Background: This study was designed to evaluate vaccination hesitancy and behaviors among parents of children with chronic conditions. Methods: This cross-sectional study was conducted from June to December 2021 in three public hospitals in southern Italy. Data were collected using a face-to-face interview of parents of children up to 17 years of age with at least one chronic condition. Results: Of the 532 parents approached, 444 agreed to participate, with a response rate of 83.4%. Almost half of parents (43%) knew that children with chronic diseases are at greater risk of complications from VPDs, and 21.6% knew all the vaccinations available in Italy. Additionally, 55.9% felt that vaccine-preventable diseases (VPDs) are very dangerous for their children, and 28.7% were very worried about the side effects of vaccines. The result of the Parent Attitudes about Childhood Vaccine (PACV) score indicated that 23.2% of parents were hesitant about vaccinations. Parental vaccine hesitancy was significantly more common among parents who had female children, among those who did not know the recommended vaccinations, among those who had a higher concern of potential side effects of the vaccines, among those who believed that the administration of the vaccinations was not useful, and among who received information on recommended vaccination from the internet, social and mass media. Conclusions: Important efforts by policy makers and healthcare providers must be implemented to counter vaccine hesitancy among parents. It is well known that the implementation of immunization programs worldwide has led to a reduction in the incidence of vaccine-preventable diseases (VPDs), with a consequent decrease in severe complications, disability, and mortality associated with VPDs, as well as saving health resources, in particular for the groups of patients at high risk, such as children and adults with chronic conditions .Haemophilus influenzae type b, hepatitis B, measles, mumps, rubella, and varicella) have been mandatory during childhood since 2017, whereas vaccinations against meningococcal disease, pneumococcal disease, rotavirus, and seasonal influenza, are recommended during childhood or to patients with chronic conditions, and are provided free of charge by primary care pediatricians or vaccination centers in Italian Local Health Units [In Italy, ten vaccinations  and one randomly selected public hospital in Calabria (Catanzaro), Italy. The target population was composed of parents of children up to 17 years of age with at least one chronic condition. Study participants were randomly approached in the waiting room before their child’s scheduled visit in the following hospital ambulatory centers: diabetic, hemato-oncology, endocrinology, nephrology, rheumatology, allergy, and clinical immunology. Only one parent per child was interviewed. A minimum target sample size of 403 was estimated, assuming that 30% of parents were hesitant according to previously published literature , with a After obtaining approval from the Ethics Committee of the Teaching Hospital of the University of Campania “Luigi Vanvitelli” (protocol number: 8666/2021), the directors of the selected hospitals received a letter explaining the purpose of the investigation and the procedure of the survey and requesting their collaboration.After the approval, experienced trained physicians not involved in the clinical care approached the participants, informed the selected parents about the study objectives and methodology, and assured them that the study participation was voluntary, that all information would remain confidential and would be analyzed anonymously, and that they had the right to refuse or to withdraw at any moment from the interview without disclosing any reason. No incentives and gift were offered to parents.A pilot study was performed among 25 parents  to evaluate the comprehensibility and the validity of the questions, and no changes were made to the survey instrument.The research team designed the questionnaire used to collect data based on previous studies conducted in several groups of population about the hesitancy and practices regarding vaccinations ,17,28. AHaemophilus influenzae type b, hepatitis B, measles, mumps, rubella, and varicella) and recommended vaccinations , and seasonal influenza) that were provided free of charge by primary care pediatricians or vaccination centers in Italian Local Health Units. The possible answers were “no”, “do not know”, and “yes”. In the third section, parents were asked about their attitude regarding childhood vaccinations . The attitudes were measured on a ten-point Likert Scale ranging from 1 representing “not at all” to 10 representing “at all”. Parents were also asked if they delayed or refused at least one shot of vaccinations for their children, and the reasons for having delayed or refused the vaccines. Parental vaccine hesitancy was assessed using the 15-item Parent Attitudes about Childhood Vaccine (PACV) survey translated into the Italian language, which had already been used in previous published studies conducted by the research team [The questionnaire consisted of 40 questions divided into four major sections. The first section investigated the socio-demographic characteristics of the parents and children . The second section was designed to assess the parents’ vaccination knowledge about the immunization program for their children in Italy, regarding the mandatory  (Model 1); having refused or delayed at least one shot of the recommended vaccinations for their children with chronic conditions  (Model 2); and parents’ vaccine hesitancy  (Model 3). The following independent variables were included in all Models: age in years (continuous), gender , marital status , baccalaureate/graduate degree , at least one parent being a healthcare professional , having more than one child , age of the children with chronic conditions , gender of the children with chronic conditions , children taking medications , parents’ perceived health status of the children with chronic conditions (continuous), knowledge about the vaccinations available in Italy , knowledge about the recommended vaccinations for their children with chronic conditions , perceived the VPDs as very dangerous for their children with chronic conditions (continuous), believing that the administration of the vaccinations is useful for their children with chronic conditions , and need for additional information about vaccinations . The following variables were also included in the different models: knowledge that children with chronic diseases are at greater risk of complications from VPDs  in Model 1; considering the recommended vaccinations very dangerous for their children (continuous) in Model 2 and 3; having received information about the recommended vaccinations for children with chronic conditions from physicians  in Model 1; having received information about the recommended vaccinations for children with chronic conditions from internet/mass media/social media  in Model 2 and 3; having had discussions with pediatricians/medical specialists about the recommended vaccinations for their children with chronic conditions  in Model 2 and 3. Values of p = 0.2 and p = 0.4 were used to select candidate variables for retention and exclusion in the final multivariate models. Results of the logistic regression models were measured using Odds Ratios (ORs) with 95% confidence intervals (CIs), whereas results of the linear regression models used standardized regression coefficients (ß). For all analyses, two-tailed tests were used and a p-value equal to or less than 0.05 was considered statistically significant. Stata statistical software version 15.1 was used to analyze the data [First, descriptive analysis, including means and standard deviations for continuous variables and proportions for categorical variables, was used to describe the main parents’ characteristics. Second, bivariate analysis was performed to assess the association between each of the independent characteristics and the different outcomes of interest, using the chi-square test for the categorical variables and Student’s the data .Of the 532 parents approached, 444 agreed to participate, with a response rate of 83.4%. The main characteristics of the study population were described in Almost half of parents (43%) knew that children with chronic diseases are at greater risk of complications from VPDs, and approximately one in five parents (21.6%) knew all the vaccinations available in Italy, with a better knowledge found for measles, mumps, and rubella vaccines (94.4%) and the influenza vaccine (93%), whereas 82% of parents knew of the HPV vaccination and only 55.6% were aware of the availability of the vaccine against rotavirus.When asked about the recommended vaccinations for children, two-thirds of parents knew that pneumococcal (69.7%) and influenza (69.1%) vaccines are recommended for children with chronic conditions, 58.3% of participants indicated the rotavirus vaccination, and more than half (56.3%) correctly knew the vaccination recommendation against meningococcal disease. Moreover, 63.5% of parents knew all the mandatory vaccinations during childhood and adolescence in Italy.The majority of parents (55.9%) felt that VPDs are very dangerous for their children with chronic conditions, with a mean value of 8.6, on a scale ranging from 1 to 10, and 28.7% were very worried about the side effects of the vaccines. More than half of the participants (53.2%) believed that the administration of the vaccinations is useful for their children, with a mean value of 8.6 on a scale ranging from 1 to 10, whereas one in four (26.7%) considered the recommended vaccinations very dangerous for their children, with an average value of 6.3. The results of multivariate linear regression analysis showed that this negative attitude was more likely among parents without a baccalaureate/graduate degree, among those who do not work as a healthcare professional, among those who knew that children with chronic diseases are at greater risk of complications from VPDs, and among those who do not believe that the administration of the vaccinations is useful for their children , forgetfulness (22%), fear of vaccines’ side effects (16%), and the lack of recommendation by pediatricians (6%). Moreover, the most frequent reasons of those refusing were fear of vaccines’ side effects (58.7%), not considering the recommended vaccinations useful (24%), and the lack of recommendation by pediatricians (6.5%). The results of the multivariate logistic regression analysis showed that parents who had not discussed with pediatricians/medical specialists on the recommended vaccinations for their children with chronic conditions , and those who had children who took medications for their chronic conditions  were more likely to have refused at least one shot of a vaccine for their children , among those who did not know the recommended vaccinations , among those who had a higher concern for potential side effects of the vaccines on their children with chronic conditions , among those who believed that the administration of the vaccinations was not useful , and among those who received information on recommended vaccinations via the internet, social and mass media  ; only 8.3% and 4.5% declared that their children had received vaccination against pneumococcal disease and