bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcription factors CEP‐1/p53 and CEH‐23 collaborate with AAK‐2/AMPK to modulate longevity in Caenorhabditis elegans.
Authors: Chang Hsin‐Wen , Pisano Steve , Chaturbedi Amaresh , Chen Jennifer , Gordon Sarah , Baruah Aiswarya , Lee Siu Sylvia
Published: May 2017

A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial. In this study, we showed that the transcription factors CEP‐1/p53 and CEH‐23 act through a similar mechanism to modulate longevity in response to defective ETC in Caenorhabditis elegans. Genomewide gene expression profiling comparison revealed a new link between these two transcription factors and AAK‐2/AMP kinase (AMPK) signaling. Further functional analyses suggested that CEP‐1/p53 and CEH‐23 act downstream of AAK‐2/AMPK signaling and CRTC‐1 transcriptional coactivator to promote stress resistance and lifespan. As AAK‐2, CEP‐1, and CEH‐23 are all highly conserved, our findings likely provide important insights for understanding the organismal adaptive response to mitochondrial dysfunction in diverse organisms and will be relevant to aging and pathologies with a mitochondrial etiology in human.
Characterization of Self‐Defining Memories in Individuals with Severe Alcohol Use Disorders After Mid‐Term Abstinence: The Impact of the Emotional Valence of Memories
Authors: Nandrino Jean‐Louis , Gandolphe Marie‐Charlotte
Published: May 2017

Background

Self‐defining memories (SDM) are distinguished from other autobiographical memory (AM) processes to delineate those associated with the sense of personal identity and continuity in one's individual history. With chronic alcohol consumption, the construction of such memories may be modified in terms of specificity, valence, meaning‐making, and evoked topics. This study sought to characterize SDM in a population of 27 patients with alcohol use disorder (AUD) who had been abstinent for at least 2 months compared with 28 control participants.

Methods

Besides cognitive and clinical assessment, participants were told to describe verbally and date 5 SDM and their narratives were recorded. For each memory, 5 dimensions were evaluated: level of specificity, emotional valence, integration of meaning, topics, and distance of memory in time.

Results

Overall, SDM of participants with AUD were specifically characterized by (i) low specificity, (ii) low integration, (iii) a predominance of memories with negative emotional valence and a low frequency of positive memories, and (iv) a low frequency of topics related to success. When different dimensions of the SDM were crossed, their characteristics depended mainly on the valence of the memory. Negative memories were more frequent, more specific and more integrated, while positive SDM were less frequent, less specific and less integrated.

Conclusions

The results underline the construction of a form of SDM with drinking problems that is mainly characterized by the disruption of positive memory and the presence of highly specific and integrated negative experiences. A disruption of the integration process modulated by the valence of memories could have repercussions on maintaining a sense of personal identity, the pursuit of personal goals and on social adaptability, and could constitute one of the main risks associated with persistent drinking problems. These results highlight the relevance of developing AM training programs for patients with AUD.
Optical coherence tomography angiography of the macular microvasculature changes in retinitis pigmentosa
Authors: Koyanagi Yoshito , Murakami Yusuke , Funatsu Jun , Akiyama Masato , Nakatake Shunji , Fujiwara Kohta , Tachibana Takashi , Nakao Shintaro , Hisatomi Toshio , Yoshida Shigeo , Ishibashi Tatsuro , Sonoda Koh‐Hei , Ikeda Yasuhiro
Published: May 2017

Purpose

To investigate the macular microvasculature changes by optical coherence tomography angiography (OCTA) and analyse the correlation between these changes and central visual function in patients with retinitis pigmentosa (RP).

Methods

We measured the area of the foveal avascular zone (FAZ) and the foveal and parafoveal flow density (FFD and PFD, respectively) in the superficial (S) and deep (D) retinal plexus by OCTA (AngioVue) and compared these values between 73 RP patients and 36 healthy controls. We analysed the relationships between these microvasculature measurements and central visual functions such as visual acuity (VA) and the values of static perimetry tests (Humphrey Field Analyzer, the central 10–2 program) in the RP patients.

Results

The FFD‐S, PFD‐S and PFD‐D were significantly decreased in the RP patients compared to the controls (all p < 0.05), whereas there was no significant difference in the FAZ‐S, FAZ‐D or FFD‐D (all p > 0.05). A subgroup analysis showed that the RP patients with VA <20/20 had increased FAZ‐S compared to the controls and RP patients with VA ≥20/20 (p = 0.01 and p = 0.007, respectively). Spearman rank testing demonstrated that PFD‐S and PFD‐D were significantly correlated with all of the central visual parameters (all p < 0.01). The FAZ‐S and FFD‐S were significantly correlated with VA, and FAZ‐D and FFD‐D showed no significant correlation.

