Introduction to this double issue: Jail diversion and collaboration across the justice continuum

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142041/1/bsl2322.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142041/2/bsl2322_am.pd

Anti-Proliferation Effect of Theasaponin E₁ on the ALDH-Positive Ovarian Cancer Stem-Like Cells

Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested that CSCs give rise to tumor recurrence and metastasis. Theasaponin E1 (TSE1), which was isolated from green tea (Camellia sinensis) seeds, has been proposed to be an effective compound for tumor treatment. However, studies on whether TSE1 takes effect through CSCs have rarely been reported. In this paper, ALDH-positive (ALDH+) ovarian cancer stem-like cells from two platinum-resistant ovarian cancer cell lines A2780/CP70 and OVCAR-3 were used to study the anti-proliferation effect of TSE1 on CSCs. The ALDH+ cells showed significantly stronger sphere forming vitality and stronger cell migration capability. In addition, the stemness marker proteins CD44, Oct-4, Nanog, as well as Bcl-2 and MMP-9 expression levels of ALDH+ cells were upregulated compared with the original tumor cells, indicating that they have certain stem cell characteristics. At the same time, the results showed that TSE1 could inhibit cell proliferation and suspension sphere formation in ALDH+ cells. Our data suggests that TSE1 as a natural compound has the potential to reduce human ovarian cancer mortality. However, more research is still needed to find out the molecular mechanism of TSE1-mediated inhibition of ALDH+ cells and possible drug applications on the disease

The Grizzly, September 24, 1991

Ursinus Day Academic Convocation Changes Face • Alcohol Policy Enforcement Tightens • Freshman Class Elections Held • Dr. Hall Honored • U.S.G.A. Minutes • Student Response Team Regroups • Demas Presents... Barry Hixson • Sororities Begin Formal Rushing • Finally! Student Center Opens • Golf Gets New Head Coach • Paul Harryn Launches Berman Season • DeLuca Hypnotizes Audience • Movie Reviews: Pacific Heights; New Jack City; Hot Shots • Volleyball Nets a Win • Lady Bears Stick It to Opponents • Nick\u27s NFL Notes • Bears Harass Hoyas in Opener • Soccer Kicks Off Season with Win • U.C. Tavern? • Questions of Freedom • Defense of History • Life Science Building Upgraded to State-Of-The-Art Facility • Pre-med Committee Evaluation Meeting • Medicine in The Gulf Warhttps://digitalcommons.ursinus.edu/grizzlynews/1277/thumbnail.jp

Psychiatric Context of Acute/Early HIV Infection. The NIMH Multisite Acute HIV Infection Study: IV

Acute/early HIV infection is a period of high risk for HIV transmission. Better understanding of behavioral aspects during this period could improve interventions to limit further transmission. Thirty-four participants with acute/early HIV infection from six US cities were assessed with the Mini International Diagnostic Interview, Beck Depression Inventory II, State-Trait Anxiety Inventory, Brief COPE, and an in-depth interview. Most had a pre-HIV history of alcohol or substance use disorder (85%); a majority (53%) had a history of major depressive or bipolar disorder. However, post-diagnosis coping was predominantly adaptive, with only mild to moderate elevations of anxious or depressive mood. Respondents described challenges managing HIV in tandem with pre-existing substance abuse problems, depression, and anxiety. Integration into medical and community services was associated with adaptive coping. The psychiatric context of acute/early HIV infection may be a precursor to infection, but not necessarily a barrier to intervention to reduce forward transmission of HIV among persons newly infected

