bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenal Function in Preterm Infants Undergoing Patent Ductus Arteriosus Ligation
Authors: EL-Khuffash Afif , McNamara Patrick J. , Lapointe Anie , Jain Amish
Published: April 2013

Background: Targeted milrinone treatment for low left ventricular output (LVO) reduces the incidence of acute cardiorespiratory instability following ligation of patent ductus arteriosus (PDA) in preterm infants. Despite this, some infants continue to experience postoperative deterioration. Adrenal insufficiency related to prematurity has been postulated as a possible mechanism. Objectives: To describe adrenal function in premature infants undergoing PDA ligation and to investigate its association with pre- and postoperative clinical and echocardiography-derived indices of disease severity. Methods: A retrospective cohort study was conducted over a 2-year period on infants who underwent PDA ligation and had preoperative adrenocorticotropic hormone (ACTH) stimulation. All infants were screened by echocardiography for low LVO at 1 h after surgery and treated with intravenous milrinone if LVO <200 ml/kg/min. The primary outcome evaluated was low LVO at 1 h after surgery. Secondary outcomes included hypotension and oxygenation and ventilation failure occurring within 24 h. Results: A total of 35 infants at a median gestation of 25.4 (24.5-26.4) weeks and weight at birth of 700 (600-810) g were included. Baseline median cortisol measured preoperatively was 202 (137-403) nmol/l. Following the ACTH stimulation test, 3 infants had cortisol ≤500 nmol/l while 15 had ≤750 nmol/l. There was no association seen between any cortisol value and low LVO postoperatively. Post-ACTH cortisol ≤750 nmol/l was significantly associated with hypotension (p = 0.03) and oxygenation (p = 0.04) and ventilation (p = 0.008) failure. Receiver-operator characteristic curve showed a high predictive value of post-ACTH cortisol for all clinical outcomes. Conclusions: Post-ACTH cortisol (≤750 nmol/l) may be associated with clinical indices of postoperative cardiorespiratory instability. Relative adrenal insufficiency may play a role in the etiology of post-PDA ligation hemodynamic and respiratory instability.
Role of Reflexology and Antiepileptic Drugs in Managing Intractable Epilepsy - a Randomized Controlled Trial
Authors: Dalal Krishna , Devarajan Elanchezhiyan , Pandey Ravindra Mohan , Subbiah Vivekanandan , Tripathi Manjari
Published: April 2013

Background: This report is based on the results of a randomized parallel controlled trial conducted to determine the efficacy of reflexology therapy in managing intractable epilepsy. Methods: Subjects who failed epilepsy surgery or were not candidates for epilepsy surgery or were non-responders of antiepileptic drugs (AEDs) took part in this study. The trial was completed by 77 subjects randomly assigned to 2 arms: control (AEDs) and reflexology (AEDs + reflexology therapy). The hypothesis was that hand reflexology therapy could produce results similar to those of vagus nerve stimulation, and foot reflexology therapy could maintain homeostasis in the functional status of individual body parts. Reflexology therapy was applied by family members. The follow-up period was 1.5 years. Quality of life in epilepsy patients was assessed with the QOLIE-31 instrument. Results: In the reflexology group, the median baseline seizure frequency decreased from 9.5 (range 2-120) to 2 (range 0-110) with statistical significance (p < 0.001). In the control arm, the decrease was less than 25% with a baseline value of 16 (range 2-150). The pretherapy QOLIE-31 scores in the control group and the reflexology group were 41.05 ± 7 and 43.6 ± 8, respectively. Posttherapy data were 49.07 ± 6 and 65.4 ± 9, respectively (p < 0.002). The reflexology method allowed detection of knee pain in 85% of the reflexology group patients (p < 0.001), and 85.3% of patients derived 81% relief from it (p < 0.001). 4 reflexology group patients reported nausea/vomiting (n = 1), change in voice (n = 2), and hoarseness (n = 1). Conclusion: Reflexology therapy together with AEDs may help reducing seizure frequency and improving quality of life in individuals with epilepsy.
A Hypnic Hypothesis of Alzheimer's Disease
Authors: Clark Camilla N. , Warren Jason D.
Published: April 2013

Background: Understanding the pathophysiology of Alzheimer's disease (AD) is of fundamental importance for improved diagnosis, monitoring and ultimately, treatment. Objective: A role for the sleep-wake cycle in the pathogenesis of AD has been proposed, but remains to be worked out in detail. Methods: Here we draw together several lines of previous work to outline a ‘hypnic hypothesis' of AD. Results: We propose that altered function of brainstem neurotransmitter pathways associated with sleep, promotes regionally specific disintegration of a cortico-subcortical ‘default mode' brain network that is selectively vulnerable in AD. Conclusion: The formation of a dynamic toxic state within this vulnerable network linked to sleep-wake disruption, would in turn lead to failure of synaptic repair, increased transmission of pathogenic misfolded proteins and a self-amplifying neurodegenerative process. We consider the evidence for this hypnic hypothesis and the implications that follow on from it.
Association of Bone Mineral Density with Albuminuria and Estimated Glomerular Filtration Rate : The Dong-gu Study
Authors: Choi Seong-Woo , Kim Hye-Yeon , Ahn Hye-Ran , Lee Young-Hoon , Kweon Sun-Seog , Choi Jin-Su , Rhee Jung-Ae , Nam Hae-Sung , Jeong Seul-Ki , Park Kyeong-Soo , Ryu So-Yeon , Song Hye-Rim , Shin Min-Ho
Published: April 2013

