Effectiveness of Group Cognitive Behavioral Therapy and Exercise in the Management of Major Depressive Disorder: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Despite evidence in scientific literature indicating the effectiveness of both cognitive behavioral therapy (CBT) and physical exercise in the management of major depressive disorder (MDD), few studies have directly compared them. OBJECTIVE: This study aims to evaluate and compare the effectiveness of group CBT, physical exercise, and only wait-listing to receive treatment-as-usual (TAU) in the management of MDD. The investigators hypothesize that participants with MDD assigned to the group CBT or exercise arms of the study will achieve superior outcomes compared with participants wait-listed to receive TAU only. METHODS: This prospective rater-blinded randomized controlled trial assesses the benefits of group CBT and exercise for participants with MDD. A total of 120 patients with MDD referred to addiction and mental health clinics in Edmonton, Canada, will be randomly assigned to one of the three equal-sized arms of the study to receive either weekly sessions of group CBT plus TAU, group exercise three times a week plus TAU, or only TAU for 14 weeks. Participants will be assessed at enrollment, 3 and 6 months post enrollment, midtreatment, and upon treatment completion for primary (functional and symptom variables) and secondary outcomes (service variables and health care utilization). In addition, participants in the intervention groups would be evaluated weekly with one functional measure. The data will be analyzed using repeated measures and effect size analyses, and correlational analyses will be completed between measures at each time point. RESULTS: The study will be conducted in accordance with the Declaration of Helsinki (Hong Kong amendment) and Good Clinical Practice (Canadian guidelines). Written informed consent will be obtained from each subject. The study received ethical clearance from the Health Ethics Research Board of the University of Alberta on September 7, 2018 (Pro 00080975) and operational approval from the provincial health authority (Alberta Health Services 43638). As of October 13, 2019, we have enrolled 32 participants. The results will be disseminated at several levels, including patients, practitioners, academics, researchers, and health care organizations. CONCLUSIONS: The results of the pilot trial may inform the implementation of a multicenter clinical trial and provide useful information for administrators and clinicians who are interested in incorporating group CBT and group exercise interventions into existing care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03731728; https://clinicaltrials.gov/ct2/show/NCT03731728. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/14309.

Exosomal Release of L-Plastin by Breast Cancer Cells Facilitates Metastatic Bone Osteolysis.

Bone metastasis from breast and prostate carcinomas is facilitated by activation of bone-resorbing osteoclasts. Using proteomics approaches, we have identified peroxiredoxin-4 (PRDX4) as a cancer-secreted mediator of osteoclastogenesis. We now report characterization of L-plastin in the conditioned media (CM) of MDA-MB-231 human breast cancer cells using immunoblotting and mass spectrometry. The osteoclastogenic potential of MDA-MB-231 CM with siRNA-silenced L-plastin was significantly reduced. L-plastin was detected in cancer-derived exosomes, and inhibition of exosomal release significantly decreased the osteoclastogenic capacity of MDA-MB-231 CM. When added to osteoclast precursors primed with RANKL for 2 days, recombinant L-plastin induced calcium/NFATc1-mediated osteoclastogenesis to the levels similar to continuous treatment with RANKL. Using shRNA, we generated MDA-MB-231 cells lacking L-plastin, PRDX4, or both and injected these cell populations intratibially in CD-1 immunodeficient mice. Micro-CT and histomorphometric analysis demonstrated a complete loss of osteolysis when MDA-MB-231 cells lacking both L-plastin and PRDX4 were injected. A meta-analysis established an increase in L-plastin and PRDX4 mRNA expression in numerous human cancers, including breast and prostate carcinomas. This study demonstrates that secreted L-plastin and PRDX4 mediate osteoclast activation by human breast cancer cells.

Randomized controlled pilot trial of supportive text messaging for alcohol use disorder patients.

