To determine the sensitivity, specificity and accuracy of ultrasound to diagnose the patients with tendon rupture of upper extremity referred to Taleghani Hospital’s center of Kermanshah in 2019.nd year resident in emergency medicine ward and the results were recorded in a checklist. Further examination of the tendon was performed as well as exploring the site for the patients after the patient was transferred to the orthopaedic service. Final result was recorded in the checklist. Data were analysed by SPSS software and sensitivity and specificity of ultrasound have been calculated.This was a diagnostic value study which performed on 113 patients with non-fracture penetrating hand trauma. In the first stage, all patients have been diagnosed with tendon injury by a first-year resident and then ultrasound was performed by a trained 2Results showed that ultrasound was able to identify 73 patients of 77 individuals with tendon injury. Of the patients with complete rupture, 45 individuals were correctly diagnosed based on the results of surgery in ultrasound test. Ultrasound and surgical findings were significantly different. Of the 36 individuals without confirmed rupture in surgery, 10 cases were diagnosed with tendon rupture by ultrasound. Of 52 cases of complete rupture based on surgical findings, 45 individuals were correctly diagnosed based on the results of surgery. Twenty-one patients were correctly diagnosed based on ultrasound out of 25 cases of partial rupture based on surgical findings.Overall, the results of the present study show that ultrasound is not very sensitive and specific in diagnosing of upper extremity tendon rupture and cannot be used as a reliable alternative in diagnosing of upper exteremity rupture; however, further studies is essential according to the limitations of this research. The limitations were low sample size in subgroups analysis based on the presence of complete or partial rupture and performing the ultrasound by an emergency medicine resident who is less experienced rather than radiologists. Tendon ruptures are common musculoskeletal injuries occurring along with penetrating trauma worldwide. These injuries are one of the most common musculoskeletal complaints responsible for 7% of all referrals to doctors in the United States . Approxiet al., [The present study was a functional diagnostic study. The sample size was determined in terms of the study by Mohamad-Rezaei et al.,  Based on the statistical population, 113 individuals with penetrating hand trauma have been enrolled in the study who referred to Taleghani Hospital Emergency ward of Kermanshah from March 22, 2018 to March 20, 2019. Inclusion criteria were penetrating trauma without fracture.All patients have been diagnosed with tendon injury by the first-year resident of emergency medicine at the first stage. Afterwards, the ultrasound was performed by the trained second-year resident of emergency medicine in the emergency department and the results were recorded in an out-of-file form. Ultrasound was performed using the Toshiba device at the time of admission. Following these steps, the patients was transferred to the orthopaedic services and the supplemental checking were also performed to examine and explore tendon site for the patients. At this stage, the patient’s outcome was recorded in a separate form and kept in the patient’s file. The results of ultrasound and orthopaedic evaluation were recorded in researcher’s and patients’ files after its completion in the operating room. The initial ultrasound results were compared with the gold standard method (orthopaedic exploration). Additionally, ultrasound sensitivity and specificity were determined. The final data were analysed by using a descriptive statistic . The statistical significance level of this study was considered as 0.05.This study was performed on 113 patients with penetrating tendon injuries. The mean age of patients was 31±7.36 years old. Kappa coefficient was used to compare the diagnostic values of ultrasound and surgery .The fingers traumatic tendon rupture is a common finding in soft tissue injury of musculoskeletal trauma. In this regard, surgery is one of the alternative treatment options to treat tendon ruptures in the fingers; however, post-operative complications like adhesion around the tendon can be observed by using this method and even experienced surgeons in treated patients. In the majority of patients, rupture or injury diagnosis of the finger’s tendon can be diagnosed by a history of trauma or clinical examination but CT scan findings are useful in cases when flexor tendon rupture cannot be diagnosed , 9. UsinNotably, there are limited findings on the efficacy of ultrasound in the diagnosis of tendon trauma in the fingers .et al., [et al., [et al., [In this study, 113 patients were studied with penetrating hand tendon injury. Of them, 86.7% were men and the mean age was 31 years old. In the study by Lee [et al.,  have bee[et al.,  were stuet al., [et al., [A study  in Netheet al.,  study wh[et al.,  in Chinaet al., [Ravnic et al.,  in the Uet al., , 15, 18,et al., [et al., [The present study found that flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) were the most common traumatic tendons and resembling with other studies such as Bianchi et al.,  and Clav[et al., . These sTherefore, these tendons were most likely to have trauma according to the fact that most of the traumatic injuries are the hand volar surface and FDP and FDS tendons have the highest contact area. In the present study, we found that ultrasound is able to fully detect all individuals with complete tendon rupture to detect sensitivity, specificity, positive and negative predictive values as 100%. However, this diagnosis was different in incomplete rupture. It was also observed that sensitivity, specificity, positive predictive value and negative predictive value was 94.8%, 72.2%, 87.9% and 86.7%, respectively in the diagnosis of incomplete rupture. et al., [In a study of Lee et al.,  20 tendoet al., [Jeyapalan et al.,  study obet al., [et al., [Complete rupture was observed in 3 patients. Surgical and exploration procedures were performed for these patients whereas in 2 patients (66.66%) an obvious rupture was observed. The results analysis showed that ultrasound could prevent the additional exploration of traumatic patients. Shekarchi et al.,  found thet al.,  claimed [et al.,  showed tet al., [et al., [et al., [Wu et al.,  showed t[et al.,  showed t[et al.,  it was r[et al.,  also repIn conclusion, the present study show that ultrasound does not have high sensitivity and specificity in diagnosis of partial tendon rupture. Therefore, it cannot be used as a reliable alternative method for diagnosis of upper extremity partial rupture. However, further studies are necessary in this field due to the limitations of this study especially low sample size in subgroups’ analysis based on the presence of complete or partial rupture and performing ultrasound by an emergency medicine resident who was less experienced than radiologists. Study Limitations and Suggestions● The results of clinical examinations were not evaluated.● Other imaging tools including CT scans and MRI were not evaluated in this study.● It is recommended that further studies must be conducted in this field and more patients should be evaluated.● It is suggested that another study should be performed in which patients will be divided into multiple groups and other imaging tools will be tested.● It is suggested that lower extremities should also be considered in the future studies.● It is suggested that ultrasound must be performed by both emergency medicine physicians and radiologists to assess the degree of agreement between them in the future studies.


This Special Issue brings together an original research report, a fascinating case report, and three timely reviews on a variety of topics related to pediatric leukemia. The original research report by Dr. Tremolada and colleagues  addresseThe case report by Prudowsky et al.  describeThis Special Issue also brings us three outstanding reviews on pertinent and rapidly evolving issues in pediatric AML therapies. The review by Epperly and colleagues  from St.The review by Chen and Glasser  providesFinally, the review by Conneely and Stevens  describe


The quest for meaning in life takes on new challenges and directions during late life. This mini-review draws on prior theory to analyze meaningfulness into six discrete dimensions  and covers research into how these apply and operate specifically during late life. Limited remaining time, concern with one's legacy, concerns with self-continuity and integration, variable challenges to self-worth, and prioritization of positivity emerge as key themes. Finding meaning in life is a potential concern for people of all ages, presumably except very young children. Meaning in life is widely regarded as an indicator of well-being Ryff, , and indLater life has been mooted as a time of particular relevance to meaningfulness concerns. Later life presents relatively few new opportunities for meaning while taking away some sources that may have been important during youth and middle age. In particular, the loss of social connection due to death or departure of loved ones can reduce meaning, given the central importance of relationships  is a theory developed to explain successful aging  stimuli, compared with younger adults (Charles et al., per se (Seeman et al., As a core need for meaning in life, efficacy means making a difference in the world, and especially to bring about progress toward those valued goals. Efficacy varies greatly among persons of any age; later in life it may well be that beliefs about efficacy, that is, self-efficacy and perceived control, may influence well-being and functionality more than efficacy There is a mixed literature regarding changes in self-esteem with increasing age; while some research supports declines in self-esteem in later life (e.g., Orth et al., Self-esteem plays an important role in buffering the effects of declines in health and functionality in later life (Sargent-Cox et al., Mattering was proposed by George and Park  as an imThe concept of mattering calls for further elucidation. Clearly the term resonates, because self-rated mattering among workers in organizations predicted a variety of positive outcomes (Reece et al., It may be difficult to sustain a sense that one's own life matters if one does not believe one's life matters to others. Taylor and Turner  discuss Comprehension was the third need postulated by George and Park . It compThere is an increasing literature examining age differences across the lifespan in self-continuity, defined as perceived associations of one's present self with past and future selves (Löckenhoff and Rutt, As human longevity continues to increase, the keys to successful aging become ever more important. An emerging consensus holds that finding or maintaining meaning is part of successful aging. We have sought here to break meaningfulness down into more precisely defined and specific needs for meaning. Such an approach holds promise for elucidating the problems, challenges, and opportunities for maximizing meaning in late life.NP's expertise on aging combined with RB's expertise on meaning. Ideas emerged from discussion. Both authors wrote parts of the manuscript.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.


