bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemokine (C‐C motif) ligand 2 and chemokine (C‐C motif) ligand 7 in angle‐closure glaucoma
Authors: Gao Xinbo , Huang Wenbin , Zhang Xiulan , Du Shaolin , Wang Jiawei , Wang Wei , Zhou Minwen , Chen Shida , Li Xingyi , Jonas Jost B.
Published: March 2015

Purpose

To compare the concentrations of chemokine (C‐C motif) ligand 2 (CCL2) and chemokine (C‐C motif) ligand 7 (CCL7) in aqueous humour of eyes with acute primary angle‐closure (APAC), primary angle‐closure glaucoma (PACG) or with age‐related cataract.

Methods

The prospective investigation included a study group of 56 patients (24 patients with APAC; 32 patients with PACG) undergoing glaucoma surgery and a control group of 21 patients undergoing routine cataract surgery. The interval between glaucoma attack and trabeculectomy was 19.4 ± 9.8 days.

Results

The concentrations of CCL2 (3037 ± 501 versus 1127 ± 141 pg/ml; p = 0.003) and CCL7 (10.5 ± 2.4 versus 2.8 ± 0.4 pg/ml; p < 0.001) were significantly higher in the APAC group than in the PACG group, while the concentrations of both cytokines did not differ significantly between the PACG group and the control group (CCL2: 1190 ± 98 pg/ml; p = 0.10; CCL7: 2.0 ± 0.6; p = 0.18). The concentrations of both cytokines were significantly and inversely correlated with the interval between the acute angle‐closure attack and surgery (CCL2: p = 0.02; ρ = −0.48; CCL7: p = 0.04; ρ = −0.42). Higher CCL2 concentrations were associated with higher prevalence of surgical failure (28.6% versus 7.1%; p = 0.036).

Conclusions

Concentrations of CCL2 and CCL7 as major inflammatory cytokines with potential influence on the risk of filtering surgery failure were significantly elevated after an acute glaucoma attack and decreased with longer interval to the attack. Trabeculectomy may have a lower risk of failure if performed later than earlier after an acute glaucoma attack, with lower CCL2 concentrations associated with better surgical outcome.
Identifying faecal impaction is important for ensuring the timely diagnosis of childhood functional constipation
Authors: Modin Line , Walsted Anne‐Mette , Jakobsen Marianne Skytte
Published: March 2015

Aim

Most research on functional constipation has been carried out at a tertiary level. We focused this study on a secondary‐level hospital outpatients' department, assessing the distribution of diagnostic criteria for childhood functional constipation and evaluating the consequences of current diagnostic practice based on current guidelines.

Methods

We enrolled 235 children, aged two to 16 years of age, with functional constipation according to the Rome III criteria and assessed them using medical histories and physical examinations, including rectal examinations and ultrasound measurements of rectal diameter. Faecal impaction was a rectal diameter exceeding 3 cm.

Results

The most frequently reported symptom was painful bowel movements (72.3%) and 39.1% had faecal incontinence. Rectal examination identified faecal impaction in 149 children (66.2%), and ultrasound showed a mean rectal diameter of 3.4 ± 0.6 cm, compared to 2.2 ± 0.6 cm in children without impaction (p < 0.001). Of the 149 children with faecal impaction, 19 (12.8%) only had one additional Rome III criterion. The rectal diameter exceeded 3 cm in 79.9% of cases.

Conclusion

Identifying faecal impaction is important for ensuring the timely diagnosis of childhood functional constipation at the secondary care level. Ultrasound examination proved a reliable alternative to rectal examination or abdominal radiography when identifying faecal impaction.
Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection
Authors: Cammarota G. , Masucci L. , Ianiro G. , Bibbò S. , Dinoi G. , Costamagna G. , Sanguinetti M. , Gasbarrini A.
Published: March 2015

Background

Faecal microbiota transplantation (FMT) from healthy donors is considered an effective treatment against recurrent Clostridium difficile infection.

Aim

To study the effect of FMT via colonoscopy in patients with recurrent C. difficile infection compared to the standard vancomycin regimen.

Methods

In an open‐label, randomised clinical trial, we assigned subjects with recurrent C. difficile infection to receive: FMT, short regimen of vancomycin (125 mg four times a day for 3 days), followed by one or more infusions of faeces via colonoscopy; or vancomycin, vancomycin 125 mg four times daily for 10 days, followed by 125–500 mg/day every 2–3 days for at least 3 weeks. The latter treatment did not include performing colonoscopy. The primary end point was the resolution of diarrhoea related to C. difficile infection 10 weeks after the end of treatments.

Results

The study was stopped after a 1‐year interim analysis. Eighteen of the 20 patients (90%) treated by FMT exhibited resolution of C. difficile‐associated diarrhoea. In FMT, five of the seven patients with pseudomembranous colitis reported a resolution of diarrhoea. Resolution of C. difficile infection occurred in 5 of the 19 (26%) patients in vancomycin (P < 0.0001). No significant adverse events were observed in either of the study groups.

