bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of single‐nucleotide polymorphism rs4236601 near caveolin 1 and 2 with primary open‐angle glaucoma: a meta‐analysis
Authors: Huang Wenbin , Wang Wei , Zhou Minwen , Zhang Xiulan
Published: September 2013

Background

To clarify the effects of a single‐nucleotide polymorphism, rs4236601[A] near caveolin 1 and 2, on primary open‐angle glaucoma (POAG) risk.

Design

Meta‐analysis.

Participants

A total of 5774 patients and 40 598 controls from previously reported case–control studies were included.

Methods

A comprehensive literature search was performed for studies published up to April 2013. Summary odds ratios (ORs) and 95% confidence intervals (CI) were calculated, employing random‐ or fixed‐effects models according to between‐study heterogeneity. Publication bias of the literature articles was evaluated using funnel plots and Egger's test.

Main Outcome Measures

OR for the effects of rs4236601[A] on POAG risk.

Results

Five eligible studies were included in this meta‐analysis. Overall, the association between rs4236601[A] and risk for POAG was statistically significant (OR = 1.23, 95% CI 1.12–1.34; P < 0.001). Stratified analyses showed that the association between rs4236601[A] and POAG risk was statistically significant in Caucasians (OR = 1.25, 95% CI 1.18–1.33; P < 0.001) and Asians (OR = 3.33, 95% CI 1.56–7.08; P = 0.003) but not in Africans. Increased risks were found in age‐ and sex‐matched studies (OR = 1.26, 95% CI 1.14–1.40; P < 0.001), but no statistically significant risk was found in unmatched studies.

Conclusions

This meta‐analysis suggests that rs4236601[A] is associated with increased risk for POAG in Caucasian and Asian populations. However, well‐designed gene–environment interaction studies and studies including more ethnic groups are required in further investigations.
Risk of having BRCA1 mutation in high‐risk women with triple‐negative breast cancer: a meta‐analysis
Authors: Tun NM , Villani G , Ong K , Yoe L , Bo ZM
Published: September 2013

Testing for BRCA1 mutation has important clinical implications such as identifying risk of second primary cancers and risk of cancer in the family. This study seeks to quantify the risk of having BRCA1 mutation in female breast cancer patients with triple‐negative phenotype compared with those with other phenotypes. We undertook a search of MEDLINE and EMBASE databases for relevant studies through 10 May 2013. Outcomes were calculated and reported as risk ratio and risk difference. 12 studies comprising 2533 breast cancer patients were included in the analysis. It was found that almost all eligible studies were performed on high‐risk population with breast cancer. By analyzing the incidence rates of BRCA1 mutation in patients with triple‐negative breast cancer (TNBC) and non‐TNBC, our meta‐analysis provides a relative risk of 5.65 [95% confidence interval (CI), 4.15–7.69] and risk difference of 0.22 (95% CI, 0.15–0.29). This implies that, in selected population with high‐risk features, women with TNBC are approximately five and a half times more likely to have BRCA1 mutation compared with non‐TNBC phenotype, and approximately two in nine women with TNBC harbor BRCA1 mutation. Triple‐negative phenotype significantly increases the risk of having BRCA1 mutation in high‐risk breast cancer patients compared with non‐TNBC.
Spatially Explicit Power Analyses for Occupancy‐Based Monitoring of Wolverine in the U.S. Rocky Mountains
Authors: ELLIS MARTHA M. , IVAN JACOB S. , SCHWARTZ MICHAEL K.
Published: September 2013

Conservation scientists and resource managers often have to design monitoring programs for species that are rare or patchily distributed across large landscapes. Such programs are frequently expensive and seldom can be conducted by one entity. It is essential that a prospective power analysis be undertaken to ensure stated monitoring goals are feasible. We developed a spatially based simulation program that accounts for natural history, habitat use, and sampling scheme to investigate the power of monitoring protocols to detect trends in population abundance over time with occupancy‐based methods. We analyzed monitoring schemes with different sampling efforts for wolverine (Gulo gulo) populations in 2 areas of the U.S. Rocky Mountains. The relation between occupancy and abundance was nonlinear and depended on landscape, population size, and movement parameters. With current estimates for population size and detection probability in the northern U.S. Rockies, most sampling schemes were only able to detect large declines in abundance in the simulations (i.e., 50% decline over 10 years). For small populations reestablishing in the Southern Rockies, occupancy‐based methods had enough power to detect population trends only when populations were increasing dramatically (e.g., doubling or tripling in 10 years), regardless of sampling effort. In general, increasing the number of cells sampled or the per‐visit detection probability had a much greater effect on power than the number of visits conducted during a survey. Although our results are specific to wolverines, this approach could easily be adapted to other territorial species.

Poder de Análisis Espacialmente Explícito para el Monitoreo Basado en Ocupación del Glotón (Gulo gulo) en las Montañas Rocallosas de Estados Unidos
The Bethesda system for reporting thyroid cytopathology: an institutional experience of the outcome of indeterminate categories
Authors: Önder S. , Firat P. , Ates D.
Published: September 2013

Objective

In this study, we investigated the efficacy of the Bethesda system (TBS) for reporting thyroid cytopathology in determining the risk of malignancy for indeterminate cases. These cases comprised atypia or follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasia or suspicious for follicular neoplasia (FN/SFN) and suspicious for malignancy (SM) categories. AUS/FLUS cases were further subcategorized according to their patterns, and the malignancy rate for each subcategory was calculated.

