bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐acting testosterone injections for treatment of testosterone deficiency after brachytherapy for prostate cancer
Authors: Balbontin Felipe G. , Moreno Sergio A. , Bley Enrique , Chacon Rodrigo , Silva Andres , Morgentaler Abraham
Published: February 2014

Objective

To evaluate the clinical and biochemical effects of long‐acting testosterone undecanoate injections in men with prostate cancer treated with brachytherapy, as the use of testosterone therapy (TTh) in men with prostate cancer is highly controversial, with limited published safety data, particularly after brachytherapy treatment.

Patients and Methods

In all, 20 men treated with brachytherapy for prostate cancer received TTh for symptoms of testosterone deficiency from February 2005 to August 2013. Symptoms of testosterone deficiency included low libido, erectile dysfunction, and fatigue. The mode of TTh was long‐acting testosterone undecanoate injections in all cases. Sexual function was assessed by Sexual Health Inventory for Men (SHIM) questionnaire. Serum PSA and testosterone concentrations were recorded monthly for 3 months, then every 3 months for the first year, every 6 months for the second year, and annually then after.

Results

The mean (range) age was 62 (49–74) years and the mean (range) serum PSA level at the time of prostate cancer diagnosis was 6.2 (2–11.5) ng/mL. The Gleason score was 2 + 3 in one patient, 3 + 3 in 15 patients, 3 + 4 in three patients and 4 + 4 in one patient. In all, 15 men were stage T1c and five were T2a. The mean (range) baseline total testosterone concentration was 343 (200–592) ng/dL, and 6.9 (2.1–9.7) ng/dL for free testosterone. The mean SHIM scores improved with treatment from 16.1 at baseline to 22.1 with TTh (P = 0.002). There was a decrease in mean PSA level from baseline of 0.7 ng/mL before initiation of TTh to 0.1 ng/mL at last follow‐up (P < 0.001), with a median (range) follow‐up of 31 (12–48) months. There were no cases of prostate cancer progression or recurrence.

Conclusions

With a median of 31‐months follow‐up, long‐acting testosterone injections in men with prostate cancer treated with brachytherapy produced significant clinical benefits. There were no cases of rising serum PSA, prostate cancer progression or recurrence.
Multiparametric magnetic resonance imaging (MRI) and subsequent MRI/ultrasonography fusion‐guided biopsy increase the detection of anteriorly located prostate cancers
Authors: Volkin Dmitry , Turkbey Baris , Hoang Anthony N. , Rais‐Bahrami Soroush , Yerram Nitin , Walton‐Diaz Annerleim , Nix Jeffrey W. , Wood Bradford J. , Choyke Peter L. , Pinto Peter A.
Published: February 2014

Objective

To describe the detection rate of anteriorly located prostate cancer (PCa) with the addition of magnetic resonance imaging (MRI)/ultrasonography (US) fusion‐guided biopsy (FGB) to the standard transrectal ultrasonography (TRUS)‐guided biopsy.

Patients and Methods

All patients, regardless of their biopsy history, who were referred for clinical suspicion of PCa (i.e elevated prostate‐specific antigen (PSA) level and abnormal digital rectal examination) underwent 3T multiparametric‐MRI (mpMRI) screening; and those with suspicious lesions in the anterior region of the prostate were identified. Patients then received a FGB of all suspicious lesions in addition to a systematic 12‐core extended sextant TRUS‐guided biopsy. We conducted a lesion‐based analysis comparing cancer detection rates of anterior targets using FGB vs systematic cores taken from the same anatomic sextant within the prostate. Lengths of cancer in the most involved core were also compared between the two biopsy techniques used. Patients with only anterior targets were analysed separately.

Results

Of 499 patients undergoing FGB, 162 had a total of 241 anterior lesions. The mean age, PSA level and prostate volume in this group were 62 years, 12.7 ng/dL, and 57 mL, respectively. In total, PCa was diagnosed in 121 anterior lesions (50.2%) identified on mpMRI. Sixty‐two (25.7%) of these anterior lesions were documented as positive for cancer on systematic 12‐core TRUS‐guided biopsy cores, while 97 (40.2%) were positive on the targeted FGB cores (P = 0.001). In lesions that were positive on both FGB and TRUS biopsy, the most involved core was 112% longer on FGB (3.7 vs 1.6 mm, P ≤ 0.01). Forty‐two patients had only anterior lesions on mpMRI; of these, 24 (57.1%) were found to have cancer on the FGB + TRUS biopsy platform. Six patients were positive on FGB only and 13 were positive on both biopsy techniques; however, 7/13 patients were upgraded to a higher Gleason score after FGB. All five patients positive on TRUS biopsy only were candidates for active surveillance.

