bluuebunny/crossref_metadata_2025 huggingface dataset:
STATs in Lung Development: Distinct Early and Late Expression, Growth Modulation and Signaling Dysregulation in Congenital Diaphragmatic Hernia
Authors: Piairo Paulina , Moura Rute S. , Baptista Maria João , Correia-Pinto Jorge , Nogueira-Silva Cristina
Published: January 2018

Background: Congenital diaphragmatic hernia (CDH) is a life-threatening developmental anomaly, intrinsically combining severe pulmonary hypoplasia and hypertension. During development, signal transducers and activators of transcription (STAT) are utilized to elicit cell growth, differentiation, and survival. Methods: We used the nitrofen-induced CDH rat model. At selected gestational time points, lungs were divided into two experimental groups, i.e., control or CDH. We performed immunohistochemistry and western blotting analysis to investigate the developmental expression profile of the complete family of STATs (STAT1-6), plus specific STATs activation (p-STAT3, p-STAT6) and regulation by SOCS (SOCS3) in normal lungs against those of diseased lungs. The normal fetal lung explants were treated with piceatannol (STAT3 inhibitor) in vitro followed by morphometrical analysis. Results: Molecular profiling of STATs during the lung development revealed distinct early and late expression signatures. Experimental CDH altered the STATs expression, activation, and regulation in the fetal lungs. In particular, STAT3 and STAT6 were persistently over-expressed and early over-activated. Piceatannol treatment dose-dependently stimulated the fetal lung growth. Conclusion: These findings suggest that STATs play an important role during normal fetal lung development and CDH pathogenesis. Moreover, functionally targeting STAT signaling modulates fetal lung growth, which highlights that STAT3 and STAT6 signaling might be promising therapeutic targets in reducing or preventing pulmonary hypoplasia in CDH.
Early Detection of Subclinical Myocardial Damage in Chronic Aortic Regurgitation and Strategies for Timely Treatment of Asymptomatic Patients
Authors: Lee Joe K.T. , Franzone Anna , Lanz Jonas , Siontis George C.M. , Stortecky Stefan , Gräni Christoph , Roost Eva , Windecker Stephan , Pilgrim Thomas
Published: January 2018

A series of hemodynamic and pathological responses occur in chronic aortic regurgitation, which eventually result in myocardial fibrosis and irreversible left ventricular dysfunction. According to guidelines, valvular surgery is recommended with the development of symptoms, left ventricular systolic dysfunction, or left ventricular dilatation. The optimal timing of surgical intervention has recently been questioned with documentation of irreversible myocardial damage resulting in incomplete left ventricular recovery and adverse clinical outcomes after surgery. Recognizing the shortcomings of the guidelines, we performed a comprehensive review on the novel diagnostic methods that have been shown to improve the detection of subclinical ventricular dysfunction in chronic aortic regurgitation and to improve prediction of outcomes.
Long‐Term Exposure of Fine Particulate Matter Causes Hypertension by Impaired Renal D
1
Receptor–Mediated Sodium Excretion via Upregulation of G‐Protein–Coupled Receptor Kinase Type 4 Expression in Sprague‐Dawley Rats
Authors: Lu Xi , Ye Zhengmeng , Zheng Shuo , Ren Hongmei , Zeng Jing , Wang Xinquan , Jose Pedro A. , Chen Ken , Zeng Chunyu
Published: January 2018

Background

Epidemiological evidence supports an important association between air pollution exposure and hypertension. However, the mechanisms are not clear.

Methods and Results

Our present study found that long‐term exposure to fine particulate matter (PM
2.5
) causes hypertension and impairs renal sodium excretion, which might be ascribed to lower D
1
receptor expression and higher D
1
receptor phosphorylation, accompanied with a higher G‐protein–coupled receptor kinase type 4 (GRK4) expression. The in vivo results were confirmed in in vitro studies (ie,
PM
2.5
increased basal and decreased D
1
receptor mediated inhibitory effect on Na
+
‐K
+
ATP
ase activity, decreased D
1
receptor expression, and increased D
1
receptor phosphorylation in renal proximal tubule cells). The downregulation of D
1
receptor expression and function might be attributable to a higher
GRK
4 expression after the exposure of renal proximal tubule cells to
PM
2.5
, because downregulation of
GRK
4 by small‐interfering
RNA
reversed the D
1
receptor expression and function. Because of the role of reactive oxygen species on D
1
receptor dysfunction and its relationship with air pollution exposure, we determined plasma reactive oxygen species and found the levels higher in
PM
2.5
‐treated Sprague‐Dawley rats. Inhibition of reactive oxygen species by tempol (4‐hydroxy‐2,2,6,6‐tetramethylpiperidin‐1‐oxyl) reduced blood pressure and increased sodium excretion in
PM
2.5
‐treated Sprague‐Dawley rats, accompanied by an increase in the low D
1
receptor expression, and decreased the hyperphosphorylated D
1
receptor and
GRK
4 expression.

