Decreased Resting State Inter- and Intra-Network Functional Connectivity Is Associated with Perceived Stress in a Sample of University Students: An eLORETA Study.

INTRODUCTION: Although the study of the Triple Network (TN) model has gained attention in the exploration of stress-related processes, the neurophysiological mechanisms of TN in relation to perceived stress have been relatively understudied in nonclinical samples so far. The main objective of the present study was to investigate, in a sample of university students, the association of perceived stress with resting state electroencephalography (EEG) functional connectivity in the TN. METHODS: Ninety university students (40 males and 50 females; mean age 22.30 ± 2.43 years; mean educational level 16.60 ± 1.62 years) were enrolled. EEG data were analyzed through the exact low-resolution electromagnetic tomography (eLORETA). RESULTS: Higher levels of perceived stress were associated with decreased delta EEG connectivity within the central executive network (CEN) and between the CEN and the salience network (SN). Higher levels of perceived stress were also associated with decreased theta EEG connectivity between the CEN and the SN. The associations between perceived stress and EEG connectivity data were significant even when relevant confounding factors (i.e., sex, age, educational level, and psychopathological symptoms) were controlled for. DISCUSSION: Taken together, our results suggest that higher levels of perceived stress are associated with a dysfunctional synchronization within the CEN and between the SN and the CEN. This functional pattern might in part reflect the negative impact of high levels of perceived stress on cognitive functioning.

Health-Related Fitness as a Predictor of Anxiety Levels Among School Adolescents: An observational cross-sectional study.

Background: There is an inverse association between cardiorespiratory fitness and general anxiety levels in adolescents. Obesity also is associated with a higher risk of anxiety in this population. However, little is known about the association between other health-related fitness elements with anxiety symptoms in this population. The authors explored the relationship between health-related fitness and anxiety symptoms in a large sample of Brazilian youth. Methods: This was an observational cross-sectional study with a sample comprised of 257 school adolescents, who were 136 girls (52.9%) and 121 boys (47.1%). The health-related fitness elements were evaluated by FitnessGram® test and anxiety levels by Multidimensional Anxiety Scale for Children - 39. Hierarchical regression analyses were used to determine the association between health-related fitness elements and anxiety symptoms in both sexes. Results: In male adolescents, only the cardiorespiratory fitness was significantly associated with anxiety symptoms (F(1, 119) = 6.472; P = 0.012; R2 = 0.052; adjusted R2 = 0.044). In turn, the anxiety symptoms showed an inverse small relationship with cardiorespiratory fitness (r = - 0.227; P < 0.01). However, in female adolescents, no association was found between health-related fitness elements and anxiety symptoms. Conclusion: The level of cardiorespiratory fitness may represent a marker of anxiety in male adolescents.

In vivo brain levels of acetylcholine and 5-hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement.

The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that has been linked to the modulation of several physiological functions, including the sleep-wake cycle. The PPARα recognizes as endogenous ligands the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which in turn, if systemically injected, they exert wake-promoting effects. Moreover, the activation of PPARα by the administration of OEA or PEA increases the extracellular contents of neurotransmitters linked to the control of wakefulness; however, the role of PPARα activated by OEA or PEA on additional biochemicals related to waking regulation, such as acetylcholine (ACh) and 5-hydroxytryptamine (5-HT), has not been fully studied. Here, we have investigated the effects of treatments of OEA or PEA on the contents of ACh and 5-HT by using in vivo microdialysis techniques coupled to HPLC means. For this purpose, OEA or PEA were systemically injected (5, 10 or 30 mg/kg; i.p.), and the levels of ACh and 5-HT were collected from the basal forebrain, a wake-related brain area. These pharmacological treatments significantly increased the contents of ACh and 5-HT as determined by HPLC procedures. Interestingly, PPARα antagonist MK-886 (30 mg/kg; i.p.) injected before the treatments of OEA or PEA blocked these outcomes. Our data suggest that the activation of PPARα by OEA or PEA produces significant changes on ACh and 5-HT levels measured from the basal forebrain and support the conclusion that PPARα is a suitable molecular element involved in the regulation of wake-related neurotransmitters.

Natural Cannabinoids as Templates for Sleep Disturbances Treatments.

