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This article examines legal and social discourses surrounding the phenomenon of child pornography, considering the legal responses to child pornography (particularly when an individual is found to be in possession of such material), and the way in which such material, the child, and the possessor of child pornography are socially constructed. The article raises the question of whether there has been a moral panic regarding child pornography and the possession of such material, but also considers whether there are real reasons to consider that the possession of child pornography should remain illegal. Research studies which aim to establish the existence of a causal link between possessing child pornography and the act of committing child sexual abuse are examined, as is the argument that criminalizing the possession of child pornography reduces the market for such material. Finally, there is an analysis of the possible impact of social constructions of the child as innocent. [ABSTRACT FROM AUTHOR]

Since the Monkeypox virus outbreak erupted in May 2022, infection has been reported across all ages. Few cases exist in the medical literature about Monkeypox infection in neonates, and little is known about its clinical manifestations, disease course, or side effects of available antiviral agents in this age group. In this report, we describe the case of a 10-day-old neonate from the southern United States who presented with fevers and generalized papulopustular rash. She was treated empirically as a febrile neonate but mpox infection was suspected early because of the characteristic exanthem and its similarity to her mother's rash that she had developed a few days before the patient's presentation. Oral tecovirimat was initiated on the third day of admission and mpox was later confirmed by polymerase chain reaction analysis. The patient tolerated oral tecovirimat well and experienced a favorable outcome without lasting effects of infection., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: SJ733, a newly developed inhibitor of P. falciparum ATP4, has a favorable safety profile and rapid antiparasitic effect but insufficient duration to deliver a single-dose cure of malaria. We investigated the safety, tolerability, and pharmacokinetics of a multidose SJ733 regimen and a single-dose pharmacoboost approach using cobicistat to inhibit CYP3A4, thereby increasing exposure., Methods: Two multidose unboosted cohorts (n = 9) (SJ733, 300 mg and 600 mg daily for 3 days) followed by three single-dose boosted cohorts combining SJ733 (n = 18) (75-, 300-, or 600-mg single dose) with cobicistat (150-mg single dose) as a pharmacokinetic booster were evaluated in healthy volunteers (ClinicalTrials.gov: NCT02661373)., Findings: All participants tolerated SJ733 well, with no serious adverse events (AEs), dose-limiting toxicity, or clinically significant electrocardiogram or laboratory test findings. All reported AEs were Grade 1, clinically insignificant, and considered unlikely or unrelated to SJ733. Compared to unboosted cohorts, the SJ733/cobicistat-boosted cohorts showed a median increase in area under the curve and maximum concentration of 3·9 × and 2·6 ×, respectively, and a median decrease in the ratio of the major CYP3A-produced metabolite SJ506 to parent drug of 4·6 × . Incorporating these data in a model of parasite dynamics indicated that a 3-day regimen of SJ733/cobicistat (600 mg/150 mg daily) relative to a single 600-mg dose ± cobicistat would increase parasite clearance from 10 6 to 10 12 parasites/µL., Interpretation: The multidose and pharmacoboosted approaches to delivering SJ733 were well-tolerated and significantly increased drug exposure and prediction of cure. This study supports the further development of SJ733 and demonstrates an innovative pharmacoboost approach for an antimalarial., Funding: Global Health Innovative Technology Fund, Medicines for Malaria Venture, National Institutes of Health, and American Lebanese Syrian Associated Charities., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: (+)-SJ000557733 (SJ733) is a novel, orally bioavailable inhibitor of Plasmodium falciparum ATP4. In this first-in-human and induced blood-stage malaria phase 1a/b trial, we investigated the safety, tolerability, pharmacokinetics, and antimalarial activity of SJ733 in humans., Methods: The phase 1a was a single-centre, dose-escalation, first-in-human study of SJ733 allowing modifications to dose increments and dose-cohort size on the basis of safety and pharmacokinetic results. The phase 1a took place at St Jude Children's Research Hospital and at the University of Tennessee Clinical Research Center (Memphis, TN, USA). Enrolment in more than one non-consecutive dose cohort was allowed with at least 14 days required between doses. Participants were fasted in seven dose cohorts and fed in one 600 mg dose cohort. Single ascending doses of SJ733 (75, 150, 300, 600, 900, or 1200 mg) were administered to participants, who were followed up for 14 days after SJ733 dosing. Phase 1a primary endpoints were safety, tolerability, and