AIMS: To evaluate the effectiveness of an addiction-related supportive text messaging mobile intervention to improve treatment outcomes for patients with alcohol use disorder (AUD). METHODS: A single-rater-blinded randomized trial was conducted involving 59 AUD patients who completed a residential addiction treatment program. Patients in the intervention group (n = 29) received supportive text messages for three months following discharge. Patients in the control group (n = 30) received a text message thanking them for participating in the study. The primary outcome of this study was the three months Cumulative Abstinence Duration (CAD); secondary outcomes (units of alcohol per drinking day, numbers of days to first drink) and exploratory outcomes (health utilization) were evaluated. Subgroup analyses were also done. The enrollment rate in the study was 84%, and of those who enrolled, 73% were retained. RESULTS: When primary and secondary outcome measures were examined via effect size analysis, the number of days to first drink was longer in the intervention than control group (large effect size, although not statistically significant). The intervention group's mean first day to drink was over twice the length of the control group (e.g., approximately 60 vs. 26 days, respectively, with a mean difference of 34.97 and 95% CI of -5.87-75.81). Small to moderate effects were found for CAD and units of alcohol per drinking day. Small to negligible effects were found for health utilization. On subgroup analyses, the participants who received text messages, among those who did not attend follow-up outpatient counselling, showed a longer CAD. CONCLUSIONS: The results suggest text messaging is a feasible and effective opportunity for follow-up care in patients discharged from residential AUD treatment.

Prevalence Rates and Predictors of Generalized Anxiety Disorder Symptoms in Residents of Fort McMurray Six Months After a Wildfire.

The Fort McMurray wildfire was the costliest disaster in Canadian history, with far-reaching impacts. The purpose of this paper is to examine the prevalence and risk factors of elevated generalized anxiety disorder (GAD) symptomatology in residents of Fort McMurray 6 months after the wildfire. Data were collected via random selection procedures from 486 participants. Generalized anxiety disorder symptoms were measured via the GAD-7. The 1-month prevalence rate for GAD symptomatology 6 months after the disaster was 19.8% overall, regression analyses revealed six variables with significant unique contributions to prediction of GAD symptomatology. Significant predictors were: pre-existing anxiety disorder, witnessing of homes being destroyed by the wildfire, living in a different home after the wildfire, receiving limited governmental support or limited family support, and receiving counseling after the wildfire. Participants with these risk factors were between two to nearly seven times more likely to present with GAD symptomatology. In addition, participants who presented with elevated symptomatology were more likely to increase use or problematically use substances post-disaster. This study extends the literature on mental health conditions and risk factors following disasters, specifically in the area of generalized anxiety. Findings and implications are discussed.

Impact of oil recession on community mental health service utilization in an oil sands mining region in Canada.

OBJECTIVES: This retrospective clinical audit compared changes in community mental health service utilization before and during an economic recession in an oil sands region in Canada which was characterized by a doubling of unemployment rates and poor economic outlook. METHODS: Sociodemographic descriptors, psychiatric antecedents, clinical characteristics and follow-up care were compared before and during the recession for newly assessed patients in community mental health clinics located across a Northern Alberta oil mining region. Data were collected retrospectively as part of a clinical audit process and then analysed with descriptive statistics, cross-tabular univariate analyses with chi-square tests using SPSS version 20. RESULTS: A total of 1,465 patients were included. Sociodemographic factors disproportionately elevated during the recession included male sex, Caucasian ethnicity, own home ownership, higher levels of education and unemployment. More patients seeking mental health care were already taking psychotropic medications (e.g. antipsychotics, benzodiazepines and stimulants). At the same time, disproportionately fewer patients engaged in substance abuse or had a prior formal history of mental health problems. The referral reasons during recession were less likely to be associated with substance abuse or mood concerns and more likely for 'other' reasons. The patients seeking psychiatric help during a recession were disproportionately likely to be diagnosed with personality disorders and 'other' less common diagnostic categories and less likely to suffer from mood or trauma-related diagnoses. Referrals for counselling and social services were also disproportionately more common during the recession. CONCLUSION: This study provides a comprehensive description of longitudinal patterns of mental health service utilization before and during a recession. The findings provide important evidence for policy and planning decisions to encourage resource allocation to help promote accessibility of the most needed community mental health resources.

Convergence and divergence of neurocognitive patterns in schizophrenia and depression.