rotavirus, respectively, and no parent reported that their children had received vaccination against meningococcal disease. Moreover, only 10.6% of parents indicated that their child had been vaccinated against seasonal influenza in the last year, and only 28.5% of parents of boys/girls aged ≥12 years had immunized their children against HPV.A large majority of parents declared that they had discussions with pediatricians/medical specialists regarding the recommended vaccinations for their children with chronic conditions (87.4%) and, when parents were asked about the vaccination coverages of children, 94.6% self-reported that their children had received the current mandatory vaccinations in Italy  reported pediatricians/medical specialists as their main source of information on recommended vaccinations for their children with chronic conditions, and other sources of knowledge were the internet (33.8%), mass media (29%), and social media (20%). One-third (34.7%) of participants expressed the need for more information about the vaccinations.This study provides relevant information about the hesitancy and behaviors towards vaccinations among parents of children with chronic conditions in Italy and the relative determining factors.Regarding the parents’ knowledge of vaccinations, it is important to underline that not even half of the parents who participated in the study knew that children with chronic diseases are at greater risk of complications from VPDs, and only one in five knew all the vaccinations available in Italy for their children. These results are very alarming, as correct awareness of the risk of contracting infectious diseases and correct knowledge of parents about the available vaccinations are a fundamental prerequisite for being able to effectively implement all vaccination coverage strategies during childhood and adolescence. In particular, healthcare professionals should spend more time correctly informing the parents of the benefit of vaccinations, as in our study, knowledge about vaccinations is quite low, despite self-reported parents’ trust in the pediatricians reaching a high value and pediatricians/medical specialists being the main sources of knowledge on vaccinations reported by parents.Regarding the parents’ attitudes and behaviors about vaccinations, a positive attitude was found regarding the dangerousness of VPDs and the usefulness of vaccinations, even if one-third of parents were very concerned about the vaccines’ side effects. The fear of side effects in this study is also the most frequent reason of those refusing at least one shot of a vaccine for their children with chronic conditions, and it has been reported in previous studies in the literature as an important barrier for vaccine uptake ,28,29,31The results of the PACV score indicated that the 23.2% of parents were hesitant about childhood vaccinations. It is important to take into account that this result may be influenced by the fact that this study has been performed during the COVID-19 pandemic. Indeed, a recent review showed that the COVID-19 vaccine hesitancy rate in Italy is 59.9% , and thiThe results of the multivariate regression analysis showed that parental vaccine hesitancy was more likely among those who considered the recommended vaccinations dangerous for their children and among those who received information on recommended vaccination via the internet, social and mass media. This result is alarming, as it is known that internet use and social networks can spread false and misleading information on vaccinations and can increase parents’ concerns about vaccine safety and negatively affect the coverage rates . Thus, iIn our sample, despite a large majority that reported having discussions with pediatricians/medical specialists about the recommended vaccinations for their children with chronic conditions, inadequate coverage rates were observed for the recommended vaccines, with only a very small proportion of the parents reported having vaccinated their children against pneumococcal disease, rotavirus infection, and seasonal influenza. These coverages are concerning, and have also been found in Italy at a national level , and theThis investigation has several potential limitations due to study design and methodology that must be taken into consideration when analyzing the findings. The first is that it is not possible to establish the temporal direction of the association between the outcomes of interest and the influencing factors in the cross-sectional study. The second is that the data were collected through interviews, and it is possible that respondents may be influenced in their responses by the defined socially appropriate attitudes and behaviors, and this could overestimate the positive attitudes and behaviors towards vaccinations. To address this limitation, the interviews were carried out without reporting the information on the participant’s identification and the confidentiality of the answers was ensured. Third, there may be a recall bias that could lead to underestimating or overestimating vaccination coverage because parents were asked to self-report the children’s vaccination status. Despite these limitations, the sample size was appropriate, with a high response rate, and the results of this survey provided important information on parental hesitancy towards vaccinations of children with underlying chronic medical conditions in Italy.In conclusion, important efforts by policy makers and healthcare providers must be implemented to counter vaccine hesitancy among parents of children with chronic conditions. Therefore, educational interventions aimed at addressing the concerns about vaccinations should be more widely carried out, as the fear of the adverse effects of vaccines is the primary concern of parents in this study. The role of pediatricians and specialists as a source of information and in administering vaccines must be strengthened within immunization programs, given the trust they have among parents and given that the study findings had showed that many parents are exposed to vaccine information on the internet and social media, and this can lead to misinformation and mistrust. Therefore, the vaccinations recommendation of pediatricians and medical specialists is a key factor for decision making of parents regarding vaccination in order to improve their knowledge of vaccines, and it is pivotal to increase the coverage rates, as the results of our survey showed that the coverage for recommended vaccinations in Italy is worryingly insufficient. Further investigations are needed to explore the attitudes and behaviors of HCWs regarding recommended vaccinations for children with chronic conditions.


Mental disorders and ADHD in people with ID are higher than in the general population.Clinicians may be reluctant to diagnose ADHD in people with ID. They could be denied effective treatment.The purpose of the study was to ascertain antipsychotic use in people with ID before and after the a diagnosis of ADHD.A casenote review in an ID service for aduls with ADHD. Data collected on psychotropic use before and after the diagnosis.Forty-eight aduls with ADHD-ID were identified. 38(79%) were male and 10(21%) were female. 19 to 58 years of age. Four (8%) had mild ID; 44 (92%) had moderate to severe ID. 27(56%) had anxiety, mood disorders or psychosis. 21(44%) had ADHD only. Challenging behaviour was reported in 24 (50%) of cases. Thirty-three (68%) used psychotropic medication prior to the diagnosis of ADHD and after the diagnosis. Post-diagnosis, 20(60%) continued to use antipsychotic medication indicating the elimiation of antipsychotic use in 13(40%) of people. The level of medication use remained the same in spite of the reduction of antipsychotic medication. The diagnoses of challenging behaviour was not affected by the reduction in antipsychotic medication and the increase in ADHD medication use.The use of antipsychotic medication in people with intellectual disaibilities and ADHD is high. ADHD should be considered when people present wtih challenging behaviour. ADHD medication can be effective in treating ADHD-ID and can lead to a significant reduction in the use of antipsychotic medication.No significant relationships.


The presence of the C=S functional group in TU regulates the crystallization dynamics of Cs3Sb2I9−xClx films and generates the (201) preferred orientation of Cs3Sb2ClxI9−x films, which could effectively improve the carrier transport and film morphology. As a result, the Cs3Sb2I9−xClx perovskite solar cells (PSCs) delivered a power conversion efficiency (PCE) of 2.22%. Moreover, after being stored in nitrogen at room temperature for 60 days, the devices retained above 87.69% of their original efficiency. This work demonstrates a potential pathway to achieve high-efficiency Sb-based PSCs.All-inorganic Sb-perovskite has become a promising material for solar cell applications owing to its air stability and nontoxic lead-free constitution. However, the poor morphology and unexpected (001) orientation of Sb-based perovskite films strongly hinder the improvement of efficiency. In this work, two-dimensional Cs Howeverironment .3Sb2I9 perovskites have also attracted significant interest because of their high absorption coefficient (>105 cm−1) and excellent moisture and thermal stability [3Sb2I9, namely, the zero-dimensional (dimer) and two-dimensional (layered) phases [3Sb2I9 lattice can effectively suppress the formation of undesirable 0 D phases [3Sb2ClxI9−x films with a PCE of 2.15% [3Sb2I9 via a HCl-assisted solution method, but the rapid crystallization rate produced smaller grain sizes (~50 nm), limiting the efficiency to 1.21% [3+, which could retard the perovskite formation process through an intramolecular exchange [3Sb2I9 is parallel to the substrate, which is a big obstacle preventing the improvement of the device performance. As we know, it is expected that the perovskite crystal grows vertical to the electrodes to enable an efficient charge transport up and down [Recently, all-inorganic Csficient >5 cm−1 antability . In gene) phases . The 0 D) phases . Jiang eof 2.15% . Umar etto 1.21% . To decrexchange ,15,16. Gand down .3Sb2I9 crystal orientation to facilitate carrier transport was an issue of concern for Cs3Sb2I9 solar cells. Singh et al. found that introducing the coordination molecule indacenodithiophene-based organic acceptor (ITIC) into Cs3Sb2I9 films could effectively enhance the (201) orientation and achieve a PCE of 3.25% [− or coordination molecules could improve the crystallization of Sb-based perovskite and enhance the photovoltaic performance.Therefore, modulation of the Csof 3.25% . Accordi3Sb2I9−xClx films with the preferential orientation of the (201) plane have been successfully fabricated by introducing TU to regulate perovskite crystallization. It was determined that the C=S group in TU can combine with Sb3+ to form a complex in the perovskite precursor, which significantly retards the crystallization. X-ray photoelectron spectra (XPS) verified that the TU could be eventually removed from the films, which had no effect on the component of the perovskite films. Based on the density functional theory (DFT) calculations, TU has a much lower adsorption energy (−0.22 eV) on the perovskite (003) crystalline plane than it does on the (201) plane (−0.36 eV). The perovskite (003) crystalline plane with a lower adsorption energy grows