Catalase usually scavenges H2O2 in mammals; however, this enzyme is absent in parasitic platyhelminths. Thus, the architecture of the antioxidant systems is different, depending primarily on the superoxide dismutase, glutathione peroxidase, and peroxiredoxin enzymes represented mainly in the tegument. Here, we discuss the adaptations that parasitic flatworms have developed to be able to transit from the different metabolic conditions to those they are exposed to during their life cycle.During the evolution of the Earth, the increase in the atmospheric concentration of oxygen gave rise to the development of organisms with aerobic metabolism, which utilized this molecule as the ultimate electron acceptor, whereas other organisms maintained an anaerobic metabolism. Platyhelminthes exhibit both aerobic and anaerobic metabolism depending on the availability of oxygen in their environment and/or due to differential oxygen tensions during certain stages of their life cycle. As these organisms do not have a circulatory system, gas exchange occurs by the passive diffusion through their body wall. Consequently, the flatworms developed several adaptations related to the oxygen gradient that is established between the aerobic tegument and the cellular parenchyma that is mostly anaerobic. Because of the aerobic metabolism, hydrogen peroxide (H Currently, it is accepted that this change began with the origin of cyanobacteria and the development of oxygenic photosynthesis . In. In90]. detected . Additiodetected  were abltegument ,94.E. granulosus, Echinococcus multilocularis, Hymenolepis microstoma, and T. solium) [In the case of the metabolic pathways of lipids and proteins, there are great changes, which may be due to the adaptation to the conditions of a parasite related to what the host provides. In 2013, Tsai and a large team of collaborators reported the massive sequencing and comparison of four cestode genomes ( solium) . Basical2 and allow the NADH generated during glycolysis to be oxidized to NAD+, a necessary substrate for, so that this path can continue , can be used in other alternative pathways known as fermentative pathways; they occur in the absence of Ocontinue .Moniezia expansa [E. granulosus [E. multilocularis [A classic adaptation of anaerobic metabolism is lactate fermentation, in which pyruvate is reduced to lactate (Lac) by the enzyme lactate dehydrogenase (LDH) using electrons from NADH. It is now known that this pathway is also used in parasitic helminths. Direct evidence of its presence is the secretion of Lac into the medium, as has been reported in cestodes such as  expansa ,96, E. ganulosus , and E. ocularis .M. expansa [E. granulosus [T. crassiceps [E. multilocularis [In addition to Lac secretion, the secretion of other reduced compounds such as succinate (Succ), acetate, and propionate (PPO) has been reported. This has been reported in  expansa , and conanulosus , T. crasassiceps , and E. ocularis , where tMalate dismutation is the main anaerobic pathway present in parasitic platyhelminths ,97,98,99T. crassiceps, as well as in the cysticerci of T. solium removed from pig brains [E. multilocularis [The fumarate produced is a substrate for the enzyme fumarate reductase (FDR) that reduces it to Succ; this is the main product of electron secretion in cestodes ,100,101.g brains ,96. Addig brains ; and (b)g brains . This coocularis .S. mansoni, P. westermani, C. sinensis, and F. hepatica [Ostertagia ostertagi, Anisakis simplex, and Brugia malayi. Although the presence of the gene encoding for ASCT in cestodes has not been reported, it is possible to suggest the presence of the enzyme  since the presence of acetate has been reported as an end-product of anaerobic respiration in both T. solium [E. multilocularis [The other malate dismutation reaction is the one that produces acetate where, as mentioned, the pyruvate generated in the mitochondrial matrix, through the mME (and in addition NAD(P)H is generated) ,101 and hepatica , as well. solium  and E. mocularis .Em′ = −63 mV, which is lower than that of UQ (Em′ = +110 mV) [c oxidase activity, of SDH, as well as the sensitivity of the electron transport chain (ETC) to different inhibitors (such as cyanide), are indicative of aerobic metabolism [2  instead of reducing the ubiquinone (UQ). This transfer of electrons is favorable because RQ has a redox potential of +110 mV) ,107. The+110 mV) . The mea+110 mV) ,109 is i+110 mV) ,99, whertabolism ,110. Oneolism [2 .A. suum, there are isoforms in two of the four subunits as well; Fp and CybS are different between the aerobic larva and the anaerobic adult; no isoforms have been reported for the Ip and CybL subunits [In anaerobic metabolism , FRD persubunits .Considering the above, we can note that anaerobiosis-specific reactions are those catalyzed by FRD and ASCT. However, it is the presence of RQ that appears to be the only real difference between aerobic and anaerobic energy metabolism , as FRD It occurs in two cell compartments: cytosol and mitochondrionIt is coupled to the generation of the proton gradient produced in complex I of the ETC, when the NADH coming from the formation of Acetyl-CoA and the one resulting from the activity of mME are oxidized .2 since the redox potential difference between NAD+/NADH (Em′ = −320 mV) and fumarate/succinate (Em′ = +30 mV) is sufficient for its synthesis [ATP is produced in the absence of Oynthesis ,63At the end of the pathway, several reduced compounds are obtained, including succinate, acetate, and propionate .To recapitulate, in the cytosol of muscle cells under hypoxic conditions, lactate is produced by lactic acid fermentation. Unlike this, malate dismutation or malic fermentation has the following relevant aspects:The need for a final electron acceptor moleculeMaintenance of redox balanceBoth are carried out in the mitochondrial compartments, which allows the formation of a proton gradient and therefore the synthesis of ATP.However, both aerobic and anaerobic metabolisms have the following aspects in common:Regardless of the type of energy metabolism, the redox balance is maintained. To keep it, organisms recycle their electron transporting coenzymes; thus, the number of reactions that produce NADH is equal to the reactions that consume it, or else, electrons are excreted in form to water, in aerobic organisms, and through succinate mainly in anaerobes .The parasite-host relationship is, in most cases, a reciprocal interaction, in which the behavior of the parasite causes feedback in the host and vice versa. Because of this, analyzing this type of feedback mechanism is essential to understand the complex connections between animal behavior, ecology, and parasite evolution . Up to tS. mansoni for more than 30 years and the case of a patient infected with E. granulosus for 53 years [One consequence of the foregoing is the parasite’s need to interact with its host and be able to maintain its ecological niche by engaging in chemical communication with it. It is not surprising then that the parasite has developed and fine-tuned mechanisms to evade the immune response. For example, it is known that some adult schistosomes can live from three to 10 years in humans, despite the harsh intravascular environment and their constant exposure to the immune system . In fact53 years .T. crassiceps during its proliferation in the peritoneal cavity. This made it possible to describe some of these complex interactions [T. crassiceps. Apparently, this sexual dimorphism is mediated by hormonal factors, since estrogens favor and androgens hinder the asexual reproduction of cysticerci [The feedback between parasitic flatworms and their hosts has been studied using model organisms. For example, the murine experimental model of cysticercosis has made it possible to evaluate the interaction of the host (mice) with the cysticercus of ractions , like thsticerci . Interessticerci . The lasOpisthorchis viverrini, induce chronic inflammation of the hepatobiliary system, exposing themselves to large amounts of ROS/RNS released by activated inflammatory cells [Taenia hydatigena occurs in the peritoneum, an increase in the infiltration of small peritoneal macrophages responsible for a high production of nitric oxide (NO) can be observed, which harms the parasite and modulates the immune response [F. hepatica through the liver parenchyma [During establishment of the infection, the parasites induce a rapid immune response in the host, although it is nonspecific . In genery cells . Similarresponse . Howeverrenchyma .2•−), which is generated in leukocytes through the integral membrane enzyme NADPH oxidase (NOX), and by transferring an electron from NADPH to O2. O2•− can undergo a spontaneous dismutation reaction generating hydrogen peroxide (H2O2) and O2. H2O2 can serve as a substrate for the enzyme myeloperoxidase (MPO) to generate the microbicidal compound hypochlorous acid (HClO). In the presence of transition elements such as ferrous (Fe2+) or copper (Cu+) ions, H2O2 can be reduced by the Fenton reaction, which produces the hydroxyl anion (HO−) and the hydroxyl radical (HO•). The HO• radical is highly reactive, so it can subtract electrons from other biomolecules, like proteins, changing their properties and biological activities, with DNA generating mutations and membrane lipids initiating the lipid peroxidation process. This damage can lead to altered metabolism and eventually cell death Superoxide Dismutase and Peroxidases• is chemically very reactive, so the first line of defense of parasitic flatworms is to prevent its production, the controlled reduction of H2O2 to H2O being vital. The classic enzyme that carries out this reaction in aerobic organisms is catalase (CAT), which is absent in the genomes of parasitic flatworms [2•− scavenging.As mentioned before, HOlatworms ,133 but latworms . Hence, 2•−, generating O2 and H2O2. In animals, it is possible to identify two isoforms: (a) cytoplasmic SOD dependent on one atom of copper and another of Zn (Cu/Zn SOD); (b) mitochondrial SOD, dependent on a manganese atom (Mn SOD). Experimentally, it has been possible to isolate the enzyme [T. solium; thus, it was not surprising to confirm that, in genomes/transcriptomes, both trematode [SOD is a family of metalloenzymes specialized in carrying out the dismutation of Oe enzyme  or clonee enzyme  from somrematode  and cestrematode ,136 generematode , althougrematode .2O2 to H2O, requiring electrons from two molecules of the tripeptide glutathione (GSH), taking it to its oxidized disulfide form (GSSG). Although this family has many representatives in mammals [S. mansoni [Fasciola gigantica [E. granulosus [2 to which the parasite is exposed, finding its highest expression in the aerobic life cycle stages and its lowest in the anaerobic [C. sinensis under in vitro conditions [GPx comprises isoenzymes that carry out the reduction of H mammals , in trem mammals  and cest mammals  correspo mammals  of the d mansoni  and Fascigantica , and of anulosus . Like SOnaerobic . Howevernditions . Cai et nditions .2O2 and alkyl hydroperoxides to water and alcohol, respectively. The electrons that translocate frequently come from the 12 kDa protein thioredoxin (Trx), which is why these enzymes are also called thioredoxin peroxidases (TPx), although some isoforms can also obtain electrons from GSH. Despite the abundance of Prxs, their catalytic efficiency is lower than that of CAT or GPxs by one to three orders of magnitude [2O2 degradation process, both in trematodes and cestodes. In fact, in the genomes of E. granulosus, E. multilocularis, H. microstoma, and T. solium, it has been possible to identify three different genes encoding Prx 1–3 [S. mansoni [O. viverrini, OvTPx-1 is expressed in all stages of development; even if its location is different, depending on the isoenzyme [Schistosoma japonicum it has been possible to locate Prx-1 in the tegument whereas Prx-2 has been found associated with the parenchyma, vitelline glands, and gastric epithelium [H. diminuta, a peroxidase-like activity was described in 1968 [Prxs are homodimeric proteins that catalyze the reduction of Hagnitude . However Prx 1–3 , which i mansoni . Wang et mansoni . Using wsoenzyme . For exaithelium . In H. d in 1968 .