The sleep-wake cycle is a complex composition of specific physiological and behavioral characteristics. In addition, neuroanatomical, neurochemical and molecular systems exerts influences in the modulation of the sleep-wake cycle. Moreover, homeostatic and circadian mechanisms interact to control the waking or sleeping states. As many other behaviors, sleep also develops pathological features that include several signs and symptoms corresponding to medical conditions known as sleep disorders.In addition to the neurobiological mechanisms modulating sleep, external elements also influence the sleep-wake cycle, including the use of Cannabis sativa (C. sativa). In this regard, and over the last decades, the interest of studying the pharmacology of Δ9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive constituent of C. sativa, has been addressed. Moreover, in recent years, the focus of scientific interest has moved on to studying the second plant constituent with non-psychotropic pharmacological properties: Cannabidiol (CBD).The pharmacological and pharmaceutical interest of CBD has been focus of attention due to the accumulating body of evidence regarding the positive outcomes of using CBD for the treatment of several health issues, such as psychiatric and neurodegenerative disorders, epilepsy, etc. Since the most prominent sleep disruptions include excessive daytime sleepiness (EDS), current treatments include the use of drugs such as stimulants of antidepressants. Notwithstanding, side effects are commonly reported among the patients under prescription of these compounds. Thus, the search of novelty therapeutical approaches aimed to treat ESD may consider the use of cannabinoid-derived compounds, such as CBD. In this chapter, we will show experimental evidence regarding the potential role of CBD as a wake-inducing compound aimed to manage EDS.

Effects of Cannabis Consumption on Sleep.

Despite the fact that medical properties of Cannabis have been recognized for more than 5000 years, the use of Cannabis for medical purposes have recently reemerged and became more accessible. Cannabis is usually employed as a self-medication for the treatment of insomnia disorder. However, the effects of Cannabis on sleep depend on multiple factors such as metabolomic composition of the plant, dosage and route of administration. In the present chapter, we reviewed the main effect Cannabis on sleep. We focused on the effect of "crude or whole plant" Cannabis consumption (i.e., smoked, oral or vaporized) both in humans and experimental animal models.The data reviewed establish that Cannabis modifies sleep. Furthermore, a recent experimental study in animals suggests that vaporization (which is a recommended route for medical purposes) of Cannabis with high THC and negligible CBD, promotes NREM sleep. However, it is imperative to perform new clinical studies in order to confirm if the administration of Cannabis could be a beneficial therapy for the treatment of sleep disorders.

A qualitative study of community perspectives surrounding cleaning practices in the context of Zika prevention in El Salvador: implications for community-based Aedes aegypti control.

BACKGROUND: In El Salvador, Aedes aegypti mosquitoes transmitting Zika and other arboviruses use water storage containers as important oviposition sites. Promotion of water storage container cleaning is a key element of prevention programs. We explored community perceptions surrounding cleaning practices among pregnant women, male partners of pregnant women, and women likely to become pregnant. METHODS: Researchers conducted 11 focus groups and 12 in-depth interviews which included individual elicitations of Zika prevention measures practiced in the community. Focus group participants rated 18 images depicting Zika-related behaviors according to effectiveness and feasibility in the community context, discussed influencing determinants, voted on community intentions to perform prevention behaviors, and performed washbasin cleaning simulations. In-depth interviews with male partners of pregnant women used projective techniques with images to explore their perceptions on a subset of Zika prevention behaviors. RESULTS: General cleaning of the home, to ensure a healthy environment, was a strong community norm. In this context, participants gave water storage container cleaning a high rating, for both its effectiveness and feasibility. Participants were convinced that they cleaned their water storage containers effectively against Zika, but their actual skills were inadequate to destroy Aedes aegypti eggs. A further constraint was the schedule of water availability. Even during pregnancy, male partners rarely cleaned water storage containers because water became available in homes when they were at work. Furthermore, prevailing gender norms did not foster male participation in domestic cleaning activities. Despite these factors, many men were willing to provide substantial support with cleaning when their partners were pregnant, in order to protect their family. CONCLUSIONS: Behavior change programs for the prevention of Zika and other arboviruses need to improve community members' mosquito egg destruction skills rather than perpetuate the promotion of non-specific cleaning in and around the home as effective. Egg elimination must be clearly identified as the objective of water storage container maintenance and programs should highlight the effective techniques to achieve this goal. In addition, programs must build the skills of family members who support pregnant women to maintain the frequency of effective egg destruction in all water storage containers of the home.

