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The prevalence of obesity worldwide has increased in recent decades not only among adults, but also in children and adolescents. This phenomenon contributes to an increased risk of cardiovascular diseases (CVD), also after the adjustment for conventional risk factors such as hypertension, diabetes and dyslipidemia. Indeed, obesity contributes to the development of insulin resistance, endothelial dysfunction, sympathetic nervous system activation, increased vascular resistance and inflammatory and prothrombotic state which promote the incidence of major cardiovascular events. On the basis of this evidence, in 2021 obesity has been acknowledged as a definite pathological identity and identified as a recurrent, chronic non-communicable disease. Therapeutic strategies for the pharmacological treatment of obesity include the combination of naltrexone and bupropione and the lipase inhibitor orlistat and they have been recently implemented with the glucagon like peptide-1 receptor agonists semaglutide and liraglutide, which have produced positive and sustained effects on body weight reduction. If drug interventions are not effective, bariatric surgery may be considered, representing an efficacious treatment option for extreme obesity or obesity with comorbidities. The present executive paper is aimed to increase knowledge on the relationships between obesity and CVD, to raise the perception of this condition which is currently insufficient and to support the clinical practice management.

Background: Anorexia nervosa (AN) is a serious and potentially life-threatening eating disorder characterized by starvation and malnutrition, a high prevalence of coexisting psychiatric conditions, marked treatment resistance, frequent medical complications, and a substantial risk of death. Body mass index (BMI) is a key measure of treatment outcome of AN and it is necessary to evaluate the long-term prognosis of AN. This study aimed to better assess the BMI course trend between different medications and timepoints in order to improve AN treatment in clinical practice. Methods: During the period 2010–2021, we retrospectively reviewed historical data of all patients diagnosed with AN. There were two groups in this study, which were based on the duration of follow-up. Group A was a 6-month follow-up group, comprising 93 patients (mean age 19.6 ± 6.8 years), with BMI assessed at three consecutive time points: first outpatient visit (T0), three months follow-up (T3), and six months follow-up (T6). Group B was a 12-month follow-up group comprising 36 patients (mean age 17.0 ± 5.2 years) with BMI assessed at five consecutive time points: first outpatient visit (T0), three months follow-up (T3), six months follow-up (T6), nine months follow-up (T9), and twelve months follow-up (T12). In our study, we retrospectively compared BMI courses based on patients’ usage of medication using the following variables: single medication, switching medications, combined medications, and without medications. The primary outcome measurement was BMI recorded at the 6-month follow-up and the 12-month follow-up respectively. In our study, which was conducted at Taichung Veterans General Hospital, we reviewed outpatient medical records of all patients with AN who were seen at the hospital during the period 2010–2021. Results: In Group A (6-month follow-up), patients treated with antidepressants showed a mean BMI increase of 1.3 (p < 0.001); patients treated with antipsychotics showed a mean BMI increase of 1.1 (p = 0.01); patients treated with switching medications showed a mean BMI increase of 0.1 (p = 0.397); patients treated with combined medications showed a mean BMI increase of 0.5 (p = 0.208); and patients treated without medications showed a mean BMI increase of 0.1 (p = 0.821). The results indicated that patients with AN had a significant BMI increase after treatment with antidepressants and antipsychotics in the 6-month follow-up group. In Group B (12-month follow-up), patients treated with antidepressants showed a mean BMI increase of 2.7 (p < 0.001); patients treated with antipsychotics showed a mean BMI increase of 2.8 (p = 0.168); patients treated with switching medications showed a mean BMI decrease of 0.8 (p = 0.595); patients treated with combined medications showed a mean BMI increase of 1.6 (p = 0.368); and patients treated without medications showed a mean BMI increase of 1.0 (p = 0.262). The results indicated that patients with AN had a significant BMI increase after treatment with antidepressants at the 12-month follow-up. Conclusions: AN is a complex disease caused by multiple factors. Evaluating its long-term prognosis is crucial. Our study provides insights and highlights three key findings: 1) medication adherence is crucial in treating AN, 2) frequent switching of medications may not promote weight gain and may also require a re-establishment of rapport with patients with AN, and 3) pharmacotherapy, especially antidepressants, is more effective than no treatment. Further research is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Interest in the use of anticholinergics to prevent the development of epilepsy after traumatic brain injury (TBI) has grown since recent basic studies have shown their effectiveness in modifying the epileptogenic process. These studies demonstrated that treatment with anticholinergics, in the acute phase after brain injury, decreases seizure frequency, and severity, and the number of spontaneous recurrent seizures (SRS). Therefore, anticholinergics may reduce the risk of developing posttraumatic epilepsy (PTE). In this brief review, we summarize the role of the cholinergic system in epilepsy and the key findings from using anticholinergic drugs to prevent PTE in animal models and new clinical trial protocols. Furthermore, we discuss why treatment with anticholinergics is more likely to prevent PTE than treatment for other epilepsies. [ABSTRACT FROM AUTHOR]

Carcinoid syndrome represents a debilitating paraneoplastic disease, caused by the secretion of several substances, occurring in about 10–40% of patients with well-differentiated neuroendocrine tumors (NETs). The main signs and symptoms associated with carcinoid syndrome are flushing, diarrhea, hypotension, tachycardia, bronchoconstriction, venous telangiectasia, dyspnea and fibrotic complications (mesenteric and retroperitoneal fibrosis, and carcinoid heart disease). Although there are several drugs available for the treatment of carcinoid syndrome, the lack of therapeutic response, poor tolerance or resistance to drugs are often reported. Preclinical models are indispensable tools for investigating the pathogenesis, mechanisms for tumor progression and new therapeutic approaches for cancer. This paper provides a state-of-the-art overview of in vitro and in vivo models in NETs with carcinoid syndrome, highlighting the future developments and therapeutic approaches in this field. [ABSTRACT FROM AUTHOR]

