bluuebunny/crossref_metadata_2025 huggingface dataset:
Robson Ten Group Classification System Applied to Women with Severe Maternal Morbidity
Authors: Ferreira Elton Carlos , Costa Maria Laura , Cecatti José Guilherme , Haddad Samira M. , Parpinelli Mary Angela , Robson Michael S. ,   the Brazilian Network for Surveillance of Severe Maternal Morbidity Study Group
Published: February 2015

Objective

To evaluate the distribution of women with severe maternal morbidity according to Robson Ten Group Classification System (RTGCS).

Methods

Secondary analysis of a multicenter cross‐sectional study in 27 obstetric units in Brazil, using RTGCS. Cases were classified into potentially life‐threatening condition or a maternal near miss or death, according to severity. Certain groups were subdivided for further analysis. Cesarean delivery (CD) rates were reported.

Results

Among 7,247 women with severe maternal morbidity, 73.2 percent underwent CD. Group 10 (single, cephalic, preterm) was the most prevalent (33.9%). Groups mostly associated with a severe maternal outcome were: 7 (multiparous, breech), 9 (all abnormal lies, single, term), 8 (all multiple), and 10. Groups 1 (nulliparous, single, cephalic, term, spontaneous) and 3 (multiparous, single, cephalic, term, spontaneous) were associated with better maternal outcome. Group 3 had one severe maternal morbidity to 29 cases of potentially life‐threatening, but the ratio was 1:10 for women undergoing CD, indicating a worse outcome. Group 4a (multiparous, no previous CD, single, cephalic, term, induced labor) had a better maternal outcome than those delivered by CD before labor (group 4b). Hypertension was the most common condition of severity.

Conclusions

The RTGCS was useful to consider severe maternal morbidity, showing groups with higher CD rates and worse maternal outcomes.
Coping with structural disadvantage: Overcoming negative effects of perceived barriers through bonding identities
Authors: Bakouri Mouna , Staerklé Christian
Published: February 2015

Members of socially disadvantaged groups often experience societal devaluation, material hardship, and restricted opportunities, especially during critical life‐course transitions. In this study, we investigate whether what we term ‘bonding identities’, that is identities connecting the self to significant persons whether in terms of social relationships (e.g., family relations) or in terms of categorical collective identities, help individuals negotiate structural constraints on life‐course opportunities. We develop and test a model according to which greater perceived barriers to one's life projects are psychologically harmful. We then test whether bonding identities function as a buffer against these stressors' negative psychological effects. Data were collected with a standardized questionnaire from pre‐apprentices, apprentices, and young employees in two institutions (N = 365). Results confirm that perceiving barriers to one's life project was harmful for self‐esteem. However, for participants who defined themselves in terms of bonding identities, greater perceived barriers did not decrease their perceived coping efficacy and were less harmful for their self‐esteem. These findings point to the empowering role of bonding identities (and the social relationships that they imply) for disadvantaged group members.
A review of detrusor overactivity and the overactive bladder after radical prostate cancer treatment
Authors: Thiruchelvam Nikesh , Cruz Francesco , Kirby Mike , Tubaro Andrea , Chapple Christopher R. , Sievert Karl‐Dietrich
Published: February 2015

There are various forms of treatment for prostate cancer. In addition to oncologic outcomes, physicians, and increasingly patients, are focusing on functional and adverse outcomes. Symptoms of overactive bladder (OAB), including urinary frequency, urgency and incontinence, can occur regardless of treatment modality. This article examines the prevalence, pathophysiology and options for treating OAB after radical prostate cancer treatment. OAB seems to be more common and severe after radiation therapy than after surgical therapy and even persisted longer with complications, suggesting an advantage for surgery over radiotherapy. Because OAB that occurs after radical prostate surgery or radiotherapy can be difficult to treat, it is important that patients are made aware of the potential development of OAB during counselling before decisions regarding treatment choice are made. To ensure a successful outcome of both treatments, it is imperative that clinicians and non‐specialists enquire about and document pretreatment urinary symptoms and carefully evaluate post‐treatment symptoms.
Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation
Authors: Bashashati M , Nasser Y , Keenan C M , Ho W , Piscitelli F , Nalli M , Mackie K , Storr M A , Di Marzo V , Sharkey K A
Published: February 2015

Background and Purpose

Endocannabinoids are a family of lipid mediators involved in the regulation of gastrointestinal (GI) motility. The expression, localization and function of their biosynthetic enzymes in the GI tract are not well understood. Here, we examined the expression, localization and function of the enzyme diacylglycerol lipase‐α (DAGLα), which is involved in biosynthesis of the endocannabinoid 2‐arachidonoylglycerol (2‐AG).

Experimental Approach

Cannabinoid CB1 receptor‐deficient, wild‐type control and C3H/HeJ mice, a genetically constipated strain, were used. The distribution of DAGLα in the enteric nervous system was examined by immunohistochemistry. Effects of the DAGL inhibitors, orlistat and OMDM‐188 on pharmacologically induced GI hypomotility were assessed by measuring intestinal contractility in vitro and whole gut transit or faecal output in vivo. Endocannabinoid levels were measured by mass spectrometry.

