Physical Dependence Research Articles

Reliability Modeling of Mutual DCFP Considering Failure Physical Dependency

Reliability Modeling of Mutual DCFP Considering Failure Physical Dependency

Is balance a marker of health status in patients with reduced left ventricular ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. A significant percentage of patients hospitalized for the coronary disease have a decrease in left ventricular ejection fraction (LVEF), limiting their ability to perform their daily activities and increasing their dependence. Mobility is one of the most affected factors, namely postural balance, walking, transfers, hygiene care, among others. This fact can hinder the resolution of the underlying pathology, delay its resolution, facilitate the appearance of comorbidities, and cause prolonged hospitalization, causing a greater state of fragility. The implementation of measures that improve this dependence and fragility will hypothetically have effects on quality of life and prognosis. Exercise inertia is a well-defined cardiovascular (CV) risk factor, that causes greater physical dependence, greater frailty, and less responsiveness to disease. The authors consider that any improvement in this aspect will lead to a better CV prognosis. Purpose To assess the physical fitness of patients undergoing a phase I rehabilitation program to improve their cardiac condition Methods Longitudinal, prospective, and experimental study hospitalized for coronary disease. Physical fitness was evaluated: 1) dynamic balance and mobility (Fullerton test battery that already includes the 6-minute walk test and body composition), 2) upper body strength (handgrip strength test), 3) cardiorespiratory fitness, and 4) body composition. Morisky Medication Adherence Scale and STOP-Bang scale (Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender) were also applied. The descriptive and inferential analysis was performed using the R version 4.2.2 program, all test results with p<0.05 are considered statistically significant. Results 65 patients were evaluated, with a median age of 63 and interquartile range (57, 72), of which 23% had LVEF≤40%; 86% had high blood pressure, 80% have dyslipidemia, 73% drank alcohol daily and only 23% practice regular physical exercise. When applying the Fullerton balance test, we found that: 74% cannot safely turn 360º, needing four or more steps in both directions; 92% cannot walk independently and without interruptions on a straight line on the ground; 74% cannot balance on one leg autonomously and maintain the position for 20 seconds. We also found that 68% had a high risk of sleep apnea (STOP-Bang scale). LVEF data were divided into classes (LVEF ≤40; LVEF 41-50; LVEF >50) and the association was evaluated using Fisher's exact test and Kruskal-Wallis test, and it was verified that there is a positive association between balance and LVEF (p-value = 0.2) and 6mTM and LVEF (p-value = 0.07). Conclusion The positive associations found between balance and mobility limitations in this sample suggest that specific programs may improve balance and, consequently, the patient's general state of health.

Epistemic uncertainty quantification in structural systems using improved universal grey theory

It is important to account for uncertainties in structures during the analysis and design. Based on the source and nature, the uncertainties can be classified as aleatory and epistemic. Aleatory uncertainties arise due to the intrinsic randomness nature of physical system, whereas epistemic uncertainties realize on account of insufficient knowledge. When the information about the system is grey (i.e., partially available as range or interval), methods such as combinatorial approach, interval methods (IM) and universal grey theory (UGT) are generally adopted. The combinatorial optimization becomes computationally expensive when the dimension of uncertain system is large. Interval analysis leads to overestimation due to violations of the physical law and dependency problem. The satisfaction of the physical law (distributive law) that arises out of defining the arithmetic relations, contributes to the UGT free from dependency problem, and makes the approach more efficient. The traditional UGT is ineffective in certain conditions, wheneither one or both the bounds are negative with the absolute value of the upper bound being smaller i.e.,x¯⩽x̲. Therefore, this paper proposes a necessary modification in arithmetic operations to overcome the incapability of traditional UGT. The efficiency of proposed method is demonstrated through three numerical examples. Comparisons have been made with the conventional techniques to substantiate the proposed methodology, and the results obtained show that the proposed method is computationally efficient in terms of efforts and accuracy.

