Statement on Virginity Testing: Independent Forensic Expert Group

Virginity examinations are practiced in many countries, and often forcibly, in a number of contexts, including in detention places; on women who allege rape; on women who are accused by authorities of prostitution; and as part of public or social policies to control sexuality. In other states, the practice is illegal. The purpose of this medico-legal statement is to provide legal experts, adjudicators, healthcare professionals, and policymakers, among others, with an understanding of the physical and psychological effects of forcibly conducting virginity examinations on females and to assess whether, based on these effects, forcibly conducted virginity examinations constitute cruel, inhuman, or degrading treatment or torture. This medico-legal statement also addresses the medical interpretation and relevance of such examinations and the ethical implications. This opinion considers an examination to be ‘forcibly conducted’ when it is “committed by force, or by threat of force or coercion, such as caused by fear of violence, duress, detention, psychological oppression or abuse of power, against such person incapable of giving genuine consent.”   For full details about the Independent Forensic Expert Group please visit http://www.irct.org/our-support/ medical-and-psychological-case-support/forensic-expertgroup.aspx

Anal Examinations in Cases of Alleged Homosexuality

Anal examinations are forcibly conducted in many countries where consensual anal intercourse is considered a criminal act. They are conducted almost exclusively on males in an effort to “prove” that they are “homosexuals” despite the fact that anal intercourse is not a necessary determinant of “homosexual activity.” Forcibly conducted anal examinations are usually initiated at the request of law enforcement officials, the prosecutor, or the court and conducted in the absence of informed consent or in circumstances where individuals are not capable of giving genuine informed consent or where refusal to give consent would be interpreted as self-incrimination. This may be presumed to be the case when examinations are conducted on individuals in detention, subsequent to allegations of criminalised sexual acts by the authorities. The purpose of this medico-legal statement is to provide legal experts, adjudicators, health care professionals, and policymakers, among others, with an understanding of: 1) the validity of forcibly conducted anal examinations as medical and scientific evidence of consensual anal intercourse; 2) the likely physical and psychological consequences of forcibly conducted anal examinations; and 3) whether, based on these effects, forcibly conducted anal examination constitutes cruel, inhuman, or degrading treatment or torture

Cardiomyocyte BRAF and type 1 RAF inhibitors promote cardiomyocyte and cardiac hypertrophy in mice in vivo

The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade promotes cardiomyocyte hypertrophy and is cardioprotective, with the three RAF kinases forming a node for signal integration. Our aims were to determine if BRAF is relevant for human heart failure, whether BRAF promotes cardiomyocyte hypertrophy, and if Type 1 RAF inhibitors developed for cancer (that paradoxically activate ERK1/2 at low concentrations: the “RAF paradox”) may have the same effect. BRAF was upregulated in heart samples from patients with heart failure compared with normal controls. We assessed the effects of activated BRAF in the heart using mice with tamoxifen-activated Cre for cardiomyocyte-specific knock-in of the activating V600E mutation into the endogenous gene. We used echocardiography to measure cardiac dimensions/function. Cardiomyocyte BRAFV600E induced cardiac hypertrophy within 10 d, resulting in increased ejection fraction and fractional shortening over 6 weeks. This was associated with increased cardiomyocyte size without significant fibrosis, consistent with compensated hypertrophy. The experimental Type 1 RAF inhibitor, SB590885, and/or encorafenib (a RAF inhibitor used clinically) increased ERK1/2 phosphorylation in cardiomyocytes, and promoted hypertrophy, consistent with a “RAF paradox” effect. Both promoted cardiac hypertrophy in mouse hearts in vivo, with increased cardiomyocyte size and no overt fibrosis. In conclusion, BRAF potentially plays an important role in human failing hearts, activation of BRAF is sufficient to induce hypertrophy, and Type 1 RAF inhibitors promote hypertrophy via the “RAF paradox”. Cardiac hypertrophy resulting from these interventions was not associated with pathological features, suggesting that Type 1 RAF inhibitors may be useful to boost cardiomyocyte function

Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop

In 1993, Przyklenk and colleagues made the intriguing experimental observation that 'brief ischemia in one vascular bed also protects remote, virgin myocardium from subsequent sustained coronary artery occlusion' and that this effect '.... may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion'. This seminal study laid the foundation for the discovery of 'remote ischemic conditioning' (RIC), a phenomenon in which the heart is protected from the detrimental effects of acute ischemia/reperfusion injury (IRI), by applying cycles of brief ischemia and reperfusion to an organ or tissue remote from the heart. The concept of RIC quickly evolved to extend beyond the heart, encompassing inter-organ protection against acute IRI. The crucial discovery that the protective RIC stimulus could be applied non-invasively, by simply inflating and deflating a blood pressure cuff placed on the upper arm to induce cycles of brief ischemia and reperfusion, has facilitated the translation of RIC into the clinical setting. Despite intensive investigation over the last 20 years, the underlying mechanisms continue to elude researchers. In the 8th Biennial Hatter Cardiovascular Institute Workshop, recent developments in the field of RIC were discussed with a focus on new insights into the underlying mechanisms, the diversity of non-cardiac protection, new clinical applications, and large outcome studies. The scientific advances made in this field of research highlight the journey that RIC has made from being an intriguing experimental observation to a clinical application with patient benefit

Remote Ischaemic Conditioning and its Effect on Maladaptive Cardiac Remodelling Following Myocardial Infarction

Remote ischaemic conditioning (rIC) has shown benefit in protecting the myocardium from ischemia/reperfusion injury. However it’s potential to attenuate maladaptive remodelling post myocardial infarction (MI) associated with the development of heart failure is less well investigated. Using cellular models of endothelin-1 (ET-1) driven hypertrophy and fibrosis, we investigated the role that serum taken from healthy volunteers undergoing rIC (rICserum) had on various markers of both hypertrophy and fibrosis as well as attempting to elucidate some of the mechanisms involved. Furthermore we established a clinical trial to assess the degree to which repeated rIC post-MI can positively influence heart failure outcomes. Hypertrophy was assessed by measuring H9c2 cardiomyoblast cell size using immunofluorescence, protein to DNA ratio and by abrogation of the expression of the pro-hypertrophic foetal genes BNP, βMHC, α-ACT and MS-1. This anti-hypertrophic mechanism was shown include the activation of the PKCε/AMPKα/eNOS/cGMP pathway and up-regulation of the anti-hypertrophic microRNAs miR-1 and miR-133. RIC-serum was also shown to attenuate ET-1 induced markers of fibrosis including differentiation of fibroblasts to pathological myofibroblasts and proliferation of fibroblasts in a neonatal rat cardiac fibroblast model. Both unconditioned serum and rICserum attenuated ET-1 induced expression of α-SMA and increased the expression of MMP-2 and TIMP-1 but neither had any effect on ET-1 induced MMP-9. Unconditioned serum also proved to have weak anti-hypertrophic properties which were greatly augmented by rIC. Increasing age diminished the innate protection afforded by unconditioned-serum and individuals with high levels of physical activity displayed higher levels of innate protection from hypertrophy akin to rIC. Finally we describe the design and management of the DREAM study (Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction), a phase 2 randomised control trial established to evaluate the role of repeated rIC post-MI in modulating maladaptive cardiac remodelling with the presentation of some preliminary secondary outcome data

The usefulness of cadaveric fungi as an investigation tool

In forensic pathology, it is common practice to date the postmortem interval (PMI) only as an approximation. Interval estimation is based on cadaveric phenomena, which are very dynamic and at the same difficult to quantify and reproduce experimentally, that is, cooling, hypostasis, rigor mortis, and postmortem changes. The important role that the chronology after death plays in order to assess the time of death and the continuous lack of objective evidence for this assessment prompted the interest of numerous scholars to study this subject in depth. Nevertheless, one of the possible contributions to establish the PMI might be provided by mycology