In patients with idiopathic normal pressure hydrocephalus (iNPH) with features of Disproportionately Enlarged Subarachnoid-space Hydrocephalus (DESH), ventriculomegaly and the tight high-convexity and medial subarachnoid spaces appear in magnetic resonance (MR) images before the occurrence of objective symptoms. There are few reports of longitudinal observation of clinical course in DESH-type iNPH patients with no objective symptom.We longitudinally observed 4 patients  with features of DESH who visited the neuropsychological clinic in our hospital, whose symptoms were not apparent in the first visit. We evaluated the triad symptoms with iNPHGS and conducted the cognitive and gait examinations once a year. We also evaluated quantitative rCBF of those patients by 123I-IMP single photon emission computed tomography (SPECT) using the autoradiography (ARG) method.Based on the scores of iNPHGS, we classified 4 patients into two groups; two stable patients and two deteriorated patients. In one patient of the stable group, the score of the Mini-mental State Examination (MMSE) did not change and the score of the Frontal Assessment Battery (FAB) and the Timed Up & Go Test (TUG) improved, however, in the other patient, the score of MMSE, FAB and TUG worsened. In the deteriorated group, one patient expressed the gait disturbance and the other patient did the gate disturbance and the cognitive impairment. In the former patient, the score of MMSE and FAB worsened and a wide-based gate and the disturbance of the dynamic equilibrium appeared, although the score of TUG did not change. In the latter patient, the score of FAB and TUG worsened but the score of MMSE did not change. The changes of quantitative rCBF of 4 patients were various.The different clinical courses and changes of quantitative rCBF were observed in each patient.


Realities remote from the objective value of molecular allergology / component-resolved diagnosis may explain the gap in clinical implementation between Europe and North America. If the latter is to assert a dominant role in the field of allergy, its professionals will have to embrace change and provide leadership in molecular allergology. As for sublingual immunotherapy, inaction on the part of allergy professionals will leave to commercial and industrial interests the definition of the business model and ultimately the patients' health care options.Was America sleeping on its laurels or just snubbing molecular allergology / component-resolved diagnosis? The clinical implementation of molecular allergology testing in Europe dates back to the early 2000's. Although the importance of major allergens seems to have been readily recognized by allergy professionals in North America, more exhaustive exploration and clinical use of molecular allergology is still waiting. In this day and age of instant communication and worldwide professional collaboration, it is surprising that such a gap could have developed. A review of factors that may have led to this situation represents an opportunity to identify important dynamics that sometimes hinders the introduction of valuable science and/or technologies to our patient care. In France, the model of physician remuneration may have set up the opportunity for the professional cooperation that developed the science and its integration to government-sponsored healthcare services. In Canada, the lack of expertise and demand for molecular allergology services has hindered the country-specific certification process of laboratory technology otherwise widely recognized. In the US, the FDA is still restricting its endorsement to the "Peanut-You-Know" portion of Thermofisher's line of molecular allergy testing products. All the while and until recently, pioneering US-based research in oral immunotherapy (OIT) neglected basic data concerning peanut allergy molecular profiles at a time when comprehensive protocols were routine clinical practice in some French centers. Whereas


The use of the extra-vertebral balloon osteoplasty is increasing and in the meanwhile it has become a safe surgical technique in the treatment of tibial head, distal radius and calcaneus fractures. In addition, we already could show in a biomechanical setup that the balloon osteoplasty might be a safe tool for reduction in the treatment of Hill-Sachs lesions, but clinical application has not been performed so far.We report the case of a 53 year- old male patient who was referred to our Trauma department (level I trauma center) after the first manifestation of a posterior shoulder dislocation due to an epileptic seizure, originated in a- up to this date unknown -glioblastoma. After closed reduction of the dislocated shoulder the X-ray showed a subcapital fracture of the proximal humerus with a large reversed Hill-Sachs lesion. We performed an open surgery via a deltoideopectoral approach and balloon osteoplasty was used to reduce the impression fracture (Hill-Sachs lesion) before fixing the fracture with a locking plate. In the post-operative CT scan we could show an anatomical reduction of the Hill-Sachs lesion. At the follow-up examination one year after surgery the patient reached full range of motion and stated no re-dislocation of the shoulder nor instability or pain.The reduction of an impressed humeral head fracture by use of balloon osteoplasty is a safe technique. This technique could be a new option in the treatment of Hill-Sachs lesions and might be an alternative to well known standard procedures like the remplissage or tendon transfers without affecting rotation. The use of the balloon-guided kyphoplasty is a safe and reliable operative technique  and in tA 53- year- old male patient who sustained a posterior shoulder dislocation with combined subcapital fracture and reversed Hill-Sachs lesion see Fig.  was refeIn a first step the reverse Hill-Sachs lesion was reduced using an inflatable balloon as used in kyphoplasty. In contrast to our experimental set-up  were we The patient recovered well from this surgical intervention, achieved a free range of motion and had no re-dislocation at the one year follow-up. No technique-related complications occured. Unfortunately, we are not able to report about the long-term follow-up as the patient died of complications caused by his glioblastoma 22 months after surgical intervention.Posterior dislocation of the shoulder is a rare entity and therefore often misdiagnosed . Once diAs an alternative technique Keppler et al.  describeThe presented case describes the reduction of the reverse Hill-Sachs lesion using a regular kyphoplasty balloon  in a firSome questions are left unanswered and remain for future research. Though we used a open deltoideo-pectoral approach due to the accompanying subcapital fracture and the need of additional plating we are convinced that this technique is suitable under arthroscopic conditions thereby further reducing the surgical trauma and remaining minimal-invasive. From our own experience the Hill-Sachs lesions has then to be treated as close to the accident as possible. To enable exact arthroscopic intervention a guiding instrument as we know it from ACL reconstruction might be helpful as well as a fenestrated cannula likewise we used in tibial head reconstruction as an abutment and lesion indicator . In addiThe other remaining point is the matter of defect filling after reduction of the reverse Hill-Sachs lesion. In our case we were able to save the reduction by positioning of the locking plate. In those cases where you would have an isolated impaction fracture it might be sufficient to limit range of motion to leave the defect unaffected for the first 6 weeks. As an alternative, defect filling would be possible either with cancellous bone or bone substitues and would probably be superior to filling of the emerging hollow with bone cement as described by Jacquot et al.  in the tDespite all positive reports on the inflation osteoplasty, this new surgical technique is not free from complications and as in all emerging techniques there is always the risk of potentially harm patients until the technique is well established and validated . In thisHowever, this is a first report on the described technique in the reduction of a reversed Hill-Sachs lesion and further studies are needed with special remark on complications and their management.In our described case the reduction of the reverse Hill-Sachs lesion by use of inflation osteoplasty enabled us to achieve an almost anatomical reduction in the humeral head without limitation of external rotation as commonly found in patients after remplissage or tendon transfers and there we see the great advantage of the presented technique. In cases with isolated reverse Hill-Sachs lesions the application of the balloon osteoplasty might be even performed arthroscopically and thereby further reducing the comorbidity of the open surgical approach.Written informed consent has been obtained from the patient for the publication of this case report and any accompanying images.A copy of the written consent is available for review for the editor-in-chief of this journal.


Since the discovery of the structure of the DNA double helix in 1953 by Watson and Crick . It tookHans-Achim WagenknechtKarlsruhe, November 2014


The cell's fate is largely governed by the dynamics of cellular events, brought about by the interplay of various proteins, in which post-translational modifications (PTMs) play a key role. Therefore, a better understanding of post-translational modification is of utmost importance to a biochemist. Over the years much work in this regard has been achieved through mass spectrometry, however, the “on-off” nature of PTMs, which accounts for cell's dynamics, has posed a serious challenge in quantitating them, especially with regards to measuring the occupancy of PTMs on a particular site. Protein phosphorylation has served as the best model for which measurement of occupancy has been attempted by employing stable isotope labeling and label-free approaches. But the reliability of these methods has mainly been limited to the relative quantitation between samples. Although the fractional occupancy/absolute quantitation of phosphorylation has been determined by grossly applying these methods, but overall they fall short of testability. Moreover, the field demands a broad approach which can even encompass a more challenging task of absolute quantitation of Cys-based PTMs.For quantitation, differential labeling of samples with stable isotopes or in the label-free approach the peak intensity of a peptide ion or identification frequency of the peptides of a particular protein is used for measurement. Stable isotope labeling is achieved through metabolic labeling in cell culture or by chemical labeling in post-metabolic stage. For the metabolic labeling of proteins, the cell cultures are grown in the presence of naturally abundant amino acids (light version), and amino acids  labeled with heavy isotopes , this method is known as stable isotope labeling with amino acids in cell culture (SILAC). The ratio of the ion intensities of the peptide (light vs. heavy) in the MS scan is used for quantitation (Ong et al., per se. These standards are the pre-selected synthetic peptides from the protein of interest that gets labeled with an isotope. A known amount of the isotope labeled peptides are mixed with the sample and then introduced into the mass spectrometer. Absolute abundance of the PTM can be obtained by measuring the relative abundance of the modified and unmodified peptides and comparing it with the amount of standard used. Notably, stable isotope labeling and synthetic peptide standards were used in absolute quantitation of phosphorylation on Ser1526 in human separase (Stemmann et al., Stable isotope labeling for absolute quantitation requires internal standards that are used to measure protein abundance Interestingly, an integrated phosphatase treatment and stable isotope labeling approach was adapted for determining the absolute phosphorylation occupancy in the yeast proteome. This approach did not make use of any standard, instead equal amounts of protein lysates after protease-digestion were either mock- or phosphatase treated, differentially labeled with stable isotope and subsequently mixed. The absolute phosphorylation site occupancy was represented by the single ratio between the non-phosphorylated peptides with and without phosphatase treatment (Wu et al., per se is very low. Thus, looking at the fast pace of the field and the continuous out-flux of ideas from the think-tank, the doorway for site occupancy measurement of Cys-based PTMs is already open but to come up with a foolproof method, would require some sound strategizing.With the present day, state-of-the-art technology and improved methodology we have made significant progress in characterizing phosphorylation and the databank is increasing every day. Nonetheless, another segment of the field; Cys-based PTMs considerably lags behind! The mechanistic insight of Cys-based modifications, in particular, S-nitrosylation and S-palmitoylation, is ever growing, and their involvement in regulating various cellular events is quite plausible. There are few remarkable methods developed over the years to identify the Cys-sites of these modifications with mass spectrometry, like the biotin-switch technique and SNO-Rac for S-nitrosylation (Jaffrey et al., The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The term onco-nephrology has been coined in an attempt to highlight the evolution of an increasingly complex and important sub-specialty in the practice of renal medicine.The term onco-nephrology has been coined in an attempt to highlight the evolution of an increasingly complex and important sub-specialty in the practice of renal medicine. Given the improved survival and aging population, the prevalence of comorbidities is ever expanding and chronic kidney disease (CKD) is a major constituent. Between 2005 and 2009 >75% of cancer diagnoses occurred in individuals aged ≥65 years . When thMMA is the single author of the manuscript.The author declared no competing interests.Ethical issues  have been completely observed by the author.None.