Conclusions

Our present study indicated that long‐term exposure of
PM
2.5
increases blood pressure by decreasing D
1
receptor expression and function; reactive oxygen species, via regulation of
GRK
4 expression, plays an important role in the pathogenesis of
PM
2.5
‐induced hypertension.
Relationship Between Dietary Vitamin D and Deaths From Stroke and Coronary Heart Disease
Authors: Sheerah Haytham A. , Eshak Ehab S. , Cui Renzhe , Imano Hironori , Iso Hiroyasu , Tamakoshi Akiko
Published: January 2018

Background and Purpose—

There is growing evidence about the importance of vitamin D for cardiovascular health. Therefore, we examined the relationship between dietary vitamin D intake and risk of mortality from stroke and coronary heart disease in Japanese population.

Methods—

A prospective study encompassing 58 646 healthy Japanese adults (23 099 men and 35  547 women) aged of 40 to 79 years in whom dietary vitamin D intake was determined via a self-administered food frequency questionnaire. The median follow-up period was 19.3 years (1989–2009). The hazard ratios and 95% confidence intervals of mortality were calculated using categories of vitamin D intake.

Results—

During 965 970 person-years of follow-up, 1514 stroke and 702 coronary heart disease deaths were documented. Vitamin D intake was inversely associated with risk of mortality from total stroke especially intraparenchymal hemorrhage but not from coronary heart disease; the multivariable hazard ratios (95% confidence intervals) for the highest (≥440 IU/d) versus lowest (<110 IU/D) categories of vitamin D intake were 0.70 (0.54–0.91;
P
for trend=0.04) for total stroke and 0.66 (0.46–0.96;
P
for trend=0.04) for intraparenchymal hemorrhage.

Conclusions—

Dietary vitamin D intake seems to be inversely associated with mortality from stroke.
Individual Behavior and Global Environmental Problems
Authors: DeSombre Elizabeth R.
Published: January 2018

Global environmental problems are often the aggregated effect of behavior by individuals, but is persuading people individually to change their behavior useful for addressing these problems? Understanding why it is that people behave individually in ways that have collectively problematic environmental effects is key to understanding what works—and doesn’t work—to change this individual behavior. This article argues that because of the problem characteristics and social structures that underpin large-scale environmental problems, a focus on trying to persuade people to behave in ways that are less environmentally problematic is ineffective at best and possibly even counterproductive. Instead we should focus on changing systems and structures to provide incentives, routines, and contexts in which we can simultaneously change the behavior of large groups of people, whether or not their behavior change is undertaken intentionally for environmental benefit.
Mapping the Trade and Environment Nexus: Insights from a New Data Set
Authors: Morin Jean-Frédéric , Dür Andreas , Lechner Lisa
Published: January 2018

Environment and trade are increasingly linked through preferential trade agreements. Despite the encompassing nature of environmental provisions in trade agreements, studies on causes and consequences of the trade and environment linkage are scarce. A main cause hindering research in this area is the lack of data. In this research note, we introduce an original data set (TREND) on environmental provisions found in 630 trade agreements signed between 1947 and 2016—the most comprehensive data set in terms of both variables coded and agreements covered. We illustrate the data set’s usefulness by assessing the question of why countries include environmental provisions in trade agreements. Are trade negotiations opportunities to promote stringent environmental standards? Or are environmental provisions window dressing covering protectionist interests? We find evidence that democracies, countries that face import competition, and countries that care about the environment are more likely to include environmental provisions in trade agreements. The database is of particular relevance for research on international institutional design, policy innovation, regime complexity, policy diffusion, and regime effectiveness.
Control Changes the Way We Look at the World
Authors: Wen Wen , Haggard Patrick
Published: January 2018

The feeling of control is a fundamental aspect of human experience and accompanies our voluntary actions all the time. However, how the sense of control interacts with wider perception, cognition, and behavior remains poorly understood. This study focused on how controlling an external object influences the allocation of attention. Experiment 1 examined attention to an object that is under a different level of control from the others. Participants searched for a target among multiple distractors on screen. All the distractors were partially under the participant's control (50% control level), and the search target was either under more or less control than the distractors. The results showed that, against this background of partial control, visual attention was attracted to an object only if it was more controlled than other available objects and not if it was less controlled. Experiment 2 examined attention allocation in contexts of either perfect control or no control over most of the objects. Specifically, the distractors were under either perfect (100%) control or no (0%) control, and the search target had one of six levels of control varying from 0% to 100%. When differences in control between the distractors and the target were small, visual attention was now more strongly drawn to search targets that were less controlled than distractors, rather than more controlled, suggesting attention to objects over which one might be losing control. Experiment 3 studied the events of losing or gaining control as opposed to the states of having or not having control. ERP measures showed that P300 amplitude proportionally encoded the magnitude of both increases and decreases in degree of control. However, losing control had more marked effects on P170 and P300 than gaining an equivalent degree of control, indicating high priority for efficiently detecting failures of control. Overall, our results suggest that controlled objects preferentially attract attention in uncontrolled environments. However, once control has been registered, the brain becomes highly sensitive to subsequent loss of control. Our findings point toward careful perceptual monitoring of degree of one's own agentic control over external objects. We suggest that control has intrinsic cognitive value because perceptual systems are organized to detect it and, once it has been acquired, to maintain it.
Transitory Inhibition of the Left Anterior Intraparietal Sulcus Impairs Joint Actions: A Continuous Theta-Burst Stimulation Study
Authors: Sacheli Lucia M. , Tieri Gaetano , Aglioti Salvatore M. , Candidi Matteo
Published: January 2018

