The dangers of using diagnoses outside of established psychiatric nosology in the courtroom: Analysis and discussion of current Swiss legal precedent from a medical perspective.

Akin to many jurisdictions, Switzerland has a dual system of sanctions comprising sentences and measures. To order a therapeutic measure per Article 59 or 63 of the Swiss Criminal Code, the presence of a "severe mental disorder" must be determined. Before the new legal precedent, this required a medical diagnosis according to recognised classification systems like the ICD or DSM. The court then decided if a disorder was "severe" in the legal sense, thereby requiring such a therapeutic measure. However, in two 2019 rulings, the Swiss Federal Supreme Court concluded that a severe mental disorder could legally exist without a diagnosis according to the ICD or DSM, if it is based on offence- and risk-relevant personality-related factors amenable to risk-reducing therapy. We examine the details and context of the rulings, alongside their wider dangers. Specifically, we outline how undue influence could be exerted by non-ICD/DSM diagnostic systems, which were developed within individual theoretical schools of thought and lack empirical validation, like in these two court cases. Such non-manual diagnoses could make the presence of a severe mental disorder dependent upon whether an expert witness employs a particular diagnostic system, which would undermine principles of legality. Moreover, the Court's requirement that the disorder is based on personality-related risk factors amenable to risk-reducing therapy is problematic because research has highlighted the low effectiveness of treatment provided independently of a psychiatric disorder. Finally, broadening entry criteria may increase the number of offenders who require psychiatric treatment, thus endangering the quality of care for those with ICD/DSM-based diagnoses that are known to respond well to treatment (e.g. schizophrenia). In short, fulfilling the Court's request that any non-manual diagnoses are based on personality-related risk factors that are amenable to risk-reducing therapy is not possible for such non-manual diagnoses. Using unvalidated diagnoses could also render the system susceptible to ethical issues and hypothetical misuse, which may adversely affect society's most vulnerable people. To counter these dangers, we suggest that in order to be admissible in court, any diagnostic system must mandatorily fulfil sufficient scientific standards.

The Human Milk Oligosaccharide 2'-Fucosyllactose Alleviates Liver Steatosis, ER Stress and Insulin Resistance by Reducing Hepatic Diacylglycerols and Improved Gut Permeability in Obese Ldlr-/-.Leiden Mice.

Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disorder that is associated with gut dysbiosis, enhanced gut permeability, adiposity and insulin resistance. Prebiotics such as human milk oligosaccharide 2'-fucosyllactose are thought to primarily improve gut health and it is uncertain whether they would affect more distant organs. This study investigates whether 2'-fucosyllactose can alleviate NAFLD development in manifest obesity. Obese hyperinsulinemic Ldlr-/-.Leiden mice, after an 8 week run-in on a high-fat diet (HFD), were treated with 2'-fucosyllactose by oral gavage until week 28 and compared to HFD-vehicle controls. 2'-fucosyllactose did not affect food intake, body weight, total fat mass or plasma lipids. 2'-fucosyllactose altered the fecal microbiota composition which was paralleled by a suppression of HFD-induced gut permeability at t = 12 weeks. 2'-fucosyllactose significantly attenuated the development of NAFLD by reducing microvesicular steatosis. These hepatoprotective effects were supported by upstream regulator analyses showing that 2'-fucosyllactose activated ACOX1 (involved in lipid catabolism), while deactivating SREBF1 (involved in lipogenesis). Furthermore, 2'-fucosyllactose suppressed ATF4, ATF6, ERN1, and NUPR1 all of which participate in endoplasmic reticulum stress. 2'-fucosyllactose reduced fasting insulin concentrations and HOMA-IR, which was corroborated by decreased intrahepatic diacylglycerols. In conclusion, long-term supplementation with 2'-fucosyllactose can counteract the detrimental effects of HFD on gut dysbiosis and gut permeability and attenuates the development of liver steatosis. The observed reduction in intrahepatic diacylglycerols provides a mechanistic rationale for the improvement of hyperinsulinemia and supports the use of 2'-fucosyllactose to correct dysmetabolism and insulin resistance.

A Randomized, Placebo-Controlled, Double-Blind Crossover Study to Assess a Unique Phytosterol Ester Formulation in Lowering LDL Cholesterol Utilizing a Novel Virtual Tracking Tool.

Elevated blood concentration of low-density lipoprotein cholesterol (LDLc) is a primary risk factor for developing cardiovascular disease. Lifestyle interventions including an increase in dietary phytosterols as well as medications have proven effective in lowering LDLc. The primary objective of this randomized, placebo controlled, double blind, crossover study was to determine the impact of a new phytosterol emulsion for dietary supplements (1.5 g/day phytosterol equivalents) on LDLc concentrations. Thirty-two healthy adults were randomly assigned to receive placebo or treatment followed by a washout period, followed by placebo or treatment, each phase lasting one month. Secondary endpoints related to cardiovascular health were also assessed. Study management, including screening, recruitment, monitoring, compliance, and data collection, were done remotely (a siteless clinical trial) utilizing a novel virtual tool. Phytosterol supplementation significantly lowered LDLc concentrations by 10.2% (16.17 mg/dL or 0.419 mmol/L, p = 0.008 by paired t-test, p = 0.014 by Wilcoxon signed rank testing). No secondary biomarkers were found to change significantly. Supplementation with phytosterols in a new dietary supplement formulation efficiently and safely decreases LDLc within one month in a free-living setting.