Neural cell adhesion molecule (NCAM) plays important roles in the regulation of the brain plasticity during its development and in adulthood. NCAM functions may be regulated by the addition of long linear homopolymers of alpha 2-8-linked sialic acid (PSA). PSA is attached to NCAM via either of two specific sialyltransferases: ST8SiaII and ST8SiaIV. PSA-NCAM is expressed abundantly in the retina and optic nerve during development and adulthood. In the retina PSA-NCAM is expressed in the glial cells in close proximity to retinal ganglion cell (RGC). The functions of the PSA-NCAM in the retina remain unknown. The aim of this study was to investigate the roles of PSA-NCAM in the survival of RGCs after administration of the exitotoxin kainic acid (KA). Intraocular administration of KA induced reduction in the density of RGCs approximately by 60%. Administration of endoneuraminidase (Endo-N) an enzyme, which removes PSA residues from the surface of NCAM, enhanced the toxic effect of KA on RGC. In knockout mice with constitutive deficiency of either ST8SiaII or ST8SiaIV genes, the levels of PSA-NCAM did not differ from those in wild type mice. The toxicity of KA on RGC in these animals also did not differ from control. It should be noted, however, that in knockout ST8SiaII-/- adult mice a reduced number of RGCs was found despite the presence of high levels of PSA-NCAM. These data suggest that during development ST8SiaII ensures high levels of PSA-NCAM, which necessary for the developmental survival of RGCs. The PSA-NCAM in the adult retina ensures the resistance of RGCs to injury.


Recognition of systemic autoinflammatory diseases (SAIDs) in the last decade is growing rapidly. About 250 children is under care with suspicion or diagnosis of SAIDs in our centre and monitoring of inflammatory markers is fundamental in their diagnosis and monitoring of treatment.To check the practical usefulness of home CRP monitoring in patients during diagnosis or monitoring of autoinflammatory diseases.Ten patients with genetically confirmed or suspicion of AIDs  were monitored at home with both use of diary of symptoms/treatment and regular CRP measurement.CRP levels were checked by parents at home using ready-to-use system on a finger-prick blood sample of their child.Ready-to-use system provided patients with very fast, easy to perform and safe CRP measurement, having obtained reliable results.Children and their parents found avoidance of frequent outpatient clinic visits and painful collection of blood from veins extremely important. Parents were able to use the system properly just after 2-3 hours of practical training.Regular, up to twice a day measurement of CRP greatly facilitated the diagnosis and monitoring of patients' treatment. It proved to be extremely useful in an appropriate modification of treatment with the use of steroids in PFAPA or IL1-blockers in TRAPS.The results of introductory pilot study of home measurement of CRP levels in children with autoinflammatory diseases are encouraging. The opportunity of fast, regular monitoring of inflammatory marker in home conditions improved both diagnostic-therapeuthical process as well as quality of children's life.


The considerable pressure on healthcare systems, exerted by increasing expenditures for new drugs, urges specific initiatives, including the development of new models, to optimize the managed entry of new medicines and guarantee their sustainability.To develop a forecasting model for drug utilization and expenditure of emerging medicines identified, prioritized and critically assessed by the Italian Horizon Scanning Project (IHSP), integrating a cellular automata (CA) model describing the diffusion process on the market with the budget impact analysis (BIA), performed before the market entry of a new drug.Selection and critical evaluation of high-impact emerging medicines. Development of CA and BIA models for emerging drugs, using medical prescription data from the administrative ARNO-CINECA databases.The first-in-class emerging anti-diabetic dapagliflozin was selected and critically evaluated by the IHSP about 12 months before the European Marketing Authorization (MA). Other competitors already on the market were identified. A CA model describing the diffusion process of more than 200 Italian specialties of oral antidiabetic drugs (ATC A10B), sold between 2000 and 2014 has been developed and validated.A protocol for the identification of the real-world target population in the ARNO-CINECA database was set up on the grounds of the expected indication for dapaglifozin. The estimation of the budget impact of dapagliflozin is ongoing based on the estimation of market shares, through the application of the CA model, the analysis of the identified target population and the analysis of the potential variations in related healthcare costs for the treatment of type 2 diabetes, after the introduction of dapagliflozin.The proposed forecasting model (C-ToBIA model) predicts the impact of emerging drugs on the National Health System (NHS), under the sufficient conditions for estimability. The originality of the C-ToBIA model is basically related to the assessment of emerging drugs 12 months before the MA date, and the estimation of the diffusion process and the potential financial impact before market entry.The C-ToBIA model will help to timely estimate the possible utilization pattern of new medicines and their potential impact on the NHS before their market entry.


We examined the extent to which the two generic health- related quality of life (HRQL) measures recommended for use in adult, general critical care  - the SFA patient-based conceptual framework for survivors' HRQL was built using: a systematic review of the literature; secondary analysis of 40 in-depth interviews with adult critical care survivors; and primary analysis of in-depth interviews with a maximum variation sample of 25 white critical care survivors in England. Two methods were then used to assess the extent to which the SF-36 and EQ-5D captured their HRQL, as detailed in the framework: the content of both instruments was examined, alongside data collected from the in-depth interviews; and the opinions that survivors expressed about how accurately the SF-36 and EQ-5D reflected their ideas on health and HRQL were analysed and taken into account.The patient-based framework was in two parts: the first covered survivors' personal status which consisted of their physical status, emotional/psychological status and cognitive status; and the second comprised nine subdomains affected by their personal status. The latter were: activities and behaviours; physical zone of comfort and/or activity; interactions and relationships with others; perception of, interpretation of, and responses to life; personality; external appearance; suitability and availability of clothes; place of residence; and finances. The current generic measures recommended on the basis of expert consensus for use with survivors of adult, general critical care have substantial gaps in their coverage of this conceptual framework for survivors' HRQL, particularly in relation to their cognitive status and its subsequent impact.The two most commonly used generic HRQL measures in adult, general critical care have significant gaps in their coverage of survivors' HRQL. Any (new) critical care-specific HRQL measure should be designed specifically to capture the impact of critical illness on survivors' cognitive status and its subsequent effects.


In recent years, small-world graphs have gained considerable interest as models of real-world systems, which often display features residing between regularity and randomness. The most notable of these models is the Watts-Strogatz graph , though Theoretical investigations of small-world graph models have generally applied asymptotic evaluations in the limit of large system size  or the cWe then utilize the exact nonasymptotic expression for the clustering coefficient in order to assess the small-worldness of structural brain networks in an analytic setting. Using the number of nodes and edges of the given brain networks to construct the equivalent small-world network, we observe that a significant edge rewiring of at least 20% up to 60% is required to produce the small-worldness indices observed in these networks. Importantly, the maximum of the small-worldness index however occurs in all cases at one order of magnitude lower than the required rewiring found. This result suggests that neural graphs reside far away from the small-world regime of the Watts-Strogatz model.


In recent years the study of age-related derangements of the gonadotropin releasing hormone (GnRH) synthesis and secretion resulting from both the GnRH gene expression changes and interaction of glia with GnRH-ergic neurons of the hypothalamus is a focus of attention. It was demonstrated earlier that this could result from the decreased activity of monoaminergic and peptidergic systems that control the GnRH preovulatory secretion surge initiation, specifically from the loss of the signal coming from the suprachiasmatic nuclei (SCN) of the hypothalamus. This signal is critical for the emerging of the GnRH regular cyclic secretion, which is mediated prominently by vasoactive intestinal peptide (VIP). We have studied age-related changes in the biogenic amines and VIP content in the hypothalamic structures responsible for the GnRH synthesis and secretion. It has been shown by us that the GnRH level in the median eminence with the arcuate nuclei (ME-Arc) of the hypothalamus of 22-month-old rats is half as high compared to that of 7-8-month-old animals. Beside that, the VIP level in the SCN tended to decrease, with the norepinephrine, dopamine, and 5-hydroxyindoleacetic acid levels decreased significantly in the median preoptic area of the hypothalamus responsible for the GnRH synthesis and in the ME-Arc exercising its secretion into the portal vein of the pituitary. It has been shown that the initial phase of the reproductive failure with 13-14-month-old animals having irregular estrous cycles is characterized by gradual disappearance of the normal biogenic amine diurnal dynamics in the studied hypothalamic structures, which could be due to the loss of regulatory signals coming from the SCN.


