Important Considerations for ADHD 'Patient and Public' Involvement and Engagement in Research.

In this letter, we summarise key points of learning from research projects on attention deficit hyperactivity disorder (ADHD) that have had patient and public involvement and engagement (PPIE) as a key part of the research process. We share learning from our experiences in delivering research working with PPIE groups with ADHD, as top tips for researchers. Our aim is to highlight the importance of including lived-experience in ADHD research, share learning and highlight some of the (potentially invisible) differences in functioning that someone with ADHD can experience in relation to attentional focus, organisation, and time management. Specifically, how these might impact working practices of PPIE groups that include people with ADHD.

Gallic acid inhibits celecoxib-induced mitochondrial permeability transition and reduces its toxicity in isolated cardiomyocytes and mitochondria.

BACKGROUND: Mitochondria are the main target organelles through which drugs and chemicals exert their toxic effect on cardiomyocytes. The mitochondria-related mechanisms of celecoxib-induced cardiotoxicity have been extensively studied. Accumulated evidence shows natural molecules targeting mitochondria have proven to be effective in preventing cardiotoxicity. PURPOSE: In the present study, we examined the ameliorative effect of gallic acid (GA) against celecoxib-induced cellular and mitochondrial toxicity in isolated cardiomyocytes and mitochondria. RESEARCH DESIGN: The isolated cardiomyocytes and mitochondria were divided into various group, namely, control, celecoxib, celecoxib + GA (10, 50, and 100 µM). Several cellular and mitochondrial parameters such as cell viability, lipid peroxidation, succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling were assessed in isolated cardiomyocytes and mitochondria. RESULTS: Our results showed that administration of celecoxib (16 µg/ml) induced cytotoxicity and mitochondrial dysfunction at 6 h and 1 h, respectively, which is associated with lipid peroxidation intact cardiomyocytes, mitochondrial ROS formation, MMP collapse, and mitochondrial swelling. The cardiomyocytes and mitochondria treated with celecoxib + GA (10, 50, and 100 µM) significantly and dose-dependently restore the altered levels of cellular and mitochondrial parameters. CONCLUSIONS: We concluded that GA through antioxidant potential and inhibition of mitochondrial permeability transition (MPT) pore exerted ameliorative role in celecoxib-induced toxicity in isolated cardiomyocytes and mitochondria. The data of the current study suggested that GA supplementation may reduce celecoxib-induced cellular and mitochondrial toxicity during exposure and may provide a potential prophylactic and defensive candidate for coxibs-induced mitochondrial dysfunction, oxidative stress, and cardiotoxicity.

Reduction of doxorubicin-induced cytotoxicity and mitochondrial damage by betanin in rat isolated cardiomyocytes and mitochondria.

Doxorubicin (DOX) is an anticancer drug which is used for treatment of several types of cancers. But the clinical use of doxorubicin is limited because of its cardiotoxicity and cardiomyopathy. Mitochondrial-dependent oxidative stress and cardiac inflammation appear to be involved in doxorubicin-induced cardiotoxicity. Betanin as a bioactive compound in Beetroot (Beta vulgaris L.) displays anti-radical, antioxidant gene regulatory and cardioprotective activities. In this current study, we investigated the protective effect of betanin on doxorubicin-induced cytotoxicity and mitochondrial-dependent oxidative stress in isolated cardiomyocytes and mitochondria. Isolated cardiomyocytes and mitochondria were treated with three concentrations of betanin (1, 5 and 10 µM) and doxorubicin (3.5 µM) for 6 h. The parameters of cellular and mitochondrial toxicity were analyzed using biochemical and flow cytometric methods. Our results showed a significant toxicity in isolated cardiomyocytes and mitochondria in presence of doxorubicin which was related to reactive oxygen species (ROS) formation, increase in malondialdehyde (MDA), increase in oxidation of GSH to GSSG, lysosomal/mitochondrial damages and mitochondrial swelling. While betanin pretreatment reverted doxorubicin-induced cytotoxicity and oxidative stress in isolated cardiomyocytes and mitochondria. These results suggest that betanin elicited a typical protective effect on doxorubicin-induced cytotoxicity and oxidative stress. It is possible that betanin could be used as a useful adjuvant in combination with doxorubicin chemotherapy for reduction of cardiotoxicity and cardiomyopathy.

