a Q&A format. The conversations range over many subjects, including accomplishments of NSSL, Kessler's role as its manager, and the many people who were crucial to the lab's growth. The entire conversation is published by BAMS online, but here we've selected Kessler's words regarding the move to Norman, the community that evolved there, and how NSSL thrived there because of—and despite—the bureaucratic changes that federal agencies underwent at that time.—The Editors
Hegemonic Masculine Conceptualisation in Gang Culture
Authors: Luyt Russell , Foster Don
Published: March 2013

This research sought to investigate the relationship between gang processes and differing forms of masculine expression. Three hundred and sixteen male participants, drawn from secondary schools within Cape Town, were included in the study. These schools were in areas differentially characterised by gang activity. The questionnaire included the newly devised Male Attitude Norm Inventory designed to explore hegemonic conceptualisations of masculinity. Factor analytic procedures rendered a three-factor model stressing the importance of male toughness, success and control. Through a series of t-tests for independent samples, as well as supporting qualitative data, participants from areas characterised by high gang activity were found to support these hegemonic elements to a significantly greater extent.
The (un)Fair Usage of the 16PF (SA92) in South Africa: A Response to C.H. Prinsloo and I. Ebersöhn
Authors: Abrahams F.
Published: March 2013

A study completed in 1996, challenged the continued usage of the 16PF (SA92), and found that this imported test was biased against black mother-tongue speakers in the South African context. Six years later, Prinsloo and Ebersohn questioned the methodological and statistical techniques employed in the study. This article is a response to their claims and reaffirms the results and position that the necessary research must be conducted on imported tests, prior to it's adoption within South Africa.
Psychotherapy is Delicate Psychosurgery
Authors: Pitman Michael M.
Published: March 2013

The paper involves an attempt to draw out the implications of a ‘moderate materialism’ for the understanding of mental illness. The argument of the paper is that once a moderate materialism which navigates carefully between the poles of (materialist) reductionism and dualism has been unpacked, the relations between the manifestations, bases, aetiologies and treatments of mental illnesses emerge as being considerably more complex than is often allowed for. Specifically, the conceptual tools required within a moderate materialist position about the mind allow us to expose potential fallacies in thinking about the nature of mental illnesses, in inferences drawn from these ‘natures’ to ideal modes of treatment, and in inferences drawn from treatment response. It is concluded that moderate materialism undermines the oversimplifications which tend to cloud ‘biophysical versus psychosocial’ debates in the field of psychopathology, in part because psychological change is physiological change, and because physiological change and/or intervention need not ‘cure’ by removing a physiological cause.
The Experience of Person-Role Conflict in Doctors Expected to Terminate Pregnancies in the South African Public Sector
Authors: da Costa Patricia Caldas , Donald Fiona
Published: March 2013

This study examines the experiences of person-role conflict amongst doctors working in obstetrics and gynaecology with regard to the provision of abortion services in the public sector. Fifteen doctors were interviewed in order to assess their personal experiences and the role forces that were evident, especially in situations where doctors were confronted with the expectation that they terminate pregnancies either on demand or for social reasons. This study explores the role forces that are operating, attitudes towards abortion versus willingness to perform abortions, the potential impact on the quality of service provided, and the personal implications of person-role conflict for the doctors.
Suicide in a South African Town: A Cultural Psychological Investigation
Authors: Laubscher Leswin R.
Published: March 2013

Paarl, a large South African town, has experienced a dramatic increase in suicide among young, professional Coloured men during the period 1990 to 2000. Interviews were conducted with surviving family members and friends, and subjected to a qualitative, interpretative analysis. Theoretically and methodologically, cultural psychology is presented as a critical alternative to mainstream academic literature on suicide within psychology and sociology. Hence, the suicides of the young men are read as a cultural phenomenon within a particular post-Apartheid context. Cultural certitude and identity are presented as organising dialectic and phenomenological hermeneutic.
A Psychometric Analysis of the Maslach Burnout Inventory-General Survey in the South African Police Service
Authors: Storm K. , Rothmann S.
Published: March 2013

The objectives of this study, which was undertaken by two members of the WorkWell Research Unit, were to validate the Maslach Burnout Inventory-General Survey (MBI-GS) for the South African Police Service and to determine the construct equivalence of this Inventory and bias for different race groups. A cross-sectional survey design was used. Stratified random samples ( N=2396) were taken of police members from nine provinces in South Africa. The study was based on the MBI-GS and a biographical questionnaire. Structural equation modelling confirmed a 3-factor model of burnout, consisting of Exhaustion, Cynicism and Professional Efficacy. All three factors showed acceptable internal consistencies. An exploratory factor analysis with target rotations confirmed the construct equivalence of the three factors for different race groups in the SAPS. No evidence was found for uniform or non-uniform bias of the items of the MBI-GS for different race groups.
Patients' Coaching Behaviours, Transference Testing and the Corrective Emotional Experience: Transcending the Self in Psychotherapy
Authors: Knight Zelda G.
Published: March 2013

