bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐occurring malformations of cortical development and SCN1A gene mutations
Authors: Barba Carmen , Parrini Elena , Coras Roland , Galuppi Anna , Craiu Dana , Kluger Gerhard , Parmeggiani Antonia , Pieper Tom , Schmitt‐Mechelke Thomas , Striano Pasquale , Giordano Flavio , Blumcke Ingmar , Guerrini Renzo
Published: June 2014

Objective

To report on six patients with SCN1A mutations and malformations of cortical development (MCDs) and describe their clinical course, genetic findings, and electrographic, imaging, and neuropathologic features.

Methods

Through our database of epileptic encephalopathies, we identified 120 patients with SCN1A mutations, of which 4 had magnetic resonance imaging (MRI) evidence of MCDs. We collected two further similar observations through the European Task‐force for Epilepsy Surgery in Children.

Results

The study group consisted of five males and one female (mean age 7.4 ± 5.3 years). All patients exhibited electroclinical features consistent with the Dravet syndrome spectrum, cognitive impairment, and autistic features. Sequencing analysis of the SCN1A gene detected two missense, two truncating, and two splice‐site mutations. Brain MRI revealed bilateral periventricular nodular heterotopia (PNH) in two patients and focal cortical dysplasia (FCD) in three, and disclosed no macroscopic abnormality in one. In the MRI‐negative patient, neuropathologic study of the whole brain performed after sudden unexpected death in epilepsy (SUDEP), revealed multifocal micronodular dysplasia in the left temporal lobe. Two patients with FCD underwent epilepsy surgery. Neuropathology revealed FCD type IA and type IIA. Their seizure outcome was unfavorable. All four patients with FCD exhibited multiple seizure types, which always included complex partial seizures, the area of onset of which co‐localized with the region of structural abnormality.

Significance

MCDs and SCN1A gene mutations can co‐occur. Although epidemiology does not support a causative role for SCN1A mutations, loss or impaired protein function combined with the effect of susceptibility factors and genetic modifiers of the phenotypic expression of SCN1A mutations might play a role. MCDs, particularly FCD, can influence the electroclinical phenotype in patients with SCN1A‐related epilepsy. In patients with MCDs and a history of polymorphic seizures precipitated by fever, SCN1A gene testing should be performed before discussing any epilepsy surgery option, due to the possible implications for outcome.
IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low‐grade gliomas
Authors: Liubinas Simon V. , D'Abaco Giovanna M. , Moffat Bradford M. , Gonzales Michael , Feleppa Frank , Nowell Cameron J. , Gorelik Alexandra , Drummond Katharine J. , O'Brien Terence J. , Kaye Andrew H. , Morokoff Andrew P.
Published: June 2014

Objective

The isocitrate dehydrogenase 1 (IDH1) R132H mutation is the most common mutation in World Health Organization (WHO) grade II gliomas, reported to be expressed in 70–80%, but only 5–10% of high grade gliomas. Low grade tumors, especially the protoplasmic subtype, have the highest incidence of tumor associated epilepsy (TAE). The IDH1 mutation leads to the accumulation of 2‐hydroxyglutarate (2HG), a metabolite that bears a close structural similarity to glutamate, an excitatory neurotransmitter that has been implicated in the pathogenesis of TAE. We hypothesized that expression of mutated IDH1 may play a role in the pathogenesis of TAE in low grade gliomas.

Methods

Thirty consecutive patients with WHO grade II gliomas were analyzed for the presence of the IDH1‐R132H mutation using immunohistochemistry. The expression of IDH1 mutation was semiquantified using open‐source biologic‐imaging analysis software.

Results

The percentage of cells positive for the IDH1‐R132H mutation was found to be higher in patients with TAE compared to those without TAE (median and interquartile range (IQR) 25.3% [8.6–53.5] vs. 5.2% [0.6–13.4], p = 0.03). In addition, we found a significantly higher median IDH1 mutation expression level in the protoplasmic subtype of low grade glioma (52.2% [IQR 19.9–58.6] vs. 13.8% [IQR 3.9–29.4], p = 0.04).

Significance

Increased expression of the IDH1‐R132H mutation is associated with seizures in low grade gliomas and also with the protoplasmic subtype. This supports the hypothesis that this mutation may play a role in the pathogenesis of both TAE and low grade gliomas.
Sudden unexpected death in epilepsy: Assessing the public health burden
Authors: Thurman David J. , Hesdorffer Dale C. , French Jacqueline A.
Published: June 2014

Objective

There is not yet a clear consensus on the incidence of sudden unexpected death in epilepsy (SUDEP) or the extent of its burden on public health. In this systematic review, we seek to summarize the incidence of SUDEP and its age distribution, as well as the years of potential life lost and cumulative risks of SUDEP for persons with epilepsy.

Methods

We conducted a systematic search for epidemiologic studies of sudden death in epilepsy and rated their quality of evidence. We pooled data from comparable higher quality population‐based studies of SUDEP incidence across all age groups, calculating the overall incidence of SUDEP per 100,000 population, and per 1,000 people with epilepsy. Using standard formulas, we also calculated the years of potential life lost and cumulative risks associated with SUDEP.

Results

SUDEP has an estimated overall crude annual incidence rate of 0.81 cases per 100,000 population, or 1.16 cases per 1,000 patients with epilepsy. Comparing years of potential life lost from SUDEP with selected other neurologic diseases, SUDEP ranks second only to stroke.

