As the situation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is still deteriorating, there has been a huge increase in the demand and use of disinfectants. Electrolyzed water (EW), as a novel broad-spectrum disinfectant and cleaner, has been widely used for several years. EW can be produced in an electrolysis chamber which contains dilute salt and tap water. It is an effective antimicrobial and antibiofilm agent, with several advantages such as on-the-spot, cheap, environmentally friendly and safe for human beings. Therefore, EW holds potential significance for high-risk settings in hospitals and other clinical facilities. EW can also be applied for wound healing, advanced tissue care, and dental clinics. The present review article highlights the latest developments and new perspectives of EW, especially in clinical fields. Furthermore, the main action modes of antibiofilm and antimicrobial will be summarized. The Center for Disease Control and Prevention (CDC) has recently reported that there is at least one person who has a healthcare-associated infection in every 31 hospital patients in any given day . HAIs arTherefore, developing effective disinfectants and antiseptics for killing pathogens and destroying the biofilm formation in the environment and human healthcare is one of the most significant steps for infection prevention and control. The medical industry has employed a number of decontamination techniques throughout the hospital and healthcare clinical field ,14,15. HElectrolyzed water (EW) is a novel disinfectant and cleaner which has been widely used in the food industry for several years to ensure the sterilization of surfaces and safety of food ,20,21,22However, some studies have reported that the application of EW is limited by factors such as the corrosion of equipment which is in contact with acidic or basic EW and the ability of organics materials  to shorten its shelf life ,38. To oThe aim of this review was to introduce recent developments and provide a new perspective with EW in the clinical field. Many characteristics of electrolyzed water in this review article were introduced including the physiochemical properties, history, limitation principle, generation methodologies, and the impact of these characteristics on the sanitizing efficacy of EW. In addition, applications of EW for microbial control in the clinical field are also discussed.The development history of electrolyzed water can be traced back for more than a century . The conElectrolyzed reduced water was invented in the early 19th century . ResearcIn 1994, with the support of the Ministry of Health, Labor, and Welfare of Japan, the functional water foundation was established to promote the use of electrolyzed water in society. Based on considerable scientific evidence related to the risk assessment of EW, in 2005, the Drugs, Cosmetics and Medical Instruments Act of Japan was revised and re-authorized an ERW-producing device as a home-managed medical device. In 2002, the Ministry authorized the use of hypochlorous acid water on designated food additives. Recently, in 2017, the US Food and Drug Administration (USFDA) also authorized hypochlorous acid  for use on food contact surfaces (FCS) . In addiElectrolyzed water (EW) is produced in an electrolysis chamber which contains hydrogen chloride (HCl) solution or dilute salt (NaCl) . Accordi− ions [These solutions are produced by the electrolysis of dilute salt (NaCl) passing through two or three cell electrolyzers with the anode and cathode separated by a diaphragm. It can produce two types of water simultaneously. Acidic electrolyzed water (AEW), with a pH of 2 to 3, available chlorine concentration (ACC) of 10 to 90, and oxidation–reduction potential (ORP) >1100 Mv, is produced at the anode side . At the − ions . The det− ions .2, OCl−, and HOCl), ORP, and pH directly play an important role in the antimicrobial efficacy of EW  decreased by the bacteria by 3.26 log CFU/mL [− are different. HOCl is neutral, whereas the hypochlorite ion (OCl−) and bacterial membrane are both negative [2. When the pH value is above 7.5, HOCl is decomposed into hydrogen ion (H+) and hypochlorite ion (OCl−) in the reversible reaction [The concentration of chlorine  indirectly influence the effectiveness of EW is better than that of underground water (hardness = 12 ppm). The hardness of water is mainly dependent on the content of calcium and magnesium [Kim et al.  examinedagnesium . There iagnesium . Moreover, the water flow rate affects the ACC. Hsu et al. reported that the total ACC and ORP of electrolyzed oxidizing water was significantly decreased when water flow rate and salt concentration increased in the feed solution . The reaThere are many advantages of EW over its toxic counterparts  in different areas such as agriculture, food hygiene, medical field and even in human surface disinfection. The advantages of electrolyzed water can be easily enumerated. 2O2) in our body as a substrate to react with neutrophils. [Salmonella or E. coli reduced >1.45 Log10 CFU/egg and >6.39 Log10 CFU/egg, respectively, after 30 s treatment of NEW [First, EW has been proposed as an environmentally friendly alternative to physical and chemical methods, which do not contain undesirable toxic contaminants . As prevrophils. . HOCl isrophils. . Medina t of NEW . Third, t of NEW . The volt of NEW . Therefot of NEW ,81,82. Ft of NEW .When tackling the disadvantages and advantages of EW, we also need to point out the adverse impact of this novel technology. First, EW is a sanitizer produced from tap water with sodium chloride (NaCl) without the addition of harmful chemicals . However2, −OCl, and HOCl) plays an important role in the antimicrobial efficacy of electrolyzed water [2O)) and its electrical neutrality [S. aureus [+, protein and DNA, which indicated that the cell wall and membrane were damaged [– cannot penetrate the microbial cell and microbial membrane because there is a lipid bilayer in the plasma membrane (hydrophobic layer) [− only exhibits an oxidizing action from outside the cell, which would inactivate functional proteins localized in the plasma membrane [– reaction on pathogens. The exact pattern of EW on microbial cells is still unclear and requires more investigations to clarify in the future.In order to produce the safe and effective use of disinfectants, numerous disinfection methods have been studied and reported over the years. Many researchers have fully studied the mechanism of traditional disinfection methods such as physical treatments (heat and irradiation etc.) and chemical disinfectants (hydrogen peroxide and chlorine dioxide etc.) . Howevered water . HOCl cautrality . In addiutrality . These m. aureus . Further damaged . Howeverc layer) . OCl− onmembrane . In addimembrane . Figure Recently, the Ministry of Health of the People’s Republic of China released three Chinese standards for materials and restricted substances in disinfectants, general requirements for hand disinfectants and general requirements for the disinfectants of mucous membrane in April 2020 ,96. In s® as an instillation fluid with a novel foam dressing and negative pressure wound therapy for the patient, the wound bed showed dramatic improvement after three days of treatment [Staphylococcus aureus count by about 3.80 log/cm2 reduction without any detrimental effect [2) in wounds while breaking biofilms, which is an important key differentiator from other products [A topical antibacterial agent, which can reduce the bacterial biological load of the wound without impairing the healing ability, is an imperative condition for therapy . Wound hreatment . Sasai el effect . Scientil effect . Additiol effect . HOCl  and catholyte (CEW) on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus hirae, Candida albicans. They found that StAEW, SAEW, and MEW reduced the agents significantly. StAEW was especially effective against test microorganism  populations, which all decreased by 100% in 1 min [Hand sanitization is the most important but simple way to remove germs, prevent the spread of germs to others and avoiding illness . For EW-in 1 min . HOCl  showed antimicrobial effectiveness (>99.9%) against S. mutans after soaking treatment for 3 min [The dental community has long sought for appropriate antibacterial products to try to control and prevent the proliferation of oral microbiome, especially during dental surgery when host barrier function is often impaired. Microorganisms related to oral hygiene include comitans ,137,138.comitans . Hsieh eor 3 min . The conor 3 min ,141. A sor 3 min . Nakano or 3 min .Experts generally agree that the daily careful cleaning and/or disinfection of environmental surfaces is an essential way to prevent hospital infection . The potThe COVID-19 pandemic has placed an immense burden on healthcare systems and economies around the world. At the time of the study, there was no effective approved vaccine and drug against SARS-CoV-2 available. With increasing hygiene and safety challenges, electrolyzed water holds a potential significance for clinical fields since disinfecting is a critical step during cutting off route transmission . Researc®, Avenova®, Ecasol™, MicroSafe® and Microcyn®. These companies claim to produce EW-based products that have a remarkable antimicrobial effect, while being safe to use around the nose, mouth, and eyes. However, the limitation of EW is that it has not been widely studied, notably for efficacy against multidrug- and extensively drug-resistant Gram-negative bacteria according with World Health Organization priority pathogens list.All the EW exhibits strong antimicrobial efficacy in different fields such as food and hard surface as well as agriculture, medical, and dentistry without irritation . EW has SAEW is the most studied EW and has shown its pH-neutral properties. HOCl was found to be nonirritating and non-sensitizing in various animal safety models. The composition of SAEW solution is relatively simple, and once it becomes exposed to the air, the active ingredients will decompose and its sanitizing efficacy drops . Researc2 off-gassing. It recently emerged with great potential for clinical applications. However, the antimicrobial effect of EW is influenced by the presence of organic matter, water pollutants, and the hardness of the product. Therefore, a dynamic and advanced EW production system or the hurdle technology of combing with multiple technologies-based EW that are able to overcome currently limitations. These may expand the use of EW in clinical applications.EW is an effective disinfectant, with several advantages such as on-the-spot, cheap, environmentally friendly and safety production. Nowadays, with the development of a novel popular type of SAEW, some limitations have been resolved. It has been reported that SAEW does not irritate the hands, skin, and mucous membranes, and causes no safety issues from Cl


