Boya Nugraha

Metabolomics Study With Gas Chromatography-Mass Spectrometry for Predicting Valproic Acid–induced Hepatotoxicity and Discovery of Novel Biomarkers in Rat Urine

Three different doses of valproic acid (20, 100, and 500 mg/kg/d) are administered orally to Sprague-Dawley rats for 5 days, and the feasibility of metabolomics with gas chromatography–mass spectrometry as a predictor of the hepatotoxicity of valproic acid is evaluated. Body weight is found to decrease with the 100-mg/kg/d dose and significantly decrease with the 500-mg/kg/d dose. Mean excreted urine volume is lowest in the 500-mg/kg/d group among all groups. The plasma level of α-glutathione-S-transferase, a sensitive and earlier biomarker for hepatotoxicity, increases significantly with administration of 100 and 500 mg/kg/d; however, there is not a significant difference in α-glutathione-S-transferase plasma levels between the control and 20-mg/kg/d groups. Clusters in partial least squares discriminant analysis score plots show similar patterns, with changes in physiological conditions and plasma levels of α-glutathione-S-transferase; the cluster for the control and 20-mg/kg/d groups does not clearly separate, but the clusters are separate for 100- and 500-mg/kg/d groups. A biomarker of hepatotoxicity, 8-hydroxy-2′-deoxyguanosine and octanoylcarnitine, is identified from nontargeted and targeted metabolic profiling. These results validate that metabolic profiling using gas chromatography–mass spectrometry could be a useful tool for finding novel biomarkers. Thus, a nontargeted metabolic profiling method is established to evaluate the hepatotoxicity of valproic acid and demonstrates proof-of-concept that metabolomic approach with gas chromatography–mass spectrometry has great potential for predicting valproic acid–induced hepatotoxicity and discovering novel biomarkers.

Brain-derived neurotrophic factor and exercise in fibromyalgia syndrome patients: a mini review

Fibromyalgia syndrome (FMS) is a common chronic pain condition characterized by chronic widespread pain and decreased pain threshold, with hyperalgesia and allodynia. Associated signs include fatigue, morning stiffness, non-restorative sleep, mood disturbance, depression, irritable bowel syndrome, and headache. In addition to the administration of drugs, psychological therapies treatment of FMS mainly consists of physical therapies. Although the precise pathogenesis of FMS remains elucidated, modern understanding conceptualizes FMS as central sensitization as a consequence of altered endogenous pain- and stress-response system and continuous nociceptive input. Altered brain-derived neurotrophic factor (BDNF) levels in FMS suggest that BDNF—well known for its effects on neuronal plasticity—is involved in this sensitization process. Exercise leads to changes in serum BDNF levels, too. This association highlights the importance of exercise in FMS and other chronic pain conditions.

Serum level of brain-derived neurotrophic factor in fibromyalgia syndrome correlates with depression but not anxiety.

Brain-derived neurotrophic factor (BDNF) has been known to play a role in fibromyalgia syndrome (FMS) patients. Depression and anxiety are quite common additional symptoms in FMS. However the role of BDNF in these symptoms still needs to be elucidated. Although BDNF has been shown to be relevant in major depression, however studies could not show such differences between FMS patients with and without major depression. As mood-related symptom occurs frequently and differs in its intensity in FMS patients, BDNF level should be measured in subgroup regarding depression and anxiety scale. Therefore the aim of this study was to evaluate the correlation of BDNF in serum of FMS with intensity of depression and anxiety. Additionally, interleukin (IL)-6 was measured. This study showed that serum level of BDNF was age-dependent in HCs. FMS patients had higher level of serum BDNF as compared to HC. Additionally, serum level of BDNF showed correlation with depression, but not with anxiety. Serum level of BDNF increased with depression score in FMS. However, serum level of IL-6 was not correlated with both depression and anxiety scores. Taken together, BDNF is involved in the pathophysiology of FMS. Additionally, it seems to be correlated with intensity of depressive symptoms in FMS.

Re: ISPRM discussion paper: Proposing dimensions for an international classification sytem for service organization in health-related rehabilitation.