Background: Smoking among people with severe mental illness (SMI) is highly prevalent and strongly associated with poor physical health. Currently, evidence-based smoking cessation interventions are scarce and need to be integrated into current mental health care treatment guidelines and clinical practice. Therefore, the present study aims to evaluate the implementation and effectiveness of a smoking cessation intervention in comparison with usual care in people with SMI treated by Flexible Assertive Community Treatment (FACT) teams in the Netherlands. Methods: A pragmatic, cluster-randomised controlled trial with embedded process evaluation will be conducted. Randomisation will be performed at the level of FACT teams, which will be assigned to the KISMET intervention or a control group (care as usual). The intervention will include pharmacological treatment combined with behavioural counselling and peer support provided by trained mental health care professionals. The intervention was developed using a Delphi study, through which a consensus was reached on the core elements of the intervention. We aim to include a total of 318 people with SMI (aged 18–65 years) who smoke and desire to quit smoking. The primary outcome is smoking status, as verified by carbon monoxide measurements and self-report. The secondary outcomes are depression and anxiety, psychotic symptoms, physical fitness, cardiovascular risks, substance use, quality of life, and health-related self-efficacy at 12 months. Alongside the trial, a qualitative process evaluation will be conducted to evaluate the barriers to and facilitators of its implementation as well as the satisfaction and experiences of both patients and mental health care professionals. Discussion: The results of the KISMET trial will contribute to the evidence gap of effective smoking cessation interventions for people treated by FACT teams. Moreover, insights will be obtained regarding the implementation process of the intervention in current mental health care. The outcomes should advance the understanding of the interdependence of physical and mental health and the gradual integration of both within the mental health care system. Trial registration: Netherlands Trial Register, NTR9783. Registered on 18 October 2021. [ABSTRACT FROM AUTHOR]

Objective: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan. Methods: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls. Results: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04–1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59–2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09–1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women. Conclusion: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs. [ABSTRACT FROM AUTHOR]

The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug is available nowadays. Researchers still work in drug development and are finding new molecular targets to treat AD. Therefore, this study aimed to summarize main advances in AD pharmacological therapy. Clinical trials registered in the National Library of Medicine database were selected and analyzed accordingly to molecular targets, therapeutic effects, and safety profile. The most common outcome was the lack of efficacy. Only seven trials concluded that tested drugs were safe and induced any kind of therapeutic improvement. Three works showed therapeutic effects followed by toxicity. In addition to aducanumab recent FDA approval, antibodies against amyloid-β (Aβ) showed no noteworthy results. 5-HT6 antagonists, tau inhibitors and nicotinic agonists' data were discouraging. However, anti-Aβ vaccine, BACE inhibitor and anti-neuroinflammation drugs showed promising results. [ABSTRACT FROM AUTHOR]

The aim of this debate article is to discuss whether effective treatments are available for mixed urinary incontinence (MUI). Because patients with MUI have both stress and urgency urinary incontinence (SUI and UUI) episodes and current treatment guidelines currently recommend treating the predominant symptom first, this article presents standard and emerging treatments for both SUI and UUI before discussing how well these treatments meet the medical needs of patients with MUI. Standard treatments presented include noninvasive options such as lifestyle changes and pelvic floor exercises, pharmacological agents, and surgery. Treatment of all three types of urinary incontinence (UI) is usually initiated with noninvasive options, after which treatment options diverge based on UI subtype. Multiple pharmacological agents have been developed for the treatment of UUI and overactive bladder, whereas surgery remains the standard option for SUI and stress‐predominant MUI. The divide between UUI and SUI options seems to be propagated in emerging treatments, with most novel pharmacological agents still targeting UUI and even having SUI and stress‐predominant MUI as exclusion criteria for participation in clinical trials. Considering that current treatment options focus almost exclusively on treating the predominant symptom of MUI and that emerging pharmacological treatments exclude patients with stress‐predominant MUI during the development phase, effective treatments for MUI are lacking both in standard and emerging practice. Ideally, agents with dual mechanisms of action could provide symptom benefit for both the stress and urgency components of MUI. [ABSTRACT FROM AUTHOR]

Aim: This study aims to systematically review the interventional studies from Turkey published in national and international databases for the treatment and management of COVID-19. Material and Methods: The studies conducted between January- 2020 and August-2021 were searched through PubMed, Cochrane, CINAHL, EBSCHO, Web of Science, Google Scholar, Turkey Citation Index, ULAKBİM, and COVID-19 Turkey Web Portal. Fourteen studies meeting the criteria were included. Results: The studies were conducted with randomized controlled (n=6), clinical trial (n=1), interventional double-controlled trial (n=1), and quasi-experimental study design (n=5). One is a randomized, prospective crossover, model simulation study. The evaluated studies include non-pharmacological (n=8) and pharmacological (n=6) approaches. Tele-rehabilitation or online methods were used in all non-pharmacological studies. Six studies aimed at reducing the stress, depression, and anxiety levels of individuals. Pharmacological studies were (n=6) aimed at evaluating the effectiveness of different treatment modalities. The result shows that interventions in non-pharmacological studies are highly effective, and treatment methods applied in pharmacological studies also have a positive effect. Conclusion: This review will contribute to the literature by shedding light on future research. Moreover, there is a need for more comprehensive studies on the diagnosis, treatment, symptoms, effects, and management of COVID-19, including children and older people at risk. [ABSTRACT FROM AUTHOR]