Although temporal coordination is a hallmark of motor interactions, joint action (JA) partners do not simply synchronize; rather, they dynamically adapt to each other to achieve a joint goal. We created a novel paradigm to tease apart the processes underlying synchronization and JA and tested the causal contribution of the left anterior intraparietal sulcus (aIPS) in these behaviors. Participants had to synchronize their congruent or incongruent movements with a virtual partner in two conditions: (i) being instructed on what specific action to perform, independently from what action the partner performed (synchronization), and (ii) being instructed to adapt online to the partner's action (JA). Offline noninvasive inhibitory brain stimulation (continuous theta-burst stimulation) over the left aIPS selectively modulated interpersonal synchrony in JA by boosting synchrony during congruent interactions and impairing it during incongruent ones, while leaving performance in the synchronization condition unaffected. These results suggest that the left aIPS plays a causal role in supporting online adaptation to a partner's action goal, whereas it is not necessarily engaged in social situations where the goal of the partner is irrelevant. This indicates that, during JAs, the integration of one's own and the partner's action goal is supported by aIPS.
Intraspecific call variation in a Neotropical gladiator frog with a complex advertisement call
Authors: Turin Rubens A.F. , Nali Renato C. , Prado Cynthia P.A.
Published: January 2018

Vocalisation is one of the most conspicuous behavioural traits in different animals, but its emission can be variable within species, depending on environmental, morphological, and/or social factors. Understanding how acoustic parameters vary can provide information about sexual selection mechanisms that might have shaped the species’ evolutionary history. We quantified and compared the variation of five call parameters within and among the males of Bokermannohyla ibitiguara, a Neotropical treefrog with complex reproduction and advertisement calls. The parameters were classified as static (dominant frequency), intermediate (note durations) or dynamic (pulse rate of the long note and call duration). Despite these differences, all of them varied more among individuals than within individuals, and most were associated with individual discrimination, showing potential acoustic recognition by males and females. A multiple regression analysis showed that all temporal parameters were affected by abiotic factors, except pulse rate of the long note; body size affected dominant frequency, duration of the long notes and call duration. This high variability in parameters, and the strong support for individual discrimination, indicate the existence of sexual selection mechanisms operating on calls; however, the individual recognition system is very complex and not limited to a single characteristic of the call. This is supported by the reproductive behavior of this species, including choosy females, elaborate courtships, and male-male vocal contests and physical combats. Fine-scale playback experiments with males and females will help us further understand sexual selection mechanisms in this and other acoustically oriented animals.
Rigidotubus tephroleucus gen. et sp. nov. (Cystostereaceae, Agaricales) evidenced by morphological characters and phylogenetic analyses
Authors: SONG JIE , XING JIA-HUI , JI XING , SUN YI-FEI , CUI BAO-KAI , DAI YU-CHENG
Published: January 2018

A new poroid wood-inhabiting fungal genus, Rigidotubus, is proposed to accommodate  R. tephroleucus sp. nov. based on morphological characters and molecular evidence. The genus is characterized by tough and poroid basidiomata, white to grayish white pore surface, white sterile margin, a monomitic hyphal system with clamped generative hyphae, ovoid to ellipsoid basidiospores negative in Melzer’s reagent and Cotton Blue. The phylogenetic analyses inferred from the internal transcribed spacer (ITS) and nuclear large subunit (28S) ribosomal RNA gene regions confirmed that Rigidotubus belongs to Cystostereaceae in Agaricales. A key to the accepted genera of Cystostereaceae is provided.
Pollen morphology of some Verbascum (Scrophulariaceae) taxa in Turkey
Authors: ÖZTÜRK AYŞE , GÜNEY KUDRET BETÜL , BANİ BARIŞ , GÜNEY KERİM , KARAVELİOĞULLARI FAİK AHMET , PINAR NUR MÜNEVVER , ÇETER TALİP
Published: January 2018

Pollen morphology of six Verbascum (Scrophulariaceae) taxa belonging to five different groups in the genus [V. georgicum (group E), V. nudatum var. nudatum (group F), V. cariense (group F), V. bithynicum (group H), V. pycnostachyum (group K), and V. lasianthum (group L)] was studied. Pollen slides were prepared according to the Woodhouse method and were examined with light-microscopy (LM) and Scanning Electron Microscopy (SEM). All studied pollen grains are generally monads, though tetrads (5 %) were observed in Verbascum nudatum var. nudatum. Pollen grains of all studied taxa were determined as isopolar and radially symmetric. In general terms, aperture types are trizonocolporate, but also trisyncolpate (V. lasianthum 10 %, V. pycnostachum 1 %, and V. georgicum 4 %) and trizonocolpate (V. cariense 10 %, V. bithynicum 10%, V. lasianthum 90%, V. pycnostachyum 9%, and V. georgicum 96 %) aperture types were observed. The shapes of the pollen grains were determined as prolate, subprolate, prolate-spheroidal and oblate-spheroidal. The sculpture was reticulate in all cases. The results of the study corroborate that morphological features, such as pollen shape, polar axis length (P), equatorial axis length (L), aperture type, surface ornamentation, muri thickness, and lumina shape, show differences which can be taken into consideration in the systematic discrimination within the groups, and also for discrimination of the groups in the genus.
Inscribed Blocks from Tomb Chapels at Hawara
Authors: Fiore-Marochetti Elisa
Published: January 2018

