Polysubstance use in the U.S. opioid crisis.

Interventions to address the U.S. opioid crisis primarily target opioid use, misuse, and addiction, but because the opioid crisis includes multiple substances, the opioid specificity of interventions may limit their ability to address the broader problem of polysubstance use. Overlap of opioids with other substances ranges from shifts among the substances used across the lifespan to simultaneous co-use of substances that span similar and disparate pharmacological categories. Evidence suggests that nonmedical opioid users quite commonly use other drugs, and this polysubstance use contributes to increasing morbidity and mortality. Reasons for adding other substances to opioids include enhancement of the high (additive or synergistic reward), compensation for undesired effects of one drug by taking another, compensation for negative internal states, or a common predisposition that is related to all substance consumption. But consumption of multiple substances may itself have unique effects. To achieve the maximum benefit, addressing the overlap of opioids with multiple other substances is needed across the spectrum of prevention and treatment interventions, overdose reversal, public health surveillance, and research. By addressing the multiple patterns of consumption and the reasons that people mix opioids with other substances, interventions and research may be enhanced.

Essential components of physician health program monitoring for substance use disorder: A survey of participants 5 years post successful program completion.

BACKGROUND AND OBJECTIVES: Physician health programs (PHPs) have demonstrated efficacy, but their mechanism of influence is unclear. This study sought to identify essential components of PHP care management for substance use disorder (SUD), and to assess whether positive outcomes are sustained over time. METHODS: Physicians with DSM-IV diagnoses of Substance Dependence and/or Substance Abuse who had successfully completed a PHP monitoring agreement at least 5 years before the study (N = 343) were identified as eligible. Of the 143 (42%) that could be reached by phone, 93% (n = 133; 86% male) completed the anonymous online survey. RESULTS: Virtually all PHP program components were rated as being at least "somewhat helpful" in promoting recovery, with the plurality of respondents rating almost all components as "extremely helpful." The top-rated components were: signing a PHP monitoring agreement, participation in the PHP, formal SUD treatment, and attending 12-step meetings, with each receiving a mean rating of at least 6.2 out of 7. Notably, 88% of respondents endorsed continued participation in 12-step fellowships. Despite the significant financial burden of PHP participation, 85% of respondents reported they believed the total financial cost of PHP participation was "money well spent." DISCUSSION AND CONCLUSIONS: Components of PHP monitoring were viewed as acceptable and helpful to physicians who completed the program, and outcomes were generally sustained over 5 years. More studies are needed to confirm these preliminary findings. SCIENTIFIC SIGNIFICANCE: This study documents the perceived cost-benefit of participation in a PHP among a small sample of program completers.

Drug use among youth: National survey data support a common liability of all drug use.

The prevalence of substance use disorders in adults is higher if substance use is initiated during adolescence, underscoring the importance of youth substance use prevention. We examined whether the use of one substance by adolescents is associated with increased risk for using any other substance, regardless of use sequences. In 2017 we examined data from 17,000 youth aged 12-17 who participated in the 2014 National Survey on Drug Use and Health, a sample of nationally representative data on substance use among the U.S. civilian, noninstitutionalized population aged 12 or older. Descriptive analyses and multivariable logistic regression models were applied. After controlling for age, sex, and race/ethnicity, compared with youth without past-month marijuana use, youth with past-month marijuana use were 8.9 times more likely to report past-month cigarette use, 5.6, 7.9 and 15.8 times more likely to report past-month alcohol use, binge use, or heavy use (respectively), and 9.9 times more likely to report past-month use of other illicit drugs. The prevalence of past-month use of cigarettes, marijuana, and other illicit drugs was significantly higher among past-month alcohol users compared with youth without past-month alcohol use, and increased as intensity of alcohol use rose. Among past-month cigarette smokers, the prevalence of marijuana, other illicit drugs, and alcohol use were each significantly higher than youth without past-month cigarette use. Youth marijuana use, cigarette smoking, or alcohol consumption is associated with other substance use. This finding has importance for youth prevention, supporting a message no use by youth of any substance.

Cellular photo digital breathalyzer for monitoring alcohol use: a pilot study.