Background: Kidney dysfunction and albuminuria may be associated with BMD. However, little evidence has been reported on relationships between BMD and eGFR and albuminuria. Methods: A total of 8,992 subjects aged 50 years or older participated in a survey conducted. Participants had their lumbar spine and femoral neck BMD measured by a Lunar Prodigy bone densitometer (GE, Madison, WI). Kidney function was assessed using MDRD eGFR and diagnosis of albuminuria was based on albumin-creatinine ratio. Results: ACR was negatively associated with lumbar spine and femur neck BMD in females (lumbar spine: 1.001, 0.988, 0.974 and 0.979 g/cm2, p < 0.001; femur neck: 0.796, 0.790, 0.783 and 0.782 g/cm2, p = 0.002), but not in males, after adjusting for covariates. Additionally, eGFR was shown to be negatively associated with lumbar spine BMD after adjusting for covariates (male: 1.181, 1.166, 1.152 and 1.149 g/cm2, p = 0.001; female: 0.997, 0.980, 0.979 and 0.982 g/cm2, p = 0.005), but demonstrated no association with femur BMD. Conclusions: ACR in females was negatively associated with lumbar spine and femur neck BMD, but not in males. eGFR was negatively associated with lumbar spine BMD in both males and females.
Immunocytochemical Detection of Raf Kinase Inhibitor Protein and Human Papillomavirus Profiling of Normal and Abnormal Cervical ThinPrep Samples
Authors: Al-Awadhi Rana , Husain Sawsan , Chehadeh Wassim , Al-Jassar Waleed , Kapila Kusum , Al-Mulla Fahd
Published: April 2013

Objectives: This study investigates the potential value of Raf kinase inhibitor protein (RKIP) as a marker of normal squamous cells in ThinPrep slides. RKIP was evaluated for its ability to distinguish between normal and abnormal cervical samples in the context of human papillomavirus (HPV) infections. Study Design: A total of 316 ThinPrep samples were taken from women with normal and abnormal cervices. ThinPrep slides were Papanicolaou stained and reported. Residual samples were used for RKIP immunostaining and HPV PCR-based sequencing. Results: RKIP expression was seen in both nuclei and cytoplasm in 83.7% of samples. RKIP expression was highest (84.6%) in samples with a diagnosis of high-grade squamous intraepithelial lesion (HSIL) or worse; expression was lower in low-grade squamous intraepithelial lesions (73%) and was lowest in samples with normal cytology (p = 0.0023). A total of 74% of HPV-infected ThinPrep samples were immunopositive, and 67% of samples that did not harbor HPV were also immunopositive (p = 0.414). Sensitivity and specificity of RKIP were 84.6 and 34.6%, respectively, for the detection of samples with HSIL or worse. Conclusions: This study showed that RKIP expression may be of some value as a marker for abnormal cervical cells. Combined RKIP expression and HPV testing could improve the identification of samples with abnormal cytology.
Intra-Amniotic Delivery of Amniotic-Derived Neural Stem Cells in a Syngeneic Model of Spina Bifida
Authors: Turner Christopher G. , Pennington Elliot C. , Gray Fabienne L. , Ahmed Azra , Teng Yang D. , Fauza Dario O.
Published: April 2013

Objective: Neural stem cells (NSCs) may promote spinal cord repair in fetuses with experimental spina bifida. We sought to determine the fate of amniotic-derived NSCs (aNSCs) after simple intra-amniotic injection in a syngeneic model of spina bifida. Methods: Fetal neural tube defects were induced on 20 pregnant Lewis dams by prenatal administration of retinoic acid. Ten dams served as amniotic fluid donors for epigenetic isolation of aNSCs, which were expanded and labeled with 5-bromo-2′-deoxyuridine. The remaining 10 dams received intra-amniotic injections of the processed aNSCs, blindly in all their fetuses (n = 37) on gestational day 17 (term = E21-22). Fetuses with spina bifida underwent screening for the presence of donor aNSCs in the spinal cord at term. Results: Donor cells were identified in 93.3% of the animals with spina bifida, selectively populating the neural placode, typically in clusters, retaining an undifferentiated morphology, and predominantly on exposed neural surfaces, though some were detected deeper in neighboring neural tissue. Conclusions: The amniotic cavity can serve as a route of administration of NSCs in experimental spina bifida. Simple intra-amniotic delivery of NSCs may be a practical adjuvant to regenerative strategies for the treatment of spina bifida.
Thyroid Incidentalomas on FDG PET/CT in Patients with Non-Thyroid Cancer - a Large Retrospective Monocentric Study
Authors: Kim Heeyoung , Kim Seong-Jang , Kim In-Joo , Kim Keunyoung
Published: April 2013

Background: The purpose of this study was to compare the incidence of thyroid cancer among patients with primary non-thyroid cancer, who showed focal thyroid uptake in 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT). Material and Methods: We reviewed a total of 22,674 FDG PET/CTs performed at our institution between March 2005 and June 2011. A retrospective review was conducted on 433 non-thyroid cancer patients (male: n = 90, female: n = 343) who had thyroid incidentaloma on FDG PET/CT. In 286 patients, diagnostic confirmation was done by ultrasound-guided fine needle aspiration biopsy (FNAB). Results: Among 22,674 FDG PET/CT scans, 483 subjects (2.1%) showed focal thyroid uptake. Among the 286 patients who underwent FNAB, 280 were included in the study. Of those, 68 patients (24.3%) demonstrated papillary thyroid carcinoma on the final pathologic findings. We divided patients into 7 groups depending on the primary cancer. Conclusion: In patients with cancer of non-thyroid origin, incidental FDG uptake in the thyroid gland was observed in 2.1% and associated with a 24.3% risk for well-differentiated thyroid carcinoma. However, there was no statistically significant difference in the malignant risk of focal FDG uptake of the thyroid gland according to the underlying primary non-thyroid cancer type.
A Screening Trial of Helicobacter pylori-Specific Antigen Tests in Saliva to Identify an Oral Infection
Authors: Yee Kuo Ching , Wei M.H. , Yee Hsian Ching , Everett Karin D.E. , Yee Hsian Pei , Hazeki-Talor Noriko
Published: April 2013