Aggression is a clinical symptom of various psychiatric disorders that can be conceptualised as a physical act towards another person with the intent to cause harm. In antisocial personality disorder (ASPD), aggression is a frequent manifestation that differently compromise therapeutic and prognostic goals according to its impulsive or premeditated categorisation. ASPD is characterised by high levels of impulsivity, psychopathic traits, and a high prevalence of co-morbid substance use disorders (SUDs). Aggression in ASPD patients may determine long and recurrent imprisonment thus representing a challenge clinicians and legal experts face.Our aims were to characterise impulsive and premeditated aggression in male ASPD offenders as well as to determine the potential role of SUDs, impulsivity, and psychopathic traits as predictors.In this cross-sectional study we evaluated a sample of ASPD offenders with a battery of clinical and psychometric, standardised instruments: the Psychopathy Checklist-Revised (PCL-R), the European Version of the Addiction Severity Index (EuropASI), the Barratt Impulsivity Scale Version 11 (BIS-11), and the Impulsive/Premeditated Aggression Scale (IPAS).We used a total sample of 134 offenders, all of whom were male. ASPD patients (n = 96) had a 71.9% prevalence of impulsive aggression and a 28.1% prevalence of premeditated aggression. ASPD patients with impulsive aggression had significantly lower scores of total PCL-R (p<0.01) factor 1 and interpersonal facet 1 (p<0.05), compared with ASPD patients with premeditated aggression. ASPD patients with impulsive aggression and ASPD patients with premeditated aggression had comparable BIS-11 mean scores, and exhibited an equal prevalence of SUDs. The interpersonal facet 1of the PCL-R predicted the aggression type (p<0.05) in ASPD patients, and the exponential beta value for facet 1 was 1.42 .The aggression type that is associated with ASPD is mainly impulsive in nature. ASPD patients who have higher scores of psychopathic traits have a lower probability of exhibiting impulsive aggression and a higher probability of exhibiting premeditated aggression. Although ASPD patients have high levels of impulsivity and a high frequency of SUDs, these two variables were not predictors of the aggression type. Physical aggression is common in individuals with antisocial personality disorder (ASPD) and is linked to criminal acts, psychopathy, impulsivity, and substance use disorders (SUDs) . AlthougResearch on aggressive behaviours in incarcerated populations is supported by the World Health Organization due to its double interest: it is an issue of a minority population, and it is related to high levels of human suffering. Aggression is a public health issue that can certainly be prevented .The prison context is characterised by a high prevalence of aggressive acts and inmate-to-inmate victimisation . The wayThe assessment of aggressive acts involves the evaluation of an individual’s physical and mental health state as well as the motivations that led to those aggressive acts . When deHuman aggression can be classified into two types: impulsive aggression, also called reactive aggression, and premeditated aggression, also called instrumental or proactive. Non-dichotomic classifications include other forms of aggression namely those associated with psychotic psychopathology . This clActs of impulsive aggression are characterised by uncontrolled and exaggerated responses to the stimuli which provoke them. Individuals who exhibit this type of aggression tend to show high levels of physiological arousal associated with stress, neurocognitive difficulties, and impulsive personality traits , 13.Conversely premeditated aggression corresponds to acts that materialise a previously defined plan aiming at a specific kind of gain. This type of aggression is associated with individuals who not only exhibit low physiological activation associated to stress, but who also present psychopathic personality traits , 13.The clinical approach to aggression implies that each aggressive act should be classified as impulsive or premeditated such that the best possible strategy is selected at each moment , 14. A fFor clinical and research purposes, aggression can be categorised using self-administered instruments, such as the Impulsive/Premeditated Aggression Scale (IPAS)  and the It is important to distinguish the concept of aggression from the concept of impulsivity and, even more, impulsive aggression from impulsivity. The clinical conceptualisation of impulsivity, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), implies a behavioural and cognitive disinhibition, an immediate reaction to stimuli, an unplanned reaction at the spur of the moment, or a reaction with no regard for consequences .The Barratt Impulsiveness Scale (BIS-11) is one of the most widely used psychometric instruments for research purposes concerning impulsivity . The defThe relationship between impulsive aggression, premeditated aggression, and impulsivity is highlighted in various studies that address the classification of aggression.For example, impulsivity—measured by the BIS-11—was positively correlated with both impulsive and premeditated aggression dimensions as measured by the IPAS , 22, 23 ASPD is a psychiatric diagnosis defined as a pervasive and persistent pattern of behaviour and emotional response characterised by a failure to conform to lawful and ethical behaviour; an egocentric, callous lack of concern for others, accompanied by deceitfulness, irresponsibility, manipulativeness, risk taking, and high levels of impulsivity. To be diagnosed with ASPD, an individual must be aged 18 years or older at the time of diagnosis and should have displayed features of conduct disorder prior to the age of 15 .One of the most relevant features of ASPD is its high prevalence, which is 3% in the general population and may reach up to 50% in the prison population , 26–28.Aggressive behaviour is a symptom of ASPD that is associated with poor prognosis and difficult treatment. ASPD is the only psychiatric disorder associated with an increase of impulsive and premeditated aggression acts –31.On the other hand, children and adolescents who display aggressive acts are more prone to developing ASPD in their adult lives , which rPsychopathy is a concept related to ASPD, and discussion has been held regarding the relationship between the two. ASPD tends to focus on antisocial behaviour, while psychopathy tends to focus on emotional dysregulation . There sPsychopathy can be defined as a clinical syndrome composed of a set of characteristics that manifest in interpersonal relationships, affective reactions, and behaviours. Affected individuals demonstrate egocentrism, pathological lying, manipulation, irresponsibility, impulsivity, novelty pursuit, limited behavioural control, insensitive affection, lack of empathy, guilt, or remorse, and a set of unethical and antisocial behaviours that are not necessarily criminal. These characteristics appear to be hereditary, manifest in childhood, and are relatively stable throughout adolescence and adulthood .The Psychopathy Checklist-Revised (PCL-R) is the gold standard for the diagnosis of psychopathy . ScientiSUDs are highly comorbid with ASPD and are related to both aggression and criminal behaviour , 39. AltThe present study’s objective was to firstly determine the prevalence of impulsive and premeditated aggression in patients with ASPD in a prison context, and secondly determine whether or not impulsivity, psychopathy, and SUD are predictors of aggression type.Centro Hospitalar de São João (Document no. 48.14) and the hosting institution, the General Direction of Probation and Prison Services. Participation was voluntary, no reward was offered in exchange for participation. The participants were able to leave the research at any time without any consequences, and the individuals who decided not to participate received the same treatment offered to participants. In accordance with the Declaration of Helsinki, written, informed consent was obtained after explaining the procedures to each participant. The study followed a cross-sectional design.The sample of the present study included 134 male inmates of a medium-high security penitentiary institution in the North of Portugal. The subjects were recruited through the use of a convenience sampling strategy between January and March of 2015. All the individuals in this institution had received sentences longer than 10 years. The penitentiary institution had a total number of 710 inmates at the time of the protocol application. The research protocol was formally approved by the ethics committee of the Participants were included if they were aged 18 years or older and had been referred to the clinical services after preforming acts of physical aggression towards other inmates. Their ability to read and provide their written, informed consent was also considered for their inclusion. Participants were excluded if they exhibited a psychiatric or neurological disorder in an acute and non-treated episode.After the occurrence of a physical aggression incident in the forensic institution the inmates were referred for a clinical psychiatric evaluation. The local forensic psychiatrist, who had prior clinical knowledge of all the institution inmates, established the psychiatric diagnoses using the Mini-International Neuropsychiatric Interview (MINI). After the establishment of the appropriated treatment plan for each individual, the participation in