Conclusions

Faecal microbiota transplantation using colonoscopy to infuse faeces was significantly more effective than vancomycin regimen for the treatment of recurrent C. difficile infection. The delivery of donor faeces via colonoscopy has the potential to optimise the treatment strategy in patients with pseudomembranous colitis.
Systematic review with meta‐analysis: pharmacological interventions for eosinophilic oesophagitis
Authors: Sawas T. , Dhalla S. , Sayyar M. , Pasricha P. J. , Hernaez R.
Published: March 2015

Background

Eosinophilic oesophagitis (EoE) is a growing cause of dysphagia. Current therapies include dietary manipulation, steroids and biological drugs.

Aim

To perform a systematic review and summarise the effect of different medical interventions on EoE.

Methods

Two reviewers searched Pubmed and Embase for studies on treatment for EoE. We included randomised controlled trials (RCT) limited to pharmacological interventions. Two reviewers selected studies. Meta‐analysis was done using random effects model to estimate odds ratio (OR). Heterogeneity was determined by Cochran's Q statistic and I2.

Results

Seventeen references met our inclusion criteria. Eleven RCTs involving 455 participants were included in the meta‐analysis. 325 participants were evaluated for symptomatic improvement and 330 were evaluated for histological remission. Symptomatic improvement with topical steroids (7 studies, 250 participants) compared to the control group (placebo or PPI) was noted (OR: 3.03, 95% confidence interval, CI: 1.57–5.87). Histological remission was also noted in nine studies involving 330 participants (OR: 13.66, 95% CI: 2.65–70.34) comparing topical steroids to a control (placebo or PPI). There was no difference between anti‐IL‐5 drugs and placebo in terms of symptomatic improvement (OR: 0.69, 95% CI: 0.34–1.42).

Conclusions

Topical steroids induce significant symptomatic and histological remission, and should be considered as a first line treatment. Anti‐IL‐5 therapy has a minor effect on eosinophilic oesophagitis. Future research in eosinophilic oesophagitis should standardise methodology according to published guidelines to improve quality and allow direct comparison between therapies.
Plant beta‐diversity is enhanced around grassland–forest edges within a traditional agricultural landscape
Authors: Ohara Ryohei G. , Ushimaru Atushi
Published: March 2015

Questions

Are there positive edge effects on beta‐ and alpha‐diversity of plant species across semi‐natural grassland–secondary forest gradients located within a traditional agricultural landscape? Is beta‐diversity (dissimilarity in plant species composition between two given plots) well explained by environmental differences for both grasslands and forests? Do gradients of environmental factors created by forest edges influence spatial variation in alpha‐diversity from edges to grasslands and forests?

Location

Semi‐natural grasslands and secondary forests (or conifer plantation) around paddy fields in a traditional agricultural landscape, western Japan.

Methods

Vegetation survey and environmental (soil water content and sunlight) measurements were conducted on 11 transects passing through grassland–forest ecosystems. Spatial variations in plant beta‐ and alpha‐diversity and environmental variables and their relationships were examined.

Results

We quantitatively demonstrated common positive edge effects on beta‐diversity in both grasslands and forests. Our results suggest that among‐edge variations in light conditions, which likely depend on edge aspect and forest type, promote high grassland plant beta‐diversity in the vicinity of edges. However, the high beta‐diversity of forest floor communities in the proximity of edges cannot be explained by this mechanism. Alpha‐diversity tended to be lower within grassland plots located around edges than in grassland interiors, while the richness of the forest community increased toward the edge. This alpha‐diversity pattern was suggested to be attributable to resource gradients created by the forest edges.

Conclusions

Although plant alpha‐diversity may not be consistently high in the vicinity of edges, beta‐diversity in the communities bordering grassland–forest edges will generally be high in the traditional agricultural landscape. Thus, maintenance of environmental heterogeneity among grassland–forest edges in agricultural ecosystems should be prioritized for local biodiversity conservation.
Pevonedistat (MLN4924), a First‐in‐Class NEDD8‐activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study
Authors: Swords Ronan T. , Erba Harry P. , DeAngelo Daniel J. , Bixby Dale L. , Altman Jessica K. , Maris Michael , Hua Zhaowei , Blakemore Stephen J. , Faessel Hélène , Sedarati Farhad , Dezube Bruce J. , Giles Francis J. , Medeiros Bruno C.
Published: March 2015

This trial was conducted to determine the dose‐limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8‐activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Pevonedistat was administered via a 60‐min intravenous infusion on days 1, 3 and 5 (schedule A, n = 27), or days 1, 4, 8 and 11 (schedule B, n = 26) every 21‐days. Dose escalation proceeded using a standard ‘3 + 3’ design. Responses were assessed according to published guidelines. The MTD for schedules A and B were 59 and 83 mg/m2, respectively. On schedule A, hepatotoxicity was dose limiting. Multi‐organ failure (MOF) was dose limiting on schedule B. The overall complete (CR) and partial (PR) response rate in patients treated at or below the MTD was 17% (4/23, 2 CRs, 2 PRs) for schedule A and 10% (2/19, 2 PRs) for schedule B. Pevonedistat plasma concentrations peaked after infusion followed by elimination in a biphasic pattern. Pharmacodynamic studies of biological correlates of NAE inhibition demonstrated target‐specific activity of pevonedistat. In conclusion, administration of the first‐in‐class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed.
Dose‐intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma: a randomized phase II study
Authors: Ishida Takashi , Jo Tatsuro , Takemoto Shigeki , Suzushima Hitoshi , Uozumi Kimiharu , Yamamoto Kazuhito , Uike Naokuni , Saburi Yoshio , Nosaka Kisato , Utsunomiya Atae , Tobinai Kensei , Fujiwara Hiroshi , Ishitsuka Kenji , Yoshida Shinichiro , Taira Naoya , Moriuchi Yukiyoshi , Imada Kazunori , Miyamoto Toshihiro , Akinaga Shiro , Tomonaga Masao , Ueda Ryuzo
Published: March 2015