Conclusion

Both the superficial and deep layers of the parafoveal microvasculature are attenuated in RP and correlated with reduced central visual function. The foveal microvasculature, especially in the deep layer, was relatively preserved until mild‐to‐moderately advanced stages.
Pharmacogenetic analysis of irreversible severe cisplatin‐induced nephropathy: a case report of a 27‐year‐old woman
Authors: de Jong Corine , Sanders Stefan , Creemers Geert‐Jan , Burylo Artur M. , Taks Margot , Schellens Jan H.M. , Deenen Maarten J.
Published: May 2017

In this report we describe a young patient diagnosed with bulky FIGO stage IIIb squamous cell cervix carcinoma with severe and irreversible nephropathy after three weekly low‐doses of cisplatin. Besides several known risk factors such as hypomagnesemia and hypoalbuminemia, the patient also proved to be homozygously polymorphic for two polymorphisms within the COMT gene (c.615 + 310C>T and c.616–367C>T). As COMT polymorphism has been associated with cisplatin‐induced ototoxicity, its effect on nephrotoxicity of cisplatin should be the subject of further investigation.
Pharmacokinetics of Transdermal Etofenamate and Diclofenac in Healthy Volunteers
Authors: Drago Sara , Imboden Roger , Schlatter Philipp , Buylaert Mirabel , Krähenbühl Stephan , Drewe Juergen
Published: May 2017

Little is known about the course of the plasma concentration and the bioavailability of non‐steroidal anti‐inflammatory drugs (NSAIDs) contained in dermal patches. We compared an etofenamate prototype patch (patent EP 1833471) and a commercially available diclofenac epolamine patch regarding the bioavailability of the active ingredients relative to respective i.m. applications and regarding their plasma concentration–time course. Twenty‐four healthy human volunteers were treated using a parallel group design (n = 12 per group) with a single dermal patch (removed after 12 hr) followed (after a latency of 48 hr) by eight consecutive dermal patches every 12 hr to reach steady‐state conditions. The patches were generally well tolerated, but one volunteer treated with etofenamate developed an allergic contact dermatitis. After the first patch, Cmax was 0.81 ± 0.11 (mean ± S.E.M.) ng/mL (reached 12 hr after patch removal) for diclofenac and 31.3 ± 3.8 ng/mL for flufenamic acid (reached at patch removal), the main metabolite of etofenamate. Etofenamate was not detectable. After repetitive dosing, trough plasma concentrations after the eighth dose were 1.72 ± 0.32 ng/mL for diclofenac and 48.7 ± 6.6 ng/mL for flufenamic acid. Bioavailabilities (single dose) relative to i.m. applications were 0.22 ± 0.04% for diclofenac and 1.15 ± 0.06% for flufenamic acid. In conclusion, the relative bioavailability (compared to the respective i.m. application) of both drugs is low. The maximal plasma concentrations after topical administration of these drugs are well below the IC50 values for COX‐1 and COX‐2, explaining the absence of dose‐dependent toxicities.
Cannabinoid CB1/CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity‐based anorexia
Authors: Scherma Maria , Satta Valentina , Collu Roberto , Boi Maria Francesca , Usai Paolo , Fratta Walter , Fadda Paola
Published: May 2017

Background and Purpose

Anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug‐related therapy of this disease and this leads to high relapse rate. Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients.

Experimental Approach

The activity‐based anorexia (ABA) rodent model mimics the severe body weight loss and increased physical activity, as well as the neuroendocrine disturbances (i.e. hypoleptinaemia and hypercortisolaemia) in AN. This study investigated whether cannabinoid agonists can effectively modify anorexic‐like behaviours and neuroendocrine changes in rats subjected to a repeated ABA regime that mimics the human condition in which patients repeatedly undergo a recovery and illness cycle.

Key Results

Our data show that subchronic treatment with both the natural CB1/CB2 receptor agonist Δ9‐tetrahydrocannabinol and the synthetic CB1/CB2 receptor agonist CP‐55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioural effects were accompanied by an increase in leptin signalling and a decrease in plasma levels of corticosterone.

Conclusion and Implications

Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance.
Management of an asymptomatic patient with the apical variant of hypertrophic cardiomyopathy
Authors: Trojan Meghan K. Borden , Biederman Robert W.
Published: May 2017

Healthcare professionals are faced with challenging decisions regarding patient evaluation and management on a daily basis. Once a diagnosis is made, additional challenges include how to proceed with the management. Here, we present an eighty‐two‐year‐old female who was incidentally diagnosed with the apical variant of hypertrophic cardiomyopathy on a transthoracic echocardiogram. She was found to have newly diagnosed atrial fibrillation, but was otherwise asymptomatic from a cardiomyopathy standpoint. No specific guidelines exist for this patient population. Therefore, how does one proceed with the management of an asymptomatic patient with the apical variant of hypertrophic cardiomyopathy?
Image of a left atrial mass after a cardiopulmonary bypass in a child
Authors: Hadeed Khaled , Leobon Bertrand , Dulac Yves , Acar Philippe
Published: May 2017

Invagination of an appendage into the left atrium is a rare complication. It occurs spontaneously or after open‐heart surgery. In our case, a postoperative transesophageal echocardiogram, after closure of a ventricular septal defect in a 5‐month‐old infant, revealed a large mass in the left atrium. A diagnosis of a left appendage inversion was confirmed after external examination of the heart. Herein, we provide echocardiographic images before, during, and after manual reversion of the left appendage. Misdiagnosis of this complication could have led to an additional unnecessary surgical procedure that could have impacted on the patient's morbidity.
Platelet distribution width as the prognostic marker in coronary bifurcation treatment
Authors: Kern Adam , Gil Robert J. , Bojko Krystian , Sienkiewicz Ewa , Januszko‐Giergielewicz Beata , Górny Jerzy , Bil Jacek
Published: May 2017

Background

Mean platelet volume (MPV) was proved to be a reliable prognostic factor in cardiac patients. However, platelet distribution width (PDW) was disclosed to be more specific marker of platelet reactivity. The aim of study was to evaluate whether baseline PDW value can predict the outcome in patients undergoing percutaneous coronary interventions (PCI) with drug‐eluting stent implantation within coronary bifurcation lesions.

