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Given the limitations of prescription antidepressants, many individuals have turned to natural remedies for the management of their mood disorders. We review three selected natural remedies that may be of potential use as treatments for depressive disorders and other psychiatric or neurological conditions. The best studied and best supported of these three remedies is S-adenosyl-l-methionine (SAMe), a methyl donor with a wide range of physiological functions in the human organism. With the increasing legalization of cannabis-related products, cannabidiol (CBD) has gained popularity for various potential indications and has even obtained approval in the United States and Canada for certain neurological conditions. Kratom, while potentially useful for certain individuals with psychiatric disorders, is perhaps the most controversial of the three remedies, in view of its greater potential for abuse and dependence. For each remedy, we will review indications, doses and delivery systems, potential anti-inflammatory and immunomodulatory action, adverse effects, and will provide recommendations for clinicians who may be considering prescribing these remedies in their practice., Competing Interests: Declaration of Competing Interest Dr Mischoulon has received research support from Nordic Naturals. He has provided unpaid consulting for Pharmavite LLC and Gnosis USA, Inc. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, Blackmores, Harvard Blog, and PeerPoint Medical Education Institute, LLC. He has received royalties from Lippincott Williams & Wilkins for published book “Natural Medications for Psychiatric Disorders: Considering the Alternatives.” The other authors report no significant conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We performed a screen for drugs that specifically interact with the 5' untranslated region of the mRNA coding for the Alzheimer's Amyloid Precursor Protein (APP). Using a transfection based assay, in which APP 5'UTR sequences drive the translation of a downstream luciferase reporter gene, we have been screening for new therapeutic compounds that already have FDA approval and are pharmacologically and clinically well-characterized. Several classes of FDA-pre-approved drugs (16 hits) reduced APP 5'UTR-directed luciferase expression (> 95% inhibition of translation). The classes of drugs include known blockers of receptor ligand interactions, bacterial antibiotics, drugs involved in lipid metabolism, and metal chelators. These APP 5'UTR directed drugs exemplify a new strategy to identify RNA-directed agents to lower APP translation and A beta peptide output for Alzheimer's disease therapeutics.

Aim: Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality of both young adults and the elderly, and is a key contributing factor in about 30% of all injury‐associated deaths occurring within the United States of America. Albeit substantial impact has been made to improve our comprehension of the mechanisms that underpin the primary and secondary injury stages initiated by a TBI incident, this knowledge has yet to successfully translate into the development of an effective TBI pharmacological treatment. Developing consent suggests that a TBI can concomitantly trigger multiple TBI‐linked cascades that then progress in parallel and, if correct, the multifactorial nature of TBI would make the discovery of a single effective mechanism‐targeted drug unlikely. Discussion: We review recent data indicating that the small molecular weight drug (−)‐phenserine tartrate (PhenT), originally developed for Alzheimer's disease (AD), effectively inhibits a broad range of mechanisms pertinent to mild (m) and moderate (mod)TBI, which in combination underpin the ensuing cognitive and motor impairments. In cellular and animal models at clinically translatable doses, PhenT mitigated mTBI‐ and modTBI‐induced programmed neuronal cell death (PNCD), oxidative stress, glutamate excitotoxicity, neuroinflammation, and effectively reversed injury‐induced gene pathways leading to chronic neurodegeneration. In addition to proving efficacious in well‐characterized animal TBI models, significantly mitigating cognitive and motor impairments, the drug also has demonstrated neuroprotective actions against ischemic stroke and the organophosphorus nerve agent and chemical weapon, soman. Conclusion: In the light of its tolerability in AD clinical trials, PhenT is an agent that can be fast‐tracked for evaluation in not only civilian TBI, but also as a potentially protective agent in battlefield conditions where TBI and chemical weapon exposure are increasingly jointly occurring. [ABSTRACT FROM AUTHOR]

The US Environmental Protection Agency's (USEPA's) current ambient water quality criteria (AWQC) for lead (Pb) in freshwater were developed in 1984. The criteria are adjusted for hardness, but more recent studies have demonstrated that other parameters, especially dissolved organic carbon (DOC) and pH, have a much stronger influence on Pb bioavailability. These recent studies have been used to support development of a biotic ligand model (BLM) for Pb in freshwater, such that acute and chronic Pb toxicity can be predicted over a wide range of water chemistry conditions. Following USEPA guidelines for AWQC development and using a methodology consistent with that used by the USEPA in developing its recommended BLM-based criteria for copper in 2007, we propose acute and chronic BLM-based AWQC for Pb in freshwater. In addition to the application of the BLM approach that can better account for site-specific Pb bioavailability, the toxicity data sets presented are much more robust than in 1984, and there are now sufficient chronic Pb toxicity data available that use of an acute-to-chronic ratio is no longer necessary. Over a range of North American surface waters with representative water chemistry conditions, proposed acute BLM-based Pb criteria ranged from approximately 20 to 1000 μg/L and chronic BLM-based Pb criteria ranged from approximately 0.3 to 40 μg/L. The lowest criteria were for water with low DOC (1.2 mg/L), pH (6.7), and hardness (4.3 mg/L as CaCO3), whereas the highest criteria were for water with high DOC (9.8 mg/L), pH (8.2), and hardness (288 mg/L as CaCO3). Environ Toxicol Chem 2017;36:2965-2973. © 2017 SETAC [ABSTRACT FROM AUTHOR]