Effects on Volume Load and Ratings of Perceived Exertion in Individuals' Advanced Weight Training After Transcranial Direct Current Stimulation.

Lattari, E, Rosa Filho, BJ, Fonseca Junior, SJ, Murillo-Rodriguez, E, Rocha, N, Machado, S, and Maranhão Neto, GA. Effects on volume load and ratings of perceived exertion in individuals' advanced weight training after transcranial direct current stimulation. J Strength Cond Res 34(1): 89-96, 2020-The aim of this study was investigate the effects of transcranial direct current stimulation (tDCS) on volume load and ratings of perceived exertion. Fifteen young healthy individuals, aged between 20 and 30 years in advanced strength training were recruited. Test and retest of the 10 maximum repetitions (10RM) were performed to determine the reliability of load used. Subjects performed 3 experimental conditions in a randomized, double-blinded crossover design: anodic stimulation (a-tDCS), cathodic stimulation (c-tDCS), and sham (2 mA for 20 minutes targeting the dorsolateral prefrontal cortex left). Immediately after the experimental conditions, subjects completed 1 set of maximum repetitions with 10RM load (volume load) and answered to OMNI-RES (poststimulation) (level of significance p ≤ 0.05). The volume load showed main effect for condition (F(2, 28) = 164.801; p < 0.001). In poststimulation, a-tDCS was greater than c-tDCS (p ≤ 0.001) and sham (p ≤ 0.001). For ratings of perceived exertion (OMNI-RES), the results showed main effect for condition (F(2, 28) = 9.768; p ≤ 0.05). In poststimulation, c-tDCS was greater than a-tDCS (p ≤ 0.05) and sham (p ≤ 0.05). We conclude that the use of a-tDCS may promote increase in volume load for the LP45 exercise. Moreover, higher volume loads are necessary to maximize muscle strength and anabolism.

Exergames for Children and Adolescents with Autism Spectrum Disorder: An Overview.

Autistic Spectrum Disorder (ASD) is a complex neurodevelopmental disorder associated with various etiologies and characterized by deficits in social interaction, emotional reciprocity, communication, motor skills and cognitive functions. Studies have proposed that limited levels of physical activity and late motor skills and fitness, particularly in children and adolescents with ASD, may accentuate social and emotional deficits. In view of this, exergames, which are active video-games, can be considered a low-cost and safe type of exercise for children and adolescents with ASD, since they are more enjoyable than ordinary physical activities, influencing on treatment adherence. Thus, our study aims to evidence the effects of exergames on physical fitness, cognitive functions, and repetitive behaviors in children and adolescents with ASD. Despite the small number of studies investigating the effects of exergames as new strategy in children and adolescents with ASD, results suggest exergames as potential tool for the treatment of children and adolescents with ASD for improvement in physical fitness, cognitive functions and repetitive behavior. Our review pointed towards the importance of exergames for children and adolescents with ASD. Despite few studies conducted about this issue, we can consider exergames a potential tool to increase physical fitness, cognitive functions and to decrease repetitive behavior in children and adolescents with ASD. Moreover, health professionals should be careful when attempting to help this population, because the current literature is unclear yet about the improvement of ASD features through exergames.

Neurotoxicity to dopamine neurons after the serial exposure to alcohol and methamphetamine: Protection by COX-2 antagonism.

A significant co-morbidity exists between alcohol and methamphetamine (Meth) in humans but the consequences and mechanisms underlying their co-morbid effects remain to be identified. A consequence associated with the abuse of either alcohol or Meth involves inflammation but little is known about the role of inflammation in a possible neurotoxicity arising from their co-exposure. Sprague Dawley rats were allowed 28 days of intermittent, voluntary access to 10% ethanol (EtOH) followed by a neurotoxic binge administration of Meth. EtOH drinking followed by Meth increased microglial cell counts and produced morphological changes in microglia of the substantia nigra pars compacta 2 h after Meth administration that were distinct from those produced by either EtOH or Meth alone. These effects preceded the activation of cleaved caspase-3 in dopamine cell bodies, as well as decreases in tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and dopamine transporter (DAT) immunoreactivity in the striatum measured at 7 days after Meth. Intervention with a selective COX-2 inhibitor during EtOH drinking prevented the changes in microglia, and attenuated the increase in cleaved caspase-3, and decreases in TH and DAT after Meth administration. Furthermore, motor dysfunction measured by a rotarod test was evident but only in rats that were exposed to both EtOH and Meth. The motor dysfunction was ameliorated by prior inhibition of COX-2 during EtOH drinking. The exaggerated neurochemical and behavioral deficits indicate that the comorbidity of EtOH and Meth induces a degeneration of the nigrostriatal pathway and support the role of inflammation produced by EtOH drinking that primes and mediates the neurotoxic consequences associated with the common co-morbidity of these drugs.