Materials and methods

It was a two‐centre observational study, which included patients who underwent PCI within bifurcation lesions between January 2014 and December 2014. Thrombocytopenia below 100 000/μL and STEMI were the exclusion criteria. Analysed data came entirely from in‐hospital records and information obtained from the 12‐month telephone follow‐up.

Results

We included 269 patients. Mean PDW value was 13·4 ± 2·5 fL, whereas median was 13 (Q1 < 11·6 fL, Q2 11·6–13 fL, Q3 13–14·8 fL and Q4 > 14·8 fL). We found strong correlation between PDW and MPV (r = 0·96, P < 0·001), but no correlation was revealed between red blood cell distribution width (RDW) and PDW (r = 0·003, P = 0·95) as well as RDW and MPV (r = 0·0018, P = 0·98). Receiver operating characteristics (ROC) curve showed that PDW for cutoff 15·8% can predict MACE rate with sensitivity of 79% and specificity of 47% (area under curve – AUC 0·654; P = 0·01). A ROC curve for PDW categorized by 1‐year TLR rate was described by optimal cutoff 16·3%, with sensitivity 69% and specificity 54% (AUC 0·697; P = 0·0015).

Conclusions

PDW is an affordable and reliable predictor of 1‐year MACE and TLR rate after PCI within coronary bifurcation lesions.
Mass rearing and sterile insect releases for the control of Anastrepha spp. pests in Mexico – a review
Authors: Orozco‐Dávila Dina , Quintero Luis , Hernández Emilio , Solís Eduardo , Artiaga Trinidad , Hernández Refugio , Ortega Carlos , Montoya Pablo
Published: May 2017

The sterile insect technique (SIT) requires the rearing, sterilization, and release of large numbers of insects to induce sterility within wild pest populations. In 1992, the Mexican government launched a national campaign against economically important fruit fly pests, with the aim of establishing free areas and strengthening fruit exports. To achieve these objectives, the Moscafrut facility began operations in 1993 with the mass rearing of Anastrepha ludens (Loew) (Diptera: Tephritidae: Toxotrypanini) and in 2002 with Anastrepha obliqua (McQuart). Field releases of sterile insects began in the north of the country, and currently 51% of the country is free of these pests. In this review, we describe the mass‐rearing process and the quality control tests used in the production of the above‐mentioned species. As a case study, we also describe the achievements of applying the SIT against A. ludens populations in the citrus‐growing zone of the state of San Luis Potosí, which has resulted in dramatic reductions in both wild fly populations and the use of chemical sprays. We discuss the implications, achievements, and perspectives regarding the use of this technology to control Anastrepha pests in Mexico.
Inoculation of susceptible and resistant potato plants with the late blight pathogenPhytophthora infestans: effects on an aphid and its parasitoid
Authors: Lazebnik Jenny , Tibboel Marianne , Dicke Marcel , van Loon Joop J.A.
Published: May 2017

Plants are exposed to microbial pathogens as well as herbivorous insects and their natural enemies. Here, we examined the effects of inoculation of potato plants,Solanum tuberosumL. (Solanaceae), with the late blight pathogenPhytophthora infestans(Mont.) de Bary (Peronosporales:Pythiaceae) on an aphid species commonly infesting potato crops and one of the aphid's major parasitoids. We observed the peach‐potato aphid,Myzus persicaeSulzer (Hemiptera:Aphididae), and its natural enemy, the biocontrol agentAphidius colemaniViereck (Hymenoptera:Braconidae), on potato either inoculated with water orP. infestans. Population growth of the aphid, parasitism rate of its natural enemy, and other insect life‐history traits were compared on several potato genotypes, the susceptible cultivar Désirée and genetically modified (GM) isogenic lines carrying genes conferring resistance toP. infestans. Effects ofP. infestansinoculation on the intrinsic rate of aphid population increase and the performance of the parasitoid were only found on the susceptible cultivar. Insect traits were similar when comparing inoculated with non‐inoculated resistantGMgenotypes. We also tested howGM‐plant characteristics such as location of gene insertion and number of R genes could influence non‐target insects by comparing insect performance amongGMevents. Different transformation events leading to different positions of R‐gene insertion in the genome influenced aphids either with or withoutP. infestansinfection, whereas effects of position of R‐gene insertion on the parasitoidA. colemaniwere evident only in the presence of inoculation withP. infestans. We conclude that it is important to study different transformation events before continuing with further stages of risk assessment of thisGMcrop. This provides important information on the effects of plant resistance to a phytopathogen on non‐target insects at various trophic levels.
Synergistic protection against acute flurothyl‐induced seizures by adjuvant treatment of the ketogenic diet with the type 2 diabetes drug pioglitazone
Authors: Simeone Timothy A. , Matthews Stephanie A. , Simeone Kristina A.
Published: May 2017

Objective

We have previously found that the transcription factor peroxisome proliferator‐activated receptor γ (PPARγ) contributes to the mechanism of action of the ketogenic diet (KD), an established treatment for pediatric refractory epilepsy. We have found that the KD increases brain PPARγ and that inhibition or genetic loss of PPARγ prevents the antiseizure effects of the KD on (1) acutely induced seizures in nonepileptic mice and (2) spontaneous recurrent seizures in epileptic mice. Here, we tested the hypothesis that adjuvant treatment of KD‐treated mice with a PPARγ agonist, pioglitazone, would result in an additive effect.