much more quickly than the (201) crystalline plane. In accordance with the Bravais–Riedel–Donnay–Harker laws, there is a tendency for crystalline planes growing quickly to decrease or even vanish [3Sb2I9−xClx films with the (201) preferential orientation and a large grain size have been successfully obtained by optimizing the amount of TU in the precursors. The PCE has been promoted to 2.22%, with a notable multiplied SCJ of 6.77 mA cm−2, OCV of 0.65 V, and FF of 50.3%. Moreover, the devices retained 87.69% of its initial efficiency after being stored in a nitrogen environment at room temperature for 60 days.In this work, high quality Csn vanish . As a re3 , SbCl3 , Bis-(trifluoromethane) sulfonimide lithium salt , Thiourea (TU) , tert-butylpyridine (tBP) , CsI , spiro-OMeTAD , DMF , Isopropanol , and FK209-cobalt (III)-TFSI  were used as received.SbI2 and mp–TiO2 layers were deposited according to our previous method [3, and 0.02 M SbI3 in a 1 mL mixed of DMSO and DMF  and stirred at 70 °C for 12 h. Then the solution was spin–coated on FTO/c–TiO2/mp–TiO2 substrates at 3000 rpm for 30 s. After spin coating, the films annealed at 70 °C for 10 min to remove the solvents, followed by a SbI3 vapour annealing at 250 °C for 15 min. The SbI3 vapour was prepared by a 30 wt% SbI3 DMF solution (5 µL) dropping to the corner of the petri dish during annealing. For the TU additive sample, the desired amount of TU was added into the precursor and the above-mentioned film-formation protocol was followed. After that, the hole transporting layer and electrode were deposited according to our previous method [The FTO substrates were cleaned with deionized water and ethanol for 20 min in an ultrasonic bath and then a UV–ozone treatment was performed for 30 min. The compact TiOs method . The pres method .−1). The morphologies and roughness were measured with the SU8010 SEM  and 5500 AFM , respectively. Steady–state photoluminescence (PL) spectra were collected with a Fluorolog–322 . Time-resolved photoluminescence (TRPL) spectra were measured with the FLS1000 . The FTIR spectrum was acquired with the Excalibur 3100 . X–ray spectra (XPS) were acquired with the ESCALab250Xi, Thermo Fisher Scientific, Waltham, MA, USA. Impedance spectroscopy was measured via a Zahner electrochemical workstation  with a bias potential of 0.50 V in the dark with the frequency ranging from 100 Hz to 1 MHz. The J–V curves were tested via a Keithley 2400 source-meter under AM 1.5G 100 mW cm−2 from a sunlight simulator . The capacitance-voltage (C–V) measurements was performed using a Zahner electrochemical workstation in the dark at a frequency of 10 kHz and the AC amplitude was 10 mV. The incident photon–to–electron conversion efficiency (IPCE) was recorded by a QE-R measurement system .UV–vis spectra were acquired with the UV–2450  from 400 nm to 900 nm. XRD patterns were obtained via an X-ray diffractometer  with Cu–Kα radiation (1.5418)  with the Perdew–Burke–Ernzerhof (PBE) function was employed [−5 eV and −0.1 eV/ang were used as the convergence criteria for SCF and force, respectively.The first–principles calculations were done with VASP (Vienna Ab–initio Simulation Package) . In ordeemployed . A proje3 vapour at 250 °C for 15 min. Finally, the perovskite film was obtained. The high SbI3 vapour pressure was considerable at 250 °C and effectively prevented the Cs3Sb2I9−xClx film from losing SbI3 [3 vapour annealing process. 3Sb2I9−xClx films containing various amounts of TU additives. The diffraction peaks at 8.7°, 17.2°, 21.0°, 25.7°, 25.9°, 29.9°, 42.7°, and 42.9° were ascribed to the (001), (002), (102), (003), (201), (022), (204), and (220) planes of the 2D Cs3Sb2I9−xClx crystal phase, respectively [3Sb2I9−xClx films was 1.516, 0.464, 0.436, and 0.454, respectively. The crystallite size of the Cs3Sb2I9−xClx films was calculated by the Scherrer equation [3Sb2I9−xClx films was 31.88, 2.96, 2.61, and 2.85, respectively. The lattice constants for control, 0.1 M, 0.2 M, and 0.3 M are also listed in 3Sb2I9−xClx films. To further understand the influence of TU on the crystal orientation of the Cs3Sb2I9−xClx, we calculated the peak intensity ratio (201)/(003) for the Cs3Sb2I9−xClx films, and the results are shown in 3Sb2ClxI9−x films exhibits the preferred (201) growth orientation of the Cs3Sb2I9−xClx crystals  [3Sb2I9−xClx films with the addition of different amounts of TU obtained from top-view SEM images using nano measurer software is shown in 3Sb2ClxI9−x films show a maximum average grain size of 282.4 nm, which is much larger than that of the control film of 162.3 nm , 2, (003),crystals . Figure thout TU c shows athout TU d–f exhiblization ,27. Howe + CH2N) . Meanwhi162.3 nm g. The inntration . Additiolx films . As show3Sb2I9−xClx films with different SbI3 vapour annealing times are shown in 3 vapour annealing time. The shift is especially obvious for 3 min in SbI3 vapour annealing. The (201) diffraction peak could not be seen in 3Sb2I9−xClx lattice, and then it was eliminated from the Cs3Sb2I9−xClx lattice during SbI3 vapour annealing due to the small ionic radius of Cl−. Furthermore, the intensity of the (003) peak increased as the SbI3 vapour annealing time increased, indicating the enhanced crystallinity of Cs3Sb2I9−xClx films. The (003) and (201) peaks in 3 vapour annealed for 10 min  was performed. 3Sb2I9−xClx films before and after SbI3 vapour annealing. It clearly indicates the presence of Cs, Sb, I, Cl, and S in the films before SbI3 vapour annealing. 3Sb2I9−xClx films before and after SbI3 vapour annealing. For the control and 0.2 M TU additive Cs3Sb2I9−xClx films before SbI3 vapour annealing, the Sb 3d5/2 peaks are located at 529.88 eV and 530.1 eV, respectively, which indicates a strong intermolecular interaction between Sb3+ and TU [3Sb2I9−xClx film after SbI3 vapour annealing. This result also indicates no residual TU in the final perovskite film. To further verify this point, we study the high-resolution S 2p and N 1s XPS spectra for the 0.2 M TU additive Cs3Sb2I9−xClx films after different SbI3 vapour annealing times. As shown in 3 vapour annealing. In 3 vapour annealing. Therefore, we deduced that TU was removed from the perovskite film during SbI3 vapour annealing [To further investigate the elemental characteristics of the control and 0.2 M TU additive Cs+ and TU . Moreovennealing .3Sb2I8Cl (001) and (201) surfaces with the TU molecule. In 3Sb2I8Cl (003) and (201) planes, in which the C=S groups anchor at the central Sb ion. The theoretical results based on DFT reveal that TU is adsorbed strongly on the (201) plane with an adsorption energy of −0.36 eV, which is much larger than that on the (003) plane of −0.22 eV. In addition, the large adsorption energy indicates that TU molecules interact strongly with the (201) oriented Cs3Sb2I9−xClx plane. According to previous studies, the (003) plane with a lower adsorption energy with TU grows much faster than the (201) plane and eventually disappears, which agrees with the XRD results [3Sb2I9−xClx film. For the W/O TU case, the Cs3Sb2I9−xClx films crystallize rapidly during annealing. For the W/TU case, the intermediate phase CsI·SbI3·SbCl3·TU could effectively delay the rapid nucleation during the annealing to obtain dense and smooth Cs3Sb2I9−xClx films along with TU decomposition [ results . Figure position .3Sb2I9−xClx films containing a different content of TU additive. Tauc plots for the assessed band gap value are shown in 3Sb2I9−xClx films, and its structure was glass substrate/Cs3Sb2I9−xClx film. As shown in 3Sb2I9−xClx film shows a trend of increasing first and then decreasing with the increases of TU from 0.1 M to 0.3 M. The 0.2 M TU additive film exhibits the highest PL peak intensity, which indicates that the nonradiative recombination was suppressed [4N2S = H2S + CH2N) [3Sb2I9−xClx film with the 0.2 M TU additive were further confirmed by TRPL, as shown in 3Sb2I9−xClx films. The TRPL results were in good agreement with the steady-state PL results. Therefore, the smooth surface, large grain size, and high crystallinity of Cs3Sb2I9−xClx films played a crucial role in reducing the defects states and further suppressing the nonradiative recombination.ppressed . When th + CH2N) . Meanwhitrap) was calculated. We also measured J–V curves of devices in the dark . For the 0.2 M TU additive Cs3Sb2I9−xClx films, the lower trap-filled limit voltage (VTFL) was 0.23 V for electron-only, which indicated the trap density had an impressive reduction. Ultraviolet photoelectron spectroscopy (UPS) results in 3Sb2I9−xClx films have valence band maxima at −6.01 eV, −6.03 eV, −6.08 and −6.08 eV, respectively. 3Sb2I9−xClx PSCs. The energy-level alignment of the conduction band minimum between Cs3Sb2I9−xClx and TiO2 was improved through the addition of TU into Cs3Sb2I9−xClx film. The VB/CB edge of the absorber shifted downwards upon the addition of TU. These downshifts in VB/CB benefited the electric charge transport and improved the PCE [Moreover, to evaluate the charge transfer properties of the devices, the electron state density , respectively. It is apparent that the 0.2 M TU additive Cs3Sb2I9−xClx film grains exhibit a uniform structure from bottom to top. The uniform and dense perovskite grains will enhance the carrier transport in the device [J–V curves for devices fabricated with Cs3Sb2I9−xClx films with different amounts of TU are presented in SCJ) improves, and the 0.2 M TU additive Cs3Sb2I9−xClx films devices obtain the highest efficiency of 2.22% under the 1–sun condition, which is attributed to the preferred orientation, smooth surface, and high crystallinity of perovskite films resulting in an improved carrier transport. The comparison of the efficiency with representative studies of Cs3Sb2I9−xClx PSCs summarized in SCJ for PSCs while maintaining an excellent PCE [3Sb2I9−xClx films with 0.3 M TU additive exhibited a poor photoelectric performance as a result of the appearance of a pinhole in the film. The external quantum efficiency (EQE) spectrum is shown in SCJ from 5.75 mA cm−2 to 6.77 mA cm−2 upon the addition of 0.2 M TU was in accordance with the measured SCJ from the J–V plots. The data of the fabricated PSCs are counted in 3Sb2I9−xClx PSCs device shows the largest charge recombination resistance (Rrec) (178.1) compared to the control device (99.1). The series resistance of the 0.2 M TU additive of the Cs3Sb2I9−xClx PSCs device exhibits a lower value (7.2 Ω) than that of control (9.4 Ω) due to the improved crystal orientation and morphology of perovskite film, demonstrating the boosting of charge transfer and the enhancing of the fill factor (FF) value. Capacitance-voltage (C−V) was carried out to explain the kinetics of the charge recombination and the increment of voltage values. The built−in potentials can be extracted in accordance with the Mott–Schottky Equation (1): [bi is the built–in potential, A is the device area, ε is the relative permittivity, ε0 is the vacuum permittivity, and NA is the carrier concentration. As shown in bi of 0.2 M TU additive Cs3Sb2I9−xClx PSCs was 0.65 V, which was higher than that of the control, 0.1 M TU additive, and 0.3 M TU additive devices 0.49 V, 0.46 V, and 0.45 V, respectively. The increasing Vbi benefitted the separation of the photogenerated carriers, which suppressed the electron-hole recombination and the [3Sb2I9−xClx solar cells in N2 environment conditions was observed : .(1)1C2= and the . The lonobserved f. The PC3Sb2I9−xClx film using a TU additive. TU promoted Cs3Sb2I9−xClx oriented crystallization. The induced Cs3Sb2I9−xClx perovskites prefered to grow in the (201) orientation, which is favourable for carrier transport. Moreover, TU also reduced the crystallization rate of Cs3Sb2I9−xClx perovskites and improved the morphology of the film. The regulated crystallization orientation and morphology efficiently assisted in reducing the trap state density, restraining nonradiative recombination, and elongating the carrier lifetime. As a result, the 0.2 M TU additive devices displayed an optimal PCE of 2.22%, along with a prolonged lifetime of 87.69% for the initial PCE after 60 days in N2 environment. This work shows a good prospect for modulating the crystallization process and orientation for high-performance Cs3Sb2I9−xClx perovskite photovoltaic devices.In summary, we successfully fabricated a high-quality Cs


Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inappropriate levels of attention, hyperactivity, and impulsivity that interfere with individual functioning. The international guidelines recommend targeting ADHD-related neurochemical brain abnormalities by intervening via drug treatment, such as methylphenidate (MPH), as first choice. Drug treatments are usually associated with a huge amount of cost for families and the healthcare system, suspension for low compliance, poor long-term efficacy, and side effects. Transcranial direct current stimulation (tDCS) has been suggested as a possible noninvasive means to safely manipulate brain activity and, in turn, improve behavior and cognition in developmental ages. Several studies have shown that tDCS has the potential to improve ADHD-related cognitive deficits, but the effect of tDCS compared with MPH has never been evaluated. The aim of the present within-subject, sham-controlled, randomized proof-of-concept study is to demonstrate the positive effect of one-session anodal tDCS analogous to the MPH drug on inhibitory control and working memory in children and adolescents with ADHD. We strongly believe that this study protocol will serve to accelerate research into low-cost, drug-free, feasible interventions for ADHD. Emerging during childhood, attention deficit/hyperactivity disorder (ADHD) is one of the most common lifelong brain-based disorders characterized by a mixture of inappropriate levels of inattention and/or hyperactivity/impulsivity . With a Several studies have attributed the symptoms of ADHD primarily to a deficit in executive functions, especially working memory (WM), response inhibition, and set shifting ,5,6,7,8.Transcranial direct current stimulation (tDCS) has been suggested as a promising technique to scaffold the key dysfunctional brain regions associated with ADHD, with the potential to alleviate the symptoms and the related cognitive deficits ,22,23,24Considering safety, several studies have demonstrated that tDCS induces minimal side effects, which are summarized as mild tingling and itching sensations under the electrodes, predominantly in the first few seconds of the stimulation session ,27. A reWith these premises, tDCS could be promoted as a valid alternative approach to drug-based treatment that may improve cognition, as well as prompt greater adherence and reduce side effects compared to pharmacological interventions . To dateTo the best of our knowledge, studies that directly compare the effect of brain-based intervention  and treatment as usual  on executive functions—especially inhibitory control and WM—are still missing in children and adolescents with ADHD. A detailed reporting of study protocols and procedures would be useful to accelerate the reproducibility of the results and to ensure the soundness of the methods.Investigating whether one session of anodal tDCS over left DLPFC will improve inhibitory control compared to placebo condition (sham tDCS) and to MPH;Exploring whether one session of anodal tDCS over left DLPFC will enhance WM compared to placebo condition (sham tDCS) and to MPH.This is a proof-of-concept study that aims at demonstrating the effectiveness of tDCS and MPH in improving executive functions in children and adolescents with ADHD. In particular, the project aims at:ClinicalTrials.gov (ID: NCT04964427) on the 13 July 2021. This study will be performed following the Declaration of Helsinki. The protocol adheres to the SPIRIT guidelines .Ethical approval for the study was granted by the local research ethics committee (process number 2185_OPBG_2020) and was registered at Children and adolescents will be recruited at the Child and Adolescent Neuropsychiatry Unit of the Bambino Gesù Children’s Hospital in Rome. All participants and their parents will be fully informed of the procedures and the purpose of the experiment, and the principal investigator will obtain written consent from both parents and the adolescent over the age of 12 before entering the study. Participation will be on a purely voluntary basis. Only patients for whom a clinical indication has already been given for the introduction of drug therapy with MPH and who come to the hospital for the administration of the first test dose will be recruited.The inclusion criteria will be the following: 1) participants of both genders, diagnosed with severe ADHD (combined presentation) accordingly to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition—DSM-5 . The investigator agrees to provide reliable data and all information requested by the protocol accurately and legibly according to the instructions provided and to ensure direct access to source documents to the ethics committee representatives. If any particular circuits have to be defined, particular attention should be paid to the confidentiality of the participant’s data to be transferred.In this case, the investigator may appoint such other individuals as he/she may deem appropriate as sub-investigators to assist in the conduct of the clinical trial following the clinical trial protocol. All sub-investigators shall be timely appointed and listed. The sub-investigators will be supervised by and under the responsibility of the investigator. The investigator will provide them with a clinical trial protocol and all necessary information.The participant’s data will be anonymous and coded. The hard files will be placed in a closed drawer. The database will be protected by a password. The investigator will allow the monitoring with an appropriate frequency. The original documents will be available at any moment to be verified by the clinical monitor and the regulatory authority.The sample size is calculated by a priori analysis in G*Power, version 3.1.9.7 .The estimated result will be obtained on the assumption that participants, receiving a single dose of MPH or a single session of active tDCS, will decrease the SSRT compared to the baseline, whereas participants receiving a single session of sham tDCS will not significantly change their SSRT compared to the baseline.Because the design of this project has never been employed in children and adolescents with ADHD, we will refer to studies in which patients with ADHD completed the SST before (baseline) and after interventions (a single dose of MPH or a single session of tDCS). Regarding MPH, Rosch and collaborators’ study  on SSRT Based on these observations, we estimate an f effect size of 0.25.With an estimated f = 0.25, α value = 0.05 , and β = 0.80 , the sample size is 24 as calculated using a Repeated-measures analysis of variance (RM-ANOVA) model with four within factors .The Shapiro–Wilk test will be used to test the normality of the data and Levene’s test for the homogeneity of variances. When data is normally distributed and the assumption of homogeneity will not be violated, parametric analyses will be computed. When one assumption will not be met, non-parametric tests will be conducted or a log-transformation of the distribution will be applied, if appropriate. When appropriate, sphericity will be verified by Mauchly’s sphericity test. When sphericity will not be met, Greenhouse–Geisser correction will be applied.Categorical data will be represented as count and proportion, while continuous data as mean and standard deviation or median and range. Chi-Square analyses will be used to compare the groups on demographic and safety measures .A preliminary analysis to test the effect of the four repetitions of the tasks  for WM and SSRT will be conducted.RM-ANOVA will be used to compare SST measures  and visual N-Back index, separately, with conditions  as a within-subjects factor.p2) will be used as measures of effect sizes.Post hoc comparisons will be assessed using Tukey’s honest significance test. Partial eta squares  and of a brain-directed intervention  in producing clinically meaningful impact on cognitive function in patients with ADHD.This study will represent the first attempt to test whether a single session of anodal tDCS is as effective as a single dose of MPH, or even more so. The results will represent a significant step toward implementing large-scale multi-sessions clinical trials in the field.The choice to compare tDCS and MPH is based on the observation that they have similar mechanisms of action at the neural level since they both modulate dopaminergic neurotransmission system in the basal ganglia-thalamocortical circuit. Specifically, MPH intervenes on dopamine active transporter DAT-1 ,49, the Concerning electrode placement, the methodological decision of placing anode over DLPFC was based on the aforementioned evidence. The left lateralization of the excitatory electrode over DLPFC was supported by neuroimaging studies demonstrating the involvement of left DLPFC in response stopping ,58, as wConcerning tDCS parameters, such as intensity, the selection was based on previous studies using tDCS in children with ADHD . The appWe choose to administer online tDCS instead of offline tDCS . Indeed,Concerning neuropsychological measures, we selected inhibitory control  and WM t®) with an interval session of 24 h, according to previous studies from our lab [In the current within-subject study, the participants will be exposed in a random order to a single shot of anodal tDCS session, a single shot of sham tDCS session, and a single dose of immediate-release MPH (Ritalin our lab . The pot our lab ,68,69. STo ascertain the absence of carry-over effects, a preliminary analysis will be conducted by evaluating the effect of the order of the four condition repetitions.The possibility to demonstrate the non-inferiority of tDCS to improve ADHD symptoms compared to MPH would promote its investigation as reliable and evidence-based intervention for children with ADHD. This clinical study could lay the foundation for future research perspectives on interventions for children with ADHD, speeding up the process of the understanding of this technique in pediatric rehabilitation.Further studies are needed to compare MPH and tDCS effects in multisession double-blind treatment studies and in larger group of patients with ADHD. In addition, functional neuroimaging studies should be designed to verify that dopamine release caused by tDCS has a brain effect comparable to that of MPH.We firmly believe that detailed reporting of clinical trial protocols would reduce the publication bias of future research, by prompting the reproducibility and the reliability of experimental designs.


