Correction: Brain structure in pediatric Tourette syndrome.

In this published article, members of 'The Tourette Association of America Neuroimaging Consortium' were not cited in PubMed. These consortium members are listed in the associated correction.

Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics.

BACKGROUND: A major goal of asthma therapy is to achieve disease control, with maintenance of lung function, reduced need for rescue medication, and prevention of exacerbation. Despite current standard of care, up to 70% of patients with asthma remain poorly controlled. Analysis of serum and sputum biomarkers could offer insights into parameters associated with poor asthma control. OBJECTIVE: To identify signatures as determinants of asthma disease control, we performed proteomics using Olink proximity extension analysis. METHODS: Up to 3 longitudinal serum samples were collected from 23 controlled and 25 poorly controlled asthmatics. Nine of the controlled and 8 of the poorly controlled subjects also provided 2 longitudinal sputum samples. The study included an additional cohort of 9 subjects whose serum was collected within 48 hours of asthma exacerbation. Two separate pre-defined Proseek Multiplex panels (INF and CVDIII) were run to quantify 181 separate protein analytes in serum and sputum. RESULTS: Panels consisting of 9 markers in serum (CCL19, CCL25, CDCP1, CCL11, FGF21, FGF23, Flt3L, IL-10Rß, IL-6) and 16 markers in sputum (tPA, KLK6, RETN, ADA, MMP9, Chit1, GRN, PGLYRP1, MPO, HGF, PRTN3, DNER, PI3, Chi3L1, AZU1, and OPG) distinguished controlled and poorly controlled asthmatics. The sputum analytes were consistent with a pattern of neutrophil activation associated with poor asthma control. The serum analyte profile of the exacerbation cohort resembled that of the controlled group rather than that of the poorly controlled asthmatics, possibly reflecting a therapeutic response to systemic corticosteroids. CONCLUSIONS AND CLINICAL RELEVANCE: Proteomic profiles in serum and sputum distinguished controlled and poorly controlled asthmatics, and were maintained over time. Findings support a link between sputum neutrophil markers and loss of asthma control.

Brain structure in pediatric Tourette syndrome.

Previous studies of brain structure in Tourette syndrome (TS) have produced mixed results, and most had modest sample sizes. In the present multicenter study, we used structural magnetic resonance imaging (MRI) to compare 103 children and adolescents with TS to a well-matched group of 103 children without tics. We applied voxel-based morphometry methods to test gray matter (GM) and white matter (WM) volume differences between diagnostic groups, accounting for MRI scanner and sequence, age, sex and total GM+WM volume. The TS group demonstrated lower WM volume bilaterally in orbital and medial prefrontal cortex, and greater GM volume in posterior thalamus, hypothalamus and midbrain. These results demonstrate evidence for abnormal brain structure in children and youth with TS, consistent with and extending previous findings, and they point to new target regions and avenues of study in TS. For example, as orbital cortex is reciprocally connected with hypothalamus, structural abnormalities in these regions may relate to abnormal decision making, reinforcement learning or somatic processing in TS.

Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

Bias in beliefs about the self is associated with depressive but not anxious mood.

BACKGROUND: Biases in beliefs about the self are associated with psychopathology and depressive and anxious mood, but it is not clear if both negative and positive beliefs are associated with depression or anxiety. We examined these relationships in people who present with a wide range of depressive and anxious mood across diagnostic categories. METHODS: We probed positive and negative beliefs about the self with a task in which 74 female participants with either affective disorder (depression and/or anxiety), borderline personality disorder or no psychiatric history indicated the degree to which 60 self-related words was "like them" or "not like them". Depressive and anxious mood were assessed with the Beck Depression Inventory-II and the Beck Anxiety Inventory. RESULTS: The participants with no psychiatric history (n=25) reported a positive bias in their beliefs about the self, the participants with affective disorder (n=23) reported no bias, and the participants with BPD (n=26) reported a negative bias. Two hierarchical multiple regressions demonstrated that the positive and negative beliefs contributed additively to the ratings of depression (corrected for anxiety), but did not contribute to the ratings of anxiety (corrected for depression). LIMITATIONS: Despite the apparent small sample size, the regression analyses indicated adequate sampling. Anxiety is a much more heterogeneous condition than is depression, so it may be difficult to find relevant self-descriptors. Only measures of endorsement were used. CONCLUSIONS: Biases in beliefs about the self are associated with depressed, but not anxious mood, across diagnostic categories.