Purpose: Insomnia is frequent in patients with advanced cancer, and a variety of pharmacological agents is used to treat this condition. Still, few clinical trials have investigated the effectiveness of pharmacological sleep therapies in this patient group. We aimed to study the short-term effectiveness of zopiclone on sleep quality in patients with advanced cancer who report insomnia. Methods: A randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase IV clinical trial in adult patients with metastatic malignant disease and insomnia. Patients were treated with zopiclone or placebo for six subsequent nights. Primary end point was patient-reported sleep quality during the final study night (NRS 0–10). Secondary end points were patient-reported sleep onset latency (SOL) and total sleep time (TST). Results: Forty-one patients were randomized, with 18 being analyzed in the zopiclone group and 21 in the placebo group. Median age was 66, median Karnofsky performance score was 80, and 56% were male. Mean sleep quality at end of study was 2.9 (CI 2.3 to 3.8) in the zopiclone group and 4.5 (CI 3.6 to 5.4) in the placebo group (p = 0.021). At end of study, SOL was significantly different between the treatment groups: zopiclone 29 min (CI 13 to 51) and placebo 62 min (CI 40 to 87) (p = 0.045). TST was not significantly different across groups: zopiclone 449 min (403 to 496) and placebo 411 min (CI 380 to 440) (p = 0.167). Conclusion: Zopiclone improved short-term patient-reported sleep quality in this cohort of patients with advanced cancer. Trial registration: ClinicalTrials.gov Identifier: NCT02807922. [ABSTRACT FROM AUTHOR]

Non-motor symptoms (NMS) affect patients with Parkinson's disease (PD) from the prodromal to the advanced stages. NMS phenotypes greatly vary and have a huge impact on patients' and caregivers' quality of life (QoL). The management of cognitive and neuropsychiatric NMS remains an unmet need. The authors, herein, review the dopaminergic and non-dopaminergic pathogenesis, clinical features, assessment, and pharmacological and non-pharmacological treatments of cognitive and neuropsychiatric NMS in PD. They discuss the current evidence and report the findings of an overview of ongoing trials on pharmacological and selected non-pharmacological strategies. The treatment of cognitive and neuropsychiatric NMS in PD is poorly explored, and therapeutic options are unsatisfactory. Pharmacological treatment of cognitive NMS is based on symptomatic active principles used in Alzheimer's disease. Dopamine agonists, selective serotonin, and serotonin-norepinephrine reuptake inhibitors have some evidence on PD-related depression. Clozapine, quetiapine, and pimavanserin may be considered for psychosis in PD. Evidence on the treatment of other neuropsychiatric NMS is limited or lacking. Addressing pathophysiological and clinical issues, which hamper solid evidence on the treatment of cognitive and neuropsychiatric NMS, may reduce the impact on QoL for PD patients and their caregivers. [ABSTRACT FROM AUTHOR]

Copyright of Medicus (1330-013X) is the property of Pliva Hrvatska d.o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Calcinosis is common in patients with systemic sclerosis (SSc) and refers to the sub-epidermal deposition of calcium salts in the skin. SSc-related calcinosis is associated with significant morbidity, including through cutaneous ulceration and predisposition to become infected. After briefly addressing aetiopathogenesis, we describe the clinical burden of SSc-associated calcinosis and provide a structured and practical clinical approach to diagnosis and assessment, including discussion of the role of different imaging modalities. The multi-faceted treatment of SSc-associated calcinosis is presented under three broad headings of 'general measures,' and 'medical treatment' and 'surgical treatment.' We adopted a narrative approach to identify relevant manuscripts to inform our review. SSc-related calcinosis is an area of major unmet clinical need and for too long has been a neglected area of research. Safe and effective treatments are badly needed to improve patient quality of life and outcomes. To facilitate future clinical trials, we require increased understanding of pathogenesis (to inform selection of potential targeted therapies) and reliable outcome measures, including those which will measure the impact and severity of calcinosis from the patient perspective. International collaborative research is ongoing to develop outcome measures and treatments for this potentially devastating complication of SSc. [ABSTRACT FROM AUTHOR]

Copyright of Revista Enfermagem Digital Cuidado e Promoção da Saúde is the property of Revista Enfermagem Digital Cuidado e Promocao da Saude and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension. [ABSTRACT FROM AUTHOR]

Treatment resistant depression (TRD) is a subgroup of Major Depressive Disorder that does not respond to typical or first-line treatment approaches. Treatment-resistant depression is diagnosed when two appropriate antidepressant therapies fail. TRD may also be connected to lengthy stays in a hospital for medical attention. To distinguish authentic TRD, a number of definitions and standards have been presented, but no single definition or standard has yet gained acceptance. As a result, TRD poses unique difficulties for therapeutic strategies and efficient therapies. Recent meta-analyses, original studies of the PubMed literature were compiled. In this article, we'll try to give a comprehensive overview of TRD treatment options and discuss the difficulties that come with treating this condition. [ABSTRACT FROM AUTHOR]

Central neuropathic pain (CNP) affects millions worldwide, with an estimated prevalence of around 10% globally. Although there are a wide variety of treatment options available, due to the complex and multidimensional nature in which CNP arises and presents symptomatically, many patients still experience painful symptoms. Pharmaceutical, surgical, non-invasive, cognitive and combination treatment options offer a generalized starting point for alleviating symptoms; however, a more customized approach may provide greater benefit. Here, we comment on the current treatment options that exist for CNP and further suggest the need for additional research regarding the use of biomarkers to help individualize treatment options for patients. [ABSTRACT FROM AUTHOR]

