Addressing Confusion and Inconsistencies Surrounding the Provider Role in Medical Cannabis Programs.

ABSTRACT: More than 40 states in the United States have established medical Cannabis programs that authorize the use of Cannabis for specific medical conditions. Initially, these medical Cannabis programs aimed to offer compassionate care primarily for terminal or rare, untreatable conditions. However, the scope of these programs has broadened to include nonterminal and more common conditions, including various medical and mental disorders. This expansion introduces several health care challenges: a lack of robust research evidence for many listed conditions, a sense of unpreparedness among providers, and a disparity in provider roles, expectations, and responsibilities across different states, leading to potential confusion. To address these issues, medical organizations need to develop expert consensus or guidelines that underscore evidence-based shared decision-making and patient monitoring standards. Medical education should also include such training. Concurrently, medical providers must prioritize evidence-based treatment over public opinion, exercise clinical judgment, and take responsibility for their recommendations.

A Source Control Model for Treatment-Resistant Substance Use Disorder.

ABSTRACT: We propose applying the "source control" model of infectious disease treatment to the management of treatment-resistant substance use disorder (SUD). We believe that this conceptual framework complements other models for understanding SUD, fills a gap in our current understanding of treatment-resistant SUD, and advances the destigmatization of SUD by reinforcing SUD as a disease similar to other medical conditions. The model also harmonizes the need for multimodal treatment and novel interventions for both acute supportive care and long-term treatment of SUD. In this manuscript, we discuss the justification for, as well as the strengths and limitations of, the "source control" model for the management of treatment-resistant SUD. We also discuss the model's potential to direct innovative research questions and therapeutic interventions.

The Cardiovascular Side Effects of Electroconvulsive Therapy and Their Management.

ABSTRACT: Electroconvulsive therapy (ECT) remains stigmatized in the broader medical community because of misunderstandings about treatment procedures, mortality rates, and cardiovascular complications. Electroconvulsive therapy causes periprocedural hemodynamic variability because of the surges in parasympathetic and sympathetic nervous systems after the administration of the electrical charge. Patients experience an increase in cardiac workload, which is potentially dangerous for patients with preexisting heart disease. Several findings suggest that cardiac complications occur most frequently in patients with underlying cardiovascular disease. We describe the cardiovascular complications that may result from ECT treatment and offer insight on how to mitigate these concerns if they occur. PubMed was queried using terms "electroconvulsive therapy" and "cardiovascular adverse effects." A table is provided with the common cardiovascular side effects of ECT and the most recent evidence-based treatment strategies to manage them. Generally, ECT is a safe procedure in which complications are minor and manageable. Most major complications caused by ECT are related to the cardiovascular system; however, with an appropriate pre-ECT evaluation and a comprehensive multidisciplinary team approach, the cardiovascular complications can be well managed and minimized. Providing proper cardiac clearance can prevent cardiac complications and provide timely care to treatment-resistant populations who are at risk for excessive morbidity and suicide.

OliveNet™: a comprehensive library of compounds from Olea europaea.

Accumulated epidemiological, clinical and experimental evidence has indicated the beneficial health effects of the Mediterranean diet, which is typified by the consumption of virgin olive oil (VOO) as a main source of dietary fat. At the cellular level, compounds derived from various olive (Olea europaea), matrices, have demonstrated potent antioxidant and anti-inflammatory effects, which are thought to account, at least in part, for their biological effects. Research efforts are expanding into the characterization of compounds derived from Olea europaea, however, the considerable diversity and complexity of the vast array of chemical compounds have made their precise identification and quantification challenging. As such, only a relatively small subset of olive-derived compounds has been explored for their biological activity and potential health effects to date. Although there is adequate information describing the identification or isolation of olive-derived compounds, these are not easily searchable, especially when attempting to acquire chemical or biological properties. Therefore, we have created the OliveNet™ database containing a comprehensive catalogue of compounds identified from matrices of the olive, including the fruit, leaf and VOO, as well as in the wastewater and pomace accrued during oil production. From a total of 752 compounds, chemical analysis was sufficient for 676 individual compounds, which have been included in the database. The database is curated and comprehensively referenced containing information for the 676 compounds, which are divided into 13 main classes and 47 subclasses. Importantly, with respect to current research trends, the database includes 222 olive phenolics, which are divided into 13 subclasses. To our knowledge, OliveNet™ is currently the only curated open access database with a comprehensive collection of compounds associated with Olea europaea.Database URL: https://www.mccordresearch.com.au.