This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti‐CC chemokine receptor 4 antibody, to mLSG15, a dose‐intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15‐plus‐mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33–71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16–55%) and 75%, respectively. Grade ≥ 3 treatment‐emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15‐plus‐mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15‐plus‐mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887.
Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long‐Standing Model
Authors: Leão Anderson H.F.F. , Sarmento‐Silva Aldair J. , Santos José R. , Ribeiro Alessandra M. , Silva Regina H.
Published: March 2015

The administration of reserpine to rodents was one of the first models used to investigate the pathophysiology and screening for potential treatments of Parkinson's disease (PD). The reserpine model was critical to the understanding of the role of monoamine system in the regulation of motor and affective disorders, as well as the efficacy of current PD treatments, such as L‐DOPA and dopamine agonists. Nevertheless, with the introduction of toxin‐induced and genetic models of PD, reserpine became underused. The main rationale to this drawback was the supposed absence of reserpine construct validity with PD. Here, we highlight classical and recent experimental findings that support the face, pharmacological, and construct validity of reserpine PD model and reason against the current rationale for its underuse. We also aim to shed a new perspective upon the model by discussing the main challenges and potentials for the reserpine model of PD.
Cancer immunotherapy using novel tumor‐associated antigenic peptides identified by genome‐wide cDNA microarray analyses
Authors: Nishimura Yasuharu , Tomita Yusuke , Yuno Akira , Yoshitake Yoshihiro , Shinohara Masanori
Published: March 2015

Recent genome‐wide cDNA microarray analysis of gene expression profiles in comprehensive tumor types coupled with isolation of cancer tissues by laser‐microbeam microdissection have revealed ideal tumor‐associated antigens (TAAs) that are frequently overexpressed in various cancers including head and neck squamous cell cancer (HNSCC) and lung cancer, but not in most normal tissues except for testis, placenta, and fetal organs. Preclinical studies using HLA‐transgenic mice and human T cells in vitro showed that TAA‐derived CTL‐epitope short peptides (SPs) are highly immunogenic and induce HLA‐A2 or ‐A24‐restricted CTLs. Based on the accumulated evidence, we carried out a phase II clinical trial of the TAA‐SP vaccine in advanced 37 HNSCC patients. This study showed a significant induction of TAA‐specific CTLs in the majority of patients without serious adverse effects. Importantly, clinical responses including a complete response were observed in this study. Another phase II clinical trial of therapeutic TAA‐SP vaccine, designed to evaluate the ability of prevention of recurrence, is ongoing in HNSCC patients who have received curative operations. Further studies in human preclinical studies and in vivo studies using HLA class I transgenic mice showed TAA‐derived long peptides (TAA‐LPs) have the capacity to induce not only promiscuous HLA class II‐restricted CD4+ T helper type 1 cells but also tumor‐specific CTLs through a cross‐presentation mechanism. Moreover, we observed an augmentation of TAA‐LP‐specific T helper type 1 cell responses and tumor antigen‐spreading in HNSCC patients vaccinated with TAA‐SPs. This accumulated evidence suggests that therapeutic TAA‐SPs and LPs vaccines may provide a promising cancer immunotherapy.
STAT-5 is activated constitutively in T cells, B cells and monocytes from patients with primary Sjögren's syndrome
Authors: Pertovaara M , Silvennoinen O , Isomäki P
Published: March 2015

The expression and phosphorylation of signal transducer and activator of transcription-1 (STAT-1) have been shown to be markedly increased in the salivary gland epithelial cells of patients with primary Sjögren's syndrome (pSS). The present aim was to investigate the activation status of different STAT proteins in peripheral blood (PB) lymphocytes and monocytes, and their correlations with clinical parameters in patients with pSS. To this end, PB samples were drawn from 16 patients with active pSS and 16 healthy blood donors, and the phosphorylation of STAT-1, -3, -4, -5 and -6 proteins was studied in T cells, B cells and monocytes using multi-colour flow cytometry. In addition, mRNA expression of STAT molecules in PB mononuclear cells (PBMC) was studied with quantitative reverse transcriptase–polymerase chain reaction (RT–PCR). Basal phosphorylation of STAT-5 was found to be significantly higher in PB T cells, B cells and monocytes in patients with pSS than in healthy controls. The expression of STAT-5 mRNA was not increased in PBMC. pSTAT-5 levels in B cells and monocytes showed a significant correlation with serum immunoglobulin (Ig)G levels and anti-SSB antibody titres. Constitutive STAT-5 activation in monocytes and CD4+ T cells was associated with purpura. There were no major differences in the activation of other STATs between pSS patients and healthy controls. In conclusion, STAT-5 is activated constitutively in PB leucocytes in patients with pSS, and basal STAT-5 phosphorylation seems to associate with hypergammaglobulinaemia, anti-SSB antibody production and purpura.
Vitamin D and insulin resistance
Authors: Wallace Ian R. , Wallace Helen J. , McKinley Michelle C. , Bell Patrick M. , Hunter Steven J.
Published: March 2015