Background: The consequences of demographic change are already noticeable in Saxony, the federal state with the highest average age in Germany and predominantly rural areas. In order to improve medical care for patients with Parkinson's disease (PwP), a status quo analysis of current care practice is required. Objective: To what extent does the utilization of medical services by PwP differ a) between urban and rural areas in Saxony and b) between PwP with and without neurologist contact in the observation period from 2011 to 2019? Material and methods: The cohort study was based on extensive routine data for Saxony from the health insurance company AOK PLUS from 2010 to 2019. A cohort of 15,744 PwP (n = 67,448 patient-years) was compared to a matched cohort (n = 674,480 patient-years; criteria: year of birth, gender, year of insurance, place of residence: urban/rural) without an ICD-10 coding of a movement disorder. Results: Overall, there was a steady increase in the number of PwP in the dynamic cohort from 2011 (n = 6829) to 2019 (n = 8254). Urban-rural differences included a smaller proportion of patients being seen by a neurologist in rural areas. The PwP had a 3.5 to 4‑fold higher risk of dying compared to those in the comparison cohort. Changes in drug therapy for Parkinson's disease (i.e., increases in COMT and MAO inhibitors) and in remedy delivery (i.e., increases in occupational therapy and speech therapy) over the observation period were primarily seen in PwP who were seen by a neurologist. Discussion: The study identified increased morbidity and mortality in PwP who are suitable targets for innovative care concepts. The increasing number of patients and the described differences document the need for this. At the same time, changes in prescription practice show that innovative forms of treatment are being used by neurologists in outpatient care. [ABSTRACT FROM AUTHOR]

Attention deficit disorder with or without hyperactivity is a pathology prevalent during childhood that, until a few decades ago, was considered a neurobiological entity. However, subsequent research has pointed out the importance of family relationships in their clinical evolution. It has been explained that family factors in children with ADHD, are significant indicators of its persistence over time. For this reason, is very relevant to understand the role that families play in children with ADHD. Objective: to review the influence of family relationships on the evolution of ADHD. Method: the review is complemented with the presentation of a clinical case. Conclusion: if pharmacological therapy is compared with multimodal treatment, the latter presents better results. The following databases were used in the literature search: PubMed (MEDLINE), ClinicalKey (Elsevier), SpringerLink, Wiley Online Library, EBSCO Host, and UV Digital Library (Universidad de Valparaíso, Chile). [ABSTRACT FROM AUTHOR]

Copyright of Sexologies is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Objective Bupropion, an antidepressant inhibiting the reuptake of dopamine and noradrenaline, should be useful to treat depressive symptoms in patients with Parkinson’s disease (PD). Limited and conflicting literature data questioned its effectiveness and safety in depressed PD patients and extended its use to other neuropsychiatric symptoms associated with this disorder. Design The databases PubMed, Embase, Web of Sciences, Cochrane Library, and the grey literature were searched. Following a scoping review methodology, articles focusing on Bupropion uses in PD patients who manifested depressive or other neuropsychiatric alterations were reviewed. Results Twenty-three articles were selected, including 7 original articles, 3 systematic reviews or meta-analyses, 11 case reports, 1 clinical guideline, and 1 expert opinion. Bupropion showed considerable effectiveness in reducing depressive symptoms, particularly in relation to apathy. Solitary findings showed a restorative effect on compulsive behaviour secondary to treatment with dopamine as well as on anxiety symptoms. The effect on motor symptoms remains controversial. The safety profile of this medication seems positive, but additional precautions should be used in subjects with psychotic symptoms. Conclusion The available literature lacks good evidence to support the use of Bupropion in PD patients presenting depressive symptoms. Further investigations are needed to extend and confirm reported findings and to produce accurate clinical guidelines.

Tourette syndrome (TS) is a frequently observed developmental neuropsychological disorder occurring in children. The pathophysiology involves both genetic and environmental factors. In this review, clinical characteristics, pathophysiology, and treatment approaches based on the pathophysiology of TS are presented. The pathophysiology is the acceleration of developmental decrement of dopamine (DA) activity at the terminal of nigro-striatal (NS)-DA system causing DA D2 receptor up-ward regulation. Serotonergic neurons involving in development of the biphasic sleep-wake-rhythm, and locomotion may be involved. Pharmacological treatments constitute an important part in managing TS. Small dose of levodopa and aripiprazole showed the good effect controlling the tics, without side effects. Intervention with enhancing the day time activity and keeping the regular sleep-wake-rhythm, and encouraging locomotion are important. The data from Yoshiko Nomura Neurological Clinic for Children regarding the clinical features and outcomes, medication effects, and OCD and outcomes are shown. To discuss about the environmental factor, how the COVID-19 pandemic affected the TS patients is also presented.

