A micro-fabricated device (microICSI) improves porcine blastocyst development and procedural efficiency for both porcine intracytoplasmic sperm injection and human microinjection.

PURPOSE: Intracytoplasmic sperm injection (ICSI) imparts physical stress on the oolemma of the oocyte and remains among the most technically demanding skills to master, with success rates related to experience and expertise. ICSI is also time-consuming and requires workflow management in the laboratory. This study presents a device designed to reduce the pressure on the oocyte during injection and investigates if this improves embryo development in a porcine model. The impact of this device on laboratory workflow was also assessed. METHODS: Porcine oocytes were matured in vitro and injected with porcine sperm by conventional ICSI (C-ICSI) or with microICSI, an ICSI dish that supports up to 20 oocytes housed individually in microwells created through microfabrication. Data collected included set-up time, time to align the polar body, time to perform the injection, the number of hand adjustments between controllers, and degree of invagination at injection. Developmental parameters measured included cleavage and day 6 blastocyst rates. Blastocysts were differentially stained to assess cell numbers of the inner cell mass and trophectoderm. A pilot study with human donated MII oocytes injected with beads was also performed. RESULTS: A significant increase in porcine blastocyst rate for microICSI compared to C-ICSI was observed, while cleavage rates and blastocyst cell numbers were comparable between treatments. Procedural efficiency of microinjection was significantly improved with microICSI compared to C-ICSI in both species. CONCLUSION: The microICSI device demonstrated significant developmental and procedural benefits for porcine ICSI. A pilot study suggests human ICSI should benefit equally.

Factor Analysis of Therapist-Identified Treatment Targets in Community-Based Children's Mental Health.

The present study used exploratory and confirmatory factor analyses to identify underlying latent factors affecting variation in community therapists' endorsement of treatment targets. As part of a statewide practice management program, therapist completed monthly reports of treatment targets (up to 10 per month) for a sample of youth (n = 790) receiving intensive in-home therapy. Nearly 75 % of youth were diagnosed with multiple co-occurring disorders. Five factors emerged: Disinhibition, Societal Rules Evasion, Social Engagement Deficits, Emotional Distress, and Management of Biodevelopmental Outcomes. Using logistic regression, primary diagnosis predicted therapist selection of Disinhibition and Emotional Distress targets. Client age predicted endorsement of Societal Rules Evasion targets. Practice-to-research implications are discussed.

Examining the Effects of Time to Diagnosis, Income, Symptoms, and Incidental Detection on Overall Survival in Epithelial Ovarian Cancer: Manitoba Ovarian Cancer Outcomes (MOCO) Study Group.

OBJECTIVE: The primary objectives of this study were to analyze data on time to diagnosis and correlate this with overall survival. We secondarily analyzed the effects of emergency room visits, symptoms, incidental findings, residence, socioeconomic status, and residual disease on overall survival. METHODS: This retrospective population-based descriptive cohort study examined all invasive ovarian cancer cases in Manitoba, Canada, between 2004 and 2010. Clinicopathologic, socioeconomic, and outcome data were collected. Analysis was performed with Cox and logistic regression stratified by early and late stage. RESULTS: Six hundred eighty-seven ovarian cancer patients were identified, with a final cohort of 601 patients: 210 with early-stage (1/2) and 391 with late-stage (3/4) disease. No presenting symptoms were associated with survival outcome. Poorer survival was associated with increasing age (P = 0.0016) and neoadjuvant chemotherapy (P = 0.0037). Higher income within the urban setting was also associated with a survival advantage (P = 0.0037), whereas initial presentation to the emergency room (P = 0.0399) was associated with decreased survival. Finally, for advanced-stage disease, incidental diagnosis had a significantly improved overall survival (hazard ratio, 0.424; 95% confidence interval, 0.27-0.67; P = 0.0003), even when accounting for confounding factors. Time from first presentation to diagnosis was associated with survival (P = 0.0309). CONCLUSIONS: This study found that time to diagnosis did not negatively impact overall survival, although there was an association. Age, morphology, treatment type, residual disease, medical comorbidities, and income were significant prognostic factors. This is the first study to show a survival advantage to incidentally finding an ovarian cancer. Further research is needed on the outcomes of pelvic examination.

Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells.