(2)Thioredoxin-Glutathione Reductase2, respectively). Reductases responsible for reducing these substrates again and helping to maintain the homeostatic redox cycle are significantly necessary. In mammals, there are two enzymes called glutathione reductase (GR) and thioredoxin reductase (TrxR), both are NADPH-dependent for the reduction of GSSG and Trx-S2, respectively [2 and GSSG in the mouse testis. This enzyme was called thioredoxin-glutathione reductase (TGR) [To carry out peroxide hydrogen reduction, both the GPx and Prx (TPx) need to take electrons from GSH and Trx and then generate their oxidized forms, the substrates  .S. mansoni (SmTGR) [E. granulosus (EgTGR) [T. crassiceps (TcTGR) [2. Although it has been proposed that having an enzyme capable of reducing substrates belonging to two independent redox systems represents an evolutionary advantage [Although this enzyme has been identified in vertebrate organisms, including humans (hTGR) , it is i (SmTGR) , as well (EgTGR)  and T. c (TcTGR) . Later o (TcTGR) . Unlike  (TcTGR) , these odvantage , it is advantage ,160,161.Gyrodactylus salaris [S. mansoni [T. crassiceps cysticerci is sufficient to compromise the viability of the parasite by altering its redox state and glutathione metabolism [The genomes of trematodes and cestodes ,129,162, salaris , have co salaris . Despite salaris . This en mansoni . We prevtabolism , which atabolism . Due to tabolism , promotitabolism ,160,161.(3)Glutathione-S-Transferase and Other Antioxidant MoleculesGlutathione-S-transferase (GST) is a family of highly conserved detoxifying enzymes that participate in the metabolism of many xenobiotics, although, in mammals, it has been found that it can participate in other relevant physiological processes such as the synthesis of leukotrienes, prostaglandins, and steroid hormones, as well as in amino acid catabolism and modulation of signaling processes . GST canE. granulosus; one mu class and one microsomal GST [C. sinensis trematode genome suggests the presence of 12 cytosolic GSTs distributed in the mu, sigma, zeta, and omega classes; in addition to mitochondrial GST and microsomal GST [T. solium (TsMsGST), specifically expressed in the cytosol of the scolex tegument and susceptible to praziquantel  [Schistosoma as the planarian Schmidtea mediterranea [There are three families of GSTs with distinctive structural characteristics and different evolutionary origins: (a) cytosolic GSTs, (b) microsomal GSTs or also called MAPEG (Membrane associated proteins involved in eicosanoid and glutathione metabolism), and (c) kappa-class mitochondrial GSTs . Howeveromal GST . Howeveromal GST . This agomal GST . Interesma GSTs) . Finallyterranea .S. mansoni, GST transcripts were 100-times more abundant than GPx transcripts and 10-times more than SOD isoforms. However, when enzymes were localized by immunofluorescence in the adult fluke, GST isoforms were restricted to a reduced subpopulation of parenchymal cells as well as to immature germ cells in both males and females. In contrast, SOD and GPX isoforms were localized in the tegument [Regarding their location and expression in parasitic flatworms, GSTs present complex patterns and depend on both the species and the stage of the life cycle in which they are found. For example, Mei and Loverde reported that, regardless of the parasite stage, when analyzing the transcript levels of different antioxidant enzymes in tegument .C. sinensis (CsGSTo 1 and 2). It begins with a growing pattern in juveniles of two to four weeks of age, but there is no expression in the metacercaria form and, in contrast, they are overexpressed in eggs [Another example is observed in the mRNA expression of the omega class GSTs of  in eggs . This wa(a)Cytochrome p450. This cytochrome has monooxygenase activity, which allows it to oxidize multiple exogenous molecules and contributes to their detoxification. Both in the flukes of S. mansoni [Opisthorchis felineus [ mansoni  and Opisfelineus , as wellfelineus .(b)Phytochelatin synthase (PCS). This enzyme works together with GST in the detoxification of xenobiotics and in the uptake of potentially harmful transition metals [S. mansoni [Ancylostoma ceylanicum [T. crassiceps [S. mansoni and are associated with phytochelatins of different sizes [n metals  through n metals . Origina mansoni  and its  mansoni  as well ylanicum . Previouassiceps  and whosnt sizes . Signifint sizes , althougnt sizes .(c)Myoglobin (Mb). We have previously talked about the capacity of Mb to store O2. Other activities that Mb presents are peroxidase/dioxygenase, having the ability to interact with O2 molecules such as NO, CO, and H2O2 [C. sinensis (CsMb) showed peroxidase activity and that it may be important for ROS detoxification because of its overexpression after incubation with exogenous H2O2 [C. sinensis flukes under aerobic conditions or in the presence of nitric oxide or nitrite is sufficient to induce the expression of the gene encoding CsMb [and H2O2 . Ren et ous H2O2 . This waing CsMb . Interes(d)Other enzymes. Under conditions of oxidative stress, hydroxyl groups can be nonspecifically oxidized to their aldehyde form. Similarly, reactions with radicals can lead to the formation of reactive carbonyls. As part of the characterization of the response of E. granulosus protoscolex to oxidative stress by exogenous H2O2, Cancela et al. reported high levels of a type of aldo-keto reductase (AKR), estradiol-17-beta dehydrogenase, and the enzyme carbonyl reductase 1 (CBR) [ 1 (CBR) . AKRs ar 1 (CBR) . On the  1 (CBR) .(4)Complexity of the Antioxidant ResponseOther Detoxifying Proteins That Have Been Reported in Parasitic Flatworms:-Time elapsed since the establishment of the infection. Skrzycki et al. compared oxidative stress markers and the presence of antioxidant enzymes in two populations of the adult H. diminuta cestode, one with a short experimental infection time and another with a well-consolidated infection [nfection . They fo-Sexual dimorphism of the parasite. Oliveira et al. compared the contribution of nutrients and gender of unpaired adults of S. mansoni on O2 consumption pathways and susceptibility to oxidative stress [2 consumption rate was higher in males compared to females, regardless of the respiratory substrate. In contrast, the rate of ROS production and the expression of antioxidant enzymes was higher in females than in males. This suggests that the physiological process of egg production is related to an increase in endogenous ROS. Finally, females were more tolerant to exogenous oxidative stress than males, possibly due to basal overexpression of their antioxidant systems.e stress . In geneThe different antioxidant enzymes do not work in isolation because to successfully face oxidative challenges, all systems must work together and simultaneously to avoid, as much as possible, the generation of highly toxic ROS such as the HO• radical. The latter maintains the peroxidases functioning by regenerating their electron source and repairing the damage caused during oxidative stress. In addition to this, there may be other factors that influence the antioxidant response, such as:Parasitic platyhelminths establish a chemical dialogue with the host by taking elements from it and by sending molecules from the parasite, having a different impact in their relationship with the host. In addition to oxygen diffusion, this class of parasites must ensure access to the nutrients they need for their development, so the presence of a sophisticated recognition and acquisition system through the use of specific transporters (similar to those of the host) is not surprising ,188. HowE. granulosus and in the vesicular fluid of various species of the genus Taenia [Through proteomic analysis, the presence of intact and functional host proteins has been confirmed in the hydatid fluid of s Taenia . Althougs Taenia ,191,192.s Taenia ,190. In s Taenia . Surpriss Taenia ,87.T. crassiceps cysticerci under in vitro conditions and observed the appearance of GSSG in the culture medium, which led to the proposition that the cestode expels GSSG excess as a mechanism to avoid the change of the redox environment inside [T. solium, which may potentially be responsible for carrying out this function [In parasitic flatworms, the presence of various families of transporters specialized in the removal of metabolites and drugs has been reported. Although this representation is not homogeneous in flatworms, its participation in detoxification processes has been demonstrated ,200,201.t inside . By searfunction .Oxygen has a dual function in organisms. In aerobic organisms it works mainly as a final electron acceptor during respiration, which results in greater energy production through the catabolic pathways, and its presence is related to the generation of ROS resulting in the expression of antioxidant systems involved in redox homeostasis maintenance.An energy metabolism that transits between aerobiosis and anaerobiosis depending on the availability of oxygen.This is possible because they have an enzymatic repertoire with common metabolic pathways involving enzymes that catalyze reversible reactions.In anaerobiosis, in addition to