bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of ethnicity on the performance of protein‐creatinine ratio in the prediction of significant proteinuria in pregnancies at risk of or with established hypertension: an implementation audit and cost implications
Authors: Bhatti Sadia , Cordina Mark , Penna Leonie , Sherwood Roy , Dew Tracy , Kametas Nikos A.
Published: January 2018

Introduction

The replacement of 24‐h urine collection by protein‐creatinine ratio (PCR) for the diagnosis of preeclampsia has been recently recommended. However, the literature is conflicting and there are concerns about the impact of demographic characteristics on the performance of PCR.

Material and methods

This was an implementation audit of the introduction of PCR in a London Tertiary obstetric unit. The performance of PCR in the prediction of proteinuria ≥300 mg/day was assessed in 476 women with suspected preeclampsia who completed a 24‐h urine collection and an untimed urine sample for PCR calculation. Multivariate logistic regression was used to assess the independent predictors of significant proteinuria.

Results

In a pregnant population, ethnicity and PCR are the main predictors of ≥300 mg proteinuria in a 24‐h urine collection. A PCR cut‐off of 30 mg/mmol would have incorrectly classified as non‐proteinuric, 41.4% and 22.9% of black and non‐black women, respectively. Sensitivity of 100% is achieved at cut‐offs of 8.67 and 20.56 mg/mmol for black and non‐black women, respectively. Applying these levels as a screening tool to inform the need to perform a 24‐h urine collection in 1000 women, would lead to a financial saving of €2911 in non‐black women and to an additional cost of €3269 in black women.

Conclusions

Our data suggest that a move from screening for proteinuria with a 24‐h urine collection to screening with urine PCR is not appropriate for black populations. However, the move may lead to cost‐saving if used in the white population with a PCR cut‐off of 20.5.
Choroidal thickness at age 66 years in the Danish high myopia study cohort 1948 compared with follow‐up data on visual acuity over 40 years: a clinical update adding spectral domain optical coherence tomography
Authors: Fledelius Hans C. , Jacobsen Nina , Li Xiao Q. , Goldschmidt Ernst
Published: January 2018

Background and purpose

A population‐based Copenhagen birth year 1948 cohort with high myopia recorded since age 14 years (spherical equivalent less than or equivalent to −6 D) has been followed over 50 years. Despite complications, current follow‐ups have outlined a better visual prognosis than usually drawn from selected clinical series in the literature. For the present status at age 66 years, focus was on visual ability and choroidal thickness.

Methods

Twenty‐eight of the original 39 participants were available in 2014. Medical history was updated. Best‐corrected visual acuity (BCVA) data were compared with subfoveal choroidal thickness (SFCT), now measured by enhanced depth optical coherence tomography.

Results

Due to at least better eye visual acuity (VA), all patients had maintained their everyday visual capacity. Only one participant was marginal regarding visual status for a driver's licence; low vision was not on record. Based on all eyes, choroidal thickness correlated negatively with axial length (AL), which also held for the fraction with high myopia (AL >26.5 mm). In high myopia, the mean choroidal subfoveal thickness was 114 ± 75 μm versus 182 ± 94 μm in lower myopia (p = 0.01).

Conclusion

Despite the generally maintained individual visual capacity in the series, significant correlation could be demonstrated between SFCT and (i) axial elongation and (ii) recorded VA, with a negative and a positive sign, respectively. Overall, the visual prognosis was relatively benign, in particular when compared with the selected high myopia hospital series that predominate in the ophthalmic literature.
Prevalence and risk factors for problematic Internet use among rural adolescents in Korea
Authors: Lee Ju‐Yeon , Kim Seon‐Young , Bae Kyung‐Yeol , Kim Jae‐Min , Shin Il‐Seon , Yoon Jin‐Sang , Kim Sung‐Wan
Published: January 2018

Introduction

The number of Internet users is increasing dramatically due to high‐speed Internet connections and the use of cellular Internet service among rural adolescents in Korea. This study examined the prevalence of problematic Internet use (PIU) and factors associated with PIU among rural adolescents in Korea.

Methods

In total, 1168 adolescents aged 13 to 18 years from a rural area in Korea participated in this cross‐sectional school survey. Problematic Internet use was categorized with Young's Internet Addiction Test using a validated cutoff. In addition, adolescents completed a self‐report questionnaire, including questions on sociodemographic factors, the Center for Epidemiological Studies Depression Scale, and the State Anxiety Inventory for Children. Parents completed the Korean version of the Strengths and Difficulties Questionnaire (SDQ‐P).

Results

Problematic Internet use was identified in 252 of 1168 (21.6%) students. Multivariate logistic analysis showed that male gender, academic stress, early exposure to the Internet, depression, and total difficulties on the SDQ‐P were significantly associated with PIU.

Conclusions

The findings indicate a need to develop preventive interventions for PIU among rural adolescents in Korea.
‘I know I'm not invincible’: An interpretative phenomenological analysis of thyroid cancer in young people
Authors: Smith Stephanie , Eatough Virginia , Smith James , Mihai Radu , Weaver Andrew , Sadler Gregory P.
Published: January 2018

Objective

Thyroid cancer is one of the most common cancers affecting young people and carries an excellent prognosis. Little is known about the psychosocial issues that face young people diagnosed with a treatable cancer. This study explored how young people experienced diagnosis, treatment, and how they made sense of an experience which challenged their views on what it means to have cancer.