Key Results

DAGLα was expressed throughout the GI tract. In the intestine, unlike DAGLβ, DAGLα immunoreactivity was prominently expressed in the enteric nervous system. In the myenteric plexus, it was colocalized with the vesicular acetylcholine transporter in cholinergic nerves. In normal mice, inhibiting DAGL reversed both pharmacologically reduced intestinal contractility and pharmacologically prolonged whole gut transit. Moreover, inhibiting DAGL normalized faecal output in constipated C3H/HeJ mice. In colons incubated with scopolamine, 2‐AG was elevated while inhibiting DAGL normalized 2‐AG levels.

Conclusions and Implications

DAGLα was expressed in the enteric nervous system of mice and its inhibition reversed slowed GI motility, intestinal contractility and constipation through 2‐AG and CB1 receptor‐mediated mechanisms. Our data suggest that DAGLα inhibitors may be promising candidates for the treatment of constipation.
Pharmacological and electrophysiological characterization of AZSMO‐23, an activator of the hERG K+ channel
Authors: Mannikko R , Bridgland‐Taylor M H , Pye H , Swallow S , Abi‐Gerges N , Morton M J , Pollard C E
Published: February 2015

Background and Purpose

We aimed to characterize the pharmacology and electrophysiology of N‐[3‐(1H‐benzimidazol‐2‐yl)‐4‐chloro‐phenyl]pyridine‐3‐carboxamide (AZSMO‐23), an activator of the human ether‐a‐go‐go‐related gene (hERG)‐encoded K+ channel (Kv11.1).

Experimental Approach

Automated electrophysiology was used to study the pharmacology of AZSMO‐23 on wild‐type (WT), Y652A, F656T or G628C/S631C hERG, and on other cardiac ion channels. Its mechanism of action was characterized with conventional electrophysiology.

Key Results

AZSMO‐23 activated WT hERG pre‐pulse and tail current with EC50 values of 28.6 and 11.2 μM respectively. At 100 μM, pre‐pulse current at +40 mV was increased by 952 ± 41% and tail current at −30 mV by 238 ± 13% compared with vehicle values. The primary mechanism for this effect was a 74.5 mV depolarizing shift in the voltage dependence of inactivation, without any shift in the voltage dependence of activation. Structure–activity relationships for this effect were remarkably subtle, with close analogues of AZSMO‐23 acting as hERG inhibitors. AZSMO‐23 blocked the mutant channel, hERG Y652A, but against another mutant channel, hERG F656T, its activator activity was enhanced. It inhibited activity of the G628C/S631C non‐inactivating hERG mutant channel. AZSMO‐23 was not hERG selective, as it blocked hKv4.3‐hKChIP2.2, hCav3.2 and hKv1.5 and activated hCav1.2/β2/α2δ channels.

Conclusion and Implications

The activity of AZSMO‐23 and those of its close analogues suggest these compounds may be of value to elucidate the mechanism of type 2 hERG activators to better understand the pharmacology of this area from both a safety perspective and in relation to treatment of congenital long QT syndrome.
Mammal Browsers and Rainfall Affect Acacia Leaf Nutrient Content, Defense, and Growth in South African Savannas
Authors: Wigley Benjamin J. , Bond William J. , Fritz Hervé , Coetsee Corli
Published: February 2015

Five sets of herbivore exclosures situated in mesic and semi‐arid savannas in Hluhluwe‐iMfolozi Park, South Africa were used to investigate the effects of mammal browsers and savanna type on plant traits relating to leaf nutrient content, defense, and growth in seven Acacia species. Mostly, browsing did not significantly affect leaf nutrient content but for a few species (i.e., increasing foliar N and P, decreasing C/N, and total polyphenols). Browser effects on structural defenses tended to be more pronounced than for leaf nutrient content and chemical defenses, particularly for semi‐arid species, resulting in longer, thicker, and denser spines, and a lower bite size index on browsed plants for most semi‐arid species. Browsing had no significant effect on growth rates for all species. Secondly, we investigated the effect of savanna type (mesic vs. semi‐arid) on the same set of plant traits and growth rates. A trade‐off in defense strategy was evident where mesic species had lower quality leaves and invested more heavily in growth and chemical defenses, while semi‐arid species generally had higher nutrient content leaves and invested more in structural defenses and higher levels of ramification. These findings suggest that the previously documented trade‐off in plant growth, resprouting ability and architecture between herbivore versus fire‐adapted savanna woody species can possibly be extended to include browse quality and defense type.
The Dominance of Introduced Plant Species in the Diets of Migratory Galapagos Tortoises Increases with Elevation on a Human‐Occupied Island
Authors: Blake Stephen , Guézou Anne , Deem Sharon L. , Yackulic Charles B. , Cabrera Fredy
Published: February 2015