Methods

A total of 6310 thyroid fine needle aspiration (FNA) cases were analysed and 655 indeterminate cases were enrolled in the study. AUS/FLUS cases were further subcategorized into four patterns as follows: papillary thyroid carcinoma (PTC) pattern, microfollicle pattern, atypical cell pattern and Hürthle cell pattern.

Results

Malignancy rates for AUS/FLUS, FN/SFN and SM were 18.9%, 45.7% and 71%, respectively. Malignancy rates for AUS/FLUS subcategories were as follows: PTC pattern, 28%; microfollicle pattern, 6.9%; atypical cell pattern, 22.2%; and Hürthle cell pattern, 0%.

Conclusion

The Bethesda system categorizes thyroid FNAs with increasing risk of malignancy as advocated. However, our findings suggest that the risk of malignancy for AUS/FLUS might be higher than estimated. Particularly, AUS/FLUS cases with focal features suggestive of PTC seem to be associated with a much higher risk of malignancy than other patterns.
Practice considerations for the introduction and use of power mobility for children
Authors: Livingstone Roslyn , Paleg Ginny
Published: September 2013

Aim

The aim of the study was to support clinicians in recommending and justifying power mobility for children of different ages and abilities, and with different needs. The study comprised three distinct parts: a literature review; a Delphi consensus; and clinical practice considerations.

Method

A scoping review of eight electronic databases and manual searches carried out in February 2011 identified 15 themes or transferable messages among 27 articles meeting initial inclusion criteria and these formed the basis of a draft paper. Informal consensus at two international conference presentations refined and modified the paper to include 10 messages supported by 24 articles. The literature review was updated in May 2012 and a modified Delphi process sought to formalize the consensus process with an international panel of 16 expert clinicians and researchers using a priori criteria of 80% agreement.

Results

Evidence from studies was classified using the American Academy of Cerebral Palsy and Developmental Medicine guidelines, with evidence from most studies being classified as either level IV or level V, apart from one study each with evidence classified as level II and level III. Expert consensus on the content and wording of nine transferable messages may raise evidence overall to level III.

Interpretation

This paper suggests that power mobility may reasonably be considered as an effective and appropriate intervention for children lacking efficient, independent mobility from around 12 months of age including children who may never become competent drivers and children lacking independent mobility only in early childhood.
Impact of hypertension and renin–angiotensin system inhibitors in aortic stenosis
Authors: Capoulade Romain , Clavel Marie‐Annick , Mathieu Patrick , Côté Nancy , Dumesnil Jean G. , Arsenault Marie , Bédard Élisabeth , Pibarot Philippe
Published: September 2013

Background

Experimental studies revealed that renin–angiotensin system (RAS) could play a crucial role in the pathophysiology of aortic stenosis (AS). The objectives of this study were to examine (i) the impact of hypertension on AS progression and clinical events and (ii) the effect of angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin‐receptor blockers (ARBs).

Materials and methods

In this observational study, we retrospectively analysed clinical and Doppler echocardiographic data prospectively collected in 338 patients with AS. Patients were separated into four groups: patients without hypertension and not treated by RAS medication (Ctrl group), patients with hypertension but not treated by RAS medication (HTN group), patients treated with ACEIs, and patients treated with ARBs. AS progression rate was assessed by the annualized increase in peak aortic jet velocity.

Results

Compared with Ctrl group, patients in HTN group had faster stenosis progression (P = 0·01). Patients on ARBs had slower AS progression compared with Ctrl (trend P = 0·10) and HTN (P = 0·002) groups, whereas patients on ACEIs had similar progression rate compared with Ctrl group (P = NS) but lower compared with HTN group (P = 0·02). On multivariable analysis, compared with Ctrl group, HTN group was associated with faster AS progression rate (P = 0·002), whereas ARBs with slower progression (P = 0·0008). During a mean follow‐up of 6·2 ± 2·4 years, HTN (hazard ratio [HR] = 2·45; P = 0·006) and ACEI (HR = 2·30; P = 0·01) groups were associated with a significant increase in all‐cause mortality compared with Ctrl group, whereas ARB group (HR: 0·89; P = 0·80) not. In multivariable analysis, HTN and ACEI groups remained associated with increased mortality.

Conclusions

Hypertension is associated with significantly faster stenosis progression and higher incidence of clinical events in patients with AS. ARBs but not ACEs were found to abolish the increased risk of mortality associated with hypertension.
Familial mediterranean fever: a fascinating model of inherited autoinflammatory disorder
Authors: Portincasa Piero , Scaccianoce Giuseppe , Palasciano Giuseppe
Published: September 2013

Background

Familial Mediterranean fever (FMF) is a rare inherited autosomal recessive autoinflammatory disorder characterized by recurrent and self‐limited episodes of fever and painful serositis, lasting 1–3 days. FMF occurs almost exclusively among ethnic groups of the Mediterranean basin, although cases have also been found in Japan and Korean populations. Diagnosis is based on clinical features, response to colchicine and genetic analysis. Novel drugs are emerging, allowing better management of colchicine‐resistant/colchicine‐intolerant patients. This review aims to attract the attention of the readers on differential diagnosis and management of patients with FMF.

