bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological distress in medical patients seeking ED care for somatic reasons: results of a systematic literature review
Authors: Faessler Lukas , Perrig-Chiello Pasqualina , Mueller Beat , Schuetz Philipp
Published: September 2015

Objectives

The aim of this systematic literature review is to investigate (A) currently used instruments for assessing psychological distress, (B) the prevalence of psychological distress in medical emergency department (ED) patients with acute somatic conditions and (C) empirical evidence on how predictors are associated with psychological distress.

Methods

We conducted an electronic literature search using three databases to identify studies that used validated instruments for detection of psychological distress in adult patients presented to the ED with somatic (non-psychiatric) complaints. From a total of 1688 potential articles, 18 studies were selected for in-depth review.

Results

A total of 13 instruments have been applied for assessment of distress including screening questionnaires and briefly structured clinical interviews. Using these instruments, the prevalence of psychological distress detected in medical ED patients was between 4% and 47%. Psychological distress in general and particularly depression and anxiety have been found to be associated with demographic factors (eg, female gender, middle age) and illness-related variables (eg, urgency of triage category). Some studies reported that coexisting psychological distress of medical patients identified in the ED was associated with physical and psychological health status after ED discharge. Importantly, during routine clinical care, only few patients with psychological distress were diagnosed by their treating physicians.

Conclusions

There is strong evidence that psychological distress is an important and prevalent cofactor in medically ill patients presenting to the ED with harmful associations with (subjective) health outcomes. To prove causality, future research should investigate whether screening and lowering psychological distress with specific interventions would result in better patient outcomes.
Fascin-1 expression as stratification marker in borderline epithelial tumours of the ovary
Authors: El-Balat Ahmed , Arsenic Ruza , Sänger Nicole , Karn Thomas , Becker Sven , Holtrich Uwe , Engels Knut
Published: September 2015

Aims

To evaluate the actin-bundling protein fascin-1 (FSCN1) as marker for borderline ovarian tumours (BOTs).

Methods

We analysed a retrospective cohort of 140 BOTs with validated diagnosis by an independent pathologist. Immunohistochemical detection of FSCN1 was quantified as combined immunoreactive score (CIS) blinded to clinical patient data. Analyses were first performed for FSCN1 positive versus negative, and then verified using three categories derived from the observed distribution (negative, weak, strong; CIS 0, 1–2, 3–9).

Results

We detected FSCN1 positivity in 51.4%, and strong expression (CIS 3–9) in 14.3% of the samples. FSCN1 positivity was associated with serous subtype (p<0.001) and micropapillary pattern (p<0.001). Correlation with micropapillary pattern remained significant within the serous BOT (SBOT) subgroup (p=0.022). Strong FSCN1 expression (CIS 3–9) was associated both with the presence of implants (p=0.022), and a higher International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.020).

Conclusions

Our analysis links FSCN1 with SBOT with micropapillary pattern. Strong expression is associated with higher FIGO stage and the presence of implants, both related to elevated risk of recurrence. Hence, FSCN1 is an interesting marker worth further analyses of its prognostic value in BOTs.
Rosmarinic Acid Attenuates Sodium Taurocholate-Induced Acute Pancreatitis in Rats by Inhibiting Nuclear Factor-κB Activation
Authors: Fan Yu-Ting , Yin Guo-Jian , Xiao Wen-Qin , Qiu Lei , Yu Ge , Hu Yan-Ling , Xing Miao , Wu De-Qing , Cang Xiao-Feng , Wan Rong , Wang Xing-Peng , Hu Guo-Yong
Published: September 2015

Rosmarinic Acid (RA), a caffeic acid ester, has been shown to exert anti-inflammation, anti-oxidant and antiallergic effects. Our study aimed to investigate the effect of RA in sodium taurocholate ( NaTC )-induced acute pancreatitis, both in vivo and in vitro. In vivo, RA (50 mg/kg) was administered intraperitoneally 2 h before sodium taurocholate injection. Rats were sacrificed 12 h, 24 h or 48 h after sodium taurocholate injection. Pretreatment with RA significantly ameliorated pancreas histopathological changes, decreased amylase and lipase activities in serum, lowered myeloperoxidase activity in the pancreas, reduced systematic and pancreatic interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and inhibited NF-κB translocation in pancreas. In vitro, pretreating the fresh rat pancreatic acinar cells with 80 μ mol/L RA 2 h before 3750 nmol/L sodium taurocholate or 10 ng/L TNF-α administration significantly attenuated the reduction of isolated pancreatic acinar cell viability and inhibited the nuclear activation and translocation of NF-κB. Based on our findings, RA appears to attenuate damage in sodium taurocholate-induced acute pancreatitis and reduce the release of inflammatory cytokines by inhibiting the activation of NF-κB. These findings might provide a basis for investigating the therapeutic role of RA in managing acute pancreatits.
Density functional theory calculations of NO molecule adsorption on monolayer MoS2 doped by Fe atom
Authors: Wang Yanhua , Shang Xiaoyu , Wang Xiaowei , Tong Jianying , Xu Jingcheng
Published: September 2015