The distribution of resources and food selection are fundamental to the ecology, life history, physiology, population dynamics, and conservation of animals. Introduced plants are changing foraging dynamics of herbivores in many ecosystems often with unknown consequences. Galapagos tortoises, like many herbivores, undertake migrations along elevation gradients driven by variability in vegetation productivity which take them into upland areas dominated by introduced plants. We sought to characterize diet composition of two species of Galapagos tortoises, focussing on how the role of introduced forage species changes over space and the implications for tortoise conservation. We quantified the distribution of tortoises with elevation using GPS telemetry. Along the elevation gradient, we quantified the abundance of introduced and native plant species, estimated diet composition by recording foods consumed by tortoises, and assessed tortoise physical condition from body weights and blood parameter values. Tortoises ranged between 0 and 429 m in elevation over which they consumed at least 64 plant species from 26 families, 44 percent of which were introduced species. Cover of introduced species and the proportion of introduced species in tortoise diets increased with elevation. Introduced species were positively selected for by tortoises at all elevations. Tortoise physical condition was either consistent or increased with elevation at the least biologically productive season on Galapagos. Santa Cruz tortoises are generalist herbivores that have adapted their feeding behavior to consume many introduced plant species that has likely made a positive contribution to tortoise nutrition. Some transformed habitats that contain an abundance of introduced forage species are compatible with tortoise conservation.
A Matter of Scale: Historical and Environmental Factors Structure Anuran Assemblages from the Upper Madeira River, Amazonia
Authors: Dias‐Terceiro Randolpho G. , Kaefer Igor Luis , de Fraga Rafael , de Araújo Maria Carmozina , Simões Pedro Ivo , Lima Albertina P.
Published: February 2015

Biogeographical history and current ecological interactions have usually been addressed separately to explain the spatial distribution of patterns of biodiversity. In this study, we evaluated the integrated effects of biogeographical and environmental factors in structuring the diurnal amphibian anuran assemblages of the upper Madeira River, southwestern Amazonia. We used a sampling design involving 98 standardized units, distributed across seven locations covering both banks of the river's course in the state of Rondônia, Brazil. We conducted searches for frogs in three campaigns between February 2010 and February 2011, aiming to: (1) evaluate the effect of the Madeira River as a biogeographic barrier at the species‐assemblage level, and (2) test the influence of seven environmental variables (vegetation structure, vegetation cover, soil nutrients, soil structure, slope, elevation, and distance from the river bank) on the spatial structure of the frog assemblages, separately on each riverbank. Thirteen species of diurnal frogs were recorded, six of which were restricted to one of the river margins. Multivariate analysis of variance indicated a significant effect of the river as a barrier. Multiple regression analyses suggested that the environmental variables structuring frog assemblages differ on either side of the river. We found that both historical elements (on a regional scale) and environmental factors (at a local scale) shaped the occurrence and distribution of frog species in the study area.
Population Viability Analysis of the Epiphytic Ghost Orchid (Dendrophylax lindenii) in Cuba
Authors: Raventós José , González Elaine , Mújica Ernesto , Doak Dan F.
Published: February 2015

To design feasible conservation and management policies for wild species, it is critical to understand the effects of periodic disturbances, be they natural or anthropogenic. The Caribbean Basin is characterized by high cyclonic activity that has a strong impact on the demography and population dynamics of many taxa, including epiphytic orchids. We conducted a 5‐yr study of rare ghost orchid demography, Dendrophylax lindenii, to assess the stability of a protected population of this species in Cuba. Using both stochastic and deterministic integral projection models, we found that mean annual population growth rates are negative (λ = 0.975). However, we found both population growth rate and extinction risk are highly sensitive to survival rates and reproduction, a difficult to quantify rate for many orchids including our study species. While this species is fairly long‐lived, its relatively slow increase in annual survival with increasing size may reflect the lack of a protected (i.e., subterranean) storage organ—a life‐history trait that may typify other epiphytic species and increase susceptibility to disturbance events. Hurricanes, which are predicted to increase in frequency as a result of climate change, dramatically increase adult mortality. Simulations of these effects indicate that hurricanes and similar disturbances could result in near certain extinction in short time horizons (25 yr) if their annual probability of occurrence exceeds 14 percent. These results suggest a need to better quantify recruitment rates, as well as the sensitivity of population dynamics of this and other orchid species to hurricanes and other periodic disturbances.
Entry, reputation and intellectual property rights enforcement
Authors: Che Jiahua , Qiu Larry , Zhou Wen
Published: February 2015

We examine how reputation concerns induce a multinational to partly withhold its entry into a developing country under weak intellectual property rights (IPR) enforcement. Equilibrium IPR violations are shown to arise only in the presence of such concerns. Holding constant a multinational's incentive to innovate, better IPR enforcement encourages entry but reduces social welfare. The multinational's incentive to innovate may be inversely U‐shaped in the strength of IPR enforcement. If timed properly, however, stronger IPR enforcement can foster innovation without compromising social welfare. Testable implications concerning observable IPR violations are derived.
Occupations, fields of study and returns to education
Authors: Lemieux Thomas
Published: February 2015

This paper considers several possible channels behind the well‐documented effect of education on earnings. The first channel is that education makes workers more productive on a given task, as in a conventional human capital framework. The second channel is based on the idea that education helps workers get assigned to higher‐paying occupations where output is more sensitive to skill. A third and final channel is that workers are more productive and earn more when they are matched to a job related to their field of study. Using data from the 2005 National Graduate Survey and the 2006 Canadian Census, I find that channels two and three account for close to half of the conventionally measured return to education. The results indicate that the return to education varies greatly depending on occupation, field of study and the match between these two factors.
Validation study of the combined repeated‐dose toxicity and genotoxicity assay using gpt delta rats
Authors: Akagi Jun‐ichi , Toyoda Takeshi , Cho Young‐Man , Mizuta Yasuko , Nohmi Takehiko , Nishikawa Akiyoshi , Ogawa Kumiko
Published: February 2015

