bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sublingual allergen immunotherapy in HIV‐positive patients
Authors: Iemoli E. , Borgonovo L. , Fusi A. , Magni C. , Ricci E. D. , Rizzardini G. , Piconi S. 
Published: July 2015

AbstractHIV infection is a relative contraindication for allergic immunotherapy (AIT). In the last decade, highly active antiretroviral therapy (HAART) has improved the immune function and life expectancy in HIV‐infected patients whose respiratory allergic incidence is similar to the general population. We evaluated the safety and clinical effectiveness of sublingual immunotherapy in a group of grass pollen‐allergic HAART‐treated HIV‐positive patients. Thirteen patients received sublingual immunotherapy (SLIT) tablet (Oralair, Stallergenes©) and symptomatic therapy and were compared with nine patients receiving symptomatic therapy alone. Clinical benefits were evaluated by the analysis of total combined score (TCS), sum of symptom–medication score, and a quality of life (QoL) questionnaire. HIV viral load and peripheral TCD4 lymphocytes were analyzed at the beginning and at the end of the study. Clinical efficacy data showed a significant improvement in SLIT‐treated patients compared to controls (TCS: P = 0.0001; QoL: P = 0.03). We did not observe any significant alteration of TCD4 cell counts and viral load (VL) in both groups. Our preliminary data showed that SLIT therapy in viro‐immunological controlled HAART treated HIV positive patients was efficacious, safe and well tolerated.
Progression of cervical dilatation in normal human labor is unpredictable
Authors: Ferrazzi Enrico , Milani Silvano , Cirillo Federico , Livio Stefania , Piola Cinzia , Brusati Valentina , Paganelli Andrea 
Published: July 2015

AbstractIntroductionThe aim of this study was to analyze how the progression of cervical dilatation in active labor can be predicted by digital assessment in low‐risk pregnant women, in spontaneous labor at term.Material and methodsThis prospective observational study was performed on 328 women with singleton term gestations experiencing midwife‐led labor according to local protocols, progressing to full dilatation and spontaneous delivery without any medical intervention. Mixed nonlinear models were adopted to (i) model individual cervical data into centile curves and (ii) calculate the time needed to gain 1 cm in cervical dilatation (TNG1cm) modeled as a function of current dilatation. We correlated the first and the last TNG1cmon parturients with at least four cervical data points.ResultsTNG1cmshowed large variations, both before and after 6 cm. This variability of natural progression of cervical curves described by the 10th and 90th centiles exceeded the differences observed in published curves from cohorts homogeneous for parity, weight and ethnicity. There was no significant correlation between the first and the last TNG1cm. Neonatal base excess was not significantly different in women with TNG1cm<10th centile and >90th centile.ConclusionsThe rate of cervical dilatation, traced by parsimonious nonlinear mixed models, is largely unpredictable in the case of spontaneous naturally progressing labor, even when possible larger individual variability is excluded by prudent clinical rules. Future research in labor and delivery should be focused on the diagnosis of the causes that lie behind apparently erratic cervical changes.
Evaluation of response to hormone therapy in patients with measurable adult granulosa cell tumors of the ovary
Authors: van Meurs Hannah S. , van der Velden Jacobus , Buist Marrije R. , van Driel Willemien J. , Kenter Gemma G. , van Lonkhuijzen Luc R.C.W. 
Published: July 2015

AbstractIntroductionThe aim of this study was to retrospectively determine the objective response rate to hormone therapy (HT) for patients with a measurable adult granulosa cell tumor (GCT) of the ovary in a consecutive series of patients.Material and methodsAll patients with an adult GCT who were treated with HT [steroidal progestins, selective estrogen receptor modulators, aromatase inhibitors and gonadotropin‐releasing hormone agonists] within three referral hospitals were identified and their records were screened for HT administration. The main outcome measure was the objective response rate to HT.ResultsWe identified 127 patients with an adult GCT, of whom 81 (64%) had a recurrence. Twenty‐five of these patients (20%) were treated with hormones, of whom 22 had measurable disease at the start of their treatment, i.e. a tumor of more than 1 cm in diameter as seen on imaging, either as a recurrence or as residual disease. The pooled objective response rate, defined as the proportion of patients whose best overall response to hormone therapy was either complete response or partial response to HT, was 18% (4/22) (95% confidence interval 6–41%). In one patient (4.5%) a complete response and in three (14%) a partial response was described. Fourteen patients (64%) had stable disease and in four patients (18%) disease was progressive.ConclusionsAlthough several case reports described good responses to HT in patients with a GCT, we found a response in only four of 22 patients in this relatively large consecutive series of patients.
Retracted: Randomised clinical trial: the clinical efficacy and safety of an alginate‐antacid (Gaviscon Double Action) versus placebo, for decreasing upper gastrointestinal symptoms in symptomatic gastroesophageal reflux disease (GERD) in China
Authors: Sun J. , Yang C. , Zhao H. , Zheng P. , Wilkinson J. , Ng B. , Yuan Y. 
Published: July 2015