Methods

Acute seizures were induced in three groups of C57Bl/6 mice by inhalation exposure to flurothyl gas. In Group 1, mice were weaned onto either a standard diet or KD comprised of a fat:carbohydrate/protein ratio of either 6:1, 3:1, or 1:1 for 2 weeks. In Group 2, vehicle or pioglitazone (0.1, 1, 10, 80 mg/kg) was administered 4 h prior to flurothyl exposure. In Group 3, vehicle or increasing doses of pioglitazone were administered to KD‐treated mice 4 h prior to flurothyl exposure. Latency times to clonic seizures and generalized tonic–clonic (GTC) seizures were recorded, and isobolographic analysis was used to determine combinatorial interactions.

Results

Neither KD treatment nor pioglitazone alone or in combination affected clonic seizures. However, the latency to GTC seizures was dose‐dependently and significantly increased by both KD (~57%, p < 0.05) and pioglitazone (~28%, p < 0.05). Coadministration of an ineffective 1:1 KD and pioglitazone resulted in ~47–55% (p < 0.05) increase in latency to GTC. Isobolographic analysis indicated a synergistic interaction of the KD and pioglitazone.

Significance

These results suggest coadministration may enable reduction of the KD ratio without loss of seizure protection. Such adjuvant treatment could improve quality of life and limit adverse effects of a classic KD or high‐dose pioglitazone.
Predictive value of different prostate‐specific antigen‐based markers in men with baseline total prostate‐specific antigen <2.0 ng/mL
Authors: Fujizuka Yuji , Ito Kazuto , Oki Ryo , Suzuki Rie , Sekine Yoshitaka , Koike Hidekazu , Matsui Hiroshi , Shibata Yasuhiro , Suzuki Kazuhiro
Published: May 2017

Objectives

To investigate the predictive value of various molecular forms of prostate‐specific antigen in men with baseline prostate‐specific antigen <2.0 ng/mL.

Methods

The case cohort comprised 150 men with a baseline prostate‐specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate‐specific antigen‐ and age‐adjusted men who did not develop prostate cancer. Serum prostate‐specific antigen, free prostate‐specific antigen, and [−2] proenzyme prostate‐specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate‐specific antigen‐ and [−2] proenzyme prostate‐specific antigen‐related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated.

Results

The baseline free to total prostate‐specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate‐specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [−2] proenzyme prostate‐specific antigen/free prostate‐specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores.

Conclusions

Free to total prostate‐specific antigen ratio in men with low baseline prostate‐specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [−2] proenzyme prostate‐specific antigen‐related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance.
Outcomes of pulmonary arterial hypertension therapy in Australia: is monotherapy adequate?
Authors: Moonen Avalon , Garsia Roger , Youssef Peter , Torzillo Paul , Corte Tamera , Boehm Christiane , Cordina Rachael , Celermajer David , Lau Edmund
Published: May 2017

Background

In Australia, government‐subsidised treatment of pulmonary arterial hypertension (PAH) is limited to monotherapy. Recent international guidelines advocate that initial combination therapy be considered for all symptomatic PAH patients.

Aim

To characterise ‘real‐life’ outcomes in PAH patients initiated on monotherapy.

Methods

We performed a retrospective analysis of 100 consecutive PAH patients at a single centre who were commenced on monotherapy for PAH between 2004 and 2015. The composite clinical end‐point of ‘treatment failure’ was prospectively defined as (i) >15% fall in 6‐min walk distance (6MWD) on follow up, (ii) physician judgement of inadequate treatment response, (iii) adverse drug effect requiring cessation and (iv) death or transplantation.

Results

At initiation of therapy, mean age was 54 ± 18 years, and underlying diagnoses included idiopathic (36%), connective tissue disease‐associated (37%) and congenital heart disease‐associated‐PAH (25%). Baseline 6MWD was 360 ± 140 m, and 75% were in either the New York Heart Association functional classes III or IV. Over a median follow up of 38 months (interquartile range 20–67), 62% of the subjects met the criteria for a clinical failure event. Median time to monotherapy failure was 24 months (95% confidence interval 14–34), with death or transplantation being the most common clinical failure event. Estimated 1‐, 3‐ and 5‐year survival rates from time of treatment initiation were 92, 75 and 66%.