Significance

Despite limitations to the data on which our analysis is based, we conclude that the public health burden of SUDEP, which has previously been underappreciated, is substantial and deserves much more attention from clinicians, researchers, and the public health community.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Distinct functional and structural MRI abnormalities in mesial temporal lobe epilepsy with and without hippocampal sclerosis
Authors: Coan Ana C. , Campos Brunno M. , Beltramini Guilherme C. , Yasuda Clarissa L. , Covolan Roberto J. M. , Cendes Fernando
Published: June 2014

Objective

We aimed to investigate patterns of electroencephalography‐correlated functional MRI (EEG‐fMRI) and subtle structural abnormalities in patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (MTLE‐HS) or normal MRI (MTLE‐NL).

Methods

We evaluated EEG‐fMRI acquisition of the 25 patients with diagnosis of MTLE who had interictal epileptiform discharges (IEDs) in the intra‐MRI EEG: 13 MTLE‐HS and 12 MTLE‐NL. fMRI was performed using echo‐planar images in a 3T MRI coupled with EEG acquired with 64 MRI‐compatible electrodes. In the first level analyses, the time of the IEDs ipsilateral to the epileptogenic zone was used as the paradigm, and four contrasts maps were built according to the variation of the hemodynamic response function (HRF) peaks (0, +3, +5, and +7 s). Second level group analyses were performed combining the contrast maps of MTLE‐HS or MTLE‐NL patients with each different HRF obtained at the first level. Areas of gray matter atrophy were evaluated with voxel‐based morphometry (VBM) in both groups.

Results

MTLE‐HS and MTLE‐NL had IED‐related positive BOLD (posBOLD) detected in the ipsilateral anterior temporal lobe and insula. However, only MTLE‐HS had significant posBOLD on contralateral hippocampus and anterior cingulate, whereas MTLE‐NL had areas of posBOLD on ipsilateral frontal lobe. Both groups had significant IED‐related negBOLD responses in areas of the default mode network (DMN), such as posterior cingulate and precuneus. There was no overlap of both posBOLD and negBOLD and areas of atrophy detected by VBM.

Significance

Similar IEDs have different patterns of hemodynamic responses in sub‐groups of MTLE. In both MTLE‐HS and MTLE‐NL, there is a possible suppression of the DMN related to IEDs, as demonstrated by the negBOLD in these areas. The brain areas involved in the interictal related hemodynamic network are not the regions with the most significant gray matter atrophy in MTLE with or without MRI signs of HS.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Antiseizure effects of TrkB kinase inhibition
Authors: Liu Gumei , Kotloski Robert J , McNamara James O.
Published: June 2014

Objective

The principal molecular targets of conventional antiseizure drugs consist of ligand‐gated and voltage‐gated ion channels and proteins subserving synaptic function. Inhibition of the receptor tyrosine kinase TrkB limits epileptogenesis, but its effect on individual seizures is unknown. We sought to determine whether inhibition of TrkB kinase exerts an antiseizure effect.

Methods

We utilized the kindling model in combination with an inducible conditional knockout of the TrkB gene (Act‐CreER TrkBflox/flox mice treated with tamoxifen), and also with a chemical‐genetic approach in which mice carry a TrkB kinase with a phenylalanine to alanine substitution of residue 616 (TrkBF616A), which allows inhibition of the kinase by a blood–brain barrier permeable small molecule, 1′‐naphthylmethyl‐4‐amino‐1‐tert‐butyl‐3‐(p‐methylphenyl)pyrazolo[3,4‐d]pyrimidine (1NMPP1).

Results

Following induction of kindling, reduction of TrkB protein levels in Act‐CreER TrkBflox/flox mice treated with tamoxifen was associated with reduced severity of behavioral seizures evoked by stimulation. Treatment with 1NMPP1 for 2 weeks following induction of kindling reversibly elevated both focal electrographic and generalized seizure thresholds in TrkBF616A, but not wild‐type (WT), mice. In contrast to kindled animals, treatment of naive TrkBF616A mice for 2 weeks had no detectable effect on electrographic seizure threshold (EST).

Significance

This study provides proof of concept of a novel molecular target for antiseizure drugs, namely the receptor tyrosine kinase TrkB.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Efficacy and safety of pregabalin versus levetiracetam as adjunctive therapy in patients with partial seizures: A randomized, double‐blind, noninferiority trial
Authors: Zaccara Gaetano , Almas Mary , Pitman Verne , Knapp Lloyd , Posner Holly
Published: June 2014

Objectives

To assess the comparative efficacy and safety of pregabalin and levetiracetam for the reduction of seizure frequency in patients with partial seizures.

Methods

This was a randomized, double‐blind, flexible‐dose, parallel‐group noninferiority study of pregabalin and levetiracetam (randomized 1:1) as adjunctive treatment in adult patients with refractory partial seizures. The study included a 6‐week baseline phase, 4‐week dose‐escalation phase, and 12‐week maintenance phase. The primary endpoint was the proportion of patients with a ≥50% reduction in 28‐day seizure rate during the 12‐week maintenance phase, as compared with baseline. Noninferiority of pregabalin was declared if the lower limit of the 95% confidence interval (CI) for the difference in responder rates was greater than the prespecified noninferiority margin of −12%. A key secondary endpoint was the percent change from baseline in 28‐day seizure rate during the dose‐escalation and maintenance phases.