Functionalization of [Formula: see text] monolayer doped by the transition-metal Fe adatom [Formula: see text]–[Formula: see text] and NO absorption on [Formula: see text]–[Formula: see text] has been investigated computationally using first-principles calculations based on the density functional theory. We found that the system of [Formula: see text]–[Formula: see text] remains a semiconductor, with spin polarization at the Fermi level. However, for the system with absorption of NO molecule on the surface of [Formula: see text]–[Formula: see text] monolayer, its spin polarization is turned over at the Femi level, which provides a promising material for spintronic sensors.
Virtual braids and virtual curve diagrams
Authors: Chterental Oleg
Published: September 2015

There is a well-known injective homomorphism [Formula: see text] from the classical braid group [Formula: see text] into the automorphism group of the free group [Formula: see text], first described by Artin [Theory of Braids, Ann. Math. (2) 48(1) (1947) 101–126]. This homomorphism induces an action of [Formula: see text] on [Formula: see text] that can be recovered by considering the braid group as the mapping class group of [Formula: see text] (an upper half plane with [Formula: see text] punctures) acting naturally on the fundamental group of [Formula: see text]. Kauffman introduced virtual links [Virtual knot theory, European J. Combin. 20 (1999) 663–691] as an extension of the classical notion of a link in [Formula: see text]. There is a corresponding notion of a virtual braid, and the set of virtual braids on [Formula: see text] strands forms a group [Formula: see text]. In this paper, we will generalize the Artin action to virtual braids. We will define a set, [Formula: see text], of “virtual curve diagrams” and define an action of [Formula: see text] on [Formula: see text]. Then, we will show that, as in Artin’s case, the action is faithful. This provides a combinatorial solution to the word problem in [Formula: see text]. In the papers [V. G. Bardakov, Virtual and welded links and their invariants, Siberian Electron. Math. Rep. 21 (2005) 196–199; V. O. Manturov, On recognition of virtual braids, Zap. Nauch. Sem. POMI 299 (2003) 267–286], an extension [Formula: see text] of the Artin homomorphism was introduced, and the question of its injectivity was raised. We find that [Formula: see text] is not injective by exhibiting a non-trivial virtual braid in the kernel when [Formula: see text].
A mathematical boundary integral equation for analysis of the heterogeneous media, using the functionally graded elements
Authors: Ashrafi H. , Shariyat M.
Published: September 2015

In the present research, a functionally graded (FG) boundary integral equation method capable of modeling quasistatic behavior of heterogeneous media fabricated from functionally graded materials (FGMs) whose distributions of the material properties obey either power or exponential laws is developed. Two heterogeneous material gradation models were employed to present the numerical formulations and solution algorithm. Somigliana's identity in 2D displacement fields of the isotropic heterogeneous domains is numerically implemented, employing FG elements. Based on the constitutive and governing equations and the weighted residual technique, the proposed boundary integral equation formulations are implemented for behavior analysis of the elastic heterogeneous isotropic solid structures. Results are verified and the proposed boundary element (BE) formulation is employed for behavior analysis of the plates and cylinders to demonstrate the proposed procedure more adequately.
Physical Activity, Aerobic Capacity, and Total Antioxidant Capacity in Healthy Men and in Men with Coronary Heart Disease
Authors: Gawron-Skarbek Anna , Chrzczanowicz Jacek , Kostka Joanna , Nowak Dariusz , Drygas Wojciech , Jegier Anna , Kostka Tomasz
Published: September 2015

Objective.The purpose of the study was to assess total antioxidant capacity (TAC) of blood serum in relation with habitual leisure time physical activity (LTPA) and aerobic capacity in a group of 90 men with coronary heart disease (CHD) aged 34.8–77.0 years and in 90 age-matched peers without CHD.Methods.Two spectrophotometric methods were applied to assess TAC: Ferric Reducing Ability of Serum (TAC-FRAS) and 2.2-diphenyl-1-picryl-hydrazyl (TAC-DPPH) tests. Aerobic capacity was expressed as physical working capacity at 85% of the maximal heart rate (PWC85%HRmax).Results. CHD patients had higher values of TACFRAS (1.37±0.28versus1.27±0.23 mmol FeCl2·L−1;P<0.05) but there were no group differences for TAC-DPPH and for uric acid (UA). Negative correlation was found between LTPA (also when calculated per kg of body mass) and TAC-DPPH in CHD patients. In CHD patients, TAC-FRAS and UA were lower in subjects with higher aerobic capacity expressed asPWC85%HRmax/kg. Those associations were not found in healthy men.Conclusions. We conclude that TAC of blood serum is moderately adversely related to LTPA and aerobic capacity in patients with CHD. UA, as the main determinant of serum TAC, may be partially responsible for those associations.
Effect of Long-Term Treatment with Fimasartan on Transient Focal Ischemia in Rat Brain
Authors: Kim Chi Kyung , Yang Xiu-Li , Kim Young-Ju , Choi In-Young , Jeong Han-Gil , Park Hong-Kyun , Kim Dohoung , Kim Tae Jung , Jang Hyunduk , Ko Sang-Bae , Yoon Byung-Woo
Published: September 2015

