Bacteria and respiratory viruses co-occur in the nasopharynx, and their interactions may impact pathogenesis of invasive disease. Associations of viruses and bacteria in the nasopharynx may be affected by HIV.We conducted a nested case-control study from a larger cohort study of banked nasopharyngeal swabs from families with and without HIV in West Bengal India, to look at the association of viruses and bacteria in the nasopharynx of parents and children when they are asymptomatic. Quantitative polymerase chain reaction for 4 bacteria and 21 respiratory viruses was run on 92 random nasopharyngeal swabs from children--49 from children living with HIV (CLH) and 43 from HIV uninfected children (HUC)-- and 77 swabs from their parents (44 parents of CLH and 33 parents of HUC).Staphylococcus aureus (53%) was the most common bacteria, followed by Streptococcus pneumoniae (pneumococcus) (37%) in children and parents . Regardless of HIV status, viruses were detected in higher numbers (44%) in children than their parents (30%) (p = 0.049), particularly rhinovirus (p = 0.02). Human rhinovirus was the most frequently found virus in both CLH and HUC. Children with adenovirus were at six times increased risk of also having pneumococcus  regardless of HIV status. In addition, the presence of rhinovirus in children was associated with increased pneumococcal density . In CLH the presence of rhinovirus increased the risk of pneumococcal colonization by nearly sixteen times , and, pneumococcus and S. aureus dual colonization by nearly nine times (OR 8.7).Bacteria was found in 67% of children, viruses in 45%, and both in 27% of child samples. S. aureus.Children more frequently carried viruses regardless of HIV status. In CLH the presence of rhinovirus, the most frequently detected virus, significantly increased co-colonization with pneumococcus and  The nasopharyngeal ecosystem composed of respiratory viruses and bacteria is dynamic , 2. Its S. aureus disease 40–300 times, and nasopharyngeal bacterial colonization usually precedes invasive disease ; . 98% of mothers of CLH were living with HIV. Mothers contributed 92% of all parental swabs.The demographics are described in Table 3.Nearly 36% (18/49) of CLH were on antiretroviral treatment (ART) and 51% were on TMP/SMX prophylaxis Table . 53% of p = 0.06), suggesting the increased risk of otitis media in CLH.We noted the clinical history of children prior to NP specimen collection, and found 28% of CLH, and 21% of HUC, were sick in the past week. The major symptoms included fever, cough, rhinitis or diarrhea; however, during swab collection all children were afebrile (< 100.4 °F) and asymptomatic. Over 23% of CLH had a history of ear infection within 1 month prior to study, compared to 4% in HUC ; pneumococcus (20%)]. Higher rates of pneumococcus were found in children compared to parents (p = 0.02).A total of 169 NP swabs  were tested for viruses and 147  for bacteria (Table S. aureus were the most frequent bacteria co-detected (24%) in children. Viruses were detected in higher numbers (44%) in children than their parents (30%) (p = 0.049), particularly rhinovirus (p = 0.02). Viruses with bacteria were more frequently co-detected in children (26%), than virus alone (3%). For example, 13 out of 15 times rhinovirus was detected with bacteria, and adenovirus was found with bacteria 8 out of 9 times.Pneumococcus with Bacterial pathogens were tested in specimens from 43 CLH, 40 HUC, and viruses in 49 CLH, 43 HUC . Similar pneumococcus and C. pneumoniae rates were found in CLH and HUC . Nearly 69% (11/16) of CLH with pneumococcus and 51% (14/27) of CLH with S. aureus were on TMP/SMX prophylaxis. This suggests TMP/SMX did not decrease their risk for carriage. Co-occurrence of pneumococcus with S. aureus was found more often in CLH (30%), than in HUC (17%), although not significant (p = 0.17). We could not detect Hib by PCR in both the groups regardless of HibCV vaccination status.Bacteria were identified in 70% of CLH and 65% of HUC. p = < 0.001). 57% of CLH with viral positivity were not on ART. Rhinovirus was also most frequent in HUC (18%). Influenza B was identified only in HUC (9%). Being on an antibiotic in the past week, increased the risk of virus detection by 3.85 times, .In the 92 samples tested, viruses were detected in 41% of CLH and 49% of HUC. Rhinovirus and adenovirus were most frequently detected in CLH (14% each), followed by bocavirus 4%, RSV 2%, coronavirus-229 2%, human metapneumovirus 2% and human parainfluenza-3 virus (2%). Of interest, viruses were identified mainly in children with stage 2 and 3 HIV disease (13/14), than stage 1 (1/14) (p < 0.001). Interestingly, wood used for cooking within households, increased the risk of virus  and virus-bacteria detection  among children, suggesting indoor air pollution may increase the risk for viral circulation.The co-occurrence of ≥1 bacteria with ≥1 viruses was found in 28% of CLH, and 25% of HUC. The co-occurrence was mainly found in children with stage 2 and stage 3 HIV disease (11/12), as compared to stage 1 (1/12) (S. aureus was most frequent in both PCLH (51%) and PHUC (58%). Similar rates of pneumococcus (20–21%) were detected in both parents, and their children. Viruses were detected in 34% of PCLH and 27% of PHUC. Adenovirus was most common in PCLH (11%), and RSV in PHUC (12%). Virus-bacteria co-detection was found in 16% of PHUC and 12% of PCLH.Bacteria were tested in 33 PCLH and 31 PHUC specimens, and viruses in 44 PCLH and 33 PHUC. Bacteria were detected in 51% of PCLH and 58% of PHUC. S. pneumoniae + S. aureus with viruses. The remaining 5 CLH had co-occurrence of viruses with pneumococcus (2), or S. aureus (3). Among the HUC, viruses were co-detected with pneumococcus (3), S. aureus (3), S. pneumoniae + S. aureus (3), or, C. pneumoniae (1). Among parents, viruses were co-detected only with S. aureus (8/64).Virus-bacteria co-detections were found in 12 CLH and 10 HUC. Of the 12 CLH, 7 had co-occurrence of p = 0.005), and 3.65 times virus-bacteria co-detection . CLH with symptoms in the past week, had 6 times increased risk of virus detection , as compared to 2 fold in HUC .A history of respiratory symptoms in the past week was associated with more than 4 times increased risk of virus detection in children  (Table p = 0.036). Increased pneumococcal density was seen with co-detection of viruses (Coeff 3.6), multiple viruses (Coeff 5), and rhinovirus specifically (Coeff 4.5) in children regardless of their HIV status.9) Table , particuS. aureus dual colonization increased nearly 9 times in the presence of rhinovirus (OR 8.7).In CLH, the presence of rhinovirus increased the risk of pneumococcal colonization by nearly sixteen times (OR 15.6), and pneumococcus and This is the first report from India about household level prevalence and association of respiratory viruses with bacteria in parents and children in the context of HIV, using multiplex real time PCR. In this study, we found higher prevalence of bacteria and viruses in children than their parents regardless of HIV status. This suggests parents or caregivers are at increased risk of exposure to viruses and bacteria in households with children. This is in agreement with the results of our immunization study where we found bacterial carriage within the households-- carriage in children predicted the carriage in parents and thus immunization in children indirectly impacts the carriage in unvaccinated adults.S. aureus carriage in CLH, as compared to HUC [S. aureus. This could be due to the resistance of pneumococcal isolates to TMP/SMX, as we saw in 98% of isolates in the past [A majority of the CLH had moderate to severe HIV disease and were not on ART, which increased their risk for bacteria and virus detection . CLH livd to HUC –31, whild to HUC . Althougd to HUC , 32. Furd to HUC . The difd to HUC , 33. Thed to HUC , and Indd to HUC . While rd to HUC , in Brazd to HUC , Mozambid to HUC , and Soud to HUC . SerotypS. aureus in those living with HIV could be immune-mediated due to decrease in pneumococcal-specific CD4+T cells in HIV infected individuals [S. aureus seen in HIV uninfected children, has been observed following antiretroviral treatment in CLH [The co-colonization of otherwise competing pneumococcus and ividuals . The intt in CLH .S. aureus in symptomatic individuals living with HIV [S. aureus, and pneumococcus in CLH, when they were asymptomatic.Rhinovirus and pneumococcus have been observed to be positively associated in healthy children under-2 . An Indiwith HIV . We alsoViral infections commonly cause hospitalizations in CLH, and rhinovirus and adenovirus in particular are responsible for LRTI and acute otitis media (AOM) in both HUC and CLH , 17, 40.S. aureus, and nontypeable H. influenzae are particularly important in the pathogenesis of these conditions [Otitis media and LRTI cause significant morbidity and mortality in CLH . Bacterinditions . In studnditions .Association of increased pneumococcal density with viruses, has been observed during asymptomatic , and symS. aureus, and rhinovirus in CLH, supports the increased risk of polymicrobial pneumonias in CLH. Pneumococcal conjugate vaccines impact the nasopharyngeal ecology and the risk of LRTI and AOM in adults and children with HIV [The major findings of this study are the detection of viruses with increasing pneumococcal density in asymptomatic children, and rhinovirus co-detection with pneumococcus in CLH compared to age-matched HUC. Association between pneumococcus, with HIV , 55, 56.The study is limited in its sample size, therefore confidence intervals were wide for OR, and we could not do multivariate analysis for association between microbes. The swabs were part of a vaccine impact study and were combined from pre and post immunization visits, so there was an inherent bias in the selection; however, the overall pneumococcal carriage was not affected. The clinical relevance of viral activity with increasing pneumococcal density in asymptomatic children requires further study through well designed cohort studies.Pneumococcal-viral interactions are complex. Larger longitudinal studies are needed to understand the viral-bacterial dynamics in high-risk families, in both asymptomatic, and symptomatic situations. Viral load, and host immune responses, may better differentiate asymptomatic versus active viral infections . India hIn conclusion, this study demonstrates high detection of viruses and bacteria in asymptomatic children with and without HIV and shows that pneumococcal density increases in the presence of viruses.


