Ecstasy, molly, MDMA: What health practitioners need to know about this common recreational drug.

3,4-methylenedioxymethamphetamine (MDMA; commonly referred to as "ecstasy" or "molly") is a substituted amphetamine drug that is used recreationally for its acute psychoactive effects, including euphoria and increased energy, as well as prosocial effects such as increased empathy and feelings of closeness with others. Acute adverse effects can include hyperthermia, dehydration, bruxism, and diaphoresis. Post-intoxication phenomena may include insomnia, anhedonia, anxiety, depression, and memory impairment, which can persist for days following drug cessation.

Ambitions and realities: Are Global Fund investments designed to achieve resilient and sustainable systems for health? Findings from the Global Fund Prospective Country Evaluation.

Strengthening resilient and sustainable systems for health (RSSH) is central to the Global Fund's strategy, however questions persist about the Global Fund's role in the health systems strengthening space, and the extent to which investments are designed to achieve strengthening objectives, or just fill in gaps in the system. This paper reports on findings from the Prospective Country Evaluations (PCE), a multi-country multi-year evaluation of Global Fund support. We adapted a framework from Chee et al.

Clinical outcomes of adjuvant nivolumab in resected stage III melanoma: comparison of CheckMate 238 trial and real-world data.

Objectives: Nivolumab is approved as adjuvant therapy for resected stage III/IV melanoma based on the phase 3 CheckMate 238 trial. This analysis compared outcomes from CheckMate 238 with those from the real-world Flatiron Health electronic health record-derived de-identified database in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab.

Materials: Outcomes included baseline characteristics, overall survival (OS) in the CheckMate 238 cohort (randomization until death or last known alive), and real-world overall survival (rwOS) in the Flatiron Health cohort (nivolumab initiation until death or data cutoff).

Identifying and avoiding radiation damage in macromolecular crystallography.

Radiation damage remains one of the major impediments to accurate structure solution in macromolecular crystallography. The artefacts of radiation damage can manifest as structural changes that result in incorrect biological interpretations being drawn from a model, they can reduce the resolution to which data can be collected and they can even prevent structure solution entirely. In this article, we discuss how to identify and mitigate against the effects of radiation damage at each stage in the macromolecular crystal structure-solution pipeline.

Assessment of changes in blood volume during lower body negative pressure-induced hypovolemia using bioelectrical impedance analysis.

Background: Lower body negative Pressure (LBNP)-induced hypovolemia is simulating acute hemorrhage by sequestrating blood into lower extremities. Bioelectrical Impedance Analysis (BIA) is based on the electrical properties of biological tissues, as electrical current flows along highly conductive body tissues (such as blood). Changes in blood volume will lead to changes in bioimpedance.

Signal quality assessment of peripheral venous pressure.

Develop a signal quality index (SQI) for the widely available peripheral venous pressure waveform (PVP). We focus on the quality of the cardiac component in PVP. We model PVP by the adaptive non-harmonic model.

Early implementation learnings on acceptability and feasibility of "V": a multi-level PrEP intervention designed with and for adolescent girls and young women in Zimbabwe.

Introduction: Adolescent girls and young women (AGYW) remain disproportionately affected by HIV in Zimbabwe. Several HIV prevention options are available, including oral tenofovir-based pre-exposure prophylaxis (PrEP), however AGYW face unique barriers to PrEP uptake and continuation and novel approaches are therefore needed to empower AGYW to use PrEP. The objective of this study was to characterize early learnings from implementing a multi-level intervention consisting of fashionable branding (including a "V Starter Kit"), service integration, and peer education and support throughout a young woman's journey using oral PrEP across four phases of implementation, from creating demand, preparing for PrEP, initiation of PrEP, and adherence to PrEP.

Improving pulse oximetry accuracy in dark-skinned patients: technical aspects and current regulations.

Recent concerns regarding the clinical accuracy of pulse oximetry in dark-skinned patients, specifically in detecting occult hypoxaemia, have motivated research on this topic and recently reported in this journal. We provide an overview of the technical aspects of the issue, the sources of inaccuracy, and the current regulations and limitations. These insights offer perspectives on how pulse oximetry can be improved to address these potential limitations.

The CCP4 suite: integrative software for macromolecular crystallography.

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces.

Clinical characteristics and management of patients with nonalcoholic steatohepatitis in a real-world setting: analysis of the Ipsos NASH therapy monitor database.