Conclusion

The majority of patients failed initial monotherapy therapy within 2 years of treatment initiation. Broader access to approved PAH agents is needed to enable combination therapy in line with evidence‐based international guidelines.
Effects of temperature and electric field on upconversion luminescence in Er3+‐Yb3+ codoped Ba0.8Sr0.2TiO3 ferroelectric ceramics
Authors: Sun Qiu , Wang Weihua , Pan Yunxing , Liu Zhikai , Chen Xiangqun , Ye Mao
Published: May 2017

Optical and electrical properties of 1%Er3+ and different Yb3+ content (1ExY) codoped Ba0.8Sr0.2TiO3 (BST) ferroelectric ceramics fabricated by the solid‐phase reaction were investigated. Under 980 nm pump condition, two green emission bands at 525 and 549 nm wavelength corresponding to, 2H11/2→4I15/2 and 2S3/2→4I15/2 transitions, and two red emission bands at 655 and 668 nm wavelength attributed to 4F9/2→4I15/2 transition are observed. The temperature‐sensing behaviors, calculated by the intensity ratio I525/I549 suggested that, the maximum sensitivity of the green emission of the 1E8Y‐BST ceramics is 1.07×10−2 K‐1 at 293 K. Furthermore, the maximum sensitivity of 1E6Y‐BST and 1E11Y‐BST ceramics were obtained around the Curie temperature. The fluorescence lifetime of 1E8Y‐BST ceramics for 2H11/2 level and 2S3/2 level shortened with the increase in the temperatures. Moreover, the upconversion (UC) luminescence intensity of 1E8Y‐BST decreased with the increase in the external electric field and had a mutation at the coercive electric field (Ec) of about 1.24 kV/cm, which revealed that the electric field had influence on the UC luminescence.
Multilocus phylogeny of East African gerbils (Rodentia, Gerbilliscus) illuminates the history of the Somali‐Masai savanna
Authors: Aghová Tatiana , Šumbera Radim , Piálek Lubomír , Mikula Ondřej , McDonough Molly M. , Lavrenchenko Leonid A. , Meheretu Yonas , Mbau Judith S. , Bryja Josef
Published: May 2017

Aim

The rodent genus Gerbilliscus is widespread in savannas throughout sub‐Saharan Africa. The eastern clade comprises four species with distributions centred in the Somali‐Masai biogeographical region of East Africa. We investigated the genetic diversity of the group with a view to illuminating the historical (Plio‐Pleistocene) processes that formed contemporary biota of the understudied Somali‐Masai region.

Location

Somali‐Masai savanna, East Africa.

Methods

We performed multilocus genetic analyses of 240 samples from 112 localities, combining genotyping of recently collected samples (N = 145), 454‐pyrosequencing of museum material (N = 34) and published sequences (N = 61). We used Bayesian and maximum likelihood approaches for phylogenetic reconstructions, and coalescent‐based methods to delimit species. We also estimated divergence times and modelled recent and past distributions to reconstruct the major evolutionary influences in the Somali‐Masai region during the Plio‐Pleistocene.

Results

Genetic analyses provided evidence for six lineages, possibly corresponding to distinct species. The two main species groups (with two and four putative species, respectively) have overlapping distributions, but species within each group are distributed parapatrically. The origin of the eastern clade dates back to the Pliocene, while individual species diverged in the Pleistocene. The distribution of genetic diversity and ecological niche modelling point to the importance of the Rift Valley and the presence of unsuitable xeric habitats in the allopatric diversification of Gerbilliscus in the Somali‐Masai savanna within the last 5 Myr.

Conclusions

This is the first detailed phylo(bio‐)geographical study of animals with predominant distribution in the Somali‐Masai region. It revealed currently underestimated diversity of eastern clade of Gerbilliscus and proposed a scenario of its evolution during Plio‐Pleistocene. Conspicuous genetic structure of these taxa can be now used to test detailed phylogeographical hypotheses related to Plio‐Pleistocene history of gerbils and, to some extent, also biota of Somali‐Masai bioregion in general.
Efficacy and tolerability of initial high vs low doses of S‐(‐)‐amlodipine in hypertension
Authors: Chen Qi , Huang Qi‐Fang , Kang Yuan‐Yuan , Xu Shao‐Kun , Liu Chang‐Yuan , Li Yan , Wang Ji‐Guang
Published: May 2017

In an 8‐week randomized trial of patients with mild or moderate hypertension, the authors investigated the efficacy and tolerability of initial high (5.0 mg/d) vs low (2.5 mg/d) doses of S‐(‐)‐amlodipine (equivalent to 5 and 10 mg of racemic amlodipine, respectively). In the S‐(‐)‐amlodipine 2.5‐mg group (n=263), 24‐hour ambulatory systolic/diastolic blood pressure (±standard deviation) decreased from 131.5±15.0/82.1±10.7 mm Hg at baseline to 126.0±13.5/78.5±9.5 mm Hg at 8 weeks of follow‐up by a least square mean (±standard error) change of 6.0±0.6/3.8±0.4 mm Hg. In the S‐(‐)‐amlodipine 5‐mg group (n=260), the corresponding changes were from 133.6±13.7/83.1±9.9 mm Hg to 125.0±12.0/78.2±8.9 mm Hg by 8.1±0.6/4.7±0.4 mm Hg, respectively. The between‐group differences in changes in 24‐hour systolic/diastolic blood pressure were 2.1/0.9 (P=.02/.17) mm Hg. Similar trends were observed for daytime and nighttime ambulatory and clinic blood pressure. The incidence rate was similar for all adverse events. An initial high dose of S‐(‐)‐amlodipine improved ambulatory blood pressure control with similar tolerability as an initial low dose in hypertension.
Choosing the optimal method of blood pressure measurement for limited‐resource rural communities in the “Community Health Assessment Program—Philippines”
Authors: Guenter Dale , Angeles Ricardo , Kaczorowski Janusz , Agarwal Gina , Cristobal Fortunato L. , Arciaga Rosemarie , Smith John F. , Kessomboon Pattapong , Jarraya Faical , Agbulos Rodelin , Arnuco Floro Dave , Barrera Jerome , Dimitry Susan , Gregorio Elgie , Halili Servando , Jalani Norvie T. , Kessomboon Nusaraporn , Ladeza Maita , Dolovich Lisa
Published: May 2017