Methods

The current state‐of‐the‐art on FMF is outlined, with respect to epidemiological, genetic, pathophysiological and therapeutic characteristics, based on critical analysis of solid scientific literature.

Results

FMF is more frequent than it was thought before. The phenotypic expression of M694V is more severe than that of V726A. Patients with M694V/M694V homozygosity are exposed to a higher risk of developing renal amyloidosis, arthritis, dermatologic and oral lesions, higher fever and more frequent painful attacks. Life‐long therapy with colchicine (1·0–2·4 mg/day) is effective and safe to prevent recurrent attacks and renal amyloidosis and to reverse proteinuria. In nonresponder patients, alternative novel approaches include interleukin‐1 receptor antagonist anakinra and the interleukin‐1 decoy receptor rilonacept.

Conclusions

The prognosis of FMF is normal if AA amyloidosis is prevented. Colchicine remains the first‐line therapy to treat pain and prevent amyloidosis. A follow‐up should include clinical evaluation, therapeutic adjustments, measurement of serum amyloid A and proteinuria.
A list of highly influential biomedical researchers, 1996–2011
Authors: Boyack Kevin W. , Klavans Richard , Sorensen Aaron A. , Ioannidis John P.A.
Published: September 2013

We have generated a list of highly influential biomedical researchers based on Scopus citation data from the period 1996‐2011. Of the 15,153,100 author identifiers in Scopus, approximately 1% (n=149,655) have an h‐index >=20. Of those, we selected 532 authors who belonged to the 400 with highest total citation count (>=25,142 citations) and/or the 400 with highest h‐index (>=76). Of those, we selected the top‐400 living core biomedical researchers based on a normalized score combining total citations and h‐index. Another 62 authors whose focus is outside biomedicine had a normalized score that was at least as high as the score of the 400th core biomedical researcher. We provide information on the profile of these most influential authors, including the most common Medical Subject Heading terms in their articles that are also specific to their work, most common journals where they publish, number of papers with over 100 citations that they have published as first/single, last, or middle authors, and impact score adjusted for authorship positions, given that crude citation indices and authorship positions are almost totally orthogonal. We also show for each researcher the distribution of their papers across 4 main levels (basic‐to‐applied) of research. We discuss technical issues, limitations and caveats, comparisons against other lists of highly‐cited researchers, and potential uses of this resource.
Comprehensive management of a complex traumatic dental injury
Authors: Cotti Elisabetta , Esposito Stefano , Jacobs Reinhilde , Slagmolen Pieter , Bakland Leif K.
Published: September 2013

A 24‐year‐old female patient presented with complaint of palatal swelling and a sinus tract facial to tooth #22. She reported an injury to the tooth 15 years earlier and no recollection of treatment, although there was evidence of an endodontic access into the crown. Radiographically the root appeared to have stopped developing, and it was associated with a large periapical lesion. After 3 unsuccessful attempts at apexification using calcium hydroxide (CH), further examination including use of cone‐beam computed tomography (CBCT) was carried out. The latter allowed for better evaluating the situation and for better planning a more comprehensive treatment plan to include surgical removal of the apical lesion. The large radiolucent area extended from tooth #21 to #23. Using a dedicated software tool developed to be used in conjunction with CBCT, volumetric assessment of the lesion was carried out for healing follow up. The root end was filled from the apical direction with newly developed accelerated silicate cement 4–5 mm into the apical part of the canal. Subsequently, the rest of the canal was filled with the same type of cement. At the 1‐year postsurgical follow up, the tooth remained asymptomatic, and using the CBCT volumetric program, bony healing could be demonstrated.
Association between adolescents' self‐perceived oral health and self‐reported experiences of abuse
Authors: Kvist Therese , Annerbäck Eva‐Maria , Sahlqvist Lotta , Flodmark Olof , Dahllöf Göran
Published: September 2013

This study investigated the association between self‐perceived oral health and self‐reported exposure to different types of child abuse. It was hypothesized that self‐perceived oral health is compromised in exposed adolescents. All Grade‐9 compulsory school and second‐year high‐school pupils in Södermanland County, Sweden (n = 7,262) were invited to take part in a population‐based survey; 5,940 adolescents responded. Survey items on health and social wellbeing included self‐perceived oral health and exposure to abuse. The results showed that poor self‐perceived oral health was associated with self‐reported experience of physical abuse, intimate partner violence, forced sex, and bullying (adjusted OR = 2.3–14.7). The likelihood of reporting poor oral health increased from an adjusted OR of 2.1 for a single incident of abuse to an adjusted OR of 23.3 for multiple abuses. In conclusion, poor self‐perceived oral health and previous exposure to child physical abuse, intimate partner violence, bullying, and forced sex is associated. It is important that dental professionals recognize adolescents with poor subjective oral health and take into consideration child abuse as a possible cause in order to prevent these adolescents from further victimization. These results further strengthen that dental professionals are an important resource in child protection.
Historical vignette: Medical treatment of status epilepticus
Authors: Janz Dieter
Published: September 2013

