Use of micro-CT to determine tracheobronchial airway geometries in three strains of mice used in inhalation toxicology as disease models.

Aerosol dosimetry estimates for mouse strains used as models for human disease are not available, primarily because of the lack of tracheobronchial airway morphometry data. By using micro-CT scans of in-situ prepared lung casts, tracheobronchial airway morphometry for four strains of mice were obtained: Balb/c, AJ, C57BL/6, and Apoe-/- . The automated tracheobronchial airway morphometry algorithms for airway length and diameter were successfully verified against previously published manual and automated tracheobronchial airway morphometry data derived from two identical in-situ Balb/c mouse lung casts. There was also excellent agreement in tracheobronchial airway length and diameter between the automated and manual airway data for the AJ, C57BL/6, and Apoe-/- mice. Differences in branch angle measurements were partially due to the differences in definition between the automated algorithms and manual morphometry techniques. Unlike the manual airway morphometry techniques, the automated algorithms were able to provide a value for inclination to gravity for each airway. Inclusion of an inclination to gravity angle for each airway along with airway length, diameter, and branch angle make the current automated tracheobronchial airway data suitable for use in dosimetry programs that can provide dosimetry estimates for inhaled material. The significant differences in upper tracheobronchial airways between Balb/c mice and between C57BL/6 and Apoe-/- mice highlight the need for mouse strain-specific aerosol dosimetry estimates.

What are the characteristics of first time older sexual offenders?

ABSTRACTBackground:Our objective was to examine and describe the common socio-demographic and clinical characteristics of first time older sex offenders. METHODS: Research papers published in MEDLINE, PsycINFO, and EMBASE were searched systematically. Following removal of duplicates and irrelevant papers, a total of 423 papers were reviewed to determine whether the selection criteria were met. A total of seven publications were included and evaluated by two researchers. RESULTS: Of the seven publications, there were two retrospective research studies and five case reports. There was a higher proportion of neurocognitive disorder in this offender group and the victims were usually vulnerable individuals. Yet, cognitive assessments were rarely done or reported. Two subtypes of older sex offenders were identified: (i) offenders who had offended in the past but were not previously detected; (ii) first-time offenders with a high proportion of neurocognitive disorder. CONCLUSION: There is a paucity of research in first time sex offending by older people. This review has highlighted a need for better designed studies to explore the characteristics of older sex offenders. Better collaboration between forensic and old-age psychiatric services is required for improved assessment and management of older sex offenders.

Evaluation of a brief pilot psychoeducational support group intervention for family caregivers of cancer patients: a quasi-experimental mixed-methods study.

BACKGROUND: Family caregivers of cancer patients often experience an impaired quality of life (QOL) and emotional distress as a result of their caregiving duties, which may potentially influence the quality of care of their care recipients. The COPE (Caregivers of cancer Outpatients' Psycho-Education support group therapy) intervention was developed as a response to the lack of work done among family caregivers of ambulatory cancer patients in Asia. This group intervention comprised four weekly sessions simultaneously targeting psychoeducation, skills training, and supportive therapy. The present study sought to evaluate the pilot COPE intervention using both quantitative and qualitative measures. The Hospital Anxiety and Depression Scale (HADS) was used to measure both depression and anxiety, while the Caregiver QOL - Cancer (CQOLC) measured caregiver QOL. These instruments were measured at baseline pre-intervention, and immediately post-intervention. A waitlist control group design was adopted. A subset of caregivers from the intervention group were invited for a semi-structured interview post-intervention. FINDINGS: Quantitative analyses suggest that while QOL remained stable in control group participants, intervention group participants experienced QOL improvements - both in overall QOL and in the specific domain of burden. There were no significant differences in the trajectories of depression and anxiety in both groups. Qualitative analyses suggest that this might have been a result of the intervention not only equipping participants with the relevant coping skills, but also providing a platform for emotional expression and situational reappraisal. CONCLUSIONS: The COPE intervention has shown some efficacy in helping family caregivers of cancer patients, but more work is required before this can be implemented. TRIAL REGISTRATION: Current Controlled Trials NCT02120183 . Registered 17 April 2014. Retrospectively registered.