This article is broadly based within a psychodynamic approach to psychotherapy, drawing on object relations theories and, more specifically, on an object relations model outlined by Frank Summers, namely, relational psychoanalysis. The article explores the notion that because attachment to the object is central to the development of a sense of identity and belonging, individuals will seek to preserve the relationship at the expense of the development of their authentic self. In this way, those aspects of themselves that they perceive to be unacceptable to others and thus often to themselves, will be buried in order to maintain the relationship. The therapeutic relationship, as an interpersonal matrix, may echo patients' problematic modes of being and relating. However, the therapeutic relationship is potentially one in which such problematic patterns of relating may be resolved rather than re-enacted. In this context, patients may experience in therapy a ‘transcendence of the self as they begin to experience how they are relating, and more importantly, how such relating may result in the arrested development of their authentic self. The article makes links between three therapeutic phenomena in which problematic patterns of relating are embedded: (a) patients' coaching behaviours, (b) transference testing and (c) the corrective emotional experience. Such links are not clearly made in the literature. Furthermore, clinical material is drawn from the author's work as a psychotherapist and is used to illustrate transference-testing behaviours and three of its components, namely: (a) testing by compliance, (b) testing by non-compliance and (c) passive-into-active testing.
Psychological Tests Do Not Measure What They Claim to Measure: A Re-Evaluation of the Concept of Construct Validity
Authors: Wallis Taryn
Published: March 2013

Criticisms have been raised that psychological tests do not actually measure the variables that they claim to measure. As a result, the concept of construct validity is called Into question. This article explores the rationale for measurement criticisms levelled at the field as well as the implications for psychology if pseudo-measurement is perpetuated. The article argues that either a re-conceptualisation of construct validity or the development of a new form of validity evidence may be necessary, if the psychological profession is to meet the future in an ethical and scientific manner.
Cross-cultural Similarities in ADHD-Like Behaviour Amongst South African Primary School Children
Authors: Meyer Anneke , Eilertsen Dag-Erik , Sundet Jon Martin , Tshifularo Johannes , Sagvolden Terje
Published: March 2013

This study investigates whether the Disruptive Behaviour Disorders (DBDs) rating scale measures the same constructs in South African as in Western cultures, and explores the differences in scale scores as a function of language, gender and age. Teacher ratings between 1997 and 1999 of the 18 DSM-IV symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in 6 094 primary school children of six language groups in the Limpopo Province of South Africa were collected and analysed. For all language groups, the results were consistent with a two-factor model of ADHD with correlated factors. There were gender and age effects on both scales. The prevalence rates for ADHD sub-types were in line with rates in the United States of America (US) and Europe. Similarities across language groups, as well as to results reported in the US and Europe, were striking. Despite the limitations discussed, teacher ratings of ADHD symptoms on the DBD scale can be used as a screening instrument in South Africa. Separate norms for different language groups are not indicated.
HIV/AIDS in Developing Countries: Heading towards a Mental Health and Consequent Social Disaster?
Authors: Freeman Melvyn
Published: March 2013

The HIV/AIDS pandemic will have massive implications for mental health in sub-Saharan Africa. While research in developed countries is quite advanced in this area, and while some of this research is relevant and important in developing countries, understanding and dealing with a disease of relatively low prevalence and which is mostly under control is vastly different from the considerations required of a growing epidemic which seems likely to kill a significant proportion of the population. The mental health implications of HIV/AIDS will be felt by individuals, families, communities and society as a whole. This article looks at the mental health of people who are unsure of their HIV status, people diagnosed as HIV-positive, the family and caregivers of HIV-positive individuals, people left behind following AIDS deaths and of society as a whole. Given the magnitude and pervasiveness of HIV, it is argued that the mental health ‘whole’ will be far greater than the sum of the parts. This means that much more research and interventions will have to be put in place in order to obviate a potential mental health and social ‘disaster’.
Bulimic Pathology in Black Students in South Africa: Some Unexpected Findings
Authors: Edwards David , Moldan Samantha
Published: March 2013

A high frequency of behaviours and attitudes associated with bulimia nervosa among black respondents, including males, has recently been reported in South Africa. The aims of the present study were to replicate these findings using a sampling procedure which would yield few refusals or dropouts, and to interview black males with bulimic symptoms to gain an understanding of their behaviour and motivation. In total, 40 black females, 39 black males, 40 white females and 42 white males who were students in residence at Rhodes University completed the Bulimia Test (BULIT). The criterion for marked bulimic pathology was exceeded by 25% of white females, 10% of black females and 5% of black males. The mean BULIT score for white females was significantly greater than that of the other groups and the other three groups did not differ significantly among themselves. Interviews revealed marked variability in understanding technical terms related to eating disordered behaviour, particularly among black males. When respondents who answered inconsistently were identified and removed from the analysis, the main conclusions from the analysis of variance were unaltered although the mean BULIT for black males was reduced by 3.7 and only one (2.5%) black male remained above the cut-off. It is concluded that subgroups of educated blacks may show relatively little bulimic pathology, and that the previous finding of significant bulimic pathology among black males might be artifactual and needs to be replicated under carefully controlled conditions.
The Process and Phases of Arthur Inman's Suicidal Career
Authors: Appalsamy Prabashini
Published: March 2013