Comparing quality of care outcomes between assisted living and nursing homes before and during the COVID-19 pandemic.

While assisted living (AL) and nursing home (NHs) residents in share vulnerabilities, AL provides fewer staffing resources and services. Research has largely neglected AL, especially during the COVID-19 pandemic. Our study compared trends of practice-sensitive, risk-adjusted quality indicators between AL and NHs, and changes in these trends after the start of the pandemic. This repeated cross-sectional study used population-based resident data in Alberta, Canada. Using Resident Assessment Instrument data (01/2017-12/2021), we created quarterly cohorts, using each resident's latest assessment in each quarter. We applied validated inclusion/exclusion criteria and risk-adjustments to create nine quality indicators and their 95% confidence intervals (CIs): potentially inappropriate antipsychotic use, pain, depressive symptoms, total dependency in late-loss activities of daily living, physical restraint use, pressure ulcers, delirium, weight loss, urinary tract infections. Run charts compared quality indicators between AL and NHs over time and segmented regressions assessed whether these trends changed after the start of the pandemic. Quarterly samples included 2015-2710 AL residents and 12,881-13,807 NH residents. Antipsychotic use (21%-26%), pain (20%-24%), and depressive symptoms (17%-25%) were most common in AL. In NHs, they were physical dependency (33%-36%), depressive symptoms (26%-32%), and antipsychotic use (17%-22%). Antipsychotic use and pain were consistently higher in AL. Depressive symptoms, physical dependency, physical restraint use, delirium, weight loss were consistently lower in AL. The most notable segmented regression findings were an increase in antipsychotic use during the pandemic in both settings (AL: change in slope = 0.6% [95% CI: 0.1%-1.0%], p = 0.0140; NHs: change in slope = 0.4% [95% CI: 0.3%-0.5%], p < 0.0001), and an increase in physical dependency in AL only (change in slope = 0.5% [95% CI: 0.1%-0.8%], p = 0.0222). QIs differed significantly between AL and NHs before and during the pandemic. Any changes implemented to address deficiencies in either setting need to account for these differences and require monitoring to assess their impact.

Topical issues of drug addiction criminological characteristics in Ukraine

It has been noted that drug addiction is a person’s mental and physical dependence on narcotic substances that occurs as a result of systematic drug use. In the course of drug addiction, a pathological dependence on any narcotic substance develops, which is accompanied by physical and mental addiction to the drug, which in turn negatively affects the psychophysiological functioning of the body.&#x0D; It has been argued that the key problems of drug addiction in Ukraine are the following: socio-economic problems in the country; insufficient preventive work among the population; perception of drugs as a means of social interaction; lack of alternatives in solving personal problems; unproductive justice system; high level of corruption; low level of self-awareness; open borders.&#x0D; It has been stated that the criminological characteristic of drug addiction in Ukraine can be revealed through a combination of the following factors: drug addiction is a factor that contributes to the commission of crimes in order to obtain funds to buy drugs; drug addiction causes changes in the behaviour and thinking of the addict, and therefore may lead to an increase in the likelihood of committing crimes; it may be the cause of violence or other crimes, as it promotes aggressive behaviour and reduces inhibition; it reduces the social adaptation of the addict, which increases the likelihood that the person will become a criminal; drug addiction can cause a loss of control over one's own behaviour and a decrease in self-esteem, which, in turn, is a determining factor in crime.&#x0D; It has been summarised that crime and drug addiction are directly interrelated, which requires a comprehensive approach to counteract them. To combat this problem, it is necessary not only to provide medical care for drug addicts, but also to develop social and criminal policies that will help reduce the spread of drug addiction and the number of crimes committed.