Quality of life of family caregivers of cancer patients in Singapore and globally.

INTRODUCTION: Family caregivers of cancer patients often suffer from impaired quality of life (QOL) due to stress arising from the responsibility of caregiving. Most research on such QOL impairments was conducted in Western populations. Thus, this exploratory study sought to (a) examine the QOL levels of family caregivers of cancer patients in an Asian population in Singapore, in relation to caregivers from other countries within and outside of Asia; and (b) investigate the association between sociodemographic factors and QOL impairments in family caregivers in Singapore. METHODS: A total of 258 family caregivers of cancer patients who were receiving outpatient treatment completed the Caregiver Quality of Life Index-Cancer (CQOLC) and a sociodemographic survey. We compared the published CQOLC total scores from Turkey, Iran, Taiwan, South Korea, the United Kingdom, the United States and Canada with the Singapore dataset and examined the demographic relationships. RESULTS: Caregivers in Singapore and Asia had lower CQOLC total scores than their Western counterparts. Caregivers who were male, of Chinese ethnicity, had parental relationships with their care recipient, or cared for advanced-stage cancer patients were found to have impaired QOL. CONCLUSION: The findings of this study highlight possible areas in which support can be provided for family caregivers of cancer patients, and underscore the need to reconcile cultural diversity, values, societal expectations and demographic characteristics in Singapore.

Psychosocial concerns of cancer patients in Singapore.

AIMS: Psychosocial needs are high among cancer patients, and screening for these is recognized as integral to quality cancer care. This study identified the psychosocial needs of cancer patients at their first visit at a hematology-oncology clinic. METHODS: Fifty-four new consecutive patients completed the Distress Thermometer and the Problem List, the Hospital Anxiety and Depression Scale, and the EuroQol Quality of Life Scale at their first visit to plan for chemotherapy. Data were analyzed with SPSS. RESULTS: Analyses revealed that participants had an average of 2.8 ± 2.3 problems, with 82% having psychosocial needs. Emotional concerns formed the top four psychosocial needs of the cohort (worry 46%, fears 26%, nervousness 26%, sadness 24%), with the fifth being a practical concern (insurance/finance 22%). The former were more frequent among 41- to 50-year-olds and significantly correlated with distress scores. Practical concerns were significantly correlated with depressive symptoms. Family concerns were more significant in women. The overall score on the Problem List correlated with distress, anxious symptomatology and poorer quality of life scores. CONCLUSIONS: Distress and psychosocial needs are high in cancer patients even at an early stage prior to chemotherapy. Attention to these needs is crucial as they cause significant distress and affect the patient's quality of life.

Strengthening Resilience and Reducing Stress in Psychosocial Care for Nurses Practicing in Oncology Settings.

The current study examined whether continuing education programs on psychosocial oncology patient care would improve nurses' resilience and reduce their stress. Analyses revealed postprogram improvements in resilience, which was related to reduction in stress. Findings provide preliminary evidence that such programs may also be helpful in other domains.

A pilot, quasi-experimental, mixed methods investigation into the efficacy of a group psychotherapy intervention for caregivers of outpatients with cancer: the COPE study protocol.