lactic fermentation, they have another fermentation pathway known as malate dismutation that allows them to obtain a greater amount of energy even in the absence of oxygen. Additionally, this pathway allows them to maintain their redox balance by eliminating the electrons in molecules that are secreted into the medium, mainly succinate, acetate, and propionate.2 diffuses.Due to the absence of a circulatory system, they developed a tegument through which OThe diffusion of oxygen generates the formation of a concentration gradient, its presence being greater in the tegument than in the parenchyma.Two populations of mitochondria, aerobic and anaerobic, have been described; the first located mainly in the tegument.2 implies a greater production of ROS in it, as indirectly demonstrated by a significant presence of antioxidant enzymes in this region .Finally, the exposure of the tegument to a higher concentration of OAmong flatworms, trematodes and cestodes have life cycles that develop in environments with different oxygen tension, which determine the development of special characteristics that have allowed them to adapt to varied conditions, such as:2. However, as Boyunaga comments [2 tension where these parasites develop” with the type of energy metabolism they carry out, since the reports in the literature can be controversial. Thus, an important aspect that must be considered is the presence of both types of metabolism, aerobic and anaerobic, in the same organism and its relation to the size of the parasite, the stage of the life cycle, and the degree of purity of the mitochondrion . Having pure populations of mitochondria would make it possible to determine with greater certainty what type of energy metabolism occurs at what time in the life cycle and in what region of the parasite.These overall data provide more information on the type of metabolism that is performed in the parasite in relation to pOcomments , “one mu


Although anesthetics play an important role in electroconvulsive therapy (ECT), the clinical efficacy and seizure adequacy of sevoflurane in the course of ECT remain unclear. The purpose of this study was to examine the clinical efficacy and seizure adequacy of sevoflurane, compared with those of thiopental, in the course of ECT in patients with mood disorders.n = 26) or thiopental (n = 26) were included. Factors associated with ECT and treatment outcomes were compared between the two groups using propensity score (PS) matching. Between-group differences were examined using an independent t-test for continuous variables and a χ2-test for categorical variables.We conducted a retrospective chart review. Patients who underwent a course of ECT and received sevoflurane  and sessions  and had more inadequate seizures . Remission and response rates were similar in both groups.Patients who received sevoflurane needed more stimulations (sevoflurane: 13.2 ± 4 times, thiopental: 10.0 ± 2.5 times, The present findings indicate that sevoflurane should be used with caution in ECT and only when the clinical rationale is clear. Major depressive disorder (MDD) is a common and debilitating psychiatric disorder and a leading cause of disability worldwide . DespiteAt our institution, intravenous anesthesia using thiopental  has beenThe data used in this study included a retrospectively collected dataset from the Keio Neuropsychiatry ECT Database. Therefore, informed consent was not required from the patients. The database includes patients who received ECT for an MDD episode at the Keio University Hospital, Tokyo, Japan. This study included patients undergoing treatment between April 2012 and March 2019. This study was approved by the Ethics Committee of the Keio University School of Medicine and adhered to the tenets of the Declaration of Helsinki.Patients were included in this study if they received ECT for an MDD episode (including bipolar depression) at the Keio University Hospital, had a diagnosis of MDD or bipolar disorder based on the Diagnostic Statistical Manual of Mental Disorders (DSM) IV-TR or DSM-5, and received thiopental or sevoflurane for general anesthesia during ECT. To ensure the validity of the diagnosis, more than two psychiatrists  evaluated the diagnosis of all the cases retrospectively. If the same patient underwent more than one course of ECT during the study period, the data from the first ECT course were used for the analysis.Patients were excluded from this study if the anesthetic agent was changed over the course of ECT and if they underwent fewer than five ECT sessions.Data on the participants’ demographic and clinical characteristics were extracted from our database, including age, sex, diagnosis, years of education, age at diagnosis, number of episodes, height, and weight.The baseline severity of MDD was assessed using the Clinical Global Impression–Severity scale (CGI-S). The CGI-S is a seven-point scale, where a score of 1 point indicates a normal state and a score of 7 points indicates severe illness . In addiResponse to ECT was assessed using the clinical note Global Impression Improvement scale (c-CGI) , which i1 Based on the ATC classification, we identified hypnotics (ATC code: N05C), antidepressants (ATC code: N06A), anxiolytics (ATC code: N05B), antipsychotics (ATC code: N05A), anti-epileptics (ATC code: N03), and mood stabilizers (ATC code: N05AN). DDD is defined as an assumed average daily maintenance dose of a drug in a typical adult. When a patient receives two or more drugs, a summed DDD value is calculated per category.The Anatomical Therapeutic Chemical (ATC) classification system and Defined Daily Dose (DDD) are recommended by the World Health Organization as measuring units for drug utilization studies.At our hospital, modified brief-pulse (0.5 ms) ECT  was administered twice or thrice weekly to inpatients. Bitemporal ECT using the half-age method was selected for all patients during the study period. When the initial stimulation did not cause adequate seizures based on the clinical judgment of the attending psychiatrist, the stimulation intensity was increased, and the patient received up to three more stimulations.Treatment duration was determined by the clinical outcome and possible adverse events . SpecifiThe following ECT-related factors were evaluated: number of ECT sessions per course (referred to as “number of ECT sessions”), number of stimulations per ECT course (referred to as “number of ECT stimulations”), charge used at the last ECT session, average charge used for ECT stimulations, average post-ictal suppression index, average seizure length, and number of inadequate seizures (defined as a seizure lasting < 20 s on EEG).Sodium thiopental (3–5 mg/kg) or sevoflurane (8%) was used for general anesthesia, and succinylcholine (0.5–1.0 mg/kg) was used to induce muscle relaxation. The choice of anesthetic was determined by the attending anesthetists based on clinical standards .t-test for continuous variables and a χ2-test for categorical variables. All analyses were two-sided with an α-level set at 0.05. Data were analyzed using R Version 3.4.3.Participants’ characteristics were reported as descriptive statistics. Patients were divided into the sevoflurane and thiopental groups, and between-group differences were examined using an independent To control for confounding factors, we used PS matching analysis. PS matching reduces bias due to confounding factors by matching patients on baseline variables using a multivariable logistic regression model. PS matching was performed on the following factors: weight, height, and medications , diagnosis of MDD or bipolar disorder , CGI scoAmong 186 patients with MDD included in the database, 83 received sevoflurane or thiopental for all ECT sessions and were included in the present analysis. A total of 52 patients (26 patients per group) were compared using PS matching .df = 82, p = 0.006), experienced more inadequate seizures , and received a higher average charge  than the thiopental group.Demographic and clinical characteristics of the overall sample are presented in df = 51, p = 0.001), more ECT sessions , and experienced more inadequate seizures  than the thiopental group. The characteristics of the PS-matched participants are presented in Although the area under the receiver operating characteristic curve was 0.696  , 3, PS mThis study examined the clinical efficacy and seizure adequacy associated with ECT in patients with MDD who received sevoflurane or thiopental throughout the ECT course. In the present study, the number of stimulations, ECT sessions, and inadequate seizures were significantly higher in the sevoflurane group than in the thiopental group. These findings suggest some disadvantages of the routine use of sevoflurane as a general anesthetic for ECT.ECT is a treatment option for the most severe psychiatric disorders, making it difficult to conduct a randomized controlled trial on the impact of the anesthetic type used during treatment administration ; consequIn the present study, the sevoflurane and thiopental groups achieved similar treatment outcomes; this finding is consistent with that of a previous study , which cThis study had some limitations. First, data were collected retrospectively, including information on treatment outcomes. Specifically, the retrospective use of CGI-S and c-CGI may attenuate the reliability of treatment outcomes. Future research may need a structured assessment of symptoms. Second, the time interval between anesthetic and ECT administrations and depth of anesthesia were not evaluated; all of these factors may affect seizure quality . ConsequThe present findings suggest potential disadvantages of sevoflurane for ECT, as it may increase the number of ECT stimulations and sessions required and that of inadequate seizures experienced by patients. The present findings suggest that sevoflurane for ECT should be used cautiously and only when the clinical rationale is clear.The datasets presented in this article are not readily available because participants of this study did not consent to their data being shared publicly. Requests to access the datasets should be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Ethics Committee of the Keio University School of Medicine. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.TY, TU, and JH were involved in the analysis, design, and interpretation of the data, wrote the first draft of the manuscript, and supervised the entire project. TY, TU, AT, MW, SK, KN, HN, BY, MM, and JH contributed to the interpretation of the data. All authors contributed to the article and approved the final 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.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.