DRD1 and DRD2 dopamine receptor single nucleotide polymorphisms (SNPs) as potential risk factors for ASD, ADHD, and ASD/ADHD overlap. Genetic data were obtained from four groups: 75 ASD patients, 75 ADHD patients, 30 patients with ASD/ADHD overlap, and 75 healthy controls. All participants were between 2 and 17 years old. We compared the genotypic and allelic frequency of 18 SNPs among all of the study groups. Moreover, in the case of statistically significant differences, odds ratios (OR) were obtained to evaluate if the presence of SNPs might be a risk factor of developing a specific clinical phenotype. This study found that DRD1 and DRD2 receptors SNPs might be considered as potential risk factors for ASD and ADHD. However, only DRD2-12 (rs7131465) was significantly associated with a higher risk for the ASD/ADHD overlap. These data support the hypothesis of the genetic neuromodulation of the DS in the neurobiology of these conditions.The dopaminergic system (DS) is one of the most important neuromodulator systems involved in complex functions that are compromised in both autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), conditions that frequently occur in overlap. This evidence suggests that both disorders might have common neurobiological pathways involving the DS. Therefore, the aim of this study was to examine the  Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), as well as bipolar disorder or schizophrenia, are neuropsychiatric disorders characterized by strong genetic bases . The dopThese alterations may be related to different consequences: a selective deficit of dopamine (DA), and genetic mutations to the genes involved in synaptic homeostasis, as DA receptors, membrane transporters, or the enzymes designated to DA degradation or reuptake.Genome-wide association studies (GWAS) significantly contributed to the identification of several genome variants known as single nucleotide polymorphisms (SNPs) associated with neuropsychiatric disorders . These gGiven the multitude of gene variants and possible mechanisms, several studies investigated the correlation between the SNPs involving the DS and ASD or ADHD.Attention deficit/hyperactivity disorder is a neurodevelopmental disorder (NDD) characterized by a persistent pattern ofattention deficit, hyperactivity, and impulsivity; it is one of the most common NDDs with a complex etiology and a strong genetic component . The cliAs in ADHD, the DS is also involved in the ethology of ASD . ASD is Recent studies have already identified hundreds of ASD-related gene variant encoding for synaptic proteins, transcription factors, epigenetic modulators and molecules involved in intracellular signaling . The DS Autism spectrum disorder and ADHD share common clinical features related to the impairment of several functions, such as attention skills, executive functions, and motor and social skills . The oveAccording to a recent review, the prevalence of ASD/ADHD overlap has increased over the years, and these disorders seem to share genetic heritability and some clinical features . Other sTherefore, the purpose of this study was to provide new results that might confirm and support the involvement of DS in the pathogenesis of ASD, ADHD, and their overlap, focusing on dopaminergic receptor SNPs as possible genetic risk factors for these conditions.For the study, patients diagnosed with ASD, ADHD, and ASD/ADHD overlap were recruited at the Childhood and Adolescence Neuropsychiatry Unit, University of Bari Aldo Moro, from 2015 to 2019.The inclusion criteria were patients diagnosed with ASD, ADHD, and ASD/ADHD overlap, and aged between 2 and 17 years. The diagnoses were made according to the diagnostic criteria of the DSM-5 . We deciThe exclusion criteria were patients suffering from ASD and ADHD attributable to known genetic syndromes or other medical conditions .For comparison and risk assessment of genotypes, 75 subjects aged between 2 and 17 years that had surgery and without any neurodevelopmental disorders were recruited at the Pediatric Surgery Unit, Giovanni XXIII Hospital, Bari, as controls.The study was approved by the Local Ethical Committee (protocol number 592/12) and for all participants, informed consent was collected from their parents.DRD1 and some DRD2 SNPs involved in this study were already known in the literature. Furthermore, using http://www.ncbi.nlm.nih.gov/nuccore/209977039?report=genbank&to=72685, we searched for all polymorphisms of the DRD2 gene that are currently identified.The choice of polymorphisms was influenced by several factors. https://www.ebi.ac.uk/Tools/seqstats/emboss_cpgplot/) we identified two regions within the introns of the DRD2 gene that are unusually enriched with CpG dinucleotides; the first extends from nucleotide 4,634 up to nucleotide 5,660 (therefore longer than 1 kb), and the second extends from nucleotide 5,740 up to 5,953 (214 base pair long).Since the methylation profiles of regions containing CpG islands could influence the levels of gene expression, using the CpGplot program of the EMBOSS package  in principle and, among these, only those that could be discriminated using the restriction fragment length polymorphism (RFLP) technique were considered.This technique involves the use of restriction enzymes that recognize and cut specific DNA sequences. The enzymatic cutting is usually carried out in correspondence with the polymorphic sequence, allowing the recognition of the nucleotide variation.1. The first program used was NEBcutter®2, which allows the identification of restriction enzymes able to discriminate the polymorphic sequence. We then moved on to the Primer3 program (see 0.4.0) (available at http://bioinfo.ut.ee/primer3-0.4.0/primer3/) to design amplification primers for the restriction sites and, finally, the REBsites program3 was used to predict the length of the fragments obtained after the restriction enzyme cutting. The genotyping of the recruited subjects was carried out using venous blood samples from patients and controls. To isolate the leukocytes of the study subjects, a sample was taken in tubes containing sodium citrate. A total of 10 ml of peripheral blood was mixed in a 1:1 ratio with Emagel  heparinized (5 U.I. of heparin per ml of Emagel). The obtained solution was placed on a rotor for 10 min at the end of which the red cells were left to settle. The supernatant thus obtained was centrifuged at 1,600 rpm for 10 min. The pellet was re-suspended in 5 ml of 1X PBS and centrifuged at 1,600 rpm for 10 min. To remove the present cells, an osmotic shock was applied: the pellet was then re-suspended in 1 ml of 0.2% NaCl and vortexed for 1 min. Subsequently, 1 ml of 1.6% NaCl was added and the suspension was then centrifuged at 1,200 rpm for 10 min. Where necessary, the osmotic shock was repeated. The pellet was finally re-suspended in 1 ml of physiological solution and the leukocytes were counted in the Burker chamber. After cell counting, 10 × 106 cell aliquots were used to extract DNA using DNAzol® Reagent .The search for restriction enzymes to be used was conducted using the programs available on the New England Biolabs websiteThe DNA concentration was measured by spectrophotometer and the solution was diluted with H2O RNasi and DNasi free (SIGMA) to obtain a final value of 100 ng/μl. Each polymorphic region was amplified using 100 ng DNA, 5 μl 10X PCR buffer, 3 μl 25 mM MgCl2, 2 μl 10 mM dNTPs mix, 0.5 μl AmpliTaq Gold 5 U/μl  and 1 μl of specific primer . The thermal protocol used was the same for all reactions, with an annealing temperature of 57°C and several cycles equal to 40. Cac8I, which was purchased from New England Biolabs . Then, 10 μl of amplified obtained from the PCR reaction was used for enzymatic cutting. The digestion mix was prepared using 2 μl of specific digestion buffer and 1 U of the enzyme in a total volume of 20 μl. The reaction was carried out for 1 h in a thermostatic bath by varying the temperature depending on the enzyme used, as specified in All of the endonucleases used were purchased from Thermo Scientific  except for the enzyme The information about each polymorphism is obtainable from the NCBI database; db SNPs with the relative expected digestion fragments predicted by the REBsite software are described in detail in the DRD1-B (rs4532) polymorphism, is shown in An example of genotyping, regarding DRD SNPs under study and the risk of childhood ADHD, ASD and ASD/ADHD overlap phenotypes, both genotypic and allelic frequencies related to each SNP were compared among the groups reported above and the group of subjects unaffected by any neuropsychiatric pathology (control group) by the Chi-squared test or the Fisher’s Exact test, where appropriate, .To determine the relationship between Further the genotypic association analysis under the dominant and recessive models of inheritance were performed.P-value was < 0.05.The differences were considered statistically significant if the For the latter, the odds ratio (OR) and the 95% confidence interval (95% CI) were then calculated to assess the risk of expressing or not expressing the pathological phenotype for the group under examination compared to the reference group, based on the presence of the minor allele.P-value). Data were analyzed with R version 4.0.2.A multiple testing correction  was performed to guard against the potential for false positive associations .About rs2245805 and rs7131465 appeared to be associated with the increased risk of developing ASD/ADHD overlap compared to the other clinical phenotypes.The most relevant results came from the analysis of D2 receptor polymorphisms. Indeed, rs144851051 and rs2734832 seems to promote the development of a singular clinical disease, that is ADHD vs. controls for rs144851051  and ADHD or ASD vs. overlap for rs2734832 .The presence of the minor allele in rs11608185 and rs61902807 could be protective factors for the development of the overlap condition.By contrast, rs7131465 (DRD2-12), both in genotypic and allelic distribution, remained after the correction.However, the false discovery rate method dramatically reduced the number of significantly different SNPs and only rs7131465, located in the 5′-terminal untranslated region (5′ UTR) of the DRD2 gene, seems to be a strong risk factor of developing ASD/ADHD overlap vs. a singular clinical disease, that is ASD or ADHD .The presence of the minor allele in SNP Actual results are impacted by the reduced sample size of overlap group and low statistical power of the comparison groups. To solve a similar situation, On our side, an enlarged ADHD or ASD group, including ADHD/ASD overlap, would lead to the loss of distinctive feature and prediction of specific risk for overlap patients.To support our findings about rs7131465 SNP, we took a different approach that is dominant and recessive models of inheritance .