Fimasartan is a newly developed angiotensin receptor blocker, which may have protective effects during myocardial infarction or atherosclerosis. In this context, we investigated the effects of long-term treatment with low-dose fimasartan on focal ischemia in rat brain. We induced focal ischemia in brain by transient intraluminal occlusion of middle cerebral artery (MCA) and administered low-dose (0.5 mg/kg) or regular doses (1 or 3 mg/kg) of fimasartan via intravenous routes. After the administration of low-dose (0.5 mg/kg) fimasartan, blood pressure did not decrease compared to the phosphate-buffered saline- (PBS-) control with MCA occlusion (MCAO) group. The infarct volume and ischemic cell death were reduced in the low-dose fimasartan-treated group (46 ± 41 mm3for 0.5 mg/kg and 153 ± 47 mm3for PBS-control with MCAO;P<0.01) but not in the regular-dose groups. Low-dose fimasartan treatment improved functional recovery after ischemia and significantly decreased mortality. In our study, fimasartan reduced the degradation of IκB and the formation of an inflammatory end-product, COX-2. As a result, the recruitment of inflammatory cells in the peri-infarct area decreased in fimasartan-treated group. We have demonstrated that long-term, low-dose fimasartan treatment improved outcomes after focal ischemia in the brain via a reduction of inflammation.
Pannus Is the New Prepuce? Penile Cancer in a Buried Phallus
Authors: Manwaring Jared , Vourganti Srinivas , Nikolavsky Dmitriy , Valente Alfredo L. , Byler Timothy
Published: September 2015

Two males presented to our urology department with complaints of bleeding and malodor from buried phallus within a suprapubic fat pad. Although both men had neonatal circumcisions, advanced penile carcinoma was found in both men. Formal penectomies showed high grade, poorly differentiated squamous cell carcinoma invading the corporal bodies and urethra. Buried penis represents a difficulty in early detection of suspicious lesions but may also provide an environment susceptible to poor hygiene and subsequent chronic inflammation. Patients with buried penis may be at a higher risk for development of invasive penile cancer and may benefit from regular and thorough genital exams.
Clinical Impact of the KL-6 Concentration of Pancreatic Juice for Diagnosing Pancreatic Masses
Authors: Matsumoto Kazuya , Takeda Yohei , Harada Kenichi , Onoyama Takumi , Kawata Soichiro , Horie Yasushi , Sakamoto Teruhisa , Ueki Masaru , Miura Norimasa , Murawaki Yoshikazu
Published: September 2015

Background and Aim. Pancreatic juice cytology (PJC) is considered optimal for differentially diagnosing pancreatic masses, but the accuracy of PJC ranges from 46.7% to 93.0%. The aim of this study was to evaluate the clinical impact of measuring the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses.Methods. PJC and the KL-6 concentration measurements of pancreatic juice were performed for 70 consecutive patients with pancreatic masses (39 malignancies and 31 benign).Results. The average KL-6 concentration of pancreatic juice was significantly higher for pancreatic ductal adenocarcinomas (PDACs) (167.7±396.1 U/mL) and intraductal papillary mucinous carcinomas (IPMCs) (86.9±21.1 U/mL) than for pancreatic inflammatory lesions (17.5±15.7 U/mL,P=0.034) and intraductal papillary mucinous neoplasms (14.4±2.0 U/mL,P=0.026), respectively. When the cut-off level of the KL-6 concentration of pancreatic juice was 16 U/mL, the sensitivity, specificity, and accuracy of the KL-6 concentration of pancreatic juice alone were 79.5%, 64.5%, and 72.9%, respectively. Adding the KL-6 concentration of pancreatic juice to PJC when making a diagnosis caused the values of sensitivity and accuracy of PJC to increase by 15.3% (P=0.025) and 8.5% (P=0.048), respectively.Conclusions. The KL-6 concentration of pancreatic juice may be as useful as PJC for diagnosing PDACs.
Specific Correlation between the Hegu Point (LI4) and the Orofacial Part: Evidence from an fMRI Study
Authors: Kong Su-ping , Tan Qi-wen , Liu Ying , Jing Xiang-hong , Zhu Bing , Huo Yong-jun , Nie Bin-bin , Yang Dian-hui
Published: September 2015

Acupoint specificity is a foundational concept in acupuncture theory. It is closely related to the function of the acupoint. In this study, we sought to probe the central mechanisms of the specific correlation between LI4 and orofacial part in Bell’s palsy patients. In total, 36 patients with left Bell’s palsy were divided into three groups in random order, and each group received transcutaneous electrical acupoint stimulation (TEAS) at only one of three acupoints (LI4, ST6, and a sham point). A single-block fMRI design paradigm was applied to separately detect neural activity related to different stages of TEAS (prestimulation resting state, stimulation, and poststimulation resting state). Functional magnetic resonance imaging data were acquired during TEAS. There were extensive neuronal activities in the LI4 and ST6 groups and significant differences between stimulation at real and sham points. Brain regions were activated more by real acupoint TEAS than by sham point TEAS. Brain regions that were activated with LI4 and ST6 were broadly overlapping and adjacent. Our results provide supplementary neuroimaging evidence for the existence of acupoint specificity. These results may confirm the central mechanisms of the specific correlation between the Hegu point and the orofacial part.
Dominant Modes of Tropospheric Ozone Variation over East Asia from GOME Observations
Authors: Liu Yi , Zhang Yuli , Wang Yong , Liu Chuanxi , Cai Zhaonan , Konopka Paul , Müller Rolf
Published: September 2015