Objective:Helicobacter pylori infection places a heavy burden on medical and economic resources. Standard diagnosis requires the presence of established H. pylori gastric disease. Study Design and Setting: A multicenter screening trial assessing 2 immunochromatographic H. pylori antigen oral tests was carried out with 201 participants. The analysis also included a urea breath test (UBT), a Campylobacter-like organism test, silver stain, culture, serology, and stool tests. Results: The participants were grouped into UBT positive (UBT+) and UBT negative (UBT-) people, using conventional methods with congruent clusters based on p values from McNemar's paired χ2 analysis and 95% CI estimates. Both oral tests were also positive in 82% of the seropositive UBT- people. However, oral antigen and seroprevalence divided UBT- people into 2 statistically separate CI subgroups: the UBT- symptomatic (highly positive) group and the UBT- asymptomatic (mostly negative) group. 90.5% of all people whose oral tests were both negative were also UBT-. Conclusions: Saliva H. pylori antigen is an important indicator in UBT- asymptomatic patients. Currently, its clinical significance remains uncertain, but saliva may be a reservoir from where H. pylori is transmitted to the stomach. In symptomatic patients, it is strongly associated with stomach infection.
Surgical Exploration as the Definitive Means of Diagnosing a Unilateral Idiopathic Retroperitoneal Fibrosis: Report of a Case
Authors: Troja Achim , El-Sourani Nader , Antolovic Dalibur , Raab Hans-Rudolph
Published: April 2013

Background: Retroperitoneal fibrosis is considered as one of the rare diseases, with an incidence rate of 1/200,000. A guideline for its diagnosis and therapy does not exist. In the past centuries, case studies and small-scale series have therefore been used for diagnostic purposes. Case Report: We report the case of a 45-year-old female patient who approached the emergency department complaining of flank pain. The primary diagnostics including computed tomography, magnetic resonance imaging, sonography, and laboratory testing showed a distension of the Musculus psoas and Musculus iliacus on the right side with an unclear genesis. Accessorily performed diagnostic analysis including scintigraphy and intestinal endoscopy did not provide additional information. Because of persisting complaints, a surgical exploration of the right retroperitoneal space was performed resulting in a histological diagnosis of an idiopathic fibrosis (Morbus Ormond). Conclusion: Despite the permanent improvement of diagnostic imaging in general, a surgical exploration accompanied by histological investigation is the diagnostic tool of choice in selected cases.
Hyperuricemia Is an Independent Risk Factor for Mortality Only if Chronic Kidney Disease Is Present
Authors: Chung Wookyung , Kim Ae Jin , Ro Han , Chang Jae Hyun , Lee Hyun Hee , Jung Ji Yong
Published: April 2013

Background/Aims: Hyperuricemia has been considered a risk factor for renal disease and cardiovascular disease. However, the potential contribution of hyperuricemia to mortality remains uncertain, and the results in the available literature vary according to kidney function. The aim of this study was to determine the association between hyperuricemia and mortality in patients undergoing percutaneous coronary intervention (PCI) across the interaction of kidney function. Method: We retrospectively reviewed patients who underwent PCI from 2003 to 2009. Propensity scores for hyperuricemia (>7 mg/dl for males and >6 mg/dl for females) were used to assemble a matched cohort of 693 pairs of patients with and without hyperuricemia for analysis from the 3,201 patients who fulfilled the inclusion criteria among the 4,842 patients who underwent PCI. Results: Of the 3,201 patients who underwent PCI and for whom data were available regarding their baseline serum uric acid level, 763 (23.8%) had hyperuricemia. The hyperuricemia-associated hazard ratios (HRs) [95% confidence intervals (CIs)] for all-cause mortality were 1.780 (1.270-2.495) in the unmatched cohort and 1.655 (1.109-2.468) in the matched cohort. The HRs (95% CI) for all-cause mortality among those with and without chronic kidney disease (CKD) were 2.080 (1.318-3.283) and 1.592 (0.778-3.256), respectively (p for interaction, 0.001). Conclusions: Hyperuricemia is an independent risk factor for all-cause mortality in those patients with CKD but not in those without CKD.
Akupunkturbehandlungsmodalitäten bei künstlicher Befruchtung - ein Vergleich der Behandlungspraxis in schweizerischen, deutschen und österreichischen Kinderwunschzentren mit Erhebungen in randomisierten kontrollierten Studien
Authors: Nedeljković Marko , Bouzas-Ammann Gabrielle , Zimmermann Lukas , Stute Petra , Ausfeld-Hafter Brigitte
Published: April 2013

