bluuebunny/crossref_metadata_2025 huggingface dataset:
Snoring: Is It in the Ear of the Beholder?
Authors: Hoffstein V. , Mateika S. , Anderson D.
Published: February 2017

Complaint of snoring, which is usually voiced by a patient's bedpartner, frequently leads to investigations in the sleep laboratory that are designed to assess snoring objectively and determine whether it is a symptom of sleep apnea. How well this subjective complaint of the listener is confirmed by the objective measurement of snoring is not known. Consequently, we designed a study i) to test the validity of self-perception of snoring and ii) to compare subjective perception of snoring by the sleep technologist with objective measurement of its frequency and loudness. We studied 613 unselected patients referred to our sleep clinic because of snoring and suspicion of sleep apnea. They all had nocturnal polysomnography that included measurements of snoring, expressed as the number of snores per hour of sleep [snoring index (SI)] and mean (dBmean) and maximum (dBmax) nocturnal sound intensity. Following the sleep study, the technologist (and patient) independently rated a patient's snoring as none, mild, moderate or severe. Kruskall-Wallis test, Spearman rank correlations and Cohen's kappa statistics were used to compare the groups, examine the correlations between subjective and objective measurements, and check the agreement between them. We found that i) most patients who snore (471 of 613) were unaware of this behavior; ii) snoring index increased progressively from the “none” group (median SI = 26) to the “severe” group (median SI = 755), with a significant but moderate correlation between the technologist's impression and SI (r = 0.68, p < 0.0005) and poor correlation between the technologist's impression and dBmean (r = 0.34, p < 0.0005); and iii) most of those patients who claim to be able to judge the severity of their snoring have a different perception of it than the listener, with poor agreement between patient's and technologist's subjective impression (Cohen's kappa = 0.22, 95% confidence limits: 0.14−0.33). We conclude that to a large extent snoring is “in the ear of the beholder”, showing only moderate correlation with objective measurement.
Relationship of Slow and Rapid EEG Components of CAP to ASDA Arousals in Normal Sleep
Authors: Parrino Liborio , Smerieri Arianna , Rossi Mariano , Giovanni Mario
Published: February 2017

Summary/Abstract:

Study Objectives:

Besides arousals (according to the ASDA definition), sleep contains also K-complexes and delta bursts which, in spite of their sleep-like features, are endowed with activating effects on autonomic functions. The link between phasic delta activities and enhancement of vegetative functions indicates the possibility of physiological activation without sleep disruption (i.e., arousal without awakening). A functional connection seems to include slow (K-complexes and delta bursts) and rapid (arousals) EEG events within the comprehensive term of activating complexes. CAP (cyclic alternating pattern) is the spontaneous EEG rhythm that ties both slow and rapid activating complexes together during NREM sleep. The present study aims at exploring the relationship between arousals and CAP components in a selected sample of healthy sleepers.

Design:

Polysomnographic analysis according to the scoring rules for sleep stages and arousals. CAP analysis included also tabulation of subtypes A1 (slow EEG activating complexes), A2 and A3 (activating complexes with fast EEG components).

Setting:

40 sleep-lab accomplished recordings.

Participants:

Healthy subjects belonging to a wide age range (38 ± 20 yrs.).

Interventions:

N/A

Measurement and Results:

Of all the arousals occurring in NREM sleep, 87% were inserted within CAP. Subtypes A2 and A3 of CAP corresponded strikingly with arousals (r=0.843 ; p<0.0001), while no statistical relationship emerged when arousals were matched with subtypes A1 of CAP. Subtypes A1 instead correlated positively with the percentages of deep sleep (r=0.366; p<0.02).

Conclusions:

The CAP subtype classification encompasses both the process of sleep maintenance (subtypes A1) and sleep fragmentation (subtypes A2 and A3), and provides a periodicity dimension to the activating events of NREM sleep.
Self-Reported Nap Behavior and Polysomnography at Home in Midlife Women with and without Insomnia
Authors: Johnston Sandra K. , Landis Carol A. , Lentz Martha J. , Shaver Joan L.F.
Published: February 2017

Study Objectives:

To describe self-reported nap behavior and relationships among nap history, nap behavior during the study, indicators of subjective and objective insomnia, and self-reported daytime sleepiness from data previously obtained in a week-long field study of sleep in midlife women with and without insomnia.

Design:

Descriptive/comparative secondary analysis.

Setting:

Individual homes of the participants.

Participants:

Midlife women (mean age 46±4 years) with self-reported insomnia (n=101) and women with adequate sleep (n=30).

Interventions:

N/A

Measurements and Results:

Sleep patterns were assessed by polysomnography (PSG), daily diaries, and a sleep history form. Although all women were requested not to nap, 47% of the women reported nap behavior during the study. Strong relationships were observed between a history of daytime naps and nap behavior (c2=25.63, p≤.001), and a history of feeling sleepy or struggling to stay awake during the daytime (i.e., sleepiness) and nap behavior (c2=18.05, p≤.001) during the study. There was also a modest significant (p≤.05) correlation (r=. 25) between tiredness and nap duration during the study. There were no statistical differences in sleep variables between the napping and non-napping groups. In the napping group, there were no differences between women with sleep efficiency < 85% (objective insomnia) and those with sleep efficiency>85%.