The treatment of status epilepticus has changed over the past five decades since the first colloquium on status epilepticus, held in Marseille in 1962. New intravenous drugs, such as valproate, levetiracetam, lacosomide or ketamine and new routes of administration, such as intranasal or bucal, as well as high‐class randomized clinical trials in the prehospital setting and early stages of status have changed the field. However it is remarkable, how the basic principles and difficulties of treatment of status epilepticus have remained the same. This article is as a translation of a narrative review authored by Dieter Janz at the Marseille Colloquium 1962, published in 1967. The medical practice and all available treatment at that time have been reviewed critically in the article. The translation of the original French article has been kept as close as possible to the original, to give a detailed account on the treatment of status at that time.
The London‐Innsbruck Status Epilepticus Colloquia 2007–2011, and the main advances in the topic of status epilepticus over this period
Authors: Shorvon Simon , Trinka Eugen
Published: September 2013

In this article, the three previous London‐Innsbruck Colloquia on Status Epilepticus are reviewed. The background to the colloquia and the range of topics covered in each colloquium are outlined. The areas in which advances in the study of status epilepticus, and also areas in which advances have been disappointing are highlighted.
A role for inflammation in status epilepticus is revealed by a review of current therapeutic approaches
Authors: Janigro Damir , Iffland II Philip H. , Marchi Nicola , Granata Tiziana
Published: September 2013

A significant number of patients with epilepsy fail to respond to currently available antiepileptic drugs. This suggests a need for alternative approaches to reduce the occurrence of seizures in these patients. Recent data have shown that in addition to well‐known neuronal mechanism, seizures may be a consequence of misguided inflammatory response and blood–brain barrier disruption. Both peripheral and brain proinflammatory events have been demonstrated to govern the onset of status epilepticus. Evidence deriving from the experimental and clinical realms supports the notion that a role for proinflammatory and cerebrovascular events in seizure disorders is broader than previously suspected. As a result, methods to pharmacologically reduce blood–brain barrier permeability and reduce inflammation have emerged as means to reduce seizure burden. For instance, corticosteroids have been shown to be beneficial and the same agents may be able to further reduce seizure burden in conjunction with currently prescribed antiepileptic drugs.
Intrinsic epileptogenicity of dysplastic cortex: Converging data from experimental models and human patients
Authors: Battaglia Giorgio , Colciaghi Francesca , Finardi Adele , Nobili Paola
Published: September 2013

Focal cortical dysplasia (FCD) is a brain malformation associated with particularly severe drug‐resistant epilepsy that often requires surgery for seizure control. The molecular basis for such enhanced propensity to seizure generation in FCD is not as yet elucidated. To investigate cellular and molecular bases of epileptogenic mechanisms and possible effect of severe epilepsy on the malformed cortex we have here performed a parallel analysis of a rat model of acquired cortical dysplasia previously established in our laboratory, i.e., the methylazoxymethanol/pilocarpine (MAM‐PILO) rats, and surgical samples from patients with type IIB FCD.

Data from the MAM‐PILO rat model and human FCD samples reveal in both conditions: (1) that status epilepticus (SE) and/or seizures can further modify the cellular and molecular settings of the malformed cortex; (2) excitation/inhibition imbalance, and dysregulation of the N‐methyl‐d‐aspartate/ membrane‐associated guanylate kinase (NMDA/MAGUK) expression; (3) activation of cell death in neurons and glia. The data therefore highlight the mechanistic relevance of glutamate/NMDA hyperactivation in FCD epileptogenesis and suggest that epilepsy is a pathologic process capable of affecting structure and function of both neurons and glia.
Neurogenesis and neuronal regeneration in status epilepticus
Authors: Rotheneichner Peter , Marschallinger Julia , Couillard‐Despres Sebastien , Aigner Ludwig
Published: September 2013

Neurogenesis in the adult central nervous system has been well documented in several mammals including humans. By now, a plethora of data has been generated with the aim of understanding the molecular and cellular events governing neurogenesis. This growing comprehension will provide the basis for modulation of neurogenesis for therapeutic purposes, in particular in neurodegenerative diseases. Herein, we review the current knowledge on neurogenesis, in particular in the frame of epilepsy, since seizures have massive effects on neurogenesis. Conversely, some studies have suggested that aberrant neurogenesis might contribute to the development or manifestation of epilepsy and, moreover, chronic inhibition of neurogenesis in epilepsy might contribute to comorbidities of epilepsy such as cognitive deficits. Therefore, a better understanding of neurogenesis in the context of epilepsy is still required for future therapeutic purposes.
Autoimmunity, seizures, and status epilepticus
Authors: Davis Rebecca , Dalmau Josep
Published: September 2013

The recent discovery of a category of autoimmune encephalitis associated with antibodies against neuronal cell‐surface and synaptic proteins has renewed interest for autoimmune causes of epilepsy. The identification of autoimmune encephalitis has changed paradigms in the diagnosis and management of several novel and treatable syndromes that occur with seizures and status epilepticus previously attributed to viral or idiopathic etiologies. This review focuses on the novel group of autoimmune encephalitis and also discusses some classical paraneoplastic syndromes that constitute another group of autoimmune disorders that may result in seizures.
The multifaceted care of status epilepticus
Authors: Wijdicks Eelco F. M.
Published: September 2013

After seizures have been controlled, long‐term care of status epilepticus may be needed and collectively involves every major organ. First, as a result of rapid escalation of antiepileptic drugs, there are initial concerns with hypotension, acid‐base abnormalities, and cardiac arrhythmias. Second, refractory status epilepticus and the continuous need for intravenous administration of anesthetic drugs will lead to a multitude of systemic complications that require long‐term complex care. Most anticipated problems are infectious complications with a high risk of pneumonia and sepsis, but thromboembolism due to immobilization and catheter placement are also common. If a good outcome is possible or anticipated in a patient with refractory status epilepticus, physicians should plan for a surveillance and treatment protocol to adequately support these patients.
What can we learn from status epilepticus registries?
Authors: Ferlisi Monica , Hocker Sara
Published: September 2013

