Exploring Drug De-addiction Treatment in Unani Medicine.

Background: Drug addiction, or substance abuse disorder, has a long history. The use of a drug that causes dependence has been used in various religious and tribal initiation ceremonies. Currently, recreational use or peer modelling leads an individual to substance abuse. The magnitude of the problem of addiction increases multifold in the presence of stressors like broken families, joblessness, occupational stress, etc. Objectives: The de-addiction process is used to relieve an individual's craving for the drug. It is a painful process, as several effects of withdrawal compel a person to return to the drugs again and again. Our aim is to explore the available literature on the use of Unani medicine for de-addiction. Methodology: We surveyed various classical books from the available literature for drug de-addiction in Unani medicine. Indexed journals were also surveyed for the available related material using various keywords like "opium addiction" and "Unani medicine and de-addiction " and the information was filtered for this review. Results: We observed that there was an elaborate scheme for de-addiction in opium addiction and the process is so general that it could serve as a framework for the de-addiction process for other similar drugs. Conclusion: Unani medicine is significant in the literature as being among the the available de-addiction addiction processes and may furnish several leads for various herbal drugs that may be used for de-addiction in the future.

Observations from a peculiar case of volatile substance dependence-A case report.

Volatile substance dependence is a relatively rare form of substance use disorders. It is predominantly noted in the adolescent age group. Higher prevalence is also seen in individuals from the lower socio-economic strata. These agents induce a rapid mood change by altering the levels of central neurotransmitters. Here we present a unique case of volatile substance dependence in a middle aged female with iron deficiency anemia. We managed this with the SSRIs and parenteral iron preparations which led to recovery. This emphasizes the fact that any treatment regimen must address all the factors, co-morbidities and patient characteristics for complete recovery.

Mephentermine dependence in a young Indian adult without psychosis.

Mephentermine is a vasopressor drug closely related to amphetamine and methamphetamine. Cases of abuse and dependence to mephentermine have dotted medical literature for a long time. Till date, 11 cases of dependence to mephentermine have been published. In this report, a case of mephentermine dependence is being discussed. The patient was a young adult male who was dependent to mephentermine for nearly 3 years. He was an athlete and was introduced to mephentermine by his peer for enhancing performance. He did not develop any major physical or psychiatric issue due to the drug. He was managed on out patient basis. Though cases of mephentermine dependence are few and far in medical literature, reports from other sources indicate that the problem could be more common and could be on rise. High index of suspicion and holistic care is likely to help patients and treating clinicians.

Δ9-tetrahydrocannabinol: Drug discrimination abuse liability testing in female Lister Hooded rats: Trials, tribulations and triumphs.

INTRODUCTION: The assessment of the abuse potential of CNS-active drugs is a regulatory requirement. Drug discrimination is one of the nonclinical tests that contribute to this assessment by providing information on a drug's potential to induce a discriminative stimulus comparable to that of a known drug of abuse. AIM: The objective was to validate drug discrimination in the rat for the purpose of supporting regulatory submissions for novel drugs with potential cannabinoid-like activity. METHODS: Ten female Lister hooded rats were trained to discriminate no-drug from Δ9-THC (1.5 mg/kg, IP) under a FR10 schedule of reinforcement. Once trained, a Δ9-THC dose-response curve was obtained using doses of 0.25, 0.75, 1.5, and 3 mg/kg, IP. This was followed by evaluation of amphetamine (0.3 mg/kg, SC); morphine (3 mg/kg, IP); midazolam (2.5 mg/kg, PO); and the synthetic cannabinoids WIN55,212-2 (0.75 to 2 mg/kg, IP), CP-47,497 (0.5 to 2 mg/kg, IP), and JWH-018 (1 mg/kg, IP) for their discriminative stimulus similarity to Δ9-THC. RESULTS: Pharmacological specificity was demonstrated by achieving the anticipated dose-response curve for Δ9-THC, and a vehicle-like response for the non-cannabinoid drugs. Although full generalisation was obtained for JWH-018, in contrast to published literature, WIN55,212-2 and CP-47,497 failed to generalise to Δ9-THC. DISCUSSION: Based on the literature review performed in light of the results obtained, contrasting and unpredictable behavioural responses produced by cannabinoids in animals and humans raises the question of the reliability and relevance of including drug discrimination and self-administration studies within an abuse potential assessment for novel cannabinoid-like drugs.