Current use of proton pump inhibitors and when to limit, stop or not start treatment

Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion that have changed treatment practice for gastric acid-related disorders. The major adequate indications for their use are treatment of gastro-esophageal reflux disease, peptic ulcers, eradication of Helicobacter pylori infection in combination with antibiotics and prophylaxis for patients on non-steroidal anti-inflammatory or antiplatelet drugs. Since their introduction, clinical success has been accompanied by widespread use of PPIs, which has steadily increased over the last decades without concomitant increase in the incidence of acid-related disorders. PPIs are now among the most widely prescribed class of medications worldwide and around 10% of Icelanders are current PPI users. This increase has been linked to PPI prescription without an indication, or continued use for longer duration than recommended. In recent years, concerns have been raised about PPI overuse and the associated increased risk of harm, not only in terms of increased costs but also the potential risk of physical dependence and long-term side effects of PPIs. The article is based on search in PubMed, the authors' own clinical experience and research, and is intended to provide practice advice on the use of PPIs with focus on appropriate prescription and deprescription of PPIs.

On QSPR Analysis of Molecular Descriptor and Thermodynamic Features of Narcotic Drugs

The use of chemical graph theory has been increased in almost every field of science in the last two decades. The graph invariants called topological descriptor are the numbers used to understand the physical and chemical properties of compounds. The use of narcotics causes many health and social issues in society. Narcotic drug addiction results in decreased pain perception, euphoria, dizziness, physical dependence, decreased breathing, and sleepiness in people. The overuse of narcotics may cause death. For the care and treatment of drug addictions, special health institutes provide proper medicines. The structures of narcotic drugs are explored with the help of degree-based graph invariants. In this article, we used degree-based topological indices to estimate the properties of narcotic drugs. Moreover, we have obtained that the topological indices utilize the antinarcotics drugs have a very strong correlation with the physicochemical properties mentioned in this manuscript.

A Study on the Attitude of Higher Secondary School Students Towards Drug and Alcohol in Papum Pare District of Arunachal Pradesh

Introduction: Addiction is a condition characterized by a strong desire to continue using a drug to which one has become addicted due to overconsumption because it produces a specific effect, most commonly a change in mental status. A strong desire to obtain the drug, a tendency to increase the dose, a mental or physical dependence, and negative consequences for the individual and society. In today's world, adolescent alcoholism and drug abuse are extremely serious problems. In our country, underage drinking is a major public health concern. Alcohol is the most commonly abused substance among today's youth, and adolescent drinking poses serious health and safety risks. Research Methodology: a. Research Design: Descriptive cum Normative survey method has been adopted for this research. b. Method of the Study: Retro prospective method of research where attempt has been made to study the Drug and Alcohol Attitude of higher secondary school students of Papum Pare of Arunachal Pradesh. Results and Discussion: The Drug and Alcohol attitude Mean Score of 300 school students of Papum Pare District was found to be 75.07. The mention mean score (75.07) comes under moderate and it is interpreted as ‘Average Drug and Alcohol’ level. Hence it shows that School students of Papum Pare district possess average Drug and Alcohol Attitude. The calculated t-value (-4.30) of Male and Female which is less than critical value (1.97) at 0.05 level of significance with Degree of Freedom (2.98). Therefore, the null hypothesis “there is no significant difference between Drug and Alcohol attitude of Male and Female School students of Papum Pare District of Arunachal Pradesh” is accepted. the calculated t-value (-1.61) of APST and NON-APST higher secondary school students is less than critical value (1.97) at 0.05 level of significance with Degree of Freedom 298. Therefore, the null hypothesis “there is no significant difference between Drug and Alcohol attitude of APST and NON-APST higher ....