There is a remarkable dearth of information about the various therapies used, often widely so, to control refractory or super‐refractory status epilepticus despite its high mortality and morbidity. As pointed out by recent literature reviews, there are no controlled studies, and information is based almost entirely on open, often small and retrospective, case series or case reports. Randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available. For this reason, we proposed an international case registry of therapies used in refractory and super‐refractory cases and their outcome. Clinicians from different countries will be asked to complete an online questionnaire when they treat a patient with refractory or super‐refractory status epilepticus. Information gathered from this database will summarize the spectrum of etiologies, treatments, and outcomes of this challenging condition and may even form the bases for treatment guidelines or future targeted treatment trials.
Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) Study
Authors: Husain Aatif M.
Published: September 2013

Nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) are electrographic seizures (ESz) that are not associated with overt clinical seizure activity. NCS are distinct ESz, whereas NCSE has ongoing, continuous electrographic seizure activity. Both are common in critically ill patients admitted to hospital intensive care units (ICUs), and studies have shown that about 20% of ICU patients undergoing continuous electroencephalography (cEEG) monitoring will have NCS/NCSE. Although the treatment for convulsive SE is well established, there is no clear consensus for the treatment of NCS/NCSE. Antiepileptic drugs (AEDs), such as phenytoin (PHT) and fosphenytoin (fPHT), used in convulsive SE are also used to treat NCS/NCSE despite lack of data for their appropriateness for these conditions. Recent studies have shown that very aggressive treatment of NCSss/NCSE can lead to worse outcomes because the AEDs used can have significant adverse effects. Recently, several intravenous (IV) AEDs have become available for substitution therapy when their oral use is not possible. There are retrospective case reports and case series that suggest that these AEDs may be beneficial for treatment of NCS/NCSE. The Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) Study will compare the efficacy and tolerability of fPHT and lacosamide in patients having NCS as noted by cEEG monitoring. The study is currently open to recruitment and has 13 sites in the United States. A total of 200 subjects will be randomized, 100 to each treatment arm.
The Established Status Epilepticus Trial 2013
Authors: Bleck Thomas , Cock Hannah , Chamberlain James , Cloyd James , Connor Jason , Elm Jordan , Fountain Nathan , Jones Elizabeth , Lowenstein Daniel , Shinnar Shlomo , Silbergleit Robert , Treiman David , Trinka Eugen , Kapur Jaideep
Published: September 2013

Benzodiazepine‐refractory status epilepticus (established status epilepticus, ESE) is a relatively common emergency condition with several widely used treatments. There are no controlled, randomized, blinded clinical trials to compare the efficacy and tolerability of currently available treatments for ESE. The ESE treatment trial is designed to determine the most effective and/or the least effective treatment of ESE among patients older than 2 years by comparing three arms: fosphenytoin (fPHT) levetiracetam (LVT), and valproic acid (VPA). This is a multicenter, randomized, double‐blind, Bayesian adaptive, phase III comparative effectiveness trial. Up to 795 patients will be randomized initially 1:1:1, and response‐adaptive randomization will occur after 300 patients have been recruited. Randomization will be stratified by three age groups, 2–18, 19–65, and 66 and older. The primary outcome measure is cessation of clinical seizure activity and improving mental status, without serious adverse effects or further intervention at 60 min after administration of study drug. Each subject will be followed until discharge or 30 days from enrollment. This trial will include interim analyses for early success and futility. This trial will be considered a success if the probability that a treatment is the most effective is >0.975 or the probability that a treatment is the least effective is >0.975 for any treatment. Proposed total sample size is 795, which provides 90% power to identify the most effective and/or the least effective treatment when one treatment arm has a true response rate of 65% and the true response rate is 50% in the other two arms.
Stiripentol in refractory status epilepticus
Authors: Grosenbaugh Denise K. , Mott David D.
Published: September 2013

Benzodiazepines (BZDs), which enhance γ‐aminobutyric acid (GABAA) receptor–mediated inhibition, are the first‐line therapy for treatment of status epilepticus (SE). However, pharmacoresistance to BZDs develops rapidly after SE initiation. This is due to an activity‐dependent internalization of BZD‐sensitive GABAA receptors during SE. Stiripentol (STP) is a positive allosteric modulator of GABAA receptors with a unique subunit selectivity profile. We report that in a rodent model of SE, STP terminates behavioral seizures and remains effective in established SE when seizures have become BZD resistant. The anticonvulsant effects of STP are age dependent, with greater potency in juvenile animals. Whole cell recordings from dentate granule cells in hippocampal slices reveal that STP potentiates GABAergic inhibitory postsynaptic currents (IPSCs) and tonic GABAergic currents by acting at a site on the GABAA receptor that is separate from the benzodiazepine binding site. This potentiation persists in established SE, whereas potentiation of GABAergic inhibition by BZDs is lost. STP potentiates IPSCs in juvenile animals with greater potency than in adult animals. We suggest that STP, either alone or as add‐on therapy, may prove useful in treating established and BZD‐resistant status epilepticus. Furthermore, STP may be particularly effective in terminating SE in children when SE is most prevalent.
Indirect Information Transfer: Three‐Spined Sticklebacks Use Visual Alarm Cues From Frightened Conspecifics About an Unseen Predator
Authors: Hogan Kelly E. , Laskowski Kate L.
Published: September 2013

