MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants ( = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions.

Prevention of pulmonary complications in sedated patients undergoing interventional procedures in the nonoperating room anesthesia setting.

Purpose Of Review: Nonoperating room anesthesia (NORA) procedures have expanded in number, variety, and complexity. NORA involves all age groups, including frail older adults and patients often considered too sick to tolerate traditional surgical interventions. Postoperative pulmonary complications are a significant source of adverse events in the perioperative setting.

Non-invasive MR imaging techniques for measuring femoral arterial flow in a pediatric and adolescent cohort.

Magnetic Resonance Imaging (MRI) is well-suited for imaging peripheral blood flow due to its non-invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI-based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric-adolescent population using phase contrast MRI, and to present test-retest reliability data for this method.

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions.

Limb movement frequency is a significant modulator of the ventilatory response during submaximal cycling exercise in humans.

Human experimentation investigating the contribution of limb movement frequency in determining the fast exercise drive to breathe has produced controversial findings. To evaluate the role of limb movement frequency in determining the fast exercise drive to breathe, endurance runners and recreationally-active controls performed two sinusoidal exercise protocols on a cycle ergometer. One protocol was performed at constant workload with sinusoidal pedaling cadence, and a second with sinusoidal workload at constant cadence.

Shame, self-acceptance and disclosure in the lives of gay men living with HIV: an interpretative phenomenological analysis approach.

Objective: HIV-related stigma is a major driver of poor prognosis for the treatment and reduced spread of HIV. The present article provides a qualitative analysis surrounding various themes related to stigma and shame as a result HIV.

Design: Eight gay men recruited from a community HIV clinic contacted the researchers in response to a study involving participation in a structured, eight-week group intervention for HIV-related stigma.

A unique alkaline pH-regulated and fatty acid-activated tandem pore domain potassium channel (K₂P) from a marine sponge.

A cDNA encoding a potassium channel of the two-pore domain family (K(2P), KCNK) of leak channels was cloned from the marine sponge Amphimedon queenslandica. Phylogenetic analysis indicated that AquK(2P) cannot be placed into any of the established functional groups of mammalian K(2P) channels. We used the Xenopus oocyte expression system, a two-electrode voltage clamp and inside-out patch clamp electrophysiology to determine the physiological properties of AquK(2P).

Diagnostic value of routine chest radiography in febrile, neutropenic children for early detection of pneumonia and mould infections.

Background: Despite recent studies failing to demonstrate the value of routine chest radiography (CXR) in the initial evaluation of the febrile neutropenic patient with cancer, this screening test is advocated by some experts. We evaluated the benefits of CXR for early diagnosis of pulmonary infection at St. Jude Children's Research Hospital (SJCRH) with emphasis on early recognition of mould infections.

Strategies to mitigate the bioactivation of 2-anilino-7-aryl-pyrrolo[2,1-f][1,2,4]triazines: identification of orally bioavailable, efficacious ALK inhibitors.

Chemical strategies to mitigate cytochrome P450-mediated bioactivation of novel 2,7-disubstituted pyrrolo[2,1-f][1,2,4]triazine ALK inhibitors are described along with synthesis and biological activity. Piperidine-derived analogues showing minimal microsomal reactive metabolite formation were discovered. Potent, selective, and metabolically stable ALK inhibitors from this class were identified, and an orally bioavailable compound (32) with antitumor efficacy in ALK-driven xenografts in mouse models was extensively characterized.

2,7-Pyrrolo[2,1-f][1,2,4]triazines as JAK2 inhibitors: modification of target structure to minimize reactive metabolite formation.

The JAK2/STAT pathway has important roles in hematopoiesis. With the discovery of the JAK2 V617F mutation and its presence in many patients with myeloproliferative neoplasms, research in the JAK2 inhibitor arena has dramatically increased. We report a novel series of potent JAK2 inhibitors containing a 2,7-pyrrolotriazine core.

2,7-Disubstituted-pyrrolotriazine kinase inhibitors with an unusually high degree of reactive metabolite formation.

There are numerous published studies establishing a link between reactive metabolite formation and toxicity of various drugs. Although the correlation between idiosyncratic reactions and reactive metabolite formation is not 1:1, the association between the two is such that many pharmaceutical companies now monitor for reactive metabolites as a standard part of drug candidate testing and selection. The most common method involves in vitro human microsomal incubations in the presence of a thiol trapping agent, such as glutathione (GSH), followed by LC/MS analysis.

2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazines: new variant of an old template and application to the discovery of anaplastic lymphoma kinase (ALK) inhibitors with in vivo antitumor activity.

A novel 2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazine scaffold has been designed as a new kinase inhibitor platform mimicking the bioactive conformation of the well-known diaminopyrimidine motif. The design, synthesis, and validation of this new pyrrolo[2,1-f][1,2,4]triazine scaffold will be described for inhibitors of anaplastic lymphoma kinase (ALK). Importantly, incorporation of appropriate potency and selectivity determinants has led to the discovery of several advanced leads that were orally efficacious in animal models of anaplastic large cell lymphoma (ALCL).

The ventilatory response to sine wave variation in exercise loads and limb movement frequency.

The current study's experiments tested the hypothesis that limb movement frequency is a significant determinant of exercise hyperpnoea. To this end, 19 healthy participants walked on a treadmill, where work was varied sinusiodally by alterations in either treadmill speed or grade. Measured responses were fitted with sine waves to determine their amplitudes and phase angles.

Tacrolimus ointment 0.1% for the treatment of peristomal skin disease: 3 case reports.

Patients with stomas face a variety of problems, such as skin breakdown or ulceration at the peristomal site, that can complicate care. Topical steroids are frequently used to treat various inflammatory conditions that affect peristomal skin with good results, but chronic use can lead to undesirable side effects. Tacrolimus ointment 0.

Synthesis and structure-activity relationships of novel pyrrolocarbazole lactam analogs as potent and cell-permeable inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1).

A series of novel pyrrolocarbazole lactams was identified as potent PARP-1 inhibitors in vitro and in a PC12 cellular NAD(+) depletion assay. The SAR trends of substituents at the 3-position, as well as the effect of blocking the indole or lactam NH-groups of the template by methylation or formylation, are discussed in relation to molecular modeling studies.

Synthesis and structure-activity relationships of novel poly(ADP-ribose) polymerase-1 inhibitors.

A series of novel pyrrolocarbazoles was synthesized as potential PARP-1 inhibitors. Pyrrolocarbazole 1 was identified as a potent PARP-1 inhibitor (IC50 = 36 nM) from our internal database. Synthesis of analogs around this template with the aid of modeling studies led to the identification of the truncated imide 14.

Effects of concurrent inspiratory and expiratory muscle training on respiratory and exercise performance in competitive swimmers.

The efficiency of the respiratory system presents significant limitations on the body's ability to perform exercise due to the effects of the increased work of breathing, respiratory muscle fatigue, and dyspnoea. Respiratory muscle training is an intervention that may be able to address these limitations, but the impact of respiratory muscle training on exercise performance remains controversial. Therefore, in this study we evaluated the effects of a 12-week (10 sessions week(-1)) concurrent inspiratory and expiratory muscle training (CRMT) program in 34 adolescent competitive swimmers.

1,2-Benzothiazine 1,1-dioxide alpha-ketoamide analogues as potent calpain I inhibitors.

A series of potent 1,2-benzothiazine 1,1-dioxide alpha-ketoamide inhibitors of calpain I is described.