Transgenic rodents carrying reporter genes to detect organ‐specific in vivo genetic alterations are useful for risk assessment of genotoxicity that causes cancer. Thus, the Organization for Economic Co‐operation and Development has established the guideline for genotoxicity tests using transgenic animals, which may be combined with repeated‐dose toxicity studies. Here, we provide evidence to support equivalence of gpt delta and wild type (WT) rats in terms of toxicological responses to a genotoxic hepatocarcinogen, N‐nitrosodiethylamine (DEN), and a non‐genotoxic hepatocarcinogen, di(2‐ethylhexyl)phthalate (DEHP). gpt delta rats treated with DEHP showed similar increases in liver and kidney weights, serum albumin, albumin/globulin ratios, and incidence of diffuse hepatocyte hypertrophy compared to WT F344 and Sprague–Dawley (SD) rats. DEN‐treated gpt delta rats showed equivalent increases in the number and area of precancerous GST‐P‐positive foci in the liver compared to WT rats. The livers of DEN‐treated gpt delta rats also showed increased frequencies of gpt and Spi− mutations; such changes were not observed in DEHP‐treated gpt delta rats. These results indicated that gpt delta rats (both F344 and SD backgrounds) showed comparable DEHP‐induced toxicity and DEN‐induced genotoxicity to those observed in WT rats. With regard to the administration period, the general toxicity of 1.2% DEHP was evident throughout the experimental period, and the genotoxicity of 10 p.p.m. DEN could be detected after 2 weeks of administration and further increased at 4 weeks. These results suggested that combined assays using gpt delta rats could detect both general toxicity and genotoxicity by the canonical 4‐week administration protocol. Therefore, this assay using gpt delta rats would be applicable for risk assessment including early detection of genotoxic carcinogens and ultimately serve to reduce cancer risks in humans from environmental chemicals.
Depressive Symptoms in Third‐Grade Teachers: Relations to Classroom Quality and Student Achievement
Authors: McLean Leigh , Connor Carol McDonald
Published: February 2015

This study investigated associations among third‐grade teachers' (N = 27) symptoms of depression, quality of the classroom‐learning environment (CLE), and students' (N = 523, Mage = 8.6 years) math and literacy performance. teachers' depressive symptoms in the winter negatively predicted students' spring mathematics achievement. This depended on students' fall mathematics scores; students who began the year with weaker math skills and were in classrooms where teachers reported more depressive symptoms achieved smaller gains than did peers whose teachers reported fewer symptoms. teachers' depressive symptoms were negatively associated with quality of CLE, and quality of CLE mediated the association between depressive symptoms and student achievement. The findings point to the importance of teachers' mental health, with implications for policy and practice.
Foetal programming by maternal thyroid disease
Authors: Andersen Stine Linding , Olsen Jørn , Laurberg Peter
Published: February 2015

Foetal programming is an emerging concept that links a wide range of exposures during foetal life to later development of disease. Thyroid disorders are common in women of reproductive age, and careful management of pregnant women suffering from thyroid disease is important considering the crucial role of thyroid hormones during early brain development. It is possible that maternal thyroid dysfunction in pregnancy may lead to structural and/or functional changes during foetal brain development. Such an effect could later predispose the offspring to an increased risk of neurologic or psychiatric disease. We recently observed that children born to mothers with thyroid dysfunction had an increased risk of developing seizure disorders, autism spectrum disorders, attention‐deficit hyperactivity disorders and psychiatric disease in adolescence and young adulthood. In the review, we discuss the concept of potential foetal programming by maternal thyroid disease.
Association of erythropoietin gene polymorphisms with retinopathy in a Chinese cohort with type 2 diabetes mellitus
Authors: Song Qi , Zhang Yue , Wu Yongzhong , Zhou Fang , Qu Yi
Published: February 2015

Background

This study was performed to investigate the correlation of erythropoietin gene polymorphisms with diabetic retinopathy (DR) in a Chinese cohort with type 2 diabetes mellitus (T2DM).

Design

Case–control study held in Qilu hospital of Shandong University, China.

Participants

792 T2DM individuals were involved, classified as groups DR (n = 448) and non‐DR (NDR; n = 344). The DR group was subdivided into groups proliferative DR (PDR; n = 220) and non‐PDR (NPDR; n = 228).

Methods

Three single‐nucleotide polymorphisms, rs1617640, rs507392 and rs551238, in the erythropoietin gene were genotyped

Main Outcome Measures

Odds ratios (ORs) for the effects of erythropoietin gene polymorphisms on DR risk.

Results

The genotype CC frequency in rs507392 was significantly lower in DR group (additive: OR, 0.45; 95% confidence interval [CI], 0.23–0.89; P = 0.027; recessive: OR, 0.44; 95%CI, 0.23–0.86; P = 0.012) or PDR group (additive OR, 0.18; 95%CI, 0.05–0.63; P = 0.002; recessive OR, 0.19; 95%CI, 0.06–0.66; P = 0.003) than in NDR group. The genotype CC frequency in rs551238 was significantly lower in DR group (additive OR, 0.42; 95%CI, 0.21–0.38; P = 0.016; recessive OR, 0.40; 95%CI, 0.20–0.79; P = 0.010) or PDR group (additive OR, 0.18; 95%CI, 0.05–0.62; P = 0.002; recessive OR, 0.18; 95%CI, 0.05–0.61; P = 0.002). No significant differences were detected in the distributions of rs1617640 genotype or all polymorphisms' alleles between groups NDR and DR, PDR or NPDR. Haplotype analyses did not provide any evidence for the correlation between the three polymorphisms and DR.