Escherichia coli and intestinal enterococci) which are not indicating the fecal pollution source. Microbial source tracking (MST) methods allow the identification of fecal pollution sources that is critical for management and remediation of water quality.Human and animal fecal pollution may adversely affect inland and coastal waters with negative consequences for water supplies, recreational water uses and shellfish production. Fecal pollution of waters is a significant health risk and can lead to economic losses due to shellfish bed closures, bathing prohibitions and serious limitations on water resources. Fecal contamination in water is currently evaluated by the enumeration of traditional fecal indicator bacteria  methods have been proposed. With the exception of chemical compounds, they are considered in the manuscripts of this special issue.Li et al.; Sinigalliano et al. and Toubiana et al.), street-level stormwater run-off  and in roof-harvested rainwater  in this Research Topic.Multiple varying sources of fecal pollution can influence water quality. Some widespread sources of fecal pollution such as discharges of untreated or treated wastewater, contamination by bathers and wild birds are investigated in beach waters . Those molecular markers targeting human fecal material, or pollution originating from livestock or birds are the methods of choice in at least 15 of the manuscripts in this current Research Topic. In an interesting trend, most studies looked for several sources and combined several methods and targets .Boukerb et al. used this approach to identify novel markers for avian and other sources. Liang et al. as well as Zimmer-Faust et al. applied the same method to investigate and model fecal pollution in rural rivers and coastal waters, respectively, combining it with PCR-based detection of host-associated MST markers.The 16S rDNA gene is also the target of bacterial community-based MST approaches by amplicon sequencing of this gene. Rytkönen et al. explored the utility of targeting 16S rRNA instead of 16S rDNA as a template in MST studies. Furthermore, manuscripts of this Research Topic have shown that it may be relevant to complement the results from MST methods with chemical parameters indicative of pollution sources. Sinigalliano et al. used isotopic tracking of nitrogen inputs while Reynolds et al. investigated correlations of ammonium, total oxidized nitrogen, and phosphorus levels with MST marker levels.Byappanahalli et al. who investigated the influence of filter pore size on marker- and community-based MST approaches while Linke et al. demonstrated the strong impact inorganic turbidity can have on DNA based water quality analysis. These studies highlight the central importance of quality and process controls in MST investigations.Highly relevant technical issues of MST investigations were explored by Denissen et al. investigated the presence of Mycobacterium tuberculosis, Yersinia spp. and Listeria monocytogenes in roof-harvested rainwater. Derx et al. used Cryptosporidium and Giardia as index pathogens in a catchment wide QMRA approach.If the use of MST markers is currently coupled with the detection of FIB, it is also done in combination with the detection of human pathogens, especially in the context of quantitative microbial risk assessment (QMRA). Ahmed et al. show that MST markers can be useful indicator for the presence of AMR genes while Toubiana et al. combined genetic MST markers with AMR gene detection to assess bathers as sources of contamination.MST methods are also used to trace and investigate the spread of antimicrobial resistant strains and the pollution they originate from in the environment. Ballesté et al. used host-associated bacteriophages as indicators for human pathogenic viruses. Kapoor et al. on the other hand used bacteriophages as a low-cost alternative for differentiate animal waste and human wastewater in Kolkata. Viral indicators together with genetic MST markers were also used as an input for a QMRA investigation by Kongprajug et al.Wu et al. used various machine learning approaches to predict sources of fecal pollution based on a broad set of parameters from land use to hydrological parameters. In another study, Green et al. used generalized linear mixed models and conditional inference trees to find predictive variable for pollution source in 68 streams in the Finger Lakes region of Upstate New York.The selection of MST markers for their combined use with each other or with other markers such as chemical ones, is becoming a useful methodological approach to determine sources of fecal contamination and improve the robustness of prediction models. The incorporation of new computational procedures such as machine learning, neural networks or in the future artificial intelligence is very likely to facilitate and improve these predictive models. Moreover, care may be taken to combine the information provided by MST markers in multilayer data studies with other information from water uses in each geographic region  and hydrological and geological data among others that will allow to have a holistic view of water resources and their exploitability by different agents and uses.On the other hand, MST studies in recent years are exploring whether the available MST markers can provide significant contributions to the control of waterborne pathogens, the transmission of antibiotic resistance through the water cycle, and to complement microbial quantitative risk assessments. It cannot be ruled out that some of the present MST markers, or others that may appear in the future, may play a key role in these topics.New contributions from metagenomic and proteomic techniques may, in the not-too-distant future, be new tools for improving the specificity and sensitivity of MST markers or for discovering new ones that provide greater accuracy in operational applications of these MST markers.MG, AB, and GR prepared the call for this Research Topic, edited the manuscripts that were submitted, and wrote this editorial. All authors contributed to the article and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The sea occupies more than 70% of the Earth’s surface and includes more than 300,000 organisms with huge biodiversity. These organisms represent an enormous source of substances with relevant potential in the pharmacological field. The diversity and potential bioactivity of structures isolated from marine organisms have always played a crucial role in the search for and discovery of novel bioactive molecules that are potentially useful in pharmacological applications. The development of new lead compounds from the sea has always been the crucial aim of drug discovery . In thisThis Special Issue, as a continuation of the previous Special Issue, ‘Synthesis of Marine Natural Products and Molecules Inspired by Marine Substances’, includes three reviews and two articles that describe the synthetic strategies and biological activities of different classes of bioactive marine metabolites and analogs essential for future pharmacological applications.A review by Munekata et al.  focuses In a review by Kazmaier and Junk , cycloheA review by Martinez et al.  focuses In an article of Aljahdali et al. , a dockiIn an article by Xiao et al. , the firMarine Drugs for their support and kind help.As guest editor, I am grateful to all the authors who contributed their excellent results to this Special Issue, all the reviewers who carefully evaluated the submitted manuscripts, and


Glaucoma is one of the main causes of blindness worldwide, among the various forms existing of this disease, the most diffuse is primary open-angle glaucoma but many other types of glaucoma are known. Nowadays, this disease is defined as a multifactorial optic neuropathy characterized by a progressive optic nerve damage causing loss of retinal ganglion cells and their axons, developing specific visual field abnormalities, affecting eyes with open anterior chamber angles.The goal of its treatment is to conserve the quality of life and the visual function of patients by lowering the intraocular pressure (IOP). Among the possible therapeutic options, physicians can choose a medical therapy with topical glaucoma drugs, laser, or surgical therapy.Last years have witnessed many innovations both in glaucoma diagnostics and in treatments.Lehmann et al. suggest considering retinal ganglion cell layer thickness as a very useful tool in highlighting the first alterations in eyes difficult to classify. Tong et al. provided an interesting review showing the relevance of OCT evaluations, both peripapillary and both in macular area to be very helpful in distinguish pre-perimetric glaucoma, early perimetric glaucoma and ocular hypertension.Early diagnosis is always considered a key factor in the successful management of every disease and more, the chronic and subtle ones such as glaucoma. OCT is considered an extremely important device also in glaucoma management. Chen X. et al. that detected a significant correlation between vessel density measured by OCT angiography and changes in IOP.Another interesting contribution about OCT and Glaucoma came from Hirooka et al. conducted a very interesting study evaluating morpho-functional changes in glaucoma eyes comparing results obtained with standardized automated perimetry (SAP), electroretinograms (ERG) and OCT showing data that could be very useful both in better understand this disease.Wen et al., purposing a low contrast visual acuity test to check visual acuity in glaucoma patients, and from Saifee et al., purposing a new software to extract data from SAP report imagines.Others helps in improving the timing and the sensitivity of glaucoma diagnosis came from Zhang N. et al., and the other one investigating the trends in treatment approaches by Storgaard et al. have been included in this Research Topic.Two very interesting reviews, one showing the prevalence of primary angle closure glaucoma by Chen J. et al. and the other one providing a new model of chronic ocular hypertension obtainable in laboratory by Mosaed et al..The more experimental studies purposed in this section are one related to the correlation between the plasma level of Δ9-tetrahydrocannabinol and the IOP fluctuations by Ma et al. suggested an innovative model of measuring ocular biomechanical properties.Zhu et al., purposed a brief report detailing the results of using a drug supposed to be a neuro-enhancer in glaucoma patients: Scutellarin, whereas Zhang H. et al. provided a study showing their experience in combining Microcatheter-Assisted Trabeculotomy and Deep Sclerectomy and Trabeculectomy in young glaucoma patients.About innovation in treatments, This sections provided very interesting and useful information to better manage the glaucoma patients.Altogether this collection of articles emphasizes the importance of measuring the CSF to assess visual function in both basic research and clinical settings. It presents some methods to perform and improve those measures, and considers their interpretation and implications.All authors contributed to manuscript revision, read, and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To the Editor:Owen et al.  recentlyWhile the authors must be congratulated for their interesting review on this relevant question, we think that their findings require some caution. First, none of the studies from the Owen et al.  report iBeyond these limitations, we fully agree with Owen et al.  that the