Conclusion

The results showed that FGB detects significantly more anteriorly located PCa than does TRUS‐guided biopsy alone and it may serve as an effective tool for the subset of patients with such tumours.
THE CONSIDERATION OF HUB‐AND‐SPOKE STATUS IN FTA FORMATION
Authors: Cao Jiyun
Published: February 2014

This paper extends the literature on the determinants of free trade area (FTA) taking hub‐and‐spoke status and hub status‐seeking into account. The analysis is based on purely cross‐sectional data and the main findings are different from previous studies. First, the hub‐and‐spoke status and hub status‐seeking are two important determinants of FTA. Moreover, the hub‐and‐spoke status and hub status‐seeking have greater partial effects on the response probabilities than other determinants. Second, the probability of forming an FTA between a pair of economies is higher if they share a common language. Finally, the probability of forming an FTA between a pair of economies falls at first but eventually increases as the difference in their relative factor endowments increases.
A Reproducible and Translatable Model of Focal Ischemia in the Visual Cortex of Infant and Adult Marmoset Monkeys
Authors: Teo Leon , Bourne James A.
Published: February 2014

Models of ischemic brain injury in the nonhuman primate (NHP) are advantageous for investigating mechanisms of central nervous system (CNS) injuries and testing of new therapeutic strategies. However, issues of reproducibility and survivability persist in NHP models of CNS injuries. Furthermore, there are currently no pediatric NHP models of ischemic brain injury. Therefore, we have developed a NHP model of cortical focal ischemia that is highly reproducible throughout life to enable better understanding of downstream consequences of injury. Posterior cerebral arterial occlusion was induced through intracortical injections of endothelin‐1 in adult (n = 5) and neonatal (n = 3) marmosets, followed by magnetic resonance imaging (MRI), histology and immunohistochemistry. MRI revealed tissue hyperintensity at the lesion site at 1–7 days followed by isointensity at 14–21 days. Peripheral macrophage and serum albumin infiltration was detected at 1 day, persisting at 21 days. The proportional loss of total V1 as a result of infarction was consistent in adults and neonates. Minor hemorrhagic transformation was detected at 21 days at the lesion core, while neovascularization was detected in neonates, but not in adults. We have developed a highly reproducible and survivable model of focal ischemia in the adult and neonatal marmoset primary visual cortex, demonstrating similar downstream anatomical and cellular pathology to those observed in post‐ischemic humans.
Inhibition of PKC‐θ preserves cardiac function and reduces fibrosis in streptozotocin‐induced diabetic cardiomyopathy
Authors: Li Zhao , Abdullah Chowdhury S , Jin Zhu‐Qiu
Published: February 2014

Background and Purpose

T‐cell infiltration, interstitial fibrosis and cardiac dysfunction have been observed in diabetic patients with cardiovascular diseases. PKC‐θ is crucial for the activation of mature T‐cells. We hypothesized that inhibition of PKC‐θ might protect diabetic hearts through inhibition of T‐cell stimulation and maintenance of tight junction integrity.

Experimental Approach

A model of type 1 diabetes was induced by streptozotocin (STZ) (50 mg kg–1 for 5 days) in male C57BL/6J wild‐type (WT) mice and Rag1 knockout (KO) mice which lack mature lymphocytes. A cell‐permeable selective PKC‐θ peptide inhibitor (PI) was administered i.p. (0.2 mg kg–1·day–1) for 4 weeks (first phase) and 2 weeks (second phase). At the end of the 11th week, cardiac contractile force was measured in isolated perfused hearts. Cardiac morphology and fibrosis were determined. Phosphorylation of PKC‐θ at Tyr358, infiltrated T‐cells and tight junction protein ZO‐1 within the hearts were detected, using immunohistochemcial techniques.

Key Results

PI did not affect high blood glucose level in both WT and Rag1 KO diabetic mice. Diabetes induced cardiac fibrosis in WT mice but not in Rag1 KO mice. PI attenuated cardiac fibrosis and improved cardiac contractility of WT diabetic hearts. PI decreased expression of phosphorylated PKC‐θ, reduced the infiltration of T‐cells and increased ZO‐1 expression within WT diabetic hearts.

Conclusion and Implications

Inhibition of PKC‐θ improves cardiac function and reduces cardiac fibrosis in WT mice with streptozotocin‐induced diabetes. Mature T‐cells play a key role in pathophysiology of diabetic cardiomyopathy.
The novel benzimidazole derivative BRP‐7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5‐lipoxygenase‐activating protein (FLAP)
Authors: Pergola C , Gerstmeier J , Mönch B , Çalışkan B , Luderer S , Weinigel C , Barz D , Maczewsky J , Pace S , Rossi A , Sautebin L , Banoglu E , Werz O
Published: February 2014

Background and Purpose

Leukotrienes (LTs) are inflammatory mediators produced via the 5‐lipoxygenase (5‐LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP‐7 as chemotype for anti‐LT agents by virtual screening targeting 5‐LOX‐activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP‐7 as an inhibitor of LT biosynthesis.

Experimental Approach

We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell‐free assays. The effectiveness of BRP‐7 in vivo was evaluated in rat carrageenan‐induced pleurisy and mouse zymosan‐induced peritonitis.

Key Results

BRP‐7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5‐LOX co‐localization with FLAP. Neither the cellular viability nor the activity of 5‐LOX in cell‐free assays was affected by BRP‐7, indicating that a functional FLAP is needed for BRP‐7 to inhibit LTs, and FLAP bound to BRP‐7 linked to a solid matrix. Compared with the FLAP inhibitor MK‐886, BRP‐7 did not significantly inhibit COX‐1 or microsomal prostaglandin E2 synthase‐1, implying the selectivity of BRP‐7 for FLAP. Finally, BRP‐7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels.