Emojis are universal tools that are frequently used to express people’s emotional states throughout daily communications. They are often applied in various fields of research, such as consumer surveys, as indicators of users’ emotional states. Further analyses of emoji interpretation among people with age are required to ensure the validity of emojis as a metric in such fields of research, thereby reducing misunderstandings. However, details regarding the effect of age on both arousal and valence, as they pertain to the interpretation of emojis, remain unclear. Therefore, in this study, we investigate the effects of the interpretation of facial emojis on the arousal-valence space among people of varying age groups. We conducted an online survey involving 2,000 participants, whereby we employed a nine-point scale to evaluate the valence and arousal levels associated with 74 facial emojis. Based on the two axes of valence and arousal among the age groups involved in this study, emojis are categorized into six similar clusters. For the two negative clusters, i.e., strongly negative and moderately negative sentiments, the group involving middle-aged participants showed significantly higher levels of arousal compared to the group involving young participants. Additionally, not all emojis classified into the aforementioned negative clusters indicate age difference. Based on these results, this study recommends using emojis with no age-related effects on the negative clusters as indices for evaluating human emotions. Across the world, people frequently use emojis to express their emotional states throughout their daily communications. Scientifically, emojis are associated with a variety of human emotions . Emojis The arousal levels of the emotions people perceive through media change with age. For example, In this study, we investigate the interpretation of facial emojis and their classification in the arousal-valence space among people of varying age groups. As mentioned above, previous studies have reported that middle-aged people perceive higher levels of arousal from media compared to young people. Therefore, this study compares the interpreted arousal and valence levels between young and middle-aged people. Based on the findings of previous studies , this stM age = 30.20, SD = 5.68. middle-aged males: 596, females: 564, M age = 49.40, SD = 5.43) participated in the survey. The participants were registered on an online panel maintained by a marketing research firm.1 They were also fluent in Japanese (the language used in the survey). Ethical approval was obtained before data collection, and the eligible participants were informed about data confidentiality. Informed consent was obtained before participation in the study. All study protocols were reviewed and confirmed by the local institutional review board .We conducted an online survey in the capital of Japan until 1,000 valid responses  were obtained for each age group. The group comprising individuals aged 20–39 years was defined as young, whereas the group comprising individuals aged 40–59 years was defined as middle-aged to avoid bias by age group or gender. A total of 2,314 participants . These questions could be easily answered if the instructions were understood . Participants who could not answer these questions correctly were excluded from further analyses.post hoc analysis after the main effect was obtained. The results of the ANOVA were considered statistically significant if the p-value was less than 0.05. Furthermore, to clarify the specific emojis that were interpreted differently between the age groups, independent-samples t-tests were conducted on all emojis classified into clusters with main effects. The results of the t-tests were considered statistically significant if the p-value was less than 0.05. Statistical analyses were conducted mainly using IBM SPSS Statistics 26 , and R software  were conducted. Specifically, hierarchical cluster analysis was conducted to investigate the way in which the 74 emojis were classified into several clusters. Two-way ANOVA was conducted to reveal the characteristics of each cluster and the differences in interpretation by the age groups. The Bonferroni correction was used for a software  was usedM age = 30.13, SD = 5.55. middle-aged males: 500, females: 500, M age = 49.71, SD = 5.44). The mean and standard deviation of the arousal and valence levels for each emoji per age group were plotted on a scatter plot  to classify similar emojis into several clusters. The Euclidean distance and Ward aggregation criterion were considered in the analyses . The optimum number of clusters was obtained from the dendrogram and the Calinski-Harabasz index. As a result, a six-cluster solution was retained for both the young and middle-aged groups. The mean (±standard deviation) for arousal and valence scores and the number of emojis classified into each cluster are displayed in F = 203.07, p < 0.001, η2 = 0.88] and the age . Furthermore, significant interactions between clusters and age were found . After the interaction between clusters and age was found, the simple main effects on both clusters and age were analyzed. Consequently, for clusters 1 and 2 only (ps < 0.05), the middle-aged group indicated significantly higher arousal scores than the young group. For valence, a significant main effect was found on the clusters  but not on age  and the interaction between clusters and age .A two-way ANOVA was performed on the mean arousal and mean valence for each emoji to analyze the effects of age group and cluster. For arousal, a significant main effect was found on the clusters [t-tests were conducted on each of the 17 emojis classified into clusters 1 and 2. The results demonstrated significant differences on three emojis, as listed in To determine specific emojis affected by age group difference and identify emojis with an age-related effect on the arousal level, independent-sample This study aimed to understand the age differences of facial emoji interpretations on the arousal-valence space. To this end, data obtained from 2,000 participants were collected, and the arousal and valence levels indicated using 74 emojis were analyzed. For both the young and middle-aged groups, emojis were distributed in a U-shape on the two axes and categorized into six clusters . These t, , and   with stronger arousal levels than young people, which is in line with the findings of , , and  , 2. Acco as well . It has  as well . Orth et, , and   showed differences in interpretation among different age groups. Based on the results, this study suggests using emojis with no age effects for negative clusters when using emojis as indices for measuring human emotions among people of various ages.This study attempted to understand age differences  and emoji interpretations on the arousal-valence space. The results demonstrated the following: (1) emojis were categorized into six similar clusters on the two axes of valence and arousal for both age groups, (2) the middle-aged group tended to indicate significantly higher levels of arousal than the young group for two negative clusters , and (3) not all emojis classified into these two negative clusters indicated age differences and only three emojis (The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.GK and YK performed the experiments and drafted the manuscript. GK analyzed the data. HU, KE, and YK provided guidance and oversight. GK and YK drafted the manuscript. All authors contributed notes and edits within the manuscript and provided critical feedback for improving 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.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.


Dietary supplements (DSs) may be useful for managing shift work disorder. But the efficiency of outcomes in clinical trials using simulated shift work populations as subjects is controversial. This review explores the potential role of DSs for improving sleep quality, daily functioning, and mood among shift workers in the real world.I2 statistics, and publication bias was assessed via Egger's regression test.A related literature search was conducted in PubMed, Web of Science, Embase, and Cochrane Library databases from their inception to July 2021. Information was collected on “shift work,” “irregular working hours,” “night shift,” “dietary supplements,” and “nutraceutical research data.” Sleep quality-related scales were the primary outcome measures. The meta-analysis was conducted using RevMan 5.4  and Stata 15.0 . Heterogeneity was examined by using p = 0.04; standard mean difference (SMD), −0.45 [−0.88 to −0.03]) and daytime function . The DS groups did not have a significant improvement in psychomotor vigilance , depression , or anxiety . All RCTs suggested a positive safety profile for DSs.Twelve studies, which involved 917 participants, met the inclusion criteria. The DS groups had significant improvement in sleep quality scores (8 randomized controlled trials [RCTs]: The findings of this meta-analysis indicated DSs may be beneficial for improving sleep quality and daytime function in shift workers. Although there is a wide range of DSs, the small amount of literature included for each type does not allow for subgroup analysis to be used to eliminate high heterogeneity. We have not yet included literatures on other languages either. Given these limitations of the study, there is still a need for more well-designed randomized controlled trials so that our review can be updated in the future to make the results more conclusive.https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273558, PROSPERO: CRD42021273558. Shift work refers to working time arrangements that differ significantly from society's traditional working hours , or even night work that is completely reversed . It cannThe prevention and treatment of shift work disorder is mostly a stepwise approach, which is generally conducted in a parallel and multimodal manner. This approach includes pharmacological interventions such as sedative-hypnotics, wake promoters, and dietary supplements (DSs)  and inclIn addition, questions concerning the applicability of measurements obtained after simulated shifts of healthy people to the real world prompted this study. Excessive stress due to work and social relationships in real life can lead to a vicious cycle of circadian rhythm disruption . TherefoThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines  16). Th. Th16). All randomized controlled trials (RCTs) (including crossover studies) were included that involved humans participating in shift work and compared the clinical efficacy of at least one dietary supplement in any form with placebos. The duration and frequency of therapy were not limited. We did not consider age, sex, education, ethnicity, and occupation of the participants. The primary outcomes were changes in the score of the Pittsburgh Sleep Quality Index, Insomnia Severity Index, or other scales used to assess sleep quality. The secondary outcomes were daytime function, as assessed by the Epworth Sleepiness Scale, Karolinska Sleep Scale, or Chalder's Fatigue Survey. We also focused on psychomotor vigilance and mood outcomes, which were evaluated by reaction time and a self-assessment scale, respectively. However, a literature report was excluded if it included participants who experienced serious underlying diseases or