Publication of inscribed and decorated Middle Kingdom blocks found by Petrie in the area around the pyramid of Amenemhat III at Hawara, together with discussion of the religious concepts reflected in some of the texts.
The Roman Quarry and Installations in Wadi Umm Wikala and Wadi Semna
Authors: Sidebotham S. E. , Barnard H. , Harrell J. A. , Tomber R. S.
Published: January 2018

A detailed surface survey of the gabbro quarry and related facilities in Wadis Umm Wikala and Semna indicates activity in the first to second or early third centuries AD. Surface pottery found associated with quarry faces, loading ramps, related huts, skopeloi, a putative temple, a main adminstrative building and nearby hydreuma attest to intensive operations here contemporary with periods of early exploitation of the larger quarries of Mons Claudianus and Mons Porphyrites farther north in the Eastern Desert. A lengthy Greek inscription of the early first century AD recovered here over a century ago records that the ancient name of the site was Ophites.
Old Kingdom Basalt Quarrying Activities at Widan El-Faras, Northern Faiyum Desert
Authors: Bloxam Elizabeth , Storemyr Per
Published: January 2018

The quarry of Widan el-Faras in the Northern Faiyum Desert was the source of basalt used mainly for paving mortuary temples floors in some of the Fourth and Fifth Dynasty pyramid complexes. An examination of the layout of the quarry and the attached infrastructure, as well as the extracted volumes and the use of the basalt, indicates a campaign-like, seasonal exploitation of the stone linked to the high level of Lake Moeris during the Fourth and Fifth Dynasties. These conditions enabled medium-sized basalt blocks to be transported largely via water to the pyramid construction sites, thus avoiding lengthy and difficult carriage overland.
The Nile Level Records of the Twenty-Second and Twenty-Third Dynasties in Karnak: A Reconsideration of their Chronological Order
Authors: Broekman Gerard P. F.
Published: January 2018

Investigation of the Nile Level Records of the Twenty-second and Twenty-third Dynasties with regard to their positions on the quay wall, their orthography and their structure can shed new light on their chronological order and on the identity of the kings mentioned. The author ascertains that in the texts the word ḥ'pj is spelled in two different ways, with one orthography going out of use and being replaced by another. As a result there is more clarity about the so far uncertain identification of some of the kings mentioned. Contrary to what is generally accepted, text No. 3 does not belong to Shoshenq I, but should be attributed either to Shoshenq IV, the successor to Shoshenq III, or, more probably, to an Upper Egyptian king Shoshenq, not known from other sources, who might be defined as Shoshenq VIa.
Alloantigen System L Affects the Outcome of Rous Sarcomas1
Authors: Medarova Zdravka , Briles W. Elwood , Taylor Robert L.
Published: January 2018

This study was designed to examine the alloantigen system L effects on Rous sarcomas in three B complex genotypes. The parental stock was 50% Modified Wisconsin Line 3 × White Leghorn Line NIU 4 and 50% inbred Line 6.15-5. Pedigree matings of two B2B5L1L2sires to five B2B5L1L2dams per sire produced experimental chicks segregating for B and L genotypes. Chicks were inoculated with 20 pock-forming units (pfu) of Rous sarcoma virus (RSV) at 6 weeks of age. Tumors were scored six times over 10 weeks postinoculation after which the tumor scores were used to assign a tumor profile index (TPI) to each chicken. Tumor growth over time and TPl were evaluated by repeated-measures analysis of variance and analysis of variance, respectively. Six trials were conducted with a total of 151 chickens. The major histocompatibility (B) complex affected the responses as the B2B2and B2B5genotypes had significantly lower tumor growth over time and TPl than the B5B5genotype. Separate analyses revealed no significant L system effect in B2B2or B2B5backgrounds. However, L genotype significantly affected (P < 0.05) both tumor growth over time and TPl in B5B5chickens. B5B5L1L2birds had TPl significantly lower than B5B5L1L1chickens but not B5B5L2L2. Mortality was lower in the B5B5L1L2birds than in B5B5L2L2chickens. The L system, or one closely linked, affects the growth and ultimate outcome of Rous sarcomas. The response may depend upon the genetic background as well as MHC type.
Hypothalamic Histamine Neurons Activate Lipolysis in Rat Adipose Tissue
Authors: Tsuda Kaoru , Yoshimatsu Hironobu , Niijima Akira , Chiba Seiichi , Okeda Toshimitsu , Sakata Toshiie
Published: January 2018