There is growing evidence of an accumulation of mutations and mechanisms of resistance to targeted therapies in cancer. Non-small-cell lung cancer (NSCLC) is still an untreatable disease and is the leading cause of cancer related deaths worldwide . Various


The nonlinear mean-field dynamics of spiking neuronal networks with non-homogeneous connectivity is studied numerically and analyzed mathematically. The network under study is comprised of three subnetworks of either excitatory or inhibitory leaky integrate-and-fire neurons, two of which are of the same type. The excitatory and inhibitory weights are arranged to establish and maintain a balance between excitation and inhibition for a constant external drive. Each subnetwork has random connectivity with fixed in-degree and fixed out-degree for all neurons belonging to a particular population (configuration model). Neurons are also randomly connected with the same probability across different subnetworks; however, depending on their identity, the connection weight is scaled by a common factor. We observed that for a certain regime of ratios of the "within" versus "between" connection weights (bifurcation parameter), network activation spontaneously switches between the two subnetworks of the same identity. In the mean-field model, this phenomenon is explained by a set of coupled stochastic differential equations of Lotka-Volterra type ,2 that eThe deterministic phase portrait is characterized by two attractors and a saddle node, its stochastic component is essentially given by the multiplicative inherent noise of the system . We obse


The control and scaling of the input-output behavior of neural networks, or gain control, is one of the main strategies used by neural systems for the processing and gating of information. This input-output behavior is often described by the so-called f-I curve, which shows the output firing rate as a function of the input current to the neuron or neural circuit . In partSeveral gain control behaviors have been found to be particularly relevant for the gating and transformation of information in neural circuits. For instance, common biological mechanisms have been found to produce subtractive effects in the f-I curve , while ain vivo in weakly electric fish.We present here (see  for furtin vitro experimental recordings in the electric fish [Our work illustrates how subtractive, divisive and non-monotonic gain control may be obtained in inhibitory feedforward neural circuits. In addition, the analysis of the conditions in which the f-I response curve of superficial pyramidal neurons becomes non-monotonic reveals a novel nonlinear gain control mechanism which agrees with ric fish .


The activator’s principle action is based on application of light of powerful light-emitting diodes with the big intensity of a luminescence of monochrome color without a thermal component.Several techniques are used for detection of dental caries including a fiber-optic light (FOL), the method of optical coherence tomography (OCT), the method of fiber optic transillumination and the infrared tomography. For an assessment of light-induced fluorescence of hard dental tissues and primary dental caries diagnosis, we propose to use the domestic light-emitting-diode activator “LED active”, , with a wavelength of 530 nanometers and illumination of 10 000 meter-candle, and also wavelength of 625 nanometers at the 140 MWt/cmThe present study employed 150 18-45 years old subjects. For the diagnosis and severity of initial caries we used – light-induced fluorescence and electrometric diagnostic tools. Caries prevention was attempted by daily applications of remineralized preparation – "Radogel-GAMK" with amino acids and hyaluronic acid for the caries precaution at the early stages for 15 days.Under the influence of a "Radogel-GAMK"’s preparation parameters of electrometry at group of surveyed patients with initial caries have decreased by one third on hillocks, in fissures and on seal border. On fragment enamel and vestibular surfaces - in half, accordingly.Under the influence of green light (530 nm) on the demineralized enamel area, zone of increased opacity was identified and, confirmed by the presence of microbial contamination and degradation products. The extent of opacity of demineralized enamel correlated with the process of demineralization and the index of fluorescence signal (+). The use of red light (625 nm) allows identifying secondary caries on borders of abutment filling, which is manifested as a center of brown pigmentation of varying intensity. Reducing opacity of demineralized tooth enamel under the green light impact, allowed assessment of the remineralization effect of dental hard tissues and restoration of its organic and mineral components.As a result of research special parameters confirming the enamel changes after the impregnation by organic components that make up the protein matrix of the tooth have been identified. Remineralizing effect was proved by a reduction of electrometry parameters and opacity of demineralized tooth areas.Thus, studies of light-induced fluorescence can offer an actual and effective method of early detection of initial carious lesions.


Over a half-century ago, the scientist Vannevar Bush explored the conundrum of how to tap the exponentially rising sea of human knowledge for the betterment of humanity. In his description of a hypothetical electronic library he dubbed the memex, he anticipated internet search and online encyclopedias Bush, . By blurShould we achieve such BCI integration, we would come up against the attentional, multi-tasking and global processing limitations of the brain. Both in terms of overall spatial architecture and in moment-to-moment engagement of the world, we appear to have a limited amount of real-estate or bandwidth to work with (Müller et al., While we can learn to pay attention to multiple things simultaneously, there appears to be an upper limit to our moment-to-moment information processing capacity after which performance on any given sub-task breaks down (Busse et al., If we can identify the neural signatures of meditative states then we can, both with traditional techniques of breathing and posture ubiquitous to prayer and meditation the world over, and with neurofeedback facilitated by neural modules designed to allow the conscious mind to gain unprecedented perception of the power spectral and ensemble unit firing activity patterns of the brain itself, move our brains into meditative states with improved attentional and integrative capacity (Dickenson et al., The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Bioactive peptides within original food-derived proteins are inactive but can be activated by being released during food processing (by enzymatic hydrolysis or fermentation) or during gastrointestinal digestion. Hence, the utilization of computer-aided techniques as screening tools may be helpful in predicting the potential of food proteins as precursors of DPP-IV inhibitory peptides. This paper reviews the current literature on DPP-IV inhibitory peptides, focusing on their in vitro activity and in vivo antidiabetic effects. In addition, the feasibility of various in silico approaches is also summarized in this review.One of the new approaches to the management of type 2 diabetes mellitus (T2DM) consists of orally administered dipeptidyl peptidase-IV (DPP-IV) inhibitors. These synthetic drug inhibitors are reported to have some side effects and that subsequently limits their applications. There is a growing interest to develop natural DPP-IV inhibitors that will be potent without undesirable side effects. Many  Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder that is characterized by insulin insensitivity as a result of impaired insulin secretion, insulin resistance, and eventual pancreatic beta-cell failure , 2. T2DMOne of the novel strategies for the treatment of T2DM consists of orally administered dipeptidyl peptidase-IV  inhibitors. The enzyme DPP-IV, a serine protease, has a specificity to remove dipeptides from the N-terminus of substrate poly-peptides by cleaving postproline or alanine residues . It is pin vitro DPP-IV inhibitory activity. Research on some DPP-IV inhibitory peptides has shown that they are effective at stimulating insulin secretion and improving glycemic control in animal models and subjects with T2DM . The authors of the study suggested that the peptide may not bind to the active site of DPP- IV as assumed in the docking prediction. Their results revealed that there is no clear relationship between the docking affinity and the DPP-IV inhibitory activities of the peptides. In addition, they showed that the utilization of molecular docking can be a predictive tool for the competitive inhibitors. Thus, docking can be used as a preliminary tool to help focus experimental screening efforts on a smaller number of candidate peptides.Additionally, a docking analysis has also been used as an in vitro or in vivo hydrolysis. Further effort is therefore needed on the development of an in silico approach capable of being used as a screening tool for the evaluation of the potential of dietary proteins for the generation of in vitro and in vivo DPP-IV inhibitors.Since the studies relied entirely on the currently available data on DPP-IV inhibitory peptide sequences, it is possible that other fragments presenting even better DPP-IV inhibitory activity are presently unknown or have not yet been reported in the literature. Furthermore, the putative peptide sequences have to be released from their parent proteins to become active, and the final conclusions on the potential of dietary proteins for DPP-IV inhibitors can be drawn only after experimentally assessing the release of these bioactive peptides upon in vivo antidiabetic effect needs to be built in more animal and clinical studies. The "BIOPEP" database is responsible for collecting all of the information about bioactive peptides from academic literature, and 707 protein sequences are also available. Further research into the establishment of in silico approaches to efficiently predict the potential of proteins as the precursors of DPP-IV inhibitory peptides is necessary.The importance and scientific understanding of DPP-IV inhibitors that may improve glycemic control in T2DM patients has increased in the last few decades. Much work has been done with food protein-derived DPP-IV inhibitory peptides; however, the evidence of their in vivo antidiabetic activity. Albeit the simulated GI digestion is a kind of model mimicking the actions of human GI enzymes, the antidi- abetic effect of the peptides released from the DPP-IV inhibitory peptides through simulated GI digestion is not guaranteed to be similar to that through the GI tract in vivo. So the possible strategies for increasing the resistance to digestive enzymes as well as the cellular permeability of the peptides are two factors that also need to be investigated.The most challenging task in the DPP-IV inhibitory peptide research is the establishment of a detection model for identification of possible mechanisms by which they can exert