cognitive-communication disorders, were pregnant, or were healthy and had undergone simulated night work. If more than one RCT was carried out with the same population, the most comprehensive one was included in the review.The following electronic databases were searched from their inception to July 31, 2021: PubMed, Web of Science, Embase, and Cochrane Library. Furthermore, the reference lists of the included literature, previous relevant reviews, and clinical trial registries were manually searched to find additional trials that met our inclusion criteria. The search was limited to English-language papers with no other restrictions applied. Exhaustive search strategies for each electronic database were developed by the review team members. The search strategy contained relevant terms, based on . Two reviewers (Y. Wu and C. Zhong) proceeded independently in a three-step sequence: removing duplicate literature, reviewing the titles and abstracts, and acquiring the full text for screening to exclude articles, based on the eligibility criteria. Any disagreements were discussed and resolved in discussion with a third reviewer (R. Wang).Two investigators (X. Huang and D. Sun) independently extracted information from the selected articles, which were collected and sorted by a predefined extraction template. The extracted information included general information ; characteristics of the patients ; characteristics of the shift work ; methodology of the trial ; characteristics of interventions; measurement of outcomes; adverse events; follow-up period; and funding. We attempted to contact the corresponding authors of the studies via email addresses to request missing data. The extracted information was cross-checked by X. Huang and D. Sun. For disagreements, mediation was conducted by a third investigator (R. Wang).https://training.cochrane.org/online-learning/core-software-cochrane-reviews/revman). Any disagreement was resolved by discussion or with the help of the third author (R. Wang).Two researchers (Y. Wu and X. Huang) independently assessed the quality of the selected studies, using the Cochrane Collaboration's tool for RCTs . Each dop-value <0.05 was considered statistically significant, unless otherwise specified. The continuous data included sleep quality, daytime function, psychomotor vigilance, depression, and anxiety, which were measured differently. The standard mean difference and 95% CI were used for effective evaluation. To ensure uniformity of the included data, all data were used in the intent-to-treat analysis. The traditional pair-wise efficacy data in populations were synthesized and statistically analyzed in Review Manager 5.4 by random effects models (weighted by the inverse of the variance). Given that a few studies did not report changes from the baseline data, we selected post-treatment data for the comparison of symptoms. If the mean or standard deviation was missing and the data were still not available after contacting the original author, we unfortunately had to exclude the data.Continuity correction was used for cells with zero values. A 2 test and I2 test. Based on the Cochrane Handbook, the I2 was considered “substantial” if its value was >60%; “moderate,” 30–60%; and “non-important,” <30% , occupation, and study quality . A sensitivity analysis was conducted in each domain of the primary outcome to assess the stability of the meta-analysis. Egger's regression test, using STATA 15.0 , was also used to statistically assess publication bias.Between-study heterogeneity was assessed using the χt,” <30% . An I2 sThe search strategy retrieved 1,340 relevant articles, after removing duplicates. After a title/abstract review, the full texts of 64 potentially eligible articles were reviewed . Of thesThe risk of bias summary for each included trial is shown in n = 243) taking placebos .This outcome indicator was assessed in 8 RCTs, 9 arms, and 520 participants. Two hundred seventy-seven participants taking DSs had a significant improvement in sleep quality scores, compared with the participants . An analysis showed that DSs could improve daytime function , but heterogeneity was significant in studies assessing anxiety . This data analysis showed that DSs could not improve depression  and anxiety  reported data on depression and four trials (representing 4 arms) reported data on anxiety. Heterogeneity was not significant in studies that compared depression scores (Adverse reactions were recorded in three of the 12 studies , 22, 28.A meta-regression was conducted to determine whether the observed efficacy on sleep quality was similar between different years of publication, DS types, occupations, and study quality. A significant association was found between sleep quality and the factors of years of publication, occupations, and study quality .Although the meta-regression revealed three potential factors contributing to heterogeneity, our attempts to further distinguish subgroups of shift workers across publication years and occupations were abandoned, as most studies of publication years did not find a pattern of grouping and their definitions of occupation were vague. Ultimately we selected different DS types and study quality for the subgroup analysis, based on the clinical characteristics of the included studies. The results showed that, compared with lower quality studies, the higher quality studies indicated a superior improvement in sleep quality for participants using DSs. However, we did not find better efficacy for DSs within the melatonin or the non-melatonin subgroups .A sensitivity analysis was conducted with the results of the primary outcome indicator sleep quality to assess the stability of the meta-analysis. When any single study was deleted, the corresponding pooled SMD remained at a 95% CI of −0.88 to −0.03, which suggested that the meta-analysis was stable . Howevert = −2.04; 95% CI, −7.13 to 0.53; p = 0.081; We found no evidence of publication bias for DS intervention when using Egger's regression test (The purpose of this review was to explore the potential role of DSs in improving sleep quality, daily functioning, and mood among shift workers. The key findings of this systematic review and meta-analysis indicated that, compared with placebos, DSs demonstrated a statistically significant difference in improving sleep quality and daytime function for participants. However, the change in psychomotor vigilance and mood was not significant. Perhaps the most important finding was that although a limited number of studies reported the presence of adverse events such as sleepiness, dizziness, and headache, all adverse effects were mild and transient, and the differences between the DS and the control groups were not statistically significant. No participants withdrew from the studies because of adverse events. In subgroup analyses, high-quality studies showed that DSs had a clear clinical effect, but low-quality studies showed no difference. It is interesting to consider that there was no difference in the efficacy of DS in either the melatonin or non-melatonin subgroups, this change in outcome may be related to the reduced sample size of the subgroups.To the best of our knowledge, this study is the first systematic review and meta-analysis to examine the effects of DSs on SWD in real working environments. In a recent systematic review  of pharmUncertainty about the action mechanism of DSs may be the primary cause contributing to their limited promotion because they affect sleep quality, endogenous melatonin metabolism, positive regulation of the sleep–wake cycle, and alterations in inflammatory conditions closely associated with insomnia . For exaCompared with other intervention options, safety and adherence are also issues to consider when choosing DSs. Pharmacological hypnotics and wake-promoting drugs have a low safety profile and significant adverse effects; thus, the ingestion of drugs to manage SWD may not meet with widespread acceptance . Light tDespite the partially encouraging results of our study, several limitations should be noted. First, heterogeneity existed in the main outcome indicators, and through a meta-regression, we identified the year of publication, occupation, and study quality as possible sources. An attempt to analyze subgroups by year of publication and occupation unfortunately failed, as no grouping pattern was found for them. We were only able to select the types of DSs and study quality for subgroup analysis based on clinical characteristics, but there was still some heterogeneity. The findings were also interesting in the results of the sensitivity analysis. The outcome of sleep quality remained stable, as demonstrated in Our meta-analysis showed that DSs improved sleep quality and daytime function in shift workers, but they had no significant effect on psychomotor vigilance and mood. Thus, DSs could potentially be valuable clinically in improving sleep quality and daytime function in shift workers. Unfortunately, the small amount of the literatures included for each type of dietary supplement does not allow us to know how the different DSs compare. More high quality multi-arm and crossover designed RCTs are needed in the future to enable us to update the findings of this meta-analysis in time and provide the best options for dietary supplement management for shift workers.The original contributions presented in the study are included in the article/YW and CZ: writing—original draft. YW, XH, CZ, and DS: methodology. XH: software. RW: supervision and validation. QZ and HL: writing—review and editing. QZ: conceptualization. HL: team management and coordination. 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.