Method

Semi‐structured interviews were conducted with eight young people diagnosed with either papillary or follicular thyroid cancer, and analysed with interpretative phenomenological analysis (IPA).

Results

Two inter‐related aspects of their experience are discussed: (1) the range of feelings and emotions experienced including feeling disregarded, vulnerability, shock and isolation; (2) how they made sense of and ascribed meaning to their experience in the light of the unique nature of their cancer. A thread running throughout the findings highlights that this was a disruptive biographical experience.

Conclusions

Young people experienced a loss of youthful immunity which contrasted with a sense of growth and shift in life perspective. Having a highly treatable cancer was helpful in aiding them to reframe their situation positively but at the same time left them feeling dismissed over a lack of recognition that they had cancer. The young peoples’ experiences point to a need for increased understanding of this rare cancer, more effective communication from health care professionals and a greater understanding of the experiential impact of this disease on young people. Suggestions to improve the service provision to this patient group are provided.

Statement of contribution

What is already known on this subject?

Differentiated thyroid cancer has an excellent prognosis.

Quality of life of thyroid cancer has marginally been explored in the literature.

Little is known on the support needs of young people diagnosed with thyroid cancer.

What does this study add?

Increased understanding of how young people make sense and cope with thyroid cancer despite the lack of support resources.

Addressing illness perceptions through improved information support may aid coping and adjustment.

Insight into the needs of young people diagnosed with thyroid cancer and recommendations on service improvements.
BAUS consensus document for the management of male genital emergencies: priapism
Authors:   BAUS Section of Andrology Genitourethral Surgery, Muneer Asif , Brown Gareth , Dorkin Trevor , Lucky Marc , Pearcy Richard , Shabbir Majid , Shukla Chitranjan J. , Rees Rowland W. , Summerton Duncan J.
Published: January 2018

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on‐site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus committee comprising members of the BAUS Section of Andrology and Genitourethral Surgery together with experts from urology units throughout the UK. Priapism requires prompt assessment and treatment and these consensus statements provide guidance for UK practice.
Phytoplankton defence mechanisms: traits and trade‐offs
Authors: Pančić Marina , Kiørboe Thomas
Published: January 2018

In aquatic ecosystems, unicellular algae form the basis of the food webs. Theoretical and experimental studies have demonstrated that one of the mechanisms that maintain high diversity of phytoplankton is through predation and the consequent evolution of defence mechanisms. Proposed defence mechanisms in phytoplankton are diverse and include physiological (e.g. toxicity, bioluminescence), morphological (e.g. silica shell, colony formation), and behavioural (e.g. escape response) traits. However, the function of many of the proposed defence mechanisms remains elusive, and the costs and benefits (trade‐offs) are often unquantified or undocumented. Here, we provide an overview of suggested phytoplankton defensive traits and review their experimental support. Wherever possible we quantify the trade‐offs from experimental evidence and theoretical considerations. In many instances, experimental evidence suggests that defences are costless. However, we argue that (i) some costs materialize only under natural conditions, for example, sinking losses, or dependency on the availability of specific nutrients, and (ii) other costs become evident only under resource‐deficient conditions where a rivalry for limiting resources between growth and defence occurs. Based on these findings, we suggest two strategies for quantifying the costs of defence mechanisms in phytoplankton: (i) for the evaluation of defence costs that are realized under natural conditions, a mechanistic understanding of the hypothesized component processes is required; and (ii) the magnitude of the costs (i.e. growth reduction) must be assessed under conditions of resource limitation.
The Blomia tropicalis allergen Blo t 7 stimulates innate immune signalling pathways through TLR2
Authors: Soongrung T. , Mongkorntanyatip K. , Peepim T. , Buaklin A. , Le Mignon M. , Malainual N. , Nony E. , Jacquet A.
Published: January 2018

Background

Although the house dust mite species Blomia tropicalis is a leading cause of allergic diseases in tropical and subtropical regions, the identification and characterization of the allergenic proteins remain incomplete.

Objective

We aimed to characterize a recombinant form of Blo t 7 (rBlo t 7) in terms of IgE reactivity, lipid‐binding activity and ability to stimulate innate immunity.

Methods

The mature Blo t 7 cDNA was cloned by PCR methods for the expression of a secreted form of the allergen in P. pastoris. The IgE reactivity to purified rBlo t 7 as well as the potential cross‐reactivity with Der p 7 was determined by ELISA. The lipid‐binding capacity of rBlo t 7 was assayed using fluorescent lipid probes. The stimulation of TLR2 signalling pathway by rBlo t 7 was examined in cell activation and reporter assays.

Results

The amplified mature Blo t 7 cDNA revealed the presence of a 60 base pair insertion compared with the reference sequence registered in the GenBank database. Multiple protein sequence alignments of group 7 mite allergens confirmed that this longer deduced amino acid sequence was the authentic Blo t 7 polypeptide chain. Analysis of IgE reactivity can classify rBlo t 7 as an intermediate B. tropicalis allergen which displayed weak cross‐reactivity with Der p 7. Purified rBlo t 7 was shown to bind selectively the naturally fluorescent lipid probe cis‐parinaric (cPNA) with a dissociation constant of 2 μmol/L. The group 7 Blomia allergen stimulated the TLR2‐, NF‐kB‐ and MAPK‐dependent production of IL‐8 and GM‐CSF in respiratory epithelial cells.