Antioxidants, entitled The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile In Vitro and In Vivo, ten research articles emphasize the significance of adopting reliable redox biomarkers to determine the antioxidant activities of bioactive compounds in vitro and to assess blood and tissue redox status in vivo. First, Chaouni et al. [The present Special Issue of i et al.  and de Ti et al.  highlighi et al. ,4, Maciei et al.  and Bouri et al. ) describi et al. , Matute i et al.  and Islai et al.  demonstri et al.  describeThe use of proton beams has been recently introduced as an alternative strategy to conventional radiotherapy against cancer and, to develop the research on this strategy, Chaouni et al.  have higIt is a fact that the pathophysiology of various diseases is redox-related, given that the impairment of redox equilibrium of blood and tissues is a clinical outcome. Therefore, the development of reliable redox biomarkers towards early diagnosis and evaluation of disease progression is a major challenge for the researchers in the field of Redox Biology. Approaching this essential issue, Toczewska et al.  have attO-glucoside, appear to be probably the main contributors of the vasorelaxing action observed during fruit juice consumption. Additionally, Islam et al. [Illicium henryi, against the lipopolysaccharide-induced acute liver damage in a murine model. The results of their study suggested that the therapeutic efficacy of the corresponding plant extract, which also exerted in vitro antioxidant activities, was attributed to the upregulation of Nrf2 and the downregulation of TLR4/NF-κB signaling pathways, hence providing hepatoprotection against oxidative damage and inflammation. The negative effects of oxidative stress can be counterbalanced by antioxidants, hence the supplementation of bioactive compounds with antioxidant properties has risen to the forefront of scientific interest during the last decades. In this regard, Bouroutzika et al.  have invm et al.  have appFinally, Karydas et al.  have devΤhe studies included in this Special Issue cover a wide range of topics that converge in highlighting the significance of adopting redox biomarkers in order to approach modern research issues both in vitro and in vivo. Undisputedly, redox biomarkers comprise a powerful tool to monitor the efficacy of antioxidant molecules in vitro and to evaluate the modifications of redox status in health and disease in in vivo models. Thus, the measurement of specific redox biomarkers is directed to shed light on complex queries in the field of Redox Biology.


Dear Editor:et al.Revista Brasileira de Medicina Tropical. However, I want to highlight an important point regarding the administration of rabies immunoglobulin.I read with considerable interest the article by Duarte The authors stated that most bites in the case of their patient cohort were on the hands  and head . It is well-known that suspected rabid bites on the hands and head are category III rabies exposure. Accordingly, in these patients, rabies vaccination and rabies immunoglobulin should be administered according to World Health Organization guidelines


Aboriginal and Torres Strait Islander holistic health represents the interconnection of social, emotional, spiritual and cultural factors on health and well-being. Social factors  are internationally described and recognised as the social determinants of health. The social determinants of health are estimated to contribute to 34% of the overall burden of disease experienced by Aboriginal and Torres Strait Islander people. Primary health care services currently ‘do what it takes’ to address social and emotional well-being needs, including the social determinants of health, and require culturally relevant tools and processes for implementing coordinated and holistic responses. Drawing upon a research-setting pilot program, this manuscript outlines key elements encapsulating a strengths-based approach aimed at addressing Aboriginal and Torres Strait Islander holistic social and emotional well-being.The Cultural Pathways Program is a response to community identified needs, designed and led by Aboriginal and Torres Strait Islander people and informed by holistic views of health. The program aims to identify holistic needs of Aboriginal and Torres Strait Islander people as the starting point to act on the social determinants of health. Facilitators implement strengths-based practice to identify social and cultural needs , engage in a goal setting process and broker connections with social and health services. An integrated culturally appropriate clinical supervision model enhances delivery of the program through reflective practice and shared decision making. These embedded approaches enable continuous review and improvement from a program and participant perspective. A developmental evaluation underpins program implementation and the proposed culturally relevant elements could be further tailored for delivery within primary health care services as part of routine care to strengthen systematic identification and response to social and emotional well-being needs. Consultet al., et al., et al., et al., et al., et al., et al., Strengths-based, person centred and empowerment approaches are often used synonymously to describe the delivery of health care for Aboriginal and Torres Strait Islander people. These approaches promote individuals control over their own lives and focus on abilities and resources to enable self-determination , a secure web platform for managing online databases (Harris et al., et al., et al., et al., et al., et al., Reflective practice and clinical supervision are recognised by many professions for their role in supporting enhanced clinical practice as well as the health and well-being of the workforce (Koivu The Cultural Pathways Program utilises these existing frameworks as well as the knowledge and experience of program staff to implement a culturally relevant reflective practice and supervision model. An experienced Aboriginal clinician supports facilitators through a range of structures including weekly clinical yarning, one to one yarning and debriefing opportunities as required. Facilitators share perspectives, feelings, challenges, barriers and enablers in relation to both clinical practice as well as system, policy and organisational factors which impact the participant, Facilitator, or the program. Fundamentally, the supervision and reflective practice model are culturally grounded in relationships and yarning to support the cultural safety for Aboriginal and Torres Strait Islander participants whilst also enabling the retention and well-being of the Aboriginal and Torres Strait Islander workforce.et al., et al., Evaluating health programs and initiatives supports implementation across different contexts utilising insights into how and why they work and whether they have been effective (Lokuge There is a knowledge to action gap on how to assess and address the social determinants of health within clinical practice to inform the development of coordinated, culturally relevant and strength-based responses to meet the holistic social and emotional well-being needs of Aboriginal and Torres Strait Islander people and communities.et al., et al., et al., Primary health care services, often as the entry point for accessing health services, are well positioned to implement coordinated health equity responses which include addressing the social determinants of health (Pereira et al., et al., et al., The ability to implement holistic approaches to Aboriginal and Torres Strait Islander health through the intersection of health and social services requires adequate resources, training and support to clinical workforce (Andermann, The Cultural Pathways Program builds on existing approaches to contribute to practice-based evidence of culturally relevant case management approaches which can be utilised as part of routine care to strengthen the systematic identification and response in primary health care delivery. The combined understandings of the elements outlined in this manuscript provide a framework to inform service planning and tailored implementation which can strengthen social and emotional well-being responses for Aboriginal and Torres Strait Islander people.