∗/C∗ homozygous minor allele or the A/C∗ heterozygous genotypes of rs7131465 showed an increased risk of overlap comparing to healthy controls , ASD  or ADHD  in a dominant model, but not a recessive model. The last two of them survived the multiple testing correction and remained statistically significant, i.e., overlap vs. ASD , overlap vs. ADHD .The group with the Crs7131465 in children with ASD or ADHD and healthy controls was observed, both in recessive or dominant model.No significant difference in the genotype distribution of DRD1 and DRD2 receptor polymorphisms might be considered as potential genetic risk factors for ASD, ADHD, and ASD/ADHD overlap.In this study, we aimed to investigate if specific D2 receptor, rs2245805 and rs7131465, respectively, DRD2-8 and DRD2-12, might be associated with ASD/ADHD overlap when compared with ASD, ADHD, and control groups. However, only the SNP rs7131465 (DRD-12) showed a statistically significant higher risk for the ASD/ADHD overlap.Our study found that two specific polymorphisms of the DRD2-12 is within the intronic region between exon 1 and exon 2 of 5′ UTR. This intronic region is large 50,391 base pair and rs7131465 is located near the beginning of exon 2. Currently, no study has been conducted that examined the effect of this polymorphism. Since UTRs are the regulatory elements of genes, acting as controllers of translation and RNA decay, as well as targets for RNA interference (RNAi) and playing a central role in post-transcriptional regulation, it should be no surprise that polymorphisms in 5′ UTRs have been linked to many human, mainly oncological and neurological, diseases , in social abilities, and in the executive functions, recent studies underlined that both ASD and ADHD retain qualitative and quantitative clinical differences in their phenotype . SNP rs7D1 and D2 receptors have been previously identified in patients with ASD  can be found in the article/The studies involving human participants were reviewed and approved by Local Ethical Committee—Policlinico of Bari (protocol number 592/12). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.MM, RP, and LM: conceptualization, writing—review and editing, supervision, and project administration. MM, RP, AnV, AlV, and RL: methodology and data curation. AnV, AlV, and RL: formal analysis. MM, RP, MP, AP, AG, OG, and RL: investigation. AnV, MP, AP, AG, and OG: resources. MM and RP: writing—original draft preparation. 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. 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This study investigated cognitive and emotional functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and disruptive, impulse-control, and conduct disorders (DICCD).Thirty patients with ADHD, 26 with DICCD, 22 with ADHD+DICCD were recruited from the outpatient department of Shanghai Changning Mental Health Center, plus 20 healthy controls (HC). Differences between the groups in cognitive and emotional functioning were examined using Golden’s Stroop and Emotional Stroop tests. For Emotional Stroop Mean reaction time (RT) of positive word (POS) and negative word (NEG) with color congruence (C) or incongruence (I) were recorded as POS-C, POS-I, NEG-C and NEG-I, respectively.For Golden’s interference scores (IGs), both errors and RTs in the ADHD group were higher than in the other groups. Longer mean RTs of POS-C, POS-I, NEG-C and neural word (NEU) of the ADHD group, and NEG-I of ADHD+DICCD and DICCD groups were observed compared to HC. After 12 weeks of methylphenidate treatment, differences between ADHD subgroups and HC on Golden’s Stroop RT disappeared, but differences in Golden’s Stroop errors and Emotional Stroop mean RTs remained. The ADHD+DICCD group showed longer mean RTs in NEG-C, NEG-I and NEU of the Emotional Stroop test than the ADHD group.Our study shows that regardless of emotional responding, deficit in cognitive control is the core symptom of ADHD. However, emotionally biased stimuli may cause response inhibitory dysfunction among DICCD with callous-unemotional traits, and the comorbidity of ADHD and DICCD tends to account for the negative emotional response characteristic of DICCD. These deficits may be eliminated by medication treatment in ADHD, but not the ADHD with comorbid DICCD. Our results support the notion that ADHD with comorbid DICCD is more closely related to DICCD than to ADHD. Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents that comprises core symptoms of high levels of inattention, motor hyperactivity, and impulsivity . ADHD raPreviously, ADHD and DICCD were classified under attention deficit and destructive behavior in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) . It was Neuropsychiatric research not only emphasizes the discussion of symptomatology, but also the neuroscientific perspective of the occurrence and development of ADHD . It is wA relevant theoretical framework is the EF model of ADHD, which is divided into two systems, “cool” and “hot” EF (CEF and HEF) . CEF, alThe pathogenicity of emotion is also closely associated with ADHD. Several theoretical models of ADHD , 20 acknThe Stroop test is the classic paradigm for CEF . In addiAll subjects were assessed using the Golden’s Stroop Test and Emotional Stroop Test to evaluate cognitive control and emotional responding. The task had been tested and validated in children , 29. Datα was set to 0.05 and power of test 1-β was 0.8. We used a completely random design to compare the mean of multiple samples for sample size estimation. The calculations showed that a sample of 80 met the minimum sample size required.Sample size was calculated using PASS 11 software. Significance level Declaration of Helsinki.This study was approved by the Institutional Ethical Committee for clinical research of Shanghai Changning Mental Health Center, Shanghai, China. All subjects were Han Chinese, and parental consent was obtained prior to participation. Written informed consent was provided in accordance with the n = 30), DICCD  and ADHD+DICCD  – plus 20 healthy controls (HC).All patients were from the outpatient department of Shanghai Changning Mental Health Center. There were three groups of patients – ADHD (The inclusion criteria were: (1) age between 9 and 16 years, pupils in grade three or above; (2) a diagnosis of ADHD or DICCD based on DSM-5 ; and (3)Diagnostic evaluation was performed by two experienced pediatric psychiatrists. Patients with suspected diagnosis or disagreement after consultation were not included in this study. HC, who were matches on age, IQ, sex, and educational background to patients, were recruited from primary and middle schools in Shanghai. HCs were screened by a psychiatrist of our team on ADHD, ODD and CD symptoms ahead of the study. See Fig. Under MPH condition - CONCERTA (methylphenidate HCl) Extended-release Tablets- , eighteen ADHD patients and 17 ADHD+DICCD patients who received the medication agreed to participate in the neuropsychological tests again after 12 weeks of treatment. The therapeutic regimen was not compulsory as our psychiatrists gave their patients to choose pharmacotherapy or general psychotherapy after being fully informed. We carry out a hotline to follow up throughout the process.WISC-IV  was usedPSQ  assessesIn Golden’s Stroop color and word test , 126 worIn the Emotional Stroop test , 60 wordAll data were evaluated by normality test and test of homogeneity of variance. Apart from the errors of Golden’s Stroop IG, the remaining variables of both Stroop tests had normal distribution and equal assumed variance. Programmer designed two emotional Stroop tests to balance the left and the right choice. Only one was kept in case that confuses participants if the rule changed during the study.n (%).The quantitative variables were expressed as mean ± standard deviation (SD) and qualitative variables as . Differences between groups were analyzed using Post Hoc tests. The sex ratio was checked by chi-square. Diagnostic classification uses four values as category variables . A two tailed p-value < 0.05 was predetermined as statistically significant. Bonferroni correction for multiple comparisons was applied, and the level was p = p’/c, c (number of pairwise comparisons) = (k (k-1)/2). After normal transformation if necessary, the non-normally distributed data were analyzed with statistical disposal for effect sizes employed by η2.SPSS 22.0 software was used to carry out statistical analyses. One-way ANOVA was conducted for variables with normal distribution and homogeneity of variance, and Kolmogorov-Smirnov Z Test or Kruskal-Wallis H Test was carried out for variables with skewed distribution or heterogeneity of variance like psychosomatic disorders, anxiety and errors of Stroop. Analysis of covariance was further conducted for the comparison of baseline and follow-up values of the Emotional Stroop test, with the difference in Golden’s Stroop RT IG before and after treatment as the covariable We compared differences in Golden’s Stroop test and Emotion Stroop test variables among the ADHD, ADHD+DICCD, DICCD and HC groups at baseline level as primary outcomes. For secondary outcomes, differences in those variables were compared between ADHD and ADHD+DICCD groups at follow-up (after 12 weeks of treatment), and differences between baseline and follow-up (cohort design) were compared within the ADHD group.