Vitamin D is a steroid hormone, which in active form binds to the vitamin D receptor. Expression of the vitamin D receptor in diverse cell types (pancreatic islet cells, myocytes, hepatocytes and adipocytes) raises the suspicion that vitamin D may be involved in multiple cellular processes, including the response to insulin. Insulin resistance is a characteristic feature of type 2 DM, and its attenuation may reduce the incidence of type 2 DM and cardiovascular disease. In observational studies, low serum 25‐hydroxyvitamin D (25‐OHD) concentrations are associated with an increased risk of type 2 DM. It has been suggested that increasing serum 25‐OHD concentrations may have beneficial effects on glucose and insulin homeostasis. However, cross‐sectional and interventional studies of vitamin D supplementation provide conflicting results and demonstrate no clear beneficial effect of vitamin D on insulin resistance. These studies are complicated by inclusion of different patient cohorts, different 25‐OHD assays and different doses and preparations of vitamin D. Any possible association may be confounded by alterations in PTH, 1,25‐dihydroxyvitamin D or tissue vitamin D concentrations. We identified 39 studies via MEDLINE and PUBMED. We review the evidence from 10 studies (seven observational and three interventional) examining vitamin D and type 2 DM incidence, and 29 studies (one prospective observational, 12 cross‐sectional and 16 interventional trials) examining vitamin D and insulin resistance. Based on this data, it is not possible to state that vitamin D supplementation has any effect on type 2 DM incidence or on insulin resistance. Data from the multiple ongoing randomized controlled trials of vitamin D supplementation due to report over the next few years should help to clarify this area.
Maternal vitamin D supplementation during pregnancy prevents vitamin D deficiency in the newborn: an open‐label randomized controlled trial
Authors: Rodda C.P. , Benson J.E. , Vincent A.J. , Whitehead C.L. , Polykov A. , Vollenhoven B.
Published: March 2015

Objective

To determine whether maternal vitamin D supplementation, in the vitamin D deficient mother, prevents neonatal vitamin D deficiency.

Design

Open‐label randomized controlled trial.

Setting

Metropolitan Melbourne, Australia, tertiary hospital routine antenatal outpatient clinic.

Participants

Seventy‐eight women with singleton pregnancies with vitamin D deficiency/insufficiency (serum 25‐OH Vit D < 75 nmol/l) at their first antenatal appointment at 12–16‐week gestation were recruited.

Intervention

Participants were randomized to vitamin D supplementation (2000–4000 IU cholecalciferol) orally daily until delivery or no supplementation.

Main outcome measures

The primary outcome was neonatal serum 25‐OH vit D concentration at delivery. The secondary outcome was maternal serum 25‐OH vit D concentration at delivery.

Results

Baseline mean maternal serum 25‐OH vit D concentrations were similar (P = 0·9) between treatment (32 nmol/l, 95% confidence interval 26–39 nmol/l) and control groups (33 nmol/l, 95% CI 26–39 nmol/l). Umbilical cord serum 25‐OH vit D concentrations at delivery were higher (P < 0·0001) in neonates of treatment group mothers (81 nmol/l, 95% CI; 70–91 nmol/l) compared with neonates of control group mothers (42 nmol/l, 95% CI; 34–50 nmol/l) with a strongly positive correlation between maternal serum 25‐OH Vit D and umbilical cord serum 25‐OH vit D concentrations at delivery (Spearman rank correlation coefficient 0·88; P < 0·0001). Mean maternal serum 25‐OH Vit D concentrations at delivery were higher (P < 0·0001) in the treatment group (71 nmol/l, 95% CI; 62–81 nmol/l) compared with the control group (36 nmol/l, 95% CI; 29–42 nmol/l).

Conclusion

Vitamin D supplementation of vitamin D deficient pregnant women prevents neonatal vitamin D deficiency.
An analysis of different therapeutic options in patients with Cushing's syndrome due to bilateral macronodular adrenal hyperplasia: a single‐centre experience
Authors: Albiger N.M. , Ceccato F. , Zilio M. , Barbot M. , Occhi G. , Rizzati S. , Fassina A. , Mantero F. , Boscaro M. , Iacobone M. , Scaroni C.
Published: March 2015

Context

Bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of Cushing's syndrome (CS). A variety of in vivo tests to identify aberrant receptor expression have been proposed to guide medical treatment. Unilateral adrenalectomy (UA) may be effective in selected patients, but little is known about recurrence during follow‐up.

Objective

To describe a series of patients with BMAH and CS treated by different approaches, with a particular focus on the benefit of UA.