Conclusions:

Habitual nap behavior may be indicative of daytime sleepiness in women with insomnia, but it is not necessarily related to subjective or objective measures of insomnia. Women who routinely nap may be unable to refrain from napping during the daytime in long-term research studies.
Feasibility of Using Unattended Polysomnography in Children for Research—Report of the Tucson Children's Assessment of Sleep Apnea Study (TuCASA)
Authors: Goodwin James L. , Enright Paul L. , Kaemingk Kris L. , Rosen Gerald M. , Morgan Wayne J. , Fregosi Ralph F. , Quan Stuart F.
Published: February 2017

Study Objectives:

The Tucson Children's Assessment of Sleep Apnea study (TuCASA) is designed to investigate the prevalence and correlates of objectively measured sleep-disordered breathing in pre-adolescent children. This paper documents the methods and feasibility of attaining quality unattended polysomnograms in the first 162 TuCASA children recruited.

Design:

A prospective cohort study projected to enroll 500 children between 5 and 12 years of age who will undergo unattended polysomnography, neurocognitive evaluation, and physiological and anatomical measurements thought to be associated with sleep-disordered breathing. Setting: Children are recruited through the Tucson Unified School District. Polysomnograms and anthropometric measurements are completed in the child's home.

Participants:

Of the 157 children enrolled in TuCASA, there were 100 children (64%) between 5–8 years old and 57 children (36%) between the ages of 9 to 12. There were 74 (47%) Hispanic children, and 68 (43%) female participants.

Interventions:

N/A

Measurements & Results:

Technically acceptable studies were obtained in 157 children (97%). The initial pass rate was 91%, which improved to 97% when 9 children who failed on the first night of recording completed a second study which was acceptable. In 152 studies (97%), greater than 5 hours of interpretable respiratory, electroencephalographic, and oximetry signals were obtained. The poorest signal quality was obtained from the chin electromyogram and from the combination thermister/nasal cannula. Parents reported that 54% of children slept as well as, or better than usual, while 40% reported that their child slept somewhat worse than usual. Only 6% were observed to sleep much worse than usual. Night-to-night variability in key polysomnographic parameters (n=10) showed a high degree of reproducibility on 2 different nights of study using identical protocols in the same child. In 5 children, polysomnograms done in the home were comparable to those recorded in a sleep laboratory.

Conclusions:

The high quality of data collected in TuCASA demonstrates that multi-channel polysomnography data can be successfully obtained in children aged 5–12 years in an unattended setting under a research protocol.
Indoor Exposure to Natural Bright Light Prevents Afternoon Sleepiness
Authors: Kaida Kosuke , Takahashi Masaya , Haratani Takashi , Otsuka Yasumasa , Fukasawa Kenji , Nakata Akinori
Published: February 2017

Study Objectives:

The present study examined the effects of indoor exposure to natural bright light on afternoon sleepiness.

Design:

Participants took part in 3 experimental conditions: (1) a natural bright light condition in which they carried out performance and arousal tests sitting near a window (3260.0 ± 1812.43 lux) from 12:40 PM to 1:10 PM, (2) a nap condition in which they were provided a nap opportunity for 20 minutes from 12:45 PM, and (3) a control condition in which they performed the tests in less than 100 lux surroundings from 12:40 PM to 1:10 PM. Before and after each treatment, the same series of tests were administered.

Setting:

A temperature- and light-controlled sleep laboratory.

Participants:

Sixteen healthy female paid volunteers aged 33 to 43 (38.1 ± 2.68) years.

Interventions:

Indoor natural bright light and a short nap.

Measurements and Results:

Arousal levels were measured by the Psychomotor Vigilance Task, Alpha Attenuation Test, Karolinska Drowsiness Test, and Karolinska Sleepiness Scale. The tests were repeated every 30 minutes from 11:00 AM to 4:10 PM. Ambient light intensity was maintained at less than 100 lux, except during natural bright light exposure. Short-term exposure to natural bright light significantly improved afternoon arousal levels, as measured by the Karolinska Drowsiness Test and Alpha Attenuation Test, the effects of which continued for at least 60 minutes (1:10–2:10 PM). However, no significant differences were observed between conditions for Psychomotor Vigilance Test performance.

Conclusions:

Brief indoor exposure to natural bright light may decrease afternoon sleepiness. This technique of light could be used in work settings in which napping is not permitted.

Citation:

Kaida K; Takahashi M; Haratani T et al. Indoor exposure to natural bright light prevents afternoon sleepiness.
Defining Insomnia: Quantitative Criteria for Insomnia Severity and Frequency
Authors: Lineberger Margaret D. , Carney Colleen E. , Edinger Jack D. , Means Melanie K.
Published: February 2017

Study Objective:

Recent efforts have been made to develop quantitative frequency, duration, and severity criteria for insomnia. The current study was conducted to test a range of frequency and severity criteria sets for discriminating primary insomnia sufferers from normal sleepers.

Participants:

Seventy-two adults with primary insomnia and 88 agematched normal sleepers.

Methods:

Participants completed 14 consecutive nights of sleep logs to monitor their home sleep patterns. Receiver-operator characteristic curve analyses were used to compare a range of severity and frequency criteria sets for discriminating the insomnia and normal-sleeper groups. In addition, sensitivity and specificity tests were conducted for a range of waketime severity cutoffs based on 2-week mean sleep-log data.

Results:

Receiver-operator characteristic curve analyses showed that no 1 combination of severity and frequency criteria maximized sensitivity and specificity. Rather, the optimal frequency cutoff decreased as the severity criterion increased. Analyses of mean sleep-log data showed that an average sleep-onset latency or middle-of-the-night wake time (ie, time awake between sleep onset and final morning awakening) cutoff of 20 minutes or longer over 2 weeks of sleep-log monitoring appeared to best maximize sensitivity (94.4%) and specificity (79.6%) for insomnia classification.