Abstract Background Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition that globally affects an average of around 5% of children and is associated with several adverse life outcomes. Comorbidity with autism spectrum disorder (ASD) is highly prevalent. Pharmacological treatment for ADHD symptoms has been shown to be effective. However, the prevailing perception is that children with ADHD and concomitant ASD symptoms report poorer efficacy and more side effects. This has been supported by studies on this population, but prospective studies directly comparing children with ADHD and different levels of ASD symptoms are lacking. We aimed to assess if children with ADHD and concomitant ASD symptoms differ regarding effects and side-effects of pharmacological ADHD treatment compared to children with ADHD without ASD traits. This is to our knowledge the second study to directly compare the effect of ADHD medication between ADHD patients with different levels of ASD symptoms. Methods In a non-randomized, observational, prospective cohort study, 323 patients aged 6 to 17 years who were diagnosed with ADHD and starting pharmacological treatment were divided into two groups: one with high level of ASD symptoms (ASD group, N=71) and one with low level of ASD symptoms (non-ASD group, N = 252). Treatment outcome was measured as ADHD symptoms, and evaluated using the Swanson, Nolan and Pelham Teacher and Parent ADHD rating scale-version IV (SNAP-IV). Side-effects were evaluated using the Pediatric Side Effects Checklist (P-SEC), at 3 months follow-up. Results From baseline to 3 months, there was no significant difference in neither treatment effect nor number of clinically significant adverse events experienced between the ASD group and the non-ASD group. Conclusions Our results did not implicate that ADHD patients with concomitant ASD symptoms have decreased treatment effect of ADHD medication than patients with ADHD without concomitant ASD symptoms. Neither did the results support that ADHD patients with ASD symptoms experienced significantly more side-effects than ADHD patients without ASD symptoms. Although, we did not analyze different medications separately, this is in line with the only previous study directly comparing methylphenidate treatment in children with or without ASD. Trial registration NCT02136147 , May 12, 2014.

Macrophages are major host cells for the protozoan Leishmania parasite. Depending on their activation state, they either contribute to the detection and elimination of Leishmania spp. or promote parasite resilience. Here, we report that the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of the NOX2/reactive oxygen species (ROS) axis in early Nrf2 activation and, subsequently, prostaglandin E2 (PGE2)/EP2r signaling in the sustenance of Nrf2 activation upon infection. Moreover, we establish a ferroptosis-like process within macrophages as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of L. infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of therapeutic approaches for the treatment of visceral leishmaniasis. [Display omitted] • ROS and the PGE2/EP2 axis mediate Nrf2 activation in MΦs to promote L.i. growth • Nrf2 promotes L.i. infection via an anti-oxidant and anti-inflammatory profile of MΦs • Nrf2 in MΦs protects L.i. from lipid peroxidation, preventing its death by ferroptosis Blot et al. demonstrate that Nrf2 is a critical transcription factor that protects Leishmania infantum from lipid peroxidation and death by a ferroptosis-like process through the induction of an anti-oxidant and anti-inflammatory profile of macrophages. Hence, pharmacological inhibition of Nrf2 constitutes a promising target for the treatment of visceral leishmaniasis. [ABSTRACT FROM AUTHOR]

This review addresses the prevalence of hypersexual behavior in Parkinson’s patients and the underlying neurobiological mechanisms, identifying risk and protective factors, comparing incidence among different treatments, and proposing recommendations for management and prevention.To conduct a review on the relationship between Parkinson’s disease and hypersexual behavior as a result of pharmacological treatment.The search strategy, guided by PRISMA and PICOS criteria, focuses on the correlation between Parkinson’s disease and hypersexual behavior due to pharmacological treatment. Utilizing databases like PubMed and Proquest, studies from the last 10 years in English or Spanish were selected, emphasizing clinical trials with Parkinson’s patients under treatment. Inaccessible, irrelevant, or mixed-sample studies were excluded. The Cochrane Scale assessed the risk of bias.Out of 122 records, 103 remained after eliminating duplicates; 48 were reviewed, and ultimately, 6 studies met the inclusion criteria for analysis.Synthesizing the risk and protective factors linked to hypersexual behavior in Parkinson’s patients receiving pharmacological treatment underscores the critical need for early detection and incorporation of these factors into clinical care. The suggested guidelines for managing and preventing hypersexual behavior in these patients carry substantial practical implications. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant inherited disease characterized by progressive ataxia and retinal degeneration. SCA7 belongs to a group of neurodegenerative diseases caused by an expanded CAG repeat in the disease-causing gene, resulting in aberrant polyglutamine (polyQ) protein synthesis. PolyQ ataxin-7 is prone to aggregate in intracellular inclusions, perturbing cellular processes leading to neuronal death in specific regions of the central nervous system (CNS). Currently, there is no treatment for SCA7; however, a promising approach successfully applied to other polyQ diseases involves the clearance of polyQ protein aggregates through pharmacological activation of autophagy. Nonetheless, the blood–brain barrier (BBB) poses a challenge for delivering drugs to the CNS, limiting treatment effectiveness. This study aimed to develop a polymeric nanocarrier system to deliver therapeutic agents across the BBB into the CNS. We prepared poly(lactic-co-glycolic acid) nanoparticles (NPs) modified with Poloxamer188 and loaded with rapamycin to enable NPs to activate autophagy. We demonstrated that these rapamycin-loaded NPs were successfully taken up by neuronal and glial cells, demonstrating high biocompatibility without adverse effects. Remarkably, rapamycin-loaded NPs effectively cleared mutant ataxin-7 aggregates in a SCA7 glial cell model, highlighting their potential as a therapeutic approach to fight SCA7 and other polyQ diseases.

Interest in the use of anticholinergics to prevent the development of epilepsy after traumatic brain injury (TBI) has grown since recent basic studies have shown their effectiveness in modifying the epileptogenic process. These studies demonstrated that treatment with anticholinergics, in the acute phase after brain injury, decreases seizure frequency, and severity, and the number of spontaneous recurrent seizures (SRS). Therefore, anticholinergics may reduce the risk of developing posttraumatic epilepsy (PTE). In this brief review, we summarize the role of the cholinergic system in epilepsy and the key findings from using anticholinergic drugs to prevent PTE in animal models and new clinical trial protocols. Furthermore, we discuss why treatment with anticholinergics is more likely to prevent PTE than treatment for other epilepsies.