Physician deaths from corona virus (COVID-19) disease.

BACKGROUND: The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. AIMS: We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. METHODS: On 15 April 2020, a Google internet search was performed using the keywords 'doctor', 'physician', 'death', 'COVID' and 'coronavirus' in English and Farsi, and Chinese using the Baidu search engine. The age, sex and medical speciality of physicians who died from COVID-19 in the line of duty were recorded. Individuals greater than 90 years of age were excluded. RESULTS: We found 278 physicians who died with COVID-19 infection, but complete details were missing for 108 individuals. The average age of the physicians was 63.7 years with a median age of 66 years, and 90% were male (235/261). General practitioners and emergency room doctors (108/254), respirologists (5/254), internal medicine specialists (13/254) and anaesthesiologists (6/254) comprised 52% of those dying. Two per cent of the deceased were epidemiologists (5/254), 2% were infectious disease specialists (4/254), 6% were dentists (16/254), 4% were ENT (9/254) and 3% were ophthalmologists (8/254). The countries with the most reported physician deaths were Italy (121/278; 44%), Iran (43/278; 15%), Philippines (21/278; 8%), Indonesia (17/278; 6%), China (16/278; 6%), Spain (12/278; 4%), USA (12/278; 4%) and UK (11/278;4%). CONCLUSIONS: Physicians from all specialities may die from COVID. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.

Mitochondrial and lysosomal protective agents ameliorate cytotoxicity and oxidative stress induced by cyclophosphamide and methotrexate in human blood lymphocytes.

Cyclophosphamide (CYP) and methotrexate (MTX) have been evaluated for their ability to induce toxicity in human peripheral blood lymphocytes (PBLs) and the protective role of mitochondrial and lysosomal stabilizing agents. The potential toxicity effects of CYP and MTX were measured in vitro by cellular parameters assays such as cellular viability, reactive oxygen species (ROS) formation, mitochondrial membrane permeability transition (mitochondrial membrane potential (MMP)) collapse, lysosomal membrane damage, intracellular reduced glutathione (GSH), extracellular oxidized glutathione (GSSG), and lipid peroxidation. Separately, human lymphocytes were treated with concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 ng/mL for CYP and 1, 2, 5, and 10 µg/mL for MTX for 6 h. Statistical evaluations showed that CYP and MTX significantly decreased the cell viability at the three highest concentrations when compared with both the negative and solvent controls. In addition, CYP and MTX were significantly induced ROS formation, MMP collapse, lysosomal membrane damage, lipid peroxidation, and GSH depletion compared with the controls. Mitochondrial and lysosomal protective agents like cyclosporine A and chloroquine, respectively, decreased cytotoxicity and oxidative stress induced by CYP and MTX. The present results indicate that CYP and MTX are toxic to human PBLs and their toxicity could be ameliorated by mitochondrial and lysosomal protective agents.

Bio-based thermosetting epoxy foam: Tannic acid valorization toward dye-decontaminating and thermo-protecting applications.

Bio-resourced thermosetting epoxy foam was synthesized from tannic acid toward two different applications e.g., dye-decontaminating and thermo-insulating. Epoxidized tannic acid (ETA) foam was produced without using of organic volatile compounds or flammable foaming gases. The foam density, thermal conductivity and closed-cell content were studied. Besides, TGA showed high char yield (49% in N2 and 48.3% in air) at 600 °C accompanied by high LOI (37.1 in N2 and 36.8 in air). The high thermo-stability and intumescent char yield along with low thermal conductivity recommends the foam suitability for being used as an insulating material. Additionally, sorption of methylene blue onto ETA foam was kinetically investigated. The study of contact time, ionic strength, solution pH, initial sorbate concentration and desorption revealed the dependency of the sorption process to pH and initial sorbate concentration. The experimental data fitted well with the Langmuir isotherm (R2 = 0.997), yielding maximum sorption capacity of 36.25 mg/g (ETA foam = 0.05 g, pH = 7, MB concentration = 50 ppm, Volume = 25 mL). The kinetic data verified that MB sorption could be represented by the pseudo second-order model. Overall, the ETA foam can be introduced as a candidate for removing cationic pollutants, thermal insulator, and self-extinguishing/intumescent materials.