Conclusions:

The optimal quantitative insomnia criteria found herein differ from those previously proposed. Nonetheless, results suggest that quantitative criteria derived from sleep-log data may be useful for classification of primary insomnia.

Citation:

Lineberger MD; Carney CE; Edinger JD et al. Defining insomnia: quantitative criteria for insomnia severity and frequency.
Time Estimation in Chronic Insomnia Sufferers
Authors: Rioux Isabelle , Tremblay Sébastien , Bastien Célyne H.
Published: February 2017

Study Objective:

The objective of the present study is 2-fold: (1) compare the time-estimation performance of chronic insomnia sufferers to that of good sleepers and (2) evaluate the severity of the sleep complaint in order to assess its association with the time-estimation performance.

Design:

Between subjects design.

Participants:

The sample included 11 individuals suffering from chronic primary insomnia (7 women and 4 men, mean age = 44.64 years, SD = 12.71) and 11 good sleepers (5 women and 6 men, mean age = 48.00 years, SD = 7.86).

Interventions:

N/A.

Measurements and Results:

All participants completed a time-estimation task, namely a finger-tapping task. The results indicate no significant between-group differences on time-estimation data, as well as no significant relationship between severity of insomnia complaint and estimation of time.

Conclusion:

These results suggest that the tendency to misestimate sleep difficulties is not linked to impaired time estimation-specific processes in insomnia sufferers, as measured with the present task.
How activity dependent feedback inhibition may maintain head direction signals in mouse presubiculum
Authors: Simonnet Jean , Nassar Mérie , Stella Federico , Cohen Ivan , Mathon Bertrand , Boccara Charlotte N. , Miles Richard , Fricker Desdemona
Published: February 2017

Orientation in space is represented in specialized brain circuits. Persistent head direction signals are transmitted from anterior thalamus to the presubiculum, but the identity of the presubicular target neurons, their connectivity and function in local microcircuits are unknown. Here we examine how thalamic afferents recruit presubicular principal neurons and Martinotti interneurons and the ensuing synaptic interactions between these cells. Pyramidal neuron activation of Martinotti cells in superficial layers is strongly facilitating such that high frequency head directional stimulation efficiently unmutes synaptic excitation. Martinotti cell feedback plays a dual role: precisely timed spikes may not inhibit the firing of in-tune head direction cells, while exerting lateral inhibition. Autonomous attractor dynamics emerge from a modeled network implementing wiring motifs and timing sensitive synaptic interactions in the pyramidal - Martinotti cell feedback loop. This inhibitory microcircuit is therefore tuned to refine and maintain head direction information in the presubiculum.
Cryptic diversity and discordance in single‐locus species delimitation methods within horned lizards (Phrynosomatidae: Phrynosoma)
Authors: Blair Christopher , Bryson Robert W.
Published: February 2017

Biodiversity reduction and loss continues to progress at an alarming rate, and thus, there is widespread interest in utilizing rapid and efficient methods for quantifying and delimiting taxonomic diversity. Single‐locus species delimitation methods have become popular, in part due to the adoption of the DNA barcoding paradigm. These techniques can be broadly classified into tree‐based and distance‐based methods depending on whether species are delimited based on a constructed genealogy. Although the relative performance of these methods has been tested repeatedly with simulations, additional studies are needed to assess congruence with empirical data. We compiled a large data set of mitochondrial ND4 sequences from horned lizards (Phrynosoma) to elucidate congruence using four tree‐based (single‐threshold GMYC, multiple‐threshold GMYC, bPTP, mPTP) and one distance‐based (ABGD) species delimitation models. We were particularly interested in cases with highly uneven sampling and/or large differences in intraspecific diversity. Results showed a high degree of discordance among methods, with multiple‐threshold GMYC and bPTP suggesting an unrealistically high number of species (29 and 26 species within the P. douglasii complex alone). The single‐threshold GMYC model was the most conservative, likely a result of difficulty in locating the inflection point in the genealogies. mPTP and ABGD appeared to be the most stable across sampling regimes and suggested the presence of additional cryptic species that warrant further investigation. These results suggest that the mPTP model may be preferable in empirical data sets with highly uneven sampling or large differences in effective population sizes of species.
Homology‐guided mutational analysis reveals the functional requirements for antinociceptive specificity of collapsin response mediator protein 2‐derived peptides
Authors: Moutal Aubin , Li Wennan , Wang Yue , Ju Weina , Luo Shizhen , Cai Song , François‐Moutal Liberty , Perez‐Miller Samantha , Hu Jackie , Dustrude Erik T , Vanderah Todd W , Gokhale Vijay , Khanna May , Khanna Rajesh
Published: February 2017

Background and Purpose

N‐type voltage‐gated calcium (Cav2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Cav2.2 channel antagonists are recommended as first‐line treatment for neuropathic pain, calcium‐current blocking gabapentinoids inadequately alleviate chronic pain symptoms and often exhibit numerous side effects. Collapsin response mediator protein 2 (CRMP2) targets Cav2.2 channels to the sensory neuron membrane and allosterically modulates their function. A 15‐amino‐acid peptide (CBD3), derived from CRMP2, disrupts the functional protein–protein interaction between CRMP2 and Cav2.2 channels to inhibit calcium influx, transmitter release and acute, inflammatory and neuropathic pain. Here, we have mapped the minimal domain of CBD3 necessary for its antinociceptive potential.