Hintergrund: Unerfüllter Kinderwunsch belastet jedes fünfte Paar. Zur Wirksamkeitssteigerung der künstlichen Befruchtung werden oftmals Akupunkturbehandlungen durchgeführt. Wenig ist über die Akupunkturbehandlungsmodalitäten in Kinderwunschzentren bekannt. Ziel der vorliegenden Arbeit war es, diese zu erfassen und mit den in randomisierten kontrollierten Studien (RCTs) untersuchten Akupunkturbehandlungsmodalitäten zu vergleichen. Methoden: 180 Kinderwunschkliniken, die auf den Webseiten der schweizerischen, deutschen und österreichischen reproduktionsmedizinischen Vereinigungen aufgeführt waren, wurden zur Teilnahme an einer Onlinebefragung über das Akupunkturangebot bei künstlicher Befruchtung eingeladen. Die Umfrageergebnisse wurden den Angaben aus 17 RCTs gegenübergestellt. Ergebnisse: Akupunktur wird von 33 (38,4%) aller an der Umfrage beteiligten Kinderwunschkliniken (n = 86) angeboten (Rücklaufquote = 47,8%). Die Wahl der Akupunkturpunkte ist in 39,4% der Kliniken standardisiert, in 24,2% semi-standardisiert und in 27,3% erfolgt sie individuell nach TCM-Diagnose. Körperakupunktur mit Nadelstimulierung wurde am häufigsten genannt (84,8%). In einigen Kliniken wird ergänzend zur Körperakupunktur auch Ohrakupunktur (24,2%) und Moxibustion (21,2%) angewendet. Die Leistungserbringer sind überwiegend ärztliche Akupunkturtherapeuten (84,8%). Im Vergleich zu den RCTs wurden große Unterschiede hinsichtlich Bestimmung der Akupunkturpunkte, Stimulierungsverfahren und beruflichem Hintergrund der Akupunktur-Leistungserbringer festgestellt. Schlussfolgerungen: Weniger als 40% aller Akupunktur anbietenden Kinderwunschkliniken im deutschsprachigen Raum verwenden standardisierte Akupunkturpunkteprotokolle. Um die externe Validität der Akupunkturforschung in der Reproduktionsmedizin zu erhöhen und die klinische Wirksamkeit dieser adjuvanten Behandlungsform zu untersuchen, sollten in zukünftigen Studien semi-standardisierte und individuelle Bestimmungen der Akupunkturpunkte berücksichtigt und der Einsatz von angelerntem Personal vermieden werden.
How Accurately Do Nephrologists Predict the Need for Dialysis within One Year?
Authors: Green Darren , Ritchie James P. , New David I. , Kalra Philip A.
Published: April 2013

Background/Aims: Knowing when patients with chronic kidney disease will need dialysis can improve patient counselling and timing of vascular access. We aimed to assess the accuracy of clinician judgement in predicting the need for dialysis within 12 months. Methods: We asked the nephrologists in a dedicated pre-dialysis clinic to predict the time until initiation of dialysis for patients. We compared predicted with actual time to dialysis and the accuracy of predictions made by different grades of clinician. Multivariate logistic regression compared clinical parameters that correlated with predicted and actual time to dialysis. Results: One hundred and eighty-four patients were included. The sensitivity of clinician judgement as a predictor of dialysis within 12 months was 95% and the specificity was 62%. Consultants were correct in 71% of cases and trainees in 68% of cases. Estimated glomerular filtration rate (eGFR) was the only independent correlate of predicted time to dialysis [odds ratio (OR) = 1.6 per 1 ml/min/1.73 m2 reduction, p < 0.001]. eGFR was also associated with actual time to dialysis (OR = 1.6 per 1 ml/min/1.73 m2, p < 0.001) along with age (OR = 0.94 per year increase, p = 0.005) and itch (OR = 3.7, p = 0.048). Conclusion: Clinical judgement is sensitive but not specific in predicting the need for dialysis. Educating the clinicians may improve the specificity of judgement and improve the accuracy of prognostic information given to patients.
Locoregional Transarterial Therapies for Hepatocellular Carcinoma: Transarterial Chemoembolization and Radioembolization
Authors: Iñarrairaegui Mercedes , D'Avola Delia , Sangro Bruno
Published: April 2013

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third most common cause of cancer-related mortality. Despite the widespread implementation of surveillance programs, more than half of the patients with HCC are diagnosed at late stages, when curative treatments (resection or liver transplantation) cannot be applied. For patients presenting with unresectable, non-transplantable HCC and a relatively preserved liver function, locoregional transarterial therapies are the main therapeutic options. Therefore, locoregional transarterial treatments play a key role in the management of HCC. The concept of catheter transarterial therapies is to selectively deliver anticancer treatments to liver tumors. This is possible due to the unique double irrigation of the liver and the predominantly arterial irrigation of liver tumors. Method: An exhaustive analysis of the literature, focused mainly on the last 25 years, has been carried out. Results: This review discusses the scientific evidence supporting the use of transarterial therapies for patients with HCC, including chemoembolization with conventional materials or drug-eluting beads, and internal radiation procedures such as the injection of radiation-loaded microspheres. Conclusion: Transarterial chemoembolization has been shown to improve the survival of those patients with unresectable HCC who have a preserved liver function and a low tumor burden. Recently developed devices and procedures, particularly drug-eluting beads and radioactive microspheres, may further improve the clinical outcome of patients receiving transarterial therapies. The combination with antiangiogenic agents is an appealing approach that should be explored.
Association of Functional Kallikrein-1 Promoter Polymorphisms and Acute Kidney Injury: A Case-Control and Longitudinal Cohort Study
Authors: Susantitaphong Paweena , Perianayagam Mary C. , Kang Sun Woo , Zhang Wenyi , Rao Fangwen , O'Connor Daniel T. , Jaber Bertrand L.
Published: April 2013