Conclusions & Clinical Relevance

Through its propensity to transport fatty acids/lipids and to stimulate TLR2 signalling pathways in airway epithelial cells, Blo t 7 can represent a key allergen for the initiation of the B. tropicalis‐induced airway inflammation.
Generalized reactions during skin testing with clindamycin in drug hypersensitivity: a report of 3 cases and review of the literature
Authors: Papakonstantinou Eleni , Müller Sabine , Röhrbein Jan H. , Wieczorek Dorothea , Kapp Alexander , Jakob Thilo , Wedi Bettina
Published: January 2018

Background

The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described.

Objectives

To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature.

Methods

Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients.

Results

All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients.

Conclusions

Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work‐up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended.
Significance of tumor‐associated autoantibodies in the early diagnosis of lung cancer
Authors: Du Qiang , Yu Ruofei , Wang Han , Yan Dong , Yuan Qi , Ma Yixin , Slamon Dennis , Hou Dongmei , Wang Huiling , Wang Qi
Published: January 2018

Objectives

Autoantibodies tumor‐associated antigens (TAAs) could be a valuable tool for the diagnosis or early detection of cancer due to their relatively high specificity and stability. The purpose of this study is to detect the level of tumor‐associated autoantibodies in lung cancer and assess the diagnostic potential of autoantibodies in screening strategy for early stage lung cancer.

Materials and Methods

Levels of tumor‐associated autoantibodies (AAbs) were measured against a panel of seven TAAs (p53, PGP9.5, SOX2, GAGE7, GBU4‐5, CAGE and MAGEA1) in 397 patients with pulmonary lesions (305 with newly diagnosis of NSCLC, 47 with SCLC and 45 with benign nodule) and 74 control persons without any nodules in the lung after chest MDCT scan. The sensitivity, specificity for patients and control persons, positive rate of the panel in different pathology, stage, size of lesion, age and gender were compared and analyzed.

Results

The AAbs panel could distinguish malignant lesions from benign lesions and control people, with sensitivity of 56.53% and specificity of 91.60%. The specificity could be further increased to 95.80%, when combined with CT. The AAbs also showed high diagnostic value of malignant nodule, and it would be a new method for judgment of malignant nodules that are less than 8 mm in diameter. No significant differences were seen based on pathology, NSCLC stages, tumor size, age or gender.

Conclusion

This assay confirms the value of AAbs panel as a diagnostic tool combined with CT scan.
Phonological processing during silent reading in teenagers who are deaf/hard of hearing: an eye movement investigation
Authors: Blythe Hazel I. , Dickins Jonathan H. , Kennedy Colin R. , Liversedge Simon P.
Published: January 2018

There has been considerable variability within the literature concerning the extent to which deaf/hard of hearing individuals are able to process phonological codes during reading. Two experiments are reported in which participants’ eye movements were recorded as they read sentences containing correctly spelled words (e.g., church), pseudohomophones (e.g., cherch), and spelling controls (e.g., charch). We examined both foveal processing and parafoveal pre‐processing of phonology for three participant groups—teenagers with permanent childhood hearing loss (PCHL), chronological age‐matched controls, and reading age‐matched controls. The teenagers with PCHL showed a pseudohomophone advantage from both directly fixated words and parafoveal preview, similar to their hearing peers. These data provide strong evidence for phonological recoding during silent reading in teenagers with PCHL.
To share or not to share: Incentivizing data sharing in life science communities
Authors: Bezuidenhout Louise
Published: January 2018

Most scientists recognize the importance of sharing data online in an open fashion. Nonetheless, many studies have documented the concerns that accompany data sharing activities, including loss of credit or IP, misuse and the time needed to curate interoperable data. To this end, discussions around data sharing often identify incentives that could potentially ameliorate these disincentivising concerns.

Nonetheless, current Open Data discussions often rely on evidence‐based studies to identify the disincentives to overcome. This results in highly specific and directed interventions. In contrast, this paper offers a different interpretation of these concerns. To do so, it makes use of the Thomas Theorem which suggests that: “If men define situations as real, they are real in their consequences”.

Using empirical evidence from sub‐Saharan African (bio)chemistry laboratories, this paper illustrates how individual perceptions of research environments – whether associated with evidence or not – are highly influential in shaping data sharing practices. It concludes with the suggestion that discussion on incentivising data sharing amongst scientific communities need to take a broader set of concerns into account and offer a more creative approach to ameliorating environmental disincentives.
Adult presentation of ALCAPA: Echo and CT diagnosis
Authors: Kerut Edmund Kenneth , Kogos Philip G. , Anderson Jason H. , Turner Michael , Ascuitto Robert , Ross‐Ascuitto Nancy , Said Sameh M.
Published: January 2018