In vitro proliferation and differentiation of human bone marrow mesenchymal stem cells into osteoblasts on nanocomposite scaffolds based on bioactive glass (64SiO2-31CaO-5P2O5)-poly-l-lactic acid nanofibers fabricated by electrospinning method.

Electrospinning method was employed for fabrication of SiO2-CaO-P2O5 bioactive glass (BG) nanofibers, poly-l-lactic acid (PLLA) nanofibers and nanocomposite scaffolds fabricated from as-prepared nanofibers. Characterization of the prepared nanofibers and scaffolds by XRD, FTIR, and SEM techniques revealed the formation of nanofibers with mean diameter of about 500nm and fully fibrous scaffolds with porous structure and interconnected pores. The growth, viability and proliferation of cultured human bone marrow mesenchymal stem cells in the fabricated nanofibers and bioactive glass-poly-l-lactic acid (BG-PLLA) nanocomposite scaffolds were studied using various biological assays including MTT, ALP activity, calcium deposit content, Alizarin red staining, and RT-PCR test. Based on the obtained results, incorporation of BG nanofibers in the nanocomposite scaffolds causes the better biological behavior of the scaffolds. In addition, three-dimensional and fibrous-porous structure of the scaffolds further contributes to their improved cell behavior compared to the components.

A study to demonstrate the use of FNA cytology rather than biopsy in the diagnosis of neonatal biliary atresia.

OBJECTIVE: To study the use of fine needle aspiration (FNA) cytology in neonatal biliary atresia (BA). METHODS: Twelve female and nine male patients (age range, 3-7 months; mean age, 4.5 months) with a pre-operative diagnosis of BA, who were scheduled for Kasia portoenterostomy and selected for intraoperative FNA, were studied. RESULTS: Cholestasis, bile deposits, bile infarcts, hepatitic rosettes enclosing bile plugs, feathery degeneration of hepatocytes and inflammatory cells were seen in the cytological slides. Bile infarcts, rosette formation and inflammatory cells were mainly noticed in type 3 BA. Bile infarcts and hepatitic rosettes are surrogate findings for the diagnosis of the obstructive type of cholestasis. CONCLUSION: With the help of imaging studies, FNA in a multidisciplinary setting can be diagnostic of neonatal BA when cytological features suggest the obstructive nature of cholestasis, but this procedure cannot replace completely liver biopsy for this diagnosis.

Fermentation, fractionation and purification of streptokinase by chemical reduction method.

BACKGROUND AND OBJECTIVES: Streptokinase is used clinically as an intravenous thrombolytic agent for the treatment of acute myocardial infarction and is commonly prepared from cultures of Streptococcus equisimilis strain H46A. The objective of the present study was the production of streptokinase from strain H46A and purification by chemical reduction method. MATERIALS AND METHODS: The rate of streptokinase production evaluated under the effect of changes on some fermentation factors. Moreover, due to the specific structure of streptokinase, a chemical reduction method employed for the purification of streptokinase from the fermentation broth. The H46A strain of group C streptococcus, was grown in a fermentor. The proper pH adjusted with NaOH under glucose feeding in an optimum temperature. The supernatant of the fermentation product was sterilized by filtration and concentrated by ultrafiltration. The pH of the concentrate was adjusted, cooled, and precipitated by methanol. Protein solution was reduced with dithiothreitol (DTT). Impurities settled down by aldrithiol-2 and the biological activity of supernatant containing streptokinase was determined. RESULTS: In the fed -batch culture, the rate of streptokinase production increased over two times as compared with the batch culture and the impurities were effectively separated from streptokinase by reduction method. CONCLUSION: Improvements in SK production are due to a decrease in lag phase period and increase in the growth rate of logarithmic phase. The methods of purification often result in unacceptable losses of streptokinase, but the chemical reduction method give high yield of streptokinase and is easy to perform it.

Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran.

INTRODUCTION: The aim of this retrospective study was to assess ultra-rapid opiate detoxification (UROD) and to estimate the retention rate in naltrexone maintenance treatment. METHODS: 45 opiate-addicted male patients (DSM-IV 304.00; opiate per oral or per inhalation n=40, heroin intravenous n=5; concomitant cannabis abuse n=6) were detoxified by 6 h of naloxone infusion under general anesthesia with midazolam, propofol, clonidine and atracurium. Withdrawal signs were evaluated by the objective opiate withdrawal scale (OOWS, range 0-13) up to 24 h after awakening. After UROD, naltrexone 50 mg/day was prescribed for 9 months with assessments in 4-week intervals. RESULTS: Adverse events after UROD were prolonged unconsciousness (n=1), transient confusion (n=8) and depressive mood (n=6). The total sample showed a median OOWS score of 2 (mild withdrawal syndrome). The only two extreme outliers were found only in the subgroups "intravenous" (score 8) and "cannabis" (score 11). 96% (43/45) of the patients could be discharged the day after UROD. Thirty-six patients (80%) continued naltrexone therapy for the entire 9-month observation period. DISCUSSION: UROD and subsequently induction of naltrexone maintenance therapy can be regarded as safe and effective in patients with pure opiate addiction. Owing to cultural and economical factors our Iranian results may not correspond to European and American treatment modalities.

A simplified acute physiology score in the prediction of acute organophosphate poisoning outcome in an intensive care unit.

Organophosphate poisoning (OPP) occurs frequently and accounts for a large number of intoxication cases treated in intensive care units (ICU). Poisoning by these agents is a serious public health problem. Among pesticides, OPs are the main cause of poisoning and death in Loghman-Hakim Poison Center of Tehran, Iran. The aim of this study was to determine the impact of the Simplified Acute Physiology Score (SAPS II) in the prediction of mortality in patients with acute OPP requiring admission to the ICU of Loghman-Hakim Hospital Poison Center over a period of 12 months. This study was a prospective, case-control of records of patients with acute OPP admitted to the ICU between January 2006 and December 2006. The Demographic data were collected and SAPS II score was recorded. During the study period, 24 subjects were admitted to the ICU with acute OPP. All 24 patients (15 male) required endotracheal intubation and mechanical ventilation in addition to gastric decontamination and standard therapy with atropine and oximes and adequate hydration. Of these, 24 patients, eight (five male) died. SAPS II score was significantly higher in the non-survival group than the survival group. Mortality following acute OPP remains high despite adequate intensive care and specific therapy with atropine and oximes. One-third of the subjects needing intensive care die within the hospitalization period. SAPS II scores calculated within the first 24 hours were recognized as good prognostic indicator among patients with acute OPP that required ICU admission. It is concluded that SAPS II score above 11 within the first 24 hours is a predictor of poor outcome in patients with acute OPP requiring ICU admission.

Comparison between optimized geometries and vibrational frequencies calculated by the DFT methods for the Anderson-type heteropolyanion: hexamolybdoaluminate(III), [AlIII(OH)6Mo6O18]3-.

Optimized geometries and vibrational frequencies were calculated for the hexamolybdoaluminate(III), [AlIII(OH)6Mo6O18]3-, Anderson-type heteropolyanion with the HF, B3LYP, B3PW91, B3P86 and B1LYP methods of theory using the LanL2DZ, SDD and combination of LanL2DZ with 6-31G (d, p) basis sets. The agreement between the optimized and experimental geometries was in the decreasing order: HF, B3P86, B3PW91, B1LYP and B3LYP. The calculated frequencies by the B3LYP have the smallest mean root mean square (RMS) error. The effect of the basis set on the calculated bond lengths and frequencies by the density functional calculations (DFT) methods was minor. The agreement between the previously reported IR and Raman spectra and the calculated values is, in general, good.