BACKGROUND: Monitoring alcohol use is important in numerous situations. Direct ethanol metabolites, such as ethyl glucuronide (EtG), have been shown to be useful tools in detecting alcohol use and documenting abstinence. For very frequent or continuous control of abstinence, they lack practicability. Therefore, devices measuring ethanol itself might be of interest. This pilot study aims at elucidating the usability and accuracy of the cellular photo digital breathalyzer (CPDB) compared to self-reports in a naturalistic setting. METHOD: 12 social drinkers were included. Subjects used a CPDB 4 times daily, kept diaries of alcohol use and submitted urine for EtG testing over a period of 5 weeks. RESULTS: In total, the 12 subjects reported 84 drinking episodes. 1,609 breath tests were performed and 55 urine EtG tests were collected. Of 84 drinking episodes, CPDB detected 98.8%. The compliance rate for breath testing was 96%. Of the 55 EtG tests submitted, 1 (1.8%) was positive. CONCLUSIONS: The data suggest that the CPDB device holds promise in detecting high, moderate, and low alcohol intake. It seems to have advantages compared to biomarkers and other monitoring devices. The preference for CPDB by the participants might explain the high compliance. Further studies including comparison with biomarkers and transdermal devices are needed.

Patterns of abstinence or continued drug use among methadone maintenance patients and their relation to treatment retention.

The efficacy and effectiveness of methadone maintenance treatment (MMT) in the medical management of opioid addiction has been well-established, but treatment outcomes are compromised by the continued use of licit and illicit drugs during MMT. The present study examined the relationship between in-treatment illicit drug use and retention and dropout of 604 MMT patients in Washington, D.C. Sixty-eight percent of patients did not test positive for an unprescribed drug during the study period. Of patients who tested positive for an illicit drug during the baseline period, 55% tested positive for cocaine, 44% for opiates, 23% for THC, 20% for benzodiazepines, 7% for PCP, and 4% for amphetamines. Those testing positive were three times more likely to leave treatment than those who did not test positive. Testing positive for one drug doubled the rate of attrition; testing positive for multiple drugs quadrupled the risk of attrition. Non-prescribed opioid or benzodiazepine use was a predictor of MMT dropout, but prescribed opioid or benzodiazepine use was not. Continued illicit drug use poses significant risk for subsequent premature termination of MMT. Assertive clinical management of continued illicit drug use could provide mechanisms to enhance MMT retention and long-term recovery outcomes.

Functional nanoporous graphene superlattice.

Two-dimensional (2D) superlattices, formed by stacking sublattices of 2D materials, have emerged as a powerful platform for tailoring and enhancing material properties beyond their intrinsic characteristics. However, conventional synthesis methods are limited to pristine 2D material sublattices, posing a significant practical challenge when it comes to stacking chemically modified sublattices. Here we report a chemical synthesis method that overcomes this challenge by creating a unique 2D graphene superlattice, stacking graphene sublattices with monodisperse, nanometer-sized, square-shaped pores and strategically doped elements at the pore edges. The resulting graphene superlattice exhibits remarkable correlations between quantum phases at both the electron and phonon levels, leading to diverse functionalities, such as electromagnetic shielding, energy harvesting, optoelectronics, and thermoelectrics. Overall, our findings not only provide chemical design principles for synthesizing and understanding functional 2D superlattices but also expand their enhanced functionality and extensive application potential compared to their pristine counterparts.

Phosphatidylethanol: the potential role in further evaluating low positive urinary ethyl glucuronide and ethyl sulfate results.

BACKGROUND: Whereas urinary ethyl glucuronide (EtG) levels above 1,000 ng/ml reflect with a high probability ethanol (EtOH) consumption, levels below this cutoff are difficult to interpret as both extraneous (nonbeverage) EtOH exposure, recent drinking, and more distant high EtOH intake (several days ago) might yield similar results. This might be of particular relevance in medico-legal cases. To overcome this dilemma, phosphatidylethanol (PEth) might be a promising marker, because blood PEth is only positive following significant alcohol use. The aim of our study was therefore to employ PEth as a marker to differentiate between the different conditions. METHODS: Subjects included were 252 participants in monitoring with the Alabama Physician Health Program. All subjects testing positive for EtG and/or ethyl sulfate (EtS) who denied drinking after routine supportive confrontation were subject to information about PEth testing. If they still denied drinking, PEth testing was performed and the result communicated. EtG, EtS, and PEth testing was performed in a commercial laboratory using liquid chromatography tandem mass spectrometry methods. RESULTS: Of a total of 18 subjects who tested positive for EtG and/or EtS, 10 denied drinking. Of the 7 who denied drinking after PEth explanation, in 5 cases, their claim was supported by a negative PEth result. In 2 cases, a positive PEth result was in contrast to their claim. CONCLUSIONS: PEth results in combination with previous low positive EtG/EtS results allow differentiating between innocent/extraneous exposure and drinking. Negative PEth testing following low positive EtG/EtS results helps to further elucidate the findings and support the claim of the patient of recent alcohol abstinence. Positive PEth testing following positive EtG/EtS results confirms recent drinking.