Psychiatric treatments have specific and non-specific components. The latter has been addressed in an extensive literature on the placebo-effect in pharmacology and on common factors in psychotherapy. In the practice of mental health care, pharmacological, psychotherapeutic and social treatments are combined in complex interventions. This paper aims to review non-specific components across diverse psychiatric treatments and consider implications for practice and research.We conducted a non-systematic review of non-specific components across psychiatric treatments, their impact on treatment processes and outcomes, and interventions to improve them.The identified research is heterogeneous, both in design and quality. All non-specific components capture aspects of how clinicians communicate with patients. They are grouped into general verbal communication – focusing on initial contacts, empathy, clarity of communication, and detecting cues about unspoken concerns – non-verbal communication, the framing of treatments and decision-making. The evidence is stronger for the impact of these components on process measures – i.e. therapeutic relationship, treatment satisfaction and adherence than on clinical outcomes – i.e. symptoms and relapse. A small number of trials suggest that brief training courses and simple methods for structuring parts of clinical consultations can improve communication and subsequently clinical outcomes.Methodologically, rigorous research advancing current understandings of non-specific components may increase effectiveness across different treatments, potentially benefitting large numbers of patients. Brief training for clinicians and structuring clinical communication should be used more widely in practice. Various treatments have been established in psychiatry, based on different ideas, approaches and methods. They are usually classified as biological, psychological and social, with each category containing a wide range of treatments. These treatments consist of specific and non-specific components. The specific components are defined by the theoretical model for how and why the given treatment is effective.et al., In addition to these specific components, there are also other components that may have a therapeutic effect. For example, the way treatments are presented to patients may fill them with optimism resulting in more positive engagement and improved mood Thomas, . The suget al., et al., In psychiatry, there is a long history of considering non-specific treatment components, and the term ‘non-specific’ itself has occasionally been used in the literature since the 1960s  a wide search of disparate databases and sources, (b) forward and backward citation tracking, (c) safeguards against potential biases by using a team of researchers with different backgrounds and (d) some overlap of the searching, analysing and writing-up stages of the review  and three research psychologists at different career stages, educated in different countries.All non-specific components identified in the review capture aspects of how clinicians communicate with patients. They fell into the groups of general verbal communication, non-verbal communication, treatment framing and decision-making. Research evidence is first presented for these components and then for interventions to improve clinical communication.et al., et al., et al., et al., et al., et al., et al., et al., Extensive evidence shows that a more positive patient–clinician relationship is associated with better adherence and more favourable clinical outcomes across treatments (Fenton et al., Good communication matters right from the very first contact. How psychiatrists introduce themselves can already make a difference. In an experimental study, patients preferred an introduction with an explanation about what to expect in the first consultation over brief introductions without explanation or longer introductions in which clinicians disclosed personal problems (Priebe et al., et al., et al., et al., Beyond the initial consultation, a central component of beneficial clinical communication is empathy which concerns sensing patients' emotions and concerns and making them feel understood (Rickels et al., et al., et al., et al., et al., A number of studies of video-recorded consultations have studied the empathy of psychiatrists in more detail and highlighted how they detect and respond to patients' hints about their concerns (Rimondini et al., Communication with patients is not solely verbal. Non-verbal behaviour, including posture, rate of speech, intonation and pitch of voice are critical in interpreting the meaning of verbal utterances and can convey additional messages. Non-verbal communication appears to be particularly relevant for showing that the clinician is listening, taking the patient seriously, demonstrating empathy and establishing a positive rapport (Beck et al., et al., Most research on non-verbal behaviour has been observational, exploring associations with patient satisfaction and treatment outcomes. One systematic review suggests that non-verbal indicators of clinician warmth and clinician listening are linked with greater patient satisfaction (Henry et al., Communication, including non-verbal communication, is reciprocal. The non-verbal behaviour of psychiatrists and patients with schizophrenia during a consultation has been shown to be linked: when psychiatrists showed more pro-social behaviour in the form of gestures and open posture – inviting rather than avoiding interaction – patients reciprocated. This was associated with higher patient satisfaction and lower symptom levels (Lavelle et al., Non-verbal clinical communication has been investigated also in experimental designs. A study of actors pretending to be clinicians found that manipulating gaze and body orientation had a significant effect on how empathetic participants perceived their clinicians to be (Brugel et al., et al., et al., et al., et al., Patient expectation has consistently been linked to variation in clinical outcome across a range of medical disciplines, including psychiatry (Carver and Dunham, et al., et al., et al., The majority of studies assessing the effect of treatment framing across different psychiatric conditions have focused on help-seeking behaviours and on the uptake of treatment. Findings from these studies have been mixed (O'Keefe and Jensen, et al., In addition to presenting a specific positive or negative treatment frame as discussed above, clinicians can express their optimism or scepticism about treatment in more general terms. An experimental study using video-clips of real psychiatrists manipulated how optimistic or sceptical they were about a possible pharmacological or psychological treatment. Patients who were newly referred to mental health services preferred an optimistic treatment presentation. However, this was not the case for patients who had already been in psychiatric services for more than 2 years and had experienced that treatments in psychiatry are not always, at least not for them, a resounding and lasting success (Priebe et al., Decision-making is central to most psychiatric treatment encounters, often relating to starting, reviewing or changing pharmacological or other treatments. Involving patients in the decision-making process is widely regarded as good clinical practice NICE, . The levet al., et al., et al., et al., et al., et al., Much of the recent literature uses the concept of shared decision-making which suggests that decisions about treatment should be arrived at in a shared and non-directive discussion between patient and clinician (Hamann et al., et al., et al., et al., Improving communication with involuntary patients may be particularly challenging (Thornicroft et al., et al., et al., et al., However, the precise preferences of patients for how decisions should be made can vary depending on patient characteristics, therapeutic situations – e.g. an acute emergency and a consultation in long-term treatments – and types of treatment (De Las Cuevas The importance of clinical communication raises the question of how clinicians' communication can be improved to make treatments more effective. Communication may be influenced through training or through interventions which structure communication during consultations, or both.et al., et al., A Cochrane review of communication training in the context of severe mental illness in psychiatry identified only one RCT in this area (Papageorgiou et al., et al., In a primary care study, training in the form of structured discussions was tested to help clinicians elicit concerns from parents and children and to raise their treatment expectations. Three 1-hour discussions around video examples of family-clinician communication were followed by practice sessions with patients and self-evaluation. The training reduced the distress of parents and for some children, impairment across a range of disorders (Wissow et al., et al., et al., et al., et al., An alternative to training practitioners is to modify the structure of clinician-patient communication. Some interventions focus on improving decision-making through the use of decision aids. They are typically checklists assessing patients' preferences and providing information about available treatments. They are intended to help patients and clinicians arrive at a treatment decision. A Cochrane review of the effects of decision aids in people facing treatment decisions across medicine identified 105 studies covering over 31 000 participants (Stacey et al., et al., There are a small number of interventions to structure part of the patient-clinician meeting and directly guide communication. Focusing on 20 common needs, a communication checklist asks patients before a consultation to indicate the areas they want to discuss with their psychiatrist (Van Os Although much less research in psychiatry has explored non-specific than specific treatment components, an increasing body of evidence highlights the importance of such components across treatments. The existing evidence suggests that the way clinicians generally communicate with patients both verbally and non-verbally, and how they frame treatments and involve patients in the decision-making process can influence uptake, adherence and outcomes of treatments. Overall, there is more evidence for the impact of non-specific components on process measures, such as satisfaction and adherence, than on clinical and social outcomes of treatments.The summarising nature of our review did not consider the methodological quality of the referenced studies. While the review included some high-quality RCTs and meta-analyses, overall the studies are heterogeneous in their design and quality. Many studies were exploratory in nature and the results should be interpreted with caution. Moreover, we did not specify effect sizes. Most studies of non-specific components were intended to establish only that the given component is relevant in principle. Hardly any studies were designed and implemented with sufficient rigour to determine the effect sizes.Future research should go beyond establishing the effects of widely acknowledged non-specific components. There is no need for further studies showing that patients are more likely to come back for the next appointment if their clinician shows empathy and addresses their concerns. What is required is research that advances our understanding of non-specific components and the underlying mechanisms. This may include experimental studies with clinical and non-clinical samples that test the effects of varying such components in ways that would be feasible in clinical practice.In RCTs, one might try to standardise the delivery of at least some non-specific components, in both the experimental and control groups. If achieved, this should reduce the variance in outcomes and therefore help to detect the effects of the specific treatment components being tested.In addition, research should aim not only to understand non-specific components better but also to utilise them more effectively. The few studies on improving clinical communication indicate that such improvements are possible and can lead to better outcomes.et al., et al., Much research on psychiatric treatments has focused on finding patient characteristics that predict a positive response to specific treatment methods. Recently, such efforts have sometimes been referred to as personalised medicine. For non-specific components, individual responsiveness may possibly vary even more than for specific ones. Which characteristics of the patient and context determine how best to communicate with the patient remains largely unknown. The literature provides some hints about patient characteristics and experiences predicting different responses to placebo or optimistic treatment framing (Bialik et al., et al., et al., Non-specific components are part of all treatments in practice, with one review suggesting that they explain up to 60% of the variance in outcomes (Walach Communication skills are important for all clinicians working in mental health care. Short and effective training courses exist and could be rolled out into routine care at limited costs. Another simple and even less expensive option for refining communication skills is video-recordings of consultations to review what works and what may be improved. Yet, neither training nor reviews of video-recordings are widely used in routine care.Beyond that, a focus on communication skills may have positive implications for clinicians working in psychiatric care. Improving communication skills will require more training and supervision, but might also be an opportunity to strengthen the specific professional profile of clinicians in psychiatry. Clinicians in routine psychiatric care are expected to engage and communicate with patients in widely varying settings and treatment situations. These include acute crises, involuntary treatment or long-term rehabilitation, with variable time frames and changing treatment goals. The challenge for clinicians is to develop and flexibly utilise a repertoire of skills to achieve the optimal benefit for the patient. These skills are likely to vary across individuals and be influenced by personal styles and individual strengths so that much of the training will have to be individualised. Yet, such training may provide clinicians in psychiatry with a relatively unique skill-set and strengthen their professional expertise.Over the last four decades, extensive research on specific treatment components has led to only limited improvement of effects of psychiatric treatments. A stronger focus on non-specific treatment components in both practice and research may improve the effectiveness of complex interventions with pharmacological, psychological and/or social approaches. This would potentially benefit large numbers of patients across settings and treatment methods and therefore have a substantial public health effect beyond the improvement of confined specific treatment components.