the study protocol was proposed to the inmates. Those who agreed to participate after verbal information about the study protocol and procedures signed an informed written consent form and were submitted to the application of four psychometric instruments: two in the form of a standardized clinical interview, the Psychopathy checklist revised (PCL-R) and the Addiction severity index European version (EuropASI); and two self-administration psychometric instruments, the Barratt Impulsivity Scale eleven version (BIS-11), and the Impulsive Premeditated Aggression Scale (IPAS). The participants were interviewed and submitted to the psychometric assessment in the penitentiary institution’s clinical department. Finally, all inmates were subject to forensic security measures and received the appropriate treatment whether or not they had accepted to participate in the study protocol .The primary outcome was the categorisation of aggression by applying IPAS, while the secondary outcomes were impulsivity, psychopathic traits, and the presence and severity of SUDs.The MINI is a short, structured, diagnostic interview for psychiatric disorders and is performed according to the DSM-IV and ICD-10 criteria. It was designed to allow a brief and accurate psychiatric evaluation, which proves useful in clinical trials and epidemiologic studies. In this study, the MINI was used to diagnose ASPD and psychiatric co-morbidities, such as SUDs, as well as anxiety and depressive disorders. Participants were assessed with the Brazilian Portuguese version 5.0.0 of the MINI .The specificity values for the diagnoses performed with the MINI’s aid were between 0.95 and 0.97, while the sensitivity values were between 0.67 and 0.94 .The PCL-R measures psychopathic traits by collecting information from clinical records and conducting a semi-structured interview . The 20 The PCL-R’s reliability was recently re-evaluated  . The PCLThe PCL-R’s quotation implies extensive clinical knowledge of the patients was obtained during the interview as well as from alternative sources. In this study, the PCL-R was quoted by the admitted patients’ assistant psychiatrist. This psychiatrist (with eight years of experience working with ASPD patients in forensic settings) had access to each patient’s clinical information as well as information from other sources, namely records from other physicians who had contact with the patient, legal and court records, and prison records held by guards and educators; in other words, the psychiatrist that quoted the PCL-R had detailed clinical and contextual knowledge of each participant.The EuropASI was applied to access the SUDs’ severity. This semi-structured interview offers an inventory of problems that occurred over the previous month in six areas: physical health, work income, drug use, legal status, family and social relationships, and psycho-emotional status. The EuropASI also assesses one’s history of suicide attempts, and one’s criminality type. This multidimensional clinical and research instrument is an adapted version of the Addiction Severity Index (fifth version) .The composite scores of each dimension ranged from 0 to 1, while higher scores indicated greater severity. The reliability measures indicated moderate to good internal consistency in the European samples  , 51.The Barratt Impulsivity Scale Version 11 (BIS-11) is a self-report questionnaire used to assess a patient’s general impulsivity . The curThe IPAS is a 30-item self-report questionnaire used to rate aggressive acts that occurred over the previous six months . Items aThe structural properties of the IPAS were previously validated in a Portuguese forensic population. Each individual’s IA and PM levels were obtained through the sum of 21 of the IPAS’s 30 items; the IA factor comprised ten items , while the PM factor comprised eleven items . In the Portuguese validation study, inmates’ IA and PM subscales scored Cronbach’s alpha values of 0.89 and 0.88, respectively [Analyses were carried out using IBM SPSS Statistics for Mac, Version 22.0  Descriptive statistical measures were used to characterise the groups. Parametric (t-test for independent samples) and/or non-parametric tests  were used to test the hypotheses, and a logistic regression analysis was employed to investigate the significant variables associated with the prediction of aggression categorisation using Vittinghoff’s recommendations for small samples .The sample comprised 134 individuals with a mean age of 37.8 ± 9.2 years, of which 71.9% (n = 96) were single and 49.4% (n = 66) had children. The mean education level was 7.1 ± 2.9 years, while the mean length of imprisonment at the time of assessment was 112.9 ± 70.6 months. A total of 64.2% (n = 86) of the inmates had been convicted for violent crimes .In the entire sample, 71.6% (n = 96) of the individuals had ASPD, 56.7% (n = 76) of the individuals presented SUDs, 31.5% (n = 42) had depressive disorders, 28.1% (n = 37) had anxiety disorders, 28.4% (n = 38) exhibited psychopathy, 30.3% (n = 41) had personal histories of suicide attempts .Impulsive aggression was detected in 71.8% (n = 69) of the individuals with ASPD, while premeditated aggression was detected in 28.2% (n = 27) of the individuals with ASPD. Individuals with ASPD had a lower frequency of impulsive aggressive acts  and a higher frequency of premeditated aggressive acts  than individuals without ASPD.Individuals with ASPD had a higher mean score in the IPAS premeditated aggression dimension (p<0.05) than individuals without ASPD. Individuals with ASPD and those without ASPD had comparable scores in the IPAS impulsive aggression dimension.Individuals with ASPD and those without ASPD were comparable in terms of their sociodemographic characteristics, their prevalence of anxiety and depressive disorders, and their personal history of suicide attempts.Individuals with ASPD had a higher mean score in all PCL-R factors and facets (p<0.05) than individuals without ASPD. The BIS-11 impulsivity measure was comparable in both groups—those with and without ASPD .By comparing ASPD individuals with psychopathy (n = 37) to ASPD individuals without psychopathy (n = 59), we observed that, in our sample, they were comparable in terms of sociodemographic characteristics, psychiatric co-morbidities, as well as BIS-11 and EuropASI scores.ASPD individuals with SUDs had higher mean scores in the self-control first-order factor and non-planning second-order factor of the BIS-11 than ASPD individuals without SUDs (p<0.05).Individuals with ASPD had a higher frequency of both violent crimes  and SUDs  than individuals without ASPD. Addiction severity in all the EuropASI dimensions was similar in both groups either with or without ASPD .ASPD individuals with impulsive aggression (n = 69) had significantly lower scores of total PCL-R , factor 1, and facet 1  (p<0.05) than ASPD individuals with premeditated aggression (n = 27). ASPD individuals with impulsive aggression had a lower probability of exhibiting psychopathy  than those with premeditated aggression. ASPD individuals with premeditated aggression had a higher probability of showing psychopathy  than those with impulsive aggression, while ASPD individuals with psychopathy had a 51.4% prevalence of impulsive aggression (n = 19).ASPD individuals with impulsive aggression were similar to ASPD individuals with premeditated aggression regarding impulsivity, as measured by the BIS-11, in both the total score and the first and second-order factors. ASPD individuals with impulsive aggression were similar to ASPD individuals regarding premeditated aggression in their sociodemographic and criminal characteristics, prevalence and severity of SUDs, prevalence of anxiety and depressive disorders.2 of 0.14). The exponential beta value for facet 1 was 1.42 , meaning that, for each increase in one unit of the interpersonal facet, the OD for premeditated aggression increased by 1.42.A binary logistic regression was performed to determine possible predictive factors of aggression type in ASPD individuals. Using a forward, stepwise, conditional methodology, variables that were different between impulsive and premeditated ASPD individuals were included in the analysis, including psychopathy, the PCL-R, factor 1, and facet 1 . Facet 1 reliably distinguished between impulsive and premeditated aggression in ASPD individuals  had higher mean scores of PCL-R factor 1 and facet 2 than those who had not committed violent crimes (n = 48) (p<0.05). The frequency of violent crimes was higher in individuals with ASPD , lower in individuals with SUDs , and higher in single-status individuals  than the frequency of individuals who did not commit violent crimes. Individuals who committed violent crimes and those who did not commit violent crimes were comparable in their aggression categorisation, BIS-11 scores, EuropASI scores, prevalence of anxiety and depressive disorders, and in their personal history of suicide attempts.Impulsive aggression, expressed as a dimension, was positively correlated with the BIS-11 total score and all first- and second-order factors (p<0.05). Impulsive aggression wasn´t correlated with neither the PCL-R nor the EuropASI.Premeditated aggression, expressed as a dimension, was positively correlated with the BIS-11 total score and all first- and second-order factors (p<0.05). Premeditated aggression was positively correlated with the PCL-R total score, facet 1 , and facet 3 (lifestyle) (p<0.05). Premeditated aggression was not correlated with the EuropASI .In this study we observed that ASPD individuals commit less impulsive aggressive acts and more premeditated acts than individuals without ASPD. Nevertheless, impulsive aggression was the principal aggression type in ASPD individuals.Furthermore, the interpersonal facet 1 of PCL-R was a predictor of the aggression type in ASPD patients. Specifically, individuals with ASPD who presented glibness, superficial charm, grandiose sense of self-worth, pathologic lying, conning, and manipulative behaviour  were more likely to exhibit acts of premeditated aggression, while individuals with preserved emotional function were more likely to express impulsive aggression.These personality characteristics