χ2 = 2.734, p = 0.434), age , and IQ . See Table The four groups of participants (three groups of patients plus HC) did not differ in sex ratio , and they were further analyzed using Post Hoc comparisons for subgroups. The scores of CIH, Impulsivity/ Hyperactivity in the DICCD group were significantly lower than the ADHD and ADHD+DICCD groups but higher than the HC group. The scores of Conduct Problems in the ADHD group were lower than the ADHD+DICCD and DICCD groups but higher than the HC group. The scores of Difficulties in learning for all three disorder groups were higher than the HC group, but there was no statistical difference among the disorder groups. Compared to the HC group, scores of Anxiety of the ADHD group were significantly increased. The values were shown in Table The statistical difference scores of PSQ factors among the groups included CIH, Conduct Problems, Difficulties in Learning, Impulsivity/Hyperactivity, and Anxiety  and IG RT  yielded differences between groups. Post Hoc showed that IG errors in the ADHD group were higher than the ADHD+DICCD, DICCD and HC groups, and the IG RT was higher in the ADHD group compared to the HC group.In the Golden’s Stroop test, IG errors . Post Hoc tests showed that the longer POS-C of ADHD was observed compared to HC while longer POS-I, NEG-C and NEU of ADHD and ADHD+DICCD were observed compared to HC. However, longer mean RTs of NEG-I of ADHD+DICCD and DICCD were observed compared to HC while it yielded no difference between ADHD and HC. See Table In the Emotional Stroop test, the mean RT exhibited statistical difference among the groups , except for Psychosomatic Disorders  and Anxiety  subscales. In addition, the only significant difference in PSQ was Conduct Problems between ADHD subgroups  at follow-up. See Table After 12 weeks of MPH treatment (18 mg/d dose), there were still significant differences in the subscale scores of PSQ among the three groups . However, Emotional Stroop test showed that the mean RTs of NEG-C, NEG-I and NEU of ADHD+DICCD were longer compared to ADHD . See Table At follow-up, there were no statistical differences in the variables of Golden’s Stroop test between ADHD subgroups (p’s ≥ 0.05). No difference in Golden’s Stroop test RT was observed among the ADHD, ADHD+DBD and HC groups , but errors of Golden’s Stroop test for ADHD was higher than that for HC . For variables of Emotional Stroop test, statistical differences among the 3 groups were observed . Post Hoc tests showed that the mean RTs of NEG-I and NEU of ADHD+DICCD patients were significantly longer than those of ADHD patients and HC while the mean RTs of POS-C, POS-I, and NEG-C were significantly longer in the ADHD and ADHD+DICCD groups than those in the HC group. See Table In the cohort design, there were no differences in the variables of Golden’s or Emotional Stroop test in the ADHD or ADHD+DBD groups between the first test and 12-week retest  were able to distinguish between ADHD, DICCD and comorbidity. Moreover, the PSQ assessment of symptom reduction was also essential for the quantitative analysis of therapeutic effectiveness.Evidence supports the use of extended-release MPH to improve symptoms of ADHD in adolescents. Psychosocial treatments were associated with inconsistent effects on ADHD symptoms and greater benefit for academic and organizational skills . The priThe errors of IG showed a statistical difference between the ADHD subgroups at baseline level (before treatment), which disappeared after the 12-week treatment, but the errors for the patient groups were still higher than those of the HC group. On the other hand, the RT of IG normalized to HC level at follow-up. Results also verify CEF deficit as a phenotype of ADHD, and that the function can be improved by MPH treatment. Although there were differences in Emotional Stroop test between ADHD children and typically-developing children at baseline, there were no differences between the ADHD subgroups.Red has the additional meaning of Yang/positive/hot while blue implies Yin/negative/cold on the other hand. Yin and Yang are the two opposing principles in nature in the Chinese tradition. Therefore, red and blue were defined as “positive”and “negative” respectively, which is consistent with the theory of HEF and CEF. However, the significant differences were observed in the mean RT of NEG-I, and NEU among the ADHD subgroups. Our results suggest abnormal processes in negative emotional responding in the ADHD+DICCD group, which verifies our hypothesis that negative emotional responding of ADHD+DICCD is refractory even after MPH treatment. This may be a different phenotype of the EF of ADHD.Firstly, we assessed CEF using a classic test for cognitive control. Our results indicated that cognitive control deficit is a core symptom of ADHD, regardless of whether emotional responding plays a role. ADHD patients undergo dysregulation of sustained and selective attention and behavioral traits, leading to the deficit of cognitive control within CEF .Secondly, we speculated that the emotional impairment may be closely correlated with CU traits and violent tendencies . In a stAt baseline, it was found that the negative emotional stimuli may impact the corresponding cognitive control via Stroop interference effect, but the interference does not seem to be neutral . It has The results of Golden’s Stroop test demonstrated that there was no significant difference between the DICCD and HC groups when emotional responding was not involved. Additionally, deficits in response inhibition and emotional responding were not observed in the ADHD+DICCD group, except for the NEG-I variable. After the inconsistency of emotional responses was added, the emotional effect on the DICCD group was significantly different from that of the HC group. In particular the NEG-I subunit, which was the most affected variable, did not differ between ADHD and HC at baseline, but differed for DICCD and ADHD+DICCD subgroups. In a previous Chinese study of ADHD comorbidity, ADHD+DICCD subgroup displayed better performance in naming colors and color words, and also had a tendency for shorter word interference time than pure ADHD group . We concIn regard to Golden’s Stroop IG, there was also no difference between the ADHD+DICCD group and the DICCD group. Our evaluations showed that the cognitive control deficit of these two groups was less severe than ADHD patients. However, this result can not explain the normality of cognitive control of the DICCD. We suggest that the ADHD+DICCD group may have a different phenotype of neuropsychology. One explanation is that the CU traits of DICCD are more likely to reflect the clinical features of patients with comorbidities . Blair eLastly, we compared treatment effects on ADHD subgroups. MPH is the first-line pharmacotherapy for ADHD. It has been shown that MPH, which activates and normalizes ADHD neural network, is the most widely used prescription drug for ADHD . HoweverFor emotional responding, however, a different pattern of results was observed. Compared to typically-developing children, the mean RTs of ADHD and ADHD+DICCD in the Emotional Stroop test were longer. Dysfunction among ADHD+DICCD was further increased. Although ADHD treatment improved Stroop test performance, indicated by reduced errors, the mean RT of Emotional Stroop among ADHD+DICCD yielded no improvement. The mean RT of ADHD+DICCD was significantly longer than ADHD and HC after treatment. ADHD and CU traits highlighted the importance of understanding the impact of conduct problems on cognitive and emotional functioning and psychopathology of youth. Children in the ADHD+DICCD group may be less likely to be normalized by MPH treatment, depending on the presence of CU traits in ADHD . AnotherCU traits  are kinds of personality traits, and have been found to moderate functional impairment in ADHD. Specifically, functional impairment in ADHD are positively regulated by CU traits at low and moderate levels. For functional impairments in ODD, however, no such associations are observed . Frick aWe verified the notion that ADHD comorbid with DICCD is more closely related to DICCD than to ADHD . This maThe purpose of many clinical research endeavors is to draw a conclusion regarding differences between disorder and health. However, the exploration of such patterns tends to ignore the comparison between correlated neuropsychiatric disorders, forming isolated disease characteristic from the process of clinical diagnosis without considering the diversity and generality between disorders. Results were largely limited by bringing subjectivity and uncertainty to differential diagnosis. Given these considerations, our research team included ADHD, DICCD and comorbidity together in the current neuropsychological study to observe cognitive and emotional functioning among different patients.There remain, however, some limitations in the current study. First, we used the knowledge from neuroscience in our research proposal , 26, 28,To assess emotional responding of ADHD with comorbid DICCD, testing should be designed not only for specific affective symptoms, but as a standardized measuring tool for effectively screen carriers of symptoms. The effectiveness of classical neuropsychological tools in classifying different neuropsychological processes may be improved by integrating theoretical and empirical research findings.