Myelination is a fundamental molecular event within the vertebrate central nervous system (CNS) where oligodendrocytes wrap around axons to form a myelin sheath which allows rapid “saltatory” conduction of action potentials along the axons  triggers the unfolded protein response (UPR), which aims or serves to maintain protein homeostasis by multiple mechanisms including attenuation of protein translation and the prevention of translocation of newly synthesized proteins from cytosol to ER  was found to be vital in the process of myelin thinning. This was confirmed by showing an exacerbation of myelin thinning, tremoring phenotypes, and a shortened lifespan in Sel1L and PLP double knockout mice compared to Sel1L deficient mice. This confirmed that diminished myelin protein translation was responsible for myelin thinning. They also ruled out the possibility of myelin thinning resulting neither from remyelination, (no myelin loss or oligodendrocyte death), nor from regeneration, (no increase in oligodendrocyte precursor cells or oligodendrocyte proliferation). Importantly, PERK inactivation in oligodendrocytes (Sel1L and PERK double knockout) restored myelin protein translation, reversed myelin thinning, attenuated tremoring phenotypes, prolonged survival, and prevented oligodendrocyte death compared to Sel1L deficient mice. The joint role of UPR and ERAD in myelin thinning as mediated by oligodendrocyte specific deficiency of Sel1L is summarized in In a recent study published in u et al.  providedu et al. . Specifiu et al.  was attrWhile Wu et al.  found noSimilar to these findings (Wu et al., In contrast to MS and other demyelinating diseases (Luo et al., In addition to the association of PERK activation in myelin thinning in Sel1L deficient mice (Wu et al., Since demyelination leads to slowed axonal conduction, electrophysiological recordings in the future can address to what extent myelin thinning in Sel1L knockout mice reduces the speed of conduction in the CNS axons (Mu et al., Taken altogether, this opinion article discussed the landmark work (Wu et al., MKS and MJH designed the scope, wrote and edited the manuscript. All authors contributed to the article and approved the submitted version.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 National Institutes of Health define, rehabilitation technology as tools that help people recover their function after injury or illness. In recent years, advances in rehabilitation technology have created exciting opportunities and generated significant improvements in the autonomy and quality of life of people with neurological health conditions. Virtual reality (VR) in particular, is a rehabilitation technology that has rapidly risen to prominence and is achieving promising results in improving the sensorimotor function for people with neurological disabilities –3. VirtuGiven the growing interest in the use of technology in neurological rehabilitation, studies are needed to justify the safe effective use of Virtual Reality in clinical practice. This special issue aimed to collect insightful and multi-disciplinary evidence of the development, testing and application of virtual reality innovations for sensorimotor rehabilitation of neurological health conditions across the lifespan.Espy et al. presents a conceptual framework to guide clinical-decision making for the selection, adaptation, modulation, and progression of virtual reality or gaming when used as a therapeutic exercise modality. The study of Oliveira et al. found benefits in using virtual reality-based exercise in spatial navigation of institutionalized older persons. Cheng et al. investigated performance variability over time during learning of standing postural control tasks in a non-immersive virtual environment in children with cerebral palsy. Benady et al. studied the contribution of vision to locomotion in a dynamic immersive environments to support rehabilitation strategies for neurological disorders associated with gait impairments.Ten papers were published in this Research Topic with contributions to support practice. Tong et al.; Finley et al.; Al-Sharman et al.; Lubetzky et al.; Da silva et al. and Fluet et al.). Although evidence suggesting that non-custom commercial games can be successfully used in clinical settings, they have limitations such as calibration of a game's difficulty for persons with different abilities, game scores or progress measurements being to generic, lacking specificity in tracking the progress of persons with different abilities, and many require movements that cannot be performed by people with disabilities  and the movements of their intact limbs are mirrored in the avatar, providing participants with the illusion that their limbs respond as if they were both intact and functional. They found that repetitive exposure to VR intervention led to reduced pain and improvements in anxiety, depression, and a sense of embodiment of the virtual body.Finley et al. presented a custom VR game where individuals with Parkinson's disease have to complete a puzzle that consisted of a word with missing letters in the virtual environment. The player had to determine which letters were necessary to complete the puzzle, collect the necessary virtual letters as they floated in 3D space, and then place the letters in the appropriate location. Al-Sharman et al. created a non-immersive VR task to be used with Microsoft Kinect sensor and found improvement in participants with Parkinson's disease when asked to steer a helicopter up and down to collect coins and to avoid specific number of obstacles by moving from sitting to standing and vice versa. Lubetzky et al. created two VR tasks (one using stars on the sky and the other a busy street) with Head Mounted Displays (Oculus Rift) and found significant differences in performance between environments evaluating Postural and Head Control in individuals with unilateral vestibular hypofunction and monaural hearing. Da silva et al. in a study protocol presented two non-immersive custom virtual reality games developed for individuals with disabilities (movehero and moveletrando), both can be used with computer webcam. Fluet et al., presented different studies using a home-based virtual rehabilitation system and a robot assisted virtual rehabilitation to improve paretic hand and arm of persons with chronic stroke. They suggested that persons with stroke may adapt to virtual rehabilitation of hand function differently based on their level of impairment and stage of recovery.We believe that the studies published in this special issue present research on the benefits of using virtual reality in the rehabilitation for persons with neurological health conditions. It is noteworthy that many authors are integrating game mechanics into their virtual rehabilitation. The research will need to be ongoing to facilitate application to clinical practice.All authors read and approved the final editorial.HD was funded by the Elizabeth Casson Trust and the NIHR Oxford Health Biomedical Research Centre. CM was funded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)- Finance Code: 2017/24991-7 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). JD was funded by NIH (1R15AG063348-01).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