Background: Kallikrein-1 (KLK1) is a highly conserved serine protease that is expressed in the kidney and involved in blood pressure regulation. The activity of this enzyme is diminished in acute kidney injury (AKI). Methods: We first evaluated the potential role of functional multiallelic KLK1 promoter gene polymorphisms in a case-control study of 481 subjects (214 hospitalized patients with AKI of mixed causes and 267 healthy subjects). The complex, multiallelic G/C-rich repeat region of the proximal KLK1 promoter was determined by direct Sanger/capillary resequencing. Results: 16 alleles were identified in a complex, polymorphic G/C-rich region of the KLK1 proximal promoter; 5 of these alleles (F, G, H, I, and K) were associated with development of AKI. Alleles I and G were classified as risk-alleles (unadjusted OR 1.86; 95% CI 1.23, 2.81; p = 0.003), whereas alleles F, H, and K were classified as protective-alleles (unadjusted OR 0.32; 95% CI 0.22, 0.46; p < 0.001) according to their directional association with development of AKI. After adjustment for sex, race, preexisting chronic kidney disease and APACHE II score, the KLK1 risk-allele (I or G) carrier state was associated with the composite of ≥2-fold increase in serum creatinine, oliguria, or dialysis requirement (adjusted OR 2.71; 95% CI 1.14, 6.44; p = 0.02). The KLK1 risk-allele carrier state was also marginally associated with the composite of ≥2-fold increase in serum creatinine, oliguria, dialysis requirement, or in-hospital death (adjusted OR 2.33; 95% CI 0.98, 5.52; p = 0.06). Conclusions:KLK1 promoter polymorphisms are associated with development of AKI and adverse outcomes. Further studies are needed to validate these findings.
Ayurvedic Management of Ulcerative Colitis - a Non-Randomized Observational Clinical Study
Authors: Patel Kalapi B , Patel Manish , Mehta Charmi S , Gupta Shivenarain , Kessler Christian S.
Published: April 2013

No abstract available
The Potential Value of Phosphohistone-H3 Mitotic Index Determined by Digital Image Analysis in the Assessment of Pancreatic Endocrine Tumors in Fine-Needle Aspiration Cytology Specimens
Authors: Draganova-Tacheva Rossitza , Bibbo Marluce , Birbe Ruth , Daskalakis Constantine , Solomides Charalambos
Published: April 2013

Objective: According to the World Health Organization, pancreatic endocrine tumors are graded by assessment of the Ki67 proliferation index and/or mitotic count. The objective was to find comparable grading on the basis of the novel mitotic marker phosphohistone-H3 (PHH3). Study Design: A computer-assisted system was used to assess 23 cell blocks stained with PHH3 and Ki67 antibodies. We investigated possible cut-points for PHH3 and computed percent agreement between the PHH3- and Ki67-based grading. Results: The Spearman correlation between percent Ki67 positive and percent PHH3 positive was 0.76 (p = 0.001). A value of 0.3% for the lower cut-point (‘cut-point 1', differentiating between grades 1 and 2) and values of about 1.8-1.9% for the higher cut-point (‘cut-point 2', differentiating between grades 2 and 3) shows optimal agreement between PHH3 and Ki67 grading. The percentage of positive cells was much higher for Ki67 than for PHH3 (mean 10.6 vs. 3.0%). Conclusions: PHH3 has good correlation with Ki67, but the range of PHH3 positivity is much narrower than that of Ki67 (range 0-4% for PHH3 vs. 0-50% for Ki67). Therefore, to be as accurate, grading on the basis of PHH3 requires evaluation of a larger number of tumor cells for a precise determination of percent PHH3-positive nuclei.
Systemische Therapie des hepatozellulären Karzinoms
Authors: Kirstein Martha M. , Vogel Arndt
Published: April 2013

Hintergrund: Das hepatozelluläre Karzinom (HCC) ist eine der häufigsten Tumorerkrankungen weltweit. Mit dem Multikinase-Inhibitor Sorafenib konnte erstmals ein signifikanter Überlebensvorteil bei Patienten mit fortgeschrittenem HCC gezeigt werden. Bis heute ist Sorafenib die einzige zugelassene systemisch wirksame Substanz für Patienten mit fortgeschrittenem HCC. Die weiteren Behandlungsoptionen für Patienten mit einem fortgeschrittenen HCC sind jedoch beschränkt. Es fehlen insbesondere Second-line-Therapien für Patienten, die Sorafenib nicht tolerieren und/oder hierunter progredient werden. Methode: Neue molekulare Therapien befinden sich in klinischer Entwicklung, bislang allerdings mit zumeist ernüchternden Ergebnissen. Ergebnisse: Untersuchungen der alternativen Angiogenese-Inhibitoren Sunitinib und Brivanib, der EGFR(epidermaler Wachstumsfaktor-Rezeptor)-Inhibitoren Erlotinib, Gefitinib, Lapatinib und Cetuximab sowie des MEK(Mitogen-aktivierte Proteinkinase)-Inhibitors Selumetinib waren bislang nicht zielführend. Erfolg versprechend erscheint die Inhibition von c-MET mit Tivantinib, die bei c-MET-überexprimierenden Patienten eine signifikante Verlängerung des Überlebens und der Zeit zur Progression erbrachte. Untersuchungen von anderen Zielgruppen wie unter anderem Inhibitoren von mTOR, PI3K/ Akt und IGFR befinden sich in teils noch früher klinischer Entwicklung und bleiben abzuwarten. Schlussfolgerungen: Die Entwicklung der systemischen Behandlung des HCC bleibt anspruchsvoll. Zunehmend zeichnet sich ab, dass bei HCC-Patienten eine schwierige Balance zwischen Toxizität der Behandlung und antitumoraler Wirkung besteht, die eine signifikante Verbesserung des Überlebens der Patienten ermöglicht. Eine Lösung dieses Dilemmas könnte in der Identifikation von prognostischen und prädiktiven Faktoren wie c-MET bestehen, die eine personalisierte und effektive Therapie in Subgruppen der HCC-Patienten ermöglichen sollte.
Laboratory diagnostic outcome applying detection criteria recommended by the Scientific and Standardization Committee of the ISTH on Lupus Anticoagulant
Authors: Biguzzi Eugenia , Asti Daniela , Palmucci Claudia , Tripodi Armando , Chantarangkul Veena
Published: April 2013