Additionally, a Pearson correlation was done. The most representative age category was between 18 and 22 years old (42.7%), the ones using dietary supplements most frequently. There were significant differences by group of age regarding the consumption of food supplements (p < 0.05) and also by gender (p < 0.05).Food supplements contain a variety of combinations of vitamins, minerals, plant extracts, and other substances. Any physical effort requires energy from balanced and healthy nutrition. This research aimed to identify the categories of dietary supplements used by active and very active participants who attend the sports and leisure centers from Targu Mures city. The survey was developed in paper and online forms using the Internet and supported multimedia and self-administration. The sample consists of 517 subjects chosen randomly from the research population and divided into the active and highly active PAI subgroups based on age, education, and gender. IBM SPSS Statistics Version 20.0 was used to process the collected data. All data were analysed descriptively. Differences between independent groups were assessed using an Independent sample t-test and a Chi-square test. Statistical significance was accepted when  The benefits of exercise for the population are often presented in the literature . AccordiThe Physical Activity Index (PAI) is the most commonly used questionnaire in Romania to assess health-related physical fitness. It comprises three items based on the intensity of the effort, the time spent attending the physical activity, and the frequency of participation in PA ,5,6. TheTo increase the population’s PA level, sports and leisure centers are ideal for providing PA equipment within gyms, exercise class activities, and swimming pool facilities . Gyms haTherefore, for a healthy life, the WHO makes a series of recommendations regarding the number of calories per day, limiting the consumption of sugar, salt, and saturated fat, increasing the consumption of vegetables and fruits, and a diet with essential micronutrients, such as vitamins and minerals .According to European legislation, food supplements represent concentrated sources of nutrients or other substances with a nutritional or physiological effect, and whose purpose is to supplement the diet. Therefore, they are marketed in the form of capsules, lozenges, tablets, pills powder sachets, liquid ampoules, dropper bottles, and other similar liquids and powders intended to be taken in small measured unit quantities . ScientiNumerous pieces of evidence paid attention to nutritional supplements essential for sports performance and physical activity ,20,21,22Globally, the market for dietary supplements is constantly growing. However, excessive consumption of these nutritional supplements can have detrimental consequences on the body . RelatedIncreasing interest in food supplements and increasingly abusive and uncontrolled consumption requires an increasingly rigorous attitude from the authorities and national nutrivigilance.Various studies on dietary supplements used by the active population have been conducted internationally, but none of these were performed in Romania. The study aimed to investigate (1) the type of dietary supplement intake; (2) the sources of supplement acquisition; (3) the effect of dietary supplements used by the active population from Targu Mures city. Furthermore, information on the reason for consuming dietary supplements, and the type of supplements used according to gender, age, and PA level may provide insights into the need for age-specific education on the safe use of supplements for improved health, body composition, and physical fitness.The study’s general research sample consisted of Targu-Mures City residents aged 18 to 62 who attended sports and leisure centers.Respondents were selected for having a Physical Activity Index (PAI) over 61. There were two groups of physical activity in the layer: active (PAI between 61 and 80) and very active (between 81 and 100).To determine the PAI ,7 the paSix hundred participants were recorded during the survey period and were observed as two PAI subgroups .Participants were informed that their contribution was voluntary and anonymous and that they could withdraw without providing any reason. Eighty-three were excluded from processing the data due to incomplete data or not meeting the inclusion criteria.The sample includes 517 subjects randomly drawn from the research population according to age, education level, gender, and PAI subgroups.Regarding education , out of The participants in this study had the choice to participate in the survey either on paper or online using Google Workspace’s web instrument form, which was built as part of the project  and alloCronbach’s Alpha was 0.786 which is greater than the acceptable range of 0.7 indicated score , and gooThe purpose of the empirical study starts from the premise that active populations use dietary supplements to support physical effort in the gym or during performance training with expected effects.-identifying the reasons why food supplements are consumed, and-identifying how these food supplements are obtained.In addition, the study’s overarching goal is to pinpoint the significant subcategories of dietary supplements consumed by the group’s elderly, active, and very active population. The objectives of the study consisted of:Due to the lack of similar studies in the international and national literature and based on the authors’ professional experience in physical activity and supplement consumption. The research hypotheses of the study were intuitively established as follows:H1: Young adults, residents in Targu Mures city who attend sports and leisure centers, between the 18–24 age group consume more food supplements than other age categories.H2: Active and very active men with over 61 Physical Activity Index score take more nutritional supplements than women.The questionnaire included personal data such as age, gender, weight, height, BMI, and level of education. Additionally, there are inquiries concerning the quality, quantity, and duration of physical activity.If such supplements were taken, more inquiries were made regarding the kind of dietary supplements taken, how they were obtained, the sources of acquisition, and the anticipated effects.The survey is an extensive study designed to capture, in statistical form, the frequency of characteristics or characteristic variables  at the level of some populations .Studies of beliefs, attitudes, motivation, and aspirations, in other words, studies of human life can become the center of complicated subject investigations. Nevertheless, it does not end with them .The study was approved by the Ethics Committee of the University of Medicine and Pharmacy, Science, and Technology “G.E. Palade” Targu Mures and conducted under the Helsinki Declaration. The study also complied with all applicable laws about data protection, privacy rights, and personal information. All participants were made aware of the goal and aim of the study as well as the voluntary nature of their participation. They were free to leave the study without giving a reason.The questionnaire was applied online by sending an invitation and later reminders through email and social media and printed to respondents attending sports and leisure centers. Respondents followed a link to the online survey, and informed consent was assumed from the respondents’ compilation. Printed forms were distributed in the sports and leisure centers.We considered a questionnaire valid only when that questionnaire was completed in full by the respondents from Targu Mures city and considered active and very active according to the Physical Activity Index.All data were recorded into Google Workspace automatically for the online survey and manually for the printed version.p-value under 0.05 was considered statistically significant. The item analysis was performed using Pearson correlation coefficients, and the associations were interpreted as not existing (r = 0), very weak (0.00 < r < 0.10), weak (0.10 ≤ r < 0.30), moderate (0.30 ≤ r < 0.50), strong (0.50 ≤ r < 0.70), very strong (0.70 ≤ r < 1), or perfect (r = 1), according to the value of r [The Excel database was exported to Statistical Package for the Social Sciences (SPSS 20 IBM for Windows). It included descriptive statistics of mean, SD, and the frequency of occurrence expressed in absolute values or percentages. Additionally, an Independent sample t-test was performed for the following variables: age, height, and weight. Chi-square tests were applied to verify the distribution of answers regarding the variables used. A Pearson correlation (r) was applied to determine the correlations between variables in the “type of dietary supplements” category. A lue of r .N = 370, 63.8%), while males were 136 (23.45%) and females were 194 (40.35%) (The study population was comprised of 264 (51.06%) males and 253 (48.93%) females, categorized according to PAI as active and very active people. Most participants from the active population have a normal BMI ((40.35%) .Of 517 study participants, 240 reported consuming dietary supplements. 2 = 25.010. df = 8, p = 0.002).There was a significant difference between the observed and expected frequencies in the case of age categories regarding the preference for the use of dietary supplements (xVitamins (68%) and proteins (64.1%) are the supplements that people in the population who assumed dietary consumption use the most, followed by amino acids (23.8%) and minerals (39%). The participants that consumed supplements stated the following sources of purchase: instructors (48.1%), pharmacies (24.7%), the Internet, TV (21.3%), profile store (17.4%), and colleagues (12.3%). Therefore, it was determined that gaining muscle mass , energy and endurance , and post-exercise recovery  were the primary motivations for using nutritional supplements .Making a correlation between the types of supplements  we obserOur study aimed to investigate the consumption of dietary supplements and opinions about the type of supplements used, sources of purchase, and the effects among active and very active lifestyle populations. The results from this research are of particular interest because there is much information on the use of dietary supplements in the inactive population, and a lack of data on people who attend sports centers and leisure activities for a healthy lifestyle. Dietary supplement use is common among recreational and professional athletes ,37. The The most popular supplements consumed by the study population were vitamins, followed by proteins, minerals, and amino acids. We discovered a medium to strong correlation (r = 0.615) between vitamins and minerals ; a medium correlation r = 0.437) between minerals and amino acids ; a poor correlation (r = 0.357) between amino acids and vitamins ; poor to average correlation (r = 0.340) between protein and vitamins . Some studies have shown that the most popular dietary supplements among amateur athletes are usually sports energy drinks, vitamins and minerals, caffeine, creatine, and protein supplements 7 between,46,47,48Today, dietary supplements are widely used in modern society. Marketing claims for some dietary substances include improvements in overall health status, enhancement of cognitive or physical performance, an increase in energy, the loss of excess weight, attenuation of pain, and other favorable effects . Our resPeople frequently take supplements without thinking about possible side effects, mainly because they are said to be substances that improve fitness. However, over time, overconsumption of dietary supplements can alter health and performance .Gender-based differences in sports and exercise nutrition have been considered an important area of debate, particularly during the recent two decades ,45,46,47We discovered that 48.1% of the instructors recommended supplements which is similar to the findings of Finamore et al. (2022) with 27.9% . OverallThe present sample was characterized by using vitamins and proteins to increase muscle mass, obtain energy and endurance, and recover post-exercise at instructors’ suggestion from sport leisure centers. Moreover, consumers of dietary supplements are young males.This study provides original information on dietary supplement use, type, effects, and source for purchasing among healthy and active lifestyle residents in the city of Targu Mures, Romania. DS were used by 240 participants (50.29%). Vitamins are the most frequently consumed supplement followed by proteins. Results also indicate that both genders use supplements for energy and endurance, increased muscle mass, and post-exercise recovery, and instructors represented a reference source for prescription supplements. Our findings can raise awareness about the importance of the acquisition, clean and healthy consumption of dietary supplements, and the need to consult a nutrition specialist before using these products. Nutritional supplements should not be encouraged to the detriment of adequate nutrition.