SummaryBackgroundThere is a paucity of large‐scale studies evaluating the clinical benefit of the Gaviscon Double Action (DA) alginate‐antacid formulation for treating gastroesophageal reflux disease (GERD) symptoms.AimRandomised double‐blind placebo‐controlled parallel‐group study to evaluate efficacy and safety of GavisconDAin reducing heartburn, regurgitation and dyspepsia symptoms in individuals with mild‐to‐moderateGERDin China.MethodsParticipants with symptomaticGERD(n = 1107) were randomised to receive GavisconDAor placebo (two tablets four times daily) for seven consecutive days. The primary endpoint compared the change in Reflux Disease Questionnaire (RDQ) score for theGERD(heartburn + regurgitation) dimension between GavisconDAand placebo. Secondary endpoints compared the change inRDQscores for individual heartburn, regurgitation and dyspepsia dimensions, overall treatment evaluation (OTE) scores and incidence of adverse events (AEs).ResultsMeanRDQ GERDscores: 2.51 for GavisconDAand 2.50 for placebo at baseline; 1.25 for GavisconDAand 1.46 for placebo post treatment. GavisconDAwas statistically superior to placebo in reducingGERDand dyspepsiaRDQscores [least‐squares mean (LSM) difference:GERD−0.21,P < 0.0001; dyspepsia −0.18,P = 0.0004], despite a substantial placebo response. The GavisconDAgroup reported more favourable overall treatment responses than the placebo group across allOTEcategories (P < 0.0001). Superior relief ofGERDsymptoms was observed both in those with non‐erosive and those with erosive reflux disease (LSMdifference −0.14 [P = 0.038] and −0.29 [P < 0.0001] respectively). Incidence ofAEs was similar in both groups.ConclusionGavisconDAtablets provide effective and safe reduction in acid reflux and dyspepsia symptoms in Chinese individuals with mild‐to‐moderateGERD. ClinicalTrials.gov:NCT01869491
Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti‐TNF alpha: 5‐year follow‐up study
Authors: Pugliese D. , Guidi L. , Ferraro P. M. , Marzo M. , Felice C. , Celleno L. , Landi R. , Andrisani G. , Pizzolante F. , De Vitis I. , Papa A. , Rapaccini G. L. , Armuzzi A. 
Published: July 2015

SummaryBackgroundPsoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti‐TNF alpha. Patients with severe skin lesions unresponsive to topical therapy need to withdraw from treatment.AimTo estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti‐TNF alpha and to analyse its clinical correlates.MethodsA retrospective cohort study on all IBD patients who started anti‐TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time‐dependent predictors were updated at each available time point.ResultsFour hundred and two patients were included. Participants contributed a total of 839 person‐years of follow‐up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person‐years. Cox‐regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36–4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12–0.92; P = 0.03).ConclusionsParadoxical psoriasis is a relevant side effect of anti‐TNF alpha therapy, with an incidence rate of five per 100 person‐years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti‐TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.
Taste organ growth and development in the direct developing frog Eleutherodactylus coqui (Lissamphibia: Eleutherodactylidae)
Authors: Budzik Karolina A. , Żuwała Krystyna , Buchholz Daniel R. 
Published: July 2015

AbstractPrevious research on amphibian taste organs concerned amphibians with a biphasic life history, that is, with larval period and metamorphosis. Direct developing frog species, such as Eleutherodactylus coqui, undergo a cryptic metamorphosis before hatching, and many larval‐specific features are vestigial or have been lost entirely from their ontogeny. Taste buds are present in larval stages of biphasically developing anurans and are replaced by taste discs during metamorphosis. One goal of this study was to characterize the ontogeny of taste buds and/or discs in E. coqui. The other goal was to examine correlations between body size and taste organ density and size in different regions of oral epithelium. The research reveals the presence of only one type of taste organ, characteristic of metamorphs of biphasic amphibians, namely taste disc. In addition, taste disc density and the area of the taste disc sensory zone change dramatically during growth.
Microscopic structures of the ovary and female genital ducts of Supachai's caecilian, Ichthyophis supachaii Taylor, 1960 (Amphibia: Gymnophiona)
Authors: Pewhom Akkanee , Chumnanpuen Pramote , Muikham Itsares , Chatchavalvanich Kannika , Srakaew Nopparat 
Published: July 2015