Results

Five hundred nine patients were randomized to pregabalin (n = 254) or levetiracetam (n = 255) and 418 (208 pregabalin, 210 levetiracetam) completed the maintenance phase. With both pregabalin and levetiracetam, the proportion of patients with a ≥50% reduction in 28‐day seizure rate was 0.59 (difference between groups [95% CI], 0.00 [−0.08 to 0.09]). Because the lower bound of the 95% CI was greater than the prespecified noninferiority margin of −12%, pregabalin was not inferior to levetiracetam. There was no significant difference between pregabalin and levetiracetam in the percent change in 28‐day seizure rate (median difference [95% CI], 4.1 [−2.6 to 10.9], p = 0.3571). In a post hoc analysis, the proportion of patients who were seizure‐free for the maintenance phase was lower with pregabalin (8.4%) than with levetiracetam (16.2%), p = 0.0155. Safety profiles were similar and consistent with prior trials.

Significance

These results indicate that pregabalin is noninferior, and has a similar tolerability, to levetiracetam as adjunctive therapy in reducing seizure frequency in patients with partial seizures.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Lennox‐Gastaut syndrome and phenotype: Secondary network epilepsies
Authors: Archer John S. , Warren Aaron E. L. , Stagnitti Monique R. , Masterton Richard A. J. , Abbott David F. , Jackson Graeme D.
Published: June 2014

Objective

Lennox‐Gastaut syndrome (LGS) is a severe epilepsy phenotype with characteristic electroclinical features despite diverse etiologies. We previously found common cerebral networks involved during slow spike‐and‐wave (SSW) and generalized paroxysmal fast activity (PFA), characteristic interictal discharges. Some patients have a Lennox‐Gastaut–like phenotype and cortical lesions. We wished to explore the interaction between cerebral networks and lesions in this group.

Methods

3 Tesla electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) on six subjects with Lennox‐Gastaut phenotype and a structural lesion. Timings of SSW and PFA events were used in an event‐related fMRI analysis, and to estimate the time course of the hemodynamic response from key regions.

Results

(1) PFA‐robust fMRI signal increases were observed in frontal and parietal association cortical areas, thalamus, and pons, with simultaneous increases in both “attention” and resting‐state (default mode) networks, a highly unusual pattern. (2) SSW showed mixed increased and decreased fMRI activity, with preevent increases in association cortex and thalamus, and then prominent postevent reduction. There was decreased fMRI activity in primary cortical areas. (3) Lesion‐variable fMRI increases were observed during PFA and SSW discharges. Three subjects who proceeded to lesionectomy are >1 year seizure‐free.

Significance

We conceptualize Lennox‐Gastaut phenotype as a being a network epilepsy, where key cerebral networks become autonomously unstable. Epileptiform activity in Lennox‐Gastaut phenotype, and by implication in LGS, appears to be amplified and expressed through association cortical areas, possibly because the attention and default‐mode networks are widely interconnected, fundamental brain networks. Seizure freedom in the subjects who proceeded to lesionectomy suggests that cortical lesions are able to establish and maintain this abnormal unstable network behavior. LGS may be considered a secondary network epilepsy because the unifying epileptic manifestations of the disorder, including PFA and SSW, reflect network dysfunction, rather than the specific initiating process.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Pericellular proteolysis by matrix metalloproteinase‐7 is differentially modulated by cholesterol sulfate, sulfatide, and cardiolipin
Authors: Yamamoto Kazuhiro , Miyazaki Kaoru , Higashi Shouichi
Published: June 2014

Matrix metalloproteinase (MMP)‐7 binds to cell surface cholesterol sulfate (CS) and acts as a membrane‐associated protease. We have previously found that CS modulates the substrate preference of MMP‐7, thereby regulating its pericellular proteolytic action. MMP‐7 potentially associates with the cell surface via sulfatide (SM4) and cardiolipin (CL) when they are overexpressed on the cell surface. Here, we investigated the molecular interaction between these acidic lipids and MMP‐7 or its substrates, and their effects on the activity of MMP‐7. Studies using MMP‐7 variants with low CS‐binding ability suggested that these lipids interact with a similar site on MMP‐7. The hydroxamate‐based MMP inhibitor TAPI‐1 markedly reduced the affinity of MMP‐7 for CS and CL, whereas that for SM4 was not affected by TAPI‐1. These three acidic lipids also had different effects on the hydrolytic activity of MMP‐7 towards a small peptide substrate: SM4, CL and CS reduced the activity to 80%, 92%, and 20%, respectively. Nevertheless, SM4 and CS similarly accelerated the MMP‐7‐catalyzed degradation of fibronectin and laminin‐332, whereas CL did not. The increased proteolysis of substrate was observed only when both substrate and enzyme had affinity for the lipid, suggesting that the lipids probably bring the reactants into closer proximity. Furthermore, MMP‐7 bound to cell surface SM4 or CS cleaved specific cell surface proteins and released similar fragments, whereas the cleavage was not stimulated by cell surface CL‐bound MMP‐7. This study provides a novel mechanism by which acidic lipids differentially regulate pericellular proteolysis by MMP‐7 through allosteric alteration of the substrate‐binding site and their inherent affinities for MMP‐7 substrates.
Fate of Nutrients in Shallow Groundwater Receiving Treated Septage, Malibu, CA
Authors: Izbicki John A.
Published: June 2014