This study shows the diagnostic outcome of an APTT-based and two dRVVT-based commercial confirmatory integrated tests with the application of the recommendations by the Scientific and Standardization Committee (SSC) on Lupus anticoagulant (LA)/antiphospholipid syndrome (APS) of the International Society on Thrombosis and Haemostasis (ISTH) issued in 2009 concerning the cut-off values for the screening, mixing and confirmatory tests for the detection of LA and the mandatory need to perform mixing tests of patient plasma with pooled normal plasma. The study population included 565 patients collected from a large central coagulation laboratory, for which the attending physicians requested LA detection. One-hundred-six healthy subjects (HS) and 131 selected patients on oral anticoagulant therapy (OAT) were included as negative controls. The results suggest that the performance of mixing tests is indicated for those methods with relatively poor specificity, but is less needed for those methods with high specificity. Furthermore, the SSC recommendation to use normal mid-value (i.e. the 50th percentile of distribution of results from healthy subjects) as the cut-off to interpret results of confirmatory tests, showed a modest increase in LA detection rate (sensitivity) but at the expense of specificity, particularly in methods with low specificity.
Clopidogrel pretreatment in primary percutaneous coronary intervention: Prevalence of high on-treatment platelet reactivity and impact on preprocedural patency of the infarct-related artery
Authors: Berdejo Javier , Roura Gerard , Gómez-Lara Josep , Romaguera Rafael , Teruel Luis , Sánchez-Elvira Guillermo , Marcano Ana , Gómez-Hospital Joan , Angiolillo Dominick , Cequier Ángel , Ferreiro José , Homs Sílvia
Published: April 2013

To date, there is limited data on levels of platelet inhibition achieved in patients with ST-elevation myocardial infarction (STEMI) who are loaded with clopidogrel and aspirin (ASA) prior to undergoing primary percutaneous coronary intervention (P-PCI). The aim of this investigation was to evaluate the percentage of STEMI patients with high on-treatment platelet reactivity (HPR) to clopidogrel at the time of initiating P-PCI and its association with the initial patency of the infarct-related artery (IRA). This prospective pharmacodynamic study included 50 STEMI patients, previously naïve to oral antiplatelet agents, who received 500-mg ASA and 600-mg clopidogrel loading doses prior to P-PCI. Platelet function assessment was performed at the beginning of the procedure using various assays, including VerifyNow™ system (primary endpoint), light transmission aggregometry and multiple electrode aggregometry. The percentage of patients with suboptimal response to clopidogrel and ASA assessed with the VerifyNow™ system was 88.0% and 28.6%, respectively. Similar results were obtained with the other assays used. A higher percentage of patients with initial patency of the IRA was observed among those patients without HPR compared with those with HPR to clopidogrel (66.7% vs 15.9%; p=0.013), while no differences were observed regarding postprocedural angiographic or electrocardiographic outcomes. In conclusion, this study shows that a high percentage of STEMI patients have inadequate levels of clopidogrel-induced and, to a lesser extent, aspirin-mediated platelet inhibition when starting a P-PCI procedure, and suggests that a poor response to clopidogrel might be associated with impaired initial TIMI flow in the IRA.
Macrophage-Derived Matrix Vesicles
Authors: New Sophie E. P. , Goettsch Claudia , Aikawa Masanori , Marchini Julio F. , Shibasaki Manabu , Yabusaki Katsumi , Libby Peter , Shanahan Catherine M. , Croce Kevin , Aikawa Elena
Published: April 2013

Rationale:

We previously showed that early calcification of atherosclerotic plaques associates with macrophage accumulation. Chronic renal disease and mineral imbalance accelerate calcification and the subsequent release of matrix vesicles (MVs), precursors of microcalcification.

Objective:

We tested the hypothesis that macrophage-derived MVs contribute directly to microcalcification.

Methods and Results:

Macrophages associated with regions of calcified vesicular structures in human carotid plaques (n=136 patients). In vitro, macrophages released MVs with high calcification and aggregation potential. MVs expressed exosomal markers (CD9 and TSG101) and contained S100A9 and annexin V. Silencing S100A9 in vitro and genetic deficiency in S100A9
−/−
mice reduced MV calcification, whereas stimulation with S100A9 increased calcification potential. Externalization of phosphatidylserine after Ca/P stimulation and interaction of S100A9 and annexin V indicated that a phosphatidylserine-annexin V-S100A9 membrane complex facilitates hydroxyapatite nucleation within the macrophage-derived MV membrane.

Conclusions:

Our results support the novel concept that macrophages release calcifying MVs enriched in S100A9 and annexin V, which contribute to accelerated microcalcification in chronic renal disease.
National Heart, Lung, and Blood Institute and the Translation of Cardiovascular Discoveries Into Therapeutic Approaches
Authors: Galis Zorina S. , Black Jodi B. , Skarlatos Sonia I.
Published: April 2013

The molecular causes of ≈4000 medical conditions have been described, yet only 5% have associated therapies. For decades, the average time for drug development through approval has taken 10 to 20 years. In recent years, the serious challenges that confront the private sector have made it difficult to capitalize on new opportunities presented by advances in genomics and cellular therapies. Current trends are disturbing. Pharmaceutical companies are reducing their investments in research, and biotechnology companies are struggling to obtain venture funds. To support early-stage translation of the discoveries in basic science, the National Institutes of Health and the National Heart, Lung, and Blood Institute have developed new approaches to facilitating the translation of basic discoveries into clinical applications and will continue to develop a variety of programs that create teams of academic investigators and industry partners. The goal of these programs is to maximize the public benefit of investment of taxpayer dollars in biomedical research and to lessen the risk required for industry partners to make substantial investments. This article highlights several examples of National Heart, Lung, and Blood Institute–initiated translational programs and National Institutes of Health translational resources designed to catalyze and enable the earliest stages of the biomedical product development process. The translation of latest discoveries into therapeutic approaches depends on continued federal funding to enhance the early stages of the product development process and to stimulate and catalyze partnerships between academia, industry, and other sources of capital.
Forecasting the Impact of Heart Failure in the United States
Authors: Heidenreich Paul A. , Albert Nancy M. , Allen Larry A. , Bluemke David A. , Butler Javed , Fonarow Gregg C. , Ikonomidis John S. , Khavjou Olga , Konstam Marvin A. , Maddox Thomas M. , Nichol Graham , Pham Michael , Piña Ileana L. , Trogdon Justin G.
Published: April 2013

Background—

Heart failure (HF) is an important contributor to both the burden and cost of national healthcare expenditures, with more older Americans hospitalized for HF than for any other medical condition. With the aging of the population, the impact of HF is expected to increase substantially.