The variation in tropospheric ozone over East Asia was analyzed using tropospheric column ozone data measured by the Global Ozone Monitoring Experiment (GOME) satellite. An empirical orthogonal function (EOF) analysis was carried out to derive the dominant modes of the variation in the tropospheric ozone volume-mixing ratio (TOVMR). The EOF1 mode, which explained 61.5% of the total variance, showed a same-sign distribution over all of East Asia, with a belt of enhanced ozone concentrations around 40°N. The principal component of EOF1 (PC1) suggested that photochemical ozone production together with Brewer-Dobson circulation and subtropical westerly jet plays important roles in modulating the seasonal variation of the TOVMR; ozone-rich air produced by photochemical processes was transported from the stratosphere to the troposphere by BD circulation and this ozone-rich air was then blocked by the subtropical westerly jet and accumulated north of the jet. The EOF2 mode explained 29.2% of the total variance with an opposite-sign pattern on the north and south side of 35°N. When anticyclonic circulation transported ozone-poor air from the upwelling area over the Bay of Bengal towards the Tibetan Plateau during the onset of the Asian summer monsoon, tropospheric ozone in this region decreased dramatically.
Dynamics of Kaolinite-Urea Nanocomposites via Coupled DMSO-Hydroxyaluminum Oligomeric Intermediates
Authors: Sempeho Siafu Ibahati , Kim Hee Taik , Mubofu Egid , Pogrebnoi Alexander , Shao Godlisten , Hilonga Askwar
Published: September 2015

Kaolinite-urea nanocomposites were prepared via intercalation reactions in an attempt to investigate the dynamic nature of kaolinite morphology for advanced applications in controlled release systems (CRS). Characterization was done using SEM-EDX, XRF, ATR-FTIR, XRD, and DT/DTG; Andreasen pipette sedimentation technique was used to determine the grain size distribution of the raw kaolinite. The X-ray diffraction pattern revealed the existence of an FCC Bravais lattice where the intercalation ratios attained were 51.2%, 32.4%, 7.0%, and 38.4% for hydroxyaluminum oligomeric intercalated kaolinite, substituted urea intercalated kaolinite, calcined DMSO intercalated kaolinite, and hydroxyaluminum reintercalated kaolinite, respectively, along with their respective crystallite sizes of 33.51–31.73 nm, 41.92–39.69 nm, 22.31–21.13 nm, and 41.86–39.63 nm. The outcomes demonstrated that the employed intercalation routes require improvements as the intercalation reactions were in average only ≈32.3%. The observations unveiled that it is possible to manipulate kaolinite structure into various morphologies including dense-tightly packed overlapping euhedral pseudo hexagonal platelets, stacked vermiform morphologies, postulated forms, and unique patterns exhibiting self-assembled curled glomeruli-like morphologies. Such a diversity of kaolinite morphologies expedites its advanced applications in the controlled release systems (CRS) such as drug delivery systems and controlled release fertilizers (CRFs).
Rheumatic Heart Disease in Kerala: A Vanishing Entity? An Echo Doppler Study in 5–15-Years-Old School Children
Authors: Nair Bigesh , Viswanathan Sunitha , Koshy A. George , Gupta Prabha Nini , Nair Namita , Thakkar Ashok
Published: September 2015

Background.Early detection of subclinical rheumatic heart disease by use of echocardiography warrants timely implementation of secondary antibiotic prophylaxis and thereby prevents or retards its related complications.Objectives.The objective of this epidemiological study was to determine prevalence of RHD by echocardiography using World Heart Federation criteria in randomly selected school children of Trivandrum.Methods.This was a population-based cross-sectional screening study carried out in Trivandrum. A total of 2060 school children, 5–15 years, were randomly selected from five government and two private (aided) schools. All enrolled children were screened for RHD according to standard clinical and WHF criteria of echocardiography.Results.Echocardiographic examinations confirmed RHD in 5 children out of 146 clinically suspected cases. Thus, clinical prevalence was found to be 2.4 per 1000. According to WHF criteria of echocardiography, 12 children (12/2060) were diagnosed with RHD corresponding to echocardiographic prevalence of 5.83 cases per 1000. As per criteria, 6 children were diagnosed with definite RHD and 6 with borderline RHD.Conclusions.The results of the current study demonstrate that echocardiography is more sensitive and feasible in detecting clinically silent RHD. Our study, the largest school survey of south India till date, points towards declining prevalence of RHD (5.83/1000 cases) using WHF criteria in Kerala.
Effectiveness of Intermittent Preventive Treatment in Pregnancy with Sulphadoxine-Pyrimethamine against SubmicroscopicfalciparumMalaria in Central Region, Ghana
Authors: Nwaefuna Ekene K. , Afoakwah Richmond , Orish Verner N. , Egyir-Yawson Alexander , Boampong Johnson N.
Published: September 2015