Inherent or acquired drug resistance is a major contributor to epithelial ovarian cancer (EOC) mortality. Novel drugs or drug combinations that produce EOC cell death or resensitize drug resistant cells to standard chemotherapy may improve patient treatment. After conducting drug tolerability studies for the multikinase inhibitors dorsomorphin (DM) and it is structural analogue LDN-193189 (LDN), these drugs were tested in a mouse intraperitoneal xenograft model of EOC. DM significantly increased survival, whereas LDN showed a trend toward increased survival. In vitro experiments using cisplatin (CP)-resistant EOC cell lines, A2780-cp or SKOV3, we determined that pretreatment or cotreatment with DM or LDN resensitized cells to the killing effect of CP or carboplatin (CB). DM was capable of blocking EOC cell cycle and migration, whereas LDN produced a less pronounced effect on cell cycle and no effect on migration. Subsequent analyses using primary human EOC cell samples or additional established EOC cells lines showed that DM or LDN induced a dose-dependent autophagic or cell death response, respectively. DM induced a characteristic morphological change with the appearance of numerous LC3B-containing acidic vacuoles and an increase in LC3BII levels. This was coincident with a decrease in cell growth and the altered cell cycle consistent with DM-induced cytostasis. By contrast, LDN produced a caspase 3-independent, reactive oxygen species-dependent cell death. Overall, DM and LDN possess drug characteristics suitable for adjuvant agents used to treat chemotherapy-sensitive and -resistant EOC.

Frequency, level, and rate of improvement for treatment targets in a children's mental health community-based intensive in-home therapeutic setting.

Frequency, level, and rate of improvement on 48 therapist-identified treatment targets were examined for 790 youth in usual care receiving intensive in-home services. Targets related to disruptive behavior, depressive mood, and functional impairment were most common. Overall, targets attained moderate levels of improvement and reached maximum gains in approximately three months. Targets associated with disruptive behavior and depressive mood disorders showed significantly greater improvement than those associated with ADHD. Anxiety-related targets improved quickest and significantly faster than disruptive behavior targets. Outcomes for targets within the same diagnostic group also varied substantially. Practice and implementation implications are discussed.

Nano-liter perfusion microfluidic device made entirely by two-photon polymerization for dynamic cell culture with easy cell recovery.

Polydimethylsiloxane (PDMS) has been the material of choice for microfluidic applications in cell biology for many years, with recent advances encompassing nano-scaffolds and surface modifications to enhance cell-surface interactions at nano-scale. However, PDMS has not previously been amenable to applications which require complex geometries in three dimensions for cell culture device fabrication in the absence of additional components. Further, PDMS microfluidic devices have limited capacity for cell retrieval following culture without severely compromising cell health. This study presents a designed and entirely 3D-printed microfluidic chip (8.8 mm × 8.2 mm × 3.6 mm) using two-photon polymerization (2PP). The 'nest' chip is composed of ten channels that deliver sub-microliter volume flowrates (to ~ 600 nL/min per channel) to 10 individual retrievable cell sample 'cradles' that interlock with the nest to create the microfluidic device. Computational fluid dynamics modelling predicted medium flow in the device, which was accurately validated by real-time microbead tracking. Functional capability of the device was assessed, and demonstrated the capability to deliver culture medium, dyes, and biological molecules to support cell growth, staining and cell phenotype changes, respectively. Therefore, 2PP 3D-printing provides the precision needed for nanoliter fluidic devices constructed from multiple interlocking parts for cell culture application.

The Basic Science of Behavior Change and Its Application to Pediatric Providers.

Pediatric primary care providers (PPCPs) are increasingly expected to know how to assess, diagnose, and treat a wide range of mental health problems in children and adolescents. For many PPCPs, this means learning and performing new practice behaviors that were not taught in their residency training. Typical continuing education approaches to engage PPCPs in new practices have not yielded the desired changes in provider behavior. This article summarizes behavior change principles identified through basic behavior science, adult education, and communication research, and discusses their application to a patient-centered pediatric primary care mental health curriculum.

Diagnostic and referral intervals for Manitoba women with epithelial ovarian cancer - the Manitoba Ovarian Cancer Outcomes (MOCO) study group: a retrospective cross-sectional study.