19 F DOSY diffusion-NMR spectroscopy of fluoropolymers.

A new pulse sequence for obtaining 19 F detected DOSY (diffusion ordered spectroscopy) spectra of fluorinated molecules is presented and used to study fluoropolymers based on vinylidene fluoride and chlorotrifluoroethylene. The performance of 19 F DOSY NMR experiments (and in general any type of NMR experiment) on fluoropolymers creates some unique complications that very often prevent detection of important signals. Factors that create these complications include: (1) the presence of many scalar couplings among 1 H, 19 F and 13 C; (2) the large magnitudes of many 19 F homonuclear couplings (especially 2 JFF ); (3) the large 19 F chemical shift range; and (4) the low solubility of these materials (which requires that experiments be performed at high temperatures). A systematic study of the various methods for collecting DOSY NMR data, and the adaptation of these methods to obtain 19 F detected DOSY data, has been performed using a mixture of low molecular weight, fluorinated model compounds. The best pulse sequences and optimal experimental conditions have been determined for obtaining 19 F DOSY spectra. The optimum pulse sequences for acquiring 19 F DOSY NMR data have been determined for various circumstances taking into account the spectral dispersion, number and magnitude of couplings present, and experimental temperature. Pulse sequences and experimental parameters for optimizing these experiments for the study of fluoropolymers have been studied. Copyright © 2016 John Wiley & Sons, Ltd.

Reappraisal of lymphatic mapping for midgut neuroendocrine patients undergoing cytoreductive surgery.

BACKGROUND: We previously reported that midgut neuroendocrine tumors (NETs) often develop alternative lymphatic drainage owing to lymphatic obstructions from extensive mesenteric lymphadenopathy, making intraoperative lymphatic mapping mandatory. We hypothesize that this innovative approach needs a longer term validation. METHODS: We updated our results by reviewing 303 patients who underwent cytoreduction from November 2006 to October 2011. Of these patients, 112 had lymphatic mappings and 98 were for midgut NET primaries. Among them, 77 mappings were for the initial cytoreduction and 35 were for reexploration and further cytoreduction. The operative findings, pathology reports, and long-term surgical outcomes were reviewed. RESULTS: Lymphatic mapping changed traditional resection margins in 92% of patients. Of the 35 patients who underwent reexploration without initial mapping, 19 (54%) showed a recurrence at or near the anastomotic sites. In contrast, none of the 112 mapped patients had shown signs of recurrence in a 1- to 5-year follow-up. Additionally, 20 of 45 ileocecal valves (44.4%) were spared in patients whose tumors were at the terminal ileum that, traditionally, would call for a right hemicolectomy. CONCLUSION: With a longer follow-up, lymphatic mapping has proven to be a safe and effective way to prevent local recurrences and preserve the ileocecal valve for selected patients.

Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica.

The availability of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is currently limited because they are produced mainly by marine fisheries that cannot keep pace with the demands of the growing market for these products. A sustainable non-animal source of EPA and DHA is needed. Metabolic engineering of the oleaginous yeast Yarrowia lipolytica resulted in a strain that produced EPA at 15% of dry cell weight. The engineered yeast lipid comprises EPA at 56.6% and saturated fatty acids at less than 5% by weight, which are the highest and the lowest percentages, respectively, among known EPA sources. Inactivation of the peroxisome biogenesis gene PEX10 was crucial in obtaining high EPA yields and may increase the yields of other commercially desirable lipid-related products. This technology platform enables the production of lipids with tailored fatty acid compositions and provides a sustainable source of EPA.