Harmful smartphone applications promoting alcohol and illicit substance use: a review and content analysis in the United States.

Few studies have conducted analysis of commercially available smartphone applications designed to promote alcohol and illicit substance use. The aim of this review is to determine harmful themes of content in applications promoting alcohol and illicit substance use found using recovery app search terms. A systematic search, via Apple iTunes and Google Play stores, was conducted of applications targeting abstinence or reduced substance use in online app stores (n = 1,074 apps) in March 2018. We conducted a secondary analysis of apps encouraging alcohol and illicit substance use in July 2018. Our initial search yielded 904 apps pertaining to alcohol and illicit substance use. Four reviewers conducted a content analysis of 102 apps meeting inclusion criteria and assessed app design, delivery features, text, and multimedia content pertaining to substance use. The initial coding scheme was refined using a data-driven, iterative method grouping in thematic categories. The number of apps coded to a specific substance include: alcohol (n = 74), methamphetamine (n =13), cocaine (n = 15), heroin (n = 12), and marijuana (n = 15), with nine apps overlapping more than one substance. Key themes identified among apps included: (i) tangibility (alcohol home delivery services); (ii) social networks (builtin social media platforms promoting substance use); (iii) software design (gamification or simulation of substance use); and (iv) aesthetics (sexual or violent imagery). Despite claims of restricting apps promoting substance use, further efforts are needed by online app stores to reduce the availability of harmful content.

Kratom Dependence and Treatment Options: A Comprehensive Review of the Literature.

Kratom, or Mitragyna speciosa Korth., is a tropical plant prevalent in Southeast Asia, and it is utilized as a traditional remedy for symptomatic relief of various illnesses. It has been labeled as an atypical opioid with significant narcotic-like properties, capable of inducing kratom dependence among those who misuse or abuse it. The prevalence of kratom use has drastically increased worldwide, raising concerns among healthcare providers, particularly regarding the availability of efficacious treatment options for kratom dependence. This manuscript provides a comprehensive narrative review of literature focusing on the psychoactive alkaloids of kratom, the possible neurobiological and pathophysiological models underlying the occurrence of kratom dependence, and the clinical presentations and effective treatment options available for kratom dependence. The psychoactive alkaloids of kratom, such as mitragynine (MG) and 7-hydroxymitragynine (7-HMG), act as partial mu opioid agonists and induce kratom dependence. As a result, regular kratom use leads to withdrawal symptoms on abstinence, along with craving, tolerance, and cross-tolerance to morphine. The psychological withdrawal symptoms reported include depressed mood, anxiety, restlessness, irritability, and feeling tense, while the physical withdrawal symptoms are myalgia and body ache, joint pain, lacrimation, running nose, yawning, insomnia, diarrhea, feverish sensation, loss of appetite, tremors, itching over the body, loss of concentration, and chills. Neonatal withdrawal symptoms, such as oral intolerance, restlessness, irritability, and vomiting, are also reported in newborns of women who are on regular kratom use. Sublingual buprenorphine-naloxone (Suboxone) is reported as a promising treatment for detoxification and maintenance replacement therapy for kratom-dependent users. Alternative treatments for in-patient detoxification include intravenous clonidine and a combination of oral dihydrocodeine and lofexidine. We conclude by adding a note on the research gap concerning kratom dependence, which future studies should focus on.

Burnout and Self Care for Palliative Care Practitioners.

Burnout is common in physicians who care for patients with serious illness, with rates greater than 60% in some studies. Risk factors for burnout include working on small teams and/or in small organizations, working longer hours and weekends, being younger than 50 years, burdensome documentation requirements, and regulatory issues. Personal factors that can protect against burnout include mindfulness, exercise, healthy sleep patterns, avoiding substance abuse, and having adequate leisure time. Institutional and work factors that can buffer against burnout include working on adequately staffed teams, having a manageable workload, and minimally burdensome electronic health record documentation.

25C-NBF, a new psychoactive substance, has addictive and neurotoxic potential in rodents.