Magnetocontrollable droplet mobility on liquid crystal-infused porous surfaces.

Magnetocontrollable droplet mobility on surfaces of both solids and simple fluids have been widely used in a wide range of applications. However, little is understood about the effect of the magnetic field on the wettability and mobility of droplets on structured fluids. Here, we report the manipulation of the dynamic behaviors of water droplets on a film of thermotropic liquid crystals (LCs). We find that the static wetting behavior and static friction of water droplets on a 4'-octyl-4-biphenylcarbonitrile (8CB) film strongly depend on the LC mesophases, and that a magnetic field caused no measurable change to these properties. However, we find that the droplet dynamics can be affected by a magnetic field as it slides on a nematic 8CB film, but not on isotropic 8CB, and is dependent on both the direction and strength of the magnetic field. By measuring the dynamic friction of a droplet sliding on a nematic 8CB film, we find that a magnetic field alters the internal orientational ordering of the 8CB which in turn affects its viscosity. We support this interpretation with a scaling argument using the LC magnetic coherence length that includes (i) the elastic energy from the long-range orientational ordering of 8CB and (ii) the free energy from the interaction between 8CB and a magnetic field. Overall, these results advance our understanding of droplet mobility on LC films and enable new designs for responsive surfaces that can manipulate the mobility of water droplets. Electronic Supplementary Material: Supplementary material (further details of the stability of LCIPS against water-induced dewetting, the interfacial tension and contact angle measurement using a goniometer, the estimation of the thickness of LC wrapping layer at air-water interface on droplets, SEM measurements, the average sliding velocity of a water droplet on 5CB, E7, silicone oil, and mineral oil films with and without a magnetic field, representative force diagram (Fd versus time) of a 3-µL water droplet moving at a speed of 0.1 mm/s on a nematic 8CB film, Fdynamic acting on 3 µL water droplets moving at speeds of 0.1-1 mm/s on an isotropic 8CB film, the calculated magnetic coherence length as a function of the magnitude of the magnetic field applied to the nematic LCIPS, and the apparent advancing and receding contact angles of a moving water droplet on nematic LCIPS as a function of time, and polarized light micrographs (top view) of a nematic 8CB film between two DMOAP-functionalized glass slides before and after applying a horizontal magnetic field) is available in the online version of this article at 10.1007/s12274-022-5318-y.

Staggered circular nanoporous graphene converts electromagnetic waves into electricity.

Harvesting largely ignored and wasted electromagnetic (EM) energy released by electronic devices and converting it into direct current (DC) electricity is an attractive strategy not only to reduce EM pollution but also address the ever-increasing energy crisis. Here we report the synthesis of nanoparticle-templated graphene with monodisperse and staggered circular nanopores enabling an EM-heat-DC conversion pathway. We experimentally and theoretically demonstrate that this staggered nanoporous structure alters graphene's electronic and phononic properties by synergistically manipulating its intralayer nanostructures and interlayer interactions. The staggered circular nanoporous graphene exhibits an anomalous combination of properties, which lead to an efficient absorption and conversion of EM waves into heat and in turn an output of DC electricity through the thermoelectric effect. Overall, our results advance the fundamental understanding of the structure-property relationships of ordered nanoporous graphene, providing an effective strategy to reduce EM pollution and generate electric energy.

Design of a self-cleanable multilevel anticounterfeiting interface through covalent chemical modulation.

Counterfeit products have posed a significant threat to consumers safety and the global economy. To address this issue, extensive studies have been exploring the use of coatings with unclonable, microscale features for authentication purposes. However, the ease of readout, and the stability of these features against water, deposited dust, and wear, which are required for practical use, remain challenging. Here we report a novel class of chemically functionalizable coatings with a combination of a physically unclonable porous topography and distinct physiochemical properties (e.g., fluorescence, water wettability, and water adhesion) obtained through orthogonal chemical modifications (i.e., 1,4-conjugate addition reaction and Schiff-base reaction at ambient conditions). Unprecedentedly, a self-cleanable and physically unclonable coating is introduced to develop a multilevel anticounterfeiting interface. We demonstrate that the authentication of the fluorescent porous topography can be verified using deep learning. More importantly, the spatially selective chemical modifications can be read with the naked eye via underwater exposure and UV light illumination. Overall, the results reported in this work provide a facile basis for designing functional surfaces capable of independent and multilevel decryption of authenticity.