Treated wastewater discharged from more than 400 onsite wastewater treatment systems (OWTS) near the Civic Center area of Malibu, California, 40 km west of downtown Los Angeles, composes 28% of the recharge to a 3.4 km2 alluvial aquifer. On the basis of δ18O and δD data, the fraction of wastewater in some samples was >70%. Ammonium and nitrate concentrations in water from 15 water‐table wells sampled in July 2009 and April 2010 ranged from <0.01 to 12 milligrams per liter as nitrogen (mg/L as N), and from <0.01 to 11 mg/L as N, respectively. Chemical and isotopic data (δ15N of ammonium and nitrate, and δ18O of nitrate) show two processes remove nitrogen discharged from OWTS. Where groundwater was reducing, sorption of ammonium resulted in 30 to 50% nitrogen removal. Where groundwater was initially oxic, nitrification with subsequent denitrification as reducing conditions developed, resulted in up to 60% nitrogen removal. Nitrogen removal through sorption dominated during the cooler April sample period, and denitrification dominated during the warmer July sample period. The combination of mixing and nitrogen removal due to denitrification, sorption, and volatilization produces a δ15N apparent fractionation factor (εapp = −5), that can be explained using laboratory‐derived fractionation factors (ε) for the individual processes. Phosphate concentrations ranged from < 0.04 to 2 mg/L as phosphorous. Sorption to iron oxides on the surfaces of mineral grains at near‐neutral pH's removed some phosphate; however, little removal occurred at more alkaline pH's (>7.3).
An Analytical Approach for Flow Analysis in Aquifers with Spatially Varying Top Boundary
Authors: Zlotnik Vitaly A. , Toundykov Daniel , Cardenas M. Bayani
Published: June 2014

Analytical models of groundwater flow with a spatially varying elevation of a top boundary are widely used. However, a vast majority of previous analytical studies truncated the irregularly shaped top section with little to no analyses of the shortcomings of the approximate solutions for the resulting rectangles or parallelepipeds. We present an analytical approach based on a perturbation technique that treats complete domains. It is especially accurate near the top boundary, where fluid circulation is most pronounced and higher accuracy is typically needed, such as in regional or hyporheic systems flow. The approach is illustrated by analyzing flow for a Tóthian unit basin.
MODFLOW‐Based Coupled Surface Water Routing and Groundwater‐Flow Simulation
Authors: Hughes J.D. , Langevin C.D. , White J.T.
Published: June 2014

In this paper, we present a flexible approach for simulating one‐ and two‐dimensional routing of surface water using a numerical surface water routing (SWR) code implicitly coupled to the groundwater‐flow process in MODFLOW. Surface water routing in SWR can be simulated using a diffusive‐wave approximation of the Saint‐Venant equations and/or a simplified level‐pool approach. SWR can account for surface water flow controlled by backwater conditions caused by small water‐surface gradients or surface water control structures. A number of typical surface water control structures, such as culverts, weirs, and gates, can be represented, and it is possible to implement operational rules to manage surface water stages and streamflow. The nonlinear system of surface water flow equations formulated in SWR is solved by using Newton methods and direct or iterative solvers. SWR was tested by simulating the (1) Lal axisymmetric overland flow, (2) V‐catchment, and (3) modified Pinder‐Sauer problems. Simulated results for these problems compare well with other published results and indicate that SWR provides accurate results for surface water‐only and coupled surface water/groundwater problems. Results for an application of SWR and MODFLOW to the Snapper Creek area of Miami‐Dade County, Florida, USA are also presented and demonstrate the value of coupled surface water and groundwater simulation in managed, low‐relief coastal settings.
Regional Frequency Analysis of Extreme Groundwater Levels
Authors: Fürst Josef , Bichler Andrea , Konecny Franz
Published: June 2014

Flood risk is generally perceived as being a consequence of surface water inundation. However, large damage is also caused by high groundwater levels. In surface hydrology, statistical frequency analysis is a standard tool to estimate discharge with a given return period or exceedance probability. First, a suitable probability distribution is fit to a series of annual maximum peaks. Second, this distribution is used to determine the discharge corresponding to the desired return period. Where only short series of recorded data are available, the estimates can often be improved by regional frequency analysis (RFA). Unfortunately, there is little information in the literature on analogous approaches for the estimation of extreme groundwater levels. In this contribution, the applicability of l‐moments‐based RFA for the estimation of extreme groundwater levels is investigated. The main issues specific to groundwater levels are (1) appropriate transformation of the data, (2) criteria for identification of statistically homogeneous regions, (3) consideration of correlation between sites, and (4) choice of distribution function. This study is based on data from more than 1100 observation sites in four shallow Austrian Aquifers with a record length of 10 to 50 years. Results show that homogeneous regions for l‐moments‐based RFA can be identified covering about one half of the total area of the aquifers. The confidence intervals for the 30‐ and 100‐year return levels can be significantly reduced by RFA. Out of the four investigated distribution functions, none is to be preferred generally.
Empire, Industry, and Globalization: Rethinking the Emergence of the Gold Standard in the 19th‐century World
Authors: Taylor Vurpillat J.
Published: June 2014