Attention Deficit Hyperactivity Disorder (ADHD) is associated with emotional dysregulation (ED) and impaired health related quality of life (HRQoL). However, the role of ED in explaining the relationship between ADHD and HRQoL is unclear. The purpose of the present study was to do so in a sample of non-referred young adults with and without ADHD.The study design was cross-sectional. A non-clinical sample of 63 young adults with ADHD  and 69 gender-matched controls  were recruited. The Adult ADHD Quality-of-Life scale was used to measure HRQoL; The Self-Report Wender–Reimherr Adult Attention Deficit Disorder Scale and the Difficulties in Emotion Regulation Scale were used to measure ED. Group differences on all measures were tested using univariate and multivariate analyses of covariance, while controlling for age. Finally, a moderation analysis was used in order to examine the impact of ED on HRQoL beyond that accounted for by ADHD symptoms.Both HRQoL and ED were significantly worse for the ADHD group compared to the control group. The medication status of the ADHD group participants had no significant effect on the level of ADHD symptoms, ED or HRQoL. ED moderated the effect of ADHD symptoms on HRQoL for the ADHD group.The findings support the centrality of ED in ADHD and its crucial influence on HRQoL. Young adults with ADHD and high levels of ED are at risk for aversive impact on their well-being regardless of their ADHD symptoms level. Young adults with Attention Deficit Hyperactivity Disorder (ADHD) struggle with poor quality of life (QoL). Emotional regulation is one’s ability to modify their emotional state to promote adaptive, goal-oriented behaviors. Emotional dysregulation is a common yet neglected feature of people with ADHD. Our results show that young adults with ADHD are twice more likely to suffer from emotional dysregulation then their peers. Moreover, higher levels of emotional dysregulation predicted lower levels of QoL. These findings support the centrality of ED in ADHD and their crucial influence on everyday QoL. These findings are important not only on the theoretical level, but may also contribute to the design of interventions that aim to promote quality of life. Quality of Life is a multidimensional concept that reflects one's subjective perception of his/her position in life in relation to their goals, expectations, standards, and concerns , 2. HealAttention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, characterized by core symptoms of inattention, impulsivity, and hyperactivity . The worEmotion dysregulation (ED), an individual's inability to modify one’s emotional state to promote adaptive, goal-oriented behaviors  has beenRegardless of the exact definition of ED in the context of ADHD, the presence of ED in ADHD is associated with multiple functional impairments . ED, as measured by ADHD-related instruments, is associated with higher levels of impairment in clinical samples of adults and young adults with ADHD, beyond what could be predicted by ADHD symptoms and comorbidity , 36, 44.Interestingly, only a handful of studies have examined the direct contribution of ED to HRQoL in ADHD, yielding mixed results. Using a clinical sample of adults with ADHD, two studies reported that ED severity was significantly associated with ADHD symptoms severity and with HRQoL, regardless of medication status , 47. On In the current study, we examined the potential moderating effect of ED on the relationship between ADHD symptoms and HRQoL in non-referred young adults with ADHD. We first examined the differences in ED between adults with and without ADHD using two different self-report measures, collectively reflecting both the transdiagnostic and the ADHD-related nature of ED. Next, we examined the moderating role of ED in explaining HRQoL in young adults with ADHD beyond the scope of ADHD symptoms. This study should contribute to understanding of the variance of HRQoL among the heterogenic population of young adults with ADHD.The current study is a part of a larger cross-sectional study which involved baseline assessments performed in the lab in addition to 5 days of ecological momentary assessments (EMA) of mood reporting and cognitive testing performed 5 times/day using participant’s mobile phones. Here we report the results of the baseline assessments only. Participants were recruited for the study via online advertisements in student organization groups and via posts in social media. Eligible participants were invited to the Computerized Neurotherapy Laboratory at the Hebrew university where baseline assessments took place. Data was collected by research assistants who were not part of the teaching stuff at the university. All participants signed an informed consent prior to participation in any study-related activities. Participants were compensated for their participation in the study, receiving US$100 for completion of the entire study. The study was approved by the Institutional Review Board (IRB) Ethics Committee of the Hebrew University of Jerusalem (reference ID: 08112017).Over a period of 1 year (from January 2018 to January 2019) 155 young adults were recruited for the study. ADHD group participants were required to present a documented valid medical diagnosis of ADHD given by a certified medial professional (neurologist or psychiatrist). Since information about the diagnostic process was not collected in the study itself, we used the clinical cutoff score of the Adult ADHD Self-Report Scale  to confirm the ADHD diagnosis , 50. IncASRS (version 1.1) Symptom Checklist  is an inWRAADDS ED, ED severity was assessed using 3 sub-scales from the Self-Report Wender–Reimherr Adult Attention Deficit Disorder Scale : temperα = 0.93) , and HRQoL . The WRAADDS ED scales temper control and over reactivity showed a large effect size (η2 = 0.155–150) and the affective lability scale showed the largest effect size (η2 = 0.324). Among the DERS scales, awareness showed a small effect size (η2 = 0.033), clarity, non-acceptance, impulse, and strategies showed a medium effect size (η2 = 0.066-0.133), and goals showed a large effect size (η2 = 0.249). Finally, the effect size of the HRQoL scales were small for life outlook (η2 = 0.053), medium for relationships and psychological health (η2 = 0.097-0.106), and large for life productivity (η2 = 0.288).Total scores for the WRAADDS ED, DERS and HRQoL in the two groups are presented in Table eft1, N=6\right=16p = 0.042) between ASRS total score and WRAADDS ED total score. The results identify ED as a negative moderator in the relationship between ADHD symptoms and HRQoL  (see Table p = 0.004). Levene’s test of Homogeneity of Variances showed no differences in the variance across the 3 levels of ED  = 1.190, p = 0.311), ruling out insufficient variability in the high ED group as a potential account for the results. In addition, there was no floor effect in the AAQoL scores.To test the hypothesis that ED moderates the relationship between ADHD symptoms and HRQoL for individuals with ADHD, we used moderating analysis of the PROCESS macro  by Hayes (2013). The outcome variable for the analysis was HRQoL. The predictor variable ASRS total score. The moderator variable evaluated for the analysis was WRAADDS ED total score. We found a significant interaction  is noteworthy, particularly given the non-clinical nature of the sample. Thus far, clinic-based studies have reported a wide range 34%-86%) of ED in adults with ADHD –32. A re%-86% of The significant impairments in all domains of HRQoL  in ADHD are in line with the large body of literature emphasizing the negative impact of ADHD on daily health outcomes , 14, 15.The significant moderating role of ED as measured by both an ADHD-specific tool and a general transdiagnostic tool provides a broader perspective of the impact of different aspects of ED on HRQoL in young adults with ADHD. The impact of the basic characteristics of the emotional experience and expression of ED, specifically in ADHD as reflected by the WRAADDS ED subscales on HRQoL, should be noted. The frequent shifts between emotional states, the disproportional over-reactivity to daily triggers, and the lack of control in face of intense negative emotions causes constant unpredicted interferences in daily life. In addition, the resulted sense of lack of control and coherence regarding the ability of an individual to react as expected might explain the harmful impact of ED on all aspects of HRQoL. The DERS, focusing on the cognitive and behavioral responses to negative emotional states may further explain the negative impact of ED on HRQoL. The difficulties in monitoring one’s emotional state might obscure the identification of the need to detect and implement effective regulatory strategies and control the reaction to negative stimuli. All of these taken together might explain the severe impact of ED on goal-directed behavior. This in turn, resonates with theories of ADHD emphasizing inherent contribution of ED to the executive failure, suggesting constructs such as emotional impulsivity as another core symptom of the disorder , 35. Morgoals subscale showed a large effect size for group differences; the awareness subscale showed a small effect size and the remaining subscales of clarity, non-acceptance, impulse, and strategies showed medium effect sizes. These findings may reflect a unique profile of ED in young adults with ADHD. Yet, they require further replication and examination in a larger sample, testing whether there are facets of ED that are uniquely associated with ADHD.The broader perspective on ED in the current study can also be discussed in light of the question whether there are facets of ED that are uniquely associated with ADHD , 37, 61.and high levels of ED form a distinct entity or sub-type [The debate regarding the specificity of ED to ADHD vs its transdiagnostic nature could also be addressed by our findings of significant interaction between ED and ADHD symptoms in explaining HRQoL. Our findings show that the strength of association between ADHD symptoms and HRQoL depends on the severity of ED. Thus, higher levels of ED account for the reduced HRQoL seen in individuals who present lower levels of ADHD symptoms. The high prevalence of ED in the ADHD group and the large effect size compared to the control group might support the positioning of ED as a central core symptom in ADHD , 33, 35.sub-type , 47, 63.The results of our study have a few clinical implications which underscore the need for the inclusion of a broader assessment addressing ED (among other impairing factors associated with ADHD)  and HRQoDespite its strengths, which included the use of multiple ED assessments and the non-referred sample of young adults with and without ADHD, in contrast to the majority of studies in this field which sample participants from clinics, our study had a few limitations that should be noted. First, the ADHD diagnosis was based on a self-reported valid medical diagnosis of ADHD confirmed by ASRS scores above clinical cutoff, rather than on a clinical interview based on DSM-5 criteria. In addition, our study included only self-report measures of ED and HRQoL, whereas more objective measures might have yielded different outcomes and should be considered in future studies. Finally, studies with larger samples should be conducted in order to confirm and elaborate the results reported here.Our results point to the high prevalence of ED in non-referred young adults with ADHD, and to the importance of ED in moderating the association between ADHD symptoms and HRQoL. Thus, high levels of ED explain the significant burden on HRQoL in ADHD beyond symptomatology. Our study is consistent with the literature which found a more severe clinical picture in adults with ADHD who also have high levels of ED , 47, 63.