Modern medicine cannot avoid the understanding of the fine-tuned communication between the many, seemingly distinct systems in the body. An excellent example of this is the challenge to understand the bi-directional communication between the brain and the immune system. Brain-immune interactions take place in different organs, involving a wide range of cells and mediators, coordinated through sensory and effector pathways in the central nervous system , a mouse model of multiple sclerosis  shape the responses of macrophages, mast cells and other immune cells throughout the body and how these interactions contribute to immune defense and diverse inflammatory conditions (Assas et al., Neuro-immune abnormalities not only affect adults and the elderly, but also play a role in diverse diseases that manifest in children. D'Angiulli et al. show that children in the Mexico City Metropolitan Area, who are chronically exposed to high concentrations of air pollutants, present with increased amounts of inflammatory mediators along with accumulation of misfolded proteins in the cerebrospinal fluid (Calderon-Garciduenas et al., Paul Ashwood and colleagues report that the behavioral characteristics, including social deficits, repetitive grooming behavior and atypical vocalizations, observed in BTBR T+tf/J mice are associated with the development of an inflammatory macrophage phenotype in this strain (Onore et al., We hope that the articles presented in this research topic give thought-provoking and valuable insight into some of the important aspects of brain-immune interactions. Neuro-immune processes are likely to contribute to diverse pathologies in both the periphery and the brain leading to complex human diseases that affect millions of people worldwide. Understanding mechanisms of neuro-immune interactions could help to find appropriate therapies to some of these conditions.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The analysis of dynamic volume-dependent compliance provides the rationale basis for PEEP titration during mechanical ventilation. Due to its volume dependence, the compliance of the respiratory system is nonlinear within each single breath , which is reflected in the compliance-volume curve (CV curve). The shape of the CV curve is determined by the PEEP level. The mechanical stress for the mechanically ventilated lung is expected to be minimal when the lung is ventilated within the volume range of maximal compliance. We present a new graphical user interface (GUI) that supports the clinician to titrate the PEEP level by means of a shape category analysis of the CV curve.A decision support system in the form of a computer-based GUI was developed and tested using respiratory data obtained from patients of the University Medical Center Freiburg. The new clinician- oriented approach provides a breath-by-breath visualization of the patient's individual intratidal CV curve. The dynamic compliance was analyzed using the gliding-SLICE method . The resThe GUI provided a breath-by-breath visualization of the intratidal CV curve and the intuitive individual compliance shape category. Based on the compliance shape category, different guidelines of PEEP titration were applied with the objective of ventilating the patient mechanically within the range of maximal compliance.The newly developed GUI allows a breath-by-breath visualization of the intratidal CV curve with high reliability. Automated classification of the intratidal CV curve into compliance shape categories provides the rationale basis for patient-individual PEEP titration.


Unexpectedly, we find that the mass enhancement of itinerant charge carriers in the strongly correlated band is dramatically reduced near the Γ point and attribute this effect to orbital mixing induced by pronounced spin-orbit coupling. Embracing the true band structure allows us to describe all low-energy electronic properties obtained in our experiments with remarkable consistency and demonstrate that superconductivity in this material is rather weak and mediated by spin fluctuations.Iron-based superconductors have been found to exhibit an intimate interplay of orbital, spin, and lattice degrees of freedom, dramatically affecting their low-energy electronic properties, including superconductivity. Albeit the precise pairing mechanism remains unidentified, several candidate interactions have been suggested to mediate the superconducting pairing, both in the orbital and in the spin channel. Here, we employ optical spectroscopy (OS), angle-resolved photoemission spectroscopy (ARPES),  The outer hole band of Fe-3dxy orbital character in The effect of electronic correlations on the low-energy electronic structure of uin zone  reveals k—quasiparticle wave vector, and E—quasiparticle energy. For a parabolic dispersion Quite surprisingly, the outer hole band’s dispersion reveals a departure from a parabolic shape , the dispersion of the hole bands at low energies shows a pronounced departure from that obtained in the non-relativistic calculation presented in The aforementioned reduction of the effective mass due to orbital mixing does not rely on the existence of strong electronic correlations and should be observable already at the level of quasiparticle band masses. Indeed, effective electronic subsystems: one with a large and the other one with a small scattering rate  from an intermediate boson. This conclusion is consistent with the association of the broad Drude component with electronic correlations based on the doping dependence of the optical conductivity in various iron-based compounds24It is tempting to assign the narrow Drude component to the combined response of charge carriers on the electron sheets of the Fermi surface  n is the electron density, e and me are the bare electron charge and mass, respectively. Quite similarly, the itinerant spectral weight  is also constant, with me substituted by the quasiparticle band mass including renormalization at energies larger than the plasma frequency. Any low-energy mass renormalization due to, e.g., coupling to phonons or other bosonic excitations will not affect this spectral weight as long as its characteristic energy is smaller than the plasma frequency of free charge carriers. On the other hand, the low-energy band structure and the plasma frequency extracted from it will be affected by such renormalization. Therefore, the comparison of the total itinerant plasma frequency obtained from OS and ARPES data provides access to purely boson-exchange–induced effective mass renormalization even when it is not immediately apparent in the experimental band structure. In the present case of λ via Fortunately, even in such complicated cases the spectral-weight analysis of the itinerant optical response bears fruit. It is well-known that the total spectral weight of any system  is constant and does not depend on the details of the band structure:  to  see . This isHaving established that only three out of five electronic bands predicted theoretically actually contribute to the itinerant carrier response of in  ref. . Our anaThe vanishing of the optical conductivity in the superconducting state  are in a very good agreement with the properties of the two effective itinerant electronic subsystems extracted in the Drude analysis of the conductivity data in Our theoretical analysis of the optical conductivity in the framework of an effective two-band Eliashberg model thus reconciles all of the characteristic energy scales and spectral features observed in trum see , below wThe remarkable agreement between different experimental probes and theoretical tools employed in this work demonstrates the importance of employing a realistic electronic band structure to interpret the low-energy electronic properties in such complex multiband systems as iron-based superconductors, if complete and consistent understanding of their properties is to be achieved. Our observation of a dramatic reduction of the effective mass in one of the electronic bands of 3–ARPES” end-station at BESSY) within the range of photon energies 20–90 eV and various polarizations on cleaved surfaces of high-quality single crystals of Angle-resolved photoemission measurements were performed using synchrotron radiation .


The North Western Mental Health Eating Disorder Program at The Royal Melbourne Hospital provides treatment for adults 18 years and over since 1994. The eating disorder program provides an in-patient and day-patient treatment program and comprehensive out-patient services.Family members have been an effective and vital support for clients with eating disorders in their treatment and recovery in our day patient program. This pilot trial is to explore the family dynamics and confidence of family members in supporting in-patient clients with anorexia nervosa during a meal. Family members would be empowered with evidence based knowledge and strategies to support their loved ones through a meal prior to discharge as part of the discharge planning.The theoretical framework for this trial is based on a modification of the Family-Based Therapy (FBT). In several controlled studies, it has proven that Family-Based Treatment to be successful in an out-patient setting especially for adolescent in helping individual in weight restoration.


The goal of public health interventions is to move the distribution of life style risk factors in a healthier direction to decrease disability-causing disease and improve quality of life in the population. We recently presented a novel method to estimate the population-level impact of a public health intervention, using changes in the distribution curve of the outcome of interest. This method makes it possible to calculate the proportion of the target population that benefited from an intervention. The objective of this study is to demonstrate the potential of the new method to estimate not only the effect, but also the cost-effectiveness of public health interventions.A population-based model called Risk factors, Health and Societal Costs (RHS) was developed to simulate changes in incidence and related societal costs of several chronic diseases, following assumed changes in four life style risk factors: obesity, tobacco smoking, physical inactivity, and risky consumption of alcohol. The RHS model is based on relative risks and simulates changes in disease incidence due the reduction of the prevalence of a risk factor that can be attributed to diverse interventions. The health gains are calculated as decreased incidence of the disease, increased health-related quality of life years (QALYs) and decreases in disability-adjusted life years (DALYs). Swedish national registers were used to retrieve disease-specific medical care costs, while local authority costs for care and sickness insurance expenses were estimated via a Swedish study. The changes in the distribution of physical inactivity as a result of a hypothetical mass-media campaign targeting the adult population in Uppsala County was used as the input parameter for the model.The hypothetical intervention was estimated to improve the distribution of physical inactivity and the overlapping area between the distribution curves at baseline and follow-up was calculated as two percent, i.e. a 2% reduction in the prevalence of physical inactivity. This reduction among the Uppsala County population under five years is estimated to lead to a health gain of 14 QALYs and societal savings  of 6 million SEK . The intervention is estimated as cost-effective if the intervention costs are less than 900,000 GBP with ICER<30,000 GBP/QALY.This study opens a new avenue to calculate the cost-effectiveness of public health interventions by using changes in the distribution curve of health-related outcomes combined with population-based modeling of risk reductions and costs.