BACKGROUND: Neurocognitive impairments are frequently observed in schizophrenia and major depressive disorder (MDD). However, it remains unclear whether reported neurocognitive abnormalities could objectively identify an individual as having schizophrenia or MDD. METHODS: The current study included 220 first-episode patients with schizophrenia, 110 patients with MDD and 240 demographically matched healthy controls (HC). All participants performed the short version of the Wechsler Adult Intelligence Scale-Revised in China; the immediate and delayed logical memory of the Wechsler Memory Scale-Revised in China; and seven tests from the computerized Cambridge Neurocognitive Test Automated Battery to evaluate neurocognitive performance. The three-class AdaBoost tree-based ensemble algorithm was employed to identify neurocognitive endophenotypes that may distinguish between subjects in the categories of schizophrenia, depression and HC. Hierarchical cluster analysis was applied to further explore the neurocognitive patterns in each group. RESULTS: The AdaBoost algorithm identified individual's diagnostic class with an average accuracy of 77.73% (80.81% for schizophrenia, 53.49% for depression and 86.21% for HC). The average area under ROC curve was 0.92 (0.96 in schizophrenia, 0.86 in depression and 0.92 in HC). Hierarchical cluster analysis revealed for MDD and schizophrenia, convergent altered neurocognition patterns related to shifting, sustained attention, planning, working memory and visual memory. Divergent neurocognition patterns for MDD and schizophrenia related to motor speed, general intelligence, perceptual sensitivity and reversal learning were identified. CONCLUSIONS: Neurocognitive abnormalities could predict whether the individual has schizophrenia, depression or neither with relatively high accuracy. Additionally, the neurocognitive features showed promise as endophenotypes for discriminating between schizophrenia and depression.

Randomized controlled pilot trial of supportive text messages for patients with depression.

BACKGROUND: Depression is projected to be the primary cause of disability worldwide by 2030. In a recent survey, the most commonly cited unmet need among 42.4% of depressed Albertans was the lack of sufficient, accessible, and affordable counselling. Our aim was to test the efficacy of a supportive text messaging mobile health intervention in improving treatment outcomes in depressed patients. METHODS: We performed a single-rater-blinded randomized trial involving 73 patients with Major Depressive Disorder. Patients in the intervention group (n = 35) received twice-daily supportive text messages for 3 months while those in the control group (n = 38) received a single text message every fortnight thanking them for participating in the study. The primary outcome of this study was: "Mean changes in the BDI scores from baseline". RESULTS: After adjusting for baseline BDI scores, a significant difference remained in the 3 month mean BDI scores between the intervention and control groups: (20.8 (SD = 11.7) vs. 24.9 (SD = 11.5), F (1, 60) = 4.83, p = 0.03, ηp2 = 0.07). The mean difference in the BDI scores change was significant with an effect size (Cohen's d) of 0.67. Furthermore, after adjusting for baseline scores, a significant difference remained in the 3 month mean self-rated VAS scores (EQ-5D-5 L scale) between the intervention and control groups, 65.7 (SD = 15.3) vs. 57.4 (SD = 22.9), F (1, 60) =4.16, p = 0.05, ηp2 = 0.065. The mean difference in change mean self-rated VAS scores was also statistically significant with an effect size (Cohen's d) of 0.51. CONCLUSIONS: Our findings suggest that supportive text messages are a potentially useful psychological intervention for depression, especially in underserved populations. Further studies are needed to explore the implications of our findings in larger clinical samples. TRIAL REGISTRATION: ClinicalTrials.gov NCT02327858 . Registered 24 December 2014.

Prevalence Rate and Demographic and Clinical Correlates of Child Sexual Abuse Among New Psychiatric Outpatients in a City in Northern Alberta.

The prevalence rate for child sexual abuse among new psychiatric outpatients in Fort McMurray was 20.7%. With an odds ratio for sex of 3.30, female patients are about 3 times more likely to report a history of child sexual abuse compared with male patients when controlling for other factors. Similarly, patients with at most high school education and those with previous contact with psychiatric services were about 2 times more likely to report a history of child sexual abuse compared to the patients with college or university education or no previous contact with psychiatric services, respectively. Similarly, patients with histories of substance abuse and patients with family histories of mental illness had higher likelihoods of reporting histories of child sexual abuse compared to patients without histories of substance abuse or family histories of mental illness, respectively. Our findings suggest that victims of child sexual abuse are an at-risk population in need of ongoing mental health and educational support.

Deep grey matter iron accumulation in alcohol use disorder.