Experimental Approach

Truncated as well as homology‐guided mutant versions of CBD3 were generated and assessed using depolarization‐evoked calcium influx in rat dorsal root ganglion neurons, binding between CRMP2 and Cav2.2 channels, whole‐cell voltage clamp electrophysiology and behavioural effects in two models of experimental pain: post‐surgical pain and HIV‐induced sensory neuropathy induced by the viral glycoprotein 120.

Key Results

The first six amino acids within CBD3 accounted for all in vitro activity and antinociception. Spinal administration of a prototypical peptide (TAT‐CBD3‐L5M) reversed pain behaviours. Homology‐guided mutational analyses of these six amino acids identified at least two residues, Ala1 and Arg4, as being critical for antinociception in two pain models.

Conclusions and Implications

These results identify an antinociceptive scaffold core in CBD3 that can be used for development of low MW mimetics of CBD3.

Linked Articles

This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc
Anxiolytic‐like effect of 2‐(4‐((1‐phenyl‐1H‐pyrazol‐4‐yl)methyl)piperazin‐1‐yl)ethan‐1‐ol is mediated through the benzodiazepine and nicotinic pathways
Authors: Brito Adriane F. , Fajemiroye James O. , Neri Hiasmin F. S. , Silva Dayane M. , Silva Daiany P. B. , Sanz Germán , Vaz Boniek G. , de Carvalho Flávio S. , Ghedini Paulo C. , Lião Luciano M. , Menegatti Ricardo , Costa Elson A.
Published: February 2017

In this study, we proposed the design, synthesis of a new compound 2‐(4‐((1‐phenyl‐1H‐pyrazol‐4‐yl)methyl)piperazin‐1‐yl)ethan‐1‐ol (LQFM032), and pharmacological evaluation of its anxiolytic‐like effect. This new compound was subjected to pharmacological screening referred to as Irwin test, prior to sodium pentobarbital‐induced sleep, open‐field and wire tests. The anxiolytic‐like effect of this compound was evaluated using elevated plus maze and light–dark box tests. In addition, the mnemonic activity was evaluated through step‐down test. In sodium pentobarbital‐induced sleep test, LQFM032 decreased latency and increased duration of sleep. In the open‐field test, LQFM032 altered behavioral parameter, that suggested anxiolytic‐like activity, as increased in crossings and time spent at the center of open field. In the plus maze test and light–dark box test, the LQFM032 showed anxiolytic‐like activity, increased entries and time spent on open arms, and increased in number of transitions and time spent on light area, respectively. Those effects was antagonized by flumazenil but not with 1‐(2‐Methoxyphenyl)‐4‐(4‐phthalimidobutyl)piperazine (NAN‐190). The LQFM032 did not alter mnemonic activity. Moreover, the anxiolytic‐like activity of LQFM032 was antagonized by mecamylamine. In summary, LQFM032 showed benzodiazepine and nicotinic pathways mediated anxiolytic‐like activity without altering the mnemonic activity.
Soil carbon sequestration due to post‐Soviet cropland abandonment: estimates from a large‐scale soil organic carbon field inventory
Authors: Wertebach Tim‐Martin , Hölzel Norbert , Kämpf Immo , Yurtaev Andrey , Tupitsin Sergey , Kiehl Kathrin , Kamp Johannes , Kleinebecker Till
Published: February 2017

The break‐up of the Soviet Union in 1991 triggered cropland abandonment on a continental scale, which in turn led to carbon accumulation on abandoned land across Eurasia. Previous studies have estimated carbon accumulation rates across Russia based on large‐scale modelling. Studies that assess carbon sequestration on abandoned land based on robust field sampling are rare. We investigated soil organic carbon (SOC) stocks using a randomized sampling design along a climatic gradient from forest steppe to Sub‐Taiga in Western Siberia (Tyumen Province). In total, SOC contents were sampled on 470 plots across different soil and land‐use types. The effect of land use on changes in SOC stock was evaluated, and carbon sequestration rates were calculated for different age stages of abandoned cropland. While land‐use type had an effect on carbon accumulation in the topsoil (0–5 cm), no independent land‐use effects were found for deeper SOC stocks. Topsoil carbon stocks of grasslands and forests were significantly higher than those of soils managed for crops and under abandoned cropland. SOC increased significantly with time since abandonment. The average carbon sequestration rate for soils of abandoned cropland was 0.66 Mg C ha−1 yr−1 (1–20 years old, 0–5 cm soil depth), which is at the lower end of published estimates for Russia and Siberia. There was a tendency towards SOC saturation on abandoned land as sequestration rates were much higher for recently abandoned (1–10 years old, 1.04 Mg C ha−1 yr−1) compared to earlier abandoned crop fields (11–20 years old, 0.26 Mg C ha−1 yr−1). Our study confirms the global significance of abandoned cropland in Russia for carbon sequestration. Our findings also suggest that robust regional surveys based on a large number of samples advance model‐based continent‐wide SOC prediction.
Exploring Greenhouse Gas‐Mitigation Strategies in Chinese Eco‐Industrial Parks by Targeting Energy Infrastructure Stocks
Authors: Guo Yang , Tian Jinping , Chertow Marian , Chen Lujun
Published: February 2017