There is controversy regarding needle aspiration for primary spontaneous pneumothorax (PSP), with contradictory recommendations between the American College of Chest Physicians consensus statement (2001) which suggests that needle aspiration has little place in the management of PSP, and the British Thoracic Society guidelines (2010) which recommend that needle aspiration be attempted first for all cases of PSP where drainage is deemed necessary. Studies have shown that there is no significant difference between needle aspiration and tube thoracostomy with regard to safety, rates of immediate success and early failure and has the advantages of decreasing pain, reducing rates of hospital admission and duration of hospital stay compared to tube thoracostomy. Point-of-care ultrasound can facilitate needle aspiration by decreasing the risk of complications and detect pneumothorax resolution during or reexpansion after the procedure.This is a case series where the sonographic finding of the "lung point" on point-of-care ultrasound was used to facilitate needle aspiration to monitor pneumothorax resolution during or reexpansion after the procedure.We report three cases of PSP in adolescents presenting to the pediatric ED, where needle aspiration was safely performed by using ultrasound to track the sonographic finding of the "lung point." This technique allows the determination of pneumothorax resolution or reexpansion in real-time.Point-of-care ultrasound may assist in the evaluation and management of spontaneous pneumothorax in the pediatric ED. Ultrasound assisted needle aspiration may be a safe and less painful option for pediatric ED patients with PSP.


Attention represents one of the main mechanisms of modulation of pain  of gamma oscillations increased  while alpha decreased (750 ms) during stimulation of the attended compared to the unattended finger. Conversely, the increase of stimulus intensity was associated with power increase in delta (300 ms) and gamma bands, and power decrease in alpha and beta bands (600 ms). Source analysis identified the contralateral insula as generator of gamma activity during top-down attentional control, and the sensory-motor and mid-cingulate regions as gamma activity generators during bottom-up capture of attention. The activation found in the sensory-motor areas during bottom-up attention is not surprising as previous studies reported the association between activity in the primary somatosensory cortex and selective nociceptive laser stimulation (Timmermann et al., A relevant aspect of Hauck et al.'s study (Hauck et al., Tiemann et al.  found thOther studies reported a gamma-band modulation by top-down attention during different sensory modalities (Fries et al., Despite differences in stimuli and methodology, altogether these studies indicate the gamma-band oscillatory activity may not only index bottom-up salience of the sensory event but also top-down relevance of the sensory representation for the ongoing behavioral goals. However, further methodological and analytical efforts will be needed to clarify the role of the gamma activity across different types of top-down attention manipulations.VN has developed most of the content of the article. EV has supervised her during the writing and he has edited the text.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Current Challenging Medical Image Analysis". This issue consists of two selected papers presented at the 35th IEEE-EMBC Workshop on Current Challenging Image Analysis and Information Processing in Life Science, which was held on 03 July 2013, Osaka, Japan; and one invited paper to reflect the theme of this issue. All three papers were accepted based on the peer-review process of BioMedical Engineering Online journal.The theme of this special issue (supplement) is "Deformable part models for object detection in medical images" by Klaus Toennies, et al., presents a novel application of a deformable model of the finite element method for the detection of objects in medical images. This proposed approach is promising for context-based detection, model-based segmentation, and shape analysis of medical objects.The first paper entitled "Motion correction of whole-body PET data with a joint PET-MRI registration functional" by Michael Fieseler, et al., makes use of the multi-modal information simultaneously provided by both PET (position emission tomography) and MRI (magnetic resonance imaging) data for the registration and correction of respiratory motion, whereas current methods for PET-MRI-based motion correction do not utilize the valuable sources of information provided by PETdata.The second paper entitled "Automated CT detection of intestinal abnormalities and ischemia for decision making in emergency medicine" by Taichiro Tsunoyama, et al., reports an original work on automated image analysis of bowel ischemia and abnormality patterns, which is important for the urgent treatment of patients in emergency departments. The combination of the sources of knowledge from medicine and imaging science offers a computer-aided tool that can be essential to surgeons to gain insights into this complex disease.The last paper entitled "BioMedical Engineering Online for his approval of the proposal of the publication of this special issue. It was a great pleasure to work with Ms. Sarah Headley of BioMed Central, who kindly and frequently communicated with the Guest Editor in all editorial aspects to help ensure the editing quality and timely publication of this special issue.Many thanks are to Professor Kenneth R. Foster, the Editor-in-Chief of December 2013Tuan D. PhamGuest EditorThe Supplement Editors declare that they have no competing interests.


Indigenous populations around the world have consistently been shown to bear a greater burden of disease, death and disability than their non-Indigenous counterparts. Despite this, little is known about what constitutes cost-effective interventions in these groups. The objective of this paper was to assess the global cost-effectiveness literature in Indigenous health to identify characteristics of successful and unsuccessful interventions and highlight areas for further research.A systematic review of the published literature was carried out. MEDLINE, PSYCINFO, ECONLIT, EMBASE and CINAHL were searched with terms to identify cost-effectiveness evaluations of interventions in Indigenous populations around the world. The WHO definition was followed in identifying Indigenous populations. 19 studies reporting on 27 interventions were included in the review. The majority of studies came from high-income nations with only two studies of interventions in low and middle-income nations. 22 of the 27 interventions included in the analysis were found to be cost-effective or cost-saving by the respective studies. There were only two studies that focused on Indigenous communities in urban areas, neither of which was found to be cost-effective. There was little attention paid to Indigenous conceptions of health in included studies. Of the 27 included studies, 23 were interventions that specifically targeted Indigenous populations. Outreach programs were shown to be consistently cost-effective.The comprehensive review found only a small number of studies examining the cost-effectiveness of interventions into Indigenous communities around the world. Given the persistent disparities in health outcomes faced by these populations and commitments from governments around the world to improving these outcomes, it is an area where the health economics and public health fields can play an important role in improving the health of millions of people. There are almost 400 million Indigenous people living in countries around the world Economic evaluation of health care programs has become an important area of applied economics over the last 30 years The objective of this review is to systematically search the literature to pull together existing evaluations that estimate the cost-effectiveness of health interventions into Indigenous populations around the world. This review allows for an exploration of the type of interventions that have been shown to be effective in these unique population groups, the specific resource requirements needed to deliver programs to these populations and the aspects of these programs that are deemed to be of value by the populations to whom they are targeted.There is an increasing recognition of the shortcomings of traditional methods of measuring health benefits in economic evaluations of healthcare programs To provide a basis for further evaluating these arguments, this review also highlights any explicit attempts by included studies to incorporate these concerns into cost-effectiveness evaluations.A systematic review of the literature was conducted to find articles that provide an economic evaluation of interventions targeting or reporting on an Indigenous population. No protocol has been previously published for this review.The inclusion criteria for this review specified three characteristics for studies. First, the studies had to examine interventions that were primarily aimed at improving the health of target populations. Second, included papers had to be economic-evaluations of an intervention that met the definition of one of the types outlined in A search was conducted of CINAHL, MEDLINE, EMBASE, PSYCINFO and ECONLIT (from inception to May 2014) using variations of the search string contained in Study review, selection and data extraction were independently undertaken by two authors (BA and JM). Abstracts, titles and keywords of the studies returned from the search were screened for compatibility with the inclusion criteria. Once studies were identified for potential inclusion, full texts were reviewed. Data were extracted from the studies using a form developed for the review based on standard techniques used in the literature and included the following items: country of origin, methodology including type of evaluation, comparators used, outcome measures, settings and participants, results and evidence of inclusion of Indigenous conceptions of health The search yielded 559 abstracts see . One furSeven studies were conducted in Australia (covering eleven interventions) Two studies evaluated interventions in urban areas, one looking at a midwifery program The majority of the studies focused on Indigenous populations with known health conditions including diabetes  Of the 27 interventions included in the study, two were carried out in infants Studies were broadly grouped into two groups. The first included group included studies where authors collected effectiveness data within the study itself (twelve studies and sixteen interventions) The types of economic evaluation are outlined in Costs were the primary outcome measure reported in eight of the studies Each included paper made some judgment as to the cost-effectiveness or cost-impact of the interventions being studied. In total, only five of the 27 interventions were deemed to be strictly not cost-effective or cost-saving The choice of comparator against which the cost-effectiveness of the intervention is assessed plays a large part in determining whether a particular intervention is cost-effective or not. Included studies could be grouped into two main categories in this regard. Fourteen of the studies assessed the cost-effectiveness of their intervention against so-called ‘business as usual’ cases where they were compared to a situation with no intervention, either through the use of a control group Only one study that met the inclusion criteria explicitly set out to capture wider benefits of culturally appropriate service provision This systematic review has found that very few cost-effectiveness studies are available in the published global Indigenous health literature. This has implications for generating investment into Indigenous health programs since the lack of such evidence limits our ability to assess the investment-case of interventions based on the criteria of cost-effectiveness, rather than solely for equity reasons or broader policy objectives. This is concerning given the significant disparities in health and access to health care that exist between Indigenous and non-Indigenous populations worldwide. Nonetheless, the evidence-base that does exist in the literature provides some isolated insights into the potential cost-effectiveness of specific types of interventions. There is potential for further work to both increase the use of economic evaluation in this area and methodological work to ensure that health economic methodologies are relevant to Indigenous populations.A total of nineteen studies met the inclusion criteria for this review. Given the broad scope of the research question and search strategy, this depicts a very limited evidence-base from which to draw insights on the potential cost-effectiveness of interventions into Indigenous populations. This finding implies that investment into the area is largely being undertaken blind, based on assumptions rather than evidence of the cost and effectiveness of particular policies and interventions.Three main reasons are offered here as potential factors explaining the lack of research in the field. First, there is a general lack of effectiveness studies in the field of Indigenous health, with the majority of research carried out in the field being observational rather than interventional in nature While the evidence-base identified in this review demonstrates that traditional health economic approaches can ostensibly be used to show the cost-effectiveness (or otherwise) of interventions aimed at improving Indigenous health, there has rarely been much attempt to incorporate Indigenous valuations of the potential gains from such programs.Examples do exist in the literature of attempts to incorporate these values into economic evaluations of health interventions. The study of the Daruk-controlled midwifery service included above attempted to do so by taking a broader cost-consequence approach rather than restricting the analysis to narrowly defined health outcomes While there was a limited amount of cost-effectiveness research of interventions to improve the health of Indigenous population groups, a number of conclusions can be drawn from the studies that were identified.First, this review highlights that interventions into Indigenous populations, in particular rural and remote Indigenous communities, can be cost-effective, a broad but important finding given the often isolated and small populations of these groups when compared to non-Indigenous populations. Of the 27 interventions examined by included studies, 21 were deemed to be cost-effective or cost-saving while of the twelve interventions targeted solely to rural and remote populations, ten were found to be cost-effective or cost-saving by the respective studies. Being able to point to a body of evidence highlighting the cost-effectiveness of such interventions is important to justify widespread implementation of such programs on more than solely equity grounds and ensure that domestic debates on service provision are informed and based on the best available evidence.The evidence-base drawn together by this review provides insights into particular interventions. Outreach programs were shown to be consistently cost-effective or cost-saving in all six interventions studied. These interventions were assessed relative to populations obtaining the services from alternative service providers. Thus they were found to be cost-saving or cost-effective despite often representing relatively high-costs for the health gains that occurred. They may be prohibitively costly in low-income environments outside of donor provision and it is also unclear how sustainable or community appropriate such models of service provision are. Explicit decisions need to be made by policy-makers in assessing the appropriateness of these services to local conditions.The four injury prevention interventions were all found to be cost-effective as was the study of telehealth. Conversely, neither of two midwifery programs studied was found to be strictly cost-effective (one found non-significant cost-savings). Nor were the two studies focused solely on interventions in urban areas, highlighting the need for further work in this area. The majority of the interventions were targeted specifically at Indigenous groups (twenty-three interventions) and most were delivered through culturally specific medical providers, such as Aboriginal Medical Services in Australia and Canada. This is in line with findings from the literature that culturally specific services are more effective in reaching these populations While the strength of the review lies in the broad search strategy and research question, the heterogeneity of included studies limited the policy implications that could be drawn from the identified literature. The studies were of varied scope and included different notions of what constituted a cost-effective intervention. There are inherent difficulties in comparing the outcome of the studies when the notion of what constituted a cost-effective intervention varied so greatly between them.The studies identified were largely drawn from high-income nations and focused at a primary-care level in rural or remote populations. There is a large gap in the literature for Indigenous populations of low and middle-income nations. Similarly, urban Indigenous communities have been largely overlooked in the literature despite these communities often representing the bulk of Indigenous populations within countries. In Australia, for example, it is estimated that the 60% of the ‘gap’ in health outcomes between the Indigenous and non-Indigenous populations is a result of the health of urban Indigenous communities Despite global commitments to reducing Indigenous health disadvantage, relatively little is known about what constitutes cost-effective investments into Indigenous populations around the world. Furthermore, the evidence that exists has often relied on pivotal evidence extrapolated from non-Indigenous settings and been based on methods that have not allowed for the values that such communities place on health to be included. Nevertheless, in light of the limited available evidence, this review suggests that interventions into these often hard to reach populations can be cost-effective. Further economic research has the potential to provide much needed guidance to policy-makers on resource allocation decisions and help improve the health of Indigenous people around the world but it needs to be based on the development of methods that incorporate values specific to the communities in question. .Checklist S1PRISMA checklist.(DOC)Click here for additional data file.