OBJECTIVE Rehabilitation is 1 of 4 main health strategies. The World Report on Disability identifies deficits in rehabilitation care for people with disabilities as an important barrier to full inclusion in society or to achieve optimal functioning. In order to overcome such deficits, to close gaps in national and/or regional rehabilitation systems, and to develop appropriate rehabilitation services, it is crucial to define uniform criteria and a widely accepted language to describe and classify rehabilitation services. The aim of this paper was therefore to develop a list of dimensions and categories to describe the organization of health-related rehabilitation services. METHODS The classification is based on a series of expert workshops including members of the International and European Society of Physical Medicine and Rehabilitation. RESULTS The proposed classification has 2 levels (dimensions and categories). The upper level distinguishes 3 dimensions: the service provider (with 9 categories), the funding of the service (with 3 categories), and the service delivery (8 subcategories). A further specification of the categories in a 3-level classification (including value sets) is needed. CONCLUSION This paper is an intermediate step towards development of a classification system with distinct categories and dimensions.

Principles of Assessment of Rehabilitation Services in Health Systems: Learning from experiences

OBJECTIVE Strengthening of health-related rehabilitation services must start from the needs of persons with health conditions experiencing disability and should be implemented within health systems. The implementation of rehabilitation services in health systems should be planned and realized according to the World Health Organizations 6 constituents of health systems (i.e. health service delivery; health workforce; health information systems; essential medicines; financing; and leadership and governance). The development of recommendations based on situation analysis and best-available data is crucial. METHODS In order to facilitate such data collection at a national level, a checklist and a related questionnaire (Rehabilitation Service Assessment Tool (RSAT)) were developed and implemented. The following steps were followed to develop a checklist for implementation of rehabilitation services: a literature search, drafting, checking and testing the list, and development of the RSAT. RESULTS The RSAT comprises 8 sections derived from 5 main domains of the most important areas of information (i.e. country profile; health system; disability and rehabilitation; national policies, laws, and responsibilities; and relevant non-governmental stakeholders). CONCLUSION The implementation of RSAT in different missions has shown that the principles are working well and that RSAT is feasible and helpful. Further field testing is important and the development of an internationally agreed tool should be promoted.

Scaling up rehabilitation - Towards an international policy agenda.

No Abstract (Guest Editorial).

Evaluation of the topic lists used in two world Congresses (2015 and 2016) in Physical and Rehabilitation Medicine

BACKGROUND Evaluation of the initial list of proposed abstract topics for Congresses of Physical and Rehabilitation Medicine (PRM) was needed in order to ensure its feasibility for use in future congress announcements and invitations for abstract submission. METHODS The initial proposals were based on 5 main areas of PRM research: biosciences in rehabilitation, biomedical rehabilitation sciences and engineering, clinical PRM sciences, integrative rehabilitation sciences, and human functioning sciences. This list became a model for structuring the abstracts for the 9th and 10th World Congresses of PRM, held in Berlin, Germany (2015) and Kuala Lumpur, Malaysia (2016), respectively. The next step was to evaluate the implementation of this model in both congresses. RESULTS It was found that the 5 main research areas were still used as the main principles (chapters) in which to organize the abstracts. However, some modifications have been made to cover topics that were not included in the initial proposal. CONCLUSION A more comprehensive list of topics has been developed, not only for topic list announcements, but also for the structuring and classification of abstracts for future international, regional or national PRM congresses.

Why the Collaboration With the World Health Organization (WHO) Is Important for Specialists in Physical and Rehabilitation Medicine

This is a question that we often are asked. Of course, there is no simple answer to such a question, but in principle there are 2 main aspects. The first one is that the specialty of PRM can provide relevant input to WHO’s conceptual developments, definitions, resolutions, and actions in the field of disability and rehabilitation, and to provide this expertise is a question of global responsibility towards the development of human rights and universal health coverage. The second one is that PRM specialists can obtain information and conceptual ideas that are useful for the global development and establishment of the specialty of PRM and its clinical service provision.