Animals can attempt to reduce uncertainty about their environment by gathering information personally or by observing others' interactions with the environment. There are several sensory modalities that can be used to transmit social information from chemical to visual to audible cues. When predation risk is variable, visual cues of conspecific behavior might be especially telling about the presence of a potential threat; however, most studies couple visual and chemical cues together. Here, we tested whether visual behavioral cues from frightened conspecifics were sufficient to indirectly transfer information about the presence of an unseen predator in three‐spined sticklebacks. Our results demonstrate that visual behavioral cues from conspecifics about the presence of a predator are sufficient to induce an antipredator response. This suggests that information transfer can occur rapidly in the absence of chemical cues and that some individuals weigh social information more heavily than others.
Risk of being undernourished in a cohort of community‐dwelling 85‐year‐olds: The Octabaix study
Authors: Farre Teresa Badia , Formiga Francesc , Ferrer Assumpta , Plana‐Ripoll Oleguer , Almeda Jesus , Pujol Ramon
Published: September 2013

Objectives

To describe the prevalence of the risk of being undernourished in a community‐dwelling population of 85‐year‐olds, and to study associated factors.

Methods

A cross‐sectional community‐based survey of 328 inhabitants assigned to seven primary healthcare teams was carried out. Geriatric assessment was based on sociodemographic variables, the Barthel Index (BI), the Lawton Index (LI), the Spanish version of the Mini‐Mental State Examination, the Charlson Comorbidity Index, chronic diseases, social risk measured by Gijon's Social‐Familial Evaluation Scale, prescriptions and blood tests. Nutritional status was assessed using the Mini Nutritional Assessment (MNA). Participants were defined as being at risk of undernourishment when they had a MNA score above or equal to 23.5. A comparative analysis was carried out between patients with and without risk of being undernourished, and a multiple logistic regression analysis was carried out.

Results

The prevalence risk of being undernourished was 34.5%. A statistically significant association was found with being female (OR 2.44, 95% CI 1.28–4.54), LI (OR 1.47, 95% CI 1.29–1.66), social risk (OR 1.15, 95% CI 1.02–1.29) and prescription drugs taken (OR 5.58, 95% CI 2.09–14.92). Cardiovascular prescription showed a protective association (OR 4.34, 95% CI 1.78–10.0). No statistical differences between the risks of being undernourished were found in the laboratory analysis.

Conclusions

There is a high risk of being undernourished in 85‐year‐old subjects. This nutritional status was positively associated with being female, disability, increased social risk and a high number of prescription drugs, whereas there was a protective relationship with cardiovascular prescription. In evaluations of nutritional status in the community, a multidisciplinary assessment is more valid than analytical findings. Geriatr Gerontol Int 2014; 14: 702–709.
Efficacy and long‐term outcomes of radiofrequency ablation in the elderly with hepatocellular carcinoma
Authors: Yamazaki Hajime , Tsuji Kunihiko , Nagai Kazumasa , Tomonari Akiko , Matsui Takeshi , Kang Jong‐Hon , Kodama Yoshihisa , Sakurai Yasuo , Maguchi Hiroyuki
Published: September 2013

Aim

The use of radiofrequency ablation (RFA) in elderly patients is increasing in those with hepatocellular carcinoma (HCC). This study compares the elderly (≥75 years old) to non‐elderly patients (<75 years old) in the outcomes of the efficacy and safety of RFA.

Methods

Three hundred and thirty‐five patients, 103 elderly and 232 non‐elderly, with naive HCC who were treated with RFA from 1999 to 2012 were enrolled. Patient characteristics, complications, length of hospital stay, overall survival (OS), median survival time (MST), recurrence‐free survival (RFS) and factors related to OS were analyzed.

Results

Median age was 79 years (range, 75–88) in the elderly group and 65 years (38–74) in the non‐elderly group. The proportion of women (45.6% and 28.0%), hepatitis C virus infection (63.1% and 50.4%) and comorbidities (78.6% and 44.0%) in the elderly group compared to the non‐elderly group, respectively, was significantly higher. No difference existed in the complications and length of hospital stay. The 5‐year OS rates and MST were 67.3% and 90.5 months in the elderly group and 60.9% and 86.4 months in the non‐elderly group, respectively (P = 0.486). The median RFS time was 20 months in the elderly group and 18.7 months in the non‐elderly group (P = 0.429). In multivariate analysis, the Child–Pugh grade and tumor–node–metastasis stage were significantly associated with OS (P < 0.001, =0.003); age was not (P = 0.355).

Conclusion

RFA in elderly patients is as effective and safe as in non‐elderly patients for the treatment of HCC.
Factors associated with self‐reported use of mouthwashes in southern Brazil in 1996 and 2009
Authors: Montenegro MM , Flores MF , Colussi PRG , Oppermann RV , Haas AN , Rösing CK
Published: September 2013

Objective

To evaluate the association between sociodemographic factors and self‐reported use of mouthwashes in a city in the south of Brazil over a time span of 13 years.