Alzheimer’s disease (AD) is the most common type of dementia in the elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug is available nowadays. Researchers still work in drug development and are finding new molecular targets to treat AD. Therefore, this study aimed to summarize main advances in AD pharmacological therapy. Clinical trials registered in the National Library of Medicine database were selected and analyzed accordingly to molecular targets, therapeutic effects, and safety profile. The most common outcome was the lack of efficacy. Only seven trials concluded that tested drugs were safe and induced any kind of therapeutic improvement. Three works showed therapeutic effects followed by toxicity. In addition to aducanumab recent FDA approval, antibodies against amyloid-β (Aβ) showed no noteworthy results. 5-HT6 antagonists, tau inhibitors and nicotinic agonists’ data were discouraging. However, anti-Aβ vaccine, BACE inhibitor and anti-neuroinflammation drugs showed promising results.

Although historically, treatment of amblyopia has been recommended prior to closure of a critical window in visual development, the existence and duration of that critical window is currently unclear. Moreover, there is clear evidence, both from animal and human studies of deprivation amblyopia, that there are different critical windows for different visual functions and that monocular and binocular deprivation have different neural and behavioral consequences. In view of the spectrum of critical windows for different visual functions and for different types of amblyopia, combined with individual variability in these windows, treatment of amblyopia has been increasingly offered to older children and adults. Nevertheless, treatment beyond the age of 7 years tends to be, on average, less effective than in younger children, and the high degree of variability in treatment response suggests that age is only one of many factors determining treatment response. Newly emerging treatment modalities may hold promise for more effective treatment of amblyopia at older ages. Additional studies are needed to characterize amblyopia by using new and existing clinical tests, leading to improved clinical classification and better prediction of treatment response. Attention also needs to be directed toward characterizing and measuring the impact of amblyopia on the patients' functional vision and health-related quality of life.

Mayra Cristina da Luz Pádua Guimarães,1 Juliana Chaves Coelho,1 Giovanio Vieira da Silva,2 Luciano Ferreira Drager,2,3 Rita de Cassia Gengo e Silva Butcher,1 Howard K Butcher,4 Angela Maria Geraldo Pierin1 1Graduate Program in Adult Health Nursing (PROESA), University of São Paulo Nursing School, São Paulo, SP, Brazil; 2Hypertension Unit, Renal Division, University of São Paulo Medical School, São Paulo, SP, Brazil; 3Hypertension Unit, Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo, SP, Brazil; 4Christine E. Lynn College of Nursing, Florida Atlantic University, Boca Raton, FL, USACorrespondence: Mayra Cristina da Luz Pádua GuimarãesGraduate Program in Adult Health Nursing (PROESA), University of São Paulo Nursing School, São Paulo, SP, BrazilEmail mayraguimaraes@usp.brObjective: To evaluate and identify variables associated with the control of hypertension and adherence to antihypertensive drug treatment in a group of patients with hypertension monitored in a specialized, highly complex outpatient service.Methods: A prospective, cross-sectional study was carried out in the hypertension unit of a tertiary teaching hospital. Patients diagnosed with hypertensive aged 18 years and over and accompanied for at least six months were included in the study. Patients with secondary hypertension and pregnant women were excluded. The sample consisted of 253 patients. Adherence/concordance to antihypertensive treatment was assessed using the Morisky Green Levine Scale. Blood pressure control was set for values less than 140/90 mmHg. Variables with p≤ 0.20 in univariate analysis were included in multiple logistic regression. The level of significance adopted was p ≤ 0.05.Results: Most of patients were white, married and women, with a mean age of 65 (13.3) years old, low income, and education levels. Blood pressure control and adherence were observed in 69.2% and 90.1% of the patients, respectively. Variables that were independently associated with blood pressure control were (OR, odds ratio; CI, 95% confidence interval): married marital status (OR 2.3; CI 1.34– 4.28), use of calcium channel blockers (OR 0.4; CI 0.19– 0.92) and number of prescribed antihypertensive drugs (OR 0.78; CI 0.66– 0.92). Adherence was not associated with any of the variables studied.Conclusion: There was a high frequency of patients with satisfactory adherence to antihypertensive drug treatment. Blood pressure control was less frequent and was associated with social and treatment-related factors.Keywords: hypertension, control, adherence, pharmacological treatment

Although little reported in daily practice, the use of systemic retinoids can cause changes in the shape, color, and texture of hair shafts. We report a case of a patient treated with isotretinoin for acne vulgaris who experienced new growing curly hair. Such hair changes are recognized during therapy with oral retinoids; however, isotretinoin-induced modifications on the hair fiber curvature are extremely rare.

