High plasma uric acid concentration: causes and consequences

High plasma uric acid (UA) is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. The main causes for higher plasma UA are either lower excretion, higher synthesis or both. Higher waist circumference and the BMI are associated with higher insulin resistance and leptin production, and both reduce uric acid excretion. The synthesis of fatty acids (tryglicerides) in the liver is associated with the de novo synthesis of purine, accelerating UA production. The role played by diet on hyperuricemia has not yet been fully clarified, but high intake of fructose-rich industrialized food and high alcohol intake (particularly beer) seem to influence uricemia. It is not known whether UA would be a causal factor or an antioxidant protective response. Most authors do not consider the UA as a risk factor, but presenting antioxidant function. UA contributes to > 50% of the antioxidant capacity of the blood. There is still no consensus if UA is a protective or a risk factor, however, it seems that acute elevation is a protective factor, whereas chronic elevation a risk for disease

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

An Examination of Defendant Sex Disparity in Capital Sentencing: A Propensity Score Matching Approach

Although much prior work has examined the influence of extralegal factors on jury capital sentencing decision-making, the influence of defendant sex has been largely omitted from previous investigations. Using propensity score matching methods, the current study analyzes data from the North Carolina Capital Sentencing Project to examine whether “sex matters” in capital sentencing. Findings demonstrated that prior to matching there was a significant difference in the likelihood of receiving the death penalty for female and male defendant cases; however, after matching cases on an array of legal and extralegal case characteristics, these differences were no longer significant. Further results revealed that male defendants’ cases included different aggravating and mitigating factors than female defendants’ cases and that female defendants had limited “paths” to capital trials. Findings suggest that any apparent sex effects that are observed in capital sentencing stem from real differences in the case characteristics found in female and male defendants’ cases rather than any direct effects of defendant sex on jury decision-making. Study limitations and implications for death penalty research are also discussed

Downregulation of the Wnt inhibitor CXXC5 predicts a better prognosis in acute myeloid leukemia

The gene CXXC5 on 5q31 is frequently deleted in acute myeloid leukemia (AML) with del(5q), suggesting that inactivation of CXXC5 might play a role in leukemogenesis. Here, we investigated the functional and prognostic implications of CXXC5 expression in AML. CXXC5 mRNA was downregulated in AML with MLL rearrangements, t(8; 21) and GATA2 mutations. As a mechanism of CXXC5 inactivation, we found evidence for epigenetic silencing by promoter methylation. Patients with CXXC5 expression below the median level had a lower relapserate (45% vs59%; P = .007) and a better over all survival (OS, 46% vs28%; P<.001) and event-free survival (EFS, 36% vs 21%; P < .001) at 5 years, independent of cytogenetic risk groups and known molecular risk factors. In gene-expression profiling, lower CXXC5 expression was associated with upregulation of cell-cycling genes and codownregulation of genes implicated in leukemogenesis (WT1, GATA2, MLL, DNMT3B, RUNX1). Functional analyses demonstrated CXXC5 to inhibit leukemic cell proliferation and Wnt signaling and to affect the p53-dependent DNA damage response. In conclusion, our data suggest a tumor suppressor function of CXXC5 in AML. Inactivation of CXXC5 is associated with different leukemic pathways and defines an AML subgroup with better outcome