The use of new psychoactive substances (NPSs) as a substitute for illegal drugs is increasing rapidly and is a serious threat to public health. 25C-NBF is a newly synthesized phenethylamine-type NPS that acts as a 5-hydroxyindoleacetic acid (5-HT) receptor agonist, but little is known about its pharmacological effects. Considering that NPSs have caused unexpected harmful effects leading to emergency and even death, scientific confirmation of the potential adverse effects of 25C-NBF is essential. In the present study, we investigated whether 25C-NBF has addictive and neurotoxic potential and causes neurochemical changes. In addictive potential assessments, high conditioned place preference (CPP) scores and stable self-administration (SA) were observed in the 25C-NBF groups (CPP [3 mg kg-1]; SA [0.01, 0.03, 0.1 mg kg-1]), suggesting the addictive liability of 25C-NBF. In neurotoxic potential assessments, 25C-NBF treatment (single super-high dose [1 × 15, 30, 40 mg kg-1]; repeated high dose [4 × 8, 15, 30 mg kg-1]) resulted in reduced motor activity (open field test), abnormal motor coordination (rota-rod test) and impaired recognition memory (novel object recognition test), suggesting that 25C-NBF is neurotoxic leading to motor impairment and memory deficits. Subsequently, immunohistochemistry showed that 25C-NBF treatment decreased tyrosine hydroxylase (TH) expression and increased ionized calcium-binding adapter molecule 1 (Iba-1) expression in the striatum. Taken together, our results clearly demonstrate the dangers of recreational use of 25C-NBF, and we suggest that people stop using 25C-NBF and other NPSs whose pharmacological effects are not precisely known.

Skin hyperpigmentation: a rare presenting symptom of nitrous oxide abuse.

Context: Recreational nitrogen oxide (N2O) abuse can cause nervous system damage. There was a sharp increase in the number of patients with neurological disorders associated with recreational N2O use in China, as recreational N2O use became popular in young people nationwide. Among cases with neurological disorders caused by N2O abuse, a few showed skin hyperpigmentation, which has rarely been reported. We explored the characteristics of hyperpigmentation in N2O abusers to draw the attention of clinicians to this rare cutaneous symptom related to N2O abuse.Methods: We retrospectively collected data of patients with neurological disorders related to recreational N2O abuse in Shengjing Hospital of China Medical University from January 2014 to June 2019. Detailed clinical data were gathered from patients who manifested skin pigmentation, including the history of N2O abuse and characteristics of neurological lesions and skin pigmentation.Results: In total, 66 patients (average age: 22.7 ± 4.5 years, 36 males) with neurological disorders due to N2O abuse were included; four of them (17-23 years old, 1 male) manifested skin hyperpigmentation. The duration of N2O abuse of the four patients ranged from 2 to 24 months, and they all had peripheral neuropathy; the two patients also had subacute combined degeneration of the spinal cord. One patient exhibited significant hyperpigmentation throughout the body (trunk, limbs, and face), with no abnormalities in cortisol and other biochemical tests. One patient presented with punctuate pigmentation throughout the trunk. Two patients presented with finger skin pigmentation, especially in the distal phalanxes. Pigmentation after N2O use remitted slowly with vitamin B12 supplementation.Conclusion: Skin hyperpigmentation is a rare symptom in N2O abusers, which can distribute locally in hands or diffusely throughout the body. Therefore, attention should be paid to a history of N2O abuse and serum vitamin B12 level should be tested.

Moral Injury, Substance Use, and Posttraumatic Stress Disorder Symptoms Among Military Personnel: An Examination of Trait Mindfulness as a Moderator.