The contribution of hypothalamic histamine neurons to the central regulation of peripheral lipid metabolism was investigated in rats using in vivo microdialysis system. A bolus infusion of l-histamine at doses of 10–103nmol/rat into the third cerebral ventricle (i3vt) dose-dependently increased glycerol concentration in the perfusate from the epididymal adipose tissue. I3vt infusion of 102nmol/rat thioperamide, an autoinhibitory H3receptor antagonist that activates histamine neurons to increase synthesis and release of neuronal histamine, convincingly mimicked histamine action in the augmented lipolysis. Intraperitoneal pretreatment with propranolol, a β-adrenoceptor antagonist, abolished the thioperamide-induced lipolytic action. An electrophysiological study demonstrated that efferent sympathetic nerves innervating the epididymal fat were activated after the i3vt infusion of thioperamide. Hypothalamic histamine neurons thus regulate peripheral lipid metabolism through the accelerating lipolytic action by activation of sympathetic β-adrenoceptor.
Reducing unnecessary culturing: a systems approach to evaluating urine culture ordering and collection practices among nurses in two acute care settings
Authors: Redwood Robert , Knobloch Mary Jo , Pellegrini Daniela C. , Ziegler Matthew J. , Pulia Michael , Safdar Nasia
Published: January 2018

Background

Inappropriate ordering and acquisition of urine cultures leads to unnecessary treatment of asymptomatic bacteriuria (ASB). Treatment of ASB contributes to antimicrobial resistance particularly among hospital-acquired organisms. Our objective was to investigate urine culture ordering and collection practices among nurses to identify key system-level and human factor barriers and facilitators that affect optimal ordering and collection practices.

Methods

We conducted two focus groups, one with ED nurses and the other with ICU nurses. Questions were developed using the Systems Engineering Initiative for Patient Safety (SEIPS) framework. We used iterative categorization (directed content analysis followed by summative content analysis) to code and analyze the data both deductively (using SEIPS domains) and inductively (emerging themes).

Results

Factors affecting optimal urine ordering and collection included barriers at the person, process, and task levels. For ED nurses, barriers included patient factors, physician communication, reflex culture protocols, the electronic health record, urinary symptoms, and ED throughput. For ICU nurses, barriers included physician notification of urinalysis results, personal protective equipment, collection technique, patient body habitus, and Foley catheter issues.

Conclusions

We identified multiple potential process barriers to nurse adherence with evidence-based recommendations for ordering and collecting urine cultures in the ICU and ED. A systems approach to identifying barriers and facilitators can be useful to design interventions for improving urine ordering and collection practices.
Head and Neck Surgical Oncology Choosing Wisely Campaign: Imaging for patients with hoarseness, fine needle aspiration for neck mass, and ultrasound for odynophagia
Authors: Eskander Antoine , Monteiro Eric , O'Connell Dan , Taylor S. Mark ,   The Canadian Association of Head and Neck Surgical Oncology (CAHNSO)
Published: January 2018

Choosing Wisely Canada, is a campaign designed to raise awareness regarding inappropriate or unnecessary tests and treatments. The Canadian Society of Otolaryngology - Head & Neck Surgery and the Canadian Association of Head and Neck Surgical Oncologists developed a Choosing Wisely Canada list to help promote high quality care for patients presenting with disorders of the head and neck: (1) Don't order imaging - computer tomography (CT) or magnetic resonance imaging (MRI) - as the initial investigation for patients presenting with a chief complaint of hoarseness, (2) Don't perform an open biopsy or excision of a neck mass without having first considered a fine needle aspiration (FNA) biopsy and, (3) Don't order neck ultrasound to investigate odynophagia (discomfort or pain with swallowing) or globus sensation.
The lived experience of CrossFit as a context for the development of women’s body image and appearance management practices
Authors: Podmore Miranda , Ogle Jennifer Paff
Published: January 2018

The purpose of this interpretive study was to explore how women’s participation in the sport of CrossFit sets a context for the development of their body images—including their thoughts and feelings about the body and their lived experiences of embodiment—as well as their perceptions of culturally constructed ideals of beauty and gender. Analyses were informed by feminist cultural studies. In-depth, face-to-face interviews were conducted with 16 women who regularly participate in CrossFit. Data were analyzed using constant comparison processes. Findings illuminate how women experienced the culture of a male-owned, co-ed, CrossFit gym and how their immersion and participation in that gym culture gave rise to varied bodily experiences and practices, including body/appearance ideals, bodily appraisals, appetites and diets, physical fitness ideologies, appearance management routines, perspectives on gender, and identity development. Participant narratives revealed diverse lived realities across accounts as well as some evidence of contradiction or ambivalence within individual accounts. Implications for professionals who work in the body image area (e.g., nutritionists, counselors/therapists, sports psychologists), for the apparel and merchandising industry, for the sport of CrossFit, and for future work in the area are discussed.
Hope or hype in the treatment of schizophrenia – what's the role of the physician?
Authors: Bressan Rodrigo A. , Grohs Geder E. M. , Matos Gabriela , Shergill Sukhi
Published: January 2018

According to the experience of people with schizophrenia, their psychiatrists' attitude towards the outcome of their illness is lacking in hope, which directly affects mutual faith in treatment. Here we discuss the scientific basis of hope and show its instrumental role in optimising the best treatment strategies for schizophrenia.