Assessment of physiological and psychological dependence of tobacco use among patients visiting the tobacco cessation center in the tertiary institute of Shimla–Himachal Pradesh

ABSTRACT Background: The study aimed to assess the physiological and psychological dependence of tobacco use among patients visiting the Tobacco Cessation Center in the tertiary institution. Methods: A cross-sectional study design with simple random sampling was used. The information obtained from the subject was through interview recorded on a structured pro forma. The information included demographic details, dependence status based on smoking history and behavior, the Fagerstrom Test for Nicotine Dependence (FTND) for physiological dependence, and the Kano Test for Social Nicotine Dependence (KTSND) for psychological dependence. Tobacco use for both the smoked tobacco (ST) and smokeless tobacco (SLT) was recorded as the number of packs per day. Results: The mean pack year score was 122.6 ± 143.8. Similarly, the mean FTND score was 6.8 ± 2.4 and the mean KTSND score was 14.3 ± 4.1. The study subjects in various behavioral stages were precontemplation (26.1%), contemplation (21.1%), preparation (31.4%), action (20%), and maintenance (1.4%), respectively. Simple linear regression shows that the mean pack year, FTND, and KTSND scores were weakly explained for various stages of behavioral changes. Conclusion: Pack year is related to dose-response relationship which indicates both intensity and duration for developing tobacco-related diseases. The mean FTND score for physiological nicotine dependence for various variables clearly indicates price inelasticity for tobacco use. The mean KTSND score for psychological nicotine dependence for various variables clearly indicates some price elasticity for tobacco use and socio-behavioral factors related to the pattern of use. Price elasticity is important for the given scale that is used for the type of nicotine dependence considering ST is price inelastic and SLT as price elastic.

A Critical Review to Understand the Role of Ayurveda in Management of Opium Withdrawal

ABSTRACT Addiction is defined as a persistent, uncontrollable psychological or physiological dependence on a substance or behavior. It is a long-term brain condition that results in obsessive drug use despite negative effects. Addiction has general as well as negative social effects on people. Any type of drug addiction that is abruptly stopped can result in a psychosomatic condition. Even though contemporary medicine has developed several methods and molecules to combat these, the desired result is far from reality. Hence, it is the need of the hour to find a better solution to combat this drug addiction by exploring the principles of Ayurveda and also by following the drugs and regimen mentioned by the Acharyas in the classics. The information for this article has been gathered from my personal clinical experiences as well as from several completed clinical studies about drug addiction, withdrawal, and its management that has been incorporated in index and nonindex journals. The Padanshik kram is a special technique mentioned in Ayurveda to stop any substance (dangerous or nondangerous) that is homologous to humans by the process of tapering gradually. To replace and tapper up Sameer Gaj Kesari Ras, Vishtinduk Vati in opium withdrawal treatment can be very much beneficial. Along with the above medication, following methods such as psychological counseling, Abhyanga, Shirodhara, Yoga, meditation, and Satvavajaya Chikitsa can also be very much beneficial. Thus, in addiction and withdrawal due to substances containing opium or its derivatives, the Ayurvedic way of treatment can be one of the most effective modes of treatment.

Targeting Opioid Receptors in Addiction and Drug Withdrawal: Where Are We Going?

This review article offers an outlook on the use of opioids as therapeutics for treating several diseases, including cancer and non-cancer pain, and focuses the analysis on the opportunity to target opioid receptors for treating opioid use disorder (OUD), drug withdrawal, and addiction. Unfortunately, as has been well established, the use of opioids presents a plethora of side effects, such as tolerance and physical and physiological dependence. Accordingly, considering the great pharmacological potential in targeting opioid receptors, the identification of opioid receptor ligands devoid of most of the adverse effects exhibited by current therapeutic agents is highly necessary. To this end, herein, we analyze some interesting molecules that could potentially be useful for treating OUD, with an in-depth analysis regarding in vivo studies and clinical trials.