Conclusions

Our data suggest that rs507392 and rs551238 in the erythropoietin gene probably act to lessen the risk for DR and PDR in the Chinese T2DM cohort.
The Growth of Ethnic Organizations in the Context of Neighborhood Change: Organizational Ecology in Postwar San Francisco
Authors: Olvera Jacqueline
Published: February 2015

Which neighborhood conditions foster the growth of ethnic organizations? This paper explores how changing unemployment, homeownership, and immigration in neighborhoods shape the growth of ethnic organizations in San Francisco from 1940 to 1970. Using hierarchical linear modeling, this paper analyzes the growth of white ethnic and racial minority organizations as postwar neighborhood changes took form. Results indicate that white ethnic and racial minority organizations experience very different growth trajectories. Findings indicate that the growth of racial minority organizations was negatively affected as foreign–born population size grew and unemployment rose. White ethnic organizations, however, were impervious to these same neighborhood changes. These results suggest that social heterogeneity and economic uncertainty stall the growth of racial minority organizations, whereas white ethnic organizations are unaffected by these conditions.
First phylogenetic analysis of the tribe Phyllotini (Rodentia: Sigmodontinae) combining morphological and molecular data
Authors: Carrizo Luz V. , Catalano Santiago A.
Published: February 2015

Previous phylogenetic analyses of the tribe Phyllotini, one of the largest components of the subfamily Sigmodontinae, have been based on a single source of evidence. In particular, morphological analyses were largely based on craniodental data, almost neglecting the potential phylogenetic information present in the postcranium. Despite the significant advances made in relation to the knowledge of phyllotine phylogeny in recent times, there are several unsolved issues that highlight the importance of a phylogenetic analysis that integrates multiple sources of evidence, including previously considered sources as well as new sources of data. We present here the first combined phylogenetic analysis (morphological and molecular) of phyllotines, which includes the widest taxon and character sampling to date. Our dataset includes 164 morphological characters, of which 83 are postcranial characters, plus 3561 molecular characters, scored for 52 species from 34 genera of Oryzomyalia. In this study 75 postcranial characters not previously considered in this group are thoroughly described, and their utility for solving the relationships within Phyllotini is evaluated by means of different complementary analyses. Phyllotini was retrieved as a monophyletic clade in the combined analysis, with a composition that matches that obtained in most other recent analyses. All genera of phyllotines were monophyletic and show high support values. Abrotrichini, Akodontini and Oryzomyini were also monophyletic. The inclusion of postcranial data appears to be of limited utility to solve the phylogenetic relationships within Phyllotini.
Abutment height influences the effect of platform switching on peri‐implant marginal bone loss
Authors: Galindo‐Moreno Pablo , León‐Cano Ana , Monje Alberto , Ortega‐Oller Inmaculada , O′Valle Francisco , Catena Andrés
Published: February 2015

Purpose

The purpose was to radiographically analyze and compare the marginal bone loss (MBL) between implants with different mismatching distance and to study the influence of the prosthetic abutment height on the MBL in association with the related mismatching distances.

Material and methods

This retrospective study included 108 patients in whom 228 implants were placed, 180 with diameter of 4.5 mm and 48 with diameter of 5 mm. All patients received OsseoSpeed™ implants with internal tapered conical connection (Denstply Implants). Different mismatching distances were obtained, given that all implants were loaded with the same uni‐abutment type (Lilac; Denstply Implants). Data were gathered on age, gender, bone substratum, smoking habits, previous history of periodontitis, and prosthetic features. MBL was analyzed radiographically at 6 and 18 months post‐loading.

Results

Mixed linear analysis of mesial and distal MBL values yielded significant effects of abutment, implant diameter, follow‐up period, bone substratum, smoking, and abutment × time interaction. MBL was greater at 18 vs. 6 months, for short vs. long abutments, for grafted vs. pristine bone, for a heavier smoking habit, and for implants with a diameter of 5.0 vs. 4.5 mm.

Conclusion

Greater mismatching does not minimize the MBL; abutment height, smoking habit, and bone substratum may play a role in the MBL over the short‐ and medium term.
Management of tailgut cysts in a tertiary referral centre: a 10‐year experience
Authors: Patsouras D. , Pawa N. , Osmani H. , Phillips R. K. S.
Published: February 2015

Aim

Tailgut cysts are rare congenital lesions typically presenting as presacral masses. A variable clinical presentation often leads to misdiagnosis and unsuccessful operations.

Method

A retrospective analysis was performed of tailgut cysts presenting to one surgeon at St Mark's hospital between 2003 and 2013. The patient demographic data and clinicopathological and radiological features, together with perioperative details and recurrence, were reviewed.

Results

A total of 17 patients (15 women) with a median age of 35 (21–64) years were included in the study. The mean duration of symptoms before referral was 40 months, with sepsis predominating in 12 cases. Fifteen of the patients had previously undergone surgery (mean 2.9 procedures). A posterior surgical approach was adopted in all patients with a coccygectomy performed in 13. A loop colostomy was formed in three patients. Two of them went on to have a secondary pull‐through operation after an initial failed local repair of rectal injury. One case was reported to show malignant degeneration on histological examination. There was one recurrence during a median follow‐up period of 13 (3–36) months.