The IR analysis confirmed binding to the metal ion by the sulfur and ethoxy oxygen atoms in the carbimazole (CMZ) ligand, while in the 6-mercaptopurine (MP) ligand, the sulfur and the N7 nitrogen atom of a purine coordinated binding to the metal ion. The third ligand showed a 1:1 molar ratio and bound via sulfonamide oxygen and the nitrogen of the pyrimidine ring. Analysis of the synthesized complexes also showed that acetate groups had monodentate binding to the (UO22+). Density Functional Theory (DFT) calculations at the B3LYP level showed similar structures to the experimental results. Theoretical quantum parameters predicted the reactivity of the complexes in the order, [(UO2)(OAc)2(SCZ)] > [(UO2)(OAc)2(MP)]> [(UO2)(OAc)2(CMZ)]. DNA binding studies revealed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb) among the uranyl complexes. Additionally, strong binding of the MP and CMZ metal complexes to human serum albumin (HSA) were observed by both absorbance and fluorescence approaches. The antibacterial activity of the complexes was also evaluated against four bacterial strains: two gram-negative; Escherichia coli and Klebsiella pneumonia, and two gram-positive; Staphylococcus aureus and Streptococcus mutans. [(UO2)(OAc)2(MP)] had the greatest antibacterial activity against Klebsiella pneumonia, the gram-positive bacteria, with even higher activity than the standard antibiotic. In vitro cytotoxicity tests were also performed against three human cancer lines, and revealed the most cytotoxic complexes to be [(UO2)(OAc)2(SCZ)], which showed moderate activity against a colon cancer cell line. Thus, uranyl addition enhances the antibacterial and anticancer properties of the free ligands.Three new uranyl complexes [(UO The method and the binding constant calculations were described earlier , where Fo is the fluorescence intensity in the absence of quencher, while F is the fluorescence intensity in the presence of uranyl complexes. KSV is the Stern–Volmer quenching constant. The value of KSV can be obtained from the slope of the plot of Fo/Fvs. [Complex]  and [(UO2)(OAc)2(CMZ)] decompose above 150°C, while [(UO2)(OAc)2(MP)] has a higher melting point.The physical properties of the  and their uranayl complexes is presented in -1 for C-O-CH3 that disappeared after coordination to the metal ion, and 1163 cm-1 assigned to O-C2H6, which showed a blue shift to 1156 cm-1 compared to the free ligand spectrum. The sulfur stretching located between 1200–1193  bond lengths, S24-O27 and N34-C29, extend after binding to (UO22+). The angle bond O27-S24-N28 in the [(UO2)(OAc)2(SCZ)] is smaller than SCZ, whereas the C29-N7-C33 became smaller to reduce the strain of the formed hexagonal ring. The bond of U-O with the acetate molecule decreased to 2.16 Å.The [ bidentate complexes are shown in 2)(OAc)2(CMZ)] while the LUMO was located in the uranyl atom orbital. In contrast, the HOMO of the [(UO2)(OAc)2(MP)] and UO2-SCZ were at the acetate molecules, and the LUMO orbitals were over the bidentate ligands.The energies of the levels of the HOMO and LUMO, and the energy gap for the free ligand that was used in this study and the metal complexes were extracted to investigate the reactivity, stability, and chemical hardness and softness of these complexes. Energy levels of the HOMO, LUMO, and the energy gap for (OAc)2(SCZ)] > [(UO2)(OAc)2(MP)] > [(UO2)(OAc)2(CMZ)], which indicates that [(UO2)(OAc)2(SCZ)] was the most reactive complex. The biological activity could be expressed by the electrophilicity index, which is the ability of an electrophile to gain an additional electronic charge from the amino base in the biological environment [2)(OAc)2(SCZ)] was considered to have potential biological activity.From ironment . AccordiTo locate the positive and negative charged electrostatic potential in the molecule, molecular electrostatic potential maps were used to predict the reactive sites in the tested complexes . The cal2)(OAc)2(SCZ)] and [(UO2)(OAc)2(MP)] showed a crystalline nature with very thin diffraction peaks, which imply a long-range ordering of the two materials  and [(UO2)(OAc)2(MP)] complex 62.91 nm and 121.2 nm, respectively.To obtain evidence of the structure of the uranyl complexes, an X-ray powder diffraction study was performed. The complex [(OAc)2(CMZ)] showed two decomposition steps, starting at the dehydration range (150–220°C) and losing coupled water molecules. The final stage ended by organic molecule elimination with 39.6%  of the sample weight. The final solid-state is (UO3) and calculated carbon atoms.[(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(MP)] curves exhibited a one-step pyrolysis process that started at 176 and ended at 245°C with a mass loss of 55.5%  and 40.9% , respectively. The remaining product is UO3 formed as a metal residue. The [(OAc)2(CMZ)], [(UO2)(OAc)2(MP)], and [(UO2)(OAc)2(SCZ)]. The peak that appeared in the CMZ spectrum at 256 nm is assigned to π→π* transitions [2)(OAc)2(CMZ)] complex. Moreover, a new peak between 400–500 nm in the metal complexes spectra could be assigned to LMCT phenomena  was observed and could arise from partially forbidden charge transfer transitions to non-bonding, unoccupied f-orbitals  exited at 340, 2)(OAc)2(MP)] and [(UO2)(OAc)2(SCZ)], 2)(OAc)2(MP)] and 430 to 433nm for [(UO2)(OAc)2(SCZ)] could be caused by the environment change to non-polar due to the bonding of the metal complex to DNA [Both [(OAc)2(CMZ)], [(UO2)(OAc)2(MP)], and [(UO2)(OAc)2(SCZ)], respectively.The Scatchard equation  was used3.9.2.1 Electronic absorption studies. The interaction between HSA and the prepared complexes was evaluated using electronic absorption spectroscopy. The free HSA λmax absorption at 279 nm is attributed to the protein chromophores, phenylalanine, tyrosine, and tryptophan. The gradual addition of the uranyl complexes, 1.4×10−5 to 4.6×10−5 M, to the constant concentration of HSA (2.4×10−5 M), presented a sharp increase in the absorption intensity. This hyperchromic mode was associated with the varied shift of the λmax, [(UO2)(OAc)2(CMZ)], 2)(OAc)2(SCZ)] complexes showed a red shift to long wavelengths, 287 nm and 282nm, respectively, which indicates strong binding of the metal complexes due to the morphological changes in the secondary structure of HSA. The binding was predominantly electrostatic interactions and could be facilitated by hydrogen bond formation [2)(OAc)2(MP)] showed a blue shift to 272 nm, ormation . In contb) of the investigated complexes can be arranged in the order, 2.26×105, 2.10×105, and 7×104 for MP, CMZ, and SCZ uranyl complexes, respectively. The obtained values suggested strong binding of MP and CMZ metal complexes to HSA, while SCZ has only moderate binding.The calculated intrinsic binding constant (K3.9.2.2 Fluorescence interaction studies. Fluorescence spectroscopy was used to gain insight into the quenching mechanism of the HSA and the uranyl complexes. The fluorescence of HSA is attributed to the amino acid residue tryptophan (Trp), which is located in subdomain IIA of the HSA structure [2)(OAc)2(CMZ)] complex showed a blue shift to 334 nm, which indicates an interaction with HSA, 2)(OAc)2(MP)] complex. The KSV values could be ordered incrementally, 9.75×106, 9.46×106, 7.2×106 for [(UO2)(OAc)2(MP)], [(UO2)(OAc)2(SCZ)], and [(UO2)(OAc)2(CMZ)], respectively. The data correlated with the absorbance results, i.e., that [(UO2)(OAc)2(MP)] binds strongly to HSA. The fluorescence spectra of HSA in the absence and presence of the [(UO2)(OAc)2(MP)] complex as a quencher in Tris–HC1 buffer (pH 7.4) is shown in tructure . The intEscherichia coli (E.coli) and Klebsiella pneumonia, and two gram-positive bacterial strains; Staphylococcus aureus (S. aureus) and Streptococcus mutans were chosen for this investigation. Two standard antibiotics were employed to evaluate the results: Gentamicin, which is used against Gram negative bacteria, and Ampicillin, which is used against Gram positive bacteria. The results are expressed as Mean ± Standard deviation (mm), and are illustrated in Klebsiella pneumonia, and [(UO2)(OAc)2(MP)] showed the highest effective inhibition (28.3 mm), even more than Gentamicin (25mm). Additionally, a similar degree of inhibition, ranging between 10–16 mm for the metal complex, was shown against E.coli. On the other hand, the [(UO2)(OAc)2(CMZ)] complex showed substantial antibacterial activity against Streptococcus mutans and S. aureus with 28.6 mm and 18.6 mm, which are close to the values of Ampicillin, i.e., 30 mm and 22mm, respectively. The uranyl complexes were found to be more active against Klebsiella pneumonia and Streptococcus mutans. This could be due to the chelation to the metal ion, which improves the free drug’s ability to permeate the lipid layer of the microorganisms  complex on the colon cancer cells while MP- UO2 complex showed sufficient efficiency on the myeloma cells with IC50 = 55.6 μM. Comparing the molecular structure of the investigated complexes, we can obseve that MP- UO2 and SCZ- UO2 have a pyrimidine ring which could rise the potency of the complexes. The attributes of pyrimidines as anticancer agent are the most extensively reported in literature [2)(OAc)2(CMZ)] complex had very limited cytotoxic effects on the cell lines.The cytotoxic effects of the metal complexes were examined against three different cancer cell lines, MCF7 (breast cancer cell line), SK-MM-1 (myeloma cell line) and Caco-2 (Colon cell line), over 24h by adding medium containing the metal complexes at varying concentrations (10–500 μg/ml), terature . In contasy(OCO) and υs(OCO) of the acetate group revealed that acetate has monodentate binding to the metal ion. The optimized geometries revealed that the complexes have distorted octahedral geometry around the uranium central atom where the metal ion binds to