Use of 1H/13C/19F Triple Resonance 3D-NMR to Characterize the Stereosequences in Poly(vinyl fluoride).

Tacticity has an enormous influence on the physical and chemical properties of polymers. There is considerable work using 1D NMR and empirical rules to study the stereosequences in polymers. This work shows that 1H/13C/19F 3D NMR experiments can provide superior resolution and atomic connectivity information, so that unambiguous resonance assignments can be made for poly(vinyl fluoride) (PVF). Compared to prior work on 3D NMR studies of stereosequence effects in fluoropolymers, the 3D NMR pulse sequence used in this work is based on single quantum coherence transfer, which eliminates the complicated splitting patterns resulting from evolution of multiple-quantum coherence. In addition, selective excitation of the 19F nuclei of interest significantly reduces the folding of peaks from other spectral regions. This greatly simplifies the spectra and makes the assignment of resonances much easier. Based on these results, it is possible to assign the 19F resonances to the pentad level. For example, consider the resonances of mm-centered sequences, which are not well resolved in 19F-19F COSY 2D NMR spectrum. 1H/13C/19F 3D NMR data provide clear evidence for all of the three pentad structures: mmmm, mmmr, and rmmr. Examples showing the resonance assignments of head-to-tail sequences are presented.

2D-NMR studies of a model for Krytox® fluoropolymers.

Multiple two-dimensional nuclear magnetic resonance (2D-NMR) techniques have been used to study the structures of Krytox(®) perfluoro(polyalkyl ether) and its mechanism of polymerization. Model compound K(4), containing four Krytox(®) fluoropolymer repeat units, was analyzed to interpret the multiplet patterns in the NMR spectra from the polymer model. (19)F {(13)C}-Heteronuclear single-quantum correlation experiments, performed with delays optimized for (1)J(CF) and (2)J(CF), provided spectra that permitted identification of resonances from individual monomer units. Selective, (19)F-(19)F COSY 2D-NMR experiments were performed with different excitation regions; these experiments were combined with selective inversion pulses to remove (19)F-(19)F J couplings in the f(1) dimension. The resulting COSY spectra were greatly simplified compared with standard (19)F-(19)F COSY spectra, which are too complicated to interpret. They give information regarding the attachments of monomer units and also provide insights into the nature of the stereoisomers that might be present in the polymer. Both infrared and NMR spectra show peaks identifying chain end structures. With the help of these studies, resonances can be assigned, and the average number of repeat units in the polymer chain can be calculated based on the assignments obtained.

Spectral separation of gaseous fluorocarbon mixtures and measurement of diffusion constants by 19F gas phase DOSY NMR.

Diffusion-ordered (DOSY) NMR techniques have for the first time been applied to the spectral separation of mixtures of fluorinated gases by diffusion rates. A mixture of linear perfluoroalkanes from methane to hexane was readily separated at 25 degrees C in an ordinary experimental setup with standard DOSY pulse sequences. Partial separation of variously fluorinated ethanes was also achieved. The constants of self-diffusion of a set of pure perfluoroalkanes were obtained at pressures from 0.25 to 1.34 atm and temperatures from 20 to 122 degrees C. Under all conditions there was agreement within 20% of experimental self-diffusion constant D and values calculated by the semiempirical Fuller method.

Characterization of n-butyl acrylate centered triads in poly(n-butyl acrylate-co-carbon monoxide-co-ethylene) by isotopic labeling and two dimensional NMR.