The Community Health Assessment Program—Philippines (CHAP‐P) is an international collaboration of investigators whose aim is to adapt a previously proven Canadian community‐based cardiovascular awareness and prevention intervention to the Philippines and other low‐middle–income countries. Choosing a method of blood pressure measurement for the research program presents a challenge. There is increasing consensus globally that blood pressure measurement with automated devices is preferred. Recommendations from low‐middle–income countries, including the Philippines, are less supportive of automated blood pressure devices. The value placed on factors including device accuracy, durability, cost, energy source, and complexity differ with local context. Our goal was to support the progress of local policy concerning blood pressure measurement while testing a comprehensive approach to community‐based screening for cardiovascular risk. The authors describe the challenges in making a choice of blood pressure device and the approach to determine optimal method of measurement for our research program.
Selective embolization therapy for intrarenal artery stenosis causing renovascular hypertension: Efficacy and follow‐up renal imaging
Authors: Mishima Eikan , Suzuki Takehiro , Seiji Kazumasa , Akiyama Yasutoshi , Ota Hideki , Hashimoto Junichiro , Takase Kei , Abe Takaaki , Ito Sadayoshi
Published: May 2017

We report the case of a young woman treated with selective renal embolization for renovascular hypertension caused by intrarenal artery stenosis and show follow‐up imaging of the treated kidney. An 18‐year‐old woman had renin‐dependent hypertension with intrarenal artery stenosis caused by fibromuscular dysplasia. A middle branch artery was nearly occluded, resulting in segmental renal ischemia with excessive renin secretion. Because our angioplasty attempt for revascularization failed as a result of technical difficulty, we performed selective embolization of the diseased vessel by anhydrous ethanol. The embolization promptly ameliorated hyperreninemia and resistant hypertension without deterioration of renal function. Findings from magnetic resonance imaging showed disappearance of the blood flow in the embolized area corresponding to the ischemic lesion that had been revealed by diffusion‐weighted imaging. Thus, selective embolization can be effective in treating renovascular hypertension by intrarenal stenosis for which angioplasty is not feasible. Additionally, renal magnetic resonance imaging is useful for evaluating the causative ischemic lesion and embolized area.
Clinical and microbiological effects of the adjunctive use of probiotics in the treatment of gingivitis: A randomized controlled clinical trial
Authors: Montero Eduardo , Iniesta Margarita , Rodrigo Marta , Marín María José , Figuero Elena , Herrera David , Sanz Mariano
Published: May 2017

Aim

To evaluate the efficacy of a probiotic combination in the treatment of gingivitis and to assess its impact on the subgingival microbiota.

Materials and Methods

A placebo‐controlled clinical trial was conducted in gingivitis subjects during 6 weeks. Test treatment consisted of the administration of two oral tablets per day containing the probiotic strains Lactobacillus plantarum, Lactobacillus brevis and Pediococcus acidilactici; the control group received the same tablets but without live bacteria. The main outcome variable was the changes in gingival index (GI). Subgingival samples were collected and analysed by quantitative polymerase chain reaction (qPCR) for five putative periodontal pathogens. Outcome variables were compared between and within groups, and multiple regression analysis was performed.

Results

A total of 59 patients (29 tests, 30 placebos) were included in the analysis. Both treatment groups experienced a statistically significant improvement in mean GI (p < .0001), but no differences between treatment groups were found for any clinical index. A significantly higher reduction in the number of sites with higher GI scores (GI = 3 at baseline) was observed in the test group. In subgingival samples, a significant reduction in T. forsythia was significant only in the test group (p < .008).

Conclusions

The use of probiotic tablets containing L. plantarum, L. brevis and P. acidilactici did not lead to significant changes in mean GI; although a significant reduction occurred in the number of sites with severe inflammation. Furthermore, the adjunctive use of this probiotic promoted a significant microbiological impact.
Performance of a new real‐time continuous glucose monitoring system: A multicenter pilot study
Authors: Zhou Jian , Zhang Shuo , Li Liang , Wang Yufei , Lu Wei , Sheng Chunjun , Li Yiming , Bao Yuqian , Jia Weiping
Published: May 2017

Aims/Introduction

The present study aimed to investigate the performance of a new real‐time continuous glucose monitoring system.

Materials and Methods

Interstitial glucose levels were monitored for 7 days in 63 patients with type 1 or type 2 diabetes using the Medtrum A6 TouchCare® CGM System. Venous blood was collected on a randomized day of the wear period. Plasma glucose levels were measured as reference values.

Results

Among 1,678 paired sensor–reference values, 90.5% (95% confidence interval 89.1–91.9%) were within ±20%/20 mg/dL of the reference values, with a mean absolute relative difference of 9.1 ± 8.7% (95% CI: 8.9–9.2%). The percentages of paired sensor–reference values falling within zone A and B of the Clarke error grid analysis (EGA) and the type 1 diabetes consensus EGA were 99.1 and 99.8%. Continuous EGA showed that the percentages of accurate readings, benign errors, and erroneous readings were 89.9, 6.3 and 3.8%, respectively. Surveillance EGA showed that 90.6, 9.2, and 0.2% of sensor–reference values with no, slight and lower moderate risk, respectively. The mean absolute relative difference was 16.6, and 96.0% of the sensor values fell within zones A and B of the consensus EGA for hypoglycemia. More than 85% of sensor values were within ±20%/20 mg/dL of reference values, the mean absolute relative difference was <11, and >99.5% of the sensor values fell in zones A and B of the consensus EGA.