emerged as predictors of premeditated aggression that point to the importance of emotional insensitivity when learning about how aggressive behaviour is used to obtain personal benefits , 57. ConIn this study, individuals with ASPD and psychopathy exhibited a higher prevalence of premeditated aggression than impulsive aggression. However, when considering the psychopathy diagnosis, the prevalence of premeditated and impulsive acts was similar, with a 1:1 ratio.The effect of the psychopathic traits on the distinction between individuals with premeditated and impulsive aggression was also verified by the absence of correlations between the impulsive aggression dimension of the IPAS and the PCL-R in addition to the presence of a positive correlation between the premeditated aggression dimension and the total score of the PCL-R, facet 1 , and facet 3 (lifestyle) of the PCL-R.Several authors suggest that the presence of psychopathy is related to an increase in an individual’s number of premeditated aggressive acts , 59–62. In the present sample, the scores obtained from the PCL-R as well as the prevalence of psychopathy were higher  than those reported by other authors in prison populations (roughly 15%) . This maAggression type was not associated with the studied sociodemographic or criminal characteristics of age, educational level, relationship status, presence of offspring, criminality type, or average time spent in prison, thus reinforcing the predictive value of facet 1. In fact, physical aggression towards others tends to arise in childhood and is maintained throughout life—regardless of the types of relationships maintained and offspring produced—and is additionally related to different types of crime .This study’s participants demonstrated a mean age, educational level, relationship status, presence of offspring, criminality type, and average time spent in prison similar to those described for the Portuguese prison population with the same type of criminal record .In the entire sample, individuals with a history of conviction for violent crimes had a higher prevalence of ASPD, a lower prevalence of SUDs, and higher scores on the PCL-R, although the history of conviction for violent crimes had no impact on the classification of current aggressive acts. Violent crime has been associated with emotional insensitivity, and in our study, we replicate this finding .In this study’s sample, the prevalence of SUD co-morbidity with ASPD was high and comparable to other studies. Other authors have also reported a high prevalence of this co-morbidity, at 55% , 53% 3838, 84.5%We expected that individuals with SUDs would have a significant increase in their frequency of impulsive acts, although this result was not realised. We also verified that neither impulsive nor premeditated dimensions of aggression correlated with the SUD severity as measured by the EuropASI. Nevertheless, drug use and problems related to consumption, such as money debts, cravings, and withdrawal , may leaInterestingly, the presence of co-morbid depressive disorders had no effect on aggression type. Depressive disorders have been associated with poorer impulse control and aggressive behaviour, and patients with major depression have shown higher impulsivity and more severe aggression than controls and were more likely to commit violent crimes . The occThe prevalence of co-morbidity between ASPD and anxiety disorders reported in the literature is 50% , 66, 74;Impulsivity, as measured by the BIS-11, was similar in individuals with and without ASPD. In ASPD patients, impulsivity was similar in individuals with impulsive aggression as well as in individuals with premeditated aggression, although individuals with premeditated aggression tended to have higher BIS-11 scores than those with impulsive aggression. The IPAS dimensions of impulsive and premeditated aggression had highly positive correlations with the BIS-11 total scores as well as first- and second-order factors. Previous studies report positive correlations between the BIS-11 and the IPAS impulsive aggression dimension as well as between the BIS-11 and the IPAS premeditated aggression dimension , 23. FurThe small sample size and the fact that the sample exclusively comprised men may limit the results’ generalisation, as we do not know whether or not aggression in ASPD women exhibits similar characteristics. There are also limitations related to the probable influence of contextual variables, since research studies within a forensic facility context can change the way inmates respond to self-assessment instruments. Firstly, inmates may believe that their participation in research might convey some personal benefits . Secondly, we should consider that the legal circumstances of each participant can modify their types of responses. Thirdly, the participants were subjected to long sentences, thus making it difficult to generalise the results to inmates with shorter sentences. In psychiatric evaluation, we should have included the screening for attention-deficit/hyperactivity disorder due to its high co-morbidity with ASPD . FinallyIn future research, including assessment tools that externally, longitudinally quantify the individual acts of aggression may prove useful, such as the Modified Overt Aggression Scale. Future studies should additionally include ASPD patients from a general population sample.The type of aggression that is associated with ASPD is mainly impulsive in nature. Individuals with emotional dysfunction have a lower probability of exhibiting impulsive aggression and a higher probability of exhibiting premeditated aggression. Although ASPD patients have high levels of impulsivity and a high frequency of SUD, these two variables were not predictors of aggression type.In order to obtain validated evidence that may guide the treatment of aggression in ASPD patients and translate research concerning aggression to clinical practice in forensic settings, the clear definition of aggression type may benefit the design of clinical trials in ASPD patients , 14.The high prevalence of aggressive acts and co-morbid psychiatric disorders in forensic settings requires a complex and integrated psychiatric assessment that should address the needs of organised forensic psychiatric services in prisons.


Catgut-embedding therapy combined with minimally invasive surgery has been used for treating slow transit constipation (STC) widely. However, the application effect of catgut-embedding therapy combined with minimally invasive surgery for STC are unclear. This study aims to evaluate the application effect of catgut-embedding therapy combined with minimally invasive surgery for STC.Randomized controlled trials of catgut-embedding therapy combined with minimally invasive surgery in the treatment of STC will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database from inception to July, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3.This study will summarize the present evidence by exploring the application effect of catgut-embedding therapy combined with minimally invasive surgery in the treatment of STC.The findings of the study will provide helpful evidence for the application effect of catgut-embedding therapy combined with minimally invasive surgery in the treatment of STC, facilitating clinical practice and further scientific studies.The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.DOI 10.17605/OSF.IO/7HVZB Some scholars have reported that the incidence of functional constipation in China is about 10% to 15%. Due to its unclear pathogenesis and unclear treatment direction, there is a lack of satisfactory therapeutic methods. According to the characteristics of intestinal and anorectal functions and dynamics that lead to constipation, there are three types: slow transit constipation (STC), outlet obstruction constipation and mixed constipation.Constipation has become an important common disease affecting people's quality of life, which is prone to induce cardiovascular and cerebrovascular diseases. This concept was first put forward by Proton and Lennard-Joners in 1986. After nearly three decades of understanding, STC is now considered to be a type of refractory functional constipation characterized by slow delivery of feces in the intestinal tract, especially in women of childbearing age. Its main clinical features are less frequent defecation for a long time, once more than 3 days, or even 6 to 10 days 1 time, or no sense of defecation, dry and hard stool, defecation is laborious, and can also be combined with abdominal distension, anxiety, depression, sleep disorders and other symptoms, the symptoms are stubborn, and the treatment is intractable.Colonic STC, also known as colonic weakness, is caused by dysfunction of large intestine and abnormal conduction, which leads to prolonged defecation cycle and difficulty in defecation. The treatment of STC by traditional Chinese medicine, such as catgut-embedding therapy, has significant advantages, that is, significant curative effect, non-toxic side effects, high cure rate and no disease recurrence. Moreover, catgut-embedding therapy combined with minimally invasive surgery has less adverse reactions and better efficacy compared with normal surgery.,7In recent years, the incidence of chronic constipation has showed a slow upward trend and STC is the most common type of chronic constipation. The etiology is not clear. At present, the main treatment methods are stimulant, biofeedback and surgery. However, long-term use of laxatives can damage intestinal function, lead to drug dependence, more persistent constipation, and even cause melanosis of the colon. Surgical resection of the intestinal segment cannot be reduced, so careful selection should be made. However, there is no systematic review and meta-analysis regarding the application effect of catgut-embedding therapy combined with minimally invasive surgery for STC. Thus, this study will assess the application effect of catgut-embedding therapy combined with minimally invasive surgery for STC.In view of the current treatment status of constipation, safety and effectiveness become the main indicators to measure a new treatment. Because STC accounts for the majority