BACKGROUND: Epithelial ovarian cancer has the highest mortality of all gynecologic cancers. The poor survival rates are often attributed to the advanced stage at which most of these cancers are detected. We sought to examine the effects of patient demographics, comorbidities and presenting symptoms on diagnostic and referral intervals by location of first presentation (emergency department v. elsewhere) and to identify factors that affect these intervals. METHODS: We performed a retrospective analysis of chart and medical record data for ovarian cancers, with the exceptions of sex cord and germ cell tumours, diagnosed between 2004 and 2010 in Manitoba, Canada. Data were collected on baseline characteristics, time to diagnosis and referral, number and type of physician visits and emergency department visits. RESULTS: The final cohort consisted of 601 patients. Sixty-three percent of patients received their diagnosis within 60 days of initial presentation, and 75.2% had their cancer diagnosed within 2 physician encounters. The median diagnostic interval for all stages of patients presenting to the emergency department was 7 days, compared with 55 days for patients presenting elsewhere. Early stage patients not presenting to the emergency department had their diagnosis a median of 34.0 days later than patients with advanced disease (95% confidence interval [CI] 22.22 to 45.69, p < 0.0001). The presence of some symptoms was associated with shortened diagnostic intervals. Patients with serous, clear-cell or endometrioid histotypes were less likely to have first presentation beginning in the emergency department (odds ratio [OR] 0.40, 95% CI 0.24 to 0.64, p = 0.0001; OR 0.28, 95% CI 0.14 to 0.59, p = 0.007) than those with unclassified epithelial histotype. INTERPRETATION: For this group of patients, the main factor associated with diagnostic and referral intervals is presentation to the emergency department. These patients likely required more urgent attention for their more symptomatic disease, leading to quicker diagnosis and referral patterns, despite poorer prognosis.

"Strength at Home" Intervention for Male Veterans Perpetrating Intimate Partner Aggression: Perceived Needs Survey of Therapists and Pilot Effectiveness Study.

Veteran and active duty populations evidence higher rates of intimate partner aggression (IPA) than comparable civilian groups, perhaps due in part to their unique service-related experiences. IPA offender treatment programs that take military background into consideration are not widely available, and it is unclear to what extent there is a perceived need for them among clinicians who serve service members and Veterans. Strength at Home (SAH) is a promising 12-session cognitive-behavioral group intervention designed to address IPA perpetration in military populations. While clinical support for SAH is emerging, the extent to which service members and Veterans find it appropriate and helpful is not yet known. Goals of the current study were threefold: (a) assess the perceived need for a military-specific IPA program among Veterans Administration and community domestic violence (DV) program providers; (b) conduct a pilot study to examine the feasibility and preliminary effectiveness of SAH in a sample drawn from a diverse, multicultural community; and (c) conduct focus groups to obtain participant feedback on the SAH protocol. Findings from the provider survey suggested a need for specialty programs to treat military personnel who perpetrate IPA of mildtomoderate severity. Results of the SAH pilot study (n = 6) indicated decreased psychological aggression and increased anger control from baseline to 6-month follow-up. Focus group feedback indicated participants found the program to be helpful and appropriate across a wide variety of ethno-cultural variables. As more service members and Veterans of the Iraq/Afghanistan war era reintegrate into our communities, it will become increasingly important for providers in both private and public sectors of care to understand the unique needs of this treatment population, and to have access to effective IPA treatment programs.

Validity of Clinician's Self-Reported Practice Elements on the Monthly Treatment and Progress Summary.

An increased demand for accountability in community mental health systems has resulted in a need for valid, reliable measures of therapeutic practice. The Monthly Treatment and Progress Summary (MTPS), developed through the Hawaii Child and Adolescent Mental Health Division, is a clinician-report measure that describes therapeutic practices, treatment targets, and progress ratings for each treatment case. The current study evaluated the validity of the therapeutic strategies reported on the MTPS by comparing coder- and clinician-reported use of practices. Using 47 audio recordings from 19 youths' therapy sessions, trained observers reliably coded 12 discrete practices. Four of the 12 practices were found to be valid according to clinician-coder agreement (intraclass correlations ≥0.60). The coding system was revised, utilizing extensiveness and experiential scales, and 100 % of practices were valid according to clinician-coder agreement. Practical use of the MTPS, implications for service systems, and future directions for research on the MTPS are discussed.