Conclusions

The Medtrum real‐time continuous glucose monitoring system was numerically and clinically accurate over a large glucose range across 7 days of wear.
Phase I randomized study of KHK4083, an anti‐OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis
Authors: Papp K.A. , Gooderham M.J. , Girard G. , Raman M. , Strout V.
Published: May 2017

Background

OX40 (CD134) is expressed in lesional but not healthy skin of patients with psoriasis. KHK4083 is a fully human monoclonal antibody against OX40.

Objective

The primary aim of this first‐in‐human phase 1 study was to determine the safety and tolerability of ascending single doses of KHK4083 in patients with mild to moderate plaque psoriasis. Secondary aims were to determine the pharmacokinetics and immunogenicity of KHK4083, and an exploratory objective was to assess clinical activity.

Methods

In phase 1a, single doses of KHK4083 0.003 and 0.001 mg/kg IV were administered open label in two cohorts (each n = 6). Phase 1b had a multicentre, randomized, double‐blind, placebo‐controlled, ascending single‐dose design in seven cohorts. Randomization was performed 3 : 1 to KHK4083 (n = 6) or placebo (n = 2) within each cohort. Ascending doses of KHK4083 were 0.03, 0.1, 0.3, 1.0, 3.0 and 10 mg/kg IV, and 1.0 mg/kg SC.

Results

There were no severe or serious adverse events (AEs), or discontinuations because of AEs. The most frequent treatment‐related AEs in the 55 patients who received KHK4083 were mild or moderate chills (9.1%), and infusion/injection site reactions (7.3%). No clinically meaningful or dose‐related changes from baseline in laboratory values, vital signs, ECG recordings or physical examinations were observed. Some KHK4083 recipients (10/54) developed anti‐KHK4083 antibodies following treatment. Mean elimination half‐life (t1/2) increased with dose, maximum serum concentration increased in a dose‐proportional manner, and area under the serum concentration–time curve increased in a more than dose‐proportional manner with increasing IV dose. Absolute bioavailability following SC administration was 73%. There was some indication of improvement in Psoriasis Area Severity Index (PASI) and sPGA scores at the highest IV doses (1.0 and 10 mg/kg) and the SC dose (1.0 mg/kg). The largest PASI 50 response and improvement in sPGA score ≥2 occurred with KHK4083 1.0 mg/kg SC.

Conclusion

KHK4083 administration as a single dose up to 10 mg/kg IV or 1.0 mg/kg SC was generally safe and well tolerated in patients with mild to moderate plaque psoriasis with no dose‐limiting AEs.
Describing mate preference functions and other function‐valued traits
Authors: Kilmer J. T. , Fowler‐Finn K. D. , Gray D. A. , Höbel G. , Rebar D. , Reichert M. S. , Rodríguez R. L.
Published: May 2017

Mate preferences are important causes of sexual selection. They shape the evolution of sexual ornaments and displays, sometimes maintaining genetic diversity and sometimes promoting speciation. Mate preferences can be challenging to study because they are expressed in animal brains and because they are a function of the features of potential mates that are encountered. Describing them requires taking this into account. We present a method for describing and analysing mate preference functions, and introduce a freely available computer program that implements the method. We give an overview of how the program works, and we discuss how it can be used to visualize and quantitatively analyse preference functions. In addition, we provide an informal review of different methods of testing mate preferences, with recommendations for how best to set up experiments on mate preferences. Although the program was written with mate preferences in mind, it can be used to study any function‐valued trait, and we hope researchers will take advantage of it across a broad range of traits.
Interspecific competition counteracts negative effects of dispersal on adaptation of an arthropod herbivore to a new host
Authors: Alzate A. , Bisschop K. , Etienne R. S. , Bonte D.
Published: May 2017

Dispersal and competition have both been suggested to drive variation in adaptability to a new environment, either positively or negatively. A simultaneous experimental test of both mechanisms is however lacking. Here, we experimentally investigate how population dynamics and local adaptation to a new host plant in a model species, the two‐spotted spider mite (Tetranychus urticae), are affected by dispersal from a stock population (no‐adapted) and competition with an already adapted spider mite species (Tetranychus evansi). For the population dynamics, we find that competition generally reduces population size and increases the risk of population extinction. However, these negative effects are counteracted by dispersal. For local adaptation, the roles of competition and dispersal are reversed. Without competition, dispersal exerts a negative effect on adaptation (measured as fecundity) to a novel host and females receiving the highest number of immigrants performed similarly to the stock population females. By contrast, with competition, adding more immigrants did not result in a lower fecundity. Females from populations with competition receiving the highest number of immigrants had a significantly higher fecundity than females from populations without competition (same dispersal treatment) and than the stock population females. We suggest that by exerting a stronger selection on the adapting populations, competition can counteract the migration load effect of dispersal. Interestingly, adaptation to the new host does not significantly reduce performance on the ancestral host, regardless of dispersal rate or competition. Our results highlight that assessments of how species can adapt to changing conditions need to jointly consider connectivity and the community context.
Three‐dimensional stereophotogrammetric analysis of 50 smiles: A study of dento‐facial proportions
Authors: Ceinos R. , Lupi L. , Tellier A. , Bertrand M. F.
Published: May 2017

Objectives

The purpose of this study was to analyze 50 smiles using 3D stereophotogrammetry (3D‐spg)‐based facial reconstruction, to calculate ratios involving measurements of the distances between dental and facial landmarks and to compare these ratios with the golden ratio φ (1.618).