Mean MCW was significantly lower among children with ADHD compared to those in the control group . Additionally, each of the MCW sides were significantly smaller in the group with ADHD compared with the control group. In conclusion, treatment with methylphenidate is associated with low MCW in children and adolescents with ADHD. Analysis of MCW on DPR may help in screening children that are at risk of bone health alterations that may result in low BMD in adulthood. Dentists may be the first to identify bone health abnormalities and should be aware of their role in referring their patients to further follow-up.Some studies have shown that children treated with psychostimulants for attention-deficit hyperactivity disorder (ADHD) have decreased bone mineral density (BMD). Mandibular cortical width (MCW) may be used as a surrogate measure for evaluating BMD. We compared the MCW measured on digital panoramic radiographs (DPR) of 38 children and adolescents with ADHD who were treated with methylphenidate for at least 12 months to the MCW of 58 children and adolescents without ADHD (control). The two groups had a similar mean age ( Attention-deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood. Among children, the pooled global prevalence of ADHD is 7.2% . The litIndividuals with ADHD have an enduring pattern of hyperactivity–impulsivity and/or inattention that interfere with functioning and/or development . Most chIn the last 40 years, there has been a debate whether psychostimulants—specifically methylphenidate—affect growth in children who use them. Some studies have shown that these medications may affect the child’s weight at the start of treatment ,14,15,16An important factor related with growth and development is bone mineral density (BMD). The potential effects of psychostimulants on growth have led researchers to evaluate whether this drug group affects the BMD of children; however, the results of these studies are not consistent.Lahat et al.  demonstrIt has previously been shown that the shape and thickness of the mandibular cortex reflects bone mass loss in the body . A signiThis cross-sectional study was carried out at the Pediatric Dentistry Department at the Goldschleger School of Dental Medicine at Tel-Aviv University, Israel. Ethical approval was granted by the institution’s Human Research Ethics Committee . Informed consent was given by the parents to use the data included in the children’s dental file.Fifty children with ADHD who were treated with methylphenidate and 50 healthy children of the same age range and ethnicity who were treated in the dental clinic at the Pediatric Dentistry Department were asked to participate in the study.The inclusion criteria for the ADHD group were children and adolescents aged 7–20 years who met the diagnostic criteria of the American Psychiatric Association for ADHD  and wereDPRs were taken as part of routine orthodontic examinations in Digital Imaging and Communications in Medicine (DICOM) format using a Planmeca ProMax unit . All measurements were performed by a single observer who was blinded to the participants’ diagnoses. Cortex thickness of both sides of the mandible was measured on the DPRs with the RadiAnt Dicom Viewer software version 5.5 . As described by Paulsson et al. , a line t tests or Mann–Whitney tests, as appropriate according to the type of distribution. Categorical variables were compared using chi-squared or Fisher’s exact test depending on the number of observations. A p value < 0.05 was considered significant. Descriptive and comparative statistics were analyzed using Statistical Software for the Social Sciences version 23 . Continuous variables were compared using Student’s p = 0.3), but the group with ADHD had a higher percentage of males . In addition, each of the MCW sides were significantly smaller in the ADHD group compared with the control group .As shown in Over eight different methods for assessing growth have been reported in studies that evaluate growth in children with ADHD. These have included methods that are prone to artifactual distortion and low sensitivity, such as direct comparisons of mean height and frequency percentiles from standardized growth charts. The issue of method sensitivity is important when evaluating growth changes in ADHD because the reported mean height deficits have usually been small . This stSince 1960, several studies have reported that specific changes associated with decreased BMD are visible in DPRs. These mainly refer to changes in the morphology of the inferior mandibular cortex and to altered trabecular bone architecture . UsuallyData from staining experiments show that the posterior surface of the ramus and the condylar and coronoid processes are the principal sites of mandible growth, while the anterior part of the mandible does not change much. In infants, the ramus is localized to the site of eruption of the primary first molar. Progressive posterior remodeling creates space for the second primary molar and then for the sequential eruption of the permanent molar teeth .The area below the mental foramina is the most often studied, due to the usual lack of muscle attachment there and the fact that the distance between the mental foramen and the inferior margin of the mandibular cortical bone remains relatively stable during the lifespan, regardless of alveolar bone resorption following tooth extraction or inflammation . A decrease in bone mass and changed morphology may be identified by the thinning and resorption of the inferior border of the mandibular cortical bone ,43. The The influence of methylphenidate on BMD may be mediated by gastrointestinal adverse effects which may change the dietary intake of calcium, thereby negatively impacting peak bone mass accrual . MethylpWhether a smaller MCW can be exclusively attributable to treatment with methylphenidate is a subject of debate. Slower growth may also be related to associated delays in cognitive and physical brain maturation or represent a digression from the typical development pattern .Diminished bone accrual during childhood and adolescence may lead to an increased risk for osteoporosis, and consequently to higher fracture risk and potentially altered fractured healing in adulthood . ChildreThe limitations of this study include its cross-sectional design; hence, changes over time could not be evaluated. The use of medication for ADHD was self-reported; therefore, we do not have data on dosage or changes in therapy. Furthermore, the MCW of children with ADHD who are not treated with methylphenidate was not evaluated. The use of DPR for measuring MCW has some limitations, including its two-dimensional representation and observer variability. Additionally, intrinsic distortional effects may occur, which may be caused by patient positioning (which is more difficult in young children), machine motion, the region studied, and mandible morphology ,50. It iThe present study suggests that treatment with methylphenidate is associated with low MCW in children and adolescents with ADHD. Analysis of MCW on DPR is a simple method that can help in screening children that are at risk for bone health changes that may cause low BMD in adulthood. Dentists may be the first to recognize alterations in bone health and should be aware of their role in referring their patients to further follow-up. Awareness should be raised among physicians and parents to the potential health risks of BMD associated with methylphenidate and other psychostimulants and to the importance of educating and improving the follow-up of this risk group. We suggest that dentists should conduct a bi-annual follow-up of MCW in children and adolescents who are treated with psychostimulants.


BackgroundDelirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention and multiple aspects of cognition that fluctuate in severity over time. The symptomatic management of delirium's behavioral manifestations remains difficult. The alpha-2 agonists, dexmedetomidine and clonidine, are efficacious, but their potential cardiovascular adverse effects limit their utilization. Guanfacine is an oral alpha-2 agonist with a lower potential for such adverse outcomes; however, its use in delirium has not been studied.MethodsA retrospective descriptive analysis of guanfacine for managing hyperactive or mixed delirium at Tampa General Hospital from January 2020 to October 2020 was conducted. The primary outcome was the time reduction in acute sedative administration. Secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT), decreased opioid use, and an incidence of cardiovascular adverse effects.ResultsOne hundred forty-nine patients were identified as having received guanfacine for managing delirium during the study period. All experienced a reduction in acute sedative use after the initiation of guanfacine. In 93 patients receiving PT/OT and no longer participating due to behavioral agitation, 74% had a documented renewal of services within four days. Of 112 patients on opioids, 70% experienced a 25% reduction in opioid administration within four days. No patients experienced consecutive episodes of hypotension that required a change in their clinical care. Two patients experienced a single episode of consecutive bradycardia that led to the discontinuation of guanfacine. ConclusionsBased on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased acute sedative use for behavioral agitation. Additionally, patients treated with guanfacine received fewer opioids and were better able to participate in PT/OT. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.  Delirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention, awareness, and multiple aspects of cognition that fluctuate in severity over time. It is the most common neuropsychiatric disorder observed in hospitalized patients, affecting 10% to 60% of medical inpatients with a general medical disorder and up to 82% of mechanically-ventilated patients in the intensive care unit (ICU) . As suchAntipsychotics have historically been used for the management of delirium's behavioral manifestations. In an international survey of 1521 intensivists, 65% reported that they manage delirium in the ICU with haloperidol, and 53% reported using a second-generation antipsychotic . Many stFurthermore, antipsychotics are not without potentially serious adverse effects, including cardiac , cerebrovascular events, central nervous system events , anticholinergic effects, and overall increased mortality ,16. ThisRecently, research into alpha-2 agonists, such as dexmedetomidine and clonidine, has been pursued with great interest due to their reported efficacy in preventing and managing delirium ,16,17. TGuanfacine is another alpha-2 agonist typically used to treat attention deficit/hyperactivity disorder (ADHD). It possesses a much higher alpha-2 receptor selectivity than dexmedetomidine and clonidine. It is reportedly 25 times more selective than clonidine and 1.65 times more selective than dexmedetomidine -28. ThisWe have conducted a retrospective analysis of guanfacine for managing delirium in our hospital's ICU and general wards. The primary outcome was the time to 25% reduction in acute sedative (rescue sedation) administration after initiation of guanfacine. Our secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT) after initiation of guanfacine, opioid use after initiation of guanfacine, and the incidence of cardiovascular adverse effects after administration of guanfacine.For this retrospective descriptive analysis, data were collected from an Epic electronic medical database via Epic SlicerDicer software at the Tampa General Hospital in Tampa, FL, USA. Records from January 2020 to October 2020 were retrieved for this study. Only patients diagnosed with delirium and for whom guanfacine (Tenex) was specifically administered for symptoms of delirium were included. The diagnosis of delirium was initially recorded by either the psychiatric consultant who evaluated the patient or the primary service team physician(s). Confirmation of the diagnosis of delirium and its subtyping (mixed or hyperactive) was established by the consulting psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition [DSM-5] and LiptElectronic medical records were reviewed for demographic and clinical characteristics, diagnoses  , hospitaA 25% reduction in acute sedative use was chosen as the primary outcome. This parameter can be used as a marker for a reduction in basal agitation in the absence of prospective delirium severity scale scores. The initial dosing and titration of guanfacine were based on individual clinical judgment and expertise. Continuous data are presented as means ± standard deviations (SD), and categorical data as percentages.This study was approved by the University of South Florida Institutional Review Board as an exempted retrospective study and determined not to require informed consent.In total, 149 patients were identified as meeting the inclusion criteria of having received guanfacine for managing delirium during the defined study period  experienced a 25% reduction in opioid administration within four days after the initiation of guanfacine Table . The choCardiovascular adverse effects were also screened for and recorded in all 149 patients  that are required for appropriate chemical sedation. Haloperidol was the most common agent prescribed in our sample, with an average 24-hour dose of 12.3mg; a 25% reduction of this represents a meaningful decrease in exposure to this medication and the side effect burden that it entails. Moreover, of our 93 patients receiving physical or occupational therapy, most demonstrated a renewed ability to participate within four days of guanfacine initiation. This was after receiving no therapy due to their delirium severity and level of cooperation. Of note, active participation in PT has been conclusively shown to decrease the incidence of developing delirium and increases the rate of recovery from delirium -38. The Regarding secondary outcomes, the reduction in opioid use was considerable. As most of our sample (n=95) was present in the ICU when diagnosed with delirium and initiated on guanfacine, this is an exciting finding. Opioids are commonly prescribed for acute pain relief, especially in the ICU. It is estimated that 80% of critically ill patients are being administered opioids at any time . EffectiFurthermore, opioids have been shown to increase the risk of delirium; thus, a decrease in their use would have the added benefit of limiting the overall deliriogenic medication burden -46. A 25Perhaps the most striking outcome observed in our study was the overall safety profile of guanfacine. It is well-known that dexmedetomidine and clonidine use is limited in delirium by their potent cardiovascular adverse effects . We hypoFinally, our study has several limitations that deserve to be mentioned. This was a retrospective descriptive analysis without a control group. We could not select a control due to our sample's heterogeneity and the general wards' inclusion. If we had only conducted a study in the ICU, it would have been more feasible to have a delineated control group. No statistical analyses were conducted as such. As we have demonstrated the safety and possible effectiveness of guanfacine for delirium, future studies should be prospectively designed for clinical trials that include randomization, a control group, and a blind to make direct comparisons. Our sample may suffer selection bias, as this study was conducted at a single, tertiary academic hospital, thus affecting the acuity, severity, and complexity of delirious patients. The average age of our patients was also younger , thus affecting the generalizability of our results to the geriatric population in terms of safety profile. There were no standardized methods for continuously assessing delirium. The outcomes of improved agitation and reduced opioid utilization were not regularly evaluated with any validated objective scales, as seen in a clinical trial. Besides their beneficial sedative and analgesic properties, alpha-2 agonists have also reportedly been helpful for improved sleep architecture in the setting of delirium . We wereBased on our retrospective review, we conclude that guanfacine is a safe and well-tolerated medication for patients with hyperactive and mixed-type delirium both in the ICU and medical wards. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased requirements for using sedative agents to manage delirium-associated behavioral agitation. Additionally, patients treated with guanfacine reduced their use of opioid medications and were better able to participate in physical and occupational therapy. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.