Design and patients

We retrospectively assessed 16 patients with BMAH and CS (11 females, five males), analysing the in vivo cortisol response to different provocative tests. Twelve of the 16 patients underwent UA and were monitored over the long term.

Results

Based on in vivo test results, octreotide LAR or propranolol was administered in one case of food‐dependent CS and two patients with a positive postural test. A significant improvement in biochemical values was seen in all patients but with limited clinical response. UA was performed in 12 patients, producing long‐term remission in three (106 ± 28 months; range: 80–135), recurrence in eight (after 54 ± 56 months; range 12–180) and persistence in one other. Four patients subsequently underwent contralateral adrenalectomy for overt CS, one received ketoconazole, and four other patients remain under observation for subclinical CS.

Conclusions

Medical treatment based on cortisol response to provocative tests had a limited role in our patients, whereas UA was useful in some of them. Although recurrence is likely, the timing of onset is variable and close follow‐up is mandatory to identify it.
Melan‐A positive dermal cells in malignant melanoma in situ
Authors: Danga Mary Elizabeth , Yaar Ron , Bhawan Jag
Published: March 2015

The presence of Melan‐A positive dermal cells in excisions for melanoma in situ represents a frequent conundrum for pathologists. These cells may represent superficially invasive melanoma, benign, incidental, dermal nevi or non‐specific staining of dermal melanophages. Occasionally, rare, Melan‐A positive dermal cells are present which do not clearly correspond to the above three categories. Our objective was to further characterize these Melan‐A positive dermal cells. To do this, immunoperoxidase staining for Melan‐A and SOX‐10 was performed on 188‐cutaneous excisions, including examples of melanoma in situ, atypical junctional melanocytic hyperplasia and non‐melanocytic tumors. These were evaluated for the presence of Melan‐A and SOX‐10 positive dermal cells. Dermal cells, positive for both markers, were identified in 17% of the excisions. The cells were present in 10% of cases from the melanocytic group and 31% of the cases from the non‐melanocytic group. These cells did not exhibit cytologic atypia and resembled neither the co‐existing neoplasm nor melanophages. We conclude that positivity of these rare Melan‐A positive cells for SOX‐10 argues that they represent true melanocytes and not non‐specific staining. The absence of cytologic atypia in these cells and their presence in excisions of non‐melanocytic neoplasms argues that they are benign, reactive, dermal melanocytes.
Sebaceous induction in dermatofibroma: a common feature of dermatofibromas on the shoulder
Authors: Zeidi Majid , North Jeffrey P.
Published: March 2015

Background

Dermatofibroma (DF) has multiple histopathological variants and overlying acanthosis, hyperkeratosis and hyperpigmentation are often present. We have frequently observed sebaceous induction in DFs on the shoulder and wanted to assess if this is a site‐specific finding.

Methods

We prospectively collected 100 DFs and assessed for sebaceous induction, the histopathologic pattern of the DF and any associated‐epidermal changes. We retrospectively searched for DFs with sebaceous induction to assess the anatomic site of the biopsy.

Results

In the 100 prospectively collected DFs, 49% occurred on the lower extremities, 39% on the upper extremities, 10% on the trunk and 2% on the head. Sebaceous induction was present in 16 DFs, 81% of which occurred on or near the shoulder. The most common variant was fibrocollagenous DF (64%), including in DFs with sebaceous induction. The retrospective search for DFs with sebaceous induction found 19 cases in which 95% occurred on the shoulder area. Sclerotic pattern DFs were most common in this retrospective cohort (47%), and seborrheic keratosis‐like hyperplasia occurred in 100% of these cases.

Conclusion

DFs occurring on the shoulder have a high incidence of sebaceous induction with seborrheic keratosis‐like epidermal hyperplasia and a fibrocollagenous or sclerotic pattern.
Parental social consequences of having a child with cerebral palsy in Denmark
Authors: Michelsen Susan I , Flachs Esben M , Madsen Mette , Uldall Peter
Published: March 2015

Aim

To analyse the social situation of parents who have a child with cerebral palsy (CP).

Method

This was a population‐based longitudinal study with linkage to public registries. Parents of children withCP(n=3671) identified in the DanishCPRegistry were compared with 17 983 parents of children withoutCP. Employment, income, cohabitation status, and presence of additional children were factors analysed during a follow‐up period of 28 years. We followed parents from before their child was born and up to the age of 43 years of the child.

Results

Mothers of children withCPunder the age of 10 were less often employed: odds ratio [OR] of employment at age 5y 0.45 (95% confidence interval [CI] 0.36–0.57), but only 11% left the labour market. Mothers of children withoutCPhad higher incomes: ratio full‐time working 1.11 (95%CI1.07–1.15). The risk of not living together was not increased among parents of children withCP: at age 5 yearsOR1.04 (95%CI0.84–1.28). Parents of children withCPas the first born postponed or more seldom had subsequent children: hazard ratio [HR] 0.75 (95%CI0.68–0.83).