Prevalence and predictors of early gestational weight gain associated with obesity risk in a diverse Australian antenatal population: a cross-sectional study.

BACKGROUND: Excess gestational weight gain (GWG) leads to adverse short- and long-term consequences for women and their offspring. Evidence suggests that excess GWG in early pregnancy may be particularly detrimental, contributing to the intergenerational cycle of obesity. The primary outcome was to investigate the prevalence and predictors of excess GWG in early pregnancy, and if women understand the risks to themselves and their offspring stratified by maternal body mass index (BMI). METHODS: This was a secondary analysis (n = 2131) of a cross-sectional study (n = 2338) conducted over 6 months in 2015 of pregnant women attending antenatal clinics at four maternity hospitals across Sydney, Australia before 22 completed weeks gestation An self-completed questionnaire was used to investigate knowledge of expected weight gain in pregnancy, understanding of risks associated with excess GWG, self-reported anthropometric measures and socio-demographic data. RESULTS: One third (34.2%) of women gained weight in excess of the recommendations by 22 completed weeks gestation. Women who were overweight (OR: 1.69, 95% CI: 1.33-2.14) or obese (OR: 1.64, 95% CI: 1.20-2.24) pre-pregnancy were more likely to gain excess weight in early pregnancy compared to normal weight women; as were women from lower socio-economic areas (OR: 1.89, 95% CI: 1.49-2.41). Half (51%) the women were unsure about the effect of excess GWG on their baby; 11% did not believe that excess GWG would affect the weight of the baby and 14% did not believe that excess GWG would affect longer term outcomes for their baby. Women who gained weight above the recommendations were significantly more likely to believe that excessive GWG in pregnancy would not have any adverse future effect on health outcomes or weight of their baby. CONCLUSIONS: The women at particular risk of excess early GWG are those who are overweight and obese and/or residing in lower socio-economic areas. These women need to be targeted for appropriate counselling preconception or in early pregnancy. Given the significant adverse outcomes associated with excess GWG in early pregnancy, preconception or early pregnancy counselling with respect to GWG and intervention research regarding best approach remains a public health priority.

The international phase 4 validation study of the EORTC QLQ-SWB32: A stand-alone measure of spiritual well-being for people receiving palliative care for cancer.

The EORTC Quality of Life Group has just completed the final phase (field-testing and validation) of an international project to develop a stand-alone measure of spiritual well-being (SWB) for palliative cancer patients. Participants (n = 451)-from 14 countries on four continents; 54% female; 188 Christian; 50 Muslim; 156 with no religion-completed a provisional 36-item measure of SWB plus the EORTC QLQ-C15-PAL (PAL), then took part in a structured debriefing interview. All items showed good score distribution across response categories. We assessed scale structure using principal component analysis and Rasch analysis, and explored construct validity, and convergent/divergent validity with the PAL. Twenty-two items in four scoring scales (Relationship with Self, Relationships with Others, Relationship with Someone or Something Greater, and Existential) explained 53% of the variance. The measure also includes a global SWB item and nine other items. Scores on the PAL global quality-of-life item and Emotional Functioning scale weakly-moderately correlated with scores on the global SWB item and two of the four SWB scales. This new validated 32-item SWB measure addresses a distinct aspect of quality-of-life, and is now available for use in research and clinical practice, with a role as both a measurement and an intervention tool.

Trends in the use of emergency contraception in Britain: evidence from the second and third National Surveys of Sexual Attitudes and Lifestyles.