Physical Exercise Addiction Among Students Based on the EDS-R Scale Adapted for Poland

The purpose of the research was to adapt the Exercise Dependence Scale – Revised (EDS-R) by H. A. Hausenblas and D. Symons Downs to the Polish context and to evaluate the exercise addiction rate among students. The research was conducted online with 290 interviewees aged 19–23 years. Factor analysis confirmed the 7-factor structure of the EDS-R test and its good internal consistency. All the subscales were characterized by adequate reliability. To evaluate scale’s accuracy, the correlation between the EDS-R scale and a question concerning the number of hours of exercise per week was measured. The number of hours spent exercising per week was favorably connected with all of the subscales of the EDS-R. Those results were confirmed by differential analysis. Based on the EDS-R test, the participants were classified as (1) at risk of exercise addiction (5.5%), (2) not addicted (symptomatic group) (72.8%) and (3) not addicted (asymptomatic) (21.7%). The material presented in the article may contribute to further research using the Polish adaptation of the EDS-R scale in different populations (e.g., due to different physical activities undertaken by the exercisers).

Identification of the Physical Dependencies of Accurate Oil Level Measurement for Automotive Applications

The presented research addresses the problem of dependency analysis of the ultrasonic signal measured by a sensor in an engine oil bath. The dependency analysis is performed on a selected ultrasonic signal sensor solution containing its own generator and an ultrasonic signal receiver detecting the level of the oil in which it is immersed. The influence of the resulting amplitude of the received ultrasonic signal is mainly due to the level of the measured oil level and the oil temperature, as shown by the regression analysis and ANOVA (Analysis of Variance) testing performed. The analyzed dependence of the time determination of the length of the generated ultrasonic signal envelope is given by a set threshold value, which can be dynamically adjusted based on the backtracking evaluation. The analysis results in the form of approximation by the dependency algorithm confirm the assumption of possible standardization of the envelope parameters with the achievement of accuracy up to 99.02%. The analyzed parameters approximated by the temperature and oil level dependence algorithms include the amplitude of the measured signal, steepness of the rising edge, duration of the envelope, and the digitally processed amplitude value.

Opioid and Methadone Use for Infants With Surgically Treated Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) requiring surgical intervention is the most common reason for surgical procedures in preterm neonates. Opioids are used to manage postoperative pain, with some infants requiring methadone to treat physiologic opioid dependence or wean from nonmethadone opioid treatment during recovery. To describe postoperative opioid use and methadone treatment for infants with surgically treated NEC and evaluate postoperative outcomes. A cohort study of infants with surgically treated NEC admitted from January 1, 2013, to December 31, 2022, to 48 Children's Hospital Association hospitals contributing data to the Pediatric Health Information System (PHIS) was performed. Infants who received methadone preoperatively, were aged 14 days or less at the time of the operation, had a congenital heart disease-related operation, or died within 90 days of the operation were excluded. Mixed-effects multivariable logistic regression was used to evaluate thresholds for duration of opioid use after the operation associated with methadone treatment and clinical outcomes associated with methadone use were enumerated. Postoperative administration of nonmethadone opioids. Methadone use and postoperative length of stay, ventilator days, and total parenteral nutrition (TPN) days. Of the 2037 infants with surgically treated NEC identified, the median birth weight was 920 (IQR, 700.0-1479.5) g; 1204 were male (59.1%), 911 were White (44.7%), and 343 were Hispanic (16.8%). Infants received nonmethadone opioids for a median of 15 (IQR, 6-30) days after the operation and 231 received methadone (11.3%). The median first day of methadone use was postoperative day 18 (IQR, days 9-64) and continued for 28 days (IQR, 14-73). Compared with infants who received nonmethadone opioids for 1 to 5 days, infants receiving 16 to 21 days of opioids were most likely to receive methadone treatment (odds ratio, 11.45; 95% CI, 6.31-20.77). Methadone use was associated with 21.41 (95% CI, 10.81-32.02) more days of postoperative length of stay, 10.80 (95% CI, 3.63-17.98) more ventilator days, and 16.21 (95% CI, 6.34-26.10) more TPN days. In this cohort study of infants with surgically treated NEC, prolonged use of nonmethadone opioids after the operation was associated with an increased likelihood of methadone treatment and increased postoperative length of stay, ventilation, and TPN use. Optimizing postoperative pain management for infants requiring an operation may decrease the need for methadone treatment and improve health care use.