Interpretation

The Danish welfare system seems to have succeeded in keeping parents in the labour market and living together with their child. Special attention needs to be paid to the financial situation of families with children withCPunder 10 years of age.
Trunk control for reaching: growing into or out of dysfunction?
Authors: Saavedra Sandra
Published: March 2015

This commentary is on the original article by van Balen et al. on pages 668–676 of this issue.
Cognition in children with neurofibromatosis type 1: data from a population‐based study
Authors: Lehtonen Annukka , Garg Shruti , Roberts Stephen A , Trump Dorothy , Evans D Gareth , Green Jonathan , Huson Susan M
Published: March 2015

Aim

This study aimed to investigate the core cognitive deficits in children with neurofibromatosis type 1 (NF1).

Method

The study recruited 49 children with NF1 (25 males, 24 females; mean age 11y 9mo [SD 3y 2mo]), 19 healthy siblings of children with NF1 (sibling comparisons; mean age 12y 7mo [SD 2y 7mo], 9 males, 10 females) and 29 healthy children from the community (community comparisons; mean age 11y [SD 2y 7mo], 12 males, 17 females). Participants completed a battery of cognitive tests including tests of intelligence, academic achievement, attention, visuoperceptual functioning, visual learning, executive functioning, and non‐verbal working memory tests.

Results

Our study, using a population‐based sample, confirmed previous findings from studies using variable sampling methods. Children with NF1 had significantly lower Full‐scale IQs (p=0.04) and lower academic achievement (p=0.026–0.005) than their siblings. Compared with their siblings, they also had significantly poorer visuospatial processing (p=0.007), visual associate learning (p=0.014), non‐verbal working memory (p=0.023), and executive function (p<0.001). Data from the community comparisons were not included because they were subject to significant selection bias.

Interpretation

Population‐based frequencies for cognitive deficits in children with NF1 are similar to the frequencies in non‐population based samples. This study highlights the heterogeneous nature of cognitive problems in children with NF1 and the need for monitoring and support at school.
A Case Report of Double‐Chambered Right Ventricle Associated with Subaterial Ventricular Septal Defect and Rupture of Right Coronary Sinus Aneurysm
Authors: Hu Guobing , Zhu Xiangming , Li Guojie , Jiang Feng , Li Jing
Published: March 2015

Double‐chambered right ventricle (DCRV) is a rare congenital heart disease in which the right ventricle (RV) is divided into two chambers by anomalous muscle bundles. Here, we report a case of DCRV associated with subarterial ventricular septal defect (VSD) and rupture of right coronary sinus aneurysm (RCSA); the patient was diagnosed by echocardiography and later confirmed by surgical operation.
Accuracy of Echocardiographic Cardiac Index Assessment in Subjects with Preserved Left Ventricular Ejection Fraction
Authors: Maeder Micha T. , Karapanagiotidis Sofie , Dewar Elizabeth M. , Kaye David M.
Published: March 2015

Introduction

We aimed to determine the accuracy of the echocardiographic assessment of cardiac index (CI) in subjects with preserved left ventricular ejection fraction (LVEF).

Methods

Thirty‐three subjects with LVEF >50%, normal sinus rhythm, and a broad spectrum of hemodynamic profiles underwent echocardiography immediately followed by right heart catheterization. As gold standards, CI was assessed using thermodilution [CI (TD)] and the Fick method [CI (F)]. Echocardiographic CI was assessed by four methods: from the left ventricular outflow tract (LVOT) velocity time integral and the LVOT diameter as measured [CI (LVOTm)] as well as estimated from body surface area [CI (LVOTe)], and from stroke volume indices assessed using the biplane [CI (BP)] and monoplane [CI (MP)] methods.

Results

The mean CI (TD), CI (F), CI (LVOTm), CI (LVOTe), CI (BP), and CI (MP) were 3.0 ± 0.9, 3.1 ± 0.7, 2.8 ± 0.6, 3.3 ± 0.6, 2.0 ± 0.6, and 2.2 ± 0.7 L/min/m2. There were modest correlations between CI (TD) and CI (F) and all four noninvasive measures of CI with r2 values ranging from 0.09 to 0.30. CI (LVOTm) underestimated CI (TD) and CI (F) by 0.3 and 0.3 L/min/m2, CI (LVOTe) overestimated CI (TD) and CI (F) by 0.3 and 0.2 L/min/m2, and CI (BP) and CI (MP) underestimated CI (TD) and CI (F) by 1.1 and 1.1 L/min/m2 and 0.9 and 0.9 L/min/m2, respectively, with large limits of agreement for all comparisons.

Conclusions

In subjects with nondilated left ventricles with preserved LVEF, flow‐ or volume‐based measures of CI by 2D echocardiography may not accurately reflect CI (TD) and CI (F). Further larger studies are required to verify our findings and to evaluate the accuracy of contrast and 3D echocardiography in this setting.
Mating status regulates post‐mating refractory period in Striacosta albicosta females
Authors: Konopka Joanna K. , McNeil Jeremy N.
Published: March 2015