pharmacokinetics of SJ733, and identification of an SJ733 dose to test in the induced blood-stage malaria model. The phase 1b was a single-centre, open-label, volunteer infection study using the induced blood-stage malaria model in which fasted participants were intravenously infected with blood-stage P falciparum and subsequently treated with a single dose of SJ733. Phase 1b took place at Q-Pharm (Herston, QLD, Australia) and was initiated only after phase 1a showed that exposure exceeding the threshold minimum exposure could be safely achieved in humans. Participants were inoculated on day 0 with P falciparum-infected human erythrocytes (around 2800 parasites in the 150 mg dose cohort and around 2300 parasites in the 600 mg dose cohort), and parasitaemia was monitored before malaria inoculation, after inoculation, immediately before SJ733 dosing, and then post-dose. Participants were treated with SJ733 within 24 h of reaching 5000 parasites per mL or at a clinical score higher than 6. Phase 1b primary endpoints were calculation of a parasite reduction ratio (PRR 48 ) and parasite clearance half-life, and safety and tolerability of SJ733 (incidence, severity, and drug-relatedness of adverse events). In both phases of the trial, SJ733 hydrochloride salt was formulated as a powder blend in capsules containing 75 mg or 300 mg for oral administration. Healthy men and women (of non-childbearing potential) aged 18-55 years were eligible for both studies. Both studies are registered with ClinicalTrials.gov (NCT02661373 for the phase 1a and NCT02867059 for the phase 1b)., Findings: In the phase 1a, 23 healthy participants were enrolled and received one to three non-consecutive doses of SJ733 between March 14 and Dec 7, 2016. SJ733 was safe and well tolerated at all doses and in fasted and fed conditions. 119 adverse events were recorded: 54 (45%) were unrelated, 63 (53%) unlikely to be related, and two (2%) possibly related to SJ733. In the phase 1b, 17 malaria-naive, healthy participants were enrolled. Seven participants in the 150 mg dose cohort were inoculated and dosed with SJ733. Eight participants in the 600 mg dose cohort were inoculated, but two participants could not be dosed with SJ733. Two additional participants were subsequently inoculated and dosed with SJ733. SJ733 exposure increased proportional to the dose through to the 600 mg dose, then was saturable at higher doses. Fasted participants receiving 600 mg exceeded the target area under the concentration curve extrapolated to infinity (AUC 0-∞ ) of 13 000 μg × h/L (median AUC 0-∞ 24 283 [IQR 16 135-31 311] μg × h/L, median terminal half-life 17·4 h [IQR 16·1-24·0], and median timepoint at which peak plasma concentration is reached 1·0 h [0·6-1·3]), and this dose was tested in the phase 1b. All 15 participants dosed with SJ733 had at least one adverse event. Of the 172 adverse events recorded, 128 (74%) were mild. The only adverse event attributed to SJ733 was mild bilateral foot paraesthesia that lasted 3·75 h and resolved spontaneously. The most common adverse events were related to malaria. Based on parasite clearance half-life, the derived log 10 PRR 48 and corresponding parasite clearance half-lives were 2·2 (95% CI 2·0-2·5) and 6·47 h (95% CI 5·88-7·18) for 150 mg, and 4·1 (3·7-4·4) and 3·56 h (3·29-3·88) for 600 mg., Interpretation: The favourable pharmacokinetic, tolerability, and safety profile of SJ733, and rapid antiparasitic effect support its development as a fast-acting component of combination antimalarial therapy., Funding: Global Health Innovative Technology Fund, Medicines for Malaria Venture, and the American Lebanese Syrian Associated Charities., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Clostridium difficile induces antibiotic-associated diarrhea due to the release of toxin A (TcdA) and toxin B (TcdB), the latter being its main virulence factor. The epidemic strain NAP1/027 has an increased virulence attributed to different factors. We compared cellular intoxication by TcdB NAP1 with that by the reference strain VPI 10463 (TcdB VPI ). In a mouse ligated intestinal loop model, TcdB NAP1 induced higher neutrophil recruitment, cytokine release, and epithelial damage than TcdB VPI . Both toxins modified the same panel of small GTPases and exhibited similar in vitro autoprocessing kinetics. On the basis of sequence variations in the frizzled-binding domain (FBD), we reasoned that TcdB VPI and TcdB NAP1 might have different receptor specificities. To test this possibility, we used a TcdB from a NAP1 variant strain (TcdB NAP1v ) unable to glucosylate RhoA but with the same receptor-binding domains as TcdB NAP1 . Cells were preincubated with TcdB NAP1v to block cellular receptors, prior to intoxication with either TcdB VPI or TcdB NAP1 . Preincubation with TcdB NAP1v blocked RhoA glucosylation by TcdB NAP1 but not by TcdB VPI , indicating that the toxins use different host factors for cell entry. This crucial difference might explain the increased biological activity of TcdB NAP1 in the intestine, representing a contributing factor for the increased virulence of the NAP1/027 strain.