OBJECTIVE: To examine the changes in the prevalence of, and the factors associated with, the use of emergency contraception (EC) in Britain between 2000 and 2010, spanning the period of deregulation and increase in pharmacy supply. DESIGN: Cross-sectional probability sample surveys. SETTING AND POPULATION: British general population. METHODS: Data were analysed from the second and third British National Surveys of Sexual Attitudes and Lifestyles (Natsal), undertaken in 1999-2001 and 2010-12. Univariate and logistic regression analyses were used to measure change in EC use amongst sexually active women aged 16-44 years not intending pregnancy. MAIN OUTCOME MEASURES: Prevalence of EC use and factors associated with use. RESULTS: Of the 5430 women surveyed in 1999-2001 and the 4825 women surveyed in 2010-12, 2.3 and 3.6%, respectively, reported using EC in the year prior to interview (P = 0.0019 for change over time). The prevalence of EC use increased amongst single women and those with higher educational attainment (adjusted odds ratio, aOR 1.51; 95% confidence interval, 95% CI 1.04-2.20; P = 0.0308). Increases in EC use were generally greater among women without behavioural risk factors, such as those with no history of abortion within 5 years (aOR 1.57; 95% CI 1.17-2.12; P = 0.0029), or those whose first heterosexual intercourse occurred after the age of 16 years (aOR 1.68; 95% CI 1.21-2.35; P = 0.0021). The increase in EC use was also more marked among women usually accessing contraception from retail sources than among those doing so from healthcare sources, which may reflect a use of condoms amongst EC users. CONCLUSION: The increase in EC use among women in Britain in the first decade of the 21st century was associated with some, but not all, risk factors for unplanned pregnancy. Advice and provision may need to be targeted at those at highest risk of unplanned pregnancy. TWEETABLE ABSTRACT: Despite pharmacy access, only a small rise in emergency contraception use has been seen in Britain over 10 years.

[Postoperative long-term results in high-grade traumatic ruptures of the spleen in children]. / Postoperative Ergebnisse höhergradiger traumatischer Milzrupturen bei Kindern im Langzeitverlauf.

BACKGROUND: Splenic rupture is the most common injury in blunt abdominal trauma at any age. The grade of rupture, haemodynamic stability and, in the case of operative treatment, the experience of the surgeon all play an important role in preserving the spleen. Due to its important immunological function preservation of the spleen should be the goal. PATIENTS: From January 2000 to August 2009 five children (4 male/1 female) with isolated grade IV or V splenic rupture, according to the Organ Injury Score (OIS), were treated operatively. At the time of the trauma the patients were 8.8 ± 3.8 (mean ± standard deviation; range, 6­15) years old. Four patients with an OIS grade IV rupture were primarily treated with partially spleen-saving surgery: one resection of 2/3 of the spleen including the splenic vessels, one hemisplenectomy and two lower pole resections; in one patient with an OIS grade V rupture splenectomy was performed immediately. RESULTS: In one patient treated with a spleen-preserving approach (hemisplenectomy) the remainder of the spleen had to be removed due to acute bleeding on the first postoperative day. This patient needed two units of blood transfused following the second operation. There were no other complications. The two patients with splenectomy and resection of ⅔ of the spleen developed a transient thrombocytosis indicating impaired clearance of the spleen. In a follow-up involving ultrasonography (median 13, range 1-101 months) all patients managed with partially spleen-saving surgery showed a large remnant spleen with arterial perfusion. CONCLUSION: The majority of primarily partially spleen-preserving operations result from OIS grade IV ruptures of the spleen. Use of a partially spleen-saving surgical approach was successful in ¾ of these patients. Low morbidity and documented perfusion of the remnant spleen at long-term follow-up indicate that a spleen-preserving technique is warranted if an operative approach is required.

Incidence and outcomes of pregnancy-associated cancer in Australia, 1994-2008: a population-based linkage study.

OBJECTIVE: To determine trends in pregnancy-associated cancer and associations between maternal cancer and pregnancy outcomes. DESIGN: Population-based cohort study. SETTING: New South Wales, Australia, 1994-2008. POPULATION: A total of 781 907 women and their 1 309 501 maternities. METHODS: Cancer and maternal information were obtained from linked cancer registry, birth and hospital records for the entire population. Generalised estimating equations with a logit link were used to examine associations between cancer risk factors and pregnancy outcomes. MAIN OUTCOME MEASURES: Incidence of pregnancy-associated cancer (diagnosis during pregnancy or within 12 months of delivery), maternal morbidities, preterm birth, and small- and large-for-gestational-age (LGA). RESULTS: A total of 1798 new cancer diagnoses were identified, including 499 during pregnancy and 1299 postpartum. From 1994 to 2007, the crude incidence rate of pregnancy-associated cancer increased from 112.3 to 191.5 per 100 000 maternities (P < 0.001), and only 14% of the increase was explained by increasing maternal age. Cancer diagnosis was more common than expected in women aged 15-44 years (observed-to-expected ratio 1.49; 95% CI 1.42-1.56). Cancers were predominantly melanoma (33.3%) and breast cancer (21.0%). Women with cancer diagnosed during pregnancy had high rates of labour induction (28.5%), caesarean section (40.0%) and planned preterm birth (19.7%). Novel findings included a cancer association with multiple pregnancies (adjusted odds ratio 1.52, 95% CI 1.13-2.05) and LGA (aOR 1.47, 95% CI 1.14-1.89). CONCLUSIONS: Pregnancy-associated cancers have increased, and this increase is only partially explained by increasing maternal age. Pregnancy increases women's interaction with health services and the possibility for diagnosis, but may also influence tumour growth.

