Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood

Venlafaxine (VEN) is an antidepressant drug mainly metabolized by the cytochrome P450 (CYP) enzyme CYP2D6 to the active metabolite O-desmethylvenlafaxine (ODV). VEN is also metabolized to N-desmetylvenlafaxine (NDV) via CYP3A4. ODV and NDV are further metabolized to N,O-didesmethylvenlafaxine (DDV). VEN is a racemic mixture of the S- and R-enantiomers and these have in vitro displayed different degrees of serotonin and noradrenaline reuptake inhibition. The aim of the study was to investigate if an enantioselective analysis of VEN and its metabolites, in combination with genotyping for CYP2D6, could assist in the interpretation of forensic toxicological results in cases with different causes of deaths. Concentrations of the enantiomers of VEN and metabolites were determined in femoral blood obtained from 56 autopsy cases with different causes of death. The drug analysis was done by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the CYP2D6 genotyping by PCR and pyrosequencing. The mean (median) enantiomeric S/R ratios of VEN, ODV, NDV and DDV were 0.99 (0.91), 2.17 (0.93), 0.92 (0.86) and 1.08 (1.03), respectively. However, a substantial variation in the relationship between the S- and R-enantiomers of VEN and metabolites was evident (S/R ratios ranging from 0.23 to 17.6). In six cases, a low S/R VEN ratio (mean 0.5) was associated with a high S/R ODV ratio (mean 11.9). Genotyping showed that these individuals carried two inactive CYP2D6 genes indicating a poor metabolizer phenotype. From these data we conclude that enantioselective analysis of VEN and ODV can predict if a person is a poor metabolizer genotype/phenotype for CYP2D6. Knowledge of the relationship between the S- and R-enantiomers of this antidepressant drug and its active metabolite is also important since the enantiomers display different pharmacodynamic profiles.     

Family Closeness and Domestic Abuse Among Caribbean and South American Women in South Florida

This paper focuses on the importance of family member closeness as a protective factor against domestic abuse. We explore the link between long-lasting relations within the family and intra-familial violence perpetrated against women in Latino households in South Florida. We use data from an Inter-generational Transmission of Drug Use between Latina Mothers and Daughters (ITDMD) study. The study includes data on family relations and domestic abuse. We estimate a series of multivariate regressions to obtain the probability of abuse against women, the types of abuse inflicted and the relationship with the abusers. Our results indicate that among abused women, the effects of long-lasting relations within the family differ depending on the type of relationship between the abuser and the victim and the degree of closeness the victim feels towards other family members. Given these findings, there is a need to further study family relations and abuse in Latino households.     

An unusual case of high-voltage electrocution of a truck driver due to inadvertent contact of the truck with an overhead wire

Electrocution deaths are mostly accidental. However, reconstruction of events in unusual electrocution death is challenging. This article reports an accidental death due to electrocution in a highly unusual circumstance, in which a truck driver reversing his vehicle was electrocuted when his truck inadvertently touched an overhead high-voltage wire. The electric injury marks were present over the sole of the right foot. The scene investigation revealed that the high-voltage wire was loose and was below the level of the prescribed height. The truck was passing over an elevated area made up of dirt and stone. The interior of the cabin of the truck revealed a few non-insulated metallic areas over the floor of the truck, between the accelerator and the brake, which were attributed as the sources of entry of electricity into the body. The electric injury marks were different than those usually seen in high-voltage electrocution as there was an intermediate object (truck) involved, and the contact period between the truck and the electric wire was minimal. This fatality was attributed to the non-proper insulation of the interior of the truck, the negligent driving of the truck driver over the elevated surface, and the loose high-voltage wire without proper maintenance.     

The role of caste in the implementation of herbal gardens in Bangalore

Over the past few decades home garden research has emphasised the promotion of home gardening for nutritional and other welfare benefits for the poor in urban areas. Still, the urban communities who cultivate plants in their home gardens are in general represented as rather uniform groups, and no distinction is made in terms of caste, ethnic groups, or social class. This article asserts that social stratification represents an important aspect that needs to be taken into account while devising educational programmes and community projects for the promotion of home herbal gardens in urban areas.     

Trigemino‐Cardiac Reflex as Lethal Mechanism in a Suicidal Fire Death Case

In the vast majority of immediate fire deaths, the mechanism of death is inhalation of toxic gases (especially carbon monoxide), direct thermal injury, or neurogenic shock due to the redistribution of the body's blood volume produced by surface heat on the skin. We present a suicidal case that is unusual because the mechanism of immediate fire death could arguably be explained in terms of a primitive autonomic reflex/the trigemino‐cardiac reflex. Although this reflex is well known to surgeons and anesthetists, with possible lethal consequences in the course of invasive surgical procedures on the head and neck region, it is much less familiar to forensic pathologists.     

Personality Traits are Related to Intimate Partner Violence Among Securely Attached Individuals

The general assumption has been that male batterers from clinical samples were mostly insecurely attached as compared to non-batterers. Recently, a large group was found (39.4 % of batterers in a clinical sample) whose main attachment style was secure. No previous studies have examined specifically the securely attached batterer. The aim of the present study was to test whether antisocial personality disorder (ASPD) and narcissistic personality disorder (NPD), but not borderline personality disorder (BPD), traits may be related to battering among securely attached individuals. Twenty-seven securely attached batterers, 45 insecurely attached batterers, 40 securely attached controls, and 22 insecurely attached controls who lived in the Netherlands, filled in self-report measures of personality disorder traits (i.e., antisocial, narcissism, borderline) and attachment (i.e., avoidant and anxious). Results showed that ASPD traits explained 19 % of the variance of battering in securely attached individuals. NPD and BPD traits are related to battering among securely attached individuals when NPD and BPD traits were entered alone in the equation.     

The EU approach to net neutrality: Network operators and over-the-top players,friends or foes?

This paper will mainly focus on the EU approach to net neutrality, notably the adequacy of existing and future EU rules to tackle the issue and the ongoing policy debate. It will also consider whether the market has effectively worked around the regulatory lacunae by looking into the relationships between the telecoms industry, as a regulated sector, and the over-the-top (OTT) players. In this regard, it will explore to what extent there is a real battle between telcos and OTTs or if both parties are already finding their own ways to overcome their (apparent) disputes.     

Right-wing Euroscepticism and populism: investigating the concept of ‘the people’

ABSTRACT

Right-wing Eurosceptic political groups gained ground in the elections for the European Parliament in May 2014. The electoral victory of right-wing Euroscepticism was accompanied by a concern that populism is (once again) spreading in Europe. Associating right-wing Eurosceptics with populism raises the question of whether critiques of populism can be directly extended to right-wing Euroscepticism. By reconstructing the right-wing Eurosceptic concept of ‘the people,’ this article demonstrates that the Eurosceptic concept of the people has a dual meaning that encompasses both a transnational and a national concept of the people. The article concludes that while Euroscepticism shares ideological features with populism, it is problematic, due to the internal structure of the promoted concept of the people and the European political environment, directly to extend recent critiques of populism to right-wing Euroscepticism.