Single-molecule visualization determines conformational substate ensembles in ß-sheet-rich peptide fibrils.

An understanding of protein conformational ensembles is essential for revealing the underlying mechanisms of interpeptide recognition and association. However, experimentally resolving multiple simultaneously existing conformational substates remains challenging. Here, we report the use of scanning tunneling microscopy (STM) to analyze the conformational substate ensembles of ß sheet peptides with a submolecular resolution (in-plane <2.6 Å). We observed ensembles of more than 10 conformational substates (with free energy fluctuations between several kBTs) in peptide homoassemblies of keratin (KRT) and amyloidal peptides (-5Aß42 and TDP-43 341-357). Furthermore, STM reveals a change in the conformational ensemble of peptide mutants, which is correlated with the macroscopic properties of peptide assemblies. Our results demonstrate that the STM-based single-molecule imaging can capture a thorough picture of the conformational substates with which to build an energetic landscape of interconformational interactions and can rapidly screen conformational ensembles, which can complement conventional characterization techniques.

Six lessons from state physician health programs to promote long-term recovery.

The success of the nation's state physician health programs (PHPs) provides important new evidence on the potential for dramatically reducing relapse and promoting long-term recovery from substance use disorders. This article summarizes the findings of the first national PHP study and outlines six lessons learned from this model of care management: (1) zero tolerance for any use of alcohol and other drugs; (2) thorough evaluation and patient-focused care; (3) prolonged, frequent random testing for both alcohol and other drugs; (4) effective use of leverage; (5) defining and managing relapses; and (6) the goal of lifelong recovery rooted in the 12-Step fellowships. PHPs are a part of a new paradigm of care management that includes the programs developed for commercial pilots (HIMS) and for attorneys (CoLAP). Elements of this model of care have been used with a dramatically different patient population, and with similar success, in the criminal justice system in HOPE Probation and 24/7 Sobriety. The authors review these programs and discuss implications for extending elements of the new paradigm more widely.

Dually reactive multilayer coatings enable orthogonal manipulation of underwater superoleophobicity and oil adhesion via post-functionalization.

Fish scale-inspired underwater superoleophobic coatings with low oil adhesion can be achieved through the creation of hierarchical surface topography on water-compatible materials (including polymeric hydrogels, metal oxides, and electrostatic multilayers). While promising, these method do not allow for the underwater superoleophobicity and oil adhesion to be independently tuned, limiting their potential applications. Here we report the design of a conceptually novel class of coatings, dually reactive multilayer coatings, whose underwater superoleophobicity and oil adhesion can be independently tuned through the orthogonal functionalization of two types of reactive moieties at ambient conditions. Moreover, the cooperative assembly of amphiphiles on the modified underwater superoleophobic coating gives rise to a switchable oil adhesion while retaining the extreme oil-repellency (advancing oil contact angle >165°). Interestingly, the reversible change in the oil adhesion of the underwater superoleophobic coatings depends on the interplay between the molecular structure and concentration of the amphiphiles and the pH of the aqueous solution. Building on these findings, we developed superoleophobic sensors that enable the real-time and naked eye identification of (1) the charge of synthetic ionic surfactants and (2) the concentration of bile acids. Overall, the results reported in this work provide design principles by which molecular self-assembly and oil adhesion can be coupled at underwater superoleophobic surfaces, and hint at principles by which physiologically important amphiphiles and metabolites can be rapidly sensed with the naked eye using our novel class of superoleophobic surfaces.

Modularizable Liquid-Crystal-Based Open Surfaces Enable Programmable Chemical Transport and Feeding using Liquid Droplets.

Droplet-based miniature reactors have attracted interest in both fundamental studies, for the unique reaction kinetics they enable, and applications in bio-diagnosis and material synthesis. However, the precise and automatic feeding of chemicals, important for the delicate reactions in these miniaturized chemical reactors, either requires complex, high-cost microfluidic devices or lacks the capability to maintain a pinning-free droplet movement. Here, the design and synthesis of a new class of liquid crystal (LC)-based open surfaces, which enable a controlled chemical release via a programmable LC phase transition without sacrificing the free transport of the droplets, are reported. It is demonstrated that their intrinsic slipperiness and self-healing properties enable a modularizable assembly of LC surfaces that can be loaded with different chemicals to achieve a wide range of chemical reactions carried out within the droplets, including sequential and parallel chemical reactions, crystal growth, and polymer synthesis. Finally, an LC-based chemical feeding device is developed that can automatically control the release of chemicals to direct the simultaneous differentiation of human induced pluripotent stem cells into endothelial progenitor cells and cardiomyocytes. Overall, these LC surfaces exhibit desirable levels of automation, responsiveness, and controllability for use in miniature droplet carriers and reactors.