acetate by monodentate binding. Molecular electrostatic potential maps showed the susceptibility of the acetate group to nucleophilic attack, while the ligand tended to be electrophilic sites. The electrophilicity values assumed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(MP)] have practical biological activity. The DNA binding ability of the UO22+ complexes was tested by two techniques, and showed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb). Strong binding for MP and CMZ metal complexes with HSA were observed by both absorbance and fluorescence methods, while [(UO2)(OAc)2(SCZ)] showed only moderate binding. The anti-microbial activity of the synthesized complexes were also investigated and showed that [(UO2)(OAc)2(MP)] has a higher inhibition effect than the standard antibiotic of gram-negative bacteria, Gentamicin, against Klebsiella pneumonia. [(UO2)(OAc)2(CMZ)] worked more effectively against Streptococcus mutans, a gram-positive bacteria, than the other tested complexes. In vitro cytotoxicity towards three human cancer lines showed a moderate inhibition for [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(MP)]. We conclude that uranyl ions can improve the antibacterial and anticancer properties of the free ligand.Three new bidentate metal complexes of uranyl were synthesized and fully characterized by spectroscopies, and thermogravimetric methods. The IR analysis indicated that the linearity of the U = O and the bond lengths were in the range 1.734–1.779 A°. The difference between the frequency of υS1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.S4 FigArrow shows the intensity change upon increasing CT–DNA concentration.(TIF)Click here for additional data file.S5 Fig(TIF)Click here for additional data file.S6 FigInset shows the plots of emission intensity I0/I vs. [complex] for determining KSV.(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.


Attention deficit hyperactivity disorder (ADHD) often co-occurs with antisocial behaviour. Several studies have shown high rates of ADHD among prisoners. However, the prevalence of crime among individuals with ADHD is less known. The aim of the present study was to estimate the prevalence of lifetime criminal conviction (CC) in a clinical sample of adults with ADHD, and the associations with the severity of ADHD and emotional dysregulation (ED).Patients were admitted to a private psychiatric outpatient clinic in Oslo between 2014 and 2018. Of the 656 patients diagnosed with ADHD, 629 (95.9%) agreed to participate in the study. CC was determined based on self-reporting of the lifetime history of criminal behaviour. ADHD was diagnosed according to the DSM-5 criteria, and ADHD severity was measured using the Adult ADHD Self-Report Scale (ASRS). ED was assessed by the eight-item version of Barkley’s Current Behaviour Scale - Self-Report (CBS-SR).p < 0.001) and ED (p = 0.006).The prevalence of self-reported CC in this clinical sample was 11.7% among women and 24.5% among men. CC was associated with hyperactive-impulsive severity (The prevalence of self-reported lifetime criminal conviction was high for both genders. CC was associated with symptom severity of hyperactivity-impulsivity and emotional dysregulation. The findings suggest the need for greater research efforts on the avoidance of criminal activity in people with ADHD and targeted intervention for ADHD treatment and CC prevention. Attention deficit hyperactivity disorder (ADHD) often co-occurs with antisocial behaviour , 2. SeveLongitudinal studies have found that children with ADHD have a high risk of later antisocial activity and criminal conviction (CC) in adulthood , 14. TheKnowledge of the prevalence of CC in an ADHD outpatient clinic may be helpful for health authorities to plan appropriate services and help clinicians plan specialized treatments for adult ADHD. Measurements of the prevalence of CC may also contribute to the elucidation of possible causes and the achievement of treatment.Several studies have indicated that CC and antisocial behaviour are correlated with the severity of ADHD , 19–23, Previous studies have found general adjustment problems to be linked to antisocial behaviour in adults with ADHD . AntisocThe aims of the present study were to estimate the prevalence of CC in a clinical sample of outpatients with ADHD and to examine its associations with ADHD symptom severity and ED.This was an observational cross-sectional clinical study.The study population consisted of adult outpatients aged 18 to 65 who were not imprisoned who fulfilled the diagnostic criteria for a diagnosis of ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) . PatientRecruitment was conducted between 2014 and 2018. ADHD was assessed using DIVA 2.0 the semi-structured Diagnostic Interview for Adult ADHD, second edition . The assOf the 656 patients (351 men and 305 women) with ADHD, 629 (95.9%) gave written informed consent to participate in the study. The study was approved by the Regional Medical Ethics Committee, South-East Norway, 2015/426. Assessments were carried out in accordance with ethical standards, and the principals of the Declaration of Helsinki.The age of the participants was recorded as their respective numbers of lived years when entering the study. Gender was recorded as ‘woman’ or ‘man’ based on information revealed by the participant. Sociodemographic information was collected as follows: Participant was married or cohabitating. If a participant was living with children inclusive partial custody, but not even though having children somewhere else. Educational level was categorized based on the number of years in education: 12 years or less, 13–15 years, or more than 15 years. Work participation was defined as ‘yes’ if work was reported as the main source of income.Criminal conviction (CC) was defined as being convicted by the court of any crime under Norwegian law. CC was recorded as positive when participants self-reported CC in response to the following question: ‘Have you ever been in prison or been convicted for any crime?’. We also recorded which crime they were convicted of.ADHD symptom severity was measured by the Adult ADHD Self-Report Scale (ASRS) Symptom Check List, v1.1 , 45 The Emotion dysregulation covers a large variety of emotion dysregulated responses as overwhelming sadness, anxiety, fear, suicidal actions, plural emotional outbursts, and is also linked to several other diagnoses as depression and anxiety , PTSD aEmotion dysregulation in ADHD could alternatively have been assessed by the Impulsivity/Emotional Lability scale from the Conners’ Adult ADHD Rating Scales (CAARS)  a 12-itAlcohol and drug use disorders were diagnosed using a module of the Mini International Neuropsychiatric Interview (M.I.N.I.), Norwegian Translation Version 6.0.0, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria , 56. Dep2) tests to compare categorical variables and independent sample T-tests to compare continuous variables. We used logistic regression analyses to examine the associations between CC as the outcome variable and age, gender, ADHD symptom severity and ED as the independent variables. To avoid bias in the regression analysis we have decided not to control for probable intermediate variables (or a proxy for an intermediate variable) in the causal pathway between ADHD severity or ED and criminal behaviour (Rothman & Greenland 1998 [Numbers with percent proportions (%) are reported for all categorical variables. Means with standard deviations (SD) are given for continuous variables. We used chi-square . For exand 1998 ). Both Aand 1998 ) and canand 1998 ). Thus, and 1998 , Gilthorand 1998 , Schisteand 1998 ).Table p < 0.05. There were no missing data. All statistical analyses were performed using the software package IBM 2016 SPSS version 22 [All tests were two-tailed, and differences were considered significant if rsion 22 . We usedTable n = 34) in women and 24.5% (n = 83) in men.The prevalence of CC was 11.7% (n = 290), the most common conviction was for selling or possessing drugs , followed by violence, , traffic crime , theft , and mixed or multiple convictions .Among women (n = 339), the most common conviction was for selling or possessing drugs , followed by violence, , traffic crime , theft , and mixed or multiple convictions .Among men  in female and male ADHD patients respectively, were considerable higher than the correspondingly 1 and 5% rates for women and men in the general Norwegian population . High riThe two or threefold higher risk of CC among men versus women is in line with other studies of ADHD patients , 16, 65.The finding that CC was associated with the severity of hyperactive-impulsive symptoms is in line with several studies that have shown associations between the severity of ADHD symptoms and different aspects of antisocial behaviour , 67–71. With this aspect in mind, it seems meaningful to address the severity of ADHD as emphasized in the DSM-5  as opposThe concept of emotional dysregulation (ED) has different aspects, with both bottom-up strong emotional responses and top-down poorer regulation of emotions. The DESR questionnaire is mostly focused on bottom-up emotionality, which has been understood as ED. In our sample, CC was associated with the severity of ED, independent of hyperactive-impulsive severity. We suggest that knowledge on ED does add significantly to the understanding of CC in people with ADHD, First, ED is a common feature of ADHD, even though it is not part of the diagnostic criteria –37, 77. We found a strong relationship between all background variables and CC. The association between low education and CC is notable since people with ADHD have lower levels of education than the general population –84. AddiThe relationship between crime and substance use disorders may be due to