Methods

The study involves a comparison of two household surveys conducted in 1996 and 2009. Respectively, 850 and 982 households were included in each year. The mother of the family answered to a structured questionnaire to provide sociodemographic data. Self‐reported use of mouthwash was evaluated in a binary manner (yes/no). Multivariate Poisson regression models were used to estimate proportion ratios (PR) and 95% confidence intervals (95% CI).

Results

The proportion of mouthwash use increased significantly from 10.8% to 24.2% after 13 years. The probability of using mouthwashes increased more than two times from 1996 to 2009 (PR = 2.25 95% CI 1.80–2.82). Higher probabilities for using mouthwashes were observed in households with higher income (PR = 2.63 95% CI 1.97–3.51) and in those households where the mothers had higher educational levels (PR = 1.46 95% CI 1.05–2.03).

Conclusion

Higher family income and higher maternal educational level were associated with self‐reported use of mouthwashes in a higher proportion of households.
Reduction in dental plaque in patients with mental disorders through the dental hygiene care programme
Authors: Mun S‐J , Chung W‐G , Min S‐H , Park J‐K , Kim C‐B , Kim N‐H , Seo H‐Y , Chang S‐J
Published: September 2013

Objective

To develop a dental hygiene care programme based on the specific needs of patients with mental disorders and to suggest practical guidelines to improve the oral health care of these patients.

Methods

A total of 73 patients with mental illness participated in the study. The patients were randomly classified into three groups and followed over 12 weeks at 4‐week intervals. A newly designed dental hygiene care programme using flash‐based video, brochures and a toothpick method was implemented by five dental hygienists. Plaque index, stimulated saliva, subjective oral dryness and dental caries activity were analysed as outcome variables.

Results

Results showed that the dental plaque index significantly decreased after each session (P < 0.0001) in all three groups, and significant differences were found between groups (P = 0.036). Patients’ oral dryness decreased significantly, but stimulated saliva and dental caries activity did not improve.

Conclusion

The results of this study suggest that the dental hygiene care programme, which made use of a short, 10‐min flash‐based video and brochures every 4 weeks, was effective in reducing the dental plaque index of patients with mental disorders.
Nanomodification of Glass Using fs Laser
Authors: Shimotsuma Yasuhiko , Miura Kiyotaka , Kazuyuki Hirao
Published: September 2013

We review the interaction of glass with intense ultrashort laser pulses revealing new phenomena and recent demonstrations of rewritable 5D optical memory and polarization imaging filter mediated by the self‐organization of nanostructure. Particularly, we experimentally verify linearly polarized intense ultrashort pulses can control the direction of local optical anisotropy in homogeneous medium based on the interference between photon and electron plasma. These so‐called “nanogratings” composed of the photoinduced oxygen defects emerge in the course of multiple laser pulses and are oriented perpendicularly to the laser polarization direction. The nanograting structures, which exhibit form birefringence, have evolved from residual birefringence along with lowering threshold for defect formation into self‐assembly of oxygen defects.
Enzymatic synthesis of medium‐ and long‐chain triacylglycerols–enriched structured lipid from Cinnamomum camphora seed oil and camellia oil by Lipozyme RM IM
Authors: Zhao Man‐Li , Hu Jiang‐Ning , Zhu Xue‐Mei , Li Hong‐Yan , Li Jing , Fan Ya‐Wei , Deng Ze‐Yuan
Published: September 2013

Medium‐ and long‐chain triacylglycerols (MLCTs)–enriched structured lipid (SL) was synthesised through enzymatic interesterification from Cinnamomum camphora seed oil (CCSO) and camellia oil (CO) using Lipozyme RM IM from Rhizomucor miehei as a biocatalyst. Effects of different reaction conditions including substrate molar ratio, reaction time and reaction temperature were investigated. Results showed that 55.81% of total MLCT species (CCO/LaCL, LaCO/LCL, COO/OCO and LaOO/OLaO) was obtained in the interesterified product under the optimal conditions of substrate molar ratio of 1:1.5 (CCSO/CO) at 60 °C for 3 h. Thereafter, fatty acid profiles, tocopherol contents and physiochemical characteristics of the interesterified product and physical blend were comparatively investigated. The fatty acid composition of the interesterified product consisted of capric acid (26.33%), lauric acid (21.29%) and oleic acid (42.33%). It should be mentioned that the interesterified product contained predominantly oleic acid (88.69%) at Sn‐2 position, while MCFAs (68.05%) at Sn‐1,3 positions. Compared with physical blend, the reduction in tocopherol contents and changes of physiochemical characteristics occurred in SL. The smoke point of the interesterified product was much higher than that of the physical blend, which meant that such MLCTs‐enriched SL could be better for cooking purpose.
Improvement in emulsifying properties of soy protein isolate by conjugation with maltodextrin using high‐temperature, short‐time dry‐heating Maillard reaction
Authors: Zhang Jinbo , Wu Nana , Lan Ting , Yang Xiaoquan
Published: September 2013