During adolescence, many individuals with gender incongruence (GI) experience distress related to body dissatisfaction. This study aims to describe the body (dis)satisfaction of Dutch adolescents referred for GI and to describe the influence of body image on their psychological functioning. Self-report measures on body satisfaction  and psychological functioning (Youth Self-Report) were obtained from 787 adolescents (aged 10–18) who were referred to the Center of Expertise on Gender Dysphoria at the Amsterdam University Medical Centers between 1996 and 2016. First, a general description of body satisfaction in adolescents with GI was developed. Secondly, multiple linear regression analyses were performed to determine the association between body image and psychological functioning, both for total problems and for internalizing and externalizing problems separately. Third, regression analyses are repeated for body area subscales. Adolescents with GI report the greatest dissatisfaction with the genital area, regardless of birth-assigned sex. For all other body areas, there were birth-assigned sex differences in satisfaction. The analyses showed that body satisfaction was significantly related to total psychological problems and both internalizing and externalizing problems. Greater body dissatisfaction is significantly associated with worse psychological functioning in adolescents with GI. Clinicians should monitor the body image of adolescents with GI over time, especially during puberty and medical interventions. Usually, sex is identified by sex chromosomes, gonads, and genitalia . Gender Body image can be defined as a person’s self-concept, consisting of attitudes, experiences, and perceptions pertaining to one’s physical appearance, in relation to the social context . PreviouWhen looking at sex assigned at birth differences in adults with GI, it has been observed that individuals assigned male at birth (AMAB) reported more body dissatisfaction than birth-assigned females (AFAB) ,10. The As described in the literature, experiences of body image and psychological functioning are related. In studies on adolescents from the general population, body dissatisfaction was found to be a significant risk factor for having psychological problems, such as eating disorders and depression ,15,16. SIn addition, it is well known that adolescents with GI tend to experience emotional and behavioral problems . In clinPrevious studies have highlighted the importance of assessing the body image of individuals with GI in relation to mental health outcomes . To the Between 1996 and 2016, 1188 adolescents were referred to the Center of Expertise on Gender Dysphoria at the Amsterdam University Medical Center (location VUmc), in Amsterdam, The Netherlands. Every individual that is referred to the Center of Expertise starts with an assessment period that includes, in addition to consultations, structural information collection with questionnaires.All individuals that completed the measures for assessing body image as well as psychological functioning were included in this study. Participants were excluded when more than 20% of the questionnaire items were missing, which led to the exclusion of 401 adolescents. This resulted in a total sample of 787 adolescents between the ages of 10 and 18, of which 297 were AMAB and 490 were AFAB. As all data for this study were collected at intake, the adolescents had not yet received any medical gender-affirming treatment. All data were anonymized and treated confidentially. This study does not fall under the scope of the Dutch Medical Research Involving Human Subjects Act (WMO) and does not require ethical approval. Participants provided informed consent following the good clinical practice guidelines.During the adolescent’s period of assessment at the center, the following questionnaires assessing demographics, IQ, gender identity, body image, and psychological functioning were administered:Demographics and IQ: Sociodemographic variables that were collected include age at intake, birth-assigned sex, parents’ marital status, and total IQ. The parents’ marital status was classified as “two biological parents” and “other” . IQ was assessed using the Dutch versions of the Wechsler Preschool and Primary Scale of Intelligence or the Wechsler Intelligence Scale for Children ,23.Body image: The Body Image Scale (BIS) was developed specifically for assessing the body satisfaction of people with GI . In the T-score values were used. Additionally, clinical range scores were reported for the scales. T-score values above 63 were scored in the clinical range [Psychological functioning: The Youth Self-Report (YSR) is a standardized measure of the psychological functioning of young people aged 6–18 years ,26. It it-tests. An ANCOVA was used to determine birth-assigned sex differences in BIS total and subscale scores, correcting for the age and marital status of the parents. Zero-order correlations were performed to determine which demographic variables had a significant correlation with the outcome variable and therefore should be included in further analyses.Differences between individuals AMAB and individuals AFAB in sociodemographic variables were explored with the use of chi-square tests and T-scores and internalizing and externalizing T-scores were analyzed with the use of a linear regression analysis. Furthermore, linear regression analyses were performed with the six body area subscales of the BIS and the dependent variable YSR total problem T-score to determine whether the association differs between body area subscales. For analyses on the subscales, Bonferroni corrections were performed. Finally, logistic regression analyses were performed on the association between body image and YSR clinical range scores for total, internalizing, and externalizing problems.To answer the research question, multiple linear regression analyses were performed with body image as the independent variable and psychological functioning as the dependent variable to examine whether body image was significantly associated with psychological functioning. YSR mean total problem Statistical analyses were performed with IBM SPSS Statistics version 24. An alpha (α) of 0.05 was used to determine statistical significance.n = 401) and included (n = 787) groups. The mean IQ of the included adolescents was significantly higher  than that of the excluded adolescents , t(937) = −2.414, p = 0.016. Adolescents from the included group more often lived with both biological parents (59.3%) than adolescents from the excluded group (51.3%), X²(1) = 4.993, p = 0.025. There were no significant differences in birth-assigned sex or age at intake.We checked for differences in demographics between the excluded (t(574) = −3.443, p = 0.01). Those AMAB more often lived with both biological parents (χ²(1) = 4.335, p = 0.037). Age at intake and marital status of the parents were thus included as covariates in all further analyses.The demographic characteristics of the study population are presented in p < 0.001), head and neck region  = 44.185, p < 0.001), muscularity and posture  = 9.010, p = 0.003), hip region  = 78.367, p < 0.001), and chest region  = 72.103, p < 0.001). Those AFAB were more dissatisfied with their hip and chest region, while those AMAB expressed more dissatisfaction with social and hair items, head and neck region, and muscularity and posture. There was no birth-assigned sex difference for the subscale genitals.T-scores were examined using multiple linear regression analyses. The outcomes are shown in T-score, with a higher score on the BIS being associated with a higher score on the YSR. No interaction effects were found with birth-assigned sex or age at intake.Psychological functioning scores can be found in T-score: social and hair items  = 17.860, p < 0.001), head and neck region  = 15.220, p < 0.001), muscularity and posture  = 16.539, p < 0.001), hip region  = 16.032, p < 0.001), and chest region  = 13.236, p < 0.001). After Bonferroni correction, the effect of the chest region on the YSR total T-score was no longer significant. All scales but the genital one were significantly associated with the YSR internalizing T-score but only the muscularity and posture subscale was significantly associated with YSR externalizing T-score. This effect did not remain significant after a Bonferroni correction, while all relations with the internalizing scale remained. Greater body dissatisfaction on any of the body area scales but the genital one was related to a higher T-score on the YSR total scale. No interaction effects with birth-assigned sex or age were found.Separate multiple linear regression analyses were performed in step 1 on birth-assigned sex, age, marital status of the parents, and IQ, and in step 2 on each of the six body area subscales of the BIS. The results are shown in Multiple logistic regression analyses with YSR clinical range as the outcome variable were performed. Step 1 included demographic control variables as predictors. Step 2 included the BIS total score as a predictor variable and showed a significant association with the clinical range for YSR total and internalizing problems, where a higher score on the BIS was related to higher odds of being in the clinical range for emotional and behavioral problems. There was no significant association with the externalizing clinical range score. The results are shown in In this study, body image, including birth-assigned sex differences, and the association between psychological functioning of adolescents with GI and their body image were explored.The first aim of our study was to describe the body (dis)satisfaction of Dutch adolescents referred for GI and determine birth-assigned sex differences. For the total group overall, dissatisfaction with the genital area was much higher than the other body areas, which has been described previously . This haIn line with the second hypothesis of our study, the main finding was that body dissatisfaction was found to be associated with experiencing clinically relevant psychological problems in adolescents with GI. These outcomes are in line with existing literature from the general population, which has shown that body dissatisfaction is associated with psychological problems, such as depressive mood, eating disorders, and low self-esteem .Regarding the third aim of the study, we found an association with total and internalizing psychological problems for all body areas but the genital area. We hypothesize that the absence of an effect for the genital area is due to a ceiling effect, as there was little variability in this scale. For adolescents with GI, it has previously been described that the sex-specific physical changes and anticipated feminization or masculinization that occur during puberty can cause distress ,30,31. TPrevious studies have shown that adolescents with GI may have a less favorable body image than adults with GI  but theyA limitation of this study is that the puberty status of the adolescents at intake was unknown. As a result, this could not be adjusted for. Moreover, it is important to remain aware of the heterogeneity of the transgender population and the multiple gender identities in the population, which is known to be related to body satisfaction and psychological functioning ,36,37.In conclusion, high levels of body dissatisfaction can lead to a negative body image and worse psychological functioning in adolescents with GI. Furthermore, it is a significant predictor of lower quality of life . Therefo