A healthy 20‐year‐old male presented with aborted sudden death. Both thoracic echocardiography and cardiac computed tomographic angiography demonstrated the characteristic findings of ALCAPA noting a dilated and tortuous right coronary artery, dilated coronary collateral arteries within the interventricular septum or along the surface of the heart, and visualization of the left coronary artery origin from the posterior aspect of the main pulmonary artery. Both imaging modalities demonstrated all three characteristic findings of this rare coronary anomaly and served as complementary imaging studies for surgical correction.
Among‐species overlap in rodent body size distributions predicts species richness along a temperature gradient
Authors: Read Quentin D. , Grady John M. , Zarnetske Phoebe L. , Record Sydne , Baiser Benjamin , Belmaker Jonathan , Tuanmu Mao-Ning , Strecker Angela , Beaudrot Lydia , Thibault Katherine M.
Published: January 2018

Temperature is widely regarded as a major driver of species richness, but the mechanisms are debated. Niche theory suggests temperature may affect richness by filtering traits and species in colder habitats while promoting specialization in warmer ones. However, tests of this theory are rare because niche dimensions are challenging to quantify along broad thermal gradients. Here, we use individual‐level trait data from a long‐term monitoring network spanning a large geographic extent to test niche‐based theory of community assembly in small mammals. We examined variation in body size among 23 communities of North American rodents sampled across the National Ecological Observatory Network (NEON), ranging from northern hardwood forests to subtropical deserts. We quantified body size similarity among species using a metric of overlap that accounts for individual variation, and fit a structural equation model to disentangle the relationships between temperature, productivity, body size overlap, and species richness. We document a latitudinal gradient of declining similarity in body size among species towards the tropics and overall increase in the dimensions of community‐wide trait space in warmer habitats. Neither environmental temperature nor net primary productivity directly affect rodent species richness. Instead, temperature determines the community‐wide niche space that species can occupy, which in turn alters richness. We suggest a latitudinal gradient of trait space expansion towards the tropics may be widespread and underlie gradients in species diversity.
Impact of tobacco, alcohol and cannabis use on treatment outcomes among patients experiencing first episode psychosis: Data from the national RAISE‐ETP study
Authors: Oluwoye Oladunni , Monroe‐DeVita Maria , Burduli Ekaterina , Chwastiak Lydia , McPherson Sterling , McClellan Jon M. , McDonell Michael G.
Published: January 2018

Aim

The primary aim of this study was to examine the effect of recent tobacco, alcohol and cannabis use on treatment outcomes among participants experiencing first episode psychosis (FEP).

Methods

Secondary data analyses were conducted on 404 participants enrolled in the Recovery After an Initial Schizophrenia Episode—Early Treatment Program (RAISE‐ETP) study. RAISE‐ETP investigated the effectiveness of a coordinated specialty care (CSC) intervention for FEP in community mental health agencies in the United States. Generalized estimating equations were used to examine whether recent tobacco smoking, alcohol, and cannabis use at baseline were associated with illness severity, number of antipsychotic pills missed, psychiatric symptoms and quality of life during the 24‐month treatment period, after controlling for duration of untreated psychosis and treatment group.

Results

At baseline, roughly 50% (n = 209) of participants reported recent tobacco, 28% (n = 113) alcohol and 24% (n = 95) cannabis use. Tobacco smokers had higher levels of illness severity (β = .24; P < .005), a higher number of missed pills (β = 2.89; P < .05), higher psychiatric symptoms and lower quality of life during treatment relative to non‐smokers. Alcohol users had a higher number of missed pills (β = 3.16; P < .05) during treatment and cannabis users had higher levels of illness severity (β = .18; P < .05) and positive symptoms (β = 1.56; P < .05) relative to non‐users.

Conclusions

Tobacco, alcohol and cannabis use are common in youth seeking treatment for FEP. Tobacco smoking was associated with more negative clinical outcomes. These findings have implications for including interventions targeting these areas of substance use within current CSC models.
Altered transcription of glutamatergic and glycinergic receptors in spinal cord dorsal horn following spinal cord transection is minimally affected by passive exercise of the hindlimbs
Authors: Chopek Jeremy W. , MacDonell Christopher W. , Shepard Patricia C. , Gardiner Kalan R. , Gardiner Phillip F.
Published: January 2018

Gene expression is altered following a spinal transection (STx) in both motor and sensory systems. Exercise has been shown to influence gene expression in both systems post‐STx. Gene expression alterations have also been shown in the dorsal root ganglia and nociceptive laminae of the spinal cord following either an incomplete spinal cord injury (SCI) or a contusive SCI. However, the effect of STx and exercise on gene expression in spinal cord laminae I‐III has not fully been examined. Therefore, the purpose of this study was to determine whether gene expression in laminae I‐III is altered following STx and determine whether superimposed passive exercise of the hindlimbs would influence gene expression post‐STx in laminae I‐III. Laser capture microdissection was used to selectively harvest laminae I‐III of lumbar spinal cord sections, and quantitative RT‐PCR was used to examine relative expression of 23 selected genes in samples collected from control, STx and STx plus exercise rats. We demonstrate that post‐STx, gene expression for metabotropic glutamate receptors 1, 5 and 8 were up‐regulated, whereas ionotropic glutamatergic receptor (Glur2) and glycinergic subunit GLRA1 expression was down‐regulated. Daily exercise attenuated the down‐regulation of Glur2 gene expression in laminae I‐III. Our results demonstrate that in a STx model, gene expression is altered in laminae I‐III and that although passive exercise influences gene expression in both the motor and sensory systems, it had a minimal effect on gene expression in laminae I‐III post‐STx.
Different responses of the right superior temporal sulcus to visual movement feedback during self‐generated vs. externally generated hand movements
Authors: Limanowski Jakub , Sarasso Pietro , Blankenburg Felix
Published: January 2018