Acetylcholine (ACh) signaling underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. Alterations in ACh signaling are involved in the pathophysiology of multiple neuropsychiatric disorders. In the central nervous system, ACh transmission is mainly guaranteed by dense innervation of select cortical and subcortical regions from disperse groups of cholinergic neurons within the basal forebrain  and the pontine-mesencephalic nuclei, respectively. Despite the fundamental role of cholinergic signaling in the CNS and the long standing knowledge of the organization of cholinergic circuitry, remarkably little is known about precisely how ACh release modulates cortical and subcortical neural activity and the behaviors these circuits subserve. Growing interest in cholinergic signaling in the CNS focuses on the mechanism(s) of action by which endogenously released ACh regulates cognitive functions, acting as a neuromodulator and/or as a direct transmitter via nicotinic and muscarinic receptors. The development of optogenetic techniques has provided a valuable toolbox with which we can address these questions, as it allows the selective manipulation of the excitability of cholinergic inputs to the diverse array of cholinergic target fields within cortical and subcortical domains. Here, we review recent papers that use the light-sensitive opsins in the cholinergic system to elucidate the role of ACh in circuits related to attention and emotionally salient behaviors. In particular, we highlight recent optogenetic studies which have tried to disentangle the precise role of ACh in the modulation of cortical-, hippocampal- and striatal-dependent functions. Acetylcholine (ACh) is essential to normal CNS function, modulating cognitive, emotional and behavioral functions, including learning and memory  or both  physiology. The role of ACh in specific behaviors has been addressed using lesions of cholinergic projections or pharmacological interventions with ACh receptor activation. Such approaches, though informative, are confounded by issues of bioavailability, lack of complete reversibility and the fact that such interventions act on time scales of unknown relevance for cholinergic driven changes in excitability With the exponential rise in the number and type of optogenetic tools developed over the last decade it is now possible to selectively stimulate or inhibit specific populations of CNS cholinergic neurons and/or their axonal terminal fields through the activation of light-sensitive opsins  reported a long-lasting ACh increase during attention-related performance tasks  to CA1 synapses  projections to the hippocampus with whole-cell patch clamp recordings and voltage sensitive dye (VSD) imaging it has been shown that inhibitory interneurons in the hippocampus receive cholinergic EPSPs in response to light stimulation of septal cholinergic fibers that are sensitive to DhβE, but not MLA  and endogenous opioid systems may participate in the generation of ACh-dependent modulation of hippocampal oscillatory activity  and the nucleus accumbens (NAc), is strongly modulated by ACh. The main source of ACh to the VTA neurons in the midbrain arises from the brainstem structures LDTg and PPTg, which play a role in acquisition of reward, and reward-related locomotor activity  and muscarinic receptors, together with the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors in the enhancement of striatal DA release. Thus, a synergy exists between ACh and glutamate in modulating the activity of the striatal network. The source of glutamate may be the striatal cholinergic interneurons themselves  to striatal cells (Dautan et al., The application of optogenetic tools has accelerated the acquisition of precise information about the varied modulatory and direct synaptic signaling by ACh in an array of brain regions and behaviors. Selective expression of optogenetic probes in ChAT+ neurons allows studies of the connectivity, functionality and anatomy of cholinergic neurons and circuits throughout the rodent brain (Atasoy et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Processing of time intervals in short temporal ranges, typically in sub- and supra-second intervals, is vital for the survival of primates and humans. Research evidence has already shown that the processing of sub- and supra-second intervals is subserved by different neural mechanisms (Buhusi and Meck, The concept of the building block for “neural oscillators” in Gupta  in essenMovement is the expressed time (Teki et al., The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Headaches and other cranio-oro-facial pains are widely distributed in the general population. Unfortunately, there is very little evidence regarding the impact of these conditions in patients admitted to rehabilitation units, regardless of the disease or syndrome requiring rehabilitation. The availability of diagnostic and therapeutic guidelines, as well as the increasing number of data coming from controlled clinical trials, should be implemented in these patients to reduce the burden of pain and improve their global outcome.http://www.doloreinneuroriabilitazione.it/).The Italian Society for Neurorehabiltation, in collaboration with the Italian Society of Physical Medicine and Rehabilitation, has promoted the Consensus Conference on Pain with the aim to foster attention on pain also in the rehabilitative field ;- Standard methods exist to evaluate migraine in terms of disability (A);- It is important to evaluate the impact of cephalic and cranio-facial pain in neurorehabilitation (D);- Standard methods or criteria exist to diagnose head and cranio-facial pain (GL);- It is important to identify predictive factors associated with the development of cephalic and cranio-facial pain in association with a condition requiring neurorehabilitation (D);- Effective pharmacological treatment exists for primary headaches and for trigeminal neuralgia (GL);- Manual therapy is indicated in the management of migraine and tension-type headache (GL);- Manual therapy may be effective in TMD-associated pain (D);- Botulinum toxin A is effective in the treatment of idiopathic trigeminal neuralgia (B);- Botulinum toxin A is effective in the treatment of hemifacial spasm (B);- Topical capsaicin is effective in chronic neuropathic pain (B);- Evidence is needed to evaluate the impact of treating cephalic and cranio-facial pain on the outcome of patients undergoing neurorehabilitation (D).The recommendations are presently under evaluation by the Consensus Conference panel.