Soy protein isolate (SPI)–maltodextrin (MD) conjugates were synthesised using Maillard reaction under high‐temperature (90, 115 and 140 °C), short‐time (2 h) dry‐heating conditions. The loss of free amino groups in proteins and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) profile confirmed that SPI‐MD conjugates were formed and higher dry‐heated temperatures could increase the glycosylation degree. The emulsifying properties of SPI and SPI‐MD conjugates were evaluated in oil‐in‐water emulsions. The emulsions stabilised with SPI‐MD conjugates synthesised at 140 °C exhibited higher emulsifying stability and excellent storage stability against pH, ionic strength and thermal treatment compared with those synthesised at 90 °C, 115 °C and SPI stabilised emulsions. This might be due to a greater proportion of conjugated MD in SPI‐MD conjugates synthesised at 140 °C because of the higher glycosylation degree, and more conjugated MD on the droplet surface could provide steric effect and enhance the stability of the droplets in the emulsions.
Role of Toll‐like receptor 2 (–196 to –174) polymorphism in susceptibility to pulmonary tuberculosis in Pakistani population
Authors: Khan Abrar‐ul‐Haq , Aslam M. A. , Hussain I. , Naz A. G. , Rana I. A. , Ahmad M. M. , Ali M. , Ahmad S.
Published: September 2013

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide. Pakistan ranks sixth on the list of 22 high‐burden tuberculosis countries in the world. The transitions from infection to clinical disease are very few signifying that host‐defence factors could lead to the development of active disease. Toll‐like receptor (TLR) 2 polymorphisms have been associated with regulation of TLR expression and development of active TB. In this study, blood samples of 187 subjects including 100 healthy and 87 TB positive were collected from three districts of Pakistan. DNA was extracted from blood and TLR 2 (–196 to –174del) polymorphism was analysed by polymerase chain reaction (PCR). The results suggest that the frequency of –196 to –174del/del polymorphism of TLR2 was significantly higher in TB‐positive patients compared with healthy. Results revealed that (–196 to –174del) polymorphism may increase the susceptibility to TB in healthy population of Pakistan. Moreover, males with heterozygous genotype (I/D) are more prone to TB than females with the same genotype. The occurrence of TB infection has been found positively associated with the age, suggesting that the population within the range of 21–45 years is more susceptible to Mycobacterium tuberculosis than other age groups studied. A significant association is also observed between smoking and the chances of developing TB, confirming that smoking strongly promotes its incidence.
Single‐nucleotide polymorphisms of IRF8 gene are associated with systemic lupus erythematosus in Chinese Han population
Authors: Li S.‐W. , He Y. , Zheng Z.‐H. , Liu D.‐W. , Liu Z.‐S.
Published: September 2013

Interferon regulatory factor 8 (IRF8) has been shown to have diverse roles in the regulation of the immune system. Two recent studies had revealed the association between the single‐nucleotide polymorphisms (SNPs; rs11644034 and rs2280381) of IRF8 and systemic lupus erythematosus (SLE) in a multiethnic population. The purpose of this study was to evaluate whether the association could be replicated in a Chinese Han population. Genotypes were determined by a multiplex polymerase chain reaction–ligase detection reaction (PCR–LDR) in 358 patients and 357 geographically matched healthy controls. Significant differences in genotype frequency were found between SLE and control individuals (rs11644034: AA vs. GG, P = 0.014, odds ratio (OR) = 0.980, 95% confidence internal (CI): 0.964–0.996; rs2280381: CC vs. TT, P = 0.005, OR = 0.150, 95% CI: 0.033–0.676). Conditional logistic regression analysis showed that the association of rs2280381 remained significant (P adjusted = 0.028) after adjustment for rs11644034, but not vice versa (P adjusted = 0.361).When stratifying patients with SLE according to clinical subtypes, SNP rs2280381 was found to be associated with low complement in patients with SLE. However, SNP rs11644034 was not found to be associated with SLE clinical subgroups. Analysis of the haplotypes revealed that haplotype G‐T and G‐C were also significantly associated with SLE (P = 0.002 and P = 0.012, respectively). Our study indicated that the IRF8 gene polymorphisms might be associated with susceptibility to SLE and with disease‐related clinical manifestations in Chinese Han population.
Interleukin‐1β triggers the differentiation of macrophages with enhanced capacity to present mycobacterial antigen to T cells
Authors: Schenk Mirjam , Fabri Mario , Krutzik Stephan R. , Lee Delphine J. , Vu David M. , Sieling Peter A. , Montoya Dennis , Liu Philip T. , Modlin Robert L.
Published: September 2013

The rapid differentiation of monocytes into macrophages (MΦ) and dendritic cells is a pivotal aspect of the innate immune response. Differentiation is triggered following recognition of microbial ligands that activate pattern recognition receptors or directly by pro‐inflammatory cytokines. We demonstrate that interleukin‐1β (IL‐1β) induces the rapid differentiation of monocytes into CD209+ MΦ, similar to activation via Toll‐like receptor 2/1, but with distinct phenotypic and functional characteristics. The IL‐1β induced MΦ express higher levels of key markers of phagocytosis, including the Fc‐receptors CD16 and CD64, as well as CD36, CD163 and CD206. In addition, IL‐1β‐induced MΦ exert potent phagocytic activity towards inert particles, oxidized low‐density lipoprotein and mycobacteria. Furthermore, IL‐1β‐induced MΦ express higher levels of HLA‐DR and effectively present mycobacterial antigens to T cells. Therefore, the ability of IL‐1β to induce monocyte differentiation into MΦ with both phagocytosis and antigen‐presenting function is a distinct part of the innate immune response in host defence against microbial infection.