of constipation, the previous treatment methods only solve one of them. Theoretically speaking, it cannot eliminate all the causes of defecation disorder, so it cannot achieve satisfactory curative effect. Catgut-embedding therapy mainly aims at slow transit problem, while anal minimally invasive surgery mainly solves outlet obstruction problem and achieves satisfactory curative effect. From total colectomy to subtotal colectomy, from peristaltic anastomosis with ileocecal preservation to retrograde peristalsis anastomosis, from single operation method to combined operation method, from open surgery to minimally invasive surgery. The establishment and development of surgical methods not only effectively improve the constipation symptoms of patients, but also reduce the pain and postoperative complications, the quality of life of patients was improved.22.1This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P). Moreover, it has been registered on open science framework (OSF) on July 20, 2020 (Registration number: DOI 10.17605/OSF.IO/7HVZB).2.2Ethical approval is not required as there is no patient recruitment and personal information collection, and the data included in our study are from published literature.2.32.3.1Randomized controlled trials (RCTs) including catgut-embedding therapy combined with minimally invasive surgery for STC will be included. The language will be limited to Chinese and English.2.3.2 regardless of nationality, race, age, gender, and source of cases.All the included cases conform to the “ RomeIVcriteria for Functional Gastrointestinal Disorders ”,2.3.3The control group was treated with minimally invasive surgery only, and minimally invasive surgery type was not limited, such as partial amputation of internal anal sphincter, circumcision of rectal mucosa and repair of anterior / posterior process of rectum; the treatment group was treated with catgut-embedding therapy combined with minimally invasive surgery. The duration of treatment in both groups was not limited.2.3.4 ④ According to Bristol fecal characteristics score, there are seven grades in this score, which can be divided into seven grades, that is, 7 points for separated hard mass, 6 points for lumpy shape, 5 points for discontinuous and cracked sausage stool, 4 points for continuous and complete sausage stool, 3 points for soft lump, 2 points for mud like stool and 1 point for water sample.⑤ Wexner constipation score: including defecation frequency, defecation difficulty, defecation time and other 8 items, the score range is 0 to 30 points, the higher the score is, the more severe the constipation degree is, and the score of healthy people is less than 8 points.⑥ Gastrointestinal quality of life index (GIQLI): including 36 questions related to physiology, psychology, social activities and family life, the questionnaire objects were graded and scored within 2 weeks. The score range was 0 to 144 points. The higher the score, the better the gastrointestinal quality of life. The reference value of healthy people was (125.8 ± 13.0).The main outcome measure was clinical efficacy. According to the score before and after treatment, ① Clinical cure rate: the proportion of patients who defecate more than 3 times a week. ② Clinical remission rate: the proportion of patients whose clinical symptoms did not reach the cure level but improved significantly compared with that before treatment. ③ Frequency of spontaneous defecation per week: the frequency of spontaneous defecation per week after treatment. Total effective rate = clinical cure rate + obvious efficiency + effective rate.2.4(1)The treatment group used other traditional Chinese medicine therapies, such as acupuncture and moxibustion, traditional Chinese medicine, and so on;(2)The outcome indicators of the original study did not meet the requirements;(3)As for duplicate published literature, select the literature with the most complete data;(4)Literature with incorrect or incomplete research data that cannot be obtained after contacting the author.2.5PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database were searched by computer to collect RCTs of catgut-embedding therapy combined with minimally invasive surgery in STC, and the retrieval time was from the establishment of each database to July 2020. At the same time, search Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry to get more comprehensive data. Keywords were:“ catgut-embedding therapy”, “ minimally invasive surgery ”, “slow transit constipation”, et al. PubMed retrieval strategies are shown in Table 2.6Endnote X7 was used for literature management. Two researchers independently screened the literature, extracted the data and cross checked them. In case of disagreement, the third researcher was consulted to assist in judgment, and the lack of data was contacted with the author as much as possible to supplement. In the process of literature screening, first read the title and abstract, and then read the full text after excluding the obviously unrelated literature to determine whether it is included. Excel 2019 was used to set up a data extraction table to extract data.The extraction contents were as follows: ① Included basic research information ; ② The treatment plan of the treatment group and the control group, such as the name and measure of the surgery used in the control group; the name and measure of the surgery, the acupoints, frequency, treatment course of catgut-embedding therapy used in the treatment group; ③ Risk evaluation items of bias in RCTs; ④ Related outcome indicators. The literature screening process is shown in Figure 2.7Two researchers independently evaluated the risk of bias in RCTs in accordance with the Cochrane Handbook of Systematic Reviewers, including the following items: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. The quality of studies was classified as being at of high, unclear or low risk of bias. In case of disagreement, a third researcher decided.2.82.8.1P≥.1, there was no inter-study heterogeneity, If P < .1, it indicated inter-study heterogeneity. At the same time, I2 value was used to quantitatively evaluate the inter-study heterogeneity. If I2≤50%, the heterogeneity was considered to be good, and the fixed-effect model was adopted. If I2 > 50%,it was considered to have significant heterogeneity, the source of heterogeneity would be explored through subgroup analysis or sensitivity analysis. If there was no obvious clinical or methodological heterogeneity, it would be considered as statistical heterogeneity, and the random-effect model would be used for analysis.Descriptive analysis was used if there was significant clinical heterogeneity between the two groups and subgroup analysis was not available.The RevMan 5.3 software provided by the Cochrane Collaboration was used for statistical analysis. ① For dichotomous variables, relative risk was used for statistics. For continuous variables, weighted mean difference was selected when the tools and units of measurement indicators are the same, Standardized Mean Difference was selected with different tools or units of measurement, and all the above were represented by effect value and 95% Confidence interval. ② Heterogeneity test: Q test was used to qualitatively determine inter-study heterogeneity. If 2.8.2If data is missing or incomplete, we will contact the relevant authors to obtain the data. If not, this study will be removed.2.8.3In order to reduce the clinical heterogeneity between studies, subgroup analysis was conducted according to the age, which were divided into minors, adults and the elderly. Subgroup analysis was carried out for the included studies according to the types of minimally invasive surgery, the time and acupoints of catgut-embedding therapy.2.8.4In order to test the stability of meta-analysis results of indicators, a one-by-one elimination method will be adopted for sensitivity analysis.2.8.5For the major outcome indicators, if the included study was≥10, funnel plot was used to qualitatively detect publication bias. Egger's and Begg's test are used to quantitatively assess potential publication bias.2.8.6 will be used to assess the quality of evidence. It contains 5 domains . And the quality of evidence will be rated as high, moderate, low, and very low.The Grading of Recommendations Assessment, Development, and Evaluation3 Due to the unknown etiology and unclear pathogenesis, there is no effective treatment for it. Western medicine treatment includes drug treatment, surgical treatment, biofeedback therapy, etc., but long-term use of laxatives and prokinetic drugs will aggravate the damage of intestinal wall nerves. Surgical treatment belongs to traumatic treatment, which is easy to cause abdominal pain and flatulence and other side effects. Clinical study found that the effective rate of catgut-embedding therapy combined with surgical treatment in STC was improved.STC is the most common type of functional constipation. It is known that the main cause is the colon dynamic disorder, the specific mechanism is not clear. Some researchers have studied fiber loss, autonomic neuropathy, and enteric and autonomic nervous systems. It is found that the number of Cajal cells in the colon of SCT patients decreased and the ultrastructure changed, the distribution was irregular and the cell volume decreased, and the cytoplasmic processes were interrupted or absent.,17 It is considered that the continuous stimulation of acupoints with thicker catgut can enhance the tension and excitability of intestinal smooth muscle and promote intestinal peristalsis.Catgut-embedding therapy is a method of embedding catgut into acupoints or body, through which can stimulate the acupoints through the long-lasting and gentle physiological, physical and biochemical stimulation. By stimulating acupoints, the regulation of meridians and collaterals can be triggered so as to change the balance of endocrine and neurohumoral in human body. It is found that catgut-embedding at acupoints can improve the status of internal sphincter and pelvic floor muscle, reduce anal pressure and promote the recovery of constipation.