Introduction: Semiconductors have similar crystal structures and matched energy levels could form a coupled heterojunction at an interface between them which may allow response to visible light, achieving efficient decomposition of organic compounds.Methods: The Bi2O2CO3/BiOI (BOC/BOI) with 2D/2D p-n heterojunction was prepared by one-pot room-temperature strategy. The prepared materials were tested by various technologies, and the three-dimensional structure, light absorption properties, electrochemical properties and other information were obtained. Photocatalytic tests have also been carried out.Results and discussion: BOC/BOI heterojunction with oxygen vacancies showed much higher photocatalytic activity than pure BOC and BOI. For example, the preferred BOC/BOI-0.5 heterojunction of the degradation rate for Rhodamine B (RhB) is 97.6 % within 2 h, which is 15.8 and 2.2 times faster than that of BiOI and BOC. In addition, the removal rates of tetracycline, ciprofloxacin and bisphenol A by BOC/ BOI-0.5 were 92.4, 80.3 and 68.6%, respectively. The 2D/2D structures of BOC/BOI-0.5 with rich in oxygen vacancies combined p-n junction can effectively inhibit the photoinduced electron-hole pair recombination and increase the production of active free radicals. The O2- and h+ are the main reactants, giving the composite catalyst potential for degrading a variety of pollutants. Changing the molar ratio of the reactants altered the photocatalytic performance as expected. And the Bi2O2CO3/BiOI heterojunction catalyst displayed very high photocatalytic activity into RhB degradation under visible light.This study therefore aimed to synthesize Bi3)3⋅5H2O), urea (CH4N2O), nitric acid (HNO3) and the scavenging agents ethylenediaminetetraacetic acid disodium salt (EDTA-2Na), isopropyl alcohol and benzoic acid—as well as the Rhodamine B were purchased from Sinopharm Chemical Reagent Co., Ltd. (China). All of the chemicals were of analytical grade.The chemicals used in the catalysts’ preparation—potassium iodide (KI), bismuth nitrate (Bi(NO2O2CO3 was obtained by mixing 970.2 mg of Bi(NO3)3·5H2O with 12 ml of nitric acid, and then adding 200 ml of pure water. The mixture was stirred at 25°C for 0.5 h, and the pH was adjusted to 10 using ammonia solution. 106 mg of Na2CO3 was then added and stirred for 12 h. The supernatant was removed, centrifuged and washed three times, and the BOC mixture was dried at 60°C.Bi3)3·5H2O was mixed with 12 ml of nitric acid, and then 200 ml of pure water was added. The mixture was stirred at 25°C for 0.5 h, the pH was adjusted to 10 using ammonia solution. 622 mg of KI was then added and stirred at 25°C for 12 h. The supernatant was removed, centrifuged and washed three times, and the resulting BOI mixture was dried at 60°C.A similar procedure was involved in the preparation of the BiOI. 970.2 mg of Bi(NO3)3·5H2O in 12 ml of nitric acid, adding 200 ml of pure water, and stirring at 25°C for 0.5 h. After adjusting the pH to 10 with ammonia, 106 mg of Na2CO3 was added and the suspension was stirred for 0.5 h. Either 83 mg, 166 mg, 322 mg, 622 mg or 1,244 mg of KI was added, and then sufficient Bi(NO3)3·5H2O was added to make the molar ratio with KI 4:1, 2:1, 1:1, 1:2 or 1:4. The mixture was stirred at 25°C for 12 h, and the supernatant was removed, centrifuged, washed three times, and dried at 60°C. The Bi2O2CO3/BiOI heterojunction catalysts obtained were designated BOC/BOI-4, BOC/BOI-2, BOC/BOI-1, BOC/BOI-0.5 BOC/BOI-0.25 to reflect the molar ratios.The binary catalyst was synthesized by dissolving 970.2 mg of Bi(NOα radiation (λ = 1.5406Å) as the X-ray source. Fourier transform infrared spectroscopy (FT-IR) was performed using a TENSOR27 spectrometer. The surface elements were detected using an ESCALAB 250Xi X-ray photoelectron spectroscope (Thermo Fisher Scientific). An A300-10/12 Bruker EPR spectrometer was used to measure the electron paramagnetic resonance (EPR) of the free radicals detected. The morphology and microstructure of the catalyst were examined using a Hitachi, S-4800 scanning electron microscope and high-resolution transmission electron microscopy (HRTEM) was performed with a Tecnai G2 F30 S-Twin instrument. The catalysts’ optical properties were characterized by UV-visual diffuse reflectance spectroscopy relying on a Hitachi U-4100 instrument. A Micromeritics ASAP 2460 instrument was used to record the Brunauer Immett Teller (BET) specific surface areas. A Renishaw inVia confocal Raman microscope was used to study the catalysts’ photoluminescence (PL). Electrochemical impedance spectroscopy (EIS) was performed and Mott Schottky diagrams were prepared in 0.2 M Na2SO4 electrolyte using a CHI760E electrochemical workstation. The ITO glass electrode was loaded with a sample containing 10 mg of a catalyst, and Ag/AgCl and Pt wires were used to form a three-electrode system. The EIS was over a frequency range of 0.01–105 Hz at 5 mV AC. The frequency of the Mott Schottky test was fixed at 10 Hz. Absorbance readings at 554 nm using a Shimadzu UV-2450 ultraviolet-visible spectrophotometer measured the concentration of RhB.X-ray diffraction (XRD) analysis was recorded using a Bruker D8 Advance X-ray diffractometer with Cu K−1 solution of RhB, and the suspension was stirred continuously in the dark for 1 h. The mixture was then illuminated with a 300 W xenon lamp (λ > 420 nm), and the 3 ml of the reaction mixture was sampled every 20 min to determine the RhB concentration using the UV-visible spectrophotometer.For RhB removal, 20 mg of catalyst was mixed with 50 ml of a 20 mg L−1 solution of bisphenol A (BPA) and same procedure was followed. Ciprofloxacin (CIP) and tetracycline (TC) degradation were also tested in the same way . The peak intensities of C-O and C=O at 1384 and 1,478 cm−1 also gradually decrease, which proves that BOC and BOI coexist in the composite. No absorption peaks attributable to impurities or solvent residue were detected.BOC characteristic bands persist in the BOC/BOI composite. As the composite’s BOI content increases, Bi-O bond traces at 550 cm3. The excess C content is due to the adsorption of carbon from the air. The curves for BOC/BOI-0.5 in The XPS spectra show the surface chemical states of the photocatalytic materials. The full spectrum survey revealed only Bi, O, C, and N in the BOC. The small amount of N may indicate the presence of BiONO7/2 and Bi 4f5/2). For BOC/BOI-0.5, the peaks attributable to Bi 4f can be decomposed into 159.4 and 164.7 eV, corresponding to the characteristics of Bi3+ (2O2]2+ (2O2CO3/BiOI may have a heterojunction (5/2) and 630.7 eV (I 3d3/2), indicating that the valence state of iodine is -1  n/2 where α is the absorption coefficient, h is Planck’s constant (eV), v is the optical frequency (Hz), Eg is the band gap (eV), and A is a fitting a constant. n depends on the optical conversion of the semiconductor  (2O2CO3 and BiOI are indirect bandgap semiconductors (n = 4) (1/2versus (hv) in g of BOC is 2.06 eV and that of BOI is 2.89 eV.The UV-visible diffuse reflectance spectra  further version) . Bi2O2CO (n = 4) . From th0/C) = kt, R2 > 0.99)  . The k v+, •O2− and •OH, respectively, the main reactive radicals in the photocatalytic process. The quenching greatly inhibited the degradation of RhB was inhibited, so h+, •O2− and •OH are involved in the photocatalytic process. Among them, h+ plays a leading role, probably because photogenerated electrons and holes react with O2 and H2O to produce •O2− and •OH, which then remove pollutants , Ciprofloxacin (CIP) and Tetracycline (TC) . Figure llutants . EPR tesllutants  further llutants  were detadiation . In the adiation , a peak adiation . These radiation .CB = X − Ee − 0.5Eg, and EVB = ECB + Eg . Photoinduced h+ interacts with water to produce •OH, which is finally decomposed by the interaction between the two radicals and pollutants  can then be effectively separated.iii. Oxygen vacancy (OV) is a kind of metal oxide defects. In this work, it is the separation of oxygen in the lattice caused by metal oxides at high temperature, which leads to oxygen loss and the formation of OVs. The existence of OVs makes the Fermi energy level of oxide move upward, and defect energy level appears in the band gap, thus reducing the band width and improving the light absorption performance. In addition, OVs promote the conversion of excitons into carriers, and accelerate the reduction reaction on the catalyst surface, leading to the separation of carriers. Moreover, the OVs may optimize the adsorption energy of reactants on the catalyst surface, thereby reducing the reaction energy barrier and promoting molecular activation. Thus, OVs plays a synergistic role with nearby active metal sites on the catalyst surface, and photo-generated charge carriers  to produce strongly oxidizing •OH to oxidize organic pollutants. As one of the active substances, h+ can also directly oxidize pollutants.iv. At the same time, e+, •O2‾ and •OH.v. RhB can be degraded under the combined action of hvi. In the process of RhB degradation, possible sensitization pathways should be considered. RhB may also be excited and inject electrons and residual holes from the excited state RhB* into the heterostructure. The residual holes will then further participate in the degradation reaction . TherefoTaken together, these findings suggest that the photocatalytic mechanism as below:Heterostructured BOC/BOI photocatalytic materials with tunable content have been prepared successfully. The BOC/BOI composite photocatalyst showed greater photocatalytic activity in the degradation of pollutants such as RhB than pure BOC or BOI. The composite’s photodegradation rate of RhB was 9.6 times that of pure BOC. The enhanced photocatalytic activity of BOC/BOI-0.5 largely depends on the p-n heterojunction structure of BOC and BOI. BOC/BOI-0.5 has good interfacial contact and oxygen vacancies. SEM and TEM images confirm that BOC/BOI-0.5 has an ultra-thin nanosheet structure. Photoinduced holes are the main active elements in BOC/BOI-0.5 for the photocatalytic degradation of organic compounds. And BOC/BOI-0.5 also degrades other organic pollutants. It is hoped that in the future this method will be widely applied to the synthesis of other visible light-driven photocatalysts containing bismuth heterostructures with controllable structure.


Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent childhood-onset neurodevelopmental disorders; however, the underlying neural mechanisms for the inattention symptom remain elusive for children with ADHD. At present, the majority of studies have analyzed the structural MRI (sMRI) with the univariate method, which fails to demonstrate the interregional covarying relationship of gray matter (GM) volumes among brain regions. The scaled subprofile model of principal component analysis (SSM-PCA) is a multivariate method, which can detect more robust brain-behavioral phenotype association compared to the univariate analysis method. This study aims to identify the GM network associated with attention in children with ADHD by applying SSM-PCA to the sMRI.The sMRI of 209 children with ADHD and 209 typically developing controls (TDCs) aged 7–14 years from the ADHD-200 dataset was used for anatomical computation, and the GM volume in each brain region was acquired. Then, SSM-PCA was applied to the GM volumes of all the subjects to capture the GM network of children with ADHD . The relationship between the expression of ADHD-related pattern and inattention symptom was further investigated. Finally, the influence of sample size on the analysis of this study was explored.r = 0.25, p = 0.0004) and the DuPaul ADHD Rating Scale IV . Finally, we found that when the sample size was 252, the results of ADHD-related pattern were relatively reliable. Similarly, the sample size needed to be 162 when exploring the relationship between ADHD-related pattern and behavioral indicator measured by CPRS-LV.The ADHD-related pattern mainly included putamen, pallium, caudate, thalamus, right accumbens, superior/middle/inferior frontal cortex, superior occipital cortex, superior parietal cortex, and left middle occipital cortex. In addition, the expression of the ADHD-related pattern was related to inattention scores measured by the Conners’ Parent Rating Scale long version (CPRS-LV; We captured a GM network associated with attention in children with ADHD, which is different from that in adolescents and adults with ADHD. Our findings may shed light on the diverse neural mechanisms of inattention and provide treatment targets for children with ADHD. Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent childhood-onset neurodevelopmental disorders characterized by inattention and/or hyperactivity and impulsivity, which impaired the school functioning and academic achievement of schoolchildren . The worFor children with ADHD, the anatomical abnormalities in the brain volume have been widely investigated through structural magnetic resonance imaging (sMRI), shedding light on the disease’s mechanisms and treatments. In a recent meta-analysis of gray matter (GM), children with ADHD showed a decreased GM volume in the right globus pallidus, putamen, and bilateral caudate . MoreoveThe scaled subprofile model of principal component analysis (SSM-PCA) is a multivariate method for network analysis , which cThus, this study aimed to identify the GM network of children with ADHD  by applying the SSM-PCA approach to sMRI and investigating the relationship between the ADHD-related pattern and inattention symptom. According to previous studies, we hypothesized that the ADHD-related pattern would comprise brain regions in frontal cortex, basal ganglia, and cerebellum, and the expression of ADHD-related pattern would relate to inattention scores.1 The ADHD-200 cohort contains 776 subjects with anatomical images aggregated from 8 independent sites (age range: 7–21 years). Demographic data including age, sex, handedness, secondary diagnosis, and medication status are also available from the website. The diagnosis of ADHD is based on the Conners’ Parent Rating Scale long version (CPRS-LV) or DuPaul ADHD Rating Scale IV (ADHD-RS) and is divided into three subtypes, including inattentive type (ADHD-I), hyperactive/impulsive type (ADHD-H), and combined type (ADHD-C). For children measured with CPRS-LV, the diagnosis of ADHD was based on a T-score greater than or equal to 65 on at least one ADHD-related index  data with poor image quality; (2) data in the site without the ADHD group or the typically developing control (TDC) group; (3) data aged under 7 years or over 14 years; (4) data diagnosed as ADHD-H; (5) some data were excluded to make group match of age and sex between ADHD and TDC; and (6) data in the site with participants less than 10. In total, 358 subjects (76 ADHDs and 282 TDCs) were excluded, and the number of the excluded subjects in each step is presented in 2) developed by Christian Gaser and Robert Dahnke  is an extension of Statistical Parametric Mapping 12 (SPM123) for anatomical computation. The segmentation and normalization were implemented using DARTEL, which utilized a single constant velocity field to generate diffeomorphic and invertible deformations. The GM segments of each participant were non-linearly registered to the automated anatomical labeling 3 (AAL3)   template3 (AAL3) .4  each column was centered to zero by subtracting the mean of each column; (3) each row was centered to zero by subtracting the mean of each row, and then the subject residual profile (SRP) was obtained; (4) the reduced singular value decomposition (SVD) was utilized to factorize the SRP:An in-house developed SSM-PCA toolbox was used for performing SSM-PCA on GM volume from the ADHD-200 dataset . As the U is an M × N matrix composed of the left unit-normalized orthogonal singular vectors as columns, Σ is an N × N diagonal matrix composed of singular values kσ, where k is the component number, and V is an N × N matrix composed of the right unit-normalized orthogonal singular vectors as columns; and (5) the group invariant subprofile  and subject scaling factor  can be computed by:where i is the region number and j is the subject number (6). The ratio of variance corresponding to each GIS to the total variance was calculated and named the variance accounting for (VAF).where Each value in the GIS matrix indicates a weight representing the contribution of a region to the corresponding pattern. Regions with relatively large weights in the pattern constitute the “network” called in some papers , 26.t-test on the first 10 SSFs with controlling for age and sex and found that the first, sixth, and tenth SSFs showed a significant difference between the two groups (p < 0.05). Finally, an ADHD-related pattern was identified by a linear combination of the first, sixth, and tenth patterns. According to previous research .As the datasets come from different scanning sites and the behavior scales vary among sites, the sample was divided into three subsamples, i.e., 198 participants measured by CPRS-LV, 142 participants measured by ADHD-RS, and 78 participants without inattention scores. Then, the Spearman correlation was performed to investigate the relationship between inattention scores and the expression of ADHD-related pattern on the two subsamples measured by CPRS-LV and ADHD-RS, separately. The above statistical analysis was based on Statistical Product and Service Solutions  first, a certain number of participants were randomly selected from the ADHD group and the TDC group to form a new sample. Due to the limitation of the number of subjects in each group, the maximum sample size was 198. Here, the sample size of each group was set as 54:18:198, and 18 subjects consisted of 9 subjects measured by CPRS-LV, 6 subjects measured by ADHD-RS, and 3 subjects without the inattention scores. (2) The SSFs of the ADHD-related pattern of the selected subjects were used to perform the group difference and correlation analysis with inattention scores from CPRS-LV and ADHD-RS. Steps 1 and 2 were repeated 1,000 times.p < 0.05) (t(416) = 4.80, Cohen’s d = 0.47, 95% CI = ; p = 2.27 × 10–6] (The VAF of each pattern is shown in  < 0.05) . After a × 10–6] . The topn = 198, r = 0.25, p = 0.0004). Similarly, the expression of the ADHD-related pattern was significantly associated with inattention scores of ADHD-RS .As shown in p-values with the sample size. The difference in SSF of the ADHD-related pattern between ADHD group and TDC group became more and more significant with the expansion of the sample size. The expression of the pattern showed significant differences between the two groups when the sample size was 180. In addition, when the sample size was 252, the p-value for SSF reached a plateau and its range became smaller and smaller. Similarly, the expression of the pattern was significantly associated with inattention scores measured by CPRS-LV when the sample size was 162. Due to the small sample size of subjects measured by ADHD-RS, the sample size effect of ADHD-RS remained elusive. In general, these results showed that sampling variability decreased and the associations stabilized along with increasing sample sizes.In this study, we performed SSM-PCA on GM volume from ADHD-200 datasets and captured the ADHD-related pattern, which mainly included the putamen, pallium, caudate, thalamus, right accumbens, superior/middle/inferior frontal cortex, superior occipital cortex, superior parietal cortex, and left middle occipital cortex. In addition, the expression of the ADHD-related pattern was significantly associated with inattention scores.As shown in the ADHD-related pattern, our results highlight the importance of basal ganglia  and bilateral superior/middle/inferior frontal cortex in ADHD. These regions demonstrated a significant reduction of GM volume in ADHD relative to TDC. These findings are in line with our hypotheses and similar brain areas and GM volume changes have been reported in previous studies , 28–33. This study finds increased GM volumes in the thalamus, superior temporal cortex, and cerebellum lobule I. For the thalamus, our result is consistent with a previous study in patients with ADHD-I from the ADHD-200 datasets . FurtherIn our study, the expressions of ADHD-related pattern were significantly associated with inattention scores measured with two different scales . Our findings are consistent with the previous studies , 51. CasIn adolescents with ADHD, previous research identified an attention-related GM network compromising the bilateral cerebellar tonsil and culmen . In adulThis study not only focused on the ADHD-related pattern but also investigated the effect of sample size on the whole data analysis. Our results showed that the difference between the ADHD group and the TDC group was enhanced with the expansion of sample size and reached stable with a sample size greater than 252. Similarly, when exploring the relationship between ADHD-related pattern and behavioral indicator measured by CPRS-LV, the sample size needs to be larger than 162. The required sample size is much less than that needed in univariate analysis methods . These rThis study also has some limitations. First, the inattention scores of participants from different sites in the ADHD-200 dataset were measured with different scales , which forces us to investigate the correlation between inattention scores and ADHD-related pattern expression, separately. Second, to test the robustness of our results, replication on other datasets is necessary. Third, due to the small number of subjects in the subtypes of ADHD-I and ADHD-C, we analyzed all the data together; however, it is important to further investigate the subject heterogeneity between these two ADHD subtypes regarding attention-related GM pattern, separately.We obtained a GM network associated with attention in children with ADHD, which is different from that in adolescents and adults with ADHD. Our findings may shed light on the diverse neural mechanisms of inattention and provide treatment targets for children with ADHD.