An important implication of several recent accounts of motor control is that sensory feedback from self‐generated movements is relatively attenuated based on predictions issued by the agent's motor system. Such a relative attenuation of sensory information during actions has already been demonstrated in the somatosensory domain. Here, we used functional magnetic resonance imaging (fMRI) and a virtual reality‐based setup to investigate a potential attenuation of brain responses to realistic visual movement feedback during active vs. passive right‐hand movements. The participants’ right unseen hand was rotated either by the participants themselves or by the experimenter, while the participants received visual movement feedback via a photorealistic virtual 3D hand driven by their real hand movements, or received no visual feedback. We observed a significant interaction between movement type (active vs. passive) and movement feedback (vision vs. no vision) in the right superior temporal sulcus (STS), which showed relatively attenuated blood‐oxygen‐level‐dependent (BOLD) signal differences in movements with vs. without visual feedback when those movements were actively vs. passively executed. This finding suggests that STS activity caused by visual feedback from the moving body may be attenuated based on the agent's motor predictions.
Neural bases of rhythmic entrainment in humans: critical transformation between cortical and lower‐level representations of auditory rhythm
Authors: Nozaradan Sylvie , Schönwiesner Marc , Keller Peter E. , Lenc Tomas , Lehmann Alexandre
Published: January 2018

The spontaneous ability to entrain to meter periodicities is central to music perception and production across cultures. There is increasing evidence that this ability involves selective neural responses to meter‐related frequencies. This phenomenon has been observed in the human auditory cortex, yet it could be the product of evolutionarily older lower‐level properties of brainstem auditory neurons, as suggested by recent recordings from rodent midbrain. We addressed this question by taking advantage of a new method to simultaneously record human EEG activity originating from cortical and lower‐level sources, in the form of slow (< 20 Hz) and fast (> 150 Hz) responses to auditory rhythms. Cortical responses showed increased amplitudes at meter‐related frequencies compared to meter‐unrelated frequencies, regardless of the prominence of the meter‐related frequencies in the modulation spectrum of the rhythmic inputs. In contrast, frequency‐following responses showed increased amplitudes at meter‐related frequencies only in rhythms with prominent meter‐related frequencies in the input but not for a more complex rhythm requiring more endogenous generation of the meter. This interaction with rhythm complexity suggests that the selective enhancement of meter‐related frequencies does not fully rely on subcortical auditory properties, but is critically shaped at the cortical level, possibly through functional connections between the auditory cortex and other, movement‐related, brain structures. This process of temporal selection would thus enable endogenous and motor entrainment to emerge with substantial flexibility and invariance with respect to the rhythmic input in humans in contrast with non‐human animals.
Sub‐threshold transcranial magnetic stimulation applied after the go‐signal facilitates reaction time under control but not startle conditions
Authors: Smith Victoria , Carlsen Anthony N.
Published: January 2018

The presentation of a startling acoustic stimulus (SAS) in a simple reaction time (RT) task significantly reduces RT due to the involuntary early initiation of a prepared movement; however, the underlying neural mechanism remains unclear. It has been proposed that a SAS triggers a cortically stored motor program by involuntarily increasing initiation‐related activation. Sub‐threshold transcranial magnetic stimulation (TMS) can be used to investigate cortical processes, as it increases cortical excitability for 6–30 ms and significantly reduces RT. The purpose of the present experiments was to determine whether the application of sub‐threshold TMS over motor cortex in close temporal proximity to a SAS would facilitate startle RT in the same manner as control RT, providing evidence for cortical involvement in startle‐related RTs. Participants completed a simple RT task requiring targeted wrist extension in response to an auditory go‐signal, which was randomly replaced by a SAS on 25% of trials. On a subset of trials, sub‐threshold TMS was applied 30 ms following the go‐signal in control trials or at −15, 0, +15 or +30 ms with respect to the SAS in startle trials. In all three experiments, sham and real TMS significantly reduced RT in control trials, with real TMS having a larger effect, but there was no effect of either real or sham TMS on startle‐related RT. These results suggest that there may be limited cortical involvement in the initiation of movements in response to a SAS. As an alternative, startle may produce the fastest possible RTs, with little room for additional facilitation.
Comparison of three gamma oscillations in the mouse entorhinal–hippocampal system
Authors: Butler James L. , Hay Y. Audrey , Paulsen Ole
Published: January 2018