Declaration of interest

R.A.B has received honoraria for educational input and non-financial support from Ache; honoraria for educational input from Lundbeck; grants, honoraria for educational input and non-financial support from Janssen; all outside the submitted work. G.E.M.G. has received honoraria for educational input and non-financial support from Janssen outside the submitted work. G.M. reports support from Janssen-Cilag, outside the submitted work, and is an employee at Janssen-Cilag. S.S. has received grants and honoraria for educational input from EnVivo Pharmaceuticals, Takeda, AbbVie and Janssen Pharmaceuticals, outside the submitted work.
Embryo Implantation: War in Times of Love
Authors: Ashary Nancy , Tiwari Abhishek , Modi Deepak
Published: January 2018

Contrary to widespread belief, the implantation of an embryo for the initiation of pregnancy is like a battle, in that the embryo uses a variety of coercive tactics to force its acceptance by the endometrium. We propose that embryo implantation involves a three-step process: (1) identification of a receptive endometrium; (2) superimposition of a blastocyst-derived signature onto the receptive endometrium before implantation; and finally (3) breaching by the embryo and trophoblast invasion, culminating in decidualization and placentation. We review here the story that is beginning to emerge, focusing primarily on the cells that are in “combat” during this process.
Development and External Validation of Risk Scores for Cardiovascular Hospitalization and Rehospitalization in Patients With Diabetes
Authors: Yu Dahai , Cai Yamei , Graffy Jonathan , Holman Daniel , Zhao Zhanzheng , Simmons David
Published: January 2018

Context

Cardiovascular disease (CVD) is a common and costly reason for hospitalization and rehospitalization among patients with type 2 diabetes.

Objective

This study aimed to develop and externally validate two risk-prediction models for cardiovascular hospitalization and cardiovascular rehospitalization.

Design

Two independent prospective cohorts.

Setting

The derivation cohort includes 4704 patients with type 2 diabetes from 18 general practices in Cambridgeshire. The validation cohort comprises 1121 patients with type 2 diabetes from post-trial follow-up data.

Main Outcome Measure

Cardiovascular hospitalization over 2 years and cardiovascular rehospitalization after 90 days of the prior CVD hospitalization.

Results

The absolute rate of cardiovascular hospitalization and rehospitalization was 12.5% and 6.7% in the derivation cohort and 16.3% and 7.0% in the validation cohort. Discrimination of the models was similar in both cohorts, with C statistics above 0.70 and excellent calibration of observed and predicted risks.

Conclusion

Two prediction models that quantify risks of cardiovascular hospitalization and rehospitalization have been developed and externally validated. They are based on a small number of clinical measurements that are available for patients with type 2 diabetes in many developed countries in primary care settings and could serve as the tools to screen the population at high risk of cardiovascular hospitalization and rehospitalization.
Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders
Authors: Selten Martijn , van Bokhoven Hans , Nadif Kasri Nael
Published: January 2018

Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders. First, we explore both patient and post-mortem evidence of inhibitory deficiency. We then discuss the function of different interneuron subtypes in the network and focus on the central role of a specific class of inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes known to be affected in different disorders and the effects that mutations in these genes have on the inhibitory system in cortex and hippocampus. We conclude that alterations to the inhibitory system are consistently identified in animal models of psychiatric disorders and, more specifically, that mutations affecting the function of parvalbumin-positive interneurons seem to play a central role in the symptoms observed in these disorders.
Immunoexpression of P63 and SOX2 in triple-negative breast cancers, Indonesia
Authors: Kamarlis Reno K , Lubis Muhammad ND , Hernowo Bethy S , Kar Azmi S
Published: January 2018

Background: Using immunohistochemical stains to target specific breast cancer markers has become indispensable for evaluation of small diagnostic tissue specimens, and therefore novel marker cocktails for specific breast cancers are required. This study was conducted to assess the immunoexpression of P63 and SOX2 in triple negative breast cancer (TNBC), and to evaluate the predictive diagnostic value of these markers for specific types of TNBC.

Methods: Histological slides and paraffin blocks of TNBC cases were collected from Dr. Hasan Sadikin Hospital, Bandung, Indonesia from 5-years period (2011-2015). Each histological slide was subjected to immunohistochemical staining for P63 (nucleus and cytoplasm) and SOX2 (nucleus), with specific primer antibodies. Immunoexpression of P63 and SOX2 was evaluated using immunoreactivity scoring. Associations between P63 and SOX2 immunoexpression and TNBC types were assessed using Mann Whitney tests. In addition, the predictive diagnostic values of these markers were assessed.