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the NITRC and 1000 Functional Connectomes Project. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.L-XY conceived and designed the experiment. X-KW performed the data analysis. X-QW and XY provided advice on the analysis and interpretation of the results. X-KW and L-XY wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The etiological and pathophysiological factors of learning disorder (LD) and attention deficit hyperactivity disorder (ADHD) are currently not well understood. These disorders disrupt some cognitive abilities. Identifying biomarkers for these disorders is a cornerstone to their proper management. Kynurenine (KYN) and oxidative stress markers have been reported to influence some cognitive abilities. Therefore, the aim was to measure the level of KYN and some oxidative stress indicators in children with LD with and without ADHD and to investigate their correlations with the abilities of children with LD.N = 69); another for children with LD and ADHD (N = 31); and a group for neurotypical (NT) children (N = 54). IQ testing, reading, writing, and other ability performance evaluation was performed for children with LD. Measuring plasma levels of KYN, malondialdehyde, glutathione peroxidase, and superoxide dismutase by enzyme-linked immunosorbent assay was performed for all participants.The study included 154 participants who were divided into 3 groups: one for children who have LD (p < 0.001). However, the biochemical measures did not show a significant statistical difference between the first two groups. KYN and glutathione peroxidase levels were correlated with one-minute writing and at-risk quotient, respectively . KYN and malondialdehyde showed the highest sensitivity and specificity values.Some IQ measures and learning skills differed between the first two groups. The biochemical measures differed between children with LD (with and without ADHD) and NT children (These biochemical measures could be involved or have a role in the abilities’ performance of children with specific learning disorder. Learning disorder (LD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders that influence some cognitive abilities . In someKynurenine (KYN) is one of the tryptophan metabolites , and its pathway activation has been linked to stress exposure and chronic inflammation. KYN is considered neurotoxic and it has been reported to be implicated in central nervous system disorders including Huntington’s disease, Alzheimer’s disease, and depression, all of which compromise memory and fine motor performance, among other problems . FurtherOxidative stress could lead to reversible or irreversible forms of oxidative modifications of cellular proteins. The modifications have been reported to be an etiological step of cellular dysfunction, particularly neurons and other brain cells. Antioxidants, which are produced by the human body, neutralize oxygen-derived free radicals, or reactive oxygen species. These species indiscriminately attack vital molecules, such as proteins, DNA, carbohydrates, and fats, which are essential structures of every cell. This would alter the function of these molecules and impair the normal course of their metabolism in cells. It’s worth noting that low concentrations of reactive oxygen species serve a useful purpose in the body for regulation of cellular homeostasis. Reactive oxygen species are necessary to activate the pathways that upregulate the activity of various antioxidant enzymes, including glutathione system enzymes. Therefore, oxidative stress could be defined as “a state where oxidative forces exceed the antioxidant systems due to loss of the balance between them”. Oxidative stress has been implicated in the pathogenesis of neurodevelopmental disorders and neurodegenerative disorders, such as vascular cognitive impairment, which hinders memory and learning in adults . In healMalondialdehyde (MDA) is a lipid peroxidation-related measure. It has long been recognized as a biomarker for oxidative stress. It is one of many reactive electrophile species that produce toxic stress in cells by forming covalent protein adducts. These adducts are known as advanced lipoxidation end products, which cause oxidative damage to cells, including neural cells . On the All of the previous biochemical measures were implicated in memory and learning in animal studies, and a few human adult studies which targeted neurological disorders influencing memory, cognition, and motor abilities , 15. InvThe participants  in this cross-sectional study, which followed the checklist for STROBE,The data obtained were collected, tabulated and then analyzed using the Statistical Package for Social Sciences. Descriptive statistics were done for quantitative data as mean ± standard deviation (SD), number and percentage for qualitative data. Inferential analysis was performed for quantitative variables using the independent t-test and for qualitative data using the Chi square test. Correlations between biochemical measures and total IQ, the at-risk quotient, and subtests of the dyslexia assessment test were investigated. For correlation analysis, Spearman correlation coefficient was used. P was considered significant when it was at or less than 0.05.p ≤ 0.05) (Table The IQ range was 70–109 (90.7 ± 9.7) in the LD group. The scores for working memory and non-verbal abilities were the lowest. The scores for quantitative reasoning were the highest. In the group of LD with ADHD, the IQ range was 80–114 (95.4 ± 7.7). The scores for working memory were the lowest. The fluid reasoning scores were the highest. Children with LD and ADHD outperformed children with LD in terms of overall IQ, verbal IQ, fluid reasoning, and knowledge with a significant statistical difference . In children with LD and ADHD, the at-risk quotient ranged from 0.3 to 3.1 (1.68 ± 0.6). The majority of participants in both groups manifested deficits in verbal fluency, rapid naming, and one-minute writing. Comparison between the groups concerning percentage of deficits revealed that the ADHD group showed more percentage of deficits in nonsense passage reading, semantic fluency, verbal fluency, backward digit span, postural stability, and bead threading when compared to the LD group. The difference between the groups was significant regarding postural stability, and bead threading only . The GPx level was negatively correlated with the at-risk quotient . This indicated that higher GPx levels were linked to better performance in the tested aptitudes. No other statistically significant correlations were detected.The level of KYN was found to be inversely correlated with one-minute writing scores, with a significant statistical difference (The KYN level (281.50 ng/ml) showed 92% sensitivity and 70% specificity. Furthermore, the MDA level (1.00 nmol/ml) showed 89.9% sensitivity and 89% specificity. These two measures exhibited higher sensitivity and specificity compared to the other measures . It showed high sensitivity and specificity values. This could offer MDA as a useful biomarker for learning disorder.Markers for oxidative stress have been targeted in this study. Participants with LD ± ADHD manifested oxidative stress in the form of high MDA, low GPx, and SOD. MDA is one of the final products of polyunsaturated fatty acids peroxidation in cells. Any rise in free radicals leads to overproduction of MDA. The MDA level is a typical indictor of oxidative stress and a lack of antioxidant status. It is one of the many reactive electrophile species that generate toxic stress in cells and form covalent protein adducts called advanced lipoxidation end products, which lead to oxidative damage. Oxidative damage includes oxidative modification of cellular macromolecules, induction of cell death by apoptosis or necrosis, as well as structural tissue damage . ElevateThe levels of GPx and SOD were reduced in the LD group indicating oxidative stress. GPx is an antioxidant enzyme which reduces hydrogen peroxide to water in order to limit its harmful effects . GPx wasTo investigate the possible role of KYN in LD, a correlation between its level and the scores of the subtests of the dyslexia assessment test was performed. There was a significant negative correlation between KYN level and scores of one-minute writing subtest. The higher the KYN level, the worse the writing performance. Motor integrity and eye-motor coordination have been linked to writing performance in children with LD . No corrThe evaluated biochemical measures did not differ between the group of children with LD without ADHD and those with LD and coexisting ADHD. The number of children who had ADHD was less than the group without ADHD, and the participants were not recruited from the general population, which could be limitations of the study. Nevertheless, the correlation analysis and the diagnostic utility were not performed for children with LD and comorbid ADHD. They were performed on children who had LD without ADHD. The correlation outputs and the diagnostic utility estimation results in this study suggest that KYN, GPx, and MDA could be promising measures that are linked to the performance of some abilities of children with specific learning disorder or developmental dyslexia. The results of this cross-sectional study suggest that changes observed in the levels of the targeted measures could be considered associations with LD. Therefore, performing future studies investigating the role of these measures as a cause or a result of having LD is recommended. Moreover, implementing other studies investigating the influence of different lines of therapy on these measures is advised.Some cognitive abilities differed between the children with LD and those with LD and ADHD, with a significant statistical difference. The presence of coexisting ADHD did not show an influence on the evaluated biochemical measures in children with LD. The KYN system and oxidative stress markers are suggested to be involved in or influence the abilities of children with LD. The mechanism by which these markers can influence cognitive abilities are complicated and could be induced by internal and/or external factors such as stress. The levels of KYN and GPx showed a significant correlation with the writing performance of school-aged children in this study and their at-risk quotients, which represented the skills and abilities involved in learning. Therefore, KYN, MDA, and GPx are proposed as measures to be evaluated and checked for alterations in children with developmental dyslexia or specific learning disorder.