Conclusions and Implications

BRP‐7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti‐inflammatory effectiveness in vivo, with promising potential for further development.
Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF‐κB and AP‐1 activity in human liver cancer cells
Authors: Hsieh Ming‐Ju , Lin Chiao‐Wen , Yang Shun‐Fa , Chen Mu‐Kuan , Chiou Hui‐Ling
Published: February 2014

Background and Purpose

High mortality and morbidity rates for hepatocellular carcinoma in Taiwan primarily result from uncontrolled tumour metastasis. Glabridin, a prenylated isoflavonoid of licorice (Glycyrrhiza glabra) roots, is associated with a wide range of biological properties, such as regulation of energy metabolism, oestrogenic, neuroprotective, anti‐osteoporotic and skin whitening. However, the effect of glabridin on the metastasis of tumour cells has not been clarified.

Experimental Approach

A wound healing model and Boyden chamber assays in vitro were used to determine the effects of glabridin on the migration and invasion of human hepatocellular carcinoma (HHC) cells. Western blot analysis, gelatin zymography, real‐time PCR and promoter assays were used to evaluate the inhibitory effects of glabridin on matrix metalloproteinase 9 (MMP9) expression in these cells.

Key Results

Glabridin significantly inhibited migration/invasion capacities of HCC cells, Huh7 and Sk‐Hep‐1, cell lines that have low cytotoxicity in vitro, even at high concentrations. Western blot analysis and gelatin zymography showed that glabridin inhibited the expression, activities and protein levels of MMP9 and the phosphorylation of ERK1/2 and JNK1/2. These inhibitory effects were associated with an up‐regulation of tissue inhibitor of metalloproteinase‐1 and a down‐regulation of the transcription factors NF‐κB and activator protein 1 signalling pathways. Finally, the administration of glabridin effectively suppressed the tumour formation in the hepatoma xenograft model in vivo.

Conclusion and Implications

Glabridin inhibited the invasion of human HCC cells and may have potential as a chemopreventive agent against liver cancer metastasis.
Sedimentary and structural record of the Albian growth of the Bakio salt diapir (the Basque Country, northern Spain)
Authors: Poprawski Y. , Basile C. , Agirrezabala L. M. , Jaillard E. , Gaudin M. , Jacquin T.
Published: February 2014

However salt has a viscous rheology, overburden rocks adjacent to salt diapirs have a brittle rheology. Evidence of deformation within the overburden has been described from diapirs worldwide. Gravity‐driven deposits are also present along the flanks of several diapirs. The well‐known example from the La Popa Basin in northern Mexico shows that such deposits may be organized into halokinetic sequences. This leads to several questions: (i) How does diapir growth contribute to overburden deformation? (ii) Are halokinetic sequence models valid for other areas beyond the La Popa Basin. The Bakio diapir and its well‐exposed overburden in Basque Country, Spain provides key elements to address these questions. The Bakio diapir consists of Triassic red clays and gypsum and is flanked by synkinematic middle to upper Albian units that thin towards the diapir. The elongate diapir parallels the Gaztelugatxe normal fault to the NE: both strike NE–SW and probably formed together during the middle Albian, as synkinematic units onlap the fault scarp. The diapir is interpreted as a reactive diapir in response to middle Albian motion on the Gaztelugatxe fault. The rate of salt rise is estimated to be about 500 m Myr−1 during this passive stage. During Late Albian, the diapir evolved passively as the Gaztelugatxe fault became inactive. Synkinematic units thinning towards the diapir, major unconformities, slumps and other gravity‐driven deposits demonstrate that most deformation related to diapir growth occurred at the sea floor. Halokinetic sequences composed of alternating breccias and fine‐grained turbidites recorded cyclic episodes of diapir flank destabilization. This work provides insights into drape fold and halokinetic sequence models and offers a new simple method for estimating rates of diapir growth. This method may be useful for outcrop studies where biostratigraphical data are available and for other passive diapirs worldwide.
Sedimentary and tectonic evolution of Lake Ohrid (Macedonia/Albania)
Authors: Lindhorst K. , Krastel S. , Reicherter K. , Stipp M. , Wagner B. , Schwenk T.
Published: February 2014

Lake Ohrid, located on the Balkan Peninsula within the Dinaride–Albanide–Hellenide mountain belt, is a tectonically active graben within the South Balkan Extensional Regime (SBER). Interpretation of multichannel seismic cross sections and bathymetric data reveals that Lake Ohrid formed during two main phases of deformation: (1) a transtensional phase which opened a pull‐apart basin, and (2) an extensional phase which led to the present geometry of Lake Ohrid. After the initial opening, a symmetrical graben formed during the Late Miocene, bounded by major normal faults on each side in a pull‐apart type basin. The early‐stage geometry of the basin has a typical rhomboidal shape restricted by two sets of major normal faults. Thick undisturbed sediments are present today at the site where the acoustic basement is deepest, illustrating that Lake Ohrid is a potential target for drilling a long and continuous sediment core for studying environmental changes within the Mediterranean region. Neotectonic activity since the Pliocene takes place along the roughly N–S‐striking Eastern and Western Major Boundary Normal Faults that are partly exposed at the present lake floor. The tectono‐sedimentary structure of the basin is divided into three main seismic units overlying the acoustic basement associated with fluvial deposits and lacustrine sediments. A seismic facies analysis reveals a prominent cyclic pattern of high‐ and low‐amplitude reflectors. We correlate this facies cyclicity with vegetation changes within the surrounding area that are associated with glacial/interglacial cycles. A clear correlation is possible back to ca. 450 kyrs. Extrapolation of average sedimentation rates for the above mentioned period results in age estimate of ca. 2 Myrs for the oldest sediments in Lake Ohrid.
Dysmorphic choroid plexuses and hydrocephalus associated with increased nuchal translucency: Early ultrasound markers ofde novothanatophoric dysplasia typeIIwith cloverleaf skull (Kleeblattschaedel)
Authors: Tonni Gabriele , Palmisano Marcella , Ginocchi Vladimiro , Ventura Alessandro , Baldi Maurizia , Baffico Ave Maria
Published: February 2014