Activation of the mu-delta opioid receptor heteromers blocks morphine rewarding effects.

Evidence has accumulated demonstrating the existence of opioid receptor heteromers and recent data suggest that targeting these heteromers could reduce opioid side effects while retaining therapeutic effects. Indeed, CYM51010 characterised as a MOR (mu opioid receptor)/DOR (delta opioid receptor) heteromers preferring agonist promoted antinociception comparable to morphine but with less tolerance. In the perspective of developing these new classes of pharmacological agents, data on their putative side effects are mandatory. Therefore, in this study, we investigated the effects of CYM51010 in different models related to drug addiction in mice including behavioural sensitization, conditioned place preference and withdrawal. We found that, like morphine, CYM51010 promoted acute locomotor activity as well as psychomotor sensitization and rewarding effect. However, it induced less physical dependence than morphine. We also investigated the ability of CYM51010 to modulate some morphine-induced behaviour. Whereas CYM51010 was unable to block morphine-induced physical dependence, it blocked reinstatement of an extinguished morphine induced-conditioned place preference. Altogether, our results reveal that targeting MOR-DOR heteromers could represent a promising strategy to block morphine reward.

Retigabine promotes ketamine's antidepressant effect in the forced swim test in male and female C57BL/6J mice

Ketamine has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added retigabine, a KCNQ channel opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female C57BL/6 J mice. Behavioral data demonstrated that intraperitoneal injection of ketamine exhibited a dose-dependent effect on animals' immobility performance in the forced swim test. Adding retigabine was sufficient to induce a remarkable antidepressant effect in mice treated with a relatively lower dose of ketamine which failed to be antidepressant when administrated separately. When simultaneously gave retigabine, ketamine's antidepressant effect in the forced swim test was significantly enhanced with a prolonged effective duration. Together, these results from both male and female mice indicated that adjunctive treatment with retigabine was an alternative to promote the antidepressant effect of ketamine, thus holding the possibility of encountering its possible physical and psychological dependence.

Geriatric depression: prevalence and its associated factors in rural Odisha.

The world's population is aging rapidly, and the epidemiological transition has led to increased mental disorders worldwide. Geriatric depression is masked by multiple comorbidities or the natural process of aging. Our study aims to estimate the prevalence of geriatric depression and find the risk factors associated with geriatric depression in rural Odisha. The study was a multistage cross-sectional study conducted in the Tangi block, district Khordha, Odisha, from August 2020 to September 2022, among 520 participants selected by probability proportional to size sampling. From the selected participants, eligible 479 older adults were interviewed using a semi-structured interview schedule, Hindi Mini Mental Scale, Geriatric Depression Scale-15, and Hamilton Depression Rating Scale. The step forward multivariable logistic regression was used to assess the associated factors of depression among older adults. Among our participants, 44.4% (213) of older adults were depressed. Substance abuse in family members [AOR: 16.7 (9.1-30.9)], history of elder abuse [AOR: 3.7 (2.1-6.7)], physical dependency [AOR: 2.2 (1.3-3.6)], and financial dependency [AOR: 2.2 (1.3-3.6)] are significant independent risk factors associated with geriatric depression. Living with children [AOR: 0.33 (0.18-0.59)] and recreational activity [AOR: 0.54 (0.34-0.85)] are significant protective factors of geriatric depression. Our study found that geriatric depression is highly prevalent in rural Odisha. Poor quality of family life and physical and financial dependency was found to be the most significant risk factor for geriatric depression.