AbstractThe structures of the female reproductive system (ovary, oviduct and cloaca) of Ichthyophis supachaii were investigated by dissection, histology and light microscopy. Paired, elongated, sac‐like ovaries are parallel to the gut and fat bodies. Follicle stages include germinal nests of oogonia and primary oocytes, early and late previtellogenic follicles, early and late vitellogenic follicles and atretic follicles. Germinal nests of oogonia comprise oogonia and prefollicular cells. Nests of primary oocytes contain clusters of synchronously developing primary oocytes enclosed by connective tissue. Primary oocytes are associated with follicular cells. Previtellogenic follicles initially form the vitelline envelope, theca cell layers and patches of ooplasmic glycoproteins. Vitellogenic follicles contain heterogeneously sized spherical yolk granules. Atresia is present in several stages of developing follicles. The oviduct is divided into the anterior, middle and posterior parts. All oviductal parts are lined by non‐ciliated epithelium. A small number of mucous cells are present in the middle part. The cloaca of female I. supachaii is divided into the anterior and posterior chambers. The anterior chamber is lined by glandular stratified columnar epithelium, while the posterior chamber has stratified cuboidal epithelium with less mucus production. Our results contribute to useful information on the reproductive biology of caecilians.
Using impairment and cognitions to predict walking in osteoarthritis: A series of n‐of‐1 studies with an individually tailored, data‐driven intervention
Authors: O'Brien Nicola , Philpott‐Morgan Siôn , Dixon Diane 
Published: July 2015

ObjectivesFirst, this study compares the ability of an integrated model of activity and activity limitations, the International Classification of Functioning, Disability and Health (ICF), and the Theory of Planned Behaviour (TPB) to predict walking within individuals with osteoarthritis. Second, the effectiveness of a walking intervention in these individuals is determined.DesignA series of n‐of‐1 studies with an AB intervention design was used.MethodsDiary methods were used to study four community‐dwelling individuals with lower‐limb osteoarthritis. Data on impairment symptoms (pain, pain on movement, and joint stiffness), cognitions (intention, self‐efficacy, and perceived controllability), and walking (step count) were collected twice daily for 12 weeks. At 6 weeks, an individually tailored, data‐driven walking intervention using action planning or a control cognition manipulation was delivered. Simulation modelling analysis examined cross‐correlations and differences in baseline and intervention phase means. Post‐hoc mediation analyses examined theoretical relationships and multiple regression analyses compared theoretical models.ResultsCognitions, intention in particular, were better and more consistent within individual predictors of walking than impairment. The walking intervention did not increase walking in any of the three participants receiving it. The integrated model and the TPB, which recognize a predictive role for cognitions, were significant predictors of walking variance in all participants, whilst the biomedical ICF model was only predictive for one participant.ConclusionDespite the lack of evidence for an individually tailored walking intervention, predictive data suggest that interventions for people with osteoarthritis that address cognitions are likely to be more effective than those that address impairment only. Further within‐individual investigation, including testing mediational relationships, is warranted.
Statement of contribution

What is already known on this subject?

N‐of‐1 methods have been used to study within‐individual predictors of walking in healthy and chronic pain populations

An integrated biomedical and behavioural model of activity and activity limitations recognizes the roles of impairment and psychology (cognitions)

Interventions modifying cognitions can increase physical activity in people with mobility limitations

What does this study add?