Prenatal diagnosis of thanatophoric dysplasia (TD) typeIIpresenting in the first trimester with increased nuchal translucency (NT) and cloverleaf skull (Kleeblattschaedel) have been scantly reported in the medical record. Abnormal choroid plexus has been seen in association with fetal anomalies. Here we described a case of increasedNTassociated with indented choroid plexuses, early onset hydrocephalus and cloverleaf skull in a fetus subsequently diagnosed at early second trimester to carry ade novomutation encoding forTDtypeII. The findings of dysmorphic choroid plexus, early onset hydrocephalus and cloverleaf skull at first trimester scan may be early, useful ultrasound markers ofTDtypeII. Molecular analysis to control for possible overlapping syndromes were performed and resulted negative. PostmortemX‐ray and3D‐CTscan confirmed the cloverleaf skull, narrow thorax, straight femur with rhizomelic shortening of the limbs and the presence of a communicating hydrocephalus.
Allee Effect and the Uncertainty of Population Recovery
Authors: KUPARINEN ANNA , KEITH DAVID M. , HUTCHINGS JEFFREY A.
Published: February 2014

Recovery of depleted populations is fundamentally important for conservation biology and sustainable resource harvesting. At low abundance, population growth rate, a primary determinant of population recovery, is generally assumed to be relatively fast because competition is low (i.e., negative density dependence). But population growth can be limited in small populations by an Allee effect. This is particularly relevant for collapsed populations or species that have not recovered despite large reductions in, or elimination of, threats. We investigated how an Allee effect can influence the dynamics of recovery. We used Atlantic cod (Gadus morhua) as the study organism and an empirically quantified Allee effect for the species to parameterize our simulations. We simulated recovery through an individual‐based mechanistic simulation model and then compared recovery among scenarios incorporating an Allee effect, negative density dependence, and an intermediate scenario. Although an Allee effect significantly slowed recovery, such that population increase could be negligible even after 100 years or more, it also made the time required for biomass rebuilding much less predictable. Our finding that an Allee effect greatly increased the uncertainty in recovery time frames provides an empirically based explanation for why the removal of threat does not always result in the recovery of depleted populations or species.

El Efecto Allee y la Incertidumbre de la Recuperación de Poblaciones
Treatments of faecal incontinence: recommendations from the French National Society of Coloproctology
Authors: Vitton V. , Soudan D. , Siproudhis L. , Abramowitz L. , Bouvier M. , Faucheron J.‐L. , Leroi A.‐M. , Meurette G. , Pigot F. , Damon H.
Published: February 2014

Faecal incontinence is common and significantly affects quality of life. Its treatment involves dietary manipulation, medical treatments, perineal rehabilitation or surgery. In this paper, the French National Society of Coloproctology offers recommendations based on the data in the current literature, including those on recently developed treatments. There is a lack of high quality data and most of the recommendations are therefore based either on grade of recommendation B or expert recommendation (Level 4). However, the literature supports the construction of an algorithm based on the available scientific evidence and expert recommendation which may be useful in clinical practice. The French National Society of Coloproctology proposes a decision‐making algorithm that includes recent developments of treatment. The current recommendations support sacral nerve modulation as the key treatment for faecal incontinence. They do not support the use of sphincter substitutions except in certain circumstances. Transanal irrigation is a novel often successful treatment of faecal incontinence due to neurological disorders.
MiR‐125b inhibits cell biological progression of Ewing's sarcoma by suppressing the PI3K/Akt signalling pathway
Authors: Li J. , You T. , Jing J.
Published: February 2014

Objectives: Increasing evidence has suggested the close relationship between microRNAs (miRNAs) dysregulation and the carcinogenesis of Ewing's sarcoma (ES), among of which miR‐125b has been reported to be decreased in ES tissues recently. Strikingly, ectopic expression of miR‐125b could suppress cell proliferation of ES cell line A673, suggesting the tumor suppressor role of miR‐125b in ES. However, the other accurate mechanistic functions and relative molecule mechanisms are largely unknown.

Materials and Methods: Herein, we completed a series of experiments to investigate the role of miR‐125b in Ewing's sarcoma. We restored the expression of miR‐125b in ES cell line A673 through transfection with miR‐125b mimics. To further understand the role of miR‐125b in ES, we detected the effects of miR‐125b on the cell proliferation, migration and invasion, cell cycle as well as cell apoptosis.

Results: We found that restored expression of miR‐125b in ES cell line A673 inhibited cell proliferation, migration and invasion, arrested cell cycle progression, and induced cell apoptosis. Moreover, bioinformatic prediction suggested the oncogene, phosphoinositide‐3‐kinase catalytic subunit delta (PIK3CD), was a target gene of miR‐125b in ES cells. Further quantitative RT‐PCR and western blot assays identified over‐expression of miR‐125b suppressed the expression of PIK3CD mRNA and protein. PIK3CD participates in regulating the PI3K signaling pathway, which has been reported to play an important role in the development of ES. Suppression of PIK3CD down‐regulated the expression of phospho‐AKT and phospho‐mTOR proteins and inhibited the biologic progression of A673 cells.