This state of the field essay surveys recent scholarship on the history of the international gold standard. Taken together, recent studies have re‐situated the emergence of the classical gold standard in historical context, emphasizing the rapidly changing world of 19th‐century globalization, industrialization, and imperialism. This work has significant implications for our understanding of the gold standard in world history. In particular, recent studies have placed new emphasis on non‐economic factors that led to the establishment of a truly international gold standard. Among these factors, the ambitions for empire and modernization among leaders in the non‐European world played a key role in the decline of regional monetary regimes based on silver or bimetallism and the emergence of the international gold standard in the late‐19th century.
The History of Mum and Dad: Recent Historical Research on Parenting in England from the 16th to 20th centuries
Authors: Bailey Joanne
Published: June 2014

Parenting has a complex but only recently examined history. This article surveys this scholarship, which is driven by the histories of gender, emotions, medicine, bodies, material culture, class and deviance to uncover how parenting is socially and culturally constructed and therefore changes over time. It traces several significant arguments. First, shifting gender constructions have reshaped expectations about mothers' and fathers' roles. Thus, while paternal breadwinning and maternal care is always important, at times fathers have been commended for caring for infants and mothers for economic provision of offspring. Secondly, the material aspects of life have powerfully affected parenting. Until relatively recently, parents struggled against implacably high rates of infant and child mortality: nursing children, preparing them for death and the afterlife, and coping with grief. Therefore, although the depth of feeling over this remained consistent, varying emotional regimes have influenced forms of parental expression and practice. Parents' responsibilities for their children's health at times of inadequate medical treatment often left them physically and mentally exhausted and woefully disempowered. Other limitations or freedoms were imposed on mothering and fathering by the objects and spaces associated with bringing up children. Thirdly, levels of wealth and social class affect parenting, with working‐class, poor and lone parents especially vulnerable to family disruption due to poverty, ill‐health and under‐ or unemployment. Fourthly, the parameters of bad parenting shift over time, and even those mothers and fathers who killed their children were viewed differently over time and place as cultural sensibilities shifted. Finally, the article concludes with some suggestions for the further development of this exciting new field.
Repositioning History for the Future ‐ Recent Academic Debates in China
Authors: Eben v.Racknitz Ines
Published: June 2014

Changes in the politics and society in post‐Deng China are reflected in the research priorities of mainland Chinese university history departments, while questions of political legitimation in China and contact with colleagues abroad in the United States and Europe continue to generate new research topics. This article intends to show how several factors contribute to the shaping of historical research in China today. Ongoing developments in China will be demonstrated through two examples, namely the field of world history and the discussion surrounding New Qing history in China.
Effect of dutasteride 0.5 mg/d in men with androgenetic alopecia recalcitrant to finasteride
Authors: Jung Jae Yoon , Yeon Je Ho , Choi Jee Woong , Kwon Soon Hyo , Kim Beom Joon , Youn Sang Woong , Park Kyoung Chan , Huh Chang Hun
Published: June 2014

Background

Finasteride at a dose of 1 mg/d has been reported to show no significant improvement in 30–50% of patients with androgenetic alopecia (AGA). Dutasteride, a dual inhibitor of both type I and type II 5 alpha‐reductase, inhibits the conversion of testosterone to dihydrotestosterone, which is the key contributor of AGA.

Materials and methods

Our aim is to evaluate clinical efficacy and tolerability of dutasteride in men with AGA who do not show clinical improvement to the conventional finasteride treatment. A total of 35 Korean men with AGA who had not shown significant clinical improvement when treated with finasteride 1 mg/d for at least six months received dutasteride at a dose of 0.5 mg/d for six months. Efficacy was evaluated by global photograph assessment and phototrichogram. Safety assessment was performed through physical examination and adverse event report.

Results

Of the 31 patients who completed the treatment, 24 patients (77.4%) were improved by the global photography (17 were slightly, six moderately, and one markedly improved) compared with the post‐finasteride treatment. There was no significant change in seven patients (22.6%), and aggravation was not reported. Hair density and thickness significantly increased by 10.3% (87 ± 12–96 ± 12/cm2) and 18.9% (0.053 ± 0.012–0.063 ± 0.011 mm), respectively, in phototrichogram assessment. Side effects included transient sexual dysfunction in six patients (17.1%).

Conclusions

Dutasteride is suggestive to be an alternative treatment option to patients with AGA who do not clinically respond to finasteride in six months.
IL36RN mutation causing generalized pustular psoriasis in a Palestinian patient
Authors: Renert‐Yuval Yael , Horev Liran , Babay Sofia , Tams Spiro , Ramot Yuval , Zlotogorski Abraham , Molho‐Pessach Vered
Published: June 2014

Deficiency of interleukin‐36 (IL‐36) receptor antagonist (DITRA; OMIM 614204) is a rare autoinflammatory disorder characterized by periodic fever associated with a generalized erythematous and pustular skin rash. A 6‐year‐old Arab‐Palestinian boy presented with a history of periodic fever and unremitting, erythematous, scaly skin rash accompanied by widespread pustules that had been present since the age of one month. The patient's skin lesions were compatible with generalized pustular psoriasis. Sequence analysis revealed a homozygous nonsense mutation, c.28C>T (p.Arg10X) in the IL36RN gene. The patient improved with oral methotrexate in combination with oral and topical corticosteroids. The molecular basis for DITRA has only recently been identified, and the mutation spectrum for this disorder in many populations is still obscure. This paper reports the presence of the c.28C>T mutation in an Arab‐Palestinian patient and thus represents the first description of this mutation in a non‐Japanese subject.
A rare case of subcutaneous phaeohyphomycosis caused by aRhytidhysteronspecies: a clinico‐therapeutic experience
Authors: Mahajan Vikram K. , Sharma Vikas , Prabha Neel , Thakur Kamlesh , Sharma Nand Lal , Rudramurthy Shivaprakash M. , Chauhan Pushpinder S. , Mehta Karaninder S. , Abhinav C.
Published: June 2014

Background

Subcutaneous phaeohyphomycosis usually results from traumatic inoculation with the fungus and generally occurs in immunosuppressed men.Cladosporium,Exophiala, andAlternariaspp. are commonly implicated pathogens.