The blood-brain barrier (BBB) regulates the transport of micro- and macromolecules between the peripheral blood and the central nervous system (CNS) in order to maintain optimal levels of essential nutrients and neurotransmitters in the brain. In addition, the BBB plays a critical role protecting the CNS against neurotoxins. There has been growing evidence that BBB disruption is associated with brain inflammatory conditions such as Alzheimer's disease and multiple sclerosis. Considering the increasing role of inflammation and oxidative stress in the pathophysiology of bipolar disorder (BD), here we propose a novel model wherein transient or persistent disruption of BBB integrity is associated with decreased CNS protection and increased permeability of proinflammatory  substances from the peripheral blood into the brain. These events would trigger the activation of microglial cells and promote localized damage to oligodendrocytes and the myelin sheath, ultimately compromising myelination and the integrity of neural circuits. The potential implications for research in this area and directions for future studies are discussed. Notably, oxidative damage to RNA -verapamil to study the function of the P-glycoprotein (Pgp) transporter at the blood-brain barrier (BBB) with PET [ in vivo and in vitro preclinical models may be particularly useful to test whether lithium and other medications commonly used in the treatment of BD can reverse and/or prevent BBB damage. If a link between BD and BBB disruption is established, this would not only advance the knowledge on the neurobiology of BD but also open numerous possibilities to investigate new treatment pathways  as a method for studying BBB disruption in vivo . Anotherwith PET . Finallyhibitors , ROS scahibitors ) for thi


We describe the treatment of a patient with BN  who completed stage one and stage two of CBT-E at a specialist eating disorders outpatient clinic. Despite good compliance with all components of the treatment, the patient did not achieve an early rapid reduction in binge-eating and purging by the stage two progress review and was considered to be at-risk of suboptimal treatment outcome. Her repetitive negative thinking (worry and rumination) was identified as significantly interfering with progress, and the primary trigger for episodes of binge-eating and vomiting. In light of this, it was decided to evaluate the usefulness of abandoning CBT-E and switching to metacognitive therapy (MCT) for repetitive negative thinking (RNT). RNT is defined as cognitive perseveration on negative themes. MCT has been shown to demonstrate excellent outcomes in patients with anxiety and depressive disorders at the same clinic. Switching to a transdiagnostic meta-cognitive was associated with achieving optimal outcomes at the end of treatment. It is recommended that clinicians routinely assess the degree to which patients have achieved an early response to CBT-E and systematically evaluate the effectiveness of switching or pursuing CBT-E in this patient group.Treatment in Community and Inpatient Settings stream of the 2014 ANZAED Conference.This abstract was presented in the


In most cases, hands of caregivers are the vehicle for the transmission of germs to the patient. Therefore, it is crucial to help medical staff and healthcare workers acquiring the skills necessary for optimal hand hygiene (HH) in order to ensure quality of care and patient safety.To give the caregivers a training tool well adapted to their needs and integrated into a blended learning (class and distance).The Hygiene Prevention and Infection Control (HPCI) Unit - Vaud, the Preventive Medicine Service of Center Hospital Universitary of Vaud (SMPH) in partnership with the collective of the Federation of Vaud Hospital, the Commission e-learning of University to Lausanne, the Center for Education and Audiovisual Communication, have developed an interactive training module of HH in 3 steps.- Identification of the academic content- Development of a teaching strategy fitted to any learning styles- Selection of the interactive teaching resources- Development of academic learning content- Development of practical content (care situations cut out in various interactive e-lessons)- Tutorial construction (integration of multimedia elements and interactivity)- Module overview by infection control professionals in Vaud institutions- Module provision through training platforms - The Module is freely accessible on the InternetAfter a brief theoretical reminder , the module content covers aspects of skills through simulation exercises. Care situations are specific for each category of professionals . Throughout the course, a knowledge assessment evaluates the benefits of training.The training module meets the predefined goals. This e-learning module broadens infection control class offer and is part of the five areas of the WHO multimodal HH strategy. The educational effectiveness will be evaluated after 9-12 months by a query filled up by the caregivers, by the participation rate, and by reality in practice (assessed during audits).None declared.


Trypanosoma cruzi causes Chagas' disease in humans  when compared to patients with heart damage, suggesting an important role for Tregs in Chagas' disease  was first identified as a growth and differentiation factor produced and utilized by T cells (Liao et al., T. cruzi, allows the elucidation of the mechanisms and conditions that may be targeted to reprogram the host immune system by using tools that interfere with components of the regulatory arm of the immune system machinery. This knowledge would certainly result in a better understanding of the necessary balance to achieve or reestablish the health of the host during T. cruzi infection, thus providing new strategies to treat Chagas' disease. In this regard, the in vivo biological activity of nondepleting antibodies to CD25 seems to reinforce rather than inhibit the function of regulatory T cells either in mice or humans (Nihei et al., in vivo administration of IL-2 or complexes of IL-2/anti-IL-2 to increase the numbers and functional activity of regulatory T cells would also be a valuable approach to be used in Chagas' disease (Letourneau et al., The study of acute and chronic phases of infection with intracellular pathogens, such as T. cruzi in combination with distinct strains of mice should be performed in order to better establish these conceptual clinical interventions, perhaps in addition to more acquiescent schemes of benznidazole treatment (Bustamante et al., The notion concerning the manipulation of Treg cells either by antibodies to CD25, IL-2, and/or IL-10 might open up a new avenue for therapeutic strategies in Chagas' disease. It should be noted that more pre-clinical studies, using different strains of JM Design the paper hypothesis, wrote the first draft. FC Design the paper hypothesis, wrote the first draft. LP Design the paper hypothesis, wrote the first draft.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Changes in the transmission properties of synapses may influence actively the processing of information. This is in particular the case for the working memory, viz the temporary storage of information, which is thought to be mediated via short-term or transient synaptic plasticity effects . The staWe implement a slightly modified version of the Tsodyks-Markram model for cyclic networks characterized by Mexican-hat type connectivity profiles for the synaptic weights. The system shows a surprisingly rich set of dynamical states, even for rings of only four neurons , such as transient state dynamics [4]. In this case one observes extended plateaus in the time series of the population firing rates, indicating well defined transient states (see left panel of Figure Going beyond the simple mean-field analysis, we present an in-depth study of the bifurcation diagram, as a function of several bifurcation parameters, such as the strength I of the external current or the integration time 1/Γ of the neural activity. Four classes of distinct limit cycles are found (see right panel of Figure


Suliman et al.  have perMuch of the research regarding a potential role for BDNF in the mechanisms underlying psychiatric disorders has been conducted in the context of animal-models of depressive disorders. Mice with a knock-in of the human loss-of-function Val66Met BDNF gene polymorphism have decreased dendrite length, as well as decreased spine-synapse density, maturity and function in the hippocampus and the prefrontal cortex , with characteristics that are thought to reproduce the phenotype of humans with the Val66Met polymorphism, has increased anxiety-related behavior in the open field and elevated plus maze (Chen et al., The evidence linking BDNF with anxiety-like behaviors in animal models is not as abundant or clear. Foot-shock stress leads to reductions of BDNF levels, arguing for a link between BDNF and anxiety disorders such as post-traumatic stress disorder (Rasmusson et al., The meta-analysis by Suliman et al.  raises nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Objective: This presentation aims to leverage the experience gained from making a projection of the impact of pandemic mitigation strategies on longevity in the early advent of the COVID-19 pandemic.Before the COVID-19 pandemic, the literature on psychosocial stressors and psycho-social protective factors already clearly indicated that the two were linked in a multitude of ways to longevity. These ways include 1) directly through increased risk in suicides with respect to psycho-social stress or lack of connectivity 2) increased risk for psychopathologies such as depression, post-traumatic stress disorder and others, which in turn can decrease longevity in indirectly, and 3) a worse/healthier lifestyle that may be associated through decreased/improved social connectivity. With the advent of the COVID-19 pandemic, the ways in which these psychosocial factors could be impacted by policy came into focus. Attempting to quantify the potential future impact of such policies on longevity through psycho-social changes appeared necessary to allow better guidance of policy making. Discussion: This presentation will discuss issues concerning quantifications of the impact of COVID-19 related policy on psychosocial health. The assumptions necessary to arrive at projective models may be at odds with parts of the current culture in the field. The presentation will discuss potential strategies in order for the scientific community to be better prepared for similar events in the future.The authors model indicated the high need for measures that are protective of the general populations’ psychosocial health in the face of a pandemic and associated mitigation strategies. No significant relationships.


This Research Topic explores some recent advances in the field of Aging and the Immune System. We asked our Editorial Board members for forward-looking contributions that describe the state of the art, outlining recent developments and accomplishments. Our goal was to shed light on some of the progress made in the past decade in the field of Aging and the Immune System and how this relates to age-related changes in the health of older adults. Collectively, these articles emphasize the point that aging of the immune system is associated with increased inflammation as well as dysregulation of both innate and adaptive immune responses, which can then contribute to the development of many age-associated diseases.Obesity Accelerates Age-Associated Defects in Human B Cells Through a Metabolic Reprogramming Induced by the Fatty Acid Palmitate, Frasca et al. examined the concept that obesity and aging may exert similar impacts on the immune system via induction of chronic inflammation. They focused on production of autoantibodies, which are increased with both obesity and aging. They found that fatty acids can reprogram the metabolism of B cells from young lean subjects to function like those from young obese or elderly lean subjects, thus linking the impact of fatty acid-induced inflammation to dysregulation of B cell responses. Duong et al., Aging Leads to Increased Monocytes and Macrophages with Altered CSF-1 Receptor Expression and Earlier Tumor-associated Macrophage Expansion in Murine Mesothelioma, examined the response to mesothelioma in young and aged mice in order to understand how aging impacts the response to tumors. They found that Ly6Chigh macrophages, which have increased proinflammatory responses, are increased in older mice with tumors and prior work has shown that these cells may contribute to diminished anti-tumor activity that occurs with aging.Two original research articles that were contributed examine how aging impacts autoimmunity and anti-tumor responses. In the article Growth Differentiation Factor-15 in Immunity and Aging by Pence examines the immunoregulatory and anti-inflammatory roles of growth differentiation factor-15 (GDF-15). GDF-15 can be a component of the senescence associated secretory phenotype (SASP) and its production is induced in response to proinflammatory conditions in order to dampen inflammation. Importantly, the plasma concentration of GDF-15 increases with aging, likely as a result of chronic age-associated inflammation. This age-related elevation of GDF-15 could also function to dampen immune responses, including those to infectious agents, which could explain why it is one of the proteins most strongly correlated with multimorbidity in older adults. The review article Inflammation, Immune Senescence, and Dysregulated Immune Regulation in the Elderly, by Shive and Pandiyan extends the analysis of inflammation and dysregulated responses in this Research Topic by providing an overview of age-related inflammation and how it impacts the immune response in older adults including an examination of inflammatory and anti-inflammatory cytokines and regulatory T cells. In the review article T Cell Aging-Associated Phenotypes in Autoimmune Disease, Zhao et al. and her colleagues focus on the adaptive arm of the immune system and discuss T cell aging associated phenotypes (TASP) and how they contribute to two age-related autoimmune diseases: rheumatoid arthritis (RA) and giant cell arteritis (GCA). RA results from premature aging of T cells, leading to excessive production of inflammatory mediators, while GCA results from age-associated loss of control of T cell induced inflammation, including loss of regulatory T cells. Finally, the review Proteolysis dysfunction in the process of aging and age-related diseases from Frankowska et al. presents current insights on how aging impacts proteolytic systems. Failure to appropriately regulate proteolysis can result in protein aggregation and chronic inflammation, which can then lead to age-related diseases.The mini-review We hope that this Research Topic provides readers with a glimpse of some of the exciting research that is happening in the field of aging and immunity and that it stimulates new ideas and future progress.