Mindfulness-based approaches have been suggested as possible methods to treat moral injury in military personnel. However, empirical research has yet to evaluate if mindfulness acts as a protective factor for the possible negative effects of moral injury, such as alcohol use, drug use, or posttraumatic stress disorder (PTSD) symptoms. In this study, we investigated if five facets of mindfulness (i.e., observing, nonjudging, nonreactivity, awareness, and describing) moderated associations between moral injury and the outcomes of PTSD symptoms, alcohol misuse, and drug abuse symptoms in a sample of military personnel. Participants were 244 military personnel (the majority were former military members) who had been deployed at least once during the Iraq War, War in Afghanistan, other wars, or humanitarian missions. The study results indicated that nonjudging, ß = -.22, and awareness, ß = -.25, had significant attenuating effects on the association between moral injury and drug abuse symptoms. However, observing, ß = .17; nonreactivity, ß = .23; and describing, ß = .15, had significant synergistic effects (i.e., they strengthened the association between moral injury and drug abuse symptoms). There were no significant moderation effects on the associations between moral injury and PTSD symptoms or between moral injury and alcohol misuse. Our results provide initial evidence that not all facets of mindfulness may protect against the challenges of coping with moral injury. Directions for future research and implications for practice are discussed.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Daño moral, uso de sustancias y síntomas de TEPT entre el personal militar: un examen de la atención consciente de los rasgos como moderador MINDFULNESS Y DAÑO MORAL EN VETERANOS Se han sugerido enfoques basados ​​en la atención plena (o mindfulness en inglés) como posibles métodos para tratar el daño moral en el personal militar. Sin embargo, la investigación empírica aún debe evaluar si la atención plena actúa como un factor protector para los posibles efectos negativos del daño moral, como el consumo de alcohol, el uso de drogas o los síntomas del trastorno de estrés postraumático (TEPT). En este estudio, investigamos si cinco facetas de la atención plena (es decir, observar, no juzgar, no reaccionar, conciencia y describir) moderaron las asociaciones entre daño moral y los resultados de los síntomas del TEPT, el uso indebido del alcohol y los síntomas del abuso de drogas en una muestra de personal militar. Los participantes eran 244 militares (la mayoría de ellos ex militares) que habían sido desplegados al menos una vez durante la Guerra de Irak, la Guerra en Afganistán, otras guerras o misiones humanitarias. Los resultados del estudio indicaron que el no juzgar, ß = −.22, y la conciencia ß = −.25, tuvieron efectos atenuantes significativos en la asociación entre daño moral y síntomas de abuso de drogas. Sin embargo, observar, ß = .17; no reactividad, ß = .23; y describir, ß = .15, tuvo efectos sinérgicos significativos (es decir, fortalecieron la asociación entre daño moral y los síntomas de abuso de drogas). No hubo efectos significativos de moderación en las asociaciones entre el daño moral y los síntomas del TEPT o entre el daño moral y el abuso del alcohol. Nuestros resultados proporcionan evidencia inicial de que no todas las facetas de la atención plena pueden proteger contra los desafíos de enfrentar el daño moral. Se discuten lineamientos para futuras investigaciones y las implicaciones para la práctica.

Phenibut (ß-Phenyl-γ-Aminobutyric Acid): an Easily Obtainable "Dietary Supplement" With Propensities for Physical Dependence and Addiction.

PURPOSE OF REVIEW: Phenibut (ß-phenyl-γ-aminobutyric acid) is a psychoactive GABA analogue currently being marketed online as an anxiolytic and nootropic dietary supplement. Its use is growing in popularity, but its pharmacological activity is well beyond that of a conventional nutritional supplement, and similar to that of a prescription strength sedative. This review will focus on the potential adversities of phenibut use and will discuss what treatment options may be beneficial to afflicted patients. RECENT FINDINGS: Over the last several years, multiple case reports have highlighted phenibut's potential to produce the conditions of physical dependence, withdrawal, and addiction. In cases involving intoxication, patients have presented with a varying degree of mental status changes, from being minimally responsive to manifesting symptoms of an agitated delirium. Phenibut is a potent psychoactive substance with GABAB agonist properties, which is emerging as a drug of misuse through growing internet sales. Its marketing as a "dietary supplement" is inaccurate and misleading, given its pharmacological profile and ability to induce the physiological changes associated with withdrawal and physical dependence.

Substance type moderates the longitudinal association between depression and substance use from pre-treatment through a 1-year follow-up.