Conclusions: Collectively, these data suggest that miR‐125b functions as a tumor suppressor by targeting the PI3K/Akt/mTOR signaling pathway, and may provide potential therapy strategy for ES patients by targeting miRNA expression.
Smoking and chronic obstructive pulmonary disease in Chinese population: a meta‐analysis
Authors: Wang Biyu , Xiao Dan , Wang Chen
Published: February 2014

Background and Aims

In recent years, some epidemiological surveys of risk factors for chronic obstructive pulmonary disease (COPD) have been done in some regions of China, but the relevance is shown different in these surveys. A meta‐analysis was undertaken to assess the relationship between smoking and COPD in Chinese population.

Methods

Twenty‐four papers were included in our study. Total number of ever smokers and never smokers were 34 191 and 58 854, the number of COPD cases in each group were 5843 and 4874, respectively. We used meta‐analysis method to analyze the selected papers quantitatively, and stratified by type of study, gender and smoking index.

Results

Risk of COPD for ever smokers is higher than never smokers [odds ratio (OR) 2.90, 95% confidence interval (CI) 2.22 ∼ 3.80]; after stratifying by gender and smoking index, risks of COPD for male and female ever smokers are higher than male and female never smokers (OR 1.93, 95%CI 1.35 ∼ 2.77; OR 2.67, 95%CI 2.01 ∼ 3.56, respectively); risks of COPD for ever smokers who belong to different smoking index group (1 ∼ 200, 200 ∼ 400, >400, <300, ≥300 cigarettes per day*year) are all higher than never smokers (OR 2.49, 95%CI 1.66 ∼ 3.74; OR 2.91, 95%CI 2.19 ∼ 3.87; OR 4.07, 95%CI 3.17 ∼ 5.23; OR 2.39, 95%CI 1.42 ∼ 4.02; OR 3.31, 95%CI 2.99 ∼ 3.66, respectively).

Conclusions

The risk of COPD is higher for ever smokers than never smokers in Chinese population. The risk of COPD is higher for female smokers than male smokers. The risk of COPD is higher with greater smoking index.
Skin tumors with matrical differentiation: lessons from hair keratins, beta‐catenin and PHLDA‐1 expression
Authors: Battistella Maxime , Carlson John A. , Osio Amélie , Langbein Lutz , Cribier Bernard
Published: February 2014

Background

Pilomatricomas are tumors that emulate the differentiation of matrix cells of the hair follicle, showing cortical differentiation, with sequential expression of K35 and K31 keratins. Beta‐catenin gene is frequently mutated in pilomatricoma, leading to beta‐catenin nuclear accumulation, and to downstream expression of LEF1. Skin matrical tumors other than pilomatricoma are very rare, and comprise purely matrical tumors and focally matrical tumors. We aimed at studying cortical differentiation, beta‐catenin pathway and expression of the follicular stem‐cell marker PHLDA1 in a series of matrical tumors other than pilomatricoma.

Methods

In 36 prospectively collected tumors, K31, K35, CK17, LEF1, HOXC13, beta‐catenin and PHLDA1 expressions were evaluated. Five pilomatricomas were used as controls.

Results

In 18 purely matrical tumors (11 matrical carcinomas, 4 melanocytic matricomas, 3 matricomas) and 18 focally matrical tumors (11 basal cell carcinomas, 3 trichoepithelioma/trichoblastomas, 4 others), sequential K35, HOXC13 and K31 expressions were found, indicating cortical differentiation. Germinative matrix cells were always CK17–, and showed nuclear beta‐catenin accumulation, with LEF1 and PHLDA1 expressions.

Conclusions

Nuclear beta‐catenin and LEF1 expression was highly conserved in matrical tumors, and suggested a common tumorigenesis driven by Wnt pathway activation. PHLDA1 was consistently expressed in matrical tumors and in areas of matrical differentiation.
Tenosynovitis with rice body formation presenting as a cutaneous abscess
Authors: Moreno Sara , Forcada Pau , Soria Xavier , Altemir Victoria , Gatius Sonia , Gil Mabel , Matías‐Guiu Xavier , Casanova Josep M. , Martí Rosa M.
Published: February 2014

A 62‐year‐old woman with a past medical history of rheumatoid arthritis was referred to the Department of Dermatology because of an enlarging cutaneous lesion on the right thumb which resembled a soft tissue infection. She had received antibiotics without significant improvement. Clinical examination revealed an erythematous nodule involving almost the whole surface of the distal phalanx with spontaneous drainage of countless of small yellowish ovoid granules. Histopathologic study of these structures showed an inner core of amorphous acidophilic material with some interspersed chronic inflammatory cells and a surrounding thin fibrin layer. Special stains and cultures were negative for parasites, bacterium and mycobacterium. Magnetic resonance imaging (MRI) revealed distension of the first and fifth finger flexor sheaths and common finger flexor sheath. These areas were filled by fluid and multiple small nodular lesions. A diagnosis of non‐infectious rice body tenosynovitis was rendered and surgical removal was performed. Total recovery was observed with no evidence of recurrence after 6 months of follow‐up. To our knowledge, this is the first report of rice body tenosynovitis presenting as a pseudoinflammatory cutaneous lesion with evolution to a cutaneous fistula with drainage of rice grain‐like structures. The description of this impressive and peculiar clinical and histopathologic picture is important to further recognize similar cases.
Assessment of upper limb capacity in children with unilateral cerebral palsy: construct validity of a Rasch‐reduced Modified House Classification
Authors: Geerdink Yvonne , Lindeboom Robert , de Wolf Sander , Steenbergen Bert , Geurts Alexander C H , Aarts Pauline
Published: February 2014

Aim

The aim of this study was to test and improve the unidimensionality and item hierarchy of the Modified House Classification (MHC) for the assessment of upper limb capacity in children with unilateral cerebral palsy (CP) using Rasch analysis. The construct validity of the Rasch‐reduced item set was evaluated.