Conclusion

Tailgut cysts are an uncommon yet important cause of chronic perianal sepsis. Suspicion should be raised in a patient, usually female, presenting with a history of unsuccessful procedures. Diagnosis can be made by clinical assessment and MRI. Complete excision usually resolves the problem.
Autologous c‐Kit+ Mesenchymal Stem Cell Injections Provide Superior Therapeutic Benefit as Compared to c‐Kit+ Cardiac‐Derived Stem Cells in a Feline Model of Isoproterenol‐Induced Cardiomyopathy
Authors: Taghavi Sharven , Sharp Thomas E. , Duran Jason M. , Makarewich Catherine A. , Berretta Remus M. , Starosta Tim , Kubo Hajime , Barbe Mary , Houser Steven R.
Published: February 2015

Background

Cardiac‐ (CSC) and mesenchymal‐derived (MSC) CD117+ isolated stem cells improve cardiac function after injury. However, no study has compared the therapeutic benefit of these cells when used autologously.

Methods

MSCs and CSCs were isolated on day 0. Cardiomyopathy was induced (day 28) by infusion of L‐isoproterenol (1,100 ug/kg/hour) from Alzet minipumps for 10 days. Bromodeoxyuridine (BrdU) was infused via minipumps (50 mg/mL) to identify proliferative cells during the injury phase. Following injury (day 38), autologous CSC (n = 7) and MSC (n = 4) were delivered by intracoronary injection. These animals were compared to those receiving sham injections by echocardiography, invasive hemodynamics, and immunohistochemistry.

Results

Fractional shortening improved with CSC (26.9 ± 1.1% vs. 16.1 ± 0.2%, p = 0.01) and MSC (25.1 ± 0.2% vs. 12.1 ± 0.5%, p = 0.01) as compared to shams. MSC were superior to CSC in improving left ventricle end‐diastolic (LVED) volume (37.7 ± 3.1% vs. 19.9 ± 9.4%, p = 0.03) and ejection fraction (27.7 ± 0.1% vs. 19.9 ± 0.4%, p = 0.02). LVED pressure was less in MSC (6.3 ± 1.3 mmHg) as compared to CSC (9.3 ± 0.7 mmHg) and sham (13.3 ± 0.7); p = 0.01. LV BrdU+ myocytes were higher in MSC (0.17 ± 0.03%) than CSC (0.09 ± 0.01%) and sham (0.06 ± 01%); p < 0.001.

Conclusions

Both CD117+ isolated CSC and MSC therapy improve cardiac function and attenuate pathological remodeling. However, MSC appear to confer additional benefit.
A case of marginal zone lymphoma with extensive emperipolesis diagnosed on pleural effusion cytology with immunocytochemistry and flow cytometry
Authors: Meykler S. , Baloch Z. W. , Barroeta J. E.
Published: February 2015

This case report describes and beautifully illustrates abnormal lymphoid cells engulfed by mesothelial cells in the very rare occurrence of emperipolesis within a pleural fluid containing lymphoma.
Neurological level at birth predicts survival to the mid‐40s and urological deaths in open spina bifida: a complete prospective cohort study
Authors: Oakeshott Pippa , Reid Fiona , Poulton Alison , Markus Hugh , Whitaker Robert H , Hunt Gillian M
Published: February 2015

Aim

To conduct a 50‐year complete, community‐based, prospective cohort study to investigate long‐term survival, causes of death, and influence of level of the lesion in treated open spina bifida.

Method

The cohort comprised 117 consecutive cases whose backs were closed non‐selectively at birth between 1963 and 1971 in Cambridge, UK. In 2013 we surveyed the survivors (n=39, 18 males, 21 females; mean age 46y, range 43–49y) by postal questionnaire and telephone interview. We compared outcomes in those born with a neurological deficit in terms of sensory and motor levels of L1 and above versus L2 and below.

Results

Two‐thirds of the cohort (78/117) had died. Causes of death were cardiorespiratory (n=26), neurological (n=24), urological (n=22), or other (n=6). Only the urological deaths were related to level of the lesion: there were none in those with a sensory level of L2 or below (p<0.001). Birth findings also predicted survival: of the 57 infants with a neurological level of L1 or above, only 12% (n=7) survived compared with 55% (30/55) of the remainder (p<0.001).

Interpretation

The increased mortality in those born with an extensive neurological deficit was mainly due to urological deaths. Neurological level, particularly the sensory level, is the best predictor of long‐term outcome and should be assessed routinely at birth.
Compstatin: a C3‐targeted complement inhibitor reaching its prime for bedside intervention
Authors: Mastellos Dimitrios C. , Yancopoulou Despina , Kokkinos Petros , Huber‐Lang Markus , Hajishengallis George , Biglarnia Ali R. , Lupu Florea , Nilsson Bo , Risitano Antonio M. , Ricklin Daniel , Lambris John D.
Published: February 2015