Systemic Injections of Cannabidiol Enhance Acetylcholine Levels from Basal Forebrain in Rats.

Cannabis sativa is a plant that contains more than 500 components, of which the most studied are Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Several studies have indicated that CBD displays neurobiological effects, including wake promotion. Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines (dopamine, serotonin, epinephrine, and norepinephrine). However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine (ACh). Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means. Moreover, the time course effects on the contents of ACh were present 5 h post-injection of CBD. Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control. This study is the first to show the effects of ACh levels in CBD-treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.

Sequential 3-dimensional computed tomography analysis of implant position following total shoulder arthroplasty.

BACKGROUND: Detection of postoperative component position and implant shift following total shoulder arthroplasty (TSA) can be challenging using routine imaging. The purpose of this study was to evaluate glenoid component position over time using 3-dimensional computed tomography (CT) analysis with minimum 2-year follow-up. METHODS: Twenty patients underwent primary TSA with sequential CT scanning of the shoulder: a preoperative study, an immediate postoperative study within 2 weeks of surgery, and a postoperative study performed at minimum 2-year follow-up (CT3). Postoperative glenoid component position and central peg osteolysis were assessed across the immediate postoperative CT scan and CT3. Glenoids with evidence of component shift and/or grade 1 central peg osteolysis on CT3 were considered at risk of loosening. RESULTS: Of the patients, 7 (35%) showed evidence of glenoid components at risk of loosening on CT3, 6 with component shift (3 with increased inclination alone, 1 with increased retroversion alone, and 2 with both increased inclination and retroversion). Significantly more patients with glenoid component shift had grade 1 central peg osteolysis on CT3 compared with those without shift (83% vs 7%, P = .002). One clinical failure occurred, with the patient undergoing revision to reverse TSA for rotator cuff deficiency. CONCLUSIONS: Three-dimensional CT imaging analysis following TSA identified changes in glenoid component position over time, with inclination being the most common direction of shift and grade 1 central peg osteolysis commonly associated with shift. These findings raise concern for glenoids at risk of loosening, but further follow-up is needed to determine the long-term clinical impact of these findings.

Physical Exercise For Parkinson's Disease: Clinical And Experimental Evidence.

BACKGROUND: National projections about the increase in the elderly population over 60 years bring with it an increase in the number of people affected by Parkinson's Disease (PD), making it an important public health problem. Therefore, the establishment of effective strategies for intervention in people with PD needs to be more clearly investigated. OBJECTIVE: The study aimed to report the effectiveness of exercise on functional capacity and neurobiological mechanisms in people with PD. METHODS: This study is a critical review of the literature. RESULTS: The progressive death of dopaminergic neurons in the substantia nigra is described as one of the main physiological mechanisms manifested before PD, directly interfering with motor behavior. However, PD is not only related to motor symptoms, but also to cognitive, autonomic, and mood impairments. Such effects may be attenuated by pharmacological influence, but also evidence suggests that the implementation of regular physical exercise programs may exhibit potential benefits over PD. The synthesis and expression of monoaminergic neurotransmitters can act positively on motor disorders, as well as directly or indirectly influence the neuronal plasticity of the brain, restoring neuronal pathways previously affected. CONCLUSION: Physical exercise contributes effectively to the treatment of PD, and can play a preventive and maintenance role of physical fitness and mental health.

Effects of Aerobic Exercise on Anxiety Symptoms and Cortical Activity in Patients with Panic Disorder: A Pilot Study.