People with Parkinson's disease (PD) have an increased risk of falling, which is often associated with the manifestation of freezing of gait (FOG) (Pelicioni et al., The main bottleneck to better understand when and why FOG emerges and how to manage it is the lack of valid markers of FOG, justifying the search for models of freezing in other effectors than in gait. Several instrumented methods for measuring FOG episodes in daily life as well as during standardized lab tests are currently in the validation pipeline (Mancini et al., Our group was one of the first to acknowledge the remarkable similarity between features of FOG and motor arrests when performing sequential finger and writing movements uni- and bimanually (Nieuwboer et al., As upper limb freezing was brought on when people with PD were subjected to similar motor challenges as in FOG, we recently investigated whether producing up-and-down strokes on a writing tablet within a funnel figure, with wide, narrow and transitioning pieces, elicited motor arrests similar to presenting a doorway to trigger FOG in a gait lab or in the home (Heremans et al., As for construct validity of non-gait freezing, a review on freezing episodes in a variety of tasks, i.e., handwriting, hand and foot tapping and speech revealed that the clinical manifestation of these events appeared to be overlapping (Vercruysse et al., As for “fast funnel freezing,” freezing events occurred in 23 out of 49 patients and its frequency was correlated to self-reported FOG severity, though this correlation was not found for %timeFR during the funnel task (Heremans et al., Prospective study conducted by Delval et al. demonstrated, that episodic events during foot-tapping, hand-tapping, and syllable repetition in early-stage PD patients without FOG were predictive of FOG emerging in the next two years, albeit in a small cohort of 30 subjects (Delval et al., Mobile neuroimaging techniques as well as local field potential recordings are increasingly applied to better understand the brain circuit dysfunctions underlying actual FOG episodes obtained during over-ground walking (Tard et al., As for seated EEG, one recent study demonstrated that movement initiation of a finger sequencing task displayed reduced beta-desynchronization in the SMA and this more so in freezers compared to non-freezers (Brugger et al., We have highlighted that studying freezing in other effectors has great potential as a model for investigating component-mechanisms of FOG. However, we also showed that further validation of non-gait freezing as a behavioral biomarker of FOG is indicated. Therefore, prospective cohort studies are needed including recently diagnosed patients with PD, as well as positive control groups with FOG to be able to track progression of both gait and non-gait freezing-severity. As for measuring repetitive finger movements, keyboards as well as tablets and smartphones technology could be used to quantify motor blocks (Trager et al., ND drafting manuscript. AN conceptualizing and revising manuscript. All authors contributed to the article and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Dear Editor, We read with interest the comment of Manzo et al. [o et al.  on our ro et al. . The autThe prevalence of neurological symptoms in pSS patients ranges between 8.5 and 70% . The reaet al. about the need for both a better assessment of cognitive dysfunction in pSS patients and searching for pSS in patients with CI, as they established in their systematic review [We also agree with the comment by Manzo c review .et al., which highlights the great importance of neurological manifestations, and CI in particular, in pSS patients.Whether CI or other neurological manifestations should be considered ‘comorbidities’ defined as ‘simultaneous presence of more than one disease in a patient’ or only clinical features of pSS in a specific system could be discussed. However, we think that that debate should not minimize the relevance of the message of Manzo Funding: No specific funding was received to carry out the work described in this article.Disclosure statement: The authors have declared no conflict of interest.Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). All data relevant to the study are included in the article.


When restoring gene flow for conservation management, genetic variation should be viewed along a continuum of genetic divergence between donor and recipient populations. On the one hand, maintaining local adaptation (low divergence between donors and recipients) can enhance conservation success in the short term. On the other hand, reducing local adaptation in the short term by increasing genetic diversity (high divergence between some donors and recipients) might have better long‐term success in the face of changing environmental conditions. Both Hoffman et al. (2020) and a paper we previously published in a Special Issue on Maladaptation in Applied Conservation  provide frameworks and syntheses for how best to apply conservation strategies in light of genetic variation and adaptation. A key difference between these two studies was that whereas Derry et al. (2019) performed a quantitative meta‐analysis, Hoffman et al. (2020) relied on case studies and theoretical considerations, yielding slightly different conclusions. We here provide a summary of the two studies and contrast of the main similarities and differences between them, while highlighting terminology used to describe and explain main concepts. We were encouraged to see Hoffmann et al.  provide Both papers framed strategies in terms of meeting short‐term versus long‐term adaptation targets of genetic variation, which we referred to as managing for ‘adaptive state’ versus ‘adaptive process’. A key difference, however, was our use of quantitative meta‐analysis to evaluate effectiveness of different conservation strategies; Hoffmann et al.  relied oOne contrast between conclusions is that we found that genetic and evolutionary rescue tended to increase fitness across multiple generations relative to immediately after conservation intervention (figure 2 in Derry et al., Importantly, Hoffmann et al.  point ouIn conclusion, we hope that the frameworks of genetic mixing along a gradient generated in Derry et al.  and HoffThere is no conflicts of interest to declare.


To the editor,Recently in the Journal, Li et al.  reportedNevertheless, beyond all these limitations, we fully agree with Li et al.  that lar We would like to thank Dr. Jourffroy and Dr. Vivien for their interest in our manuscript  and for Dr. Jourffroy et al. argued that the study by Vincent et al.  should bTwo included studies , 5 incluWe agree with Dr. Jourffroy et al. that the infectious agent itself influences the outcomes of septic patients. We attempted to convey the message that culture positivity or negativity was not associated with mortality of sepsis or septic shock patients. A positive culture does not mean a severe infection, and a negative culture does not mean a mild infection. The clinical outcomes may be associated with not only the infection sources but also the management of the sepsis and septic shock.


We read with interest the recent publication by Wu et al. . Wu et aWu et al.  stated iWu et al.  did not Camp et al.  measuredWu et al.  providedIn conclusion, Wu et al.’s provided radiographic evidence shows that the authors did not appreciate rotational deformities, with these being described as normal, which raises questions about the reliability of the provided radiographic measurements, with the use of ultrasound assistance possibly resulting in an increased rate of inadequate supracondylar humeral fracture reductions. This is in addition to the 42% mean increase of costs associated with the use of US because of the extra time under general anaesthetic in theatre, with Wu et al.  not havi


Weisshaar. However, the neurobiology of CP is complex and its causal link to the underlying diseases remains unclear as described in two papers on encoding Schmelz and central processing of pruritus Najafi et al. Experimentally, pruritus can be induced by electrical stimulation Solinski and Rukwied, Meijer et al. and reduced by affective touch. Clinically, cholestatic pruritus might be related to bile salts, steroid metabolites, serotonin, protease-activated receptor agonists or most likely lysophosphatidic acids Langedijk et al., but probably not by endogenous opioids as shown by Düll et al. The long list of potential mediators reflects the current dilemma in pruritus research: many potential mediators have been identified but unfortunately, the clinical validation in representative patient cohorts is pending.Pruritus is a burdensome symptom and defined as chronic when lasting for at least 6 weeks according to the International Forum for the Study of Itch (IFSI) . ChronicDonglang et al. guide us through translational aspects of these animal models. Liu et al. describe an acute itch model by intradermal injection of low-dose formalin which may be employed as a screening tool for potential anti-itch drugs. Also, novel topics such as the role of the gut microbiota in pruritus was investigated in an animal model and described here . Jia et al. even describe a novel functional factor which is relevant for itch signal processing, and show that the transcription factor ZBTB20 (Zinc Finger And BTB Domain Containing 20), which is expressed in small primary sensory neurons, could modulate itch regulating TRP channels.Still, animal studies are indispensable to identify novel mechanisms. Ruppenstein et al., Kabashima and Irie, and Nemmer et al. Atopic dermatitis is the most frequent inflammatory dermatosis; Legat gives an overview on its pathophysiology including the relevant neuroimmune mechanisms and also provides information on the corresponding current treatment options. While atopic dermatitis is already well-understood regarding its pathophysiology, other pruritic dermatoses, systemic diseases and neuropathic entities are not. However, in past years, several entities reached a broader understanding and novel mechanisms or therapies have been identified. Accordingly, our authors report on the latest knowledge in chronic prurigo Zeidler et al., scabies Ständer and Ständer, pruritus related to therapy with immune checkpoint inhibitors Salinas et al., chronic kidney disease Krajewski et al. and neuropathic diseases Pereira et al. as well as sensitive skin condition , and vulvar pruritus Raef and Elmariah. For poorly understood cases of pruritus cannot be linked to inflammatory or neuropathic mechanisms Misery extends the concept of nociplastic changes in the pain field and suggests using the term pruriplastic pruritus for them.Itch induction in the skin is frequently based on inflammation and neuroimmune mechanisms. The latter refers to the bidirectional communication between cells releasing inflammatory mediators such as interleukin (IL) 4 or IL 31, neurotrophins such as nerve growth factor and neuropeptides released by sensory nerve fibers. The implications of such neuroimmune interactions is presented in three papers by Lüßmann et al. describe that itch intensity and certain facets of mindfulness were associated with itch catastrophizing in AD patients. On the other hand, distraction might help to reduce itch as investigated by van Laarhoven et al. by training volunteers to reduce attention toward itch. Pruritus is a subjective symptom without objective measurement. Accordingly, patient reported outcomes are still the gold standard in the assessment of the course. However, the complex process of international harmonization and validation is still ongoing. Stepień and Reich contribute to this topic by framing severity levels in a novel questionnaire.Mental factors are important for itch perception and its progression. In sum, this collection of articles combines several up to date aspects of the neurobiology and clinics of pruritus, including also new methods and innovative concepts in itch research.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.This article was supported by the German Research Foundation (DFG/NO FOR2690 to SS and MS).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