In polyandrous insect species, males may transfer substances to reduce sperm competition by affecting female sexual receptivity. In this study, we determined the incidence of polyandry in females of Western bean cutworm (WBC), Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), and investigated the influence of both previous female and male mating history on the duration of mating, the female refractory period, and subsequent calling behavior of females under controlled laboratory conditions. The mating status of WBC males influenced mating duration, with copulations involving previously mated males taking longer, possibly related to the time required to produce an ejaculate. The duration of the female refractory period and the onset time of recalling during the scotophase were both affected by female mating history, but not by that of the males. Females had a shorter refractory period and resumed calling activity earlier after their second and third matings than after their first mating. The earlier onset of calling by previously mated females could reduce competition with virgin females and their shorter refractory period could explain the high incidence of polyandry observed in nature.
Direct effect of ozone pollution on aphids: revisiting the evidence at individual and population scales
Authors: Telesnicki Marta C. , Martínez‐Ghersa M. Alejandra , Arneodo Joel D. , Ghersa Claudio M.
Published: March 2015

Most of our knowledge about the consequences of tropospheric ozone pollution on aphid–plant interaction assumes the absence of a direct effect of ozone on aphids. However, the biological effects of ozone encompass changes in reactive oxygen species signalling, oxidative stress accumulation, and the immune response of both plants and animals. The main objective of this work was to evaluate the direct effect of ozone on Metopolophium dirhodum (Walker) aphids (Hemiptera: Aphididae), linking mechanisms that operate at individual scale (oxidative stress parameters and aphid‐bacteria symbiosis persistence) with their consequences at population scale (mortality, dispersion, and population growth). Two experiments were conducted in open‐top chambers with three contrasting ozone exposure regimes (6 h at 0.5 ± 0.3, 50 ± 5, or 150 ± 10 p.p.b.) and artificial diets to evaluate the direct effect of ozone on aphids. Exposure of aphids to ozone increased insect mortality compared to the control treatment. However, the populations established from the surviving insects of each treatment increased similarly. Consistently, aphid symbiosis with Buchnera aphidicola Munson et al. (Proteobacteria) and Hamiltonella defensa Moran et al. (Enterobacteriaceae) persisted in all treatments. Ozone also affected aphid behaviour. The proportion of insects dispersing from diet cages was lower in the ozone treatments than in the control treatment. In addition, lipid peroxidation was higher at 150 p.p.b. than at 50 p.p.b. treatment, although not different from that in the control. The reduction in aphid dispersion coupled with increased mortality suggests that direct exposure to ozone could lower aphid efficiency as virus vectors. These results could be partially associated with mechanisms operating at individual scale (accumulation of oxidative damage). Overall, these experiments encourage reconsidering the impact of the direct effects of ozone on aphids when assessing the consequences of this component of global change on plant–aphid interactions.
Musical expertise is related to neuroplastic changes of multisensory nature within the auditory cortex
Authors: Pantev Christo , Paraskevopoulos Evangelos , Kuchenbuch Anja , Lu Yao , Herholz Sibylle C.
Published: March 2015

Recent neuroscientific evidence indicates that multisensory integration does not only occur in higher level association areas of the cortex as the hierarchical models of sensory perception assumed, but also in regions traditionally thought of as unisensory, such as the auditory cortex. Nevertheless, it is not known whether expertise‐induced neuroplasticity can alter the multisensory processing that occurs in these low‐level regions. The present study used magnetoencephalography to investigate whether musical training may induce neuroplastic changes of multisensory processing within the human auditory cortex. Magnetoencephalography data of four different experiments were used to demonstrate the effect of long‐term and short‐term musical training on the integration of auditory, somatosensory and visual stimuli in the auditory cortex. The cross‐sectional design of three of the experiments allowed us to infer that long‐term musical training is related to a significantly different way of processing multisensory information within the auditory cortex, whereas the short‐term training design of the fourth experiment allowed us to causally infer that multisensory music reading training affects the multimodal processing within the auditory cortex.
The role of auditory cortices in the retrieval of single‐trial auditory–visual object memories
Authors: Matusz Pawel J. , Thelen Antonia , Amrein Sarah , Geiser Eveline , Anken Jacques , Murray Micah M.
Published: March 2015

Single‐trial encounters with multisensory stimuli affect both memory performance and early‐latency brain responses to visual stimuli. Whether and how auditory cortices support memory processes based on single‐trial multisensory learning is unknown and may differ qualitatively and quantitatively from comparable processes within visual cortices due to purported differences in memory capacities across the senses. We recorded event‐related potentials (ERPs) as healthy adults (n = 18) performed a continuous recognition task in the auditory modality, discriminating initial (new) from repeated (old) sounds of environmental objects. Initial presentations were either unisensory or multisensory; the latter entailed synchronous presentation of a semantically congruent or a meaningless image. Repeated presentations were exclusively auditory, thus differing only according to the context in which the sound was initially encountered. Discrimination abilities (indexed by d’) were increased for repeated sounds that were initially encountered with a semantically congruent image versus sounds initially encountered with either a meaningless or no image. Analyses of ERPs within an electrical neuroimaging framework revealed that early stages of auditory processing of repeated sounds were affected by prior single‐trial multisensory contexts. These effects followed from significantly reduced activity within a distributed network, including the right superior temporal cortex, suggesting an inverse relationship between brain activity and behavioural outcome on this task. The present findings demonstrate how auditory cortices contribute to long‐term effects of multisensory experiences on auditory object discrimination. We propose a new framework for the efficacy of multisensory processes to impact both current multisensory stimulus processing and unisensory discrimination abilities later in time.
Meaning in the avian auditory cortex: neural representation of communication calls
Authors: Elie Julie E. , Theunissen Frédéric E.
Published: March 2015