Results: Forty TNBC histological slides were included, and 23 (57.5%) were Basal-like type TNBC and 17 (42.5%) were Non basal-like type TNBC. Immunoexpression of P63 nucleus and SOX2 was not different between types of TNBC. However, immunoexpression of P63 in the cytoplasm in Basal-like type TNBC was significantly higher than in Non basal-like type TNBC (p=0.021). Predictor diagnostic value analysis suggested that immunoexpression of P63 in cytoplasm had 56.5% sensitivity and 70.6% specificity for diagnosing Basal-like type TNBC, with area under curve of 0.64.   

Conclusions: Immunoexpression of P63 in the cytoplasm has a relatively weak diagnostic value to discriminate Basal-like and Non basal-like types of TNBC.
Interventions to Reduce the Overuse of Imaging for Pulmonary Embolism: A Systematic Review
Authors: Deblois Simon , Chartrand‐Lefebvre Carl , Toporowicz Kevin , Chen Zhongyi , Lepanto Luigi
Published: January 2018

BACKGROUND

Imaging use in the diagnostic workup of pulmonary embolism (PE) has increased markedly in the last 2 decades. Low PE prevalence and diagnostic yields suggest a significant problem of overuse.

PURPOSE

The purpose of this systematic review is to summarize the evidence associated with the interventions aimed at reducing the overuse of imaging in the diagnostic workup of PE in the emergency department and hospital wards.

DATA SOURCES

PubMed, MEDLINE, Embase, and EBM Reviews from 1998 to March 28, 2017.

STUDY SELECTION

Experimental and observational studies were included. The types of interventions, their efficacy and safety, the impact on healthcare costs, the facilitators, and barriers to their implementation were assessed.

DATA SYNTHESIS

Seventeen studies were included assessing clinical decision support (CDS), educational interventions, performance and feedback reports (PFRs), and institutional policy. CDS impact was most comprehensively documented. It was associated with a reduction in imaging use, ranging from 8.3% to 25.4%, and an increase in diagnostic yield, ranging from 3.4% to 4.4%. The combined implementation of a CDS and PFR resulted in a modest but significant increase in the adherence to guidelines. Few studies appraised the safety of interventions. There was a lack of evidence concerning economic aspects, facilitators, and barriers.

CONCLUSIONS

A combined implementation of an electronic CDS and PFRs is more effective than purely educational or policy interventions, although evidence is limited. Future studies of high‐methodological quality would strengthen the evidence concerning their efficacy, safety, facilitators, and barriers.
The organization and work of a fetal assessment day care unit
Authors: de Lassalle SH Morris
Published: January 2018

The Government's commitment to providing a more consumer-oriented service is clearly demonstrated by its recent announcement of a Performance League Table for hospitals, and empowerment of the consumer through The Patient's Charter. The provision of a fetal assessment day care unit at the Mayday Hospital, Croydon, is a sensitive response to the needs of the local community and the Government's commitment to a high quality and cost-effective service.
The importance of encouraging women to think for themselves
Authors: Schott Judith
Published: January 2018

Becoming a parent is the biggest and most challenging role that most people take on in a lifetime. Women are expected to care for their children 24 hours a day, 7 days a week for 52 weeks a year and for a minimum of 16 years. Mothers are undervalued and unsupported by a society that is becoming ever more critical of parents, who are expected to do a job for which they have little or no training other than their own experience of being parented.
Visual Short-Term Memory Activity in Parietal Lobe Reflects Cognitive Processes beyond Attentional Selection
Authors: Sheremata Summer L. , Somers David C. , Shomstein Sarah
Published: January 2018

Visual short-term memory (VSTM) and attention are distinct yet interrelated processes. While both require selection of information across the visual field, memory additionally requires the maintenance of information across time and distraction. VSTM recruits areas within human (male and female) dorsal and ventral parietal cortex that are also implicated in spatial selection; therefore, it is important to determine whether overlapping activation might reflect shared attentional demands. Here, identical stimuli and controlled sustained attention across both tasks were used to ask whether fMRI signal amplitude, functional connectivity, and contralateral visual field bias reflect memory-specific task demands. While attention and VSTM activated similar cortical areas, BOLD amplitude and functional connectivity in parietal cortex differentiated the two tasks. Relative to attention, VSTM increased BOLD amplitude in dorsal parietal cortex and decreased BOLD amplitude in the angular gyrus. Additionally, the tasks differentially modulated parietal functional connectivity. Contrasting VSTM and attention, intraparietal sulcus (IPS) 1–2 were more strongly connected with anterior frontoparietal areas and more weakly connected with posterior regions. This divergence between tasks demonstrates that parietal activation reflects memory-specific functions and consequently modulates functional connectivity across the cortex. In contrast, both tasks demonstrated hemispheric asymmetries for spatial processing, exhibiting a stronger contralateral visual field bias in the left versus the right hemisphere across tasks, suggesting that asymmetries are characteristic of a shared selection process in IPS. These results demonstrate that parietal activity and patterns of functional connectivity distinguish VSTM from more general attention processes, establishing a central role of the parietal cortex in maintaining visual information.