Objectives

We present a case of subcutaneous phaeohyphomycosis caused byRhytidhysteronsp. that was refractory to conventional antifungal therapy.

Case report

A 72‐year‐old man with hypertension and diabetes presented with a multiloculated, large cystic swelling over the right dorsal foot. Laboratory findings and x‐rays of the chest and left foot were normal.

Results

Adequate control of the patient's diabetes was achieved, and the swelling was excised under itraconazole/terbinafine coverage. Histology showed multiple areas of neutrophilic abscess, epithelioid cells, foreign body giant cells, and multiple septate hyphae and yeast‐like cells. Dematiaceous fungus was cultured but failed to produce spores. Sequencing of the isolate showed a match of > 99% withRhytidhysteron rufulum. The patient demonstrated no response after one year of therapy with itraconazole/terbinafine. Weekly infiltration of the lesion with liposomal amphotericin B resulted in its complete resolution within 15 weeks.

Conclusions

Lesions of phaeohyphomycosis appear morphologically similar regardless of the organism implicated. Hence, their diagnosis rests entirely on the clinicopathological and microbiological presentation. Molecular studies may be required to identify a fungus if attempts to grow it in artificial culture media fail.Rhytidhysteronspp. are not known as pathogens in humans, and no treatment protocol exists. Intralesional amphotericin was highly effective in our patient and caused no systemic adverse effects. Voriconazole and posaconazole are effective against disseminated/visceral phaeohyphomycotic infections, but their efficacy againstRhytidhysteronspp. remains unstudied.
MDR1 C3435T polymorphism associated with the development of clinical features in Behçet's disease in Iranian Azeri Turkish patients
Authors: Bonyadi Mortaza , Gholizadeh Monireh , Soltan‐Ali Mahboob
Published: June 2014

Background

Behçet's disease (BD) is a systemic vasculitis of unknown cause with a higher prevalence along the ancient Silk Road. Behçet's occasional familial aggregation and its close association with genes of major histocompatibility complexes justify that genetic factors play an important role in the development of the disease. In this study, we evaluated the association of multidrug resistance (MDR1) C3435T polymorphism with the severity of BD.

Method

We investigated the distribution of MDR1 C3435T polymorphism in 69 patients from the Iranian Azeri Turks group with BD and 92 ethnically sex‐matched healthy controls, via the polymerase chain reaction–restriction fragment length polymorphism technique.

Result

Although there was no significant association of MDR1 C3435T polymorphism between two groups of patients and healthy controls, our data showed a substantial association of CC genotype with the development of several clinical features, including erythema nodosum (P = 0.001, OR = 2.686, 95%), pseudofolliculitis (P = 0.002, OR = 2.812, 95%), and skin lesions (P = 0.040, OR = 1.934, 95%).

Conclusion

These results suggest that CC genotype is a risk factor for the development of some clinical features of BD in patients from the Iranian Azeri Turk ethnic group.
Effects of a diabetes prevention programme on weight‐specific quality of life in Latino youth
Authors: Brito E. , Patrick D. L. , Konopken Y. P. , Keller C. S. , Barroso C. S. , Shaibi G. Q.
Published: June 2014

Objective

To examine the effects of a diabetes prevention programme on weight‐specific Quality of Life (QOL) in obese Latino youth.

Methods

Fifteen obese Latino adolescents (body mass index % = 96.4 ± 1.2; age = 15.0 ± 1.0) completed a 12‐week culturally grounded, community‐based intervention designed to improve physical and psychosocial health. Weight‐specific QOL was assessed by the Youth Quality of Life‐Weight module and compared with age, sex and ethnicity‐matched lean youth.

Results

At baseline, intervention youth exhibited significantly lower weight‐specific QOL compared with lean youth (70.8 ± 5.4 vs. 91.2 ± 2.2, P = 0.002). However, following the intervention, total weight‐specific QOL increased by 21.8% among obese youth (70.8 ± 5.4 to 86.2 ± 4.3, P < 0.001) and was no longer different from lean controls. Significant increases in weight‐specific QOL were noted across all subdomains including self (45.7%), social (11.9%) and environmental (36.2%) despite the fact that weight did not change (90.6 ± 6.8 to 89.9 ± 7.2, P = 0.44). The improvements in QOL were maintained for up to 12 months after the intervention.

Conclusion

Weight‐specific QOL among obese Latino youth can be improved through lifestyle interventions to a level similar to lean peers. Further, weight loss may not be necessary to observe improvements in QOL.
Efficacy of repeated exposure and flavour–flavour learning as mechanisms to increase preschooler's vegetable intake and acceptance
Authors: de Wild V. , de Graaf C. , Jager G.
Published: June 2014

Background

Dutch children's diets, like the diets of many children in Europe and the US are not balanced, do not contain enough vegetables and have been associated with a high prevalence of childhood obesity. Promoting children's vegetable intake is challenging.