This study attempted to understand the process of Arthur Crew Inman's suicidal career, and the phases and pathways leading to his eventual suicide. There remains an inadequate understanding of the phases of the suicide process, even though research has produced insight into the possible pathways leading to the suicide act. Using The Inman diary, which documents, amongst other things, the suicidal behaviour of Arthur Inman, grounded theory techniques were implemented in this study in order to understand such a process. These techniques included the constant comparative method, coding as proposed by Strauss's concept indicator model, memoing and integrative diagramming. The results revealed the existence of four phases of the suicide process, subsuming several pathways. Whilst contemporary studies have focused on pathways to the suicide act, mostly comprising relationships between different variables, it is argued that identifying phases of the process may provide a means of structuring such pathways within certain phases. These phases are characterised by specific cognito-emotive and behavioural properties. Validity and reliability issues are also addressed, together with possible methodological limitations.
Null Hypothesis Significance Testing: Ramifications, Ruminations and Recommendations
Authors: Huysamen G. K.
Published: March 2013

Criticisms of traditional null hypothesis significance testing (NHST) became more pronounced during the 1960s and reached a climax during the past decade. Among others, NHST says nothing about the size of the population parameter of interest and its result is influenced by sample size. Estimation of confidence intervals around point estimates of the relevant parameters, model fitting and Bayesian statistics represent some major departures from conventional NHST. Testing non-nil null hypotheses, determining optimal sample size to uncover only substantively meaningful effect sizes and reporting effect-size estimates may be regarded as minor extensions of NHST. Although there seems to be growing support for the estimation of confidence intervals around point estimates of the relevant parameters, it is unlikely that NHST-based procedures will disappear in the near future. In the meantime, it is widely accepted that effect-size estimates should be reported as a mandatory adjunct to conventional NHST results.
A City-Level Study of Aggressive Road Behaviours: Magnitude, and Predictors and Implications for Traffic Safety
Authors: Sukhai Anesh , Seedat Mohamed , Jordaan Esmé , Jackson Debra
Published: March 2013

Road rage and aggressive driving behaviours are reported to be huge public problems. There is a paucity of scientific South African data on driver aggression. Accordingly, a cross-sectional descriptive study was undertaken to determine the nature, extent and profile of aggressive and other hazardous road behaviours. The different categories of aggressive road behaviours were located on a continuum comprising four levels. Together with other hazardous driving behaviours, they were measured using a modified semantic differential on a scale of 1 to 10. Additionally, multiple linear regression modelling was used to identify various predictor variables for the different levels of aggressive road behaviour. The high prevalence data as well as many of the predictors of aggressive road behaviours that were found in the study are consistent with international findings. The utility of the data is discussed as part of a recommended ecological and health promotion approach for the prevention of aggressive road behaviours.
Chronic Fatigue Syndrome, the Body and the Self: A Qualitative Analysis
Authors: Lombaard Ansie , Mouton Johann
Published: March 2013

In a study directed towards the development of a greater understanding of the subjective illness experience of those who suffer from Chronic Fatigue Syndrome (CFS), we identified the sufferer's relationship with the body as one of the dimensions of the self most affected by CFS. We found that the profound changes instigated by CFS transform the relationship between the self and the body into a frontline where conflict prevails and inner dissension threaten. Participants' experiences fortunately revealed that such discord can be attenuated when the self makes it its personal responsibility to listen attentively to the body and to then respond to it in a way that will support a sensible balance between activity and restriction.
Putting the PC in IQ: Images in the Weschler Adult Intelligence Scale – Third Edition (WAIS III)
Authors: van Ommen Clifford
Published: March 2013

Images, as a form of discourse, have an ideological dimension. The third edition of the Wechsler Adult Intelligence Scale contains images revised so as to make them more ecologically valid and relevant for contemporary test takers. It is argued that the revisionists have to deal with various ideological issues so as to not make these scenes provocative. However, is it possible to produce images that are ideologically sensitive without undermining relevance and ecological validity? This question is addressed by analysing the images using the concept of ‘positionings’ and the social categories of race, gender and class. Strategies are thus articulated that introduce political correctness but may undermine the explicit goals of the revisionists. In response, the notion of ‘narrative validity’ is suggested, which refers to the comprehension of contemporary rhetorical strategies used to sidestep ideological tensions. Given this, test-wiseness takes on an ideological nuance in that test takers require a degree of familiarity with these strategies so as to effectively engage with these sub-tests. The use of the WAIS III in South Africa is consequently discussed.