PURPOSE: Evaluate brain iron accumulation in alcohol use disorder (AUD) patients compared to controls using quantitative susceptibility mapping (QSM). METHODS: QSM was performed retrospectively by using phase images from resting state functional magnetic resonance imaging (fMRI). 20 male AUD patients and 15 matched healthy controls were examined. Susceptibility values were manually traced in deep grey matter regions including caudate nucleus, combined putamen and globus pallidus, combined substantia nigra and red nucleus, dentate nucleus, and a reference white matter region in the internal capsule. Average susceptibility values from each region were compared between the patients and controls. The relationship between age and susceptibility was also explored. RESULTS: The AUD group exhibited increased susceptibility in caudate nucleus (+8.5%, p=0.034), combined putamen and globus pallidus (+10.8%, p=0.006), and dentate nucleus (+14.9%, p=0.022). Susceptibility increased with age in two of the four measured regions - combined putamen and globus pallidus (p=0.013) and combined substantia nigra and red nucleus (p=0.041). AUD did not significantly modulate the rate of susceptibility increase with age in our data. CONCLUSION: Retrospective QSM computed from standard fMRI datasets provides new opportunities for brain iron studies in psychiatry. Substantially elevated brain iron was found in AUD subjects in the basal ganglia and dentate nucleus. This was the first human AUD brain iron study and the first retrospective clinical fMRI QSM study.

Neurocysticercosis in asplenic patient, case report / Neurocisticercose em paciente asplênico, relato do caso

Neurocysticercosis is an important cause of neurologic and psychiatric disorders; it is a frequent etiology for acquired epilepsy worldwide. The parasitic infection of Taenia solium (including larval dissemination to the nervous system) can be avoided by effective means of prevention. Nonetheless, this disease remains endemic in many regions of the world. To demonstrate the importance of prophylaxis this paper reports the case of a patient without spleen, who was treated for neurocysticercosis manifested by epilepsy. In twenty years of follow up, the patient did not experience a repeat occurrence of neurocysticercosis, despite of immunological impairment (absence of spleen) and environmental exposure (living in an endemic area). Prevention was guided by a regular use of anthelmintic (Albendazole) and health education.

Neurocisticercose é uma importante causa de doenças neurológicas e psiquiátricas, é uma frequente etiologia de epilepsia adquirida, no mundo. A infecção parasitária da Taenia solium (incluindo a disseminação das larvas para o sistema nervoso) pode ser evitada por meios eficazes de prevenção; no entanto, esta enfermidade ainda é endêmica em muitas regiões do mundo. Para demonstrar a importância da profilaxia relata-se o caso de um paciente sem baço, o qual foi tratado para a neurocisticercose manifestada por epilepsia. Em vinte anos de seguimento, o paciente não repetiu a ocorrência de neurocisticercose, apesar de dano imunológico (ausência de baço) e exposição ambiental (habitação em área endêmica). A prevenção foi guiada pelo uso regular de anti-helmíntico (Albendazole) e medidas educativas em saúde.

Cross-sectional survey evaluating Text4Mood: mobile health program to reduce psychological treatment gap in mental healthcare in Alberta through daily supportive text messages.

BACKGROUND: To complement the oversubscribed counselling services in Alberta, the Text4Mood program which delivers daily supportive text messages to subscribers was launched on the 18th of January, 2016. This report presents an evaluation of self-reports of the impact of the program on the mental wellbeing of subscribers. METHODS: An online link to a survey questionnaire was created by an expert group and delivered via text messages to mobile phones of all 4111 active subscribers of the Text4Mood program as of April 11, 2016. RESULTS: Overall, 894 subscribers answered the survey (overall response rate 21.7 %). The response rate for individual questions varied and is reported alongside the results. Most respondents were female (83 %, n = 668), Caucasian (83 %, n = 679), and diagnosed with a psychiatric disorder (38 %, n = 307), including Depression (25.4 %, n = 227) and Anxiety (20 %, n = 177). Overall, 52 % (n = 461) signed up for Text4Mood to help elevate their mood and 24.5 % (n = 219) signed up to help them worry less. Most respondents felt the text messages made them more hopeful about managing issues in their lives (81.7 %, n = 588), feel in charge of managing depression and anxiety (76.7 %, n = 552), and feel connected to a support system (75.2 %, n = 542). The majority of respondents felt Text4Mood improved their overall mental well-being (83.1 %, n = 598). CONCLUSION: Supportive text messages are a feasible and acceptable way of delivering adjunctive psychological interventions to the general public with mental health problems. Given that text messages are affordable, readily available, and can be delivered to thousands of people simultaneously, they present an opportunity to help close the psychological treatment gap for mental health patients in Alberta and elsewhere.