Malaria infections undetectable by microscopy but detectable by Polymerase Chain Reaction (PCR) (submicroscopic malaria) are common in endemic areas like Ghana. Submicroscopic malaria has been linked with severe pregnancy outcomes as well as contributing to malaria transmission. In this cross-sectional study 872 consenting pregnant women (gestation ≥ 20 weeks) were recruited from 8 hospitals in Central Region, Ghana, between July and December 2009. Malaria infection was detected by microscopy and PCR. Haemoglobin was measured and anaemia was defined as haemoglobin lower than 11 g/dL. Majority of the women, 555 (63.6%), were Intermittent Preventive Treatment in Pregnancy with Sulphadoxine-Pyrimethamine (IPTp-SP) users while 234 (36.4%) were nonusers. The prevalence of malaria by microscopy was 20.9% (182/872) and 9.7% (67/688) of microscopy negative women had submicroscopic malaria. IPTp-SP usage significantly (odds ratio = 0.13, 95% confidence interval = 0.07–0.23,p=0.005) reduced the prevalence of submicroscopic malaria as more nonusers (51/234) than users (16/454) were PCR positive. After controlling for other variables the effect of IPTp-SP remained statistically significant (odds ratio = 0.11, 95% confidence interval = 0.02–0.22,p=0.006). These results suggest that Intermittent Preventive Treatment with Sulphadoxine-Pyrimethamine is useful in the reduction of submicroscopic malaria in pregnancy.
Pain Management in Pregnancy: Multimodal Approaches
Authors: Shah Shalini , Banh Esther T. , Koury Katharine , Bhatia Gaurav , Nandi Roneeta , Gulur Padma
Published: September 2015

Nonobstetrical causes of pain during pregnancy are very common and can be incapacitating if not treated appropriately. Recent reports in the literature show that a significant percentage of pregnant women are treated with opioids during pregnancy. To address common pain conditions that present during pregnancy and the available pharmacological and nonpharmacological treatment options, for each of the pain conditions identified, a search using MEDLINE, PubMed, Embase, and Cochrane databases was performed. The quality of the evidence was evaluated in the context of study design. This paper is a narrative summary of the results obtained from individual reviews. There were significant disparities in the studies in terms of design, research and methodology, and outcomes analyzed. There is reasonable evidence available for pharmacological approaches; however, these are also associated with adverse events. Evidence for nonpharmacological approaches is limited and hence their efficacy is unclear, although they do appear to be primarily safe. A multimodal approach using a combination of nonpharmacological and pharmacological options to treat these pain conditions is likely to have the most benefit while limiting risk. Research trials with sound methodology and analysis of outcome data are needed.
Activation Status of the Pregnane X Receptor Influences Vemurafenib Availability in Humanized Mouse Models
Authors: MacLeod A. Kenneth , McLaughlin Lesley A. , Henderson Colin J. , Wolf C. Roland
Published: September 2015

Vemurafenib is a revolutionary treatment for melanoma, but the magnitude of therapeutic response is highly variable, and the rapid acquisition of resistance is frequent. Here, we examine how vemurafenib disposition, particularly through cytochrome P450-mediated oxidation pathways, could potentially influence these outcomes using a panel of knockout and transgenic humanized mouse models. We identified CYP3A4 as the major enzyme involved in the metabolism of vemurafenib in in vitro assays with human liver microsomes. However, mice expressing human CYP3A4 did not process vemurafenib to a greater extent than CYP3A4-null animals, suggesting that other pregnane X receptor (PXR)–regulated pathways may contribute more significantly to vemurafenib metabolism in vivo. Activation of PXR, but not of the closely related constitutive androstane receptor, profoundly reduced circulating levels of vemurafenib in humanized mice. This effect was independent of CYP3A4 and was negated by cotreatment with the drug efflux transporter inhibitor elacridar. Finally, vemurafenib strongly induced PXR activity in vitro, but only weakly induced PXR in vivo. Taken together, our findings demonstrate that vemurafenib is unlikely to exhibit a clinically significant interaction with CYP3A4, but that modulation of bioavailability through PXR-mediated regulation of drug transporters (e.g., by other drugs) has the potential to markedly influence systemic exposure and thereby therapeutic outcomes. Cancer Res; 75(21); 4573–81. ©2015 AACR.
Panobinostat for the Treatment of Multiple Myeloma
Authors: Laubach Jacob P. , Moreau Philippe , San-Miguel Jesús F. , Richardson Paul G.
Published: September 2015

Panobinostat is a potent oral deacetylase inhibitor that alters gene expression through epigenetic mechanisms and inhibits protein degradation. It was recently approved by the FDA and EMA for use in combination with bortezomib and dexamethasone in patients with multiple myeloma who have received ≥2 prior regimens, including bortezomib and an immunomodulatory drug. Panobinostat was approved based on results from the phase III PANORAMA 1 trial in patients with relapsed or relapsed and refractory multiple myeloma, which showed that panobinostat plus bortezomib and dexamethasone significantly extended progression-free survival (median, 12.0 months) compared with placebo plus bortezomib and dexamethasone (median, 8.1 months; P < 0.0001). Additional ongoing trials are evaluating panobinostat in combination with other partners in the relapsed/refractory and newly diagnosed treatment settings. This review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. Clin Cancer Res; 21(21); 4767–73. ©2015 AACR.
Seek and Ye Shall Find: Subclonal Anaplastic Lymphoma Kinase Mutations
Authors: George Rani E.
Published: September 2015

Bellini and colleagues demonstrate the importance of next-generation sequencing to uncover subclonal anaplastic lymphoma kinase (ALK) mutations in neuroblastoma. Although the significance of these subclonal aberrations is not yet understood, deep sequencing could identify patients whose tumors may respond to ALK inhibitors. Clin Cancer Res; 21(21); 4747–9. ©2015 AACR.