Method

Modified House Classification items were scored from 369 videotaped assessments of 159 children with unilateral CP (98 males, 61 females; median age 6y 6mo, range 2y 1mo–17y 5mo). Construct validity was tested in 40 other children with unilateral CP (21 males, 19 females; median age 8y 2mo, range 3y 3mo–17y 6mo) by comparing total scores with the Manual Ability Classification System (MACS) and the ABILHAND‐Kids scale.

Results

Fifteen MHC items could be included in the Rasch analysis. The excluded items were either too easy or too difficult. Fourteen items fitted the unidimensional model (χ2=41.3, df=39, p=0.37). The hierarchy of these items was different from the original MHC. There was a significant correlation with the MACS (r=−0.901, p<0.001) and the ABILHAND‐Kids scale (r=0.558, p<0.001).

Interpretation

The original item hierarchy of the MHC can be improved in order to use its sum score for the assessment of upper limb capacity in children with unilateral CP. The Rasch‐reduced 14‐item MHC with weighted sum score shows good construct validity to measure functional capacity of the affected hand in children with unilateral CP.
Does allometry of a sexually selected ornamental trait vary with sexual selection intensity? A multi‐species test in damselflies
Authors: OUTOMURO DAVID , CORDERO RIVERA ADOLFO , NAVA‐BOLAÑOS ANGELA , CÓRDOBA‐AGUILAR ALEX
Published: February 2014

Ornaments may show hyperallometry in certain taxa, i.e. large individuals have proportionally larger ornaments than small ones. One hypothesis suggests that higher sexual selection intensity leads to steeper hyperallometric patterns.

This study tested whether an ornamental trait subject to both intra‐ and intersexual selection showed steeper allometric slopes than when subject solely to intrasexual selection.

The study employed the sexually selected male wing pigmentation of 14 calopterygid species (damselflies) that differ in sexual selection intensity (intrasexual selection versus intra‐ and intersexual selection).

Hyperallometry was not a uniform pattern in the study species. Furthermore, the allometric slopes did not differ between sexual selection intensities. The allometry of ornamental traits is therefore highly variable even among related species. Other selection pressures – probably species‐specific and at a local scale – acting on wing pigmentation might explain the diversity of allometric patterns.
Event‐related potential and eye tracking evidence of the developmental dynamics of face processing
Authors: Meaux Emilie , Hernandez Nadia , Carteau‐Martin Isabelle , Martineau Joëlle , Barthélémy Catherine , Bonnet‐Brilhault Frédérique , Batty Magali
Published: February 2014

Although the wide neural network and specific processes related to faces have been revealed, the process by which face‐processing ability develops remains unclear. An interest in faces appears early in infancy, and developmental findings to date have suggested a long maturation process of the mechanisms involved in face processing. These developmental changes may be supported by the acquisition of more efficient strategies to process faces (theory of expertise) and by the maturation of the face neural network identified in adults. This study aimed to clarify the link between event‐related potential (ERP) development in response to faces and the behavioral changes in the way faces are scanned throughout childhood. Twenty‐six young children (4–10 years of age) were included in two experimental paradigms, the first exploring ERPs during face processing, the second investigating the visual exploration of faces using an eye‐tracking system. The results confirmed significant age‐related changes in visual ERPs (P1, N170 and P2). Moreover, an increased interest in the eye region and an attentional shift from the mouth to the eyes were also revealed. The proportion of early fixations on the eye region was correlated with N170 and P2 characteristics, highlighting a link between the development of ERPs and gaze behavior. We suggest that these overall developmental dynamics may be sustained by a gradual, experience‐dependent specialization in face processing (i.e. acquisition of face expertise), which produces a more automatic and efficient network associated with effortless identification of faces, and allows the emergence of human‐specific social and communication skills.
Autosomal dominant cerebellar ataxias: a systematic review of clinical features
Authors: Rossi M. , Perez‐Lloret S. , Doldan L. , Cerquetti D. , Balej J. , Millar Vernetti P. , Hawkes M. , Cammarota A. , Merello M.
Published: February 2014

Background and purpose

To assess, through systematic review, distinctive or common clinical signs of autosomal dominant cerebellar ataxias (ADCAs), also referred to as spinocerebellar ataxias (SCAs) in genetic nomenclature.

Methods

This was a structured search of electronic databases up to September 2012 conducted by two independent reviewers. Publications containing proportions or descriptions of ADCA clinical features written in several languages were selected. Gray literature was included and a back‐search was conducted of retrieved publication reference lists. Initial selection was based on title and abstract screening, followed by full‐text reading of potentially relevant publications. Clinical findings and demographic data from genetically confirmed patients were extracted. Data were analyzed using the chi‐squared test and controlled for alpha‐error inflation by applying the Holms step‐down procedure.