This cross-sectional study investigates sales of over-the-counter iodine-containing drugs in 20 European countries between January 2021 and March 2022. Two major concerns are the potential use of nuclear weapons and the environmental consequences of the capture of nuclear sites by the Russian army.1 A nuclear war would result in many immediate deaths and delayed deaths from chronic diseases and climate disruption. Although guidelines from the World Health Organization advocate the prudent prophylactic use of iodine,3 media outlets have reported panic buying of iodine-containing drugs in Europe and other regions of the world since the beginning of the Russia-Ukraine conflict.4 Given that, to our knowledge, there is no research on this topic yet, the present pharmacoepidemiological study aimed to investigate sales of over-the-counter iodine-containing drugs in 20 European countries between January 2021 and March 2022.In February 2022, Russia invaded Ukraine and aimed to control the country rapidly.This cross-sectional study used data from the OTCims database (IQVIA), which contains data on sales of over-the-counter drugs in Europe. The present study included sell-out data of drugs with iodine as the only active ingredient. The number of packages of iodine-containing drugs sold per month was analyzed in each country between January 2021 and March 2022. Differences in percentage were assessed between February 2022 and January 2022, and March 2022 and January 2022  observed in this study may be related to the fact that these countries are geographically close to Russia and Ukraine and may, therefore, be more likely to suffer from collateral nuclear damage than other European countries. Interestingly, this is not the first time panic buying of iodine-containing drugs has occurred, and this behavior has also been reported after the Fukushima crisis.5 Panic buying of iodine-containing drugs since the beginning of the war is likely explained by the fear of the use of nuclear weapons and the fear of radiation leaks from nuclear sites.2 Despite international efforts, the nuclear threat is real, and this threat has been found to have adverse effects on mental health.6 Moreover, lack of awareness of international recommendations on iodine prophylaxis following nuclear accidents and inaccurate information from the media may potentiate the effects of the war between Russia and Ukraine on panic buying of iodine-containing drugs.The findings of this cross-sectional study are in line with recent reports from the media.The major strengths of this study are the number of countries included in the analyses and the use of empirical data obtained every month. Two critical limitations are the absence of data on prescribed iodine-containing drugs and the lack of information on the sociodemographic and clinical characteristics of buyers of iodine-containing drugs.In conclusion, the war between Russia and Ukraine was associated with increased sales of over-the-counter iodine-containing drugs in 20 European countries in February and March 2022 compared with January 2022. On the basis of the findings of this study, there is an urgent need to better inform the general population about the international recommendations on iodine prophylaxis following exposure to radioiodine.


The COVID-19 pandemic has had an enormous impact on both physical and mental health of people around the world.The aim of the study was to evaluate the number and characteristics of people seeking emergency psychiatric help during combined psychosocial stressful events in March 2020.Data for 3927 patients seeking emergency psychiatric help were collected and analyzed for the months preceding, during and after lockdown due to COVID-19 pandemic and concomitant earthquake that took place on 22nd March 2020 in Zagreb, and compared with the same months of 2019.A significant decrease in both the number of visits and admissions to the hospital was found for the month of lockdown. There was a significant decrease in the number of out-patients visits and day hospital admissions. Compared with other months, more women and younger patients sought help. There was a significant rise in the number of patients presenting with suicidal thoughts, as well as a larger percentage of involuntary admissions.Overall less people sought psychiatric help in the face of an unpredictable acute threat, which was interpreted in the light of prioritizing fear of infection over mental health issues. Alternatively, it is possible that people threatened with immediate danger mobilize short- term compensatory psychological resources which help deal with or put off mental illness. This research was conducted as part of the project of the Croatian Science Foundation CORONA-04-2086 Life in the time of COVID-19-social implications on the security and well-being of vulnerable groups in the European context.No significant relationships.


The negative consequences of transfers are known as transfer trauma. Nursing home (NH)-to-NH transfers place long-term NH residents at risk for developing transfer trauma and this risk may have increased during the COVID-19 pandemic in the setting of a state policy that increased the number of residents who transferred between NHs. The objective of this cross-sectional cohort analysis was to assess the incidence of transfer trauma and major events  among long-term NH residents who transferred from one NH to another before and during the COVID-19 pandemic using a composite measure of transfer trauma based on validated scales from Minimum Data Set (MDS) assessments. A total of 750 residents transferred in the pre-COVID cohort and 795 in the COVID cohort were eligible for assessment of transfer trauma and major events. After adjusting for demographic characteristics, residents in the COVID cohort were almost twice more likely to die and almost three times more likely to discharge within 90 days compared to those in the pre-COVID cohort . Residents in the COVID cohort were less likely to experience transfer trauma compared to those in the pre-COVID cohort. In the during-COVID cohort, 26% of residents had a COVID-19 diagnosis and they were less likely to experience transfer trauma compared to residents without a COVID-19 diagnosis . It is important to note that some residents may have not stayed in the nursing home long enough to assess them for transfer trauma.


The Editors-in-Chief would like to alert readers that concerns have been raised regarding the data in this article . SpecifiNone of the authors have responded to any correspondence from the editor or publisher about this Editorial Expression of Concern.


The 2PASS-4Health project  was founded by the Erasmus+ Sport programme of the European Union to improve the participation in sport and physical activity (PA). This project aims at examining examples of PA promotion interventions in secondary school, identifying good practices as well as the main barriers and difficulties linked to the design, implementation and evaluation of such interventions in order to improve their quality and sustainability. This project targets both the scientific community and various stakeholders involved in school-based PA promotion for adolescents to provide them with clear knowledge and usable tools. The overall design of this project will be presented as well as the first results and deliverables created to implement the interventions.In order to fill the existing gap between theory and practice by identifying evidence-based practices that work we are translating recent scientific knowledge into accessible information and tools that meet the needs of the stakeholders in the field. Furthermore, using a co-design approach involving several internationally recognised experts, stakeholders, and end-users, we developed some adapted and ready-to-use contents and we designed an optimised multicomponent school-based intervention that has been implemented in France and Spain. We evaluated these interventions not only in terms of outcomes related to PA and sedentary time, but also in relation to other important domains like implementation or maintenance based on the RE-AIM framework.We are producing: (1) a white paper geared towards professionals and policy makers, and a consensus statement intended for the scientific community; (2) two handbooks on the implementation of the intervention and its evaluation, accompanied by two scientific publications; (3) an educational toolkit to support PA promotion in schools; and (4) articles on the evaluation of the interventions held in France and Spain.System approach seems needed to implement a sustainable multilevel whole-of-school intervention co-constructed with the different stakeholders and end-users involved.


To examine associations of self-care and the quality of life (QOL) in patients with Parkinson's disease (PD) and their caregivers dyads.Patients with PD engage in self-care with motor and non-motor symptom experiences. There is insufficient knowledge about associations of self-care and QOL in patients with PD and their caregivers though PD patients and family caregivers are interdependent. Method: A total of 73 PD patients and primary family caregivers from the Korean Parkinson's Disease Association or who visited outpatient clinics of the tertiary hospitals in Korea participated in this study. Dyad members completed the survey of the self-care (the Self-Care of Chronic Illness Inventory and Caregiver Contribution to Self-Care of Chronic Illness Inventory) and QOL . The comparisons of self-care and quality of life within two dyad members were conducted via paired t-test and Pearson's correlation using SPSS 26.0 Result: PD patients reported significantly higher levels of self-care maintenance  and management  than caregivers. Patients’ self-efficacy was significantly correlated with their QOL . Caregiver contribution to self-care management was significantly correlated with their own QOL  and patients’ QOL .The self-care efficacy of patients and the contribution of caregivers to self-care management can affect the QOL of both patients and caregivers. A dyadic approach for the intervention of self-care management is crucial to improve the QOL of patients with PD and caregivers.