See related article by Bellini et al., p. 4913
Management of Mild-to-Moderate Ulcerative Colitis
Authors: Siegmund Britta
Published: September 2015

Managing mild-to-moderate ulcerative colitis on the first view appears to be a simple task. However, real life often proofs the opposite and creates a challenging situation. In theory, mild-to-moderate disease should be sufficiently treated by mesalamine or alternatively by a probiotic. Insufficient treatment comprises the danger of leading to a flare, and hence, an exacerbation of the entire disease, with risk of progressing to severe disease. What are the considerations with regard to patient management in this situation? Certainly, disease distribution is the critical information, since it allows for planning the optimal route of administration, namely local versus systemic treatment. Novel pharmacological strategies might allow for reaching high local concentrations even at the left side of the colon or alternatively administer locally active budesonide throughout the entire colon frame, thus avoiding systemic side effects. Therapy planning has to involve the patient to identify how this can be included in daily life. Including the patient implies that depending on the condition, disease activity and even life quality, the individual therapy requires timely adaption. A recent study by Pedersen et al. [Inflamm Bowel Dis 2014;20:2276-2285] provides evidence that this strategy can be followed and leads to an overall better outcome. A last thought, besides the patient not taking the appropriate dose or lacking adherence to therapy, should consider that a worsening of disease could be due to infectious complications including Clostridium difficile or cytomegalovirus colitis. If all considerations fail within a reasonable time frame, therapy should be escalated. Patients in this situation often hesitate in accepting the need of immunosuppression. Future options, potentially including phosphatidylcholine, might bridge the gap between mesalamine, probiotics and immunosuppressive strategies.
Targeting the Microbiome in Inflammatory Bowel Disease: Critical Evaluation of Current Concepts and Moving to New Horizons
Authors: Bejaoui Mohamed , Sokol Harry , Marteau Philippe
Published: September 2015

Microorganisms present in the intestine possess proinflammatory or anti-inflammatory activities which may modulate inflammatory bowel disease (IBD). The concepts followed by researchers in trying to target the microbiota in IBD were to decrease pathogens or pathobionts, or only the microbial load, and more recently, to favor growth and persistence of favorable microorganisms. We review, here, those concepts and critically analyze the clinical data (especially randomized controlled trials) obtained using antibiotics and probiotics. We eventually present and criticize the rational and data obtained so far following new research strategies including the use of new probiotics, genetically modified organisms and fecal transplantation.
Basic Self-Disturbance in the Schizophrenia Spectrum: Taking Stock and Moving Forward
Authors: Nelson Barnaby , Raballo Andrea
Published: September 2015

The concept of basic self-disturbance offers a renewed, phenomenologically oriented framework to approach both the cross-sectional and longitudinal complexity of schizophrenia spectrum psychopathology. According to this approach, schizophrenia is characterized by instability in the most foundational and irreducible dimension of selfhood, i.e. the basic sense of self. Whereas normal basic self-experience is characterized by being a self-present, single, temporally persistent, bodily and demarcated (bounded) subject of experience and action, vulnerability to schizophrenia is marked by several structural shifts in such a basic selfhood (e.g. unstable first-person perspective, diminished sense of presence, and loss of vital contact with reality). This provides the ground for the emergence of the varied symptoms of schizophrenia, such as positive, negative and disorganization symptoms. Recent empirical research confirms that basic self-disturbance is specific to the schizophrenia spectrum and might be of value in the prospective identification of prodromal patients. The concept has implications for both aetiopathogenetic research and clinical-psychotherapeutic intervention. Furthermore, it may offer an integrative framework across ‘levels' of inquiry in schizophrenia research (i.e. across psychopathological, neurocognitive and neurobiological domains).
Interest of Antiplatelet Drug Testing after an Acute Ischemic Stroke
Authors: Coignion Cyrielle , Poli Mathilde , Sagnier Sharmila , Freyburger Geneviève , Renou Pauline , Debruxelles Sabrina , Rouanet François , Sibon Igor
Published: September 2015