BACKGROUND: Research examining directionality of the relationship between depressive symptoms and substance use following treatment entry is limited. Furthermore, substances differ in their neurobiological effects on mood. The relationship between depression and substance use following treatment entry may be moderated by dependence on specific substances. The study tested (a) lagged effects between depressive symptoms and substance use frequency following substance use treatment entry through a 1-year post-treatment follow-up and (b) if substance dependence type moderates these effects. METHODS: Participants (N = 263) entering residential treatment were assessed for DSM-IV substance dependence, depressive symptoms (Beck Depression Inventory), and percentage of substance use days at post-treatment, 1-, 3-, 6- and 12-month follow-up assessments (time t0 to t4). Linear mixed effects models tested lagged effects between depressive symptoms and substance use frequency and the impact of substance type (i.e., dependence on alcohol, cannabis, opioid, cocaine, hallucinogen/PCP) on this relationship. RESULTS: After controlling for concurrent effects, substance type moderated each longitudinal relationship. Depressive symptoms significantly predicted substance use frequency at the subsequent follow-up assessment, only among individuals with pre-treatment opioid dependence (B = 5.55, SE = 0.89, z = 6.21, p < 0.01). Substance use frequency significantly predicted depressive symptoms at the subsequent follow-up assessment, but not among individuals with cannabis dependence at pre-treatment (B = 1.01, SE = 0.22, t (524) = 4.49, p < 0.01). CONCLUSIONS: The directionality of depression-substance use comorbidity may differ based on the substance of dependence at pre-treatment. Opioid users may especially benefit from treating both depression and substance use.

Making the hidden seen: A narrative analysis of the experiences of Assumption of Care at birth.

BACKGROUND: Being involved in any child protection system is complex and multifaceted and none more so than in non-voluntary Assumption of Care which occurs in New South Wales when, for child protection concerns, the Department of Family and Community Services removes a newborn baby from her/his mother. OBJECTIVE: This research studied childbearing women's and professionals' experiences of Assumption of Care at birth to increase understanding of individual participants' stories, how they made sense of meanings and how these experiences framed their lives. METHOD: A narrative inquiry framework guided interviews with four groups: childbearing women, midwives, social workers and Family and Community Services case managers. Holistic form was used for reading, interpreting and analysing the narratives. FINDINGS: This research found unwanted emotional (isolation, shame, guilt, loss, disenfranchised grief) and physical consequences (depression, substance abuse complications) for women experiencing an Assumption of Care at the time of birth. There were also conflicting ethical and moral positions for the professionals involved. The use/abuse of power, concealment of facts and disenfranchised grief were identified as intertwined plots that caused or increased tensions. DISCUSSION: Both the women and the professionals felt pressure from trying to achieve competing and overlapping roles. The unwanted effects of Assumption of Care are exacerbated by the current child protection and maternity care systems. CONCLUSION: To address the tensions raised in this study, we suggest a two-fold change to maternity care for women at risk of an Assumption of Care: a therapeutic justice model of maternity care and continuity of midwifery care with a dedicated midwife. Introducing these changes could increase women's and children's safety and wellbeing.

[FSGS collapsing variant during anabolic steroid abuse: Case Report].

Anabolic Androgenic Steroids (AAS) is an hormone family whose use has considerably increased among body-builders during the last decades. The AAS abuse, especially associated with other drugs or nutritional supplements and protein loads, may cause a variety of pathologies to several organs with a mechanism related to dosage, timing and substance. The kidney is the main metabolizer of these drugs and it can be acutely or chronically damaged with ESKD. The literature reports some cases of Focal Segmental Glomerulosclerosis (FSGS) in body-builders who abused of AAS. However, the link is not well understood and limited to some case-studies. In this paper, we report the case of a young body-builder who developed a FSGS collapsing variant with ESKD after prolonged abuse of AAS and a strongly hyperproteic diet and other dietary supplements. The patient underwent a genetic test because of the rapid and irreversibile onset of ESKD. The test showed a gene mutation of ACTN4, predisposing and causal of some genetic forms of FSGS. It was a very complex case, caused by several factors. The mutant protein of ACTN4 gene makes most vulnerable the cytoskeleton of the podocytes to external disturbances. That would explain why in those patients where the mutation has occurred, only those patients subject to "unfavorable environmental conditions", like the abuse of AAS, can develop a disease.

The renaissance in psychedelic research: What do preclinical models have to offer.

Human research with psychedelics is making groundbreaking discoveries. Psychedelics modify enduring elements of personality and seemingly reduce anxiety, depression, and substance dependence in small but well-designed clinical studies. Psychedelics are advancing through pharmaceutical regulatory systems, and neuroimaging studies have related their extraordinary effects to select brain networks. This field is making significant basic science and translational discoveries, yet preclinical studies have lagged this renaissance in human psychedelic research. Preclinical studies have a lot to offer psychedelic research as they afford tight control of experimental parameters, subjects with documented drug histories, and the capacity to elucidate relevant signaling cascades as well as conduct invasive mechanistic studies of neurochemistry and neural circuits. Safety pharmacology, novel biomarkers, and pharmacokinetics can be assessed in disease state models to advance psychedelics toward clinical practice. This chapter documents the current status of psychedelic research, with the thematic argument that new preclinical studies would benefit this field.