China has more than 1,500 industrial parks, which, collectively, play a crucial role in facilitating industrialization and urbanization. A key characteristic of these parks is that most rely on shareable energy infrastructure, an efficient configuration that can also deliver substantial and sustainable reductions in greenhouse gas (GHG) emissions. This study offers strategies for mitigating GHG emissions from Chinese industrial parks. We focus on extensive data collection for the 106 industrial parks listed in the national demonstration eco‐industrial park (EIP) program. In doing so, we carefully examine the evolution of 608 serviceable energy infrastructure units by vintage year, fuel type, energy output, and technologies of combined heat and power units. We assess direct GHG emissions from both energy infrastructure and the parks, and then identify the features and driving forces of energy infrastructure development in the EIPs. We also offer recommendations for ways to mitigate the GHG emissions from these industrial parks. The energy infrastructure stocks in Chinese EIPs are characterized by heavy coal dependence (87% of capacity) and high ratios of direct GHG emissions versus the total direct emissions of the park (median value: 75.2%). These findings establish a baseline from which both technology and policy decisions can then be made in an informed way.
Mediator of DNA damage checkpoint protein 1 (MDC1) as a prognostic marker for patients with oral squamous cell carcinoma
Authors: Dave Jigna Harshadbhai , Vora Hemangini Hasit , Ghosh Nandita Radhabinod , Trivedi Trupti Indravadan
Published: February 2017

Background

The mediator of DNA damage checkpoint protein 1 (MDC1) is involved in the regulation of cell cycle checkpoints and recruitment of several repair proteins to the site of DNA double‐stranded breaks (DSBs). This study aimed to correlate the expression of MDC1 protein with clinicopathological parameters and to evaluate its prognostic significance in patients with oral squamous cell carcinoma (OSCC).

Methods

MDC1 protein expression was evaluated immunohistochemically from untreated 100 patients with OSCC using modified H‐score method. The association of MDC1 immunostaining was evaluated with clinicopathological parameters and disease outcome using univariate and multivariate survival analysis for relapse‐free survival (RFS) and overall survival (OS).

Results

Incidence of nuclear and cytoplasmic expression of MDC1 protein was 85% & 92%, respectively. Strong nuclear MDC1 protein expression was found to be significantly correlated with lymph node metastasis (P = 0.032). For RFS, Kaplan–Meier survival analysis demonstrated that presence of metastatic lymph node (P = 0.001), lymphatic permeation (P = 0.020), and nuclear MDC1 (P = 0.005) remained significant risk predictors. In multivariate survival analysis, nuclear MDC1 (P = 0.027) entered at step 2 after presence of metastatic lymph node (P = 0.002) at step 1 for predicting reduced RFS. In relation to treatment, OSCC patients exhibiting weak expression of nuclear MDC1 protein were benefited significantly when treated with surgery followed by radiation therapy (P = 0.001).

Conclusion

Thus, this study showed that MDC1 protein expression could be used as a prognostic marker in predicting relapse‐free survival in patients with OSCC. OSCC patients expressing weak MDC1 protein could be benefited by adjuvant radiotherapy instead chemo‐radiotherapy.
Associations of gender and a proxy of female menopausal status with histological features of drug‐induced liver injury
Authors: Suzuki Ayako , Barnhart Huiman , Gu Jiezhun , Bonkovsky Herbert L. , Tillmann Hans L. , Fontana Robert J. , Kleiner David E. ,   Drug‐induced Liver Injury Network (DILIN)
Published: February 2017

Background & Aim

Gender and menopause may contribute to type and severity of drug‐induced liver injury (DILI) by influencing host responses to injury. The aim of this study was to assess the associations of gender and female age 50 [a proxy of menopause] with histological features of liver injury in 212 adults enrolled in the Drug‐Induced Liver Injury Network (DILIN) registry.

Methods

All participants had a causality score of at least ‘probable’, a liver biopsy within 30 days of DILI onset, and no prior chronic liver disease. Biochemical and histological injury types were classified as hepatocellular or cholestatic/mixed injury. The cohort was divided into three gender/age categories: men (41.0%), women <50 years (27.4%) and women ≥50 years of age (31.6%). Interaction of gender and age category (≥50 or not) was assessed.

Results

Hepatocellular injury was more prevalent in women <50 years vs. others (P=.002). After adjusting for biochemical injury types, black race and possible ageing effects, more severe interface hepatitis was noted in biopsies of women <50 years compared to those of men and women ≥50 years (P=.009 and P=.055 respectively). Compared to those of men, biopsies of women showed greater plasma cell infiltration, hepatocyte apoptosis, hepatocyte rosettes and lobular disarray but less iron‐positive hepatocytes and histological cholestasis (P<.05). These associations persisted after excluding cases of amoxicillin/clavulanic acid, anabolic steroids or nitrofurantoin DILI which showed gender‐specific distributions.

Conclusion

Gender and a proxy of menopause were associated with various features of inflammation and injury in DILI.
Phenytoin‐induced gingival overgrowth caused by death receptor pathway malfunction
Authors: Takeuchi R , Matsumoto H , Arikawa K , Taguchi C , Nakayama R , Nasu I , Hiratsuka K
Published: February 2017

Objective

In this study, we investigated the role of phenytoin (PHT) in death receptor‐induced apoptosis of gingival fibroblasts to clarify the mechanism of PHT‐induced gingival overgrowth.

Methods

Human gingival fibroblasts were cultured to semiconfluence and treated with PHT (0.025, 0.1, 0.25, and 1.0 μM) for 48 h, and then, the apoptotic cell numbers were relatively determined by absorptiometry. After 24 h of 0.25 μM PHT treatment, caspase activity was measured by absorptiometry, apoptotic and cell cycle phase distribution was analyzed by flow cytometry, expression levels of apoptotic genes were quantified by real‐time qPCR, and expression of apoptotic proteins was detected by Western blot analysis. After 48 h of 0.25 μM PHT treatment, appearance of apoptotic cells was detected by TUNEL assay.