Functions of the Temporomandibular System in Extracranial Chronic Pain Conditions: Modulatory Effects on Nocifensive Behavior in an Animal Model

OBJECTIVE Mastication may be able to activate endogenous pain inhibitory mechanisms and therefore lead to modulation of nociceptive processing. The purpose of this study was to examine the possible effect of food consistency on noxious input from the spinal system. METHODS Three groups of adult male Sprague-Dawley rats were given an injection of complete Freund adjuvant in a hind paw 10 days after eating soft or hard food (one group received a saline injection-the control group [C]; the other group (D) received no injection). Nocifensive behavior was assessed with the use of the hot plate and tail flick assays at 1, 3, 6, and 12 hours and at 6.5 days after injection for groups A/B, and c-Fos activity was assessed in the brain after testing. Groups C/D had hot plate testing at 1 hour and 6.5 days. The data were analyzed by general linear modeling and 1-way analysis of variance. RESULTS There was a small increase in the hot plate percent maximum possible effect (MPE) from -45.7 to -61.1 in group A over the length of the experiment, but a very small decrease for group B over the same period (-33.5 to -28.8). For the saline control group, there was a small increase toward 0 %MPE over the same time frame (-15.0 to 1.7). The %MPE differences were significant between groups A and C (P < .0005), but not significant between the other groups (F = 13.34, df = 2, P = .001, observed power = 99%). Using the pooled results (all time points), the differences between all groups were significant (P < .0005). There were no significant differences in the tail flick test. c-Fos was mainly observed in the raphe pallidus area with significant differences between groups A and B at 3 and 6 hours after injection of CFA (P = .027 and .022, respectively). CONCLUSIONS The results of this study indicate that food consistency (hardness) influences nocifensive behavior in this animal model via a descending pathway operating at the supraspinal level.

An exchange of ideas on the World Report on Disability.

On June 9, 2011, the World Report on Disability (WRD) was released at the United Nations in New York. The report followed the call of the World Health Assembly for a comprehensive report on the situation of people with disability around the world and has nine chapters that refer to the understanding of disability, recent epidemiologic data, general health care, rehabilitation, assistance and support, enabling environments, education, employment, and several recommendations (Fig. 1). Each of the chapters strikingly demonstrates that disability is not simply a health condition or an individual characteristic but an interaction between health-related impairments and societal and environmental barriers. These barriers include stigma and discrimination, lack of adequate health care and rehabilitation services, inaccessible transport and buildings, as well as deficient access to information and communication technologies. The crucial question is whether one is able and willing to remove these barriers to improve the life situation of persons with disabilities. In his foreword to the report, the renowned theoretical physicist Professor Stephen Hawking calls the necessary efforts ‘‘a moral duty,’’ and with much optimism, he declared his hope that ‘‘this century will mark a turning point for inclusion of people with disabilities in the lives of their societies’’ (p. IX). Indeed, the report’s publication indicates that some lessons might already be learned. The WRD is the first major health report of the World Health Organization to be available in Braille, and there is also a version for people with mental retardation consisting largely of pictures and captions. Optimism is certainly needed to face the challenges. The report demonstrates that almost one-fifth of the estimated global population lives with disabilities, and most countries do not have sufficient legislations, services, and financial and human resources to adequately respond to the needs of people with disabilities. However, the WRD is not only another document that claims a better understanding of disability and reveals attitudinal barriers and service deficits. The authors and contributors want to point forward toward concrete actions to overcome barriers that hinder participation of people with disabilities. Consequently, the WRD ‘‘focuses on measures to improve accessibility and equality of opportunity; promoting participation and inclusion; and increasing respect for the autonomy and dignity of persons with disabilities’’ (p. XXII). Rehabilitation is thereby seen as a major strategy and has a central role in the report’s structure (Fig. 1). Immediately after the launch of the WRD, the International Society for Physical and Rehabilitation Medicine (ISPRM) agreed to develop an action plan to disseminate, analyze, and implement the WRD in rehabilitation and particularly in physical and rehabilitation medicine (see the final article of this issue). Moreover, the ISPRM president’s cabinet and members of the World Health Organization Liaison Committee decided to work on a special issue on the WRD, and the Editorial Board of the American Journal of Physical Medicine & Rehabilitation kindly offered the opportunity to use this high-quality journal for publication for the resulting articles. In total, 30 authors contributed to this special issue. The authors start with a summary of the report’s main contents with a special focus on the rehabilitation chapter. Afterward, von Groote and coauthors discuss how to meet the challenge of getting publications such as the WRD into practice. The inner chapters of this issue present comments and perspectives from eight different nations including the United States of America, Mexico, Argentina, Sweden, Saudi Arabia, Ghana, Korea, and Indonesia. These nations were selected to provide examples from the three ISPRM world areas and to cover most of the subareas (Table 1). The editors of this supplement are aware of the arbitrariness of this choice. However, the editors and authors are confident