Use of a robotic sampling platform to assess young children's exposure to indoor bioaerosols.

UNLABELLED: Indoor exposures to allergens, mold spores, and endotoxin have been suggested as etiological agents of asthma; therefore, accurate determination of those exposures, especially in young children (6-36 months), is important for understanding the development of asthma. Because use of personal sampling equipment in this population is difficult, and in children <1 year of age impossible, we developed a personal sampling surrogate: the Pretoddler Inhalable Particulate Environmental Robotic (PIPER) sampler to better estimate their exposures. During sampling, PIPER simulates the activity patterns, speed of motion, and the height of the breathing zones of young children, and mechanically resuspends the deposited dust just as a young child does during running and crawling. The concentrations of allergens, mold spores, and endotoxin measured by PIPER were compared to those measured using traditional stationary air sampling method in 75 homes in central New Jersey, United States. Endotoxin was detected in all homes with median concentrations of 1.0 and 0.55 EU/m(3) for PIPER and stationary sampler, respectively. The difference in median concentrations obtained using the two methods was statistically significant for homes with carpeted floors (P = 0.0001) in the heating season. For such homes, the average ratio of endotoxin concentration measured by PIPER to the stationary sampler was 2.96 (95% CI 2.29-3.63). Fungal spores were detected in all homes, with median fungal concentrations of 316 and 380 spores/m(3) for PIPER and stationary sampler, respectively. For fungi, the difference between the two sampling methods was not statistically significant. For both sampling methods, the total airborne mold levels were statistically significantly higher in the non-heating season than in the heating season. Allergens were detected in ~15% of investigated homes. The data indicate that the traditional stationary air-sampling methods may substantially underestimate personal exposures to endotoxin, especially due to resuspension of dust from carpeted floor surfaces. A personal sampling surrogate, such as PIPER, is a feasible approach to estimate personal exposures in young children. PIPER should be seriously considered as the sampling platform for future exposure studies in young children. PRACTICAL IMPLICATIONS: This study investigated potential indoor bioaerosol exposure of young children using a Pretoddler Inhalable Particulate Environmental Robotic (PIPER) sampler platform. The results show that the traditional stationary air-sampling methods can substantially underestimate personal exposures to resuspended material, and that a personal sampling surrogate, such as PIPER, offers a feasible surrogate for measuring personal inhalation exposures of young children.

Australian primary health care nurses’ knowledge, practice and attitudes relating to preconception care: learnings for service implementation.

Preconception care (PCC) entails counselling and interventions to optimise health before pregnancy. Barriers to this service delivery include access and time. Primary healthcare nurses (PHCNs) are uniquely placed to deliver PCC. The aim of this study was to understand PHCNs' knowledge, practice and attitudes to PCC. A cross-sectional study was performed of a convenience sample of PHCNs in Australia who were seeing people of reproductive age. Recruitment was via the Australian Primary Health Care Nurses Association (APNA) electronic communication platforms. The 18-item, online, anonymous survey captured demographics, as well as PCC knowledge, practices and attitudes. Descriptive statistics were used to describe our findings. In all, 152 completed surveys were received. Of all respondents, 74% stated they discuss PCC in their practice, although only 13% do so routinely. Of these, more preconception discussions are held with women than with men. In total, 95% of respondents identified at least one barrier to delivery of PCC, with lack of time and knowledge being the most common. The findings of this study can inform targeted strategies, including education programs and resources, and consideration of incentives to support PHCNs deliver PCC. This study identifies areas for improvement at the individual, organisational and health system levels to enhance the role of PHCNs in PCC.