Methods and Results—

We estimated future costs of HF by adapting a methodology developed by the American Heart Association to project the epidemiology and future costs of HF from 2012 to 2030 without double counting the costs attributed to comorbid conditions. The model assumes that HF prevalence will remain constant by age, sex, and race/ethnicity and that rising costs and technological innovation will continue at the same rate. By 2030, >8 million people in the United States (1 in every 33) will have HF. Between 2012 and 2030, real (2010$) total direct medical costs of HF are projected to increase from $21 billion to $53 billion. Total costs, including indirect costs for HF, are estimated to increase from $31 billion in 2012 to $70 billion in 2030. If one assumes all costs of cardiac care for HF patients are attributable to HF (no cost attribution to comorbid conditions), the 2030 projected cost estimates of treating patients with HF will be 3-fold higher ($160 billion in direct costs).

Conclusions—

The estimated prevalence and cost of care for HF will increase markedly because of aging of the population. Strategies to prevent HF and improve the efficiency of care are needed.
The “Lost Mackerel” of the North East Atlantic—The Flawed System of Trilateral and Bilateral Decision-making
Authors: Ørebech Peter
Published: April 2013

Abstract

The North East Atlantic mackerel is moving westward and northward. How to integrate new coastal states whose Exclusive Economic Zone is invaded by mackerel into existing decision-making processes? The 1982 Law of the Sea Convention, the 1995 Straddling Fish Stocks Agreement, the 1980 North East Atlantic Fisheries Convention, and bilateral and trilateral agreements between “relevant coastal states” fail to provide rules for present decision-makers to incorporate newcomers. The present harvesting states are sovereign with regard to admitting or refusing newcomers. This article argues for a stricter obligation on coastal states to acknowledge the right of new harvesting nations to access decision-making processes for estimating total allowable catch and allocating quotas. Equitable distribution can occur if quota allocation is subject to principles that are less discretionary than the present ones. One solution is to estimate the ratio of biomass related to the share of coastal states in the distribution of eggs, larvae and fishable stock, and allocate a quota to each coastal and high seas fishing state accordingly.
An annotated catalog of the Iranian Dipsocoromorpha, Enicocephalomorpha, Gerromorpha, Leptopodomorpha and Nepomorpha (Hemiptera: Heteroptera)
Authors: GHAHARI HASSAN , MOULET PIERRE , OSTOVAN HADI , LINNAVUORI RAUNO E.
Published: April 2013

A catalog of aquatic and semiaquatic Heteroptera from Iran is provided based on literature reports and field collections. Representatives of 107 species and morphospecies of the infraorders Dipsocoromorpha, Enicocephalomorpha, Gerromorpha, Leptopodomorpha, and Nepomorpha are listed, and are distributed in 18 families including Aphelocheiridae (1 genus, 1 species), Belostomatidae (1 genus, 1 species), Corixidae (8 genera, 29 species), Dipsocoridae (1 genus, 2 species), Enicocephalidae (2 genera, 2 species), Gerridae (6 genera, 18 species), Hebridae (1 genus, 5 species), Helotrephidae (1 genus, 1 species), Hydrometridae (1 genus, 2 species), Leptopodidae (4 genera, 7 species), Mesoveliidae (1 genus, 2 species), Naucoridae (1 genus, 1 species), Nepidae (3 genera, 5 species), Notonectidae (2 genera, 8 species), Ochteridae (1 genus, 1 species), Pleidae (1 genus, 1 species), Saldidae (5 genera, 14 species), and Veliidae (2 genera, 7 species). Synonyms and geographical distribution of all the species are given, together with an identification key of families. According to the actual catalogs and studies eight species are doubtful for Iranian fauna.
Trans-Andean Ancistrus (Siluriformes: Loricariidae)
Authors: TAPHORN DONALD C. , ARMBRUSTER JONATHAN W. , VILLA-NAVARRO FRANCISCO , RAY C. KEITH
Published: April 2013

We review the trans-Andean species of Ancistrus from Panama, Colombia and Venezuela. Based on analyses of meristic, morphometric and pigmentation pattern data of preserved specimens, eight of sixteen species reported from this region are considered valid and two new species are described. Here we review Ancistrus chagresi Eigenmann & Eigenmann 1889 from both slopes of central Panama; A. centrolepis Regan 1913 from Pacific slopes of eastern Panama and western Colombia; Ancistrus caucanus Fowler 1943, from the Magdalena River drainage in northern Colombia; Ancistrus martini Schultz 1944, from the Lake Maracaibo Basin of Venezuela and Colombia. Ancistrus galani Pérez & Viloria 1994, from a cave in the Lake Maracaibo Basin of Venezuela is considered valid but was not examined. Ancistrus tolima new species is described from the upper Magdalena River drainage and Ancistrus vericaucanus new species is described from the up-per Cauca River drainage. Ancistrus gymnorhynchus Kner 1854 and A. falconensis Taphorn, Armbruster & Rodriguez-O. 2010 were treated previously. One specimen of A. clementinae Rendahl 1937 from the Pacific coast of Ecuador was ex-amined, it is considered a valid species. A key for identification and geographical ranges are provided.
A new species of the genus Promacrolaelaps (Acari: Laelapidae) associated with Propomacrus bimucronatus (Pallas) (Coleoptera: Scarabaeidae) in Iran
Authors: JOHARCHI OMID , HALLIDAY BRUCE , BEYZAVI GHOLAMREZA
Published: April 2013