UNLABELLED: Poly(n-butylacrylate-co-carbon monoxide-co-ethylene) (polyEBC) samples prepared from 13C-labeled monomer, n-butyl acrylate, were characterized using two dimensional (2D) pulsed field gradient (PFG) 750 MHz NMR spectroscopy. To elucidate the complex structure of the terpolymer, 2D-1H/13C-heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) experiments were conducted by selectively exciting the enhanced resonances in the spectra of two polymer samples, one polymer resulting from synthesis with 1-13C-n-butylacrylate monomer and a second polymer obtained from a synthesis with 2-13C-n-butylacrylate monomer. High-resolution 2D-NMR combined with 13C-labeling of the polymer greatly simplifies the 2D-NMR spectra, selectively enhances the weak peaks from low occurrence B-centered triad structures, and aids in their resonance assignments. In all experiments, the sample temperature was 120 degrees C, to ensure a homogeneous solution and sufficient molecular mobility. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material (1D 13C NMR spectra of the 13C-labeled and unlabeled polymers) is available in the online version of this article at http://dx.doi.org/100.1007/s00216-003-2402-3.

A suite of 3D NMR methods for characterizing complex hydrocarbon structure fragments.

A suite of triple resonance 3D NMR experiments is presented for the complete connectivity assignment of the hydrocarbon network in complex macromolecular and supramolecular organic structures. These new 3D NMR methods rely only on the presence of a unique set of (13)C resonances (from (13)C(X)) which are separated from the rest of the (13)C NMR spectrum. These experiments take the advantage of region selective excitation and selective inversion by composite pulses to provide correlations among H(A), (13)C(A); H(B), (13)C(B) and neighboring (13)C(X) resonances along three frequency dimensions. These methods include: gHC(A)C(X), gHC(A)C(X)-HH-TOCSY and gHC(A)C(X)-CC-TOCSY experiments. The utility of this approach is illustrated with spectra of selected structure fragments in poly(ethylene-co-n-butyl acrylate-co-carbon monoxide) (polyEBC) prepared from 1,2,3-(13)C(3)-n-butyl acrylate.

Communicating with patients about intimate partner violence: screening and interviewing approaches.

Intimate partner violence is a major public health concern; it contributes to poor physical and mental health in affected individuals, primarily women. Due to documented poor detection rates of intimate partner violence by physicians, the medical community has focused increasing attention on the successful identification of victims in all medical contexts. Family medicine educators need to be aware of the current status of knowledge about intimate partner violence and convey this to students and residents. In this article, we review the literature on screening tools to identify victims of partner violence, discuss the pitfalls of relying on screening tools, review barriers to identification of partner violence from clinician and patient perspectives, and recommend a patient-centered methodfor conversing with patients about intimate partner violence.

Analysis of protein/ligand interactions with NMR diffusion measurements: the importance of eliminating the protein background.

Pulsed-field gradient nuclear magnetic resonance (PFG-NMR) is a well-established method for the determination of translational diffusion coefficients. Recently, this method has found applicability in the combinatorial arena with the introduction of affinity NMR for characterizing protein/ligand interactions. Although affinity NMR has been reported to be an effective method for the identification of active compounds in a complex mixture, there are limitations of this method. We have developed a simple mathematical model to predict optimum concentration ratios of the ligand and protein in order to observe maximum changes in the ligand diffusion coefficient upon protein binding. The ligand/protein systems of L-tryptophan and ibuprofen binding to human serum albumin were chosen to demonstrate the usefulness of this model. However, even when the conditions of the mathematical model are satisfied, the spectral background arising from the protein in proton-detected experiments can be problematic. To this end, we have employed spectral subtraction of the protein spectrum to yield ligand diffusion coefficients that are in agreement with those predicted by simulation.

Interviewing when family members are present.

The presence of family members at an office visit creates unique opportunities and challenges for the physician while interviewing the patient. The physician must address issues of confidentiality, privacy, and agency. Special skills are required to respectfully and efficiently involve family members, while keeping the patient at the center of the visit. A core set of interviewing skills exists for office visit interviews with family members present. These skills include building rapport with each participant by identifying their individual issues and perspectives, and encouraging participation by listening to and addressing the concerns of all persons. Physicians should also avoid triangulation, maintain confidentiality, and verify agreement with the plan. It may be necessary to use more advanced family interviewing skills, including providing direction despite problematic communications; managing conflict; negotiating common ground; and referring members to family therapy.