Conservation and Identity Selection of Cationic Residues Flanking the Hydrophobic Regions in Intermediate Filament Superfamily.

The interplay between the hydrophobic interactions generated by the nonpolar region and the proximal functional groups within nanometers of the nonpolar region offers a promising strategy to manipulate the intermolecular hydrophobic attractions in an artificial molecule system, but the outcomes of such modulations in the building of a native protein architecture remain unclear. Here we focus on the intermediate filament (IF) coiled-coil superfamily to assess the conservation of positively charged residue identity via a biostatistical approach. By screening the disease-correlated mutations throughout the IF superfamily, 10 distinct hotspots where a cation-to-cation substitution is associated with a pathogenic syndrome have been identified. The analysis of the local chemical context surrounding the hotspots revealed that the cationic diversity depends on their separation distance to the hydrophobic domain. The nearby cationic residues flanking the hydrophobic domain of a helix (separation <1 nm) are relatively conserved in evolution. In contrast, the cationic residues that are not adjacent to the hydrophobic domain (separation >1 nm) tolerate higher levels of variation and replaceability. We attribute this bias in the conservation degree of the cationic residue identity to reflect the interplay between the proximal cations and the hydrophobic interactions.

Prescription drug abuse: an epidemic dilemma.

The nonmedical use of prescribed controlled substances has become a major public health problem. This article reviews the extent of prescription drug abuse reflected in drug overdose deaths, youth drug use and drug-impaired driving. Efforts to reduce illegal, nonmedical use of prescribed controlled drugs must be balanced so as not to interfere with appropriate medical use of these medicines. Future policy options include identifying and expanding leadership in the research and medical communities, creation of a national public education campaign, development of abuse-resistant drug formulas, increasing prescription drug monitoring programs and enforcement efforts, establishing effective drugged driving laws, and improving substance abuse treatment.

Molecular recognition of human islet amyloid polypeptide assembly by selective oligomerization of thioflavin T.

Selective oligomerization is a common phenomenon existing widely in the formation of intricate biological structures in nature. The precise design of drug molecules with an oligomerization state that specifically recognizes its receptor, however, remains substantially challenging. Here, we used scanning tunneling microscopy (STM) to identify the oligomerization states of an amyloid probe thioflavin T (ThT) on hIAPP8-37 assembly to be exclusively even numbers. We demonstrate that both adhesive interactions between ThT and the protein substrate and cohesive interactions among ThT molecules govern the oligomerization state of the bounded ThT. Specifically, the work of the cohesive interaction between two head/tail ThTs is determined to be 6.4 k B T, around 50% larger than that of the cohesive interaction between two side-by-side ThTs (4.2 k B T). Overall, our STM imaging and theoretical understanding at the single-molecule level provide valuable insights into the design of drug compounds using the selective oligomerization of molecular probes to recognize protein self-assembly.

Ultrasensitive and Selective Detection of SARS-CoV-2 Using Thermotropic Liquid Crystals and Image-Based Machine Learning.

Rapid, robust virus-detection techniques with ultrahigh sensitivity and selectivity are required for the outbreak of the pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Here, we report that the femtomolar concentrations of single-stranded ribonucleic acid (ssRNA) of SARS-CoV-2 trigger ordering transitions in liquid crystal (LC) films decorated with cationic surfactant and complementary 15-mer single-stranded deoxyribonucleic acid (ssDNA) probe. More importantly, the sensitivity of the LC to the SARS ssRNA, with a 3-bp mismatch compared to the SARS-CoV-2 ssRNA, is measured to decrease by seven orders of magnitude, suggesting that the LC ordering transitions depend strongly on the targeted oligonucleotide sequence. Finally, we design a LC-based diagnostic kit and a smartphone-based application (app) to enable automatic detection of SARS-CoV-2 ssRNA, which could be used for reliable self-test of SARS-CoV-2 at home without the need for complex equipment or procedures.