Objective

We investigated the relative effectiveness of repeated exposure and flavour–flavour learning in increasing vegetable intake and acceptance in preschoolers.

Methods

During an intervention period of 7 weeks, 39 toddlers (aged 1.5 to 4 years) consumed red beet and parsnip crisps at day‐care centres in Wageningen, the Netherlands. Half of the group received red beet crisps with a dip of tomato ketchup (Conditioned [C]) and parsnip with a neutral white sauce (Unconditioned, [UC]), whereas for the other half the order was reversed (red beet [UC], parsnip [C]). Preference and ad libitum consumption of vegetable crisps were measured once before and three times after the intervention over the course of a 6‐month follow‐up period to assess longer‐term effects.

Results

Intake increased significantly after the intervention for both vegetables (on average with 8 g; an increase of approximately 300%), and this effect was persistent even 6 months afterwards. The increase was irrespective of crisps being offered with C or UC dip sauce.

Conclusions

These results suggest a robust and persistent effect of repeated exposure but no effect of flavour–flavour learning. Offering pure vegetable tastes repeatedly is sufficient to increase intake.
Urtica dioica for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia
Authors: Hosseinabadi Reza , Heidari Mohammad , Anbari Khatereh , Pournia Yadollah
Published: June 2014

Benign prostatic hyperplasia (BPH) is a common problem of the elderly population. This study was conducted to investigate the effect of Urtica dioica on the clinical symptoms of BPH. This double‐blind clinical trial included 248 patients with symptomatic BPH in Shohada Ashayer Hospital of Khorramabad. The patients were randomly divided into four groups of treatment with U. dioica 3 g, U. dioica 5 g, U. dioica 7 g and treatment with prazosin 1 mg alone as the control group. The clinical symptoms, patients' quality of life and level of serum prostate‐specific antigen (PSA) were measured before and 2 months after the intervention. The results of the study showed significant differences between the four groups after the intervention for the scores of clinical symptoms and patients' quality of life, while no significant differences were found for serum PSA levels. Sheffe post hoc comparisons showed significant improvements in the scores of the patients' clinical symptom in the U. dioica 5 g/d and U. dioica 7 g/d groups. The results of the study showed that simultaneous consumption of higher doses of U. dioica, up to 7 g/d, plus prazosin, compared with the consumption of prazosin alone, resulted in significant improvements in the clinical symptoms of BPH.
In VitroMechanical Testing of Braided Polyurethane Elastic Fiber and Braided Polyester for Equine Laryngoplasty
Authors: Willsallen Hadley , Heller Jane , Kark Lauren , Hilbert Bryan J.
Published: June 2014

Objectives

In vitrocomparison of the mechanical properties of braided polyurethane elastomer (Lycra®) and braided polyester (Ethibond™) (1) when inserted into the muscular process of the arytenoid cartilage and (2) as suture loops.

Study Design

Experimental.

Animals

Equine cadaver larynges (n = 15).

Methods

The muscular processes (n = 30) of the arytenoid cartilages were dissected from each larynx and embedded in a resin base. Lycra® and Ethibond™ prostheses were randomly allocated to the left or right muscular process and each underwent cyclic fatigue (25–50 N) followed by load‐to‐failure testing.

Isolated suture loops of Lycra® (n = 25) and Ethibond™ (n = 25) also underwent the same cyclic fatigue followed by load‐to‐failure testing (n = 20) or a creep testing protocol (25 N for 10 min; n = 5).

Results

Lycra® prostheses pulled through the cartilage in a significantly greater proportion of cyclic tests (P = .015) and at lower mean (±SD) loads, (95.9 ± 23.4 N) during load‐to‐failure testing than Ethibond™ prostheses (155.2 ± 24.4 N;P = .0041). Lycra® had a significantly greater displacement with and without a cartilage interface when compared to Ethibond™ (P < .001,P < .002). The Lycra® isolated suture loops failed at significantly greater loads (233.0 ± 38.7 N) during load‐to‐failure testing than Ethibond™ loops (201.6 ± 47.4 N;P = .042).

Conclusions

Lycra® prostheses embedded in laryngeal cartilage pulled through the cartilage at lower loads than Ethibond™ prostheses. Lycra® suture loops were stronger than Ethibond™ suture loops. Lycra® had greater displacement than Ethibond™ in all tests as suture loops or when embedded in cartilage.
Laparoscopic Extirpation of the Medial Iliac Lymph Nodes in Normal Dogs
Authors: Steffey Michele A. , Daniel Leticia , Mayhew Philipp D. , Affolter Verena K. , Soares Joao H.N. , Fuller Mark C.
Published: June 2014

Objective

To describe a surgical technique for laparoscopic medial iliac lymph node (MILN) extirpation, and to describe the quality of biopsy specimens obtained.

Design

Experimental study.

Animals

Purpose‐bred male hound‐mix research dogs (n = 8).

Methods

Dogs were randomized to groups of left or right‐sided laparoscopic surgical approaches. Three transperitoneal portals were established with the dogs in lateral recumbency, and ipsilateral MILN dissection was achieved under CO2 pneumoperitoneum using a vessel‐sealing device.

Results

MILN ipsilateral to the approach were successfully identified and removed laparoscopically in 8 dogs. Observed complications included mild to moderate hemorrhage that was controlled laparoscopically in 4 dogs, and tearing of the MILN capsule during retraction and dissection in 3 dogs. No other major complications occurred and all dogs recovered uneventfully. Areas of either minor peripheral (9/9) or central (4/9) pinch artifact affected a median percentage of 5% of surface area (range, 5–30%) of bisected lymph nodes.