The entorhinal–hippocampal system is an important circuit in the brain, essential for certain cognitive tasks such as memory and navigation. Different gamma oscillations occur in this circuit, with the medial entorhinal cortex (mEC), CA3 and CA1 all generating gamma oscillations with different properties. These three gamma oscillations converge within CA1, where much work has gone into trying to isolate them from each other. Here, we compared the gamma generators in the mEC, CA3 and CA1 using optogenetically induced theta–gamma oscillations. Expressing channelrhodopsin‐2 in principal neurons in each of the three regions allowed for the induction of gamma oscillations via sinusoidal blue light stimulation at theta frequency. Recording the oscillations in CA1 in vivo, we found that CA3 stimulation induced slower gamma oscillations than CA1 stimulation, matching in vivo reports of spontaneous CA3 and CA1 gamma oscillations. In brain slices ex vivo, optogenetic stimulation of CA3 induced slower gamma oscillations than stimulation of either mEC or CA1, whose gamma oscillations were of similar frequency. All three gamma oscillations had a current sink–source pair between the perisomatic and dendritic layers of the same region. Taking advantage of this model to analyse gamma frequency mechanisms in slice, we showed using pharmacology that all three gamma oscillations were dependent on the same types of synaptic receptor, being abolished by blockade of either type A γ‐aminobutyric acid receptors or α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid/kainate receptors, and insensitive to blockade of N‐methyl‐d‐aspartate receptors. These results indicate that a fast excitatory–inhibitory feedback loop underlies the generation of gamma oscillations in all three regions.
Alterations in spontaneous delta and gamma activity might provide clues to detect changes induced by amyloid‐β administration
Authors: Hidisoglu Enis , Kantar‐Gok Deniz , Er Hakan , Acun Alev Duygu , Yargicoglu Piraye
Published: January 2018

Alzheimer's disease (AD) is the most prevalent form of dementia and has an increasing incidence. The neuropathogenesis of AD is suggested to be a result of the accumulation of amyloid‐β (Aβ) peptides in the brain. To date, Aβ‐induced cognitive and neurophysiologic impairments have not been illuminated sufficiently. Therefore, we aimed to examine how spontaneous brain activities of rats changed by injection of increasing Aβ doses into the brain hemispheres, and whether these changes could be used as a new biomarker for the early diagnosis of the AD. Rats were randomized into following groups: sham (Sham) and seven Aβ‐treated (i.c.v.) groups in increasing concentrations (from Aβ‐1 to Aβ‐7). After recovery, EEG recordings were obtained from implanted electrodes from eight electrode locations, and then, spectral and statistical analyses were performed. A significant decrement in gamma activity was observed in all Aβ groups compared with the sham group. In delta activity, we observed significant changes from Aβ‐4 to Aβ‐7 group compared with sham group. Delta coherence values were decreased from Aβ‐4 to Aβ‐7 and Aβ‐5 to Aβ‐7 groups for frontal and temporal electrode pairs, respectively. A gradual increment was observed in Aβ1‐42 level till Aβ‐4 group. Positive correlation for global delta power and negative correlation for global gamma power between Aβ1‐42 peptide levels were detected. Consequently, it is conceivable to suggest gamma oscillation might be used to detect early stages of AD. Moreover, changes in delta activity provide information about the onset of major pathologic changes in the progress of AD.
Unknown‐onset strokes with anterior circulation occlusion treated by thrombectomy after DWI‐FLAIR mismatch selection
Authors: Escalard S. , Gory B. , Kyheng M. , Desilles J.‐P. , Redjem H. , Ciccio G. , Smajda S. , Labreuche J. , Mazighi M. , Piotin M. , Blanc R. , Lapergue B. , Fahed R. ,   of the ETIS (Endovascular Treatment in Ischemic Stroke) Research Investigators
Published: January 2018

Background and purpose

The DAWN trial recently showed compelling evidence in treating late window and wake‐up stroke patients with thrombectomy using a clinical‐imaging mismatch. The aim was to evaluate the results of thrombectomy for unknown‐onset strokes (UOS) treated in our centres after a diffusion weighted imaging/fluid attenuated inversion recovery (DWI‐FLAIR) mismatch based selection.

Methods

A multicentre, cohort study was performed of consecutive UOS treated by thrombectomy between 2012 and 2016. UOS with proximal anterior circulation occlusion discovered beyond 6 h from ‘last seen normal’ were compared with known‐onset strokes (KOS) for whom thrombectomy was started within 6 h from onset. Time intervals were recorded from first time found abnormal. Results were adjusted for age, diabetes, hypertension, National Institutes of Health Stroke Scale, site of occlusion, DWI Alberta Stroke Programme Early CT Score, intravenous thrombolysis and use of general anaesthesia.

Results

Amongst 1246 strokes with anterior circulation occlusion treated by thrombectomy, 277 were UOS, with a ‘last time seen well’ beyond 6 h and DWI‐FLAIR mismatch, and 865 were KOS who underwent groin puncture within 6 h. Favourable outcome was achieved less often in UOS than KOS patients (45.2% vs. 53.9%, P = 0.022). After pre‐specified adjustment, this difference was not significant (adjusted relative risk 0.91; 95% confidence interval 0.80–1.04; P = 0.17). No differences were found in secondary outcomes. Time intervals from first found abnormal were significantly longer in UOS.