Understanding how the brain extracts the behavioral meaning carried by specific vocalization types that can be emitted by various vocalizers and in different conditions is a central question in auditory research. This semantic categorization is a fundamental process required for acoustic communication, and presupposes discriminative and invariance properties of the auditory system for conspecific vocalizations. Songbirds have been used extensively to study vocal learning, but the communicative function of all their vocalizations and their neural representation has yet to be examined. In this study, we first generated a library containing almost the entire zebra finch vocal repertoire, and organised communication calls along nine different categories according to their behavioral meaning. We then investigated the neural representations of thesesemanticcategories in the primary and secondary auditory areas of six anesthetised zebra finches. To analyse how single units encode these call categories, we described neural responses in terms of their discrimination, selectivity and invariance properties. Quantitative measures for these neural properties were obtained with an optimal decoder using both spike counts and spike patterns. Information theoretic metrics show that almost half of the single units encode semantic information. Neurons achieve higher discrimination of these semantic categories by being more selective and more invariant. These results demonstrate that computations necessary for semantic categorization of meaningful vocalizations are already present in the auditory cortex, and emphasise the value of a neuro‐ethological approach to understand vocal communication.
Computational modelling suggests that temporal integration results from synaptic adaptation in auditory cortex
Authors: May Patrick J. C. , Westö Johan , Tiitinen Hannu
Published: March 2015

Incoming sounds are represented in the context of preceding events, and this requires a memory mechanism that integrates information over time. Here, it was demonstrated that response adaptation, the suppression of neural responses due to stimulus repetition, might reflect a computational solution that auditory cortex uses for temporal integration. Adaptation is observed in single‐unit measurements as two‐tone forward masking effects and as stimulus‐specific adaptation (SSA). In non‐invasive observations, the amplitude of the auditory N1m response adapts strongly with stimulus repetition, and it is followed by response recovery (the so‐called mismatch response) to rare deviant events. The current computational simulations described the serial core‐belt‐parabelt structure of auditory cortex, and included synaptic adaptation, the short‐term, activity‐dependent depression of excitatory corticocortical connections. It was found that synaptic adaptation is sufficient for columns to respond selectively to tone pairs and complex tone sequences. These responses were defined as combination sensitive, thus reflecting temporal integration, when a strong response to a stimulus sequence was coupled with weaker responses both to the time‐reversed sequence and to the isolated sequence elements. The temporal complexity of the stimulus seemed to be reflected in the proportion of combination‐sensitive columns across the different regions of the model. Our results suggest that while synaptic adaptation produces facilitation and suppression effects, including SSA and the modulation of the N1m response, its functional significance may actually be in its contribution to temporal integration. This integration seems to benefit from the serial structure of auditory cortex.
Perceptual learning in the developing auditory cortex
Authors: Bao Shaowen
Published: March 2015

A hallmark of the developing auditory cortex is the heightened plasticity in the critical period, during which acoustic inputs can indelibly alter cortical function. However, not all sounds in the natural acoustic environment are ethologically relevant. How does the auditory system resolve relevant sounds from the acoustic environment in such an early developmental stage when most associative learning mechanisms are not yet fully functional? What can the auditory system learn from one of the most important classes of sounds, animal vocalizations? How does naturalistic acoustic experience shape cortical sound representation and perception? To answer these questions, we need to consider an unusual strategy, statistical learning, where what the system needs to learn is embedded in the sensory input. Here, I will review recent findings on how certain statistical structures of natural animal vocalizations shape auditory cortical acoustic representations, and how cortical plasticity may underlie learned categorical sound perception. These results will be discussed in the context of human speech perception.
Single‐unit analysis of somatosensory processing in the core auditory cortex of hearing ferrets
Authors: Meredith M. Alex , Allman Brian L.
Published: March 2015

The recent findings in several species that the primary auditory cortex processes non‐auditory information have largely overlooked the possibility of somatosensory effects. Therefore, the present investigation examined the core auditory cortices (anterior auditory field and primary auditory cortex) for tactile responsivity. Multiple single‐unit recordings from anesthetised ferret cortex yielded histologically verified neurons (n = 311) tested with electronically controlled auditory, visual and tactile stimuli, and their combinations. Of the auditory neurons tested, a small proportion (17%) was influenced by visual cues, but a somewhat larger number (23%) was affected by tactile stimulation. Tactile effects rarely occurred alone and spiking responses were observed in bimodal auditory–tactile neurons. However, the broadest tactile effect that was observed, which occurred in all neuron types, was that of suppression of the response to a concurrent auditory cue. The presence of tactile effects in the core auditory cortices was supported by a substantial anatomical projection from the rostral suprasylvian sulcal somatosensory area. Collectively, these results demonstrate that crossmodal effects in the auditory cortex are not exclusively visual and that somatosensation plays a significant role in modulation of acoustic processing, and indicate that crossmodal plasticity following deafness may unmask these existing non‐auditory functions.