Optimum Handle Location for the Hand-Assisted Sit-to-Stand Transition: A Tool

Background: The aging process contributes to the decline in physical capacity that leads to loss of independence in performing life activities. Immobility and instability are the most significant predictors and indicators of physical disability and dependence. As a result, a variety of assistive devices exist to address immobility and instability in older adults, including walkers, canes, crutches, wheelchairs and handrails. Sit-to-stand (STS) transitions are the most common transitions in daily mobility activities. The ability to perform STS transitions successfully is therefore one of the most important activities to focus attention on. As a result of physical deterioration, older adults will sooner or later be faced with their physical limitations, and in particular, will not be able to provide enough torque at critical body joints to make the STS transition. Aim: This paper suggests employing two-arm assistance using two handles located symmetrically in the body’s sagittal plane. During the aging process, people are faced with varying levels of muscle deterioration and body constraints and consequently require different levels of assistance to complete the transition successfully. This paper aims to develop a tool to find the optimum handle location for people based on their body constraints to reduce knee torque (identified as the critical joint in the STS transition). These findings are also used to measure the effects of assistive device handle position on the biomechanics of the two-arm assisted STS transition. Methods: For this purpose, a theoretical tool was developed by integrating human body kinetics with a multi-objective genetic algorithm to find the optimum hand force required at the seat-off point for a set of potential handle locations. The tool was set to achieve the minimum knee torque within the defined body constraints and assumptions. In line with the physics of the STS transition, the “seat-off point”, when subjects lose their seat support, was chosen as the most challenging point of the task. This was coupled with the “nose over toes” posture recommended to older adults by occupational therapists. Results and Discussion: The schematic of the developed tool shows that the best handle locations requiring the minimum torques at the body joints are positioned in handle zone 2, where the handles are placed vertically above the knee and below the hip joints and horizontally located ahead of the hip and behind the knee joints. Within this handle zone, both components of the hand forces (vertical downward and horizontal backward) provide assisting torque to all the body joints and consequently reduce the torques required at body joints.

Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury.

The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. We developed a mouse model of oxycodone exposure and subsequent withdrawal in the presence or absence of chronic neuropathic pain. Oxycodone withdrawal alone triggered robust gene expression adaptations in the nucleus accumbens, medial prefrontal cortex and ventral tegmental area, with numerous genes and pathways selectively affected by oxycodone withdrawal in mice with peripheral nerve injury. Pathway analysis predicted that histone deacetylase (HDAC) 1 is a top upstream regulator in opioid withdrawal in nucleus accumbens and medial prefrontal cortex. The novel HDAC1/HDAC2 inhibitor, Regenacy Brain Class I HDAC Inhibitor (RBC1HI), attenuated behavioral manifestations of oxycodone withdrawal, especially in mice with neuropathic pain. These findings suggest that inhibition of HDAC1/HDAC2 may provide an avenue for patients with chronic pain who are dependent on opioids to transition to non-opioid analgesics.

Current issues in frailty and hypertension management.

The significance of hypertension management in older individuals is greatly influenced by factors other than chronological age, as they have diverse physical, mental, and social backgrounds. Differences in physical functions, between independence, frailty and dependence, have a great impact on antihypertensive therapy in the older population. While recent clinical trials support the significance of intensive antihypertensive therapy regardless of age, there is little evidence to positively support the significance of antihypertensive therapy for older patients with physical function requiring nursing care, and observational studies suggest that antihypertensive treatment may instead be harmful in these older patients. Therefore, frailty, the transitional state between independence and dependence with the need for nursing care, is conceivable to be the tipping point at which the balance of risks and benefits of antihypertensive treatment is converted. The increased risk of acute adverse outcome is another issue that complicates management in the practice of hypertension treatment in frail patients. Particularly, increased blood pressure variability manifested by orthostatic hypotension in frail patients can induce fall and fracture leading to disability shortly after initiation or modification of antihypertensive treatment. Future challenges to optimize the management of frail hypertensive patients include developing techniques to estimate treatment efficacy, identifying safe antihypertensive regimens that reduce the risk of falls, and establishing strategies to restore frail patients to robust health.