Background: Stroke occurrence despite chronic antiplatelet drug (APD) treatment is frequent. We aimed at evaluating the relevance of platelet aggregation testing in the identification of stroke etiology in this context. Methods: Patients admitted for a suspected acute ischemic stroke, while under APD (aspirin and/or clopidogrel), were prospectively included. The efficacy of the APD was evaluated using a Multiplate™ assay. Resistance was confirmed using light transmission aggregometry. A standardized diagnostic work-up was performed to identify stroke mechanism according to the TOAST and the ASCO classifications. We evaluated the influence of APD functional status on stroke severity and identified potential determinants of resistance. Results: APD resistance was observed in 53 of the 287 patients (18.5%). No difference in stroke mechanism depending on APD efficacy was observed. Patients sensitive to APD had less severe initial stroke severity (mean National Institutes of Health Stroke Scale 3.9 ± 5.6 vs. 7.2 ± 6.8; p < 0.01). Main determinants for APD resistance were a worse control of the diabetes and higher baseline levels of inflammation (mean CRP 26.4 ± 56.0 vs. 9.3 ± 21.0; p < 0.01). Conclusions: Platelet function testing does not provide orientation concerning stroke mechanism in patients who were previously on APDs. However, the high frequency of APD resistance and its association with inflammation and stroke severity are confirmed.
A Case of Recurrent Hemorrhages due to a Chronic Expanding Encapsulated Intracranial Hematoma
Authors: Marutani Akiko , Nagata Kiyoshi , Deguchi Jun , Nikaido Yuji , Kazuki Syuji
Published: September 2015

Few case reports of encapsulated intracranial hematoma (EIH) exist, and the mechanisms underlying the onset and enlargement of EIH remain unclear. Here, we report on a 39-year-old woman with an EIH that repeatedly hemorrhaged and swelled and was ultimately surgically removed. In June 2012, the patient visited her local doctor, complaining of headaches. A magnetic resonance imaging (MRI) scan identified a small hemorrhage of approximately 7 mm in her right basal ganglia, and a wait-and-see approach was adopted. Six months later, her headaches recurred. She was admitted to our department after MRI showed tumor lesions accompanying the intermittent hemorrhaging in the right basal ganglia. After admission, hemorrhaging was again observed, with symptoms progressing to left-sided hemiplegia and fluctuating consciousness; thus, a craniotomy was performed. No obvious abnormal blood vessels were observed on the preoperative cerebral angiography. We accessed the lesion using a transcortical approach via a right frontotemporal craniotomy and removed the subacute hematoma by extracting the encapsulated tumor as a single mass. Subsequent pathological examinations showed that the hematoma exhibited abnormal internal vascularization and was covered with a capsule formed from growing capillaries and accumulating collagen fibers, suggesting that it was an EIH. No lingering neurological symptoms were noted upon postoperative follow-up. This type of hematoma expands slowly and is asymptomatic, with reported cases consisting of patients that already have neurological deficits due to progressive hematoma growth. Our report is one of a few to provide a clinical picture of the initial stages that occur prior to hematoma encapsulation.
A DISTINÇÃO ENTRE PÚBLICO E PRIVADO E SUA CARACTERIZAÇÃO NO ÂMBITO DO ESTADO BRASILEIRO
Authors: Pinto Emerson de Lima , Costa Bernardo Leandro Carvalho
Published: September 2015

O presente artigo visa problematizar a dicotomia entre as esferas pública e privada no contexto do Estado brasileiro. Inicialmente faz-se um apanhado histórico acerca da dicotomia público/privado e, em um momento posterior, busca-se uma análise acerca dos reflexos causados pela dificuldade de distinguir estas duas esferas. Para elucidar a problemática ofertada, buscar-se-á no âmbito do direito administrativo a demonstração de algumas divergências, sobretudo na Reforma do Estado brasileiro, estruturada a partir da década de 1990.
The Contemporary Safety and Effectiveness of Lower Extremity Bypass Surgery and Peripheral Endovascular Interventions in the Treatment of Symptomatic Peripheral Arterial Disease
Authors: Tsai Thomas T. , Rehring Thomas F. , Rogers R. Kevin , Shetterly Susan M. , Wagner Nicole M. , Gupta Rajan , Jazaeri Omid , Hedayati Nasim , Jones W. Schuyler , Patel Manesh R. , Ho P. Michael , Go Alan S. , Magid David J.
Published: September 2015

Background—

Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) and peripheral endovascular interventions (PVIs); however, limited comparative effectiveness data exist between the 2 therapies. We assessed the safety and effectiveness of LEB and PVI in patients with symptomatic claudication and critical limb ischemia.

Methods and Results—

In a community-based clinical registry at 2 large integrated healthcare delivery systems, we compared 883 patients undergoing PVI and 975 patients undergoing LEB between January 1, 2005 and December 31, 2011. Rates of target lesion revascularization were greater for PVI than for LEB in patients presenting with claudication (12.3±2.7% and 19.0±3.5% at 1 and 3 years versus 5.2±2.4% and 8.3±3.1%, log-rank
P
<0.001) and critical limb ischemia (19.1±4.8% and 31.6±6.3% at 1 and 3 years versus 10.8±2.5% and 16.0±3.2%, log-rank
P
<0.001). However, in comparison with PVI, LEB was associated with increased rates of complications up to 30 days following the procedure (37.1% versus 11.9%,
P
<0.001). There were no differences in amputation rates between the 2 groups. Findings remained consistent in sensitivity analyses by using propensity methods to account for treatment selection.