Cryptosporidium, and triclosan to 107 rivers draining into the Black Sea. We apply a multi-pollutant model for 2010, 2050, and 2100. In the future, over half of the rivers will be more polluted than in 2010. The population in 74 sub-basins may drop by over 25% in our economic scenario with poor wastewater treatment. Over two-thirds of the people will live in cities and the economy may grow 9-fold in the region. Advanced wastewater treatment could minimize trade-offs between economy and pollution: our Sustainability scenario projects a 68–98% decline in point-source pollution by 2100. Making this future reality will require coordinated international efforts.The population in the Black Sea region is expected to decline in the future. However, a better understanding of how river pollution is affected by declining trends in population and increasing trends in economic developments and urbanization is needed. This study aims to quantify future trends in point-source emissions of nutrients, microplastics, The online version of this article (10.1007/s13280-022-01780-6) contains supplementary material, which is available to authorized users. Surface water quality depends on human activities in drainage basins. In many world regions, population growth and urbanization are drivers of water pollution in the future (Jiang and O’Neill S1). Many rivers draining into the Black Sea are transboundary . Our study focuses on the short-term (2010–2050) and long-term (2050–2100) future. Our focus on nutrients, microplastics, Cryptosporidium and triclosan is motivated by their impacts on nature and society and that these pollutants can be considered indicators of pressing and emerging water pollution problems . We develop and evaluate a sub-basin version of the MARINA-Global model: Model to Assess River Inputs of pollutAnts to seAs . Our model is different from the original MARINA-Global model . We ran the model for 2010, 2050, and 2100 to quantify inputs of pollutants to the rivers in the sub-basins from point sources (Box S1). This means that our model is consistent in the spatial scale between the model inputs, calculation units and model outputs.Our model calculates inputs of the pollutants using sub-basins as calculation units. The previous version of the MARINA-Global model used a 0.5° grid as a calculation unit . Focusing explicitly on dissolved inorganic and organic forms allows us to better understand their sources in rivers.We split N and P into dissolved inorganic  and organic  forms following the approach of Mayorga et al. . The earCryptosporidium, triclosan and microplastics. Our current model has seven: DIN, DON, DIP, DOP, Cryptosporidium, triclosan and microplastics. This implies that the multi-pollutant focus is expanded in our model for the Black Sea.As a result, our model has been extended with more water quality variables. The earlier version , their connection rates to sewage systems, excretion or consumption rates of pollutants per capita, and the removal fractions of pollutants during wastewater treatment. Open defecation is a direct discharge of N, P, Cryptosporidium to rivers through human feces and urine . The model quantifies inputs of these pollutants to rivers from open defecation as a function of the population  practicing open defecation and excretion rates of the pollutants per capita. Below, Eqs. S1.i to rivers of sub-basins sb from all sources (sewage systems and open defecation). The unit is oocyst/year for Cryptosporidium, kg/year for nutrients, and microplastics, and g/year for triclosan. i to rivers of sub-basin sb from open defecation resulting from all population. The unit is oocyst/year for Cryptosporidium, kg/year for nutrients, and microplastics, and g/year for triclosan. i to rivers of sub-basin sb from sewage systems resulting from all population. The unit is oocyst/year for Cryptosporidium, kg/year for nutrients, and microplastics, and g/year for triclosan. i in sub-basin sb. The unit is oocyst/cap/year for Cryptosporidium, kg/cap/year for nutrients and microplastics, and g/cap/year for triclosan. The excretion rates are for N, P and Cryptosporidium in human waste (feces and urine). Consumption rates are for triclosan from personal care products and for microplastics from personal care products, car tyres, household dust and laundry. i during treatment in sub-basin sb (0–1).We develop a new sub-basin version for 107 sub-basins of the Black Sea region for 2010, 2050 and 2100 . Total, urban and rural population is available at the grid of 0.5° (Jones and O’Neill https://washdata.org/). This data was processed and provided from existing studies . We processed raw inputs to sub-basins using population. Table S2 explains how we did this. Model evaluation is described in “All data and its sources are in Fig. S6). These are a Business as Usual (BAU), Economy, and Sustainability scenario. The three scenarios are selected to reflect different future trends in socio-economic development, urbanization, and wastewater treatment. The Economy and Sustainability scenarios assume high economic development and rapid urbanization, but differ in their approaches towards sustainability. The difference between the two can be used to analyze the effects of environmental policies under economic growth. The BAU scenario is selected to show the situation in the future following the historical trends, with a lower economic growth than the Economy scenario. BAU follows trends from Shared Socio-economic Pathway 2 ”. The Economy and Sustainability scenarios are based on SSP5 and SSP1, respectively.We implemented three scenarios to analyze future pollution of rivers draining into the Black Sea based on the data from Strokal et al.  and StroS1). Strokal et al. .In our scenarios, the socio-economic development includes population , gross domestic products (GDP), and human development index (HDI). Urbanization includes connection rates of the population to sewage systems and wastewater treatment. Open defecation reflects sanitation. Population and GDP for 2050 and 2100 are based on SSP1 (for the Sustainability scenario), SSP2 (for the BAU scenario) and SSP5 (for the Economy scenario). Values for these model inputs are directly taken from existing studies . In 2010, 187 million people lived in the drainage area. By 2100, the population is projected to have decreased by 20%. HDI is expected to increase by 10% between 2010 and 2050 and further increase by 10% by 2100 . GDP is expected to increase by 366% between 2010 and 2100 . People will be richer and cities will have more sewage systems. As a result, the connection rates of people will increase, reaching 88% in 2100 . Wastewater treatment will slightly improve in the future compared to 2010 .In the BAU scenario, the population and GDP trends follow SSP2 (Table S6). Between 2010 and 2100, the population is projected to decrease by 24% . In contrast, GDP is projected to substantially increase by 774% by 2100 . Most people are expected to be connected to sewage systems . Wastewater treatment will improve, but not largely compared to BAU and 2010 .In the Economy scenario, trends in population and GDP follow SSP5 (Table S6). The population is also projected to decrease in the future , leading to higher HDI in the future . Most people will be connected to sewage systems. Open defecation and the use of P detergents will stop . However, the wastewater treatment will improve largely, which is not in the other two scenarios . This is because in this scenario, supporting the Sustainable Development Goals (SDGs) is an important aspect. People will invest in implementing the best available today technologies to remove N, P, Cryptosporidium, triclosan, and microplastics in sewage influents. Examples of such technologies are efficient ultrafiltration for Cryptosporidium , 73 kton of total dissolved P (TDP), 20 kton of microplastics, and 30 ton of triclosan . Almost all pollutants were from sewage systems and the remainder was from open defecation. Many northern sub-basins of the Danube and Dnieper received above 50 kg of TDN, 5 kg of TDP, 5 kg of microplastics, and 5 g of triclosan per km2 .Rivers received 6.7 × 10River pollution in the drainage basin is projected to increase by 25% for TDN and 5% for microplastics during 2010–2100 Fig. a. For thCryptosporidium in most sub-basins of the Danube and Dnieper during 2010–2050 and 2050–2100 . By 2100, almost all southern rivers will receive more inputs of TDN, TDP, and triclosan than in 2050 despite decreasing trends in the population . By 2100, wastewater treatment may improve especially in the Russian sub-basins . However, it will not be enough to reduce inputs of TDN and triclosan to some rivers in 2100 to below the level of 2050 , increasing trends > 25%) are projected for TDN, TDP, microplastics, and triclosan during 2010–2050 . As a result, over half of the drainage area will experience multi-pollutant problems by 2100  to − 94% (decrease) among sub-basins during 2010–2100. The range for TDN is from + 581% (increase) to − 74% (decrease). Large ranges among sub-basins are also calculated for TDP, microplastics, and triclosan . However, in this scenario, the priority is given to sustainable practices to support SDGs for cities (SDG11), clean water (SDG6), and a healthy economy (SDG8). As a result, advanced technologies will be implemented to treat wastewater. This scenario assumes the implementation of tertiary technologies  that can remove more than 75% of the five pollutants from the wastewater in sewage systems according to the existing studies  using observations of nutrients at the river mouth. Observations were available for around 2000 for eight rivers: the Danube, Dnepr, Don, Dniester, Bug, Kuban, Sakarya and Yesil  for nutrients. The other models  were evaluated with a comprehensive sensitivity analysis . Our results for N and P are in the range of the existing modeling studies (Table S7). For example, annual inputs of total N from point sources to all rivers draining into the Black Sea are 0.42 Tg in our study. The other existing studies estimate between 0.35 and 1.3 Tg/year (see Table S7). For total P, our estimate is 0.07 Tg/year, which is close to the existing studies of 0.07–0.15 Tg/year (see Table S7). For the Danube, our estimate is 95 kton of DIN and 23 kton of DON in the river. These values are 77 kton for DIN and 19 kton for DON according to Global NEWS-2. In contrast, the Don River receive 23 kton of DIN and 8 kton of DIP in 2010 according to our model, which is lower than in Global NEWS-2 . The differences between our and Global NEWS-2 models are because the models differ in time and space. We focus on the year 2010. Global NEWS provided estimates for the year 2000. Between 2000 and 2010, the socio-economic developments may have changed, leading to higher or lower pollution levels in 2010. Another reason is that we consider more rivers than Global NEWS-2. The drainage areas of our rivers were delineated using land masks and water flows from the VIC hydrological model (Markert S7). We calculate 20 kton of microplastics in all rivers, which is close to the estimate of Siegfried et al. (S7 for references).Option 2 is to compare our model outputs with existing modeling studies. We compare point-source inputs of pollutants to rivers with earlier studies . The removal efficiencies and excretion rates are uncertain. They can vary considerably across scales and pollutants. In our model, we estimate the removal efficiencies using the population that has primary, secondary, and tertiary treatments  and their removal efficiencies for each pollutant . Our removal rates are averaged values for the sub-basins. The same holds for the excretion rates. Thus, we performed a sensitivity analysis. We changed the following model inputs by + 10%: urban and rural population, fractions of the urban and rural population connected to sewage systems, removal efficiencies, and excretion or consumption rates of pollutants . For this, we ran the model 30 times separately for five pollutants and six model inputs. Then, we compared the results of the model runs with the original model run. For this, we calculated the differences that are shown in Fig. Option 3 is to better understand the sensitivity of model outputs to changes in uncertain model inputs Fig. . We downCryptosporidium, nitrogen, and phosphorus) and Dnieper (for microplastics) range from 33% (microplastics) to 60% (Cryptosporidium)  Fig. . This mium) Fig. . This isum) Fig.  used theThe three abovementioned options help us to better understand the sources of the uncertainties and their implications for the main results. Uncertainties are largely associated with our steady-state modeling approach (Options 1–2), processing model inputs (Option 3), and scenario assumptions. The steady-state modeling approach does not consider dynamics and legacy effects. These are important aspects to consider in studies on seasonality and river exports. Our study focuses on annual, long-term trends (2010–2100) in emissions of pollutants to rivers from sewage and open defecation. The other source of uncertainties is associated with our scenarios, which should not be interpreted as predictions. Rather, we aim to explore possible futures according to the BAU, Economy, and Sustainability trends. This scenario analysis is widely used in water quality assessments . We realize that many more pollutants exist in water  and long-term (2050–2100) futures. This helps to better understand the causes of water pollution in the near and far future. For example, in the short-term (2010–2050), water pollution is expected to be higher in many rivers and for most of the studied pollutants in the BAU and Economy scenarios . When studying point-source pollution in rivers, there are a few important drivers: demography, urbanization, sewage connection, and wastewater treatment . In 2010, the population density was generally higher in the western and northern parts of the Black Sea basin  compared to the eastern and southern parts . More people were generally connected to sewage systems in the western  than in the eastern part of the Black Sea basin  in 2010 . Exceptions are the Danube upstream and southern sub-basins for which we calculate increases in the population by up to 50% . Future trends differ among sub-basins . During 2050–2100, the population densities are projected to decrease in many sub-basins. Most of the population will be urban and connected to sewage systems in 2100 . People will become richer . People can afford more meat in their diets, increasing N and P intake per capita. This will lead to more N and P excretion per capita and thus more N and P in sewage systems. People can afford more cars, leading to more microplastics in sewage systems from car tire wear. In contrast, higher human development . Our multi-pollutant approach differs from many other studies focusing on single pollution types such as eutrophication Below is the link to the electronic supplementary material.