INTRODUCTION: Despite the rising trend of cancer prevalence and increase in family caregiving, little attention has been paid to the efficacy of psychosocial interventions among Asian caregiver samples, particularly support groups, given the benefits that have been shown in studies on Western populations. This trial aims to evaluate the effectiveness of a pilot 4-week group psychotherapy for Singaporean family caregivers of patients receiving outpatient care. METHODS AND ANALYSIS: Facilitated by a clinical psychologist, this intervention is primarily based on the brief integrative psychological therapy with a supportive-expressive intent. Participants will be recruited while they are accompanying their care recipients for outpatient consultations. Since this is a pilot study, a sample size of 120 participants is targeted on the basis of sample sizes of previous studies. The study adopts a quasi-experimental design, as participants are assigned the intervention or control arms based on their availability to attend the intervention. A mixed methods approach is used to evaluate the outcomes of the intervention. A self-administered battery of tests is completed at four time points: baseline, postintervention and follow-up at 1-month and 2-month postinterventions; semi-structured interviews are conducted at baseline and post-intervention. Primary outcomes are quality of life and anxious and depressive symptoms; secondary outcomes are stress and basic psychological needs. Analysis using analysis of covariance would be conducted to determine the effectiveness of the intervention. ETHICS AND DISSEMINATION: This study protocol has ethics approval from the National Healthcare Group Domain Specific Review Board (NHG DSRB Ref: 2013/00662). Written informed consent is obtained from every participant. Results will be disseminated through journals and conferences, and will be particularly relevant for clinicians intending to implement similar support groups to address the psychosocial concerns of caregivers, as well as for researchers seeking to refine the structure and evaluate the effectiveness of such programmes. TRIAL REGISTRATION NUMBER: Current Controlled Trials NCT02120183 (https://clinicaltrials.gov/show/NCT02120183).

Efficacy of a brief nurse-led pilot psychosocial intervention for newly diagnosed Asian cancer patients.

PURPOSE: Cancer patients experience distress and high levels of psychosocial concerns. However, in Asian countries like Singapore, patients are often unwilling to seek support and help from mental healthcare professionals, but, instead, are more willing to confide in nurses. This quasi-experimental study developed and tested the efficacy of a brief nurse-led psychosocial intervention to alleviate these patients' distress, minor psychiatric morbidity, and psychosocial concerns. METHODS: The semi-structured intervention comprised 20- to 30-minute face-to-face sessions with trained oncology nurses, monthly for 2 months and then bimonthly for 4 months. Patients received psycho-education on symptoms of stress, anxiety, and depression and counseling and were taught behavioral techniques such as deep breathing, progressive muscle relaxation, and positive self-talk. RESULTS: The results of this study found that patients who received the intervention had reduced distress, depression, and anxiety levels and improved quality of life (QOL) at 6 months. CONCLUSIONS: Although further research is necessary to explore the efficacy and viability of this intervention, findings support brief nurse-led psycho-educational interventions in Asian settings especially for cancer patients reluctant to seek help from mental health professionals.

The Caregiver Quality of Life Index-Cancer (CQOLC) in Singapore: a new preliminary factor structure for caregivers of ambulatory patients with cancer.

PURPOSE: The Caregiver Quality of Life Index-Cancer (CQOLC) is used worldwide to determine levels of quality of life of caregivers of patients with cancer; however, the few studies examining the underlying factor structure of the CQOLC have revealed differences between Western and Eastern cultures. This study sought to confirm the differences in the factor structures between the original CQOLC and a Taiwanese (Mandarin) version. METHODS: A total of 183 caregivers from a cancer center in Singapore participated in this exploratory cross-sectional study. All participants completed the CQOLC and a sociodemographic form; 30 participants repeated the CQOLC two weeks later. RESULTS: Test-retest reliability was adequate for the CQOLC; however, confirmatory factor analyses did not support either the original four-factor model or the Taiwanese five-factor model. Exploratory factor analyses suggested the retaining of five factors to form a 25-item Singapore version (CQOLC-S25): burden, physical/practical concerns, emotional reactivity, self-needs, and social support. Inter-factor and factor scale correlations were positively significant for all factors except Support, which was negatively correlated with emotional reactivity and self-needs. CONCLUSIONS: Cross-cultural differences, which require further investigations, appear to underlie the utility and understanding of the CQOLC. More research is needed to better understand the needs of Singapore caregivers.

Knowledge, attitudes, and practice behaviors (KAPb) of nurses and the effectiveness of a training program in psychosocial cancer care.