Efficacy of a therapeutic cocaine vaccine in rodent models.

Cocaine abuse is a major medical and public health concern in the United States, with approximately 2.1 million people dependent on cocaine. Pharmacological approaches to the treatment of cocaine addiction have thus far been disappointing, and new therapies are urgently needed. This paper describes an immunological approach to cocaine addiction. Antibody therapy for neutralization of abused drugs has been described previously, including a recent paper demonstrating the induction of anti-cocaine antibodies. However, both the rapidity of entry of cocaine into the brain and the high doses of cocaine frequently encountered have created challenges for an antibody-based therapy. Here we demonstrate that antibodies are efficacious in an animal model of addiction. Intravenous cocaine self-administration in rats was inhibited by passive transfer of an anti-cocaine monoclonal antibody. To actively induce anti-cocaine antibodies, a cocaine vaccine was developed that generated a high-titer, long-lasting antibody response in mice. Immunized mice displayed a significant change in cocaine pharmacokinetics, with decreased levels of cocaine measured in the brain of immunized mice only 30 seconds after intravenous (i.v.) administration of cocaine. These data establish the feasibility of a therapeutic cocaine vaccine for the treatment of cocaine addiction.

Clinical vignettes in Parkinson's disease: a collection of unusual medication-induced hallucinations, delusions, and compulsive behaviours.

Hallucinations, delusions, and compulsive behaviors are frequent iatrogenic complications of the treatment of motor dysfunction in Parkinson's disease (PD). Although these have been studied, and the phenomenology described, there are few detailed descriptions of the various psychiatric problems our treated PD patients live with that allow physicians who do not have a great deal of experience with PD patients to appreciate the extent of their altered lives. This report is a compilation of vignettes describing these behavioral problems that the treating neurologist or psychiatrist attributed to the medications used for treating PD.

Doctor of Physical Therapy Student Perceptions of Domestic Versus International Service-Learning Experiences: A Mixed-Methods Approach.

PURPOSE: The purpose of this study was to compare Doctor of Physical Therapy (DPT) students' perceptions of service-learning between domestic and international service-learning experiences (SLEs). METHODS: DPT students participated in semi-structured interviews (n=35) and completed the Service-Learning Benefit (SELEB) scale (n=21). Focus group questions targeted the impact of the SLE on topics related to PT services, social responsibility, cultural competence, and personal commitment to engaging in future service-related activities. The interviews were audio-recorded and transcribed. Incident coding processes analyzed transcripts of the focus groups. Differences in the students' perceptions of the benefit of SLEs using the SELEB were examined using Wilcoxon signed-rank test. RESULTS: Perceived advantages of an international SLE included improved relationship building, social responsibility, citizenship skills, cultural competence, gaining trust of others, and expansion of worldview. Perceived different benefits of the domestic SLE were planning and organizing the experience and improved commitment to the community. Additionally, students who participated in the international SLE cited more barriers (e.g., cost) than in the domestic SLEs. CONCLUSION: DPT students participating in domestic vs international SLEs appear to have different perceptions of SLE. Further research is needed to examine the perspective of other stakeholders involved in domestic and international SLEs.

Assessment of ability of murine and human anti-lipid A monoclonal antibodies to bind and neutralize lipopolysaccharide.

The use of monoclonal antibodies (mAbs) directed to lipid A for the therapy of gram-negative sepsis is controversial. In an attempt to understand their biologic basis of action, we used a fluid-phase radioimmunoassay to measure binding between bacterial lipopolysaccharide (LPS) and two IgM mAbs directed to lipid A that are being evaluated for the treatment of gram-negative bacterial sepsis. Both antibodies bound 3H-LPS prepared from multiple strains of gram-negative bacteria when large excesses of antibody were used, although binding was modest and only slightly greater than control preparations. We also studied the ability of each anti-lipid A antibody to neutralize some of the biological effects of LPS in vitro. Despite large molar excesses, neither antibody neutralized LPS as assessed by the limulus lysate test, by a mitogenic assay for murine splenocytes, or by the production of cytokines interleukin (IL)-1, IL-6, or tumor necrosis factor from human monocytes in culture medium or in whole blood. Our experiments do not support the hypothesis that either of these anti-lipid A mAbs function by neutralizing the toxic effects of LPS.