–21The lack of accurate preoperative examination of the colon lesion leads to the diversification of STC surgical treatment. There is no perfect STC procedure. Surgical methods have experienced from simple to complex, then to individual selection, from a single surgical method to a variety of surgical methods, from transabdominal open surgery to laparoscopic minimally invasive surgery. To relieve the symptoms of constipation and reduce the incidence of complications is always the goal of STC surgical treatment. Compared with other surgery, minimally invasive surgery design has the advantages of good curative effect, small trauma, quick recovery and less complications. It can meet the individual needs of different constipation groups.However, there is no systematic review and meta-analysis assessing application effect of catgut-embedding therapy combined with minimally invasive surgery for treating STC. This is the first protocol for systematic review and meta-analysis evaluating the application effect of catgut-embedding therapy combined with minimally invasive surgery for treating STC. This systematic evaluation and meta-analysis can provide evidence-based evidence for clinicians to use catgut-embedding therapy and minimally invasive surgery in the treatment of STC. However, the study has some limitations. Due to different types of acupoints, the timing of minimally invasive surgery, the results were affected and the bias was caused. In addition, we only search for articles in Chinese and English, which may cause certain publication bias.Data collection: Yanpeng Xie and Yihua FanFunding support: Xiangdong Yang and Yanfei XiangLiterature retrieval: Wei Fan and Tianyu ZhaoSupervision: Xiangdong YangWriting – original draft: Yanpeng Xie and Yihua FanWriting – review & editing: Xiangdong Yang and Yanfei Xiang


Compared to TDC, children with SPD show reduced microstructural integrity of the SCP and MCP, characterized by reduced FA and increased MD and RD, which correlates with abnormal auditory behavior, multisensory integration, and attention, but not tactile behavior or direct measures of auditory discrimination. In contradistinction, decreased CP microstructural integrity in SPD correlates with abnormal tactile and auditory behavior and direct measures of auditory discrimination, but not multisensory integration or attention. Hence, altered cerebellar white matter organization is associated with complex sensory behavior and attention in SPD, which prompts further consideration of diagnostic measures and treatments to better serve affected individuals.Sensory processing dysfunction (SPD) is characterized by a behaviorally observed difference in the response to sensory information from the environment. While the cerebellum is involved in normal sensory processing, it has not yet been examined in SPD. Diffusion tensor imaging scans of children with SPD ( Sensory processing dysfunction (SPD), also referred to as sensory integration disorder and sensory processing disorder, is a behaviorally described neurodevelopmental difference estimated to affect up to 16% of children in the general population, and 40–80% of children with other comorbid neurodevelopmental disorders, such as autism spectrum disorder (ASD) or attention deficit hyperactivity disorder  at the cellular, structural, and functional level Kern, . SeveralDTI is a neuroimaging method that measures the diffusion of water in the brain's white matter. It allows us to visualize and quantify direction, uniformity, and orientation of WM tracts for the examination of structural connectivity, e.g., between cerebellum and sensory cortex areas in ASD , as well as the major input tract to the cerebellum, the middle cerebellar peduncle (MCP), at its decussation. We also investigate two control WM regions in the brainstem, the left and right cerebral peduncles (CP-L and CP-R) at the midbrain, which contain cerebral fiber tracts that connect to subcortical structures in the lower brainstem and spinal cord . We hypoHowever, we postulate a dissociation in the relationship of WM microstructure in the cerebrum vs. cerebellum with sensory processing and behavior. We hypothesize that the CP will most strongly correlate with unimodal sensory processing measures such as the Differential Screening Test for Processing (DSTP) and the Auditory and Tactile measures of the Sensory Profile, consistent with prior results from cerebral tracts in SPD  completed either the parent-report Child Symptom Inventory or the Vanderbilt ADHD Diagnostic Rating Scale  Sensory Neurodevelopment and Autism Program phenotype database (pediLAVA) and neuroimaging collection. The study design was approved by the UCSF Institutional Review Board and informed consents and assents were obtained from primary caregivers and study participants, respectively, in accordance with IRB policy. Consistent with previous studies in our lab, research designation of SPD was determined using the long-form Sensory Profile . Scan time totaled 60 min per participant.Brain scans were performed using a 12-channel head coil on a 3-Tesla MRI scanner . Whole-brain DTI scans were obtained using a diffusion-weighted echoplanar sequence with echo time = 8,000 ms; repetition time = 109 ms, field of view = 220 mm; voxel size = 2.2 × 2.2 × 2.2 mm; 64 diffusion directions at b-value of 2,000 s/mm2 volume. To evaluate subject motion, relative displacement was quantified by calculating the transformation of each diffusion volume to the reference. Included subjects were verified to be free of image artifacts and excess movement, defined as more than 2 mm of translation and/or rotation. A heteroscedastic two-sample Student's t-test verified that there were no significant differences between SPD and TDC groups in movement during the DTI scan (p > 0.05) The registered images were skull-stripped using the Brain Extraction Tool (BET) from FSL. The Diffusion Toolbox in FSL (DTIFIT) was applied on corrected diffusion scans to calculate FA, MD, RD, and AD maps.The FMRIB Software Library (FSL) version 5.0.8  software was used for image processing. All steps of the image processing pipeline have been reported previously  in FSL , DSTP components , and the SP subtests  in the five examined tracts were investigated by each group separately. Individual one-way ANOVAs were conducted to determine group interaction effects of significant correlations. Multiple comparison corrections were not performed because a prior hypothesis existed for each statistical test performed. Additional post-hoc t-tests were run to assess differences in mean AD, FA, MD, and RD values in the SCP-L and -R, MCP, and CP-L and -R tracts between the subset of the SPD cohort with ADHD and the subset of the SPD cohort without ADHD.All statistical analyses were conducted using SPSS statistical software. Group characteristics were compared using Student's p = 0.02).A total of 42 children with SPD , and 39 TDC  were included in our analyses. p-value of 0.05, analyses shown in Using a threshold t-tests revealed no significant group differences in any of the tracts examined for AD, MD, RD, or FA.When dividing the SPD group into ADHD-positive and ADHD-negative subgroups, On the DSTP, a direct assessment of auditory discrimination, acoustic, acoustic linguistic, and DSTP total scores were significantly correlated with FA and RD in the CP-L and CP-R tracts in the SPD group but not the TDC group, consistent with our hypotheses . As expeThe SP Auditory Processing subtotal significantly correlated with RD and MD values of all five tracts examined, which include both cerebellar and cerebral peduncles, in the SPD group . AdditioIn the SPD group, the SP Tactile Processing subtotal was significantly correlated with RD and FA of the CP-L , but nonFor the SPD group, the SP Multisensory Processing subtotal was significantly correlated with RD and FA in the SCP-L and SCP-R . No signA receptor–mediated synaptic input to cerebellar NG2 cells, resulting in extensive proliferation of these cells and delayed oligodendrocyte maturation, eventually leading to dysmyelination  for more sensitive and specific evaluation of white matter microstructure  and/or type of processing issue . With an SPD sample as defined in the current study, it is possible to have a cohort of individuals with “opposite” sensory symptoms  that might obscure important findings that could be made in each distinct subgroup. Another limitation is the inclusion of children with and without ADHD in the SPD cohort. Given our results, which suggest the cerebellum plays a role in attention in children with SPD, it would be useful to assess SPD and ADHD separately in future studies. However, a In summary, the current study validates previous findings of altered WM connectivity in children with SPD compared to TDC. It also demonstrates the cerebellum's role in multisensory integration and attention in individuals with SPD. Finally, the current study contributes to the overall understanding of the neuroanatomical features present in SPD. It is important to identify these neurobiological underpinnings of the disorder, which can ultimately provide a biomarker to inform classification and diagnosis, prognostication, and interventions. It may also lend further support to SPD being considered a “brain-based” condition, rather than as a secondary symptom of ASD or a result of poor parenting, and help those with SPD obtain the knowledge and treatment options they need.https://datadryad.org/stash/share/nFhEh3cIfo635GI_yE3xWcsf40QC_q1s1lSVDubZVwA Repository: Dryad Name: Altered cerebellar white matter in sensory processing dysfunction is associated with impaired multisensory integration and attention.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: The studies involving human participants were reviewed and approved by University of California, San Francisco Institutional Review Board. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.EM and PM: conception and design of the study. AN, MR, EP, JW-J, IB, MG, AB-A, and SD: acquisition and analysis of the data. AN, MR, EP, EM, and PM: drafting significant portion of the manuscript and figures. All authors contributed to the article and approved the submitted version.MR, MG, and EM were employed by Cortica Healthcare. The remaining 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.