Data on the impact of SSRIs and depression symptoms on the neural activities in obsessive-compulsive disorder at rest.

The data provided here related to our research article (Chen et al., 2016) [1]. We provide whole-brain intrinsic functional connectivity patterns in obsessive-compulsive disorder at resting-state [1]. This article also provides supplementary information to our research article, i.e., between - group comparisons of the effect of selective serotonin reuptake inhibitors (SSRIs) and combined depression symptoms on resting-state neural activities in obsessive-compulsive disorder. The data presented here provide novel insights into the effect of SSRIs and combined depression symptoms on the neural activities at rest.

Altered resting-state functional organization within the central executive network in obsessive-compulsive disorder.

AIM: Obsessive-compulsive disorder (OCD) is associated with deficits in response inhibition and planning, which are governed by the central executive network. The objective of this study was to investigate both intra- and inter-regional resting-state connectivity within the central executive network in OCD. METHODS: Thirty OCD patients and 30 matched healthy controls were scanned using resting-state functional magnetic resonance imaging. The independent component analysis was used on a separate sample of healthy controls to generate the central executive network mask for the subsequent OCD analyses. Regional homogeneity (ReHo) and seed-based functional connectivity analyses were used to explore the differences between intra- and inter-regional synchronized activity within the central executive network in OCD patients at rest. RESULTS: Increased ReHo and functional connectivity in the key regions of the central executive network, such as the orbitofrontal cortex, dorsolateral prefrontal cortex, and the angular gyrus, were found in OCD patients. Furthermore, changes in both the ReHo within the orbitofrontal cortex and the functional connectivity between the orbitofrontal cortex and angular gyrus were negatively correlated with OCD duration. CONCLUSION: The increased resting-state functional organization within the central executive network may be related to OCD patients' deficits in cognitive control and symptom progression.

Abnormal resting-state functional connectivity of the left caudate nucleus in obsessive-compulsive disorder.

Altered brain activities in the cortico-striato-thalamocortical (CSTC) circuitry are implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, whether the underlying changes occur only within this circuitry or in large-scale networks is still not thoroughly understood. This study performed voxel-based functional connectivity analysis on resting-state functional magnetic resonance imaging (fMRI) data from thirty OCD patients and thirty healthy controls to investigate whole-brain intrinsic functional connectivity patterns in OCD. Relative to the healthy controls, OCD patients showed decreased functional connectivity within the CSTC circuitry but increased functional connectivity in other brain regions. Furthermore, decreased left caudate nucleus-thalamus connectivity within the CSTC circuitry was positively correlated with the illness duration of OCD. This study provides additional evidence that CSTC circuitry may play an essential role and alteration of large-scale brain networks may be involved in the pathophysiology of OCD.

Patients assessed by the liaison psychiatric team in the emergency department of a regional hospital in Canada - general characteristics and gender differences.

OBJECTIVE: To describe the characteristics of liaison psychiatric patients in the emergency department (ED) of a medium sized hospital in the oil sands region of Northern Alberta. METHODS: ED psychiatry services users were evaluated using a data assessment tool designed to capture all relevant demographic and clinical characteristics. RESULTS: Overall, 477 patients (48.2% male) were assessed by the psychiatric team over the 12 month period. There was a fairly balanced distribution by age, ethnicity and relationship status between both sexes. The majority of patients with a history of self-harm or childhood sexual abuse were female while male patients were significantly more likely to report medication non-compliance. A higher proportion of female patients had depressive disorders and personality disorders while a higher proportion of male patients had anxiety disorders, bipolar and related disorders, schizophrenia spectrum disorders and substance-related disorders. Nearly one in five patients was admitted for inpatient treatment with a significantly higher proportion of males being admitted involuntarily. CONCLUSIONS: There were sex-specific differences in many of the demographic and clinical measures in our ED psychiatric sample. These differences indicate a potential need for targeted education and service initiatives to promote better access to psychiatric services and treatment outcomes.

fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behavior in adolescents.

High-risk behavior in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behavior and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behavior. We recruited 21 adolescents (age 14-17) with a wide range of high-risk behavior tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behavior Screen (ARBS). ARBS risk scores correlated highly (0.78) with impulsivity scores from the Barratt Impulsivity scale (BIS). Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI) while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behavior and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behavior tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents.