Materials and Methods

Fifty subjects with no obvious malocclusion participated in this study. For each subject, 4 photographs were acquired using the LifeViz Mini™, an absolute calibration 3D‐spg system. Facial and dental landmarks (based on Farkas' definitions) were fixed, and 8 distances were measured. Four ratios were then calculated and compared with the value of 1.618.

Results

The ratio “incisal edge of the maxillary central incisor—lower border of the chin/subnasal point—incisal edge of the maxillary central incisor” (IE‐Me/SN‐IE) was 1.693 ± 0.190, the ratio “right endocanthion—left endocanthion/right exocanthion—right endocanthion” was 1.582 ± 0.173, the ratio “incisal edge of the maxillary central incisor—distal edge of the right canine/distal edge of the right canine—right labial commissure” was 1.670 ± 0.355, and the ratio “right labial commissure—left labial commissure/distal edge of the right canine—distal edge of the left canine” was 1.602 ± 0.136. In contrast, the vertical ratio IE‐Me/SN‐IE significantly differed from the golden ratio (1 sample t test, P = .009).

Conclusion

This study revealed that the observed ratios were surprisingly close to the golden ratio. Only the vertical ratio differed from the golden ratio, whereas the horizontal ratios appear to be adequately approximated by φ.

CLINICAL SIGNIFICANCE

If the distances from reference points of the face to teeth within a harmonious smile exhibited recurring esthetic proportions, knowledge of such ratios would provide an additional tool for the elaboration of esthetic treatment plans. In addition, this knowledge could provide guidance when planning tooth positions and dental proportions by encouraging consideration of the global nature of the oro‐facial sphere.
Opioid Use Disorder in Pregnancy
Authors: Roper Van , Cox Kim J.
Published: May 2017

Opioid use disorder (OUD) in pregnancy has increased significantly in the past 10 years. Women with OUD may often be undertreated or untreated because of limited accessibility to treatment, particularly in rural areas. Because detoxification is not recommended during pregnancy due to the potential for adverse outcomes in the fetus and a high risk of relapse for the woman, more primary care providers need to be well versed in opioid‐assisted therapy. In addition, recent changes in Food and Drug Administration regulations now allow nurse practitioners and physician assistants with specialized training to provide buprenorphine treatment for pregnant women with OUD in primary care settings. The purpose of this article is to provide information and guidance for clinicians working with and treating this population.
Differences in Lip Support with and without Labial Flanges in a Maxillary Edentulous Population – Part 3: Unblinded and Discriminatory Subjective Analysis
Authors: Bidra Avinash S. , Nguyen Viensuong , Manzotti Anna , Kuo Chia‐Ling
Published: May 2017

Purpose

To study the subjective differences in direct lip support assessments and to determine if dentists and laypeople are able to discern and correctly identify direct changes in lip support between flange and flangeless dentures.

Materials and Methods

A random sample of 20 maxillary edentulous patients described in part 2 of the study was used for analysis. A total of 60 judges comprising 15 general dentists, 15 prosthodontists, and 30 laypeople, the majority of who were distinct from part 2 of the study, were recruited. All images used in this study were cropped at the infraorbital level and converted to black and white tone, to encourage the judges to focus on lip support. The judges were un‐blinded to the study objectives and told what to look for, and were asked to rate the lip support of each of the 80 images on a 100 mm visual analog scale (VAS). The judges then took a discriminatory sensory analysis test (triangle test) where they were required to correctly identify the image with a flangeless denture out of a set of 3 images. Both the VAS and triangle test ratings were conducted twice in a random order, and mean ratings were used for all analyses.

Results

The overall VAS ratings of lip support for images with flangeless dentures were slightly lower compared to images with labial flanges, and this difference was statistically significant (p < 0.0001). This was true for both profile and frontal images. However, the magnitude of these differences was too small (no greater than 5 mm on a 100‐mm scale) to be clinically significant or meaningful. The differences in VAS ratings were not significant between the judges. For the triangle test, judges overall correctly identified the flangeless denture image in 55% of frontal image sets and 60% of profile image sets. The difference in correct identification rate between frontal and profile images was statistically significant (p < 0.0001). For frontal and profile images, prosthodontists had the highest correct identification rate (61% and 69%), followed by general dentists (53% and 68%) and by laypeople (53% and 50%). The difference in correct identification rate was statistically significant between various judges (p = 0.012). For all judges, the likelihood of correctly identifying images with flangeless dentures was significantly greater than 1/3, which was the minimum chance for correct identification (p < 0.0001).

Conclusions

Removal of a labial flange in a maxillary denture resulted in slightly lower ratings of lip support compared to images with a labial flange, but the differences were clinically insignificant. When judges were forced to look for differences, flangeless dentures were detected more often in profile images. Prosthodontists detected the flangeless dentures more often than general dentists and laypeople.