N‐of‐1 methods are suitable to study within‐individual predictors of walking and interventions in osteoarthritis

An integrated and a psychological model are better predictors of walking in osteoarthritis than a biomedical model

There was no support for an individually tailored, data‐driven walking intervention
Angiotensin II stimulation alters vasomotor response to adenosine in mouse mesenteric artery: role for A1 and A2B adenosine receptors
Authors: Yadav Vishal R , Nayeem Mohammed A , Tilley Stephen L , Mustafa S Jamal 
Published: July 2015

Background and PurposeStimulation of the A1 adenosine receptor and angiotensin II receptor type‐1 (AT1 receptor) causes vasoconstriction through activation of cytochrome P450 4A (CYP4A) and ERK1/2. Thus, we hypothesized that acute angiotensin II activation alters the vasomotor response induced by the non‐selective adenosine receptor agonist, NECA, in mouse mesenteric arteries (MAs).Experimental ApproachWe used a Danish Myo Technology wire myograph to measure muscle tension in isolated MAs from wild type (WT), A1 receptor and A2B receptor knockout (KO) mice. Western blots were performed to determine the expression of AT1 receptors and CYP4A.Key ResultsAcute exposure (15 min) to angiotensin II attenuated the NECA‐dependent vasodilatation and enhanced vasoconstriction. This vasoconstrictor effect of angiotensin II in NECA‐treated MAs was abolished in A1 receptor KO mice and in WT mice treated with the A1 receptor antagonist DPCPX, CYP4A inhibitor HET0016 and ERK1/2 inhibitor PD98059. In MAs from A2B receptor KO mice, the vasoconstrictor effect of angiotensin II on the NECA‐induced response was shown to be dependent on A1 receptors. Furthermore, in A2B receptor KO mice, the expression of AT1 receptors and CYP4A was increased and the angiotensin II‐induced vasoconstriction enhanced. In addition, inhibition of KATP channels with glibenclamide significantly reduced NECA‐induced vasodilatation in WT mice.Conclusions and ImplicationsAcute angiotensin II stimulation enhanced A1 receptor‐dependent vasoconstriction and inhibited A2B receptor‐dependent vasodilatation, leading to a net vasoconstriction and altered vasomotor response to NECA in MAs. This interaction may be important in the regulation of BP.
Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet‐induced obesity
Authors: Capel Frédéric , Chabrier Gwladys , Pitois Elodie , Rigaudière Jean‐Paul , Plenier Servane Le , Durand Christine , Jouve Chrystèle , de Bandt Jean‐Pascal , Cynober Luc , Moinard Christophe , Morio Béatrice 
Published: July 2015

Background and PurposeNO is a crucial regulator of energy and lipid metabolism, whose homeostasis is compromised during obesity. Combination of citrulline and atorvastatin potentiated NO production in vitro. Here we have assessed the effects of this combination in mice with diet‐induced obesity (DIO).Experimental ApproachC57BL/6J male mice were given a standard diet (control) or a high fat–high sucrose diet (DIO) for 8 weeks. DIO mice were then treated with DIO alone, DIO with citrulline, DIO with atorvastatin or DIO with citrulline and atorvastatin (DIOcit–stat) for 3 weeks. Thereafter, body composition, glucose tolerance, insulin sensitivity and liver fat metabolism were measured.Key ResultsDIOcit–stat mice showed lower body weight, fat mass and epididymal fat depots compared with other DIO groups. Unlike other DIO groups, glucose tolerance and insulin sensitivity of DIOcit–stat, along with blood glucose and insulin concentrations in response to feeding, were restored to control values. Refeeding‐induced changes in liver lipogenic activity were also reduced in DIOcit–stat mice compared with those of DIO animals. This was associated with decreased gene expression of the transcription factor SREBP‐1, liver X receptor α, ChREBP and of target lipogenic enzymes in the liver of DIOcit–stat mice compared with those of other DIO groups.Conclusions and ImplicationsThe citrulline–atorvastatin combination prevented fat mass accumulation and maintained glucose homeostasis in DIO mice. Furthermore, it potentiated inhibition of hepatic de novo lipogenesis activity. This combination has potential for preservation of glucose homeostasis in patients receiving statin therapy.
Propranolol decreases retention of fear memory by modulating the stability of surface glutamate receptor GluA1 subunits in the lateral amygdala
Authors: Zhou Jun , Luo Yi , Zhang Jie‐Ting , Li Ming‐Xing , Wang Can‐Ming , Guan Xin‐Lei , Wu Peng‐Fei , Hu Zhuang‐Li , Jin You , Ni Lan , Wang Fang , Chen Jian‐Guo 
Published: July 2015