Results

In all, 1062 publications reviewing 12 141 patients (52% male) from 30 SCAs were analyzed. Mean age at onset was 35 ± 11 years. Onset symptoms in 3945 patients revealed gait ataxia as the most frequent sign (68%), whereas overall non‐ataxia symptom frequency was 50%. Some ADCAs often presented non‐ataxia symptoms at onset, such as SCA7 (visual impairment), SCA14 (myoclonus) and SCA17 (parkinsonism). Therefore a categorization into two groups was established: pure ataxia and mainly non‐ataxia forms. During overall disease course, dysarthria (90%) and saccadic eye movement alterations (69%) were the most prevalent non‐ataxia findings. Some ADCAs were clinically restricted to cerebellar dysfunction, whilst others presented additional features.

Conclusions

Autosomal dominant cerebellar ataxias encompass a broad spectrum of clinical features with high prevalence of non‐ataxia symptoms. Certain features distinguish different genetic subtypes. A new algorithm for ADCA classification at disease onset is proposed.
New approach for evaluating habitat stability using scarce records for both historical and contemporary specimens: a case study using Carabidae specimen records
Authors: Osawa Takeshi , Watanabe Kyohei , Ikeda Hiroaki , Yamamoto Shori
Published: February 2014

Natural history collections, such as specimen records, are crucial resources for conservation and habitat management. However, these data are usually scarce compared to physical environmental data (e.g., digital terrain maps) that we often have little species data and a lot of physical environmental data with which to evaluate habitats. In this paper, we propose a method for evaluating habitat stability using scarce natural history records and abundant physical environmental data. We used both historical and contemporary specimen records of carabid beetles (areas in which records of the same species were recorded during both periods) and evaluated the attributes of these areas using terrain characteristics. We found two common terrain characteristics among the occupied areas: large total river length and low variation in elevation. These terrain characteristics suggest that habitats of carabid species have been conserved in disturbed and wet environments for a long time. These results are consistent with the ecological characteristics of carabid beetles. Our study shows that scarce natural history collections, combined with ingenuity, can be useful for evaluating habitats.
Interaction between brivaracetam (100 mg/day) and a combination oral contraceptive: A randomized, double‐blind, placebo‐controlled study
Authors: Stockis Armel , Watanabe Shikiko , Fauchoux Nicolas
Published: February 2014

This randomized, double‐blind, placebo‐controlled, two‐way crossover study aimed to assess the pharmacokinetic interactions between brivaracetam 100 mg/day and a combination oral contraceptive (OC) containing 30 μg ethinylestradiol and 150 μg levonorgestrel. The study was performed in 28 healthy women over five 28‐day menstrual cycles: baseline (OC only), two treatment cycles with brivaracetam (50 mg b.i.d.) or placebo coadministered with OC separated by a wash‐out cycle (OC only), and a follow‐up cycle (OC only). The OC was administered on days 1–21 of each cycle, and brivaracetam or placebo on days 1–28 of the treatment cycles. Pharmacokinetics of ethinylestradiol and levonorgestrel were determined on day 20; brivaracetam morning trough levels on days 20 (with OC) and 29 (without OC) were compared. Cmax (maximum plasma concentration) and AUC (area under the plasma concentration versus time curve) ratios for brivaracetam versus placebo (90% confidence interval [CI]) were 0.96 (0.88–1.04) and 0.90 (0.86–0.95) for ethinylestradiol, and 0.95 (0.91–0.99) and 0.92 (0.88–0.97) for levonorgestrel, within predefined bioequivalence limits (0.80–1.25). Brivaracetam trough levels were similar on days 20 and 29 (ratio 1.08; 90% CI 0.98–1.18). No differences in breakthrough bleeding were seen across the five cycles. It was concluded that there were no interactions between brivaracetam 100 mg/day and the OC.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Volumetric changes in hippocampal subregions and their relation to memory in pediatric nonlesional localization‐related epilepsy
Authors: Widjaja Elysa , Zamyadi Mojdeh , Raybaud Charles , Snead O. Carter , Smith Mary Lou
Published: February 2014

Objective

Developmental differences in structure and function have been reported along the hippocampal subregions. The aims of this study were to determine if there were volumetric differences in hippocampal head (HH), body (HB), tail (HT), and total hippocampus (TotH)) in children with nonlesional localization‐related epilepsy relative to controls, and the relation between hippocampal subregions with episodic memory and clinical parameters.

Methods

Forty‐eight children with nonlesional localization‐related epilepsy, consisting of 29 left‐sided and 19 right‐sided epilepsy, and 27 healthy controls were recruited. All patients and controls underwent volumetric T1‐weighted imaging, and verbal and nonverbal memory testing. The volume of hippocampal subregions was compared between patients and controls. The associations between left hippocampal subregions with verbal memory; right hippocampal subregions with nonverbal memory; and hippocampal subregions with age, age at seizure onset, and seizure frequency were assessed.

