Sublingual Buprenorphine/Naloxone and Multi-Modal Management for High-Risk Chronic Pain Patients

Patients with chronic pain managed with opioid medications are at high risk for opioid overuse or misuse. West Virginia University (WVU) established a High-Risk Pain Clinic to use sublingual buprenorphine/naloxone (bup/nal) plus a multimodal approach to help chronic pain patients with history of Substance Use Disorder (SUD) or aberrant drug-related behavior. The objective of this study was to report overall retention rates and indicators of efficacy in pain control from approximately six years of High-Risk Pain Clinic data. A retrospective chart review was conducted for a total of 78 patients who enrolled in the High-Risk Pain Clinic between 2014 and 2020. Data gathered include psychiatric diagnoses, prescribed medications, pain score, buprenorphine/naloxone dosing, time in clinic, and reason for dismissal. A linear mixed effects model was used to assess the pain score from the Defense and Veterans Pain Rating Scale (DVPRS) and daily bup/nal dose across time. The overall retention of the High-Risk Pain Clinic was 41%. The mean pain score demonstrated a significant downward trend across treatment time (p \u3c 0.001), while the opposite trend was seen with buprenorphine dose (p \u3c 0.001). With the benefit of six years of observation, this study supports buprenorphine/naloxone as a safe and efficacious component of comprehensive chronic pain treatment in patients with SUD or high-risk of opioid overuse or misuse

Modification of TiO_2 Nanoparticles with Organodiboron Molecules Inducing Stable Surface Ti^(3+) Complex

As one of the most promising semiconductor oxide materials, titanium dioxide (TiO_2) absorbs ultraviolet (UV) light but not visible light. To address this limitation, the introduction of Ti^(3+) defects represents a common strategy to render TiO_2 visible-light-responsive. Unfortunately, current hurdles in Ti^(3+) generation technologies impeded the widespread application of Ti^(3+) modified materials. Herein, we demonstrate a simple and mechanistically distinct approach to generating abundant surface-Ti^(3+) sites without leaving behind oxygen vacancy and sacrificing one-off electron donors. In particular, upon adsorption of organodiboron reagents onto TiO_2 nanoparticles, spontaneous electron injection from the dibron-bound O^(2-) site to adjacent Ti^(4+) site leads to an extremely stable blue surface Ti^(3+)‒O^(-•) complex. Notably, this defect generation protocol is also applicable to other semiconductor oxides including ZnO, SnO_2, Nb_2O_5 and In_2O_3. Furthermore, the as-prepared photoelectronic device using this strategy affords 10^3 fold higher visible light response, and the fabricated perovskite solar cell shows an enhanced performance

The Exogenous Rule of Law: Comparative Evidence about the General Duty to Obey the Law Amongst Law Students

Van Rooij will also draw from qualitative data from lawyers in China and the Netherlands as well as from farmers in China

Molecular Characterization of the 1-Deoxy-D-Xylulose 5-Phosphate Synthase Gene Family in Artemisia annua

Artemisia annua produces artemisinin, an effective antimalarial drug. In recent decades, the later steps of artemisinin biosynthesis have been thoroughly investigated; however, little is known about the early steps of artemisinin biosynthesis. Comparative transcriptomics of glandular and filamentous trichomes and 13CO2 radioisotope study have shown that the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, rather than the mevalonate pathway, plays an important role in artemisinin biosynthesis. In this study, we have cloned three 1-deoxy-D-xylulose 5-phosphate synthase (DXS) genes from A. annua (AaDXS1, AaDXS2, and AaDXS3); the DXS enzyme catalyzes the first and rate-limiting enzyme of the MEP pathway. We analyzed the expression of these three genes in different tissues in response to multiple treatments. Phylogenetic analysis revealed that each of the three DXS genes belonged to a distinct clade. Subcellular localization analysis indicated that all three AaDXS proteins are targeted to chloroplasts, which is consistent with the presence of plastid transit peptides in their N-terminal regions. Expression analyses revealed that the expression pattern of AaDXS2 in specific tissues and in response to different treatments, including methyl jasmonate, light, and low temperature, was similar to that of artemisinin biosynthesis genes. To further investigate the tissue-specific expression pattern of AaDXS2, the promoter of AaDXS2 was cloned upstream of the β-glucuronidase gene and was introduced in arabidopsis. Histochemical staining assays demonstrated that AaDXS2 was mainly expressed in the trichomes of Arabidopsis leaves. Together, these results suggest that AaDXS2 might be the only member of the DXS family in A. annua that is involved in artemisinin biosynthesis

Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial

IntroductionWhile current treatments for substance use disorder (SUD) are beneficial, success rates remain low and treatment outcomes are complicated by co-occurring SUDs, many of which are without available medication treatments. Research involving neuromodulation for SUD has recently gained momentum. This study evaluated two doses (60 and 90 W) of Low Intensity Focused Ultrasound (LIFU), targeting the bilateral nucleus accumbens (NAc), in individuals with SUD.MethodsFour participants (three male), who were receiving comprehensive outpatient treatment for opioid use disorder at the time of enrollment and who also had a history of excessive non-opioid substance use, completed this pilot study. After confirming eligibility, these participants received 10 min sham LIFU followed by 20 min active LIFU (10 min to left then right NAc). Outcomes were the safety, tolerability, and feasibility during the LIFU procedure and throughout the 90-day follow-up. Outcomes also included the impact of LIFU on cue-induced substance craving, assessed via Visual Analog Scale (VAS), both acutely (pre-, during and post-procedure) and during the 90-day follow-up. Daily craving ratings (without cues) were also obtained for one-week prior to and one-week following LIFU.ResultsBoth LIFU doses were safe and well-tolerated based on reported adverse events and MRI scans revealed no structural changes (0 min, 24 h, and 1-week post-procedure). For the two participants receiving “enhanced” (90 W) LIFU, VAS craving ratings revealed active LIFU attenuated craving for participants’ primary substances of choice relative to sham sonication. For these participants, reductions were also noted in daily VAS craving ratings (0 = no craving; 10 = most craving ever) across the week following LIFU relative to pre-LIFU; Participant #3 pre- vs. post-LIFU: opioids (3.6 ± 0.6 vs. 1.9 ± 0.4), heroin (4.2 ± 0.8 vs. 1.9 ± 0.4), methamphetamine (3.2 ± 0.4 vs. 0.0 ± 0.0), cocaine (2.4 ± 0.6 vs. 0.0 ± 0.0), benzodiazepines (2.8 ± 0.5 vs. 0.0 ± 0.0), alcohol (6.0 ± 0.7 vs. 2.7 ± 0.8), and nicotine (5.6 ± 1.5 vs. 3.1 ± 0.7); Participant #4: alcohol (3.5 ± 1.3 vs. 0.0 ± 0.0) and nicotine (5.0 ± 1.8 vs. 1.2 ± 0.8) (all p’s < 0.05). Furthermore, relative to screening, longitudinal reductions in cue-induced craving for several substances persisted during the 90-day post-LIFU follow-up evaluation for all participants.DiscussionIn conclusion, LIFU targeting the NAc was safe and acutely reduced substance craving during the LIFU procedure, and potentially had longer-term impact on craving reductions. While early observations are promising, NAc LIFU requires further investigation in a controlled trial to assess the impact on substance craving and ultimately substance use and relapse

Modification of TiO_2 Nanoparticles with Organodiboron Molecules Inducing Stable Surface Ti^(3+) Complex

As one of the most promising semiconductor oxide materials, titanium dioxide (TiO_2) absorbs ultraviolet (UV) light but not visible light. To address this limitation, the introduction of Ti^(3+) defects represents a common strategy to render TiO_2 visible-light-responsive. Unfortunately, current hurdles in Ti^(3+) generation technologies impeded the widespread application of Ti^(3+) modified materials. Herein, we demonstrate a simple and mechanistically distinct approach to generating abundant surface-Ti^(3+) sites without leaving behind oxygen vacancy and sacrificing one-off electron donors. In particular, upon adsorption of organodiboron reagents onto TiO_2 nanoparticles, spontaneous electron injection from the dibron-bound O^(2-) site to adjacent Ti^(4+) site leads to an extremely stable blue surface Ti^(3+)‒O^(-•) complex. Notably, this defect generation protocol is also applicable to other semiconductor oxides including ZnO, SnO_2, Nb_2O_5 and In_2O_3. Furthermore, the as-prepared photoelectronic device using this strategy affords 10^3 fold higher visible light response, and the fabricated perovskite solar cell shows an enhanced performance

Interband cascade laser based mid-infrared methane sensor system using a novel electrical-domain self-adaptive direct laser absorption spectroscopy (SA-DLAS)

To suppress sensor noise with unknown statistical properties, a novel self-adaptive direct laser absorption spectroscopy (SA-DLAS) technique was proposed by incorporating a recursive, least square (RLS) self-adaptive denoising (SAD) algorithm and a 3291 nm interband cascade laser (ICL) for methane (CH4) detection. Background noise was suppressed by introducing an electrical-domain noise-channel and an expectation-known-based RLS SAD algorithm. Numerical simulations and measurements were carried out to validate the function of the SA-DLAS technique by imposing low-frequency, high-frequency, White-Gaussian and hybrid noise on the ICL scan signal. Sensor calibration, stability test and dynamic response measurement were performed for the SA-DLAS sensor using standard or diluted CH4ﾠsamples. With the intrinsic sensor noise considered only, an Allan deviation of ~43.9 ppbv with a ~6 s averaging time was obtained and it was further decreased to 6.3 ppbv with a ~240 s averaging time, through the use of self-adaptive filtering (SAF). The reported SA-DLAS technique shows enhanced sensitivity compared to a DLAS sensor using a traditional sensing architecture and filtering method. Indoor and outdoor atmospheric CH4measurements were conducted to validate the normal operation of the reported SA-DLAS technique