Purpose: This study developed standardized vignettes that depict a mild traumatic brain injury (TBI) from one of several causes and subjected them to formal expert review. Method: A base vignette was developed using the World Health Organization operational criteria for mild TBI. Eight specific causes (e.g. sport vs assault) were examined. A convenience sample of mild TBI experts with a discipline background of Neuropsychology from North America, Australasia and Europe (n= 21) used an online survey to evaluate the vignettes and rated the role of cause on outcome. Results: The vignette suite was rated as fitting the mild TBI WHO operational diagnostic criteria at least moderately well. When compared to other factors, cause was not rated as significantly contributing to outcome. When evaluated in isolation, approximately half of the sample rated cause as important or very important and at least two of three clinical outcomes were associated with a different cause. Discussion: The vignettes may be useful in experimental mild TBI research. They enable the injury parameters to be controlled so that the effects of cause can be isolated and examined empirically. Such studies should advance understanding of the role of this factor in mild TBI outcome. [ABSTRACT FROM PUBLISHER]

Pleural infection is a major problem that affects 80 000 cases per year in the UK and USA. It is increasing in incidence, and in an ageing population, it presents a complex challenge that requires a combination of medical therapies and may lead to the need for surgery. This article focuses on the role of the interventional pulmonologist in the diagnosis and management of pleural infection. In particular, we examine the role of pleural ultrasound in diagnostics, thoracocentesis and real-time guided procedures, and the current management strategies, including the controversial role of medical thoracoscopy. [ABSTRACT FROM AUTHOR]

Of the estimated 5.3 million people with Alzheimer's disease in the United States, more than half would be classified as having moderate or severe disease. Alzheimer's disease is a progressive disorder with the moderate to severe stages generally characterized by significant cognitive, functional, and behavioral dysfunction. Unsurprisingly, these advanced stages are often the most challenging for both patients and their caregivers/families. Symptomatic treatments for moderate to severe Alzheimer's disease are approved in the United States and include the acetylcholinesterase inhibitor donepezil and the glutamate receptor antagonist memantine. Progressive symptomatic decline is nevertheless inevitable even with the available therapies, and therefore additional treatment options are urgently needed for this segment of the Alzheimer's disease population. An immediaterelease formulation of donepezil has been available at an approved dose of 5-10 mg/d for the past decade. Recently, the United States Food and Drug Administration approved a higher-dose (23 mg/d) donepezil formulation, which provides more gradual systemic absorption, a longer time to maximum concentration (8 hours) versus the immediate-release formulation (3 hours), and higher daily concentrations. Herein, we review (1) the scientific data on the importance of cholinergic deficits in Alzheimer's disease treatment strategies, (2) the rationale for the use of higher-dose acetylcholinesterase inhibitors in patients with advanced disease, and (3) recent clinical evidence supporting the use of higher-dose donepezil in patients with moderate to severe Alzheimer's disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acquisition of competence in performing a variety of procedures is essential during Internal Medicine (TM) residency training. PURPOSES: Determine the rate of procedural complications by TM residents; determine whether there was a correlation between having 1 or more complications and institutional procedural certification status or attending ratings of resident procedural skill competence on the American Board of Internal Medicine (ABIM) monthly evaluation form (ABIM-MEF). Assess if an association exists between procedural complications and in-training examination and ABIM board certification scores. METHODS: We retrospectively reviewed all procedure log sheets, procedural certification status, ABIM-MEF procedural skills ratings, in-training exam and certifying examination (ABIM-CE) scores from the period 1990-1999 for TM residency program graduates from a training program. RESULTS: Among 69 graduates, 2,212 monthly procedure log sheets and 2,475 ABIM-MEFs were reviewed. The overall complication rate was 2.3/1,000 procedures (95% CI: 1.4-3.1/1,000 procedure). With the exception of procedural certification status as judged by institutional faculty, there was no association between our resident measurements arid procedural complications. CONCLUSIONS: Our findings support the need for a resident procedural competence certification system based on direct observation. Our data support the ABIM's action to remove resident procedural competence from the monthly ABIM-MEF ratings. [ABSTRACT FROM AUTHOR]