High heterogeneity was found in the prevalence rates of mental disorders in adult asylum seekers and refugees in high-income countries. This may be related to different problems. Among them, there is a changing exposure to risk and protective factors for mental health at different phases of these people's life before migration, and during the migratory journey and resettlement. This study aimed at identifying and distinguishing time points in which distinct risk and protective factors for the mental health of asylum seekers and refugees may occur.Systematic review and narrative synthesis. A systematic search was carried out for the period January 2017–August 2019, given the existence of systematic reviews of the evidence up to January 2017.Two hundred and fifty-two studies were identified with our search and 31 studies were included. The critical time points identified are: (a) before the travel; (b) during the travel; (c) at initial settlement in the host country; (d) when attempting to integrate in the host country; (e) when the immigration status is challenged or revoked. Some factors such as sense of belonging in the host country can be risk factors or protective factors depending on the time point.These five critical time points can guide the development and selection of well-timed preventive and treatment interventions. They could also be used to stratify samples in epidemiological studies and meta-analyses. At present, we know much more on risk factors than on protective factors. Knowing more about protective factors may inform the development of interventions to foster them. EMBASE, PsychINFO and OVID Medline databases were searched.Papers were included if: (a) at least 50% of the research participants were refugees and/or asylum seekers; (b) they assessed risk or protective factors for mental disorders; (c) they focused on adult populations (18 or older years of age); (d) they reported on studies carried out in high-income countries (according to the World Bank Classification); (e) they reported on primary research or were literature reviews, excluding opinion pieces; (f) they were published in full articles or full reports in scientific journals, excluding grey literature and conference presentations.Papers were excluded if they focused only on aspects other than risk and protective factors for mental disorders, e.g. interventions, prevalence rates without correlates, individuals’ experience of care or barriers to access care. Qualitative studies which described patients’ or clinicians’ views about which were potential risks or potential factors for mental health were also excluded. They were deemed as ‘non-focusing on risk and protective factors for mental health’ given that they failed to demonstrate the actual association of those factors with mental health, only suggesting that this may be.From each paper identified, risk and protective factors were captured and summarised in an excel extraction table.The risk and protective factors identified from different studies were initially grouped together according to when they occurred, based on the usual framework .The analysis then continued with the aim of re-grouping risk and protective factors in more specific and discrete time points which generated the final time points described in the Results section.Our search identified 252 papers in the period January 2017–August 2019. After removal of duplicates and screening according to inclusion criteria, 31 papers were included, i.e. 28 papers reporting on primary research and three literature reviews.The PRISMA diagram can be found in The main characteristics of the included studies are synthesised in Five time points were identified, in which all the risk and protective factors identified can be categorised. These time points are: (a) before travel; (b) during travel; (c) initial settlement in the host country; (d) integration in the host country; (e) challenges to or revocation of the immigration status.A summary of risk and protective factors at all of these time points can be found in These different time points can all be experienced by individuals who are forced to migrate from their countries. However, this is not necessarily the case for all of these individuals. For example, some of them may have their asylum applications rejected and never reach the status of a refugee. Others may integrate successfully and, hence, remain in the host country as naturalised citizens without their residence status being challenged.et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Exposure to potentially traumatic events  in long-term resettled refugees (at least 5 years) than in those at first resettlement  with less of a focus on the factors associated to disorders with comparatively lower prevalence rates   social attitudes in host countries may influence the level of discrimination that refugees encounter, the investment in social integration programmes and the opportunities for refugees to flourish. This, in turn, could have a negative impact on asylum seekers’ and refugees’ mental health. Interventions provided within mental health services may not be able to address these issues on their own.


This collection of papers demonstrates a growing interest and maturity of experience within the field of patient and public involvement utilizing a range and various forms of involvement with different groups and communities. Many of the papers placed emphasis on dignity and respect, Faulkner et al, Warner et al.; others, for example Tyler et al., and Kuhne et al., highlighted the importance of listening to the patient voice. The need for shared decision making was referred to by Khan et al., having patients and young people as part of the research team was indicated in the work of Walker et al., where children and young people formed a project advisory group (CYPAG).The importance of relationships was considered key in the work of Mulvale et al., who incorporated integrative dynamics (ID) approach and experience‐based co‐design (EBCD) to overcome ‘us vs them’ thinking. Photovoice was the method of choice used by Weinstein and colleagues when working with individuals with long‐term mental illness, obesity and living in supportive housing.There are some careful explorations of appropriate methods to use with different and often marginalized groups and communities; for example, Corvin et al. examined the application of analytic hierarchy process (AHP) to inform the augmentation and implementation of an evidence‐based chronic disease self‐management programme for underserved Latinos living with both minor depression and chronic illness. Thomas and colleagues report an honest reflection of working with people from low‐income backgrounds throughout a research process; Warner et al outline a method of engaging with refugees at the early stages of research; Dewa et al explore the methods and the impact of working co‐productively with young people and saw significant impact on the research, researchers and co‐researchers.A patient‐targeted feedback intervention after depression screening using the Patient Health Questionnaire (PHQ‐9) was the focus of work by Seeralan et al. It needs to be recognized that for a variety of reasons, patients may not want to participate as outlined by Bixo and colleagues. In their study involving young people being ‘too tired/too sick to participate’ was the most common barrier for non‐participation followed by lack of time and fear of needles. However, the young people identified different ways for increasing the likelihood for participation such as simplification of procedures and information, providing rewards and feedback, and building relationships before asking. The points raised by the young people are equally as applicable to all studies where PPI is a key aspect.Several papers report on evaluations of the impact of involving service users and/or carers in the research process. In a protocol paper, Littlewood et al describe a longitudinal process of evaluating impact of working with people who self‐harm, the results of which will be interesting to see. Matheson and Weightman take the exploration of process into the therapeutic realm by viewing it as a potential part of the co‐researchers' community re‐integration stage of therapy for complex post‐traumatic stress disorder (CPTSD), contributing to their empowerment through collective action. Morse et al, in working with both service users and carers, identify an ethical dilemma at the heart of the endeavour: the ownership of the story and who can speak for whom. Along with the other studies in this collection, it becomes clear that involvement cannot be regarded as simply instrumental; it has powerful ethical and political threads running through it.'service users have not fought for a voice at the table merely to help improve the research process, but because they have a right to be there'. They advocate looking beyond impact at the quality of participatory research in relation to the ethical demands of service users, the development of service user capacities and, crucially, sharing power in domains other than just research. This collection of papers suggests a growing maturity in approaches to PPI; however, there is still a need for understanding of the difference between participation, engagement and user‐led research alongside a shared respect for the different forms and fields of knowledge.Friesen et al explore some of these ethical dilemmas in more depth, by confronting the limitations of seeking evidence of impact. They suggest that our search for evidence of the impact of involvement obscures the ethical and political grounds behind involvement, the drive to address the imbalance of power within psychiatric knowledge‐making:


Viruses constitute a significant part of the human microbiome, so wherever humans go, viruses are brought with them, even on space missions. In this mini review, we focus on the International Space Station (ISS) as the only current human habitat in space that has a diverse range of viral genera that infect microorganisms from bacteria to eukaryotes. Thus, we have reviewed the literature on the physical conditions of space habitats that have an impact on both virus transmissibility and interaction with their host, which include UV radiation, ionizing radiation, humidity, and microgravity. Also, we briefly comment on the practices used on space missions that reduce virus spread, that is, use of antimicrobial surfaces, spacecraft sterilization practices, and air filtration. Finally, we turn our attention to the health threats that viruses pose to space travel. Overall, even though efforts are taken to ensure safe conditions during human space travel, for example, preflight quarantines of astronauts, we reflect on the potential risks humans might be exposed to and how those risks might be aggravated in extraterrestrial habitats.  Viruses are a significant part of such enclosed communities  outbreak among the three Apollo 7 astronauts, which spread rapidly and reduced the ability of the astronauts to cooperate with the control center NASA, . The reaet al.,et al.,et al.,Most damaging UV radiation is filtered by Earth's atmosphere; therefore, all species on Earth are protected from most of the UVC, some UVB, and UVA to a lesser extent  coming from interstellar space  and human herpesviruses (HHV) types 1–3 ,  for several days, which guarantees that no microbes or spores can survive. In recent years, plasma sterilization has been considered an effective alternative due to its more convenient application  filters. They have been reported to efficiently filter out small aerosols  and regulatory T cell function, which have been described to maintain viral latency (Mehta et al.,Even though disinfection on space missions is thorough, it is impossible to completely neutralize the disease-inducing factors due to their prevalence in the human hosts, since a large portion of humanity is already latently infected with specific viruses. Latent infections are caused by viruses that, upon a single inoculation, can establish lifelong infections, like herpesviruses. et al.,et al.,et al.,Multiple studies have detected reactivation and shedding of viruses in human space and analog missions and environments (Pierson et al.,et al.,et al.,et al.,et al.,The reactivation of these viruses, some of which are associated with increased mortality (Ren et al.,et al.,et al.,et al.,et al.,et al.,In addition to infection by reactivation of latent viruses, there is also a possibility of virus infection on space missions that increases the risk of outbreaks in modules and habitats. Due to the limited possibility of identifying the cause of infection in space, it is challenging to recognize viral infections in addition to treating them. So, how can astronauts protect themselves from viral infections? Currently, most herpesvirus infections cannot be prevented through vaccines, with the exception of VZV, the causative agent of chickenpox and zoster (Papaloukas Currently, the standard safety procedure of human spaceflight is the preflight astronauts' quarantine and disinfection of cabins and equipment. However, we must consider the risk that some viral infections might go unnoticed during the quarantine period and cause significant harm once in the space station. Development of optimized methods for virus detection and calculating the impact of the space environment on virus spread will help address this problem and provide the basis for the development of improved protocols to control eventual outbreaks in space.g-forces or microgravity on viruses is underrepresented. It would be, for instance, interesting to test the influence of microgravity on viral spread throughout the body. Also, studies showed that hypergravity encourages the proliferation of healthy cells (Ciofani et al.,et al.,Viruses are a diverse biological group that is part of microbial communities in human-inhabited space modules. As such, they can influence astronauts' well-being and may pose a health threat to the crew. Intensive research is required in the field of space virology to improve the current knowledge on the dynamics caused by space stress. The effect of extreme Since the plans of future space missions tend to be more prolonged, preflight isolation and a healthy immune system might not be enough to protect astronauts against some viruses due to the overwhelming conditions during space travel. Hence, developing new methods for the detection and treatment of viral infections in space is a relevant topic.


To improve the medical waste management (MWM) standards in Tabriz community health centers (CHCs) through clinical audit process.Management of medical waste is not only a legally necessity but also a social responsibility in health systems. Owing to the potential risks for human health and environmental impacts, MWM is a global concern.This was an interventional research designed using clinical audit cycle that was implemented in Tabriz CHCs in 2016. MWM was assessed through observation, as well as reviewing relevant documents and interviews with waste workers in CHCs and completion of a researcher-made checklist. Intervention plans were developed and implemented based on the assessment results. To analyze the data, Excel 2016 software was used and information was reported as descriptive statistics through comparison of standards adherence before and after the interventions.Generally, 30% improvements in MWM standards adherence were experienced (45.8–75.1%) in the CHCs, after the interventions. The greatest improvement was observed in the dimensions of management and education, and separation and collection of medical waste, up to 30 and 28.5%, respectively.As the results demonstrated, standards of MWM processes were improved in Tabriz CHCs, due to the intervention. Moreover, it was experienced that using systematic method, stakeholders’ participation and evidence-based planning would lead to process improvement. MWM was an ignored issue in primary care that must be more in attention. The used model of clinical audit process has six stages of which stages 3 and 4 were repeated after the intervention. The stages of clinical audit were carried out as follows:So, the two stages of clinical audit . The checklist consisted of four dimensions, including management and training, separation and collection, transportation and temporary storage, and sterilization and disposal.These include MWM methods and process standards approved by Commission on Infrastructure Affairs of the Islamic Consultative Assembly and Environmental Protection Organization of Iran (Number: 1901/56061) . First, the officers were provided with training sessions on standards and how to complete the checklist. Then, the assessment program was developed upon which the environmental health officers of the health complexes evaluated the status quo of MWM in CHCs under their own surveillance in August 2016. They have reported the assessment results to the Tabriz regional health center officers. The assessment was carried out by observing the ongoing processes along with reviewing the relevant documentations, interviews with process owners (waste workers and other related staff) in CHCs and then completing the checklist. Checklist questions were scored by assigning number one to standards adherence and zero to non-adherence. Next, the total score of all four dimensions was calculated and divided by the number of questions of each dimension to obtain the standard adherence both in general and separately for each dimension. Regarding that the dimension ‘sterilization and disposal’ only took place in Tabriz regional health center after collection of the waste from all CHCs in the city, data on this stage were only gathered and analyzed at this level. To verify the validity of the assessments, an external expert in the field of environmental health along with an expert from the Tabriz regional health center, randomly re-evaluated some CHCs.To examine the status of MWM process in CHCs, the assessment team was formed with the participation of environmental health officers of the health complexes  was evidenced in Tabriz CHCs. This achievement was based on four major key factors: staff participation, using systematic quality improvement method, evidence-based interventions and leadership commitment and support. Similarly, waste management improvement programs implemented in a Brazilian primary health care center were successful (Moreira and Günther, et al., et al. (et al., et al., Interventions implemented in this study were not only supported by the assessment data but also by previous literature in Iran. Staff knowledge deficiency about waste management process was raised as one of the most important problems in Iran’s primary health care centers (Mesdaghinia , et al. , which w et al., . Howeveret al., et al., et al., et al., et al., Medical waste separation and collection is the most important step in waste management. Previous studies in Iran have documented that only 25% of primary health care centers separate their hazardous waste correctly (Mesdaghinia et al., et al., et al., et al., et al., According to the evidences, lack of physical site for temporary storage, failure to comply with the standard duration of infectious waste temporary storage in CHCs and low education level of the waste workers who were responsible for collection and transportation of medical waste were among the most important reasons causing failure in temporary storage of medical waste in Iran (Mesdaghinia Our intervention plan led to 17.2% standards promotion in medical waste disposal process in Tabriz regional health center. Medical waste disposal inadequacy was mostly due to inappropriate autoclave process and equipment. As an important issue in medical waste disposal, autoclave performance control using Bowie-Dick test was suggested by literature to ensure the sterilization process which was ignored in Tabriz regional health center (Crossley, MWM standards improved about 30% in Tabriz CHCs. Using systematic and scientific quality improvement method – clinical audit, staff participation, leadership commitment and evidence-based decision-making would lead to primary health care processes quality improvement. This study has provided a scientific approach to quality improvements in MWM in primary health care centers, which has the capability to expand in other cities of Iran or other countries.This study was conducted using a systematic and scientific method and supported by the city health managers. All stakeholders in the MWM process participated in the development and implementation of interventions. It also covered all CHCs in Tabriz city.We do not have control group in the study. Moreover, due to the high cost of some interventions such as temporary storage space construction, they were not implemented.


Dear Editor,XPC, XPD, XRCC1, and XRCC3 might be associated with schizophrenia risk . There al., 2008; Derakhsal., 2008; Odemis al., 2008; Taghipoal., 2008). It hasal., 2008).ATM gene (MIM 607585) is one of the most significant genes in the DNA repair pathway encoding a vital checkpoint kinase. The ATM is critical in identifying and responding to DNA damage resulting in genome stability  and risk of schizophrenia  and risk of schizophrenia, therefore, the present case-control study was carried out.The  MIM 60755 is one al., 2020). Data oal., 2005). Statisal., 2005). Thus, al., 2008). To theIn our previous report  we provHere we used pooled samples for estimating the allelic frequency of the study polymorphisms in schizophrenia and control groups, as described previously . The PCP=0.020). The frequency of the G allele of rs609429 is positively associated with the risk of schizophrenia. Statistical analysis revealed no significant association between the allelic frequencies of rs611646 and rs228593 polymorphisms and the risk of schizophrenia  and seems to be involved in splicing, therefore, it is a functional polymorphism. The G allele leads to generation of a weak additional splicing region and subsequently, reduces the expression of ATM gene (Angèle et al., 2003[ATM gene is a candidate locus for susceptibility to schizophrenia and the variant G allele of the rs609429 polymorphism may provide valuable insight into its association with schizophrenia. More association studies on larger samples from other populations are necessary to reveal the relevance of ATM polymorphisms as potential risk factors for schizophrenia and provide a deeper understanding of the genetic causes of the disease.Our present data suggest that the The authors are indebted to the participants for their close cooperation. None.