Density functional theory and Hartree-Fock studies: geometry, vibrational frequencies and electronic properties of Anderson-type heteropolyanion, [XM6O24]n- (X=TeVI, IVII and M=Mo, W) and [SbVW6O24]7-.

The geometry, IR and Raman spectra and electronic properties of Anderson-type heteropolyanions with main-group high oxidation state heteroatom, [Te(VI)Mo(6)O(24)](6-), [I(VII)Mo(6)O(24)](5-), [Sb(V)W(6)O(24)](7-), [Te(VI)W(6)O(24)](6-) and [I(VII)W(6)O(24)](5-) have been investigated using Hartree-Fock (HF) and density functional theory (DFT) methods. HF method has good results in geometry parameters but poorer than DFT method in the results of vibrational frequencies. Also we have investigated the effect of LanL2DZ augmented in the vibrational frequencies. With attention to relative charge and size of the cavity occupied by XO(6) subunit in these anions, we suggest that the general formula [XO(6)(n-)@M(6)O(18)] to describe electronic properties of these anions.

Electrocatalytic reduction of dioxygen on a glassy carbon electrode modified with adsorbed cobaloxime complex.

The preparation and electrochemical properties of a glassy carbon (GC) electrode modified with cobaloxime complex were investigated. The complex of the type [CoIII(DO)(DOH)pn)Cl2] where (DO)(DOH)pn = N2,N2'-propanediylbis-2,3-butanedione-2-imine-3-oxime) was adsorbed irreversibly and strongly on the surface of preanodized glassy carbon electrode. Electrochemical behavior and stability of modified GC electrode were investigated by cyclic voltammetry. The electrocatalytic reduction of dioxygen has been studied using this modified glassy carbon electrode by cyclic voltammetry, chronoamperometry and rotating disk electrode voltammetry as diagnostic techniques. The modified electrode showed excellent eletrocatalytic ability for the reduction of dioxygen to hydrogen peroxide in acetate buffer (pH 4.0) with overpotential 1.0 V lower than the plain glassy carbon electrode. The formal potential for this modified electrode is not shifted to more negative potentials by repeated reduction-oxidation cycles in oxygen-saturated supporting electrolyte solution. The apparent electron transfer rate constant (kS), the transfer coefficent (alpha) and the catalytic rate constant of O2 reduction at a GC modified electrode were determined by cyclic voltammetry and rotating disk electrode voltammetry and were found to be around 2.6 s(-1), 0.33 and 2.25 x 10(4) M(-1) s(-1). Based on the results, a catalytic mechanism is proposed and discussed.

Potentiation of ricin A immunotoxin by monoclonal antibody targeted monensin containing small unilamellar vesicles.

The carboxylic ionophore monensin could be successfully entrapped in small unilamellar vesicles made by the extruder method. Monensin liposomes of size range 100-150 nm were more potent in potentiating ricin A immunotoxin activity in vitro as compared to monensin liposomes of diameter 500 nm or more. These liposomes were further successfully linked to tumor specific monoclonal antibodies with full retention of immunoreactivity. Monoclonal antibody targeted monensin liposomes were 100 times more potent than monensin liposomes in potentiating the activity of ricin A immunotoxins against various tumor cell lines in vitro.

In vitro effect of recombinant interferon gamma in combination with LPS on amoebicidal activity of murine Kupffer cells.

The present study examines the role of liver macrophages (Kupffer cells), of C57BL/6 mice, as effector cells responsible for the killing of Entamoeba histolytica trophozoites in vitro. It was shown that unstimulated Kupffer cells were inefficient in the killing of E. histolytica trophozoites in vitro. Interferon gamma (IFN-gamma) alone was not able to activate Kupffer cells to amoebicidal state. However, Interferon gamma and lipopolysaccharide (LPS) acted synergistically in this phenomenon. It seems that the acquisition of amoebicidal activity is associated with the involvement of hydrogen peroxide, because the addition of catalase partially decreases the killing of this parasite by Kupffer cells. In addition, it appears that the amoebicidal activity of IFN-gamma-treated Kupffer cells is contact-dependent. Our results indicate that the immunologic production of IFN-gamma is important in the activation of Kupffer cells for controlling this parasite and that Kupffer cells are strong effector cells against the amoebae.