PURPOSE: Psychosocial distress in oncology patients may significantly interfere with their health outcomes and quality of life. Nurses work closely with their patients and are in the best position to screen for distress and provide timely intervention. It is thus important for nurses working in oncology settings to be equipped and prepared to address distressing psychosocial issues. The present study aims to investigate the impact of a training program in psychosocial care on nurses' knowledge, attitudes, and clinical practice behaviors. METHODS: A total of 180 nurses working in medical oncology and radiation oncology departments at the National University Cancer Institute Singapore underwent a training program in psychosocial care as part of their continuing nursing education curriculum. One hundred fifty four of these nurses completed a self-designed questionnaire on nurses' knowledge, attitudes, and practice behaviors (KAPb) at all four time points: baseline, post-training, and at 6 and 12 weeks post-training, respectively. RESULTS: The self-designed KAPb questionnaire proved adequate for this study. Positive gains on applied knowledge and practice behaviors were sustained over a 12-week period. There were no changes in theoretical knowledge. A decreasing trend in attitudes was noted, although this was specific to the participants' attitudes toward the importance of emotional concerns as compared to physical concerns in cancer treatment. Enrolled nurses seemed to have higher starting levels of theoretical knowledge than their registered counterparts were. There were no other differences on demographic variables in relation to the efficacy of the training program. CONCLUSIONS: The training program was successful in improving the applied knowledge and practice behaviors of nurses in providing psychosocial care for cancer patients. However, further refinement to the program, with particular attention to nurses' existing training and years of clinical nursing experience, would enhance staff empowerment and care improvement.

The Distress Thermometer as an ultra-short screening tool: a first validation study for mixed-cancer outpatients in Singapore.

INTRODUCTION: Research has shown that single-item tools, like the Distress Thermometer (DT), are comparable to longer ones, like the Hospital Anxiety and Depression Scale (HADS). In this study, we tested the validity of the DT in a population of Singapore cancer outpatients, and determined the cut-off scores on the DT for clinically relevant distress and an impaired quality of life (QOL). We also documented the prevalence of anxiety, depression, and QOL impairments in this population. METHODS: One hundred and five patients (Mdn age=51-60years, 64% female, and 71% Chinese) diagnosed with various cancers participated in this study. They completed a standard socio-demographic form, the DT and the Problem List, the HADS, and the EuroQOL Quality of Life Scale (EQ-5D). RESULTS: Almost a third of patients had clinically significant emotional distress, with 15%-16% having probable levels of anxiety and depression. Almost half (41%-55%) had an impaired QOL compared to Singapore population norms. Receiver operating characteristic curve analyses identified an area under the curve of 0.89 (SE=0.36, 95% CI [0.82, 0.96], p<.001) when compared to the HADS cut-off score of 15. A cut-off score of 5 on the DT had the best sensitivity (0.88) and specificity (0.81). Participants above the DT cut-off score of 5 reported significantly more emotional problems (worry, nervousness, depression, sadness), insurance/finance-related problems, and sleep problems. They also scored significantly lower on EQ-5D, with more QOL impairments in the domains of carrying out their usual activities and anxiety/depression. CONCLUSION: Levels of distress, anxiety, depression, and QOL impairments are high in this population. The DT was found to be a valid tool for distress screening in the Singapore cancer population, with a recommended cut-off score of 5.

Psychosocial care for cancer patients--too little, too late?

Assessment of psychosocial and psychiatric needs is an increasingly important component of cancer care. Clinical experience with patients indicate that distress, anxiety and depression are prevalent from early stages of the illness. Strategies to enhance psychosocial care are presented and these include early identification through screening, training for healthcare staff working with cancer patients and support not only for patients but their caregivers as well.

Prenatal exposure to lipopolysaccharide results in neurodevelopmental damage that is ameliorated by zinc in mice.