Results

PHT treatment decreased the proportion of apoptotic cells in gingival fibroblasts compared to a serum‐free control culture in response to the protein changes as follows: PHT upregulated c‐FLIP and, in turn, downregulated FADD, caspase‐8, and caspase‐3; PHT upregulated c‐IAP2 and downregulated TRAF2; PHT downregulated caspase‐9 and caspase‐3 via decreased RIPK1 activity and increased Bcl‐2 activity.

Conclusion

PHT‐induced gingival overgrowth may result from the above‐mentioned mechanisms involving apoptosis inhibition in gingival fibroblasts.
Characterization and functional analysis of clpB gene from Acidovorax avenae subsp. avenae RS‐1
Authors: Zhang Y. , Zhang F. , Li B. , Yang Y. Z. , Ibrahim M. , Fang Y. S. , Qiu W. , Masum M. M. I. , Oliva R.
Published: February 2017

The type VI secretion system (T6SS) has been reported to be highly associated with various cellular activities in strain RS‐1 of Acidovorax avenae subsp. avenae (Aaa), the pathogen of bacterial brown stripe of rice. However, the role of the clpB gene that presents in the T6SS gene cluster in Aaa pathogenicity has not been clarified. The aim of the current study was to characterize the function of clpB and to investigate its contribution to bacterial pathogenesis using insertional deletion mutation and complementation approaches. The results indicated that mutation of clpB significantly affected bacterial growth, virulence, exopolysaccharide (EPS) production, biofilm formation and expression of 13 other T6SS genes of Aaa RS‐1. The reduction of virulence may be also partially due to the change in EPS composition, which was characterized by the Fourier transform infrared (FTIR) spectra. Furthermore, analysis of protein homology modelling showed that the structure of ClpB is different from those of the other T6SS components. In addition, structural difference was observed between ClpB and Type IV pili (TFP) as well as Type IV pilus biogenesis proteins (PilP), whose functions are similar to ClpB. Taken together, this study demonstrated that the clpB gene plays a key role in Aaa bacterial virulence.
The cost of asthma control
Authors: Chotirmall Sanjay H.
Published: February 2017

See article, page 454
Sexual reproduction, sporophyte development and molecular variation in the model moss Physcomitrella patens: introducing the ecotype Reute
Authors: Hiss Manuel , Meyberg Rabea , Westermann Jens , Haas Fabian B. , Schneider Lucas , Schallenberg‐Rüdinger Mareike , Ullrich Kristian K. , Rensing Stefan A.
Published: February 2017

Rich ecotype collections are used for several plant models to unravel the molecular causes of phenotypic differences, and to investigate the effects of environmental adaption and acclimation. For the model moss Physcomitrella patens collections of accessions are available, and have been used for phylogenetic and taxonomic studies, for example, but few have been investigated further for phenotypic differences. Here, we focus on the Reute accession and provide expression profiling and comparative developmental data for several stages of sporophyte development, as well as information on genetic variation via genomic sequencing. We analysed cross‐technology and cross‐laboratory data to define a confident set of 15 mature sporophyte‐specific genes. We find that the standard laboratory strain Gransden produces fewer sporophytes than Reute or Villersexel, although gametangia develop with the same time course and do not show evident morphological differences. Reute exhibits less genetic variation relative to Gransden than Villersexel, yet we found variation between Gransden and Reute in the expression profiles of several genes, as well as variation hot spots and genes that appear to evolve under positive Darwinian selection. We analyzed expression differences between the ecotypes for selected candidate genes in the GRAS transcription factor family, the chalcone synthase family and in genes involved in cell wall modification that are potentially related to phenotypic differences. We confirm that Reute is a P. patens ecotype, and suggest its use for reverse‐genetics studies that involve progression through the life cycle and multiple generations.
Relativistic Energies and Scattering Phase Shifts for the Fermionic Particles Scattered by Hyperbolical Potential with the Pseudo(spin) Symmetry
Authors: Oyewumi K. J. , Oluwadare O. J.
Published: February 2017

In this paper, we studied the approximate scattering state solutions of the Dirac equation with the hyperbolical potential with pseudospin and spin symmetries. By applying an improved Greene-Aldrich approximation scheme within the formalism of functional analytical method, we obtained the spin-orbit quantum numbers dependent scattering phase shifts for the spin and pseudospin symmetries. The normalization constants, lower and upper radial spinor for the two symmetries, and the relativistic energy spectra were presented. Our results reveal that both the symmetry constants (Cps and Cs) and the spin-orbit quantum number κ affect scattering phase shifts significantly.
Retinal Image Denoising via Bilateral Filter with a Spatial Kernel of Optimally Oriented Line Spread Function
Authors: He Yunlong , Zheng Yuanjie , Zhao Yanna , Ren Yanju , Lian Jian , Gee James
Published: February 2017

Filtering belongs to the most fundamental operations of retinal image processing and for which the value of the filtered image at a given location is a function of the values in a local window centered at this location. However, preserving thin retinal vessels during the filtering process is challenging due to vessels’ small area and weak contrast compared to background, caused by the limited resolution of imaging and less blood flow in the vessel. In this paper, we present a novel retinal image denoising approach which is able to preserve the details of retinal vessels while effectively eliminating image noise. Specifically, our approach is carried out by determining an optimal spatial kernel for the bilateral filter, which is represented by a line spread function with an orientation and scale adjusted adaptively to the local vessel structure. Moreover, this approach can also be served as a preprocessing tool for improving the accuracy of the vessel detection technique. Experimental results show the superiority of our approach over state-of-the-art image denoising techniques such as the bilateral filter.
Genetic Diversity and Association Analysis for Solvent Retention Capacity in the Accessions Derived from Soft Wheat Ningmai 9
Authors: Jiang Peng , Zhang Ping-Ping , Zhang Xu , Ma Hong-Xiang
Published: February 2017