Objective: To investigate the adaptability of Comprehensive Behavioral Intervention for Tics (CBIT) for a Chinese population, and evaluate the efficacy of combined CBIT and pharmacotherapy (CBIT + PT) compared to CBIT or pharmacotherapy (PT) alone for reducing tics and for improving the quality of life (QoL) in a sample of Chinese children with chronic tic disorders (CTD) and Tourette syndrome (TS). Materials and methods: In this 10-week randomized controlled pilot trial, 37 outpatients aged between 6 and 16 years affected by TS and CTD were randomly assigned to receive CBIT (n = 22) or PT alone (n = 15). Considering the feasibility, the patients allocated to the CBIT treatment group could further choose whether to simultaneously take medicine voluntarily, resulting in a CBIT alone group (n = 12) and a CBIT + PT group (n = 10). Results: At baseline, no significant difference was found between the three groups in the demographic and clinical characteristics (p > 0.05). All three groups showed a significant reduction in tic severity after treatment assessed by the Yale Global Tic Severity Scale (YGTSS) severity score [F(2,33) = 35.05, p < 0.001, ηp² = 0.51], the score of the Clinical Global Impression scale for Improvement (CGI-I) [F(1,34) = 13.87, p = 0.001, ηp² = 0.29], and YGTSS impairment score [F(2,33) = 31.71, p < 0.001, ηp² = 0.48]. Significant interactions were found between the time-point and group in emotional functioning [F(2,29) = 4.39, p = 0.02, ηp² = 0.23], psychosocial functioning [F(2,29) = 5.93, p = 0.007, ηp² = 0.29], and total QoL score [F(1,34) = 3.72, p = 0.04, ηp² = 0.20] of Pediatric Quality of Life Inventory (PedsQL 4.0) for children suggesting a significantly larger improvement in emotional functioning, psychosocial functioning, and total QoL score of the life quality in the CBIT group for children self-report. PedsQL for proxy report only showed a significant main effect of time-point in physical functioning [F(1,33) = 8.35, p = 0.01, ηp² = 0.2], emotional functioning [F(1,33) = 10.75, p = 0.002, ηp² = 0.25], psychosocial functioning [F(1,34) = 11.38, p = 0.002, ηp² = 0.26], and total Qol score [F(1,34) = 13.21, p = 0.001, ηp² = 0.29]. Conclusion: CBIT is probably effective in reducing tic severity in Chinese children with tic disorders. CBIT + PT may not be superior to CBIT alone in reducing tic severity and improving quality of life. CBIT alone showed advantages in improving quality of life over CBIT + PT and PT alone. CBIT might be an appropriate treatment option for patients with tic disorder in Chinese mainland. [ABSTRACT FROM AUTHOR]

Pediculosis (head lice) infections are one of the more sensitive issues that may involve the school nurse. In the 3- to 11-year-old age group in the United States, head lice infections are common and can elicit anxiety in students, parents, and school personnel. Head lice do not transmit any communicable diseases and therefore exclusion from school and "no nit" policies are not warranted. Treatment and management for head lice include a range of over-the-counter products and prescription topical and oral medications. Nonpharmacologic and alternative treatments do exist; however, many do not have established efficacy studies, and some can be costly. The school nurse plays an integral role in providing education related to treatment and environmental recommendations for families affected by head lice. Through this education, the nurse can also reduce the stigma and anxiety many feel around the subject of head lice infections. [ABSTRACT FROM AUTHOR]

Interleukin 6 (IL-6) acts as a pro and anti-inflammatory cytokine, has an intense correlation with exercise intensity, and activates various pathways such as autophagy and mitochondrial unfolded protein response. Also, IL-6 is interconnected to circadian clock-related inflammation and can be suppressed by the nuclear receptor subfamily 1, group D, member 1 (Nr1d1, protein product REV-ERBa). Since IL-6 is linked to physical exercisemodulated metabolic pathways such as autophagy and mitochondrial metabolism, we investigated the relationship of IL-6 with REV-ERBa in the adaptations of these molecular pathways in response to acute intense physical exercise in skeletal muscle. The present study was divided into three experiments. In the first one, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were divided into three groups: Basal time (Basal; sacrificed before the acute exercise), 1 hour (1hr post-Ex; sacrificed 1 hour after the acute exercise), and 3 hours (3hr post-Ex; sacrificed 3 hours after the acute exercise). In the second experiment, C2C12 cells received IL-6 physiological concentrations or REV-ERBa agonist, SR9009. In the last experiment, WT mice received SR9009 injections. After the protocols, the gastrocnemius muscle or the cells were collected for reverse transcription-quantitative polymerase chain reaction (RTq-PCR) and immunoblotting techniques. In summary, the downregulation of REV-ERBa, autophagic flux, and most mitochondrial genes was verified in the IL-6 KO mice independent of exercise. The WT and IL-6 KO treated with SR9009 showed an upregulation of autophagic genes. C2C12 cells receiving IL-6 did not modulate the Nr1d1 mRNA levels but upregulated the expression of some mitochondrial genes. However, when treated with SR9009, IL-6 and mitochondrial gene expression were upregulated in C2C12 cells. The autophagic flux in C2C12 suggest the participation of REV-ERBa protein in the IL-6-induced autophagy. In conclusion, the present study verified that the adaptations required through physical exercise (increases in mitochondrial content and improvement of autophagy machinery) might be intermediated by an interaction between IL-6 and REVERBa. [ABSTRACT FROM AUTHOR]