We describe a new species of mite from Iran - Promacrolaelaps propomacrus sp. nov. (Acari: Laelapidae). The new spe-cies was collected in association with the beetle Propomacrus bimucronatus (Pallas) (Coleoptera: Scarabaeidae: Euchiri-nae) in holes in the trunk of oak trees. The genus Promacrolaelaps is redescribed and distinguished from the related genus Hypoaspis Canestrini sens. strict.
U.S. Climate Reference Network after One Decade of Operations: Status and Assessment
Authors: Diamond Howard J. , Karl Thomas R. , Palecki Michael A. , Baker C. Bruce , Bell Jesse E. , Leeper Ronald D. , Easterling David R. , Lawrimore Jay H. , Meyers Tilden P. , Helfert Michael R. , Goodge Grant , Thorne Peter W.
Published: April 2013

The year 2012 marks a decade of observations undertaken by the U.S. Climate Reference Network (USCRN) under the auspices of NOAA's National Climatic Data Center and Atmospheric Turbulence and Diffusion Division. The network consists of 114 sites across the conterminous 48 states, with additional sites in Alaska and Hawaii. Stations are installed in open (where possible), rural sites very likely to have stable land-cover/use conditions for several decades to come. At each site a suite of meteorological parameters are monitored, including triple redundancy for the primary air temperature and precipitation variables and for soil moisture/temperature. Instrumentation is regularly calibrated to National Institute for Standards and Technology (NIST) standards and maintained by a staff of expert engineers. This attention to detail in USCRN is intended to ensure the creation of an unimpeachable record of changes in surface climate over the United States for decades to come. Data are made available without restriction for all public, private, and government use. This article describes the rationale for the USCRN, its implementation, and some of the highlights of the first decade of operations. One critical use of these observations is as an independent data source to verify the existing U.S. temperature record derived from networks corrected for nonhomogenous histories. Future directions for the network are also discussed, including the applicability of USCRN approaches for networks monitoring climate at scales from regional to global. Constructive feedback from end users will allow for continued improvement of USCRN in the future and ensure that it continues to meet stakeholder requirements for precise climate measurements.
Goodness Comes From Within
Authors: Thauer Christian R.
Published: April 2013

This article makes the case for the importance of paying attention to the internal dynamics of business in order to understand why and under which conditions firms engage in corporate social responsibility (CSR). The argument is that CSR assists decision-makers in firms to resolve managerial dilemmas. By a managerial dilemma this article understands a situation whereby the execution of management’s decisions requires asset specific allocation of resources.  Asset specific allocation of resources transforms the intra-organizational mode of social coordination from a hierarchy to one in which managers become dependent on, and vulnerable to, the behavior of subordinates. It is in these situations that corporate decision-makers introduce CSR standards in their attempt to avoid the foreseeable loss of control and organizational efficiency.
Vocational Psychology in Corrections
Authors: Morgan Robert D.
Published: April 2013

This reaction to the major contribution (MC) “The Vocational Development of Offenders: Barriers, Interventions, and Implications for Social Justice” commends the authors for bringing an understudied and underdiscussed population to counseling psychologists. This reaction provides a contextual response to the MC in its entirety, as well as for the three articles comprising the MC. The authors are commended for educating readers about the complexities of correctional rehabilitation, emphasizing the role of work in the rehabilitation process to reduce criminal recidivism, and examining current vocational practices; however, this reaction provides practical suggestions for improving the integration of best correctional practices into vocational counseling, and provides suggestions for policy change. In addition, this reaction further emphasizes the necessity of counseling psychologists’ involvement in offender rehabilitation.
Temperature-curvature relationships in asymmetric angle ply laminates by considering the effects of resin layers and temperature dependency of material properties
Authors: Moore M , Ziaei-Rad S , Firouzian-Nejad A
Published: April 2013

It is well-known that asymmetric composite laminates can have bi-stable response to different kind of loadings. In this research, the non-linear temperature-curvature relationship for the asymmetric composite laminates is studied using Rayleigh–Ritz technique. Attention is focused on studying the effect of material temperature dependency and resin layers; especially in the bifurcation point by use of analytical method. To this end, the well-known analytical theories are extended and used to consider the temperature dependency of material. The results obtained from the theory are then compared with the finite element simulations results and a good correlation is obtained. Finally, an experimental investigation is carried out and several specimens with [90/0]T, [60/–30]T and [30/–30]T compositions were manufactured. In order to study the effect of resin layers, optical microscopy is utilized and the exact thickness of different layers in the manufactured specimens is determined. The thermal responses of the manufactured plates were measured and used to validate the results obtained from the analytical theory and finite element simulations.
Description of the mechanical behavior of different thermoset composites reinforced with Manicaria saccifera fibers
Authors: Oliveira AKF , d’Almeida JRM
Published: April 2013

This work describes for the first time the flexural and compression mechanical behavior of Manicaria saccifera fibers–polymer matrix composites. These lignocellulosic fibers are obtained from a palm of natural occurrence at the Amazon region. Specifically here the fibrous natural mat that protects the fruits’ palm is used. The results obtained are comparable to the data from other lignocellulosic fiber–polymer matrix composites, demonstrating the feasibility of using Manicaria saccifera fibers as reinforcement. The wear behavior of the composites was also analyzed and their use as parquet floor is pointed out as a possibility.