Solvent retention capacity (SRC) test is an effective method for quality evaluation of soft wheat. Ningmai 9 is a founder in soft wheat breeding. The SRC and genotype of Ningmai 9 and its 117 derivatives were tested. Association mapping was employed to identify the quantitative trait loci (QTL) associated with SRCs. Ningmai 9 had the allele frequency of 75.60% and 67.81% to its first- and second-generation derivatives, respectively, indicating higher contribution than theoretical expectation. Neighbor-joining cluster based on the genotyping data showed that Ningmai 9 and most of its first-generation derivatives were clustered together, whereas its second-generation derivatives were found in another group. The variation coefficients of SRCs in the derivatives ranged from 5.35% to 8.63%. A total of 29 markers on 13 chromosomes of the genome were associated with the SRCs. There were 6 markers associated with more than one SRC or detected in two years. The results suggested that QTL controlling SRCs in Ningmai 9 might be different from other varieties. Markers Xgwm44, Xbarc126, Xwmc790, and Xgwm232 associated with SRCs in Ningmai 9 might be used for quality improvement in soft wheat breeding.
Assessment of Antiretroviral Treatment Adherence among Children Attending Care at a Tertiary Hospital in Southeastern Nigeria
Authors: Akahara Cletus , Nwolisa Emeka , Odinaka Kelechi , Okolo Seline
Published: February 2017

Background. Adherence is the strongest predictor of successful treatment outcome among children infected with HIV. Our aim was to assess the antiretroviral drugs adherence status of HIV-infected children attending care at a tertiary hospital in Southeastern Nigeria.Method. The study involved a cross-sectional survey of 210 HIV-infected children attending care at a tertiary hospital in Southeastern Nigeria using self-report method of assessment. Optimal ART adherence is defined as patient taking not missing more than 1 dose of combined antiretroviral therapy medication in the preceding 2 weeks prior to the study.Result. A majority of the subjects 191 (91%) had good adherence. There was a significant relationship between adherence and patient educational level (p=0.004), duration of treatment (p=0.001), drug administrator (p=0.005), and orphan status (p=0.001). The motivating factor for adherence was “not falling sick as before” while stigma was the most discouraging factor.Conclusion. The adherence level in this study was good. Stigma was an important reason given by patient/caregivers for nonadherence. There is need for concerted effort in addressing this barrier to improve adherence and prevent the emergence of drug resistance and treatment failure.
Endoscopic Appearance of Oropharyngeal and Upper GI Kaposi’s Sarcoma in an Immunocompromised Patient
Authors: Darr Umar , Renno Anas , Khan Zubair , Alkully Turki , Moslim Maitham A. , Kamal Sehrish , Nawras Ali
Published: February 2017

Introduction. Kaposi’s sarcoma (KS) usually manifests as a cutaneous disease but GI manifestation is often rare. It is associated with human herpes virus-8 (HHV-8) and seen in immunocompromised patients. In the USA, use of highly active antiretroviral therapy (HAART) has drastically reduced incidence of KS in HIV patients. Case Presentation. A 65-year-old male with human immunodeficiency virus (HIV) was admitted to the intensive care unit (ICU) with cardiopulmonary arrest secondary to hyperkalemia of 7.5 meq/L. Following placement of orogastric and endotracheal tube (ETT), a significant amount of blood was noticed in the ETT. Hemoglobin trended down from 9.6 mg/dL to 6.7 mg/dL over five days. Stool guaiac was positive. Esophagogastroduodenoscopy (EGD) was performed and revealed multiple large hypervascularized violaceous submucosal nodular lesions with stigmata of bleeding seen on the soft palate and pharynx and within the cricopharyngeal area close to the vocal cords. Biopsy of the soft palate lesions showed proliferation of neoplastic spindle shaped cells arranged in bundles with slit-like capillary spaces containing erythrocytes consistent with Kaposi’s sarcoma. Biopsy was positive for HHV-8. Colonoscopy was unremarkable. There were no cutaneous manifestations of the disease. Conclusion. GI involvement of Kaposi’s sarcoma must be considered in immunocompromised patients and can be confirmed by endoscopic methods.
Increased Circulating Endothelial Microparticles Associated with PAK4 Play a Key Role in Ventilation-Induced Lung Injury Process
Authors: Pan Shuming , Fei Aihua , Jing Lihong , Zhang Xiangyu , Gao Chengjin
Published: February 2017

Inappropriate mechanical ventilation (MV) can result in ventilator-induced lung injury (VILI). Probing mechanisms of VILI and searching for effective methods are current areas of research focus on VILI. The present study aimed to probe into mechanisms of endothelial microparticles (EMPs) in VILI and the protective effects of Tetramethylpyrazine (TMP) against VILI. In this study, C57BL/6 and TLR4KO mouse MV models were used to explore the function of EMPs associated with p21 activated kinases-4 (PAK-4) in VILI. Both the C57BL/6 and TLR4 KO groups were subdivided into a mechanical ventilation (MV) group, a TMP + MV group, and a control group. After four hours of high tidal volume (20 ml/kg) MV, the degree of lung injury and the protective effects of TMP were assessed. VILI inhibited the cytoskeleton-regulating protein of PAK4 and was accompanied by an increased circulating EMP level. The intercellular junction protein of β-catenin was also decreased accompanied by a thickening alveolar wall, increased lung W/D values, and neutrophil infiltration. TMP alleviated VILI via decreasing circulating EMPs, stabilizing intercellular junctions, and alleviating neutrophil infiltration.
Spontaneous Heparin-Induced Thrombocytopenia and Venous Thromboembolism following Total Knee Arthroplasty
Authors: Baker Kevin , Lim Ming Y.
Published: February 2017