There is a growing awareness that complement plays an integral role in human physiology and disease, transcending its traditional perception as an accessory system for pathogen clearance and opsonic cell killing. As the list of pathologies linked to dysregulated complement activation grows longer, it has become clear that targeted modulation of this innate immune system opens new windows of therapeutic opportunity for anti‐inflammatory drug design. Indeed, the introduction of the first complement‐targeting drugs has reignited a vibrant interest in the clinical translation of complement‐based inhibitors. Compstatin was discovered as a cyclic peptide that inhibits complement activation by binding C3 and interfering with convertase formation and C3 cleavage. As the convergence point of all activation pathways and a molecular hub for crosstalk with multiple pathogenic pathways, C3 represents an attractive target for therapeutic modulation of the complement cascade. A multidisciplinary drug optimization effort encompassing rational ‘wet’ and in silico synthetic approaches and an array of biophysical, structural and analytical tools has culminated in an impressive structure‐function refinement of compstatin, yielding a series of analogues that show promise for a wide spectrum of clinical applications. These new derivatives have improved inhibitory potency and pharmacokinetic profiles and show efficacy in clinically relevant primate models of disease. This review provides an up‐to‐date survey of the drug design effort placed on the compstatin family of C3 inhibitors, highlighting the most promising drug candidates. It also discusses translational challenges in complement drug discovery and peptide drug development and reviews concerns related to systemic C3 interception.
LEAD EXPOSURE AND BEHAVIOR: EFFECTS ON ANTISOCIAL AND RISKY BEHAVIOR AMONG CHILDREN AND ADOLESCENTS
Authors: Reyes Jessica Wolpaw
Published: February 2015

It is well known that exposure to lead has numerous adverse effects on behavior and development. Using data on two cohorts of children from the National Longitudinal Survey of Youth (NLSY), this paper investigates the effect of early childhood lead exposure on behavior problems from childhood through early adulthood. I find large negative consequences of early childhood lead exposure, in the form of an unfolding series of adverse behavioral outcomes: behavior problems as a child, pregnancy and aggression as a teen, and criminal behavior as a young adult. At the levels of lead that were the norm in United States until the late 1980s, estimated elasticities of these behaviors with respect to lead range between 0.1 and 1.0. (JEL I18, J13, K49, Q53, Q58)
Functional and phylogenetic approaches reveal the evolution of diversity in a hyper diverse biota
Authors: Blaimer Bonnie B. , Brady Seán G. , Schultz Ted R. , Fisher Brian L.
Published: February 2015

Ant communities in tropical forests may be governed by varying assembly mechanisms, depending on the particular habitat investigated. We compared phylogenetic diversity and structure across two forest biomes (dry and humid) and two vertical layers (arboreal and terricolous) in ant communities in Madagascar, and assessed the influence of invasive species on this community structure. We estimated phylogenetic signal and correlated evolution for habitat and several functional traits and tested for conservatism in relevant functional and habitat traits. Ancestral states were reconstructed to illuminate the evolution of habitat traits. All analyses utilized phylogenies estimated from newly generated data from three nuclear markers for 290 Malagasy ant taxa. Dry forests, although lower in species richness, were found to support equally high lineage diversity as humid forests. In contrast, phylogenetic diversity was much lower in arboreal than in terricolous communities. We observed significant phylogenetic clustering in the combined humid forest and in the arboreal–humid, arboreal–dry and terricolous–humid communities, whereas the combined dry forest community was overdispersed. Among ant communities in Madagascar, overdispersion and competition therefore may be more prevalent in dry forest, and habitat filtering may be more dominant in humid forest. Excluding invasive ant species had little overall effect on community structure. All investigated traits showed low to intermediate conservatism; strong support for correlated evolution was found for increased eye size and an arboreal lifestyle. Habitat transitions from humid to dry and from terricolous to arboreal occurred more frequently, and ancestors of most lineages were predicted to be terricolous or humid‐forest adapted. We conclude that most Malagasy ant clades first colonized humid forests and subsequently transitioned into dry forests, indicating that previous hypotheses on the evolution of Madagascar's hyperdiverse biota may not apply to ants and other arthropods.
Molecular changes associated with the development of resistance to imatinib in an imatinib‐sensitive canine neoplastic mast cell line carrying a KIT c.1523A>T mutation
Authors: Kobayashi Masato , Kuroki Shiori , Tanaka Yu , Moriya Yukari , Kozutumi Yukari , Uehara Yuji , Ono Kenichiro , Tamura Kyoichi , Washizu Tsukimi , Bonkobara Makoto
Published: February 2015

Although imatinib has therapeutic activity for certain subsets of patients with mastocytosis, it is not always curative. Here, molecular mechanisms that confer imatinib resistance to neoplastic mast cells were investigated using an imatinib‐sensitive canine neoplastic mast cell line VI‐MC carrying a KIT c.1523A>T activating mutation. Two imatinib‐resistant sublines were established by culturing VI‐MC cells in increasing concentrations of imatinib (1 μM resistant, rVI‐MC1; 10 μM resistant, rVI‐MC10). Both sublines had a second KIT mutation c.2443G>C. Recombinant KIT with the second mutation was insensitive to 1 μM but sensitive to 10 μM imatinib. The effect of imatinib on the phosphorylation of KIT and its downstream signalling proteins was then examined using these sublines. KIT and ERK were constitutively phosphorylated in both sublines, and their phosphorylation was suppressed by 10 μM imatinib in rVI‐MC1 cells. However, KIT but not ERK phosphorylation was suppressed in rVI‐MC10 cells. The phosphorylation of ERK in rVI‐MC10 cells was also not diminished by the Src family kinase (SFK) inhibitor dasatinib. This second mutation in KIT may play an important role in imatinib resistance in neoplastic mast cells. Furthermore, KIT/SFK‐independent activation of ERK would be involved in imatinib resistance when the neoplastic cells are exposed to higher concentrations of imatinib.
Antibody binding to megakaryocytes in vivo in patients with immune thrombocytopenia
Authors: Arnold Donald M , Nazi Ishac , Toltl Lisa J , Ross Catherine , Ivetic Nikola , Smith James W , Liu Yang , Kelton John G
Published: February 2015

Objectives

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and impaired platelet production. Antibody binding to megakaryocytes may occur in ITP, but in vivo evidence of this phenomenon is lacking.