Conclusion

Thrombectomy of UOS with anterior circulation occlusion and DWI‐FLAIR mismatch appears to be as safe and efficient as thrombectomy of KOS within 6 h from onset. This pattern of imaging could be used for patient selection when time of onset is unknown.
Alternatives to animal testing in basic and preclinical research of atopic dermatitis
Authors: Löwa Anna , Jevtić Marijana , Gorreja Frida , Hedtrich Sarah
Published: January 2018

Atopic dermatitis (AD) is a chronic inflammatory skin disease of increasing prevalence, especially in industrialized countries. Roughly 25% of the children and 1%‐3% of adults are affected. Although significant progress has been made in the understanding of the pathogenesis of AD, many aspects remain poorly understood. Moreover, there is a pressing need for improved therapeutic options. Studies to elucidate the pathophysiological pathways of AD and to identify novel therapeutic targets over the last few decades have been conducted almost exclusively in animal models. However, in vitro approaches such as 3D skin disease models have recently emerged due to an increasing awareness of distinct interspecies‐related differences that hamper the effective translation of results from animal models to humans. In addition, there is growing political and social pressure to develop alternatives to animal models according to the 3Rs principle (reduction, refinement and replacement of animal models).
Major limitations to achieving “4 per 1000” increases in soil organic carbon stock in temperate regions: Evidence from long‐term experiments at Rothamsted Research, United Kingdom
Authors: Poulton Paul , Johnston Johnny , Macdonald Andy , White Rodger , Powlson David
Published: January 2018

We evaluated the “4 per 1000” initiative for increasing soil organic carbon (SOC) by analysing rates of SOC increase in treatments in 16 long‐term experiments in southeast United Kingdom. The initiative sets a goal for SOC stock to increase by 4‰ per year in the 0–40 cm soil depth, continued over 20 years. Our experiments, on three soil types, provided 114 treatment comparisons over 7–157 years. Treatments included organic additions (incorporated by inversion ploughing), N fertilizers, introducing pasture leys into continuous arable systems, and converting arable land to woodland. In 65% of cases, SOC increases occurred at >7‰ per year in the 0–23 cm depth, approximately equivalent to 4‰ per year in the 0–40 cm depth. In the two longest running experiments (>150 years), annual farmyard manure (FYM) applications at 35 t fresh material per hectare (equivalent to approx. 3.2 t organic C/ha/year) gave SOC increases of 18‰ and 43‰ per year in the 23 cm depth during the first 20 years. Increases exceeding 7‰ per year continued for 40–60 years. In other experiments, with FYM applied at lower rates or not every year, there were increases of 3‰–8‰ per year over several decades. Other treatments gave increases between zero and 19‰ per year over various periods. We conclude that there are severe limitations to achieving the “4 per 1000” goal in practical agriculture over large areas. The reasons include (1) farmers not having the necessary resources (e.g. insufficient manure); (2) some, though not all, practices favouring SOC already widely adopted; (3) practices uneconomic for farmers—potentially overcome by changes in regulations or subsidies; (4) practices undesirable for global food security. We suggest it is more realistic to promote practices for increasing SOC based on improving soil quality and functioning as small increases can have disproportionately large beneficial impacts, though not necessarily translating into increased crop yield.
Predicting survival of older community‐dwelling individuals according to five estimated glomerular filtration rate equations: The InChianti study
Authors: Corsonello Andrea , Pedone Claudio , Bandinelli Stefania , Ferrucci Luigi , Antonelli Incalzi Raffaele
Published: January 2018

Aims

There is uncertainty about which estimated glomerular filtration rate eGFR equation to use in older people with respect to the prediction of prognosis. Our aim was: (i) to compare the discriminative capacity of eGFR estimated by different equations with respect to all‐cause mortality; and (ii) to identify the eGFR threshold at which the risk of mortality starts to increase for each equation.

Methods

We used data from 828 community‐dwelling older adults aged >65 years enrolled in the InCHIANTI study. The outcome measure was all‐cause mortality at 9 years. GFR was estimated by five different equations: Chronic Kidney Disease Epidemiological Collaboration (creatinine equation [CKD‐EPIcre], and creatinine and cystatin C equation [CKD‐EPIcre‐cys]), Berlin Initiative Study (BIScre and BIScre‐cys) and full age spectrum. Sensitivity, specificity, areas under receiver operating curve (AUC) and C‐statistics were used to compare their predictive capacity.

Results

The best mix of sensitivity, specificity, AUC and C‐statistic value in predicting mortality was observed with BIS equations. BIScre (AUC 0.65, 95% CI 0.61–0.69) outperformed both CKD‐EPIcre (AUC 0.60, 95% CI 0.56–0.64; P = 0.005) and full age spectrum (AUC 0.63, 95% CI 0.59–0.67; P = 0.002) in terms of predictivity. Similarly, BIScre‐cys (AUC 0.67, 95% CI 0.63–0.71) outperformed CKD‐EPIcre‐cys (AUC 0.63, 95% CI 0.59–0.67; P = 0.01). AUC obtained with equations also including cystatin C were not significantly different compared with their creatinine‐based counterparts. The risk of long‐term mortality began to increase at under 65.6 mL/min/1.73 m2 for CKD‐EPIcre‐cys, 60.5 for CKD‐EPIcre, 60 for BIScre‐cys, 56.3 for BIScre and 55.2 for full age spectrum.

Conclusions

The BIS equation discriminates the risk of all‐cause mortality better than other equations in older community‐dwelling individuals. The eGFR threshold under which mortality starts to increase could change as a function of the equation used. Geriatr Gerontol Int 2018; 18: 607–614.
Influence of breathing patterns and orthostatic stress on postural control in older adults
Authors: Rodrigues Gabriel D , Gurgel Jonas L , Gonçalves Thiago R , Porto Flávia , Soares Pedro Paulo da S
Published: January 2018

Aim

To investigate the influence of breathing patterns and blood pressure behavior postural control in older adults.