Background: Nonalcoholic steatohepatitis (NASH) is the more severe, inflammatory type of nonalcoholic fatty liver disease (NAFLD). NASH, a leading indication for liver transplantation, is growing in prevalence. The extent of liver fibrosis, ranging from fibrosis stage (FS) of none (F0) to cirrhosis (F4), is a strong predictor of health outcomes.

Using the ear photoplethysmographic waveform as an early indicator of central hypovolemia in healthy volunteers utilizing LBNP induced hypovolemia model.

. To study the photoplethysmographic (PPG) waveforms of different locations (ear and finger) during lower body negative pressure (LBNP) induced hypovolemia. Then, to determine whether the PPG waveform can be used to detect hypovolemia during the early stage of LBNP.

Evaluation and deployment of isotype-specific salivary antibody assays for detecting previous SARS-CoV-2 infection in children and adults.

Background: Saliva is easily obtainable non-invasively and potentially suitable for detecting both current and previous SARS-CoV-2 infection, but there is limited evidence on the utility of salivary antibody testing for community surveillance.

Methods: We established 6 ELISAs detecting IgA and IgG antibodies to whole SARS-CoV-2 spike protein, to its receptor binding domain region and to nucleocapsid protein in saliva. We evaluated diagnostic performance, and using paired saliva and serum samples, correlated mucosal and systemic antibody responses.

Differential sensing with arrays of de novo designed peptide assemblies.

Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing.

Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2.

Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269).

Student reflections on an interdisciplinary pandemics course utilising systems thinking.

Issue Addressed: The complexity and uncertainty of the COVID-19 pandemic highlights the need to change training of public health professionals in higher education by shifting from siloed specialisations to interdisciplinary collaboration. At the end of 2020 and 2021, public health professionals collaboratively designed and delivered, a week-long intensive course-Public Health in Pandemics. The aim of this research study was to understand whether the use of systems thinking in the design and delivery of the course enabled students to grasp the interdisciplinary nature of contemporary health promotion and public health practice.

Amplitude and phase measurements from harmonic analysis may lead to new physiologic insights: lower body negative pressure photoplethysmographic waveforms as an example.

The photoplethysmographic (PPG) waveform contains hemodynamic information in its oscillations. We provide a new method for quantitative study of the waveform morphology and its relationship to the hemodynamics. A data adaptive modeling of the waveform shape is used to describe the PPG waveforms recorded from ear and finger.

Inaccuracy of pulse oximetry with dark skin pigmentation: clinical implications and need for improvement.

Recent reports highlight potential inaccuracies of pulse oximetry in patients with various degrees of skin pigmentation. We summarise the literature, provide an overview of potential clinical implications, and provide insights into how pulse oximetry could be improved to mitigate against such potential shortcomings.

Quantifying and comparing radiation damage in the Protein Data Bank.

Radiation damage remains one of the major bottlenecks to accurate structure solution in protein crystallography. It can induce structural and chemical changes in protein crystals, and is hence an important consideration when assessing the quality and biological veracity of crystal structures in repositories like the Protein Data Bank (PDB). However, detection of radiation damage artefacts has traditionally proved very challenging.

Coiled coils 9-to-5: rational design of α-helical barrels with tunable oligomeric states.

The rational design of linear peptides that assemble controllably and predictably in water is challenging. Short sequences must encode unique target structures and avoid alternative states. However, the non-covalent forces that stabilize and discriminate between states are weak.

Tribute to Dr. Takuo Aoyagi, inventor of pulse oximetry.

Introduction: Dr. Takuo Aoyagi invented pulse oximetry in 1974. Pulse oximeters are widely used worldwide, most recently making headlines during the COVID-19 pandemic.

Structural resolution of switchable states of a de novo peptide assembly.

De novo protein design is advancing rapidly. However, most designs are for single states. Here we report a de novo designed peptide that forms multiple α-helical-bundle states that are accessible and interconvertible under the same conditions.

Lessons Learned From Implementing Prospective, Multicountry Mixed-Methods Evaluations for Gavi and the Global Fund.

Introduction: As global health programs have become increasingly complex, corresponding evaluations must be designed to assess the full complexity of these programs. Gavi and the Global Fund have commissioned 2 such evaluations to assess the full spectrum of their investments using a prospective mixed-methods approach. We aim to describe lessons learned from implementing these evaluations.

Bringing a health systems modelling approach to complex evaluations: multicountry applications in HIV, TB and malaria.

Introduction: Understanding how to deliver interventions more effectively is a growing emphasis in Global Health. Simultaneously, health system strengthening is a key component to improving delivery. As a result, it is challenging to evaluate programme implementation while reflecting real-world complexity.