In the wake of two recent high-profile, controversial cases involving the prosecution and conviction of Drs Bramhall and Bawa-Garba, this article considers when it is socially desirable to criminalise doctors' behaviour, exploring how the matters of harm, public wrongs and the public interest can play out to justify-or not, as the case may be-the criminal law's intervention. Dr Bramhall branded his initials on patients' livers during transplant surgery, behaviour acknowledged not to have caused his patients any harm by way of injury to their organs. Dr Bawa-Garba misdiagnosed and failed to properly assess a 6-year-old boy with pneumonia and sepsis under her care, who subsequently died. Taking account of contextual and public interest concerns, can and should there be exceptions to imposing criminal liability where a doctor's behaviour is deemed grossly negligent and a significant contribution to a patient's death? And is it really appropriate to subject a doctor to penal sanction where he may have committed a private wrong against a patient, but does not set back their interests?, Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

John Kenyon Mason (19 December 1919-26 January 2017), CBE, MD, LLD, FRCPath, DMJ, FRCPE, FRSE, and known as Ken Mason to us all, was Regius Professor of Forensic Medicine at the University of Edinburgh from 1973-1985 and thereafter Emeritus Professor of Forensic Medicine and Honorary Fellow in the School of Law at the University of Edinburgh. A formal obituary to Professor Mason is published in the Scotsman (http://www.scotsman.com/news/obituaries/obituary-professor-ken-mason-medical-jurisprudence-pioneer-1-4357181). We offer some personal tributes to our friend and colleague., (© The Author 2017. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In this article, I argue that sexual exploitation in the doctor-patient relationship would be dealt with more appropriately by the law in England and Wales on the basis of a breach of fiduciary duty. Three different types of sexual boundary breaches are discussed, and the particular focus is on breaches where the patient's consent is obtained through inducement. I contend that current avenues of redress do not clearly catch this behaviour and, moreover, they fail to capture the essence of the wrong committed by the doctor-the knowing breach of trust for self-gain-and the calculated way in which consent is induced. Finally, I demonstrate that the fiduciary approach is compatible with the contemporary pro-patient autonomy model of the doctor-patient relationship., (© The Author 2016. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Two matters that have a significant presence in the contemporary Dutch assisted dying debate, are the nature of the suffering required for an assisted death to be lawful, and the issue of who can lawfully assist. This article explores whether the lawful medical assisted dying model is too restrictive in failing to recognise existential suffering, considering selected case studies involving such suffering and lay assisted death. It addresses the question whether The Netherlands would take a trip down a slippery slope if the lawful model of assisted death were extended to cases where individuals are 'tired of life'.

This article reviews newly declassified US intelligence files and other sources, including relevant trial documents, related to the Nazi killing of mentally and physically sick individuals deemed to be of little further use to society. It both supplements and revises existing work on the so-called 'Euthanasia' programme at the Kaufbeuren psychiatric institution in Bavaria, and highlights a series of gender issues related to the involvement of women nurses including Catholic nuns, in this institute. In addition, this study not only casts new light on the way in which patients were, from admission onwards, redefined as disposable objects but also emphasises contradictions within the defence case of the defendants.