Interventions for drug-using offenders with co-occurring mental health problems

Background This review represents one from a family of three reviews focusing on interventions for drug‐using offenders. Many people under the care of the criminal justice system have co‐occurring mental health problems and drug misuse problems; it is important to identify the most effective treatments for this vulnerable population. Objectives To assess the effectiveness of interventions for drug‐using offenders with co‐occurring mental health problems in reducing criminal activity or drug use, or both. This review addresses the following questions. • Does any treatment for drug‐using offenders with co‐occurring mental health problems reduce drug use? • Does any treatment for drug‐using offenders with co‐occurring mental health problems reduce criminal activity? • Does the treatment setting (court, community, prison/secure establishment) affect intervention outcome(s)? • Does the type of treatment affect treatment outcome(s)? Search methods We searched 12 databases up to February 2019 and checked the reference lists of included studies. We contacted experts in the field for further information. Selection criteria We included randomised controlled trials designed to prevent relapse of drug use and/or criminal activity among drug‐using offenders with co‐occurring mental health problems. Data collection and analysis We used standard methodological procedures as expected by Cochrane . Main results We included 13 studies with a total of 2606 participants. Interventions were delivered in prison (eight studies; 61%), in court (two studies; 15%), in the community (two studies; 15%), or at a medium secure hospital (one study; 8%). Main sources of bias were unclear risk of selection bias and high risk of detection bias. Four studies compared a therapeutic community intervention versus (1) treatment as usual (two studies; 266 participants), providing moderate‐certainty evidence that participants who received the intervention were less likely to be involved in subsequent criminal activity (risk ratio (RR) 0.67, 95% confidence interval (CI) 0.53 to 0.84) or returned to prison (RR 0.40, 95% CI 0.24 to 0.67); (2) a cognitive‐behavioural therapy (one study; 314 participants), reporting no significant reduction in self‐reported drug use (RR 0.78, 95% CI 0.46 to 1.32), re‐arrest for any type of crime (RR 0.69, 95% CI 0.44 to 1.09), criminal activity (RR 0.74, 95% CI 0.52 to 1.05), or drug‐related crime (RR 0.87, 95% CI 0.56 to 1.36), yielding low‐certainty evidence; and (3) a waiting list control (one study; 478 participants), showing a significant reduction in return to prison for those people engaging in the therapeutic community (RR 0.60, 95% CI 0.46 to 0.79), providing moderate‐certainty evidence. One study (235 participants) compared a mental health treatment court with an assertive case management model versus treatment as usual, showing no significant reduction at 12 months' follow‐up on an Addictive Severity Index (ASI) self‐report of drug use (mean difference (MD) 0.00, 95% CI ‐0.03 to 0.03), conviction for a new crime (RR 1.05, 95% CI 0.90 to 1.22), or re‐incarceration to jail (RR 0.79, 95% CI 0.62 to 1.01), providing low‐certainty evidence. Four studies compared motivational interviewing/mindfulness and cognitive skills with relaxation therapy (one study), a waiting list control (one study), or treatment as usual (two studies). In comparison to relaxation training, one study reported narrative information on marijuana use at three‐month follow‐up assessment. Researchers reported a main effect < .007 with participants in the motivational interviewing group, showing fewer problems than participants in the relaxation training group, with moderate‐certainty evidence. In comparison to a waiting list control, one study reported no significant reduction in self‐reported drug use based on the ASI (MD ‐0.04, 95% CI ‐0.37 to 0.29) and on abstinence from drug use (RR 2.89, 95% CI 0.73 to 11.43), presenting low‐certainty evidence at six months (31 participants). In comparison to treatment as usual, two studies (with 40 participants) found no significant reduction in frequency of marijuana use at three months post release (MD ‐1.05, 95% CI ‐2.39 to 0.29) nor time to first arrest (MD 0.87, 95% CI ‐0.12 to 1.86), along with a small reduction in frequency of re‐arrest (MD ‐0.66, 95% CI ‐1.31 to ‐0.01) up to 36 months, yielding low‐certainty evidence; the other study with 80 participants found no significant reduction in positive drug screens at 12 months (MD ‐0.7, 95% CI ‐3.5 to 2.1), providing very low‐certainty evidence. Two studies reported on the use of multi‐systemic therapy involving juveniles and families versus treatment as usual and adolescent substance abuse therapy. In comparing treatment as usual, researchers found no significant reduction up to seven months in drug dependence on the Drug Use Disorders Identification Test (DUDIT) score (MD ‐0.22, 95% CI ‐2.51 to 2.07) nor in arrests (RR 0.97, 95% CI 0.70 to 1.36), providing low‐certainty evidence (156 participants). In comparison to an adolescent substance abuse therapy, one study (112 participants) found significant reduction in re‐arrests up to 24 months (MD 0.24, 95% CI 0.76 to 0.28), based on low‐certainty evidence. One study (38 participants) reported on the use of interpersonal psychotherapy in comparison to a psychoeducational intervention. Investigators found no significant reduction in self‐reported drug use at three months (RR 0.67, 95% CI 0.30 to 1.50), providing very low‐certainty evidence. The final study (29 participants) compared legal defence service and wrap‐around social work services versus legal defence service only and found no significant reductions in the number of new offences committed at 12 months (RR 0.64, 95% CI 0.07 to 6.01), yielding very low‐certainty evidence. Authors' conclusions Therapeutic community interventions and mental health treatment courts may help people to reduce subsequent drug use and/or criminal activity. For other interventions such as interpersonal psychotherapy, multi‐systemic therapy, legal defence wrap‐around services, and motivational interviewing, the evidence is more uncertain. Studies showed a high degree of variation, warranting a degree of caution in interpreting the magnitude of effect and the direction of benefit for treatment outcomes

Germline selection shapes human mitochondrial DNA diversity.

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.NIHR, Wellcome Trust, MRC, Genomics Englan

3-Hydroxyterphenyllin, a natural fungal metabolite, induces apoptosis and S phase arrest in human ovarian carcinoma cells

In the present study, we evaluated 3-Hydroxyterphenyllin (3-HT) as a potential anticancer agent using the human ovarian cancer cells A2780/CP70 and OVCAR-3, and normal human epithelial ovarian cells IOSE-364 as an in vitro model. 3-HT suppressed proliferation and caused cytotoxicity against A2780/CP70 and OVCAR-3 cells, while it exhibited lower cytotoxicity in IOSE-364 cells. Subsequently, we found that 3-HT induced S phase arrest and apoptosis in a dose-independent manner. Further investigation revealed that S phase arrest was related with DNA damage which mediated the ATM/p53/Chk2 pathway. Downregulation of cyclin D1, cyclin A2, cyclin E1, CDK2, CDK4 and Cdc25C, and the upregulation of Cdc25A and cyclin B1 led to the accumulation of cells in S phase. The apoptotic effect was confirmed by Hoechst 33342 staining, depolarization of mitochondrial membrane potential and activation of cleaved caspase-3 and PARP1. Additional results revealed both intrinsic and extrinsic apoptotic pathways were involved. The intrinsic apoptotic pathway was activated through decreasing the protein levels of Bcl2, Bcl-xL and procaspase-9 and increasing the protein level of Puma. The induction of DR5 and DR4 indicated that the extrinsic apoptotic pathway was also activated. Induction of ROS and activation of ERK were observed in ovarian cancer cells. We therefore concluded that 3-HT possessed anti-proliferative effect on A2780/CP70 and OVCAR-3 cells, induced S phase arrest and caused apoptosis. Taken together, we propose that 3-HT shows promise as a therapeutic candidate for treating ovarian cancer