BACKGROUND: The effects of the aerobic exercise on anxiety symptoms in patients with Panic Disorder (PD) remain unclear. Thus, the investigation of possible changes in EEG frontal asymmetry could contribute to understand the relationship among exercise, brain and anxiety. OBJECTIVE: To investigate the acute effects of aerobic exercise on the symptoms of anxiety and the chronic effects of aerobic exercise on severity and symptoms related to PD, besides the changes in EEG frontal asymmetry. METHODS: Ten PD patients were divided into two groups, Exercise Group (EG; n=5) and Control Group (CG; n=5), in a randomized allocation. At baseline and post-intervention, they submitted the psychological evaluation through Panic Disorder Severity Scale (PDSS), Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), EEG frontal asymmetry, and maximal oxygen consumption (VO2max). On the second visit, the patients of EG being submitted to the aerobic exercise (treadmill, 25 minutes, and 50-55% of heart rate reserve) and the CG remained seated for the same period of time. Both groups submitted a psychological evaluation with Subjective Units of Distress Scale (SUDS) at baseline, immediately after (Post-0), and after 10 minutes of the rest pause (Post-10). The patients performed 12 sessions of aerobic exercise with 48-72 hours of interval between sessions. RESULTS: In EG, SUDS increased immediately after exercise practice and showed chronic decrease in BAI and BDI-II as well as increased in VO2max (Post-intervention). CONCLUSION: Aerobic exercise can promote increase in anxiety acutely and regular aerobic exercise promotes reduction in anxiety levels.

Panic disorder and cardiovascular diseases: an overview.

The association between panic disorder (PD) and cardiovascular diseases (CVD) has been extensively studied in recent years and, although some studies have shown anxiety disorders co-existing or increasing the risk of heart disease, no causal hypothesis has been well established. Thus, a critical review was performed of the studies that evaluated the association between PD and cardiovascular diseases; synthesizing the evidence on the mechanisms mediators that theoretically would be the responsible for the causal pathway between PD and CVD, specifically. This overview shows epidemiological studies, and discusses biological mechanisms that could link PD to CVD, such as pleiotropy, heart rate variability, unhealthy lifestyle, atherosclerosis, mental stress, and myocardial perfusion defects. This study tried to provide a comprehensive narrative synthesis of previously published information regarding PD and CVD and open new possibilities of clinical management and pathophysiological understanding. Some epidemiological studies have indicated that PD could be a risk factor for CVD, raising morbidity and mortality in PD, suggesting an association between them. These studies argue that PD pathophysiology could cause or potentiate CVD. However, there is no evidence in favour of a causal relationship between PD and CVD. Therefore, PD patients with suspicions of cardiovascular symptoms need redoubled attention.

Relationship Among Physical Activity Level, Mood and Anxiety States and Quality of Life in Physical Education Students.

BACKGROUND: Physical activity level (PAL) is known to play an important role in reducing risk factors associated with sedentarism, in addition to improving the mental health and health-related quality of life (HRQL). OBJECTIVE: Investigate the relationship of PAL and their domains with HRQL, mood state (MS) and anxiety. Method: 140 Physical Education students (23.6 ± 3.7 years) were evaluated. The Baecke Habitual Physical Activity and Quality of Life (QOL-36) questionnaires, State-Trait Anxiety Inventories (STAI-S and STAI-T) and Profile of Mood States (POMS) scale were used to investigate PAL, HRQL and mental health indicators. Pearson's correlation coefficient examined the association between PAL and both mental health and HRQL parameters. RESULTS: There was a correlation between state anxiety and both the domain leisure-time physical activity (LTPA) (p = 0.013) and total PAL score (p = 0.010). In relation to MS, a negative correlation was found between LTPA and total mood disorder (TMD) (p = 0.004). However, there were positive correlations between the vigor subscale and both LTPA (p=0.001) and total PAL (p=0.019). With respect to HRQL, analysis of the relationship between LTPA and total PAL demonstrated positive coefficients with the physical component summary (PCS) (p=0.000; p = 0.005), mental component summary (MCS) (p = 0.000; p = 0.006) and total HRQL (p = 0.000; p = 0.003). CONCLUSION: The findings suggest that the rise in LTPA was related to an increase in HRQL and MS. However, PAL was positively related to anxiety.

The Role of Physical Activity on Mood State and Functional Skills of Elderly Women.