Methods

We determined the proportion of megakaryocytes bound with immunoglobulin G (IgG) in bone marrow samples from primary patients with ITP (n = 17), normal controls (n = 13) and thrombocytopenic patients with myelodysplastic syndrome (MDS; n = 10). Serial histological sections from archived bone marrow biopsies were stained for CD61 and IgG. IgG binding and the number of bone marrow megakaryocytes were determined morphologically by a hematopathologist with four assessors after a calibration exercise to ensure consistency.

Results

The proportion of ITP patients with high IgG binding (>50% of bone marrow megakaryocytes) was increased compared with normal controls [12/17 (71%) vs. 3/13 (23%), P = 0.03]. However, the proportion of ITP patients with high IgG binding was no different than thrombocytopenic patients with MDS [12/17 (71%) vs. 7/10 (70%), P = 1.00]. IgG binding was associated with increased megakaryocyte numbers. Like platelet‐associated IgG, megakaryocyte‐associated IgG is related to thrombocytopenia but may not be specific for ITP.

Conclusion

Mechanistic studies in ITP should focus on antibody specificity and include thrombocytopenic control patients.
Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1‐yr Phase 2 study
Authors: Cançado Rodolfo , Melo Murilo R. , de Moraes Bastos Roberto , Santos Paulo C. J. L. , Guerra‐Shinohara Elivira M. , Chiattone Carlos , Ballas Samir K.
Published: February 2015

This open‐label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12‐month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients.
The Impact of Measurement Error on the Accuracy of Individual and Aggregate SGP
Authors: McCaffrey Daniel F. , Castellano Katherine E. , Lockwood J. R.
Published: February 2015

Student growth percentiles (SGPs) express students' current observed scores as percentile ranks in the distribution of scores among students with the same prior‐year scores. A common concern about SGPs at the student level, and mean or median SGPs (MGPs) at the aggregate level, is potential bias due to test measurement error (ME). Shang, vanIwaarden, and Betebenner (SVB; this issue) develop a simulation‐extrapolation (SIMEX) approach to adjust SGPs for test ME. In this paper, we use a tractable example in which different SGP estimators, including SVB's SIMEX estimator, can be computed analytically to explain why ME is detrimental to both student‐level and aggregate‐level SGP estimation. A comparison of the alternative SGP estimators to the standard approach demonstrates the common bias‐variance tradeoff problem: estimators that decrease the bias relative to the standard SGP estimator increase variance, and vice versa. Even the most accurate estimator for individual student SGP has large errors of roughly 19 percentile points on average for realistic settings. Those estimators that reduce bias may suffice at the aggregate level but no single estimator is optimal for meeting the dual goals of student‐ and aggregate level inferences.
The impact of lesion location on dysphagia incidence, pattern and complications in acute stroke. Part 1: dysphagia incidence, severity and aspiration
Authors: Suntrup S. , Kemmling A. , Warnecke T. , Hamacher C. , Oelenberg S. , Niederstadt T. , Heindel W. , Wiendl H. , Dziewas R.
Published: February 2015

Background and purpose

Although early identification of patients at risk for dysphagia is crucial in acute stroke care, predicting whether a particular patient is likely to have swallowing problems based on the brain scan is difficult because a comprehensive model of swallowing control is missing. In this study whether stroke location is associated with dysphagia incidence, severity and the occurrence of penetration or aspiration was systematically evaluated relying on a voxel‐based imaging analysis approach.

Methods

Two hundred acute stroke patients were investigated applying fiberoptic endoscopic evaluation of swallowing within 96 h from admission. Lesion masks were obtained from each patient's brain scan and registered to standard space. The percentage of lesioned volume of 137 atlas‐based brain regions was determined in each case. Region‐specific odds ratios were afterwards calculated with respect to presence of dysphagia, its severity and occurrence of penetration or aspiration.

Results

In all, 165 patients were diagnosed with dysphagia, 80 of whom had severe swallow impairment. For each investigated item there were significant differences of regional percentage infarction in distinct brain areas between affected patients and those who did not present with that specific dysfunction. In particular, right hemispheric lesions of the pre‐ and post‐central gyri, opercular region, supramarginal gyrus and respective subcortical white matter tracts were related to dysphagia, with post‐central lesions being especially associated with severe swallowing impairment.

Conclusions

Distinct brain lesion locations are related to the incidence, severity and pattern of swallowing dysfunction.
Understanding intellectual enrichment: how cognitive reserve impacts on hippocampal volume in multiple sclerosis
Authors: Muhlert N. , Penner I. K.
Published: February 2015

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