several mechanisms. It is reasonable that substance use and addiction can lead to crime. On the other hand, criminal activity can provide closer contact with intoxicants and drug environments. In addition, there may be common underlying factors that increase the risk of both substance use and crime. The fact that we exclusively had lifetime prevalence for both substance use and CC, and lacked hypotheses of cause-effect, led us not to adjust for substance use in the regression model.Early identification of ADHD and disruptive behaviour, with subsequent multimodal interventions might reduce the risk of a criminal trajectory. Supporting people with ADHD in attaining higher education and work and avoiding drugs is probably also a good approach to prevent CC.There are some methodological limitations to consider in this study. CC was measured based on self-report, which may have resulted in under-reporting. Patients attending a private clinic that is not governmentally funded may not be representative of patients with ADHD in general. They may have a higher socioeconomic status and be less impaired than patients in public outpatient clinics or prison inmates. Additionally, the prevalence rates of criminality and morbidity in this population may not be representative of those of the total ADHD patient population. We assume that differences in sample selection may primarily affect the prevalence rates and, to a lesser extent, their associations , 88. TheThe cross-sectional observational design limited the interpretation of causal relationships. We assume ADHD and ED are traits that develop in childhood before the criminal minimum age, which is 15 years in Norway, which may therefore indicate the direction of causality.In this clinical sample the prevalence of criminal conviction (CC) was high for both genders compared to the prevalence rates reported in the general population. CC was associated with the severity of hyperactivity-impulsivity, as well as emotional dysregulation, which indicates that knowledge on both features contributes to the understanding of CC in ADHD.Criminal behaviour is common in adults with ADHD. The findings call for research efforts to prevent criminal activity in people with ADHD. The association of higher severity of hyperactivity-impulsivity symptoms and emotional dysregulation with CC suggests that clinical manifestations should be treated carefully. Early identification as well as biological- and psychological approaches in the prevention and treatment of ADHD and externalizing behaviour should be performed early in childhood and followed up in adulthood by professionals with specific knowledge of treatment and behavioural interactions with the environment. Furthermore, targeted interventions should focus on the preventive effect of academic achievement and higher education for adolescents with ADHD, which could be crucial in avoiding illegal drug use, antisocial behaviour, and criminal activity.


In the last two decades, the importance of Computational Materials Science has continuously increased due to the steadily growing availability of computer power. At the same time, effective and sufficiently precise first-principle codes, which are based on Density Functional Theory (DFT) have been made usable for a broad community of researchers. Additionally, the progress in the field of atomistic simulations with interatomic potentials has continued. The latter method has been applied to study complex processes in systems with large number of atoms and/or over long times, i.e., for investigations of spatial and temporal scales that are not treatable by DFT.P6422-XP  polymorphs and in Reference [Pnm21 phase of XN  is investigated. These fundamental studies provide very useful data for future applications. Interfaces and grain boundaries are another field of advanced materials research by computational methods. In References [3C4 is determined in Reference [2 [1−xClx)3 [The present Special Issue provides a collection of ten articles ,7,8,9,10eference . Furthereference ,6 and foeference  and halirence [2 , and CsP1−xClx)3  not only


Around 5.29% of the world population is suffering from ADHD, and 60 million people are suffering from CVS, with an increasing rate of prevalence of these disorders. This study aimed to determine the prevalence rate of ADHD and CVS symptoms among the Bangladeshi population.p < 0.01). The Stroop effect value is also higher among the males aged 18–24, digital device users for > 6 h (48%).To assess the aim of the study, a cross-sectional survey was conducted online through stratified sampling, and 197 responses were collected from the participants. Our survey method follows these criteria where the ARSV1.1 standard questionnaire was followed for the ADHD questionnaire, and a self-administered questionnaire was established based on the symptoms of CVS. The male age ranges from 18–24 have the highest value of ADHD (34%) coincided with > 6 h digital device usage (51%), and the Stroop effect is significantly correlated with the ADHD score (0.498, With the advent of science, it is impossible to avoid digital devices as necessary. Notwithstanding, safe and appropriate use of digital media is a must for healthy living. The twenty-first century, known as the age of technology, has exposed people to various technological devices, e.g., television, video games, computers, and cellular technologies, especially people born after 1997 have been exposed to technology . Though In terms of that, ADHD— a psychiatric condition involving persistent difficulty in sustaining attention; hyperactivity, and impulsivity becomes the most common disease knocking at the door in the triumphant moment of technology progression . A meta-According to a report, 47.61 million people of Bangladesh use the internet out of 165.5 million, and the number has increased by around 7.7% from 2020 to 2021 . Accordin = 98 female (50%) and n = 99 male (50%), were mainly undergraduate students (77%) from various departments and diversified jobholders (23%) from different areas of Bangladesh. The age range for male and female participants was 18–31 years . The participants were mainly frequent computer and other digital device users and had been using these devices for about 5–10 years (44%), > 10 years (31%), 2–4 years (21%), and < 2 years (4%). The inclusion criteria of the participants were:Having a digital device.Anyone over the age of 18.Both sexes.The randomly chosen, right-handed, 197 healthy participants  categorized between Arthritis.Previous injuries.Color blindness .Not having a computer or laptop and internet connection.The exclusion of the participants was based on different factors like:The data was collected from September 2020 to October 2020 by following the cross-sectional and stratified random sampling methods. In the sampling process, data variables were arranged based on gender, occupation and age-wise. The data collection method followed the structure without missing respondents; all the participants had to respond to the entire incorporated questionnaire. The questionnaire was collected from the World Health Organization Adult ADHD Self-Report Scale (ASRS) constructed in conjunction with the revision of the WHO Composite International Diagnostic Interview (CIDI) for the ADHD symptoms prevalence data compilation . In termIn the scoring method, ADHD scores less than 4 indicate the little disposition of ADHD symptoms, whereas a score 4 or higher than 4 indicates the high prevalence of ADHD in the participants and needs to go for the further diagnostic procedure ASRS-V1.1 symptoms checklist tool . For CVSData were analyzed using the Statistical Package for Social Sciences software version 20.0 and the Microsoft Excel 2016 for professionals. The correlation between ADHD and CVS is performed by bivariate correlation and linear regression procedure. The bivariate correlation is done by Spearman—Pearson correlation coefficient at the 2-tail significance test. Correlation is significant at the 0.01 level (2-tailed). For CVS, the correlation and significance of data with gender have been estimated by the logistic regression analysis procedure with 95% confidence interval and p-value less than 0.05 have been considered statistically significant.Table p = 0.000).From Fig. From Fig. In Table From the above graph Fig. , it has From Table From Table p = 0.018)  Table .p = 0.018). The eye strain and eye fatigue pathophysiology are the repeated eye movement around the keyboard and the radiation from the digital device that hampered the eye cell and reduces the dopamine secretion from the brain which hampers our ocular nerve cell [It has been elucidated that the time will be > 6 h (51%) in the ADHD score increase where the 1–3 h (12%) of the time increases. The evidence showed that ADHD symptoms are worsening for a selected group of students, which are the majority of heavy users, approximately 80% suggesting that a particular subset of teens may possess a greater vulnerability to ADHD symptoms . Anotherrve cell . Blurredrve cell . Moreoverve cell . Becauserve cell . The slerve cell .There is minimal research-based data regarding ADHD in adults due to its challenging data collection, requiring skills and techniques that clinicians may not routinely use when assessing other disorders or age groups. That is why some underlying mechanism is still unknown . Not allADHD and CVS are two emerging disorders in the modern world with the advancement of technology. The uses of digital devices have become essential nowadays due to the nature of work and structured professional systems. Unnecessary use of digital devices and specific protection with lifestyle modification may be helpful to reduce those disorders.Dataset used in this study will be available as per request (mailing to the corresponding author).