INTRODUCTION: Ageing is associated with several physical, psychological and behavioral changes. These changes are closely related with global health and functional capacity in the elderly. Mood disturbances are common among the elderly and may significantly increase apathy, resulting in decreased habitual physical activity levels. MATERIALS AND METHODS: The purpose of this cross-sectional study was to evaluate the mood state and functional motor capacities of elderly women engaged in a public physical activity program in Brazil and compare them with physically inactive elderly. Thirty elderly women were included in the study and categorized into two groups: physically active group, composed of participants enrolled on a public physical activity program (n = 16, 69±5 years) and physically inactive group (n = 14, 68±4 years). Total mood disturbance was assessed using the Profile of Mood States, whereas functional motor capacity was evaluated with the Sitting and Rising test. Independent t test and Mann-Whitney U] were used to compare groups. RESULTS: The physically active group had lower total mood disturbance (p=0.02), confusion (p<0.01), tension (p<0.01), hostility (p=0.05) and fatigue (p=0.01) compared to the physically inactive group. There were no group differences regarding vigor, depression and sitting and rising performance (p>0.05). CONCLUSION: Lack of difference in functional motor capacity between the physically active and inactive elderly may be explained by the absence of exercise systematization in these programs.

Relationship Between Brain-Derived Neurotrofic Factor (Bdnf) and Sleep on Depression: A Critical Review.

The Brain-Derived Neurotrofic Factor (BDNF) is one of the most important neurotrophins in the brain and it is suggested influences the activity of the serotonergic, noradrenergic and dopaminergic pathways. In the last few years, it has been hypothesized that BDNF level is related with depression and sleep. Several studies show that depressive subjects present low levels of BDNF in the brain. Poor sleep quality is also related with alterations in the BDNF concentration. Some authors argue that most of the cases show that impaired sleep quality increases the stress and, consequently, the vulnerability to depressive disorders, suggesting that there is a relationship between sleep, depression and BDNF levels.

Physical Exercise As Stabilizer For Alzheimer'S Disease Cognitive Decline: Current Status.

INTRODUCTION: Mental health decline is one of the main responsible factors for augments in health care costs, and diagnosis of Alzheimer's disease (AD). Some studies stated physical exercise is useful for reduction in cognitive decline and AD. Moreover, a recent review argued that evidence are scarce due to few studies published and lack of configuration information of exercise protocol, such as intensity and duration of exercise, number of sessions and other relevant data, to allow appropriate assessment. MATERIALS AND METHODS: Here, we discussed the possible confounders or factors responsible for these differences and possible neurophysiological mechanisms. RESULTS: Most studies revealed a possible positive association between physical exercise and cognitive assessments. There are inconsistencies in studies design responsible for varying use of cognitive assessments and different assessments of fitness. However, these studies do not fail to provide evidence about the benefits of exercise, but fail to make it possible because of the lack of dose-response information in AD patients. Physical exercise of moderate intensity should be considered as standard recommendation to reduce cognitive decline, probably due to the improvement in neurodegenerative mechanisms, and the increase in neuroplastic and neuroprotective neurotrophic factors. CONCLUSION: Therefore, it is suggested that physical exercise is an important neuroprotective modulator, bringing significant control of the disease and amplifying brain functions.

Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin.

The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. Interactions of these sulfated metabolites of LC-PCBs with HSA, however, have not been previously explored. We have now determined the relative HSA-binding affinities for a group of LC-PCBs and their hydroxylated and sulfated derivatives by selective displacement of the fluorescent probes 5-dimethylamino-1-naphthalenesulfonamide and dansyl-l-proline from the two major drug-binding sites on HSA (previously designated as Site I and Site II). Values for half-maximal displacement of the probes indicated that the relative binding affinities were generally PCB sulfate ≥ OH-PCB > PCB, although this affinity was site- and congener-selective. Moreover, specificity for Site II increased as the numbers of chlorine atoms increased. Thus, hydroxylation and sulfation of LC-PCBs result in selective interactions with HSA which may affect their overall retention and toxicity.

Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part IX: Anxiety.

OBJECTIVE: As a part of a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults, this article focuses on anxiety-a significant contributor of reduced health-related quality of life, increased use of medical services, and heightened disability in older adults with CLBP. METHODS: A modified Delphi technique was used to develop an algorithm for the screening and clinical care of older adults with CLBP and anxiety. A 4-member content expert panel and a nine-member primary care panel were involved in this iterative development process. Evidence underlying the recommendations is not strictly based on VA populations; therefore, the algorithm can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice. RESULTS: We present a treatment algorithm and supporting tables to be used by providers treating older adults who have anxiety and CLBP. A case of an older adult with anxiety and CLBP is provided to illustrate the approach to management. CONCLUSIONS: To promote early engagement in evidence-based treatments, providers should routinely evaluate anxiety in older adults with CLBP using a screening and treatment algorithm.