Posttraumatic Stress Symptoms and Emerging Adult Sexual Minority Men: Implications for Assessment and Treatment of Childhood Sexual Abuse.

Emerging adulthood (EA) is a developmental period marked by unique challenges that affect health including burgeoning occupational, relational, and financial stability; and increased risk taking in terms of sexual behavior(s) and substance use. Data were collected from 296 HIV-uninfected sexual minority men with childhood sexual abuse (CSA) histories. We analyzed baseline assessment data from a multisite randomized controlled trial that tested the efficaciousness of an experimental psychosocial treatment and examined vulnerabilities known to be linked with CSA. Our analyses compared EA sexual minority men, aged 18-29, with older sexual minority men (OSMM) on posttraumatic stress disorder (PTSD) and other mental health and substance use outcomes. We found higher odds of PTSD, odds ratio (OR) = 0.57, 95% CI [0.33, 0.96]; panic disorder or panic disorder with agoraphobia, OR = 0.36, 95% CI [0.16, 0.85]; and cocaine use, OR = 0.50, 95% CI [0.25, 0.97], among OSMM and higher odds of alcohol intoxication, OR = 5.60, 95% CI [3.20, 9.82]; cannabis use, OR = 3.09, 95% CI [1.83, 5.21]; and non-HIV sexually transmitted infections, OR = 3.03, 95% CI [1.29, 7.13], among the EA men. These results present a complex picture of health risks among sexual minority men in general and EA sexual minority men in particular. HIV seroconversion linked health risk behaviors, among sexual minority men, may be better addressed via increased attention to treating trauma and comorbid mental health and substance use problems using evidence-based psychosocial assessments and integrated treatment platforms that are tailored to this population.

The gold-standard in preclinical abuse liability testing: It's all relative.

All new molecular entities (NMEs) with targeted or indirect effects on the central nervous system (CNS) must be evaluated for their abuse liability as a part of their nonclinical development plan. Inherently key in the drug control review is the term "relative abuse liability". The basis for determination of drug control is critically dependent on the nonclinical assessment of the reinforcing attributes of the NME in animals (rat is the regulatory preferred species) in a standard operant conditioning paradigm. Pharmaceutical representatives without a background in behavioral analysis or operant conditioning models must weigh through conceptually-intriguing language and constructs that accurately convey and communicate the relative potential for abuse to drug regulatory experts in the field. Effective statutory language in the preclinical assessment of relative abuse liabilities for schedule control status reviews must be 1) specific; 2) concise; 3) familiar to the regulators; 4) unambiguous; 5) constructive; and 6) formalized with respect to both international and national drug control policies. In this review we attempt to define and highlight the importance of the statutory language used to report self-administration study results to both parties engaged in NDA approval process.

Racing the clock: The role of circadian rhythmicity in addiction across the lifespan.

Although potent effects of psychoactive drugs on circadian rhythms were first described over 30 years ago, research into the reciprocal relationship between the reward system and the circadian system - and the impact of this relationship on addiction - has only become a focus in the last decade. Nonetheless, great progress has been made in that short time toward understanding how drugs of abuse impact the molecular and physiological circadian clocks, as well as how disruption of normal circadian rhythm biology may contribute to addiction and ameliorate the efficacy of treatments for addiction. In particular, data have emerged demonstrating that disrupted circadian rhythms, such as those observed in shift workers and adolescents, increase susceptibility to addiction. Furthermore, circadian rhythms and addiction impact one another longitudinally - specifically from adolescence to the elderly. In this review, the current understanding of how the circadian clock interacts with substances of abuse within the context of age-dependent changes in rhythmicity, including the potential existence of a drug-sensitive clock, the correlation between chronotype and addiction vulnerability, and the importance of rhythmicity in the mesocorticolimbic dopamine system, is discussed. The primary focus is on alcohol addiction, as the preponderance of research is in this area, with references to other addictions as warranted. The implications of clock-drug interactions for the treatment of addiction will also be reviewed, and the potential of therapeutics that reset the circadian rhythm will be highlighted.