RA); and (2) exponentially weighted moving averages (ACWREWMA)] and the injury rate in young male team soccer players aged 17.1 ± 0.7 years during a competitive mesocycle. Twenty-two players were enrolled in this study and performed four training sessions per week with 2 days of recovery and 1 match day per week. During each training session and each weekly match, training time and sRPE were recorded. In addition, training impulse (TRIMP), monotony, and strain were subsequently calculated. The rate of injury was recorded for each soccer player over a period of 4 weeks  using a daily questionnaire. The results showed that over the course of the study, the number of non-contact injuries was significantly higher than that for contact injuries . There were also significant positive correlations between sRPE and training time , ACWRRA , and ACWREWMA . In addition, small-to-medium correlations were detected between ACWR and non-contact injury occurrence . Explained variance (r2) for non-contact injury was significantly greater using the ACWREWMA model (ranging between 21 and 52%) compared with ACWRRA (ranging between 17 and 39%). In conclusion, the results of this study showed that the ACWREWMA model is more sensitive than ACWRRA to identify non-contact injury occurrence in male team soccer players during a short period in the competitive season.This study aimed to investigate the relationship between the acute to chronic workload ratio (ACWR), based upon participant session rating of perceived exertion (sRPE), using two models [(1) rolling averages (ACWR In contemporary soccer, it is important to understand the sport-specific physiological demands for performance development and injury prevention as the game has become much faster and demanding over the past two decades  . The impTo be prepared for these requirements, it is recommended that soccer players train several times during the week and, to increase the chances of success, coaches implement specific training loads to challenge the boundaries of what players can achieve without exceeding what their bodies can tolerate . HoweverIt is recommended to monitor young soccer players during training because an adequate load is essential for short-term performance development as well as for enabling the future potential of these athletes . In factThe scientific literature provides different methods, which have previously established associations between measures of training load and injury rate in athletes. In many studies, the acute to chronic workload ratio (ACWR) was used . The ACWRA) and the exponentially weighted moving average model (ACWREWMA). The ACWRRA model is calculated by dividing the current workload  with respect to the workload that an athlete has completed for the current preparedness . In contrast, the ACWREWMA model, which was first presented by The ACWR can be calculated using two models, the rolling average model  and injury occurrence in athletes using both ACWR models. Previously, s soccer , Americas soccer , and rugs soccer  and conss soccer .EWMA and ACWRRA models. Given the controversial findings in the literature with some studies reporting positive (RA and ACWREWMA) and injury rate in young team soccer players during a short competitive period. With reference to the relevant literature . The team played competitive fixtures in the Second Division of the Iranian National League during the 2019 season. The soccer team included 25 players. Three of them were goalkeepers. Due to the different demands of their activities, the goalkeepers were excluded from this study. The remaining field players consisted of eight defenders , nine midfielders , and five forwards . The sample size was calculated based on a previous study by A priori power analysis was computed using G × Power  and the t-test family. The analysis revealed that a total sample size of N = 21 would be sufficient to find significant and medium-sized correlations between workload and injury rate.Data were collected from a semi-professional U-18 soccer team  and the exponentially weighted moving average (ACWREWMA). The ACWRRA was calculated by dividing the acute workload (1-week rolling workload data) by the chronic workload (the rolling 4-week average workload data)  was calculated using two models including the rolling average (ACWRad data) .EWMA was calculated as: EWMAtoday = Loadtoday × ƛa + [(1-ƛ) × EWMAyesterday]. In this formula ƛa is calculate by 2/(N + 1) ranging value between 0 and 1 that represents a decay rate to the load value  and chronic (4-weeks) periods.The ACWRad value . The N vThese approaches were used in the previous studies which applied ACWR models to clarify associations between training load and injury rate in team sports .How was your perceived exertion in this session/game?” Players verbally indicated a number to rate their overall effort according to 0 = rest, 1 = very, very rest, 2 = easy, 3 = moderate, 4 = somewhat hard, 5 and 6 = hard, 7, 8, and 9 = very hard, and 10 = maximal. In addition, sRPE × training time in minutes was assessed for the definition of training impulse (TRIMP)  .The medical staff of the soccer club classified all injuries , with injury reports recorded and updated on a daily basis throughout the study period. Injuries were categorized by injury type (non-contact vs. contact) and body site (injury location). Injuries were classified as follows: minimal (1–3 days of soccer activity missed), mild (4–7 days of soccer activity missed), moderate (1–4 weeks of soccer activity missed), and severe (4+ weeks of soccer activity missed) depending on the days of missed activities .RA and ACWREWMA) and injury occurrence. The magnitude of the correlations was considered 0.1–0.29, small; 0.30–0.49, medium; and >0.50, large (r2) in injury occurrence  explained by the TRIMP, sRPE, training time, strain, ACWRRA, and ACWREWMA. All analyses were performed using SPSS statistics . The level of significance was set at p ≤ 0.05. The TRIMP was computed by multiplying the duration of each training session with the respective session RPE. This was computed for each player individually. The daily mean divided by the respective SD was calculated and used as an expression of monotony. The product of the weekly training load and monotony was calculated as strain. The weekly load was determined by multiplying the daily mean load by 7 . If not the data were presented as median and interquartile ranges (IQR). Due to the limited number of monitored injuries, the more conservative Spearman’s rank correlation coefficient was used to determine the relationships between training monitoring tools .r = 0.411, p = 0.039). In addition, medium- and large-sized correlations were found between weekly sRPE and ACWRRA  as well as ACWREWMA . Likewise, medium-and large-sized correlations were found between the ACWR and injury occurrence during the competitive mesocycle .The analysis revealed a positive medium-sized correlation between sRPE and training time , 34% , 39% , and 27%  of the explained variance for the sRPE, training time, TRIMP, and strain, respectively. For ACWREWMA, 21% , 40% , 52% , and 28%  of explained variance were found for sRPE, training time, TRIMP, and strain, respectively.For ACWRRA and ACWREWMA) with sRPE, which indicates positive associations between training volume and sRPE, and between load periodization and sRPE in athletes. Further, we found significant medium- to large-sized relationships between measures of internal load and the number of non-contact injuries.The aim of this preliminary study was to investigate the relationships between internal workload parameters and injury occurrence in young team soccer players throughout a 4-weeks competitive mesocycle. We found that the sRPE increased from day 1 to 28 and, that the mean sRPE increased from week 1 to 4, which indicates a progressive increase in training load for all players. In addition, TRIMP increased from week 1 to 4 following the scheduled periodized training program of the team coaches. Moreover, the current data revealed medium- to large-sized correlations between training time (min/week) and ACWR (both the ACWRRA and ACWREWMA models) and weekly sRPE  in females over a 4-week training period. In addition, RA and sRPE across the training period. Taking our findings together with those reported in the literature, it seems possible to postulate that sRPE is an appropriate marker to monitor training load.This study revealed that weekly sRPE is significantly and positively correlated with the ACWR score. This is in line with EWMA compared with the ACWRRA (r = 0.53 vs. 0.31). In line with our findings, EWMA model is a more sensitive measure of ACWR in comparison to the ACWRRA model of team athletes. In contrast, The most important finding of this study was the medium- to large-sized relationship between ACWR and the number of non-contact injuries in young soccer players. Our results revealed that this association was larger for the ACWRTo date, it appears that ACWR <1 is associated with a lower injury occurrence in athletes and ACWR >1.5 appear to be associated with an increased injury rate . In agreRA and ACWREWMA models to injury occurrence. In this study, the ACWREWMA explained between 21 and 52% in variance (r2) for the sRPE, training time, TRIMP, and strain, while the variance explained by the ACWRRA was minimally significant lower (between 17 and 39%). In line with these findings, Within the current literature, it has been suggested that when the chronic workload is much greater than the acute workload, it results in a low ACWR; i.e., a lower rate of injury can be observed . ConversThis preliminary study has a few methodological limitations that warrant discussion. First, the number of included athletes  was rather low, affecting the power of the study. However, we conducted the priori power analysis and showed that this number appears to be adequate to receive sufficient statistical power. Second, the observation period was rather short. Yet, other researchers have previously reported that 28 days (7:28 ratio) are sufficient to calculate RA and EWMA and to determine the relationship between workload variables and injury occurrence in soccer players . Third, In conclusion, findings from this preliminary study demonstrated that the ACWR using sRPE and training time is easy-to-administer and useful as a measure to monitor injury occurrence in U-18 male soccer. The most important result of this study is that ACWRs calculated with exponential weighting have stronger correlations (associations) to injury occurrence than rolling averages in male team soccer players.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethical approval were obtained from the research ethics committee of the University of Guilan, Iran. The study was conducted in accordance with the latest version of the Declaration of Helsinki. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.HA, AA, and HZ designed the study. FK collected the data. HA and AA conducted the analyses. HA, AA, HZ, and FK wrote the manuscript. HA, HZ, UG, DB, and AH were involved in the interpretation of data, and reviewed and edited the manuscript. HZ and UG made a substantial and intellectual contribution to the conception and a critical revision of the manuscript. All authors read and approved the final version 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.