Results

Patients with left‐sided epilepsy had smaller left HH (p = 0.003) and HB (p = 0.012), right HB (p = 0.021) and HT (p = 0.015), and right TotH (p = 0.020) volumes. Those with right‐sided epilepsy had smaller right HT (p = 0.018) volume. There were no statistically significant differences between verbal and nonverbal memory in left‐sided and right‐sided epilepsy relative to controls (all p > 0.025). In left‐sided epilepsy, there was a significant association between left HH volume with verbal memory (β = 0.492, p = 0.001). There was no significant association between left and right hippocampal subregions with verbal and nonverbal memory, respectively, in right‐sided epilepsy and controls (all p > 0.002). In left‐sided and right‐sided epilepsy, there was no significant association between hippocampal subregions with age, age at seizure onset, and seizure frequency (all p > 0.002).

Significance

We have found hippocampal volume reduction, but did not identify a gradient in the severity of volume reduction along the hippocampal axis in children with localization‐related epilepsy. Further study is needed to clarify if there are volumetric changes within the cornu ammonis subfields and dentate gyrus.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Diagnostic test utilization in evaluation for resective epilepsy surgery in children
Authors: Jayakar Prasanna , Gaillard William D. , Tripathi Manjari , Libenson Mark H. , Mathern Gary W. , Cross J. Helen ,   The Task Force for Paediatric Epilepsy Surgery, Commission for Paediatrics, and the Diagnostic Commission of the International League Against Epilepsy
Published: February 2014

Epilepsy surgery is highly successful in achieving seizure freedom in carefully selected children with drug‐resistant focal epilepsy. Advances in technology have aided presurgical evaluation and increased the number of possible candidates. Many of the tests employed are resource intense, and in specific cases they may be unhelpful or have adverse effects. Some standardization of the evaluation process is thus considered timely. Given the lack of class 1 or 2 evidence defining the relative utility of each test in specific clinicopathologic cohorts, a set of expert recommendations was attempted using consensus among members of the Pediatric Epilepsy Surgery Task Force of the International League Against Epilepsy (ILAE) Commissions of Pediatrics and Diagnostics These recommendations aim to limit fringe over or underutilization of use while retaining substantial flexibility in the use of various tests, in keeping with most standard practices at established pediatric epilepsy centers.

A PowerPoint slide summarizing this article is available for download in the Supporting Information sectionhere.
Long‐term seizure remission in childhood absence epilepsy: Might initial treatment matter?
Authors: Berg Anne T. , Levy Susan R. , Testa Francine M. , Blumenfeld Hal
Published: February 2014

Objective

Examine the possible association between long‐term seizure outcome in childhood absence epilepsy (CAE) and the initial treatment choice.

Methods

Children with CAE were prospectively recruited at initial diagnosis and followed in a community‐based cohort study. Children presenting with convulsive seizures, significant imaging abnormalities, or who were followed <5 years were excluded. Early outcomes included success of initial medication, early remission, and pharmacoresistance. The primary long‐term outcome was complete remission: ≥5 years both seizure free and medication free. Survival methods were used for analyses.

Results

The first medication was ethosuximde (ESM) in 41 (69%) and valproic acid (VPA) in 18 (31%). Initial success rates were 59% (ESM) and 56% (VPA). Early remission and pharmacoresistance were similar in each group. Apart from atypical electroencephalography (EEG) features (61% [VPA], 17% [ESM]), no clinical features varied substantially between the treatment groups. Complete remission occurred in 31 children (76%) treated with ESM and 7 (39%) who received VPA (p = 0.007). Children with versus without atypical EEG features were less likely to enter complete remission (50% vs. 71%, p = 0.03). In a Cox regression, ESM was associated with a higher rate of complete remission than VPA (hazards ratio [HR] 2.5, 95% confidence interval [CI] 1.1–6.0; p = 0.03). Atypical EEG features did not independently predict outcome (p = 0.15). Five‐year and 10‐year remission, regardless of continued treatment, occurred more often in children initially treated with ESM versus VPA.

Significance

These findings are congruent with results of studies in genetic absence models in rats and provide preliminary evidence motivating a hypothesis regarding potential disease‐modifying effects of ESM in CAE.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Transferrin receptor expression in serum exosomes as a marker of regenerative anaemia in the horse
Authors: Rout E. D. , WEBB T. L. , Laurence H. M. , Long L. , Olver C. S.
Published: February 2014

Reasons for performing study

Evaluation of erythrocyte regeneration in horses is challenging, as they do not release reticulocytes into the peripheral blood. This study investigated transferrin receptor 1 (TfR1) expression in exosomes as a noninvasive method of characterising the regenerative response in anaemic horses.

Objectives

To quantify TfR1 in ultraprecipitate of serum in horses before and after phlebotomy‐induced anaemia, and to identify exosomes as the source of TfR1. The hypothesis was that serum exosomal TfR1 expression would increase during a regenerative response.

Study design

Experimental model of anaemia.

Methods

Six horses were phlebotomised to achieve a 25% decrease in packed cell volume. Transferrin receptor 1 quantity in exosomes was determined by western blot and relative densitometry before and after phlebotomy. The size and density of the TfR1‐associated particles were confirmed by transmission electron microscopy and density gradient centrifugation, respectively.

Results

Regenerative anaemia was confirmed by decreased packed cell volumes and decreased myeloid:erythroid ratios in the bone marrow. In all 6 horses, TfR1 expression increased between Days 7 and 10. Mean TfR1 levels peaked on Day 10 and at 3‐fold higher than levels on Day 0. Appropriately sized particles were evident on transmission electron microscopy and sucrose density gradient fractions expected to contain exosomes also contained TfR1.

Conclusions

These data indicate that TfR1 expression in serum exosomes may provide a marker for regeneration in anaemic horses.