A 72-year-old Caucasian woman was admitted for an elective left total knee arthroplasty. Her surgery was uncomplicated and she was discharged to a rehabilitation facility. Twelve days later, she developed acute shortness of breath followed by a syncopal episode. She was hypoxic and cyanotic, requiring hospitalization and intubation, and was subsequently diagnosed with bilateral submassive pulmonary emboli and bilateral lower extremity deep vein thrombosis. She was started on unfractionated heparin infusion. Within 24 hours of exposure, she had an acute decrease in platelet count to 48,000. Heparin was discontinued and argatroban was initiated due to concern for heparin-induced thrombocytopenia (HIT). Both quantitative enzyme immunoassay and functional assay confirmed the diagnosis of HIT. The patient had no prior lifetime heparin exposure. Given the absence of preceding heparin therapy, this case is consistent with the diagnosis of spontaneous HIT.
Parental High‐Fat Diet Promotes Inflammatory and Senescence‐Related Changes in Prostate
Authors: Tikoo Kulbhushan , Vikram Ajit , Shrivastava Shweta , Jena Gopabandhu , Shah Heta , Chhabra Richa
Published: February 2017

Background. Obesity and dietary habits are associated with increased incidences of aging‐related prostatic diseases. The present study was aimed to investigate transgenerational effects of chronic high‐fat diet (HFD) feeding on inflammation and senescence‐related changes in prostate. Methods. Sprague‐Dawley rats were kept on either normal or HFD one. Senescence‐associated β‐galactosidase (SA β‐gal) activity, inflammation, and cellular proliferation were determined in the prostate. Results. Increased SA β‐gal activity, expression of p53, and cell proliferation marker PCNA were observed in ventral prostate of HFD‐fed rats. Immunostaining for p53 and PCNA revealed that the p53 immunopositive cells were primarily in stroma while PCNA immunopositive cells were epithelial cells. An increase in expression of cycloxygenase‐2 (COX‐2) and phosphorylation of nuclear factor‐kappa B (NF‐kB) was observed in prostate of weaning pups HFD‐fed parents. However, in adult pups, irrespective of dietary habit, a significant increase in the expression of COX‐2, PCNA, phosphorylation of NF‐kB, infiltration of inflammatory cells, and SA β‐gal activity was observed. Conclusions. Present investigation reports that HFD feeding promotes accumulation of p53 expressing cells, proliferation of epithelial cells, and senescence‐related changes in prostate. Further, parental HFD‐feeding upholds inflammatory, proliferative, and senescence‐related changes in prostate of pups.
Amino Acid Catabolism in Alzheimer’s Disease Brain: Friend or Foe?
Authors: Griffin Jeddidiah W. D. , Bradshaw Patrick C.
Published: February 2017

There is a dire need to discover new targets for Alzheimer’s disease (AD) drug development. Decreased neuronal glucose metabolism that occurs in AD brain could play a central role in disease progression. Little is known about the compensatory neuronal changes that occur to attempt to maintain energy homeostasis. In this review using the PubMed literature database, we summarize evidence that amino acid oxidation can temporarily compensate for the decreased glucose metabolism, but eventually altered amino acid and amino acid catabolite levels likely lead to toxicities contributing to AD progression. Because amino acids are involved in so many cellular metabolic and signaling pathways, the effects of altered amino acid metabolism in AD brain are far‐reaching. Possible pathological results from changes in the levels of several important amino acids are discussed. Urea cycle function may be induced in endothelial cells of AD patient brains, possibly to remove excess ammonia produced from increased amino acid catabolism. Studying AD from a metabolic perspective provides new insights into AD pathogenesis and may lead to the discovery of dietary metabolite supplements that can partially compensate for alterations of enzymatic function to delay AD or alleviate some of the suffering caused by the disease.
Cooccurrence of Metastatic Papillary Thyroid Carcinoma andSalmonellaInduced Neck Abscess in a Cervical Lymph Node
Authors: Kim Jae-Myung , Kim Ju-Yeon , Jung Eun Jung , Song Eun Jin , Kim Dong Chul , Jeong Chi-Young , Ju Young-Tae , Lee Young-Joon , Hong Soon-Chan , Choi Sang-Kyung , Ha Woo-Song
Published: February 2017

Cervical lymph node metastasis is common in patients with papillary thyroid carcinoma (PTC).Salmonellaspecies are rarely reported as causative agents in focal infections of the head and neck. The cooccurrence of lymph node metastasis from PTC and a bacterial infection is rare. This report describes a 76-year-old woman with a cervical lymph node metastasis from PTC andSalmonellainfection of the same lymph node. The patient presented with painful swelling in her left lateral neck region for 15 days, and neck ultrasonography and computed tomography showed a cystic mass along left levels II–IV. The cystic mass was suspected of being a metastatic lymph node; modified radical neck dissection was performed. Histopathological examination confirmed the presence of PTC in the resected node and laboratory examination of the combined abscess cavity confirmed the presence ofSalmonella Typhi. Following antibiotic sensitivity testing of the culturedSalmonella Typhi, she was treated with proper antibiotics. Cystic lesions in lymph nodes with metastatic cancer may indicate the presence of cooccurring bacterial infection. Thus, culturing of specimen can be option to make accurate diagnosis and to provide proper postoperative management.