The aim of this study was to compare demographic, clinical and biochemical characteristics, including inflammatory markers, according to the nutritional status of patients with verified atherosclerotic disease.This cross-sectional study involved 1045 consecutive patients with verified carotid disease or peripheral arterial disease (PAD). Anthropometric parameters and data on cardiovascular risk factors and therapy for hypertension and hyperlipidemia were collected for all participants.Carotid disease was positively and PAD was negatively associated with body mass index (BMI). Negative association between obesity and PAD was significant only in former smokers, not in current smokers or in patients who never smoked. Overweight and general obesity were significantly related to metabolic syndrome (p < 0.001), lower values of high - density lipoprotein cholesterol (p < 0.001), increased triglycerides (p < 0.001), hyperglycemia (p < 0.001), self-reported diabetes (p < 0.001), hypertension (p < 0.001), high serum uric acid (p < 0.001), increased high sensitivity C-reactive protein (p = 0.020) and former smoking (p = 0.005) after adjustment for age, gender and type of disease. Antihypertensive therapy seems to be less effective in patients who are overweight and obese.In conclusion, overweight and general obesity were significantly related to several cardiovascular risk factors. The aim of the present study was to compare demographic, clinical and biochemical characteristics, including inflammatory markers, according to the nutritional status of patients with verified atherosclerotic disease .This cross-sectional study involved 1045 consecutive patients who were referred to the Vascular Surgery Clinic Dedinje in Belgrade, Serbia, because of carotid disease or peripheral arterial disease (PAD). The study was conducted during the period April 2006 - November 2007.The study included subjects who had symptoms of cerebral ischemia  and carotid stenosis ≥50%, according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria In the study were not included patients under 18 years of age, and patients with malignant disease, previous endarterectomy, and rheumatoid arthritis.Using questionnaire from all participants were collected data on demographic characteristics , anthropometric and lifestyle characteristic , and data on treatment for hyper tension and hyperlipidemia.2) was used for assessment of body composition. Body weight was categorized as: normal weight (BMI <25.0 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obesity (BMI ≥30.0 kg/m2) Body Mass Index (BMI), calculated as weight (kg) divided by height  alcohol consumption, yes (current and former drinking) vs. never, and b) by calculating the total dose of alcohol consumption for each participant by adding all the individual beverages  weighted to their alcohol content .Physical activity was assessed on the basis of data for the previous month. It was defined as any type of non-occupational physical exercise lasting more than 30 min per day. As a physically active were considered only those who exercised more than once per week.Chi square test, t-test and one-way ANOVA were used for the analyses of differences between BMI categories in distribution of patients by age, sex, atherosclerotic disease category, pack years of smoking and quantity of alcohol consumption. The association between categories of BMI and these variables was analyzed by contingency coefficient. Multivariate logistic regression analysis model was used with three aims. Firstly – to analyze the relationship between BMI and PAD according to smoking status with adjustment for age and sex. Secondly – to analyze categories of BMI (lowest category is a referent one) as a potential risk factors of selected outcome variables (different cardiovascular risk factors). Association of BMI with different cardiovascular risk factors was assessed after adjustment for age, sex and type of atherosclerotic disease (carotid or PAD). Thirdly – to analyze and eventually establish the relationship between BMI and high BP, dyslipidemia and elevated hsCRP in treated (antihypertensive and lipid lowering drug intake) and untreated patients. The adjustments were made for age, sex, type of atherosclerotic disease, diabetes, education, current smoking and former smoking.A level of α = 0.05 was used to indicate statistical significance. Data were analyzed using Statistical Package for the Social Sciences, version 20 .The study was given ethical approval by the Ethics Committee at the School of Medicine in Belgrade. All patients gave their written, informed consent.Data were collected for 1045 patients, 657 with carotid disease and 388 with PAD. Out of them 361 patients (34.55%) had normal weight, 487 patients (46.6%) were overweight, and 197 (18.85%) were obese. Normal, overweight and obese patients significantly differ in age, gender and type of atherosclerotic disease , but not in the severity of the disease . Obese pThe analysis of the relationship between BMI and PAD by smoking status  showed tp < 0.001. Significant inverse association was found with current smoking and significant positive association was found with former smoking. There was no significant association with education, total cholesterol, LDL-C, fibrinogen, and other atherosclerotic diseases, alcohol consumption and physical inactivity. Compared BMI groups did not significantly differ either in pack/year of smoking (p = 0.175) or daily alcohol consumption (p = 0.802).BMI was correlated with metabolic syndrome, lower values of HDL-C, abdominal obesity, increased triglycerides, hyperglycemia, diabetes, hypertension, high serum uric acid, increased hsCRP and former smoking, as well as with lipid lowering drug intake and antihypertensive therapy . OverweiAccording to data presented in In the present study carotid disease was positively and PAD was negatively associated with BMI. Overweight and general obesity were significantly related to several cardiovascular risk factors.2 was mainly due to vascular disease. Obesity is a risk factor for coronary heart disease and carotid disease. However, data on the association of PAD and BMI are not consistent. In cross-sectional studies this association was not found, in some studies it was positive and in some of them it was negative There are numerous studies reporting the adverse effects of obesity, especially on cardiovascular health Obesity seems to be associated with CVD in two ways, as an independent risk factor and through its association with other cardiovascular risk factors.According to a large prospective study Obesity is related to many cardiovascular risk factors such as glucose intolerance, metabolic syndrome, type 2 diabetes, hypertension and dyslipidemia p < 0.001). There were no differences in the number of former smokers . It has been reported that current smokers have lower BMI compared with nonsmokers and former smokers In the present study overweight and abdominal obesity were significantly related to metabolic syndrome and all its components. The inverse association of BMI with current smoking and positive association with former smoking is probably the result of weight increase frequently seen after cessation of smoking Association of BMI and abdominal weight with serum uric acid found in the present study was reported by several investigations In the present study increased hsCRP was present in 42% of all participants and it was significantly related to BMI. It is now recognized that adipose tissue is not only depot of fat, but an endocrine organ and that it is probably an important link between increased fat mass and insulin resistance. It also produces several inflammatory products that lead to atherogenesis Although in many investigations fibrinogen has been found to be associated with obesity especially in women The fact that 34% of patients in the present study were not overweight points to the importance of some additional factors, such as genetics, in the development of CVD.In the present study in a considerable number of patients with carotid disease and PAD, cardiovascular risk factors persisted in spite of treatment and the response to antihypertensive drug therapy was worse in overweight patients. These findings are similar to the results of EUROASPIRE II study The results of the present study confirm the efficacy of statin therapy on CRP and LDL-C reduction The advantages of the present study are: the number of patients; the analysis of the negative association between BMI and PAD in subgroups according to smoking status as well as the analysis of the therapeutic control of manageable cardiovascular risk factors in relation to BMI. These analyses were performed in only few other studies or in patients with coronary heart disease. However, more detailed investigations, preferably prospective, are required in order to explain the findings of the study.Our study has limitations. The cross-sectional design makes it difficult to judge causal relations. Another limitation is that study participants were from a single hospital and they did not represent all patients with carotid disease and PAD. In addition, we did not verify smoking status by CO monitoring or a biochemical method.In conclusion, according to the results of the present study, elevated BMI is significantly related to several cardiovascular risk factors in patients with carotid disease and PAD.Funding sources: This work was supported by Ministry of Education, Science and Technological Development, Republic of Serbia, through contract no. III41002.The authors declare that they have no conflict of interest.