Conclusions—

In patients with symptomatic peripheral artery disease, in comparison with LEB, PVI was associated with fewer 30-day procedural complications, higher revascularization rates at 1 and 3 years, and no difference in subsequent amputations.
Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing
Authors: Chan Yi-Hsin , Tsai Wei-Chung , Ko Jum-Suk , Yin Dechun , Chang Po-Cheng , Rubart Michael , Weiss James N. , Everett Thomas H. , Lin Shien-Fong , Chen Peng-Sheng
Published: September 2015

Background—

Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (
I
KAS
) is activated during hypokalemia and that
I
KAS
blockade is proarrhythmic.

Methods and Results—

Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD
80
) by 26 milliseconds (95% confidence interval [CI], 14–37) during normokalemia and by 54 milliseconds (95% CI, 40–68) during hypokalemia (
P
=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts;
P
=0.009). Short-term cardiac memory was assessed by the slope of APD
80
versus activation time. The slope increased from 0.01 (95% CI, −0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23–0.44) after apamin (
P
<0.001) during right ventricular pacing and from 0.07 (95% CI, −0.05 to 0.20) to 0.54 (95% CI, 0.06–1.03) after apamin infusion (
P
=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased
I
KAS
in isolated rabbit ventricular myocytes during hypokalemia (
P
=0.038).

Conclusions—

Hypokalemia activates
I
KAS
to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing.
I
KAS
blockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction.
Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis
Authors: Fontana Marianna , Pica Silvia , Reant Patricia , Abdel-Gadir Amna , Treibel Thomas A. , Banypersad Sanjay M. , Maestrini Viviana , Barcella William , Rosmini Stefania , Bulluck Heerajnarain , Sayed Rabya H. , Patel Ketna , Mamhood Shameem , Bucciarelli-Ducci Chiara , Whelan Carol J. , Herrey Anna S. , Lachmann Helen J. , Wechalekar Ashutosh D. , Manisty Charlotte H. , Schelbert Eric B. , Kellman Peter , Gillmore Julian D. , Hawkins Philip N. , Moon James C.
Published: September 2015

Background—

The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown.

Methods and Results—

Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (
P
<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1–13.7;
P
<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3–13.1;
P
<0.05).

Conclusions—

There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors.
What Makes a Crime?
Authors: Wagner Kenneth , Owen Stephen , Burke Tod W.
Published: September 2015

The purpose of this research was to explore the perceived seriousness of crimes, such as abuse and neglect, committed against nonhuman animals. Drawing upon the methods of previous work on crime seriousness, it was hypothesized that perceptions of the harmfulness and wrongfulness of animal offenses would influence perceptions of seriousness, with wrongfulness being the most powerful predictor. A survey was administered to a sample of college students (n= 245), and the hypotheses were supported. The results also indicated that crimes against animals were ranked as more serious than property offenses but less serious than crimes against persons. Furthermore, the two predictors—harmfulness and wrongfulness—explained a greater amount of variance in the perceived seriousness of offenses against animals than for property or person offenses. Results are contextualized within policy and philosophical perspectives pertaining to how offenses against animals are viewed by society and addressed by the legal system.
Systematics of the parasitic wasp genus Phanerotomella Szépligeti (Hymenoptera: Braconidae: Cheloninae) for Australia, with descriptions of 18 new species
Authors: Kittel Rebecca N. , Jennings John T. , Austin Andrew D.
Published: September 2015

Australian chelonine wasps have been poorly studied and yet they are a common feature of the continent’s braconid fauna.PhanerotomellaSzépligeti has previously been considered to be a small genus known from three described species for Australia. However, recent intensive collecting reveals a more species rich fauna. Here we undertake a systematic revision of AustralianPhanerotomellaand, in so doing, redescribe the three previous species (P. longipesSzépligeti, 1900,P. minutaZettel, 1989 andP. sculpturataSzépligeti, 1900) and describe 18 new species;P. ashmeadisp. n.,P. brevivenasp. n.,P. castaneasp. n.,P. curtogastersp. n.,P. dentatasp. n.,P. dimorphasp. n.,P. discoloriasp. n.,P. flavenssp. n.,P. kimbaensissp. n.,P. kriegerisp. n.,P. microcellatasp. n.,P. naumannisp. n.,P. nivistigmasp. n.,P. obscurasp. n.,P. phanerotomoidessp. n.,P. pungogastersp. n.,P. szepligetiisp. n. andP. variatasp. n. A dichotomous key is included to facilitate identification of the species along with a discussion of the monophyly and distribution of the genus.
A taxonomic study of the beetle cockroaches (Diploptera Saussure) from China, with notes on the genus and species worldwide (Blattodea: Blaberidae: Diplopterinae)
Authors: LI XINRAN , WANG ZONGQING
Published: September 2015

Four taxa of beetle cockroaches (Diploptera Saussure, 1864) from South China are described and illustrated, viz., two new species D. elliptica sp. n. and D. naevus sp. n., one new subspecies D. nigrescens guani subsp. n. and one widespread known species D. punctata (Eschscholtz, 1822). The genus and known species from around the world are discussed based on types and other specimens. D. pulchra Anisyutkin, 2007 is now regarded as a junior synonym of D. bicolor Hanitsch, 1925. Whether the populations of D. punctata represent or not different species needs to be studied in the future. A key, a distribution map, and photos of species are provided.