Host control over infection and proliferation of a cheater symbiont.

Host control mechanisms are thought to be critical for selecting against cheater mutants in symbiont populations. Here, we provide the first experimental test of a legume host's ability to constrain the infection and proliferation of a native-occurring rhizobial cheater. Lotus strigosus hosts were experimentally inoculated with pairs of Bradyrhizobium strains that naturally vary in symbiotic benefit, including a cheater strain that proliferates in the roots of singly infected hosts, yet provides zero growth benefits. Within co-infected hosts, the cheater exhibited lower infection rates than competing beneficial strains and grew to smaller population sizes within those nodules. In vitro assays revealed that infection-rate differences among competing strains were not caused by variation in rhizobial growth rate or interstrain toxicity. These results can explain how a rapidly growing cheater symbiont--that exhibits a massive fitness advantage in single infections--can be prevented from sweeping through a beneficial population of symbionts.

The optical properties of vertically aligned ZnO nanowires deposited using a dimethylzinc adduct.

The optical properties of zinc oxide nanowires are critically influenced by the growth process. Herein, we describe a metal-organic chemical vapour deposition (MOCVD) process for the growth of ZnO nanowires with improved optical properties. A tetrahydrofuran adduct is used to control the reactivity of dimethylzinc to enable this. Vertically aligned zinc oxide nanowires have been grown on Si(111) substrates by liquid injection MOCVD, using a solution of [Me(2)Zn(tetrahydrofuran)] in the presence of oxygen. The ZnO morphology becomes nanowire-like in a narrow temperature range centred about 500 degrees C. Above and below this temperature range, the ZnO is deposited in the form of polycrystalline films. The ZnO nanowires grow from a polycrystalline nucleation layer, with the (0002) c-axis parallel to the Si[111] substrate orientation. High-resolution electron microscopy reveals a highly crystalline nanowire microstructure. Resonance enhanced ultraviolet Raman spectroscopy shows that the ratio of first- and second-order longitudinal optic modes is commensurate with electron-phonon coupling effects observed previously in ZnO nanostructures. Photoluminescence exhibits intense near band-edge emission with a full width at half-maximum of 110 meV at room temperature and shows negligible defect-related visible emission.

Isolation of tumour stem-like cells from benign tumours.

BACKGROUND: Cancerous stem-like cells (CSCs) have been implicated as cancer-initiating cells in a range of malignant tumours. Diverse genetic programs regulate CSC behaviours, and CSCs from glioblastoma patients are qualitatively distinct from each other. The intrinsic connection between the presence of CSCs and malignancy is unclear. We set out to test whether tumour stem-like cells can be identified from benign tumours. METHODS: Tumour sphere cultures were derived from hormone-positive and -negative pituitary adenomas. Characterisation of tumour stem-like cells in vitro was performed using self-renewal assays, stem cell-associated marker expression analysis, differentiation, and stimulated hormone production assays. The tumour-initiating capability of these tumour stem-like cells was tested in serial brain tumour transplantation experiments using SCID mice. RESULTS: In this study, we isolated sphere-forming, self-renewable, and multipotent stem-like cells from pituitary adenomas, which are benign tumours. We found that pituitary adenoma stem-like cells (PASCs), compared with their differentiated daughter cells, expressed increased levels of stem cell-associated gene products, antiapoptotic proteins, and pituitary progenitor cell markers. Similar to CSCs isolated from glioblastomas, PASCs are more resistant to chemotherapeutics than their differentiated daughter cells. Furthermore, differentiated PASCs responded to stimulation with hypothalamic hormones and produced corresponding pituitary hormones that are reflective of the phenotypes of the primary pituitary tumours. Finally, we demonstrated that PASCs are pituitary tumour-initiating cells in serial transplantation animal experiments. CONCLUSION: This study for the first time indicates that stem-like cells are present in benign tumours. The conclusions from this study may have applications to understanding pituitary tumour biology and therapies, as well as implications for the notion of tumour-initiating cells in general.