Conclusions

Laparoscopic MILN extirpation is feasible in dogs with normal MILN and may serve as a minimally invasive approach for excisional biopsy in the diagnostic staging of canine onocologic patients with normal‐sized MILN. This lateral laparoscopic approach allows dissection of the ipsilateral MILN but precludes removal of the contralateral MILN. Minimal handling of the lymph node during dissection and removal is required to reduce the risk of capsular tear, or introduction of possible histologic artifact by tissue crush that may impact diagnosis.
Canine Intrahepatic Vasculature: Is a Functional Anatomic Model Relevant to the Dog?
Authors: Hall Jon L. , Mannion Paddy , Ladlow Jane F.
Published: June 2014

Objective

To clarify canine intrahepatic portal and hepatic venous system anatomy using corrosion casting and advanced imaging and to devise a novel functional anatomic model of the canine liver to investigate whether this could help guide the planning and surgical procedure of partial hepatic lobectomy and interventional radiological procedures.

Study Design

Prospective experimental study.

Animals

Adult Greyhound cadavers (n = 8).

Methods

Portal and hepatic vein corrosion casts of healthy livers were assessed using computed tomography (CT).

Results

The hepatic lobes have a consistent hilar hepatic and portal vein supply with some variation in the number of intrahepatic branches. For all specimens, 3 surgically resectable areas were identified in the left lateral lobe and 2 surgically resectable areas were identified in the right medial lobe as defined by a functional anatomic model.

Conclusions

CT of detailed acrylic casts allowed complex intrahepatic vascular relationships to be investigated and compared with previous studies. Improving understanding of the intrahepatic vascular supply facilitates interpretation of advanced images in clinical patients, the planning and performance of surgical procedures, and may facilitate interventional vascular procedures, such as intravenous embolization of portosystemic shunts. Functional division of the canine liver similar to human models is possible. The left lateral and right medial lobes can be consistently divided into surgically resectable functional areas and partial lobectomies can be performed following a functional model; further study in clinically affected animals would be required to investigate the relevance of this functional model in the dog.
Catheter Ablation of Asymptomatic Longstanding Persistent Atrial Fibrillation: Impact on Quality of Life, Exercise Performance, Arrhythmia Perception, and Arrhythmia‐Free Survival
Authors: MOHANTY SANGHAMITRA , SANTANGELI PASQUALE , MOHANTY PRASANT , BIASE LUIGI DI , HOLCOMB SHAWNA , TRIVEDI CHINTAN , BAI RONG , BURKHARDT DAVID , HONGO RICHARD , HAO STEVEN , BEHEIRY SALWA , SANTORO FRANCESCO , FORLEO GIOVANNI , GALLINGHOUSE JOSEPH G. , HORTON RODNEY , SANCHEZ JAVIER E. , BAILEY SHANE , HRANITZKY PATRICK M. , ZAGRODZKY JASON , NATALE ANDREA
Published: June 2014

Ablation Outcome in Silent Longstanding Persistent AF

Background

Impact of catheter ablation on exercise performance, quality of life (QoL) and symptom perception in asymptomatic longstanding persistent AF (LSP‐AF) patients has not been reported yet.

Methods and Results

Sixty‐one consecutive patients (mean age 62 ±13 years, 71% males) with asymptomatic LSP‐AF undergoing first catheter ablation were enrolled. Extended pulmonary vein antrum isolation plus ablation of complex fractionated atrial electrograms and nonpulmonary vein triggers was performed in all. QoL survey was taken at baseline and 12‐months postablation, using Short Form‐36 (SF‐36). Information on arrhythmia perception was obtained using a standard questionnaire and corroborating symptoms with documented evidence of arrhythmia. Exercise tests were performed on 38 patients at baseline and 5 months after procedure. Recurrence was assessed using event recorder, cardiology evaluation, electrocardiogram, and 7‐day holter monitoring. After 20 ± 5 months follow‐up, 36 (57%) patients remained recurrence‐free off‐AAD. Of the 25 patients experiencing recurrence, 21 (84%) were symptomatic. Compared to baseline, follow‐up SF‐36 scores improved significantly in many measures. For patients with successful ablation, physical component summary (PCS) and mental component summary (MCS) demonstrated substantial improvement (MCS: 64.2 ± 22.3 to 70.1 ± 18.6 [P = 0.041]; PCS: 62.6 ± 18.4 to 70.0 ± 14.4 [P = 0.032]). Postablation exercise study in recurrence‐free patients showed significant reduction in resting and peak heart rate (75 ± 11 vs. 90 ± 17 and 132 ± 20 vs. 154.5 ± 36, respectively, P < 0.001), increase in peak oxygen pulse (13.4 ± 3 vs. 18.9 ± 16 mL/beat, Δ5.5 ± 15, P = 0.001), peak VO2/kg (19.7 ± 5 to 23.4 ± 13 mL/kg/min [Δ 3.7 ± 10, P = 0.043]), and corresponding MET (5.6 ± 1 to 6.7 ± 4 [Δ1.1 ± 3, P = 0.03]). No improvement was observed in patients with failed procedures.

Conclusion

Successful ablation improves exercise performance and QoL in asymptomatic LSP‐AF patients.