SIGNIFICANCE STATEMENTVisual short-term memory (VSTM) and attention are distinct yet interrelated processes. Cognitive mechanisms and neural activity underlying these tasks show a large degree of overlap. To examine whether activity within the posterior parietal cortex (PPC) reflects object maintenance across distraction or sustained attention per se, it is necessary to control for attentional demands inherent in VSTM tasks. We demonstrate that activity in PPC reflects VSTM demands even after controlling for attention; remembering items across distraction modulates relationships between parietal and other areas differently than during periods of sustained attention. Our study fills a gap in the literature by directly comparing and controlling for overlap between visual attention and VSTM tasks.
Regulation of Lateral Hypothalamic Orexin Activity by Local GABAergic Neurons
Authors: Ferrari Loris L. , Park Daniel , Zhu Lin , Palmer Matthew R. , Broadhurst Rebecca Y. , Arrigoni Elda
Published: January 2018

Orexin (also known as hypocretin) neurons are considered a key component of the ascending arousal system. They are active during wakefulness, at which time they drive and maintain arousal, and are silent during sleep. Their activity is controlled by long-range inputs from many sources, as well as by more short-range inputs, including from presumptive GABAergic neurons in the lateral hypothalamus/perifornical region (LH/PF). To characterize local GABAergic input to orexin neurons, we used channelrhodopsin-2-assisted circuit mapping in brain slices. We expressed channelrhodopsin-2 in GABAergic neurons (Vgat+) in the LH/PF and recorded from genetically identified surrounding orexin neurons (LH/PFVgat→ Orx). We performed all experiments in mice of either sex. Photostimulation of LH/PF GABAergic neurons inhibited the firing of orexin neurons through the release of GABA, evoking GABAA-mediated IPSCs in orexin neurons. These photo-evoked IPSCs were maintained in the presence of TTX, indicating direct connectivity. Carbachol inhibited LH/PFVgat→ Orx input through muscarinic receptors. By contrast, application of orexin was without effect on LH/PFVgat→ Orx input, whereas dynorphin, another peptide produced by orexin neurons, inhibited LH/PFVgat→ Orx input through κ-opioid receptors. Our results demonstrate that orexin neurons are under inhibitory control by local GABAergic neurons and that this input is depressed by cholinergic signaling, unaffected by orexin and inhibited by dynorphin. We propose that local release of dynorphin may, via collaterals, provides a positive feedback to orexin neurons and that, during wakefulness, orexin neurons may be disinhibited by acetylcholine and by their own release of dynorphin.

SIGNIFICANCE STATEMENTThe lateral hypothalamus contains important wake-promoting cell populations, including orexin-producing neurons. Intermingled with the orexin neurons, there are other cell populations that selectively discharge during nonrapid eye movement or rapid eye movement sleep. Some of these sleep-active neurons release GABA and are thought to inhibit wake-active neurons during rapid eye movement and nonrapid eye movement sleep. However, this hypothesis had not been tested. Here we show that orexin neurons are inhibited by a local GABAergic input. We propose that this local GABAergic input inhibits orexin neurons during sleep but that, during wakefulness, this input is depressed, possibly through cholinergically mediated disinhibition and/or by release of dynorphin from orexin neurons themselves.
Retrosplenial Cortex Indexes Stability beyond the Spatial Domain
Authors: Auger Stephen D. , Maguire Eleanor A.
Published: January 2018

Retrosplenial cortex (RSC) is highly responsive to landmarks in the environment that remain fixed in a permanent location, and this has been linked with its known involvement in scene and spatial processing. However, it is unclear whether RSC representations of permanence are a purely spatial phenomenon or whether they extend into behavioral and conceptual domains. To test this, during functional MRI scanning, we had people (males and females) read three different types of sentences that described either something permanent or transient. The first two sentence types were imageable, with a focus either on a spatial landmark or on an action. The third type of sentence involved non-imageable abstract concepts. We found that, in addition to being more active for sentences describing landmarks with a permanent location in space, RSC was also significantly engaged by sentences describing stable and consistent behaviors or actions, as long as they were rooted within a concrete imageable setting. RSC was not responsive to abstract concepts, even those that embodied the notion of stability. Similarly, it was not engaged by imageable sentences with transient contents. In contrast, parahippocampal cortex was more engaged by imageable sentences describing landmarks, whereas the hippocampus was active for all imageable sentences. In addition, for imageable sentences describing permanence, there was bidirectional functional coupling between RSC and these medial temporal lobe structures. It appears, therefore, that RSC-mediated permanence representations could be helpful for more than spatially mapping environments and may also provide information about the reliability of events occurring within them.

SIGNIFICANCE STATEMENTThe retrosplenial cortex (RSC) is known to process information about landmarks in the environment that have a fixed, permanent location. Here we tested whether this permanence response was apparent beyond the spatial domain, which could have implications for understanding the role of the RSC more widely across cognition. We found that the RSC was engaged not only by permanent landmarks but also by stable and consistent actions. It was not responsive to transient landmarks or actions or to abstract concepts, even those that embodied the notion of stability. We conclude that the RSC might do more than help to map spatial environments, by possibly also providing information about the reliability of events occurring within them.