There is converging evidence that during pregnancy a maternal immune response to infection can cause neurodevelopmental damage. Lipopolysaccharide (LPS)-mediated induction of metallothionein (MT) and subsequent hypozincaemia has been linked to fetal brain damage. Our group has demonstrated that Zn, when co-administered with LPS in early pregnancy in mice (gestation day (GD) 8), prevents fetal malformations and neurodevelopmental deficits in offspring. Others demonstrating fetal brain lesions have administered LPS much later in gestation (after GD 16), when the influence of LPS-mediated MT-induction on maternal plasma Zn levels, and the effect of Zn co-administration with LPS, are unknown. The aims of this study are firstly to examine whether LPS causes MT induction and maternal hypozincaemia in mid-to-late pregnancy, and secondly to determine if histochemical markers of inflammatory damage in fetal brain are affected by LPS and whether this damage can be alleviated with Zn treatment. Pregnant mice were injected with LPS (5 mg/kgbodywt.) or saline vehicle on GD 16 and then humanely killed at 8, 16 and 24 h for Zn and MT measurements, or concomitantly injected subcutaneously with Zn (2 mg/kgbodywt.) or saline and then killed on GD 18 and immunohistochemistry performed on fetal brain. Maternal hepatic MT was markedly induced after LPS-challenge and this was associated with a 38% reduction in maternal plasma Zn concentrations. Coincidentally, the fetuses of LPS-treated dams showed astrogliosis, extensive cell death and an increased number of cells producing TNF-α which was prevented with concomitant Zn treatment. These results support the premise that in mid-to-late pregnancy, an infection-mediated activation of a maternal immune response can cause MT induction that redistributes Zn in the mother, restricting fetal Zn supply, causing neurodevelopmental damage.

R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer.

Accumulating evidence suggests important roles for the receptor tyrosine kinase Axl in cancer progression, invasion, metastasis, drug resistance, and patient mortality, highlighting Axl as an attractive target for therapeutic development. We have generated and characterized a potent and selective small-molecule inhibitor, R428, that blocks the catalytic and procancerous activities of Axl. R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. Pharmacologic investigations revealed favorable exposure after oral administration such that R428-treated tumors displayed a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. In support of an earlier study, R428 inhibited angiogenesis in corneal micropocket and tumor models. R428 administration reduced metastatic burden and extended survival in MDA-MB-231 intracardiac and 4T1 orthotopic (median survival, >80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis. Additionally, R428 synergized with cisplatin to enhance suppression of liver micrometastasis. Our results show that Axl signaling regulates breast cancer metastasis at multiple levels in tumor cells and tumor stromal cells and that selective Axl blockade confers therapeutic value in prolonging survival of animals bearing metastatic tumors.

Dietary zinc supplementation ameliorates LPS-induced teratogenicity in mice.

Maternal infection during the first trimester of pregnancy has been associated with preterm birth, spontaneous abortion, growth retardation, and congenital anomalies. Previously, our group has shown that subcutaneous injection of zinc prevents endotoxin [lipopolysaccharide (LPS)]-induced teratogenicity. The purpose of this study was to investigate whether increasing or decreasing dietary zinc alters the teratogenic effects of LPS. Female C57BL6 mice were mated and fed diets containing 5, 35, or 100 mg/kg zinc. On gestational day (GD) 8, pregnant dams were injected with either LPS (0.5 mg/kg s.c.) or saline and killed on GD18. LPS-treated fetuses from dams fed 5 and 35 mg/kg zinc diet had a significantly higher number of abnormalities per litter (2- and 1- fold saline controls, respectively) compared with those from LPS + zinc supplemented dams, which were not significantly different from the saline control groups. The beneficial effect and importance of zinc was also reflected in the larger size of fetuses (weight and crown-rump length) from the LPS + zinc-supplemented treatment group. We have demonstrated that low dietary zinc during exposure to infection (i.e. LPS) in pregnancy augments the negative impact of LPS alone, and that dietary zinc supplementation throughout pregnancy ameliorates LPS-induced teratogenicity.