Compounds known to be successful in the treatment of alcohol use disorder include the aversive agent, Disulfiram, the glutamatergic NMDA receptor antagonist, Acamprosate, and the opioid receptor antagonists, Naltrexone and Nalmefene. Although all four are effective in maintaining abstinence or reduction of alcohol consumption, only a small percentage of patients receive pharmacological treatment. In addition, many other medications have been investigated for their therapeutic potential in the treatment of alcohol use disorder. In this review we summarize and compare Baclofen, Gabapentin, Topiramate, Ondansetron, Varenicline, Aripiprazole, Quetiapine, Clozapine, Antidepressants, Lithium, Neuropeptide Y, Neuropeptide S, Corticotropinreleasing factor antagonists, Oxytocin, PF-05190457, Memantine, Ifenprodil, Samidorphan, Ondelopran, ABT-436, SSR149415, Mifepristone, Ibudilast, Citicoline, Rimonabant, Surinabant, AM4113 and Gamma-hydroxybutyrate While some have shown promising results in the treatment of alcohol use disorder, others have disappointed and should be excluded from further investigation. Here we discuss the most promising results and highlight medications that deserve further preclinical or clinical study. Effective, patient-tailored treatment will require greater understanding provided by many more preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Background: Pharmacological treatment for ADHD exhibits much variation. Longitudinal prescription-filling trajectories are interesting objects to explore. The goal of this study is to identify distinct patterns of longitudinal prescription filling among pediatric patients who were ever diagnosed with ADHD. Methods: Longitudinal data of ADHD-specific prescription filling during 2010–2019 of children diagnosed with ADHD during 2000–2019 who were 4–17-years-old at the time of diagnosis was obtained. Clustering of prescription-filling vectors was performed using K-means. Results: Analysis of 57,110 prescription vectors yields five distinct patterns: high intensity treatment, from early childhood to late teens (5.7%); moderate intensity, from early childhood to late teens (13.3%); high intensity, from late childhood to late teens (6.1%); moderate intensity, from late childhood to late teens (14.2%); and low intensity, sporadic treatment (60.7%). These patterns correspond with observed clinical presentations. Conclusions: Identifying longitudinal prescription-filling patterns substantiates and qualifies the variation in long-term efficacy of pharmacological treatment for ADHD in a treatment-as-usual community setting. Prescription-filling implies that symptoms are present, and that treatment is efficacious, as perceived by parents' and carers. Prolonged pharmacological treatment was perceived to have had a positive net value for 40% of the children, which under appropriate reservations, provides weak evidence of efficacy. [ABSTRACT FROM AUTHOR]

• The most effective management strategy for alcohol use disorder is the combination of psychosocial interventions and pharmacological therapy. • Several medications have been tested for the treatment of alcohol use disorder over the years and some of them have been approved, even if the exact panel of approved drugs may vary across. countries. • The currently available medications for the treatment of AUD have shown good overall efficacy. • At present, drugs for AUD are markedly underutilized in clinical practice. Increasing the training of clinicians may increase familiarity with the medications, reducing the lack of confidence in their efficacy, which is an important barrier for their prescription. In the last decades, many medications have been tested for the treatment of Alcohol Use Disorder (AUD). Among them, disulfiram, acamprosate, naltrexone, nalmefene, sodium oxybate and baclofen have been approved in different countries, with different specific indications. Topiramate is not approved for the treatment of AUD, however, it is suggested as a therapeutic option by the American Psychiatric Association for patients who do not tolerate or respond to approved therapies. In this narrative review we have analyzed the main studies available in literature, investigating the efficacy and safety of these medications, distinguishing whether they were oriented towards abstinence or not. Randomized controlled studies, analyzing larger populations for longer periods were the main focus of our analysis. The medications currently available for the treatment of AUD are quite effective, yet further progress can still be achieved through the personalized strategies. Also, these medications are still markedly underutilized in clinical practice and many patients do not have access to specialized treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: To evaluate the incidence of polypharmacy in patients attended at home by the Programa Melhor em Casa Program. Material and methods: 28 medical records of patients attended by MemC in the city of Goiatuba-GO, from December 2020 to July 2021 were evaluated. The patient profile and the variables age, sex and medications used were evaluated. Results and discussion: the majority of patients were women, 64.3% (n=18) compared to 35.7% of men (n=10). During the study 5 patients died (17.24%). The mean age of the patients was 67.3 ± 19.0 years; of this total, 28.57% (n=8) were between 18 and 59 years old; and, the other 71.43% (n=20) were over 60 years old, characterizing them as elderly. The mean number of drugs used was 5.7±3.3 drugs/patient, being higher among elderly patients, 6.0±3.5. Conclusion: The exacerbated use of drugs can lead to the appearance of adverse reactions that can sometimes be confused with new symptoms. Pharmacological therapy should not be the only alternative for the patient, but should be associated with nutritional, physical and psychological support. [ABSTRACT FROM AUTHOR]

Copyright of Saúde Coletiva is the property of MPM Comunicacao and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Practical relevance: An infertile tom used to be a relatively rare presentation in feline practice. However, as a result of breeding strategies targeting specific morphological/behavioural traits, and the influence of inbreeding (especially practised in rare breeds), among other factors, feline infertility has become a genuine clinical problem. Furthermore, increased interest among cat breeders and pet owners in diagnosing and treating an 'unsuccessful' tom (including using assisted reproductive techniques [ARTs]), has made such patients more commonplace in veterinary practice. Clinical challenges: A definitive cause for male infertility is often difficult to identify. One of the biggest challenges is the lack of fertility-based reference values for semen quality and hormone levels. Moreover, the literature in this field is scant and many reproductive tract conditions described in other species have not been reported in cats. The establishment of diagnostic tools and algorithms is essential to facilitate a reliable assessment of fertility potential. Global importance: There is a growing demand for appropriate veterinary care relating to feline reproduction. There is an expectation among breeders, particularly of pedigree cats of high breeding value, that the same options widely used for dogs (including ARTs) should also be available for cats. Equipment and technical skills: Equipment required for investigating male infertility includes a microscope and ultrasound machine; a blood analyser may also be useful, but samples can instead be sent to a laboratory. The skills required are often already performed by veterinarians; for example, catheterising the urethra, performing ultrasonography and blood sampling. Evidence base: There are some reports of fertility problems in male cats in the literature, but this area of feline reproduction is still relatively undeveloped. This review draws on the comprehensive knowledge developed and shared by specialists in this field, and is supported by the authors' own clinical experience. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Ciências da Saúde da UNIPAR is the property of Associacao Paranaense de Ensino e Cultura and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)