Methods

A total of 20 older adults carried out spontaneous, controlled (15 cycles/min) and deep (6 cycles/min) breathing trials, in random order. In this session, the heart rate was recorded continuously and blood pressure measured every 3 min. In addition, the challenge from sitting to an active standing position was carried out with eyes closed during 6 min on a baropodometer plate with electromyography recording. The root mean square (RMS) of electromyography was calculated.

Results

There were significant differences in the postural control with spontaneous breathing from the first minute (center of pressure [COP]‐area 216.40 ± 116.70 mm2) in comparison with the third minute (COP‐area 79.35 ± 68.11 mm2; d = 0.89; P < 0.01) and the sixth minute (COP‐area 70.24 ± 41.26 mm2; d = 0.60; P < 0.05) of active standing. Furthermore, deep breathing significantly increases the COP‐area (158.50 ± 126.2 mm2) at the sixth minute of active standing in comparison with spontaneous breathing (70.24 ± 41.26 mm2; d = 0.80; P < 0.01). There were also significant differences in systolic blood pressure during spontaneous breathing between the baseline measures (sitting position 123 ± 11 mmHg) and the first minute of active standing (117 ± 13 mmHg; d = 0.24; P < 0.05). Furthermore, electromyography activity of the tibialis anterior increased during the deep (17.52 ± 9.21 RMS) and controlled breathing (16.75 ± 5.26 RMS) compared with the spontaneous condition (14.93 ± 5.56 RMS; d = 0.17; P < 0.05).

Conclusions

The present data provide important insight into the respiratory and hemodynamics effects of postural control in older adults. The current data confirm that deep breathing causes periodic perturbation in the neuromuscular compensation of the lower limbs. Geriatr Gerontol Int 2018; 18: 692–697.
Resident and facility characteristics associated with care‐need level deterioration in long‐term care welfare facilities in Japan
Authors: Jin Xueying , Tamiya Nanako , Jeon Boyoung , Kawamura Akira , Takahashi Hideto , Noguchi Haruko
Published: January 2018

Aim

To determine the resident and facility characteristics associated with residents’ care‐need level deterioration in long‐term care welfare facilities in Japan.

Methods

A nationally representative sample of 358 886 residents who lived in 3774 long‐term care welfare facilities for at least 1 year from October 2012 was obtained from long‐term care insurance claims data. Facility characteristics were linked with a survey of institutions and establishments for long‐term care in 2012. We used a multilevel logistic regression according to the inclusion and exclusion of lost to follow‐up to define the resident and facility characteristics associated with resident care‐need level deteriorations (lost to follow‐up: the majority were hospitalized residents or had died; were treated as deterioration in the including loss to follow‐up model).

Results

Adjusting for the covariates, at the resident level, older age and lower care‐need level at baseline were more likely to show deterioration in the care‐need level. At the facility level, metropolitan facilities, unit model (all private room settings) and mixed‐model facilities (partly private room settings) were less likely to experience care‐need level deterioration. A higher proportion of registered nurses among all nurses was negatively related to care‐need level deterioration only in the model including lost to follow‐up. A higher proportion of registered dietitians among all dietitians and the facilities in business for fewer years were negatively associated with care‐need level deterioration only in the model excluding lost to follow‐up.

Conclusions

The present study could help identify residents who are at risk of care‐need level deterioration, and could contribute to improvements in provider quality performance and enhance competence in the market. Geriatr Gerontol Int 2018; 18: 758–766.
Tumor necrosis factor‐α regulates human follicular dendritic cell‐secreted protein gene transcription in gingival epithelial cells
Authors: Iwai Yasunobu , Noda Keisuke , Yamazaki Mizuho , Kato Ayako , Mezawa Masaru , Takai Hideki , Nakayama Yohei , Ogata Yorimasa
Published: January 2018

Follicular dendritic cell‐secreted protein (FDC‐SP) is a secreted protein expressed in follicular dendritic cells, periodontal ligament and junctional epithelium. To elucidate the transcriptional regulation of the human FDC‐SP gene by tumor necrosis factor‐α (TNF‐α), we conducted real‐time PCR, Western blotting, transient transfection analyses with chimeric constructs of the FDC‐SP gene promoter linked to a luciferase reporter gene, gel mobility shift and chromatin immunoprecipitation assays using Ca9‐22 gingival epithelial cells. TNF‐α (10 ng/ml) induced FDC‐SP mRNA and protein levels at 3 hr and reached maximum at 12 hr. In transient transfection assays, TNF‐α (12 hr) increased the LUC activities of constructs between −116FDCSP and −948FDCSP including the human FDC‐SP gene promoter. Transcriptional stimulations by TNF‐α were partially inhibited in the −345FDCSP constructs that included 3‐bp mutations in the YY1, GATA, CCAAT enhancer‐binding protein 2 (C/EBP2) and C/EBP3. Transcriptional activities induced by TNF‐α were inhibited by tyrosine kinase, MEK1/2 and phosphoinositide 3‐kinase inhibitors. The results of ChIP assays showed that YY1, GATA and C/EBPβ transcription factors interacted with the YY1, GATA, C/EBP2 and C/EBP3 elements that were increased by TNF‐α. These studies show that TNF‐α stimulates human FDC‐SP gene transcription by targeting YY1, GATA, C/EBP2 and C/EBP3 in the FDC‐SP gene promoter.