Background and PurposePosttraumatic stress disorder (PTSD) is a mental disorder with enhanced retention of fear memory and has profound impact on quality of life for millions of people worldwide. The β‐adrenoceptor antagonist propranolol has been used in preclinical and clinical studies for the treatment of PTSD, but the mechanisms underlying its potential efficacy on fear memory retention remain to be elucidated.Experimental ApproachWe investigated the action of propranolol on the retention of conditioned fear memory, the surface expression of glutamate receptor GluA1 subunits of AMPA receptors and synaptic adaptation in the lateral amygdala (LA) of rats.Key ResultsPropranolol attenuated reactivation‐induced strengthening of fear retention while reducing enhanced surface expression of GluA1 subunits and restoring the impaired long‐term depression in LA. These effects of propranolol were mediated by antagonizing reactivation‐induced enhancement of adrenergic signalling, which activates PKA and calcium/calmodulin‐dependent protein kinase II and then regulates the trafficking of AMPA receptors via phosphorylation of GluA1 subunits at the C‐terminus. Both i.p. injection and intra‐amygdala infusion of propranolol attenuated reactivation‐induced enhancement of fear retention.Conclusions and ImplicationsReactivation strengthens fear retention by increasing the level of noradrenaline and promotes the surface expression of GluA1 subunits and the excitatory synaptic transmission in LA. These findings uncover one mechanism underlying the efficiency of propranolol on retention of fear memories and suggest that β‐adrenoceptor antagonists, which act centrally, may be more suitable for the treatment of PTSD.
pLR‐HL: A Novel Amphibian Bowman–Birk‐type Trypsin Inhibitor from the Skin Secretion of the Broad‐folded Frog, Hylarana latouchii
Authors: Lin Yan , Hang Haiying , Chen Tianbao , Zhou Mei , Wang Lei , Shaw Chris 
Published: July 2015

In this study, we report a novel heptadecapeptide (LIGGCWTKSIPPKPCLV) of the pLR/ranacyclin family, named pLR‐HL, whose structure was deduced from its biosynthetic precursor‐encoding cDNA cloned from the skin secretion‐derived cDNA library of the broad‐folded frog, Hylarana latouchii, by employing a ‘shotgun’ cloning technique. It contains a disulphide loop between Cys5 and Cys15 which is consistent with Bowman–Birk‐type protease inhibitors. The primary structure of pLR‐HL deduced from the cDNA sequence was confirmed by fractionating the skin secretion using reverse‐phase HPLC and subsequent analysis using MALDI‐TOF mass spectrometry and LC/MS/MS fragmentation sequencing. On the basis of the establishment of unequivocal amino acid sequence, a synthetic replicate was synthesized by solid‐phase Fmoc chemistry, and it displayed a moderately potent trypsin inhibition with a Ki of 143 nm. The substitution of Lys‐8 by Phe (Phe8‐pLR‐HL) resulted in abolition of trypsin inhibition but generation of modest inhibition on chymotrypsin with a Ki of 2.141 μm. Additionally, both the disulphide loops of pLR‐HL and Phe8‐pLR‐HL were synthesized and tested. Both of the catalytic loops retained similar inhibitory potencies towards trypsin or chymotrypsin in comparison with the original intact molecules. Thus, the replacement of reactive site residues could alter the specificity of these protease inhibitors, while the canonical reactive loop alone can independently constitute biologically active moiety.
Design and Synthesis of Nicotinic Acetylcholine Receptor Antagonists and their Effect on Cognitive Impairment
Authors: Jaikhan Pattaporn , Boonyarat Chantana , Arunrungvichian Kuntarat , Taylor Palmer , Vajragupta Opa 
Published: July 2015

Structure modification of a lead compound (NSC13378) was accomplished in the present work by an in silico target‐based design aimed at ligands acting on the nicotinic acetylcholine receptor (nAChR) for neurodegenerative diseases. A 187‐compound focused library derived from the scaffold of the lead compound was screened against acetylcholine‐binding proteins (AChBPs). Six compounds were identified and synthesized for binding and biological evaluations. Five compounds were found to bind with AChBPs. Among these compounds, QN1 and BZ1 showed the highest affinity binding with AChBP, with Kd values of 260 and 10 nm, respectively. Functional assays on isolated cell lines containing ligand‐gated ion channels revealed that QN1 and BZ1 are α4β2‐nAChR antagonists. QN1 and BZ1 significantly alleviated the memory impairment caused by the muscarinic cholinergic antagonist scopolamine (p < 0.05) in mice. Our findings demonstrate the potential of nAChR antagonists in drug development for cognitive impairments.