Effect of recombinant tumor necrosis factor alpha on in vitro amoebicidal activity of murine Kupffer cells.

The present study was undertaken to determine whether recombinant tumor necrosis factor alpha (TNF) could induce Kupffer cells to kill Entamoeba histolytica parasite in vitro. C57BL/6 mice were used in this study. The liver was perfused and Kupffer cells harvested and treated with TNF for 6 h. It was found that Kupffer cells treated with TNF are able to kill amoebic trophozoites in vitro. These results further show that amoebicidal activity of TNF-activated Kupffer cells is dependent on the ratio of Kupffer cells to amoebic trophozoites. The maximum amoebicidal activity of Kupffer cells was observed with the ratio of one Kupffer cell to five amoebae. This study also shows that the optimal concentration of TNF is required in the induction of amoebicidal activity in Kupffer cells (10(5) units). It seems that both oxidative-dependent and -independent mechanisms are important for the killing of amoebae by the TNF-treated Kupffer cells. It is likely that TNF-treated Kupffer cells produce endogenous TNF or other cytotoxic molecules which are capable of mediating the parasite killing. Our results indicate that the immunologic production of TNF is important in the activation of Kupffer cells to kill amoebic trophozoites.

Potentiation of antitumor immunotoxins by liposomal monensin.

BACKGROUND: The cytotoxicity of specific ricin A-chain immunotoxins is greatly enhanced in vitro by the carboxylic ionophore monensin. However, the highly lipophilic nature of monensin, which is reflected in its poor solubility and short half-life, has restricted its use in in vivo animal studies. PURPOSE: The purpose of this study was to assess the ability of monensin incorporated in unilamellar vesicles (liposomes) to potentiate antitumor immunotoxins in vitro and in vivo. METHODS: Monensin was incorporated into liposomes and used in combination with specific immunotoxins against human tumor cell lines in vitro and in vivo. Inhibition of [3H]leucine incorporation was used to evaluate the cytotoxic action of immunotoxin with or without monensin in vitro on the following human tumor cell lines: H-MESO-1 malignant mesothelioma, LS174T colorectal carcinoma, and U373, U87, and MG-1 glioblastomas. For the in vivo studies of immunotoxins and liposomal monensin, BALB/c nu/nu mice were inoculated intraperitoneally with H-MESO-1 cells. RESULTS: Liposomal monensin potentiated the cytotoxic action of cell-specific anti-human transferrin receptor immunotoxin on H-MESO-1 target cells at a molar concentration of monensin that was 160-fold lower than the concentration of monensin in buffer that produced the same effect (0.3 nM versus 0.05 microM). Moreover, immunotoxin plus 0.1 microM liposomal monensin was fivefold more toxic for H-MESO-1 cells and 1000-fold and 2200-fold more toxic for human glioblastoma U373 and U87 cells, respectively, than immunotoxin plus 0.1 microM free monensin in buffer. Liposomal monensin produced similar effects when it was combined with different specific immunotoxins and other target cell lines (i.e., LS174T, U87, and CEM). Immunotoxin specificity was preserved with liposomal monensin, as shown by the absence of effect with non-cell-binding immunotoxins or on antigen-negative cell lines. In mice, liposomal monensin in combination with specific immunotoxin substantially prolonged survival, and three (21%) of 14 mice bearing H-MESO-1 xenografts treated with the liposomes showed no evidence of tumor at day 160 after treatment. Treatment with control immunotoxin plus liposomal monensin was ineffective. CONCLUSION: These findings suggest that encapsulation of monensin into liposomes increased the capacity of monensin to enhance the potency of cell-specific immunotoxin in vitro and in vivo.