Neural correlates of high-risk behavior tendencies and impulsivity in an emotional Go/NoGo fMRI task.

Improved neuroscientific understanding of high-risk behaviors such as alcohol binging, drug use, and unsafe sex will lead to therapeutic advances for high-risk groups. High-risk behavior often occurs in an emotionally-charged context, and behavioral inhibition and emotion regulation play important roles in risk-related decision making. High impulsivity is an important potential contributor to high-risk behavior tendencies. We explored the relationships between high-risk behavior tendencies, impulsivity, and fMRI brain activations in an emotional Go/NoGo task. This task presented emotional distractor pictures (aversive vs. neutral) simultaneously with Go/NoGo stimuli (square vs. circle) that required a button press or withholding of the press, respectively. Participants' risk behavior tendencies were assessed with the Cognitive Appraisal of Risky Events (CARE) scale. The Barratt Impulsivity Scale 11 (BIS) was used to assess participant impulsivity. Individuals with higher CARE risk scores exhibited reduced activation related to response inhibition (NoGo-Go) in right orbital frontal cortex (OFC) and ventromedial prefrontal cortex. These regions did not show a significant relationship with impulsivity scores. Conversely, more impulsive individuals showed reduced emotion-related activity (aversive-neutral distractors) in dorsomedial prefrontal cortex, perigenual anterior cingulate cortex, and right posterior OFC. There were distinct neural correlates of high-risk behavior tendency and impulsivity in terms of brain activity in the emotional Go/NoGo task. This dissociation supports the conception of high-risk behavior tendency as a distinct construct from that of impulsivity. Our results suggest that treatment for high-risk behavior may be more effective with a nuanced approach that does not conflate high impulsivity necessarily with high-risk behavior tendencies.

Gold nanoparticles induce nuclear damage in breast cancer cells, which is further amplified by hyperthermia.

Gold nanoparticles have emerged as promising tools for cancer research and therapy, where they can promote thermal killing. The molecular mechanisms underlying these events are not fully understood. The geometry and size of gold nanoparticles can determine the severity of cellular damage. Therefore, small and big gold nanospheres as well as gold nanoflowers were evaluated side-by-side. To obtain quantitative data at the subcellular and molecular level, we assessed how gold nanoparticles, either alone or in combination with mild hyperthermia, altered the physiology of cultured human breast cancer cells. Our analyses focused on the nucleus, because this organelle is essential for cell survival. We showed that all the examined gold nanoparticles associated with nuclei. However, their biological effects were quantitatively different. Thus, depending on the shape and size, gold nanoparticles changed multiple nuclear parameters. They redistributed stress-sensitive regulators of nuclear biology, altered the nuclear morphology, reorganized nuclear laminae and envelopes, and inhibited nucleolar functions. In particular, gold nanoparticles reduced the de novo biosynthesis of RNA in nucleoli, the subnuclear compartments that produce ribosomes. While small gold nanospheres and nanoflowers, but not big gold nanospheres, damaged the nucleus at normal growth temperature, several of these defects were further exacerbated by mild hyperthermia. Taken together, the toxicity of gold nanoparticles correlated with changes in nuclear organization and function. These results emphasize that the cell nucleus is a prominent target for gold nanoparticles of different morphologies. Moreover, we demonstrated that RNA synthesis in nucleoli provides quantitative information on nuclear damage and cancer cell survival.

New ruthenium(II)-letrozole complexes as anticancer therapeutics.

Novel ruthenium-letrozole complexes have been prepared, and cell viability of two human cancer cell types (breast and glioblastoma) was determined. Some ruthenium compounds are known for their cytotoxicity to cancer cells, whereas letrozole is an aromatase inhibitor administered after surgery to post-menopausal women with hormonally responsive breast cancer. A significant in vitro activity was established for complex 5·Let against breast cancer MCF-7 cells and significantly lower activity against glioblastoma U251N cells. The activity of 5·Let was even higher than that of 4, a compound analogous to the well-known drug RAPTA-C. Results from the combination of 5·Let (or 4) with 3-methyladenine (3-MA) or with curcumin, respectively, revealed that the resultant cancer cell death likely involves 5·Let-induced autophagy.