Serum Concentrations of Cotinine and Trans-3'-Hydroxycotinine in US Adults: Results From Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study.

INTRODUCTION: The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative cohort of tobacco product users and nonusers. The study's main purpose is to obtain longitudinal epidemiologic data on tobacco use and exposure among the US population. AIMS AND METHODS: Nicotine biomarkers-cotinine (COT) and trans-3'-hydroxycotinine (HCT)-were measured in blood samples collected from adult daily tobacco users and nonusers during Wave 1 of the PATH Study (2013-2014; n = 5012; one sample per participant). Participants' tobacco product use and exposure to secondhand smoke were categorized based on questionnaire responses. Nonusers were subdivided into never users and recent former users. Daily tobacco users were classified into seven tobacco product use categories: exclusive users of cigarette, smokeless tobacco, electronic cigarette, cigar, pipe, and hookah, as well as polyusers. We calculated sample-weighted geometric mean (GM) concentrations of cotinine, HCT, and the nicotine metabolite ratio (NMR) and evaluated their associations with tobacco use with adjustment for potential confounders. RESULTS: The GMs (95% confidence intervals) of COT and HCT concentrations for daily tobacco users were 196 (184 to 208) and 72.5 (67.8 to 77.4) ng/mL, and for nonusers they were 0.033 (0.028 to 0.037) and 0.021 (0.018 to 0.023) ng/mL. Exclusive smokeless tobacco users had the highest COT concentrations of all user groups examined. The GM NMR in daily users was 0.339 (95% confidence interval: 0.330 to 0.350). CONCLUSIONS: These nationally representative estimates of serum nicotine biomarkers could be the basis for reference ranges characterizing nicotine exposure for daily tobacco users and nonusers in the US adult population. IMPLICATIONS: This report summarizes the serum nicotine biomarker measurements in Wave 1 of the PATH Study. We are reporting the first estimates of HCT in serum for daily tobacco users and nonusers in the noninstitutionalized, civilian US adult population; the first nationally representative serum COT estimates for daily exclusive users of different tobacco products and daily polyusers; and the first nationally representative estimate of the serum NMR in daily tobacco users by age, race/ethnicity, and sex.

Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

INTRODUCTION: The tobacco-specific nitrosamines (TSNAs) are an important group of carcinogens found in tobacco and tobacco smoke. To describe and characterize the levels of TSNAs in the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014), we present four biomarkers of TSNA exposure: N'-nitrosonornicotine, N'-nitrosoanabasine, N'-nitrosoanatabine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) which is the primary urinary metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. METHODS: We measured total TSNAs in 11 522 adults who provided urine using automated solid-phase extraction coupled to isotope dilution liquid chromatography-tandem mass spectrometry. After exclusions in this current analysis, we selected 11 004 NNAL results, 10 753 N'-nitrosonornicotine results, 10 919 N'-nitrosoanatabine results, and 10 996 N'-nitrosoanabasine results for data analysis. Geometric means and correlations were calculated using SAS and SUDAAN. RESULTS: TSNA concentrations were associated with choice of tobacco product and frequency of use. Among established, every day, exclusive tobacco product users, the geometric mean urinary NNAL concentration was highest for smokeless tobacco users (993.3; 95% confidence interval [CI: 839.2, 1147.3] ng/g creatinine), followed by all types of combustible tobacco product users (285.4; 95% CI: [267.9, 303.0] ng/g creatinine), poly tobacco users (278.6; 95% CI: [254.9, 302.2] ng/g creatinine), and e-cigarette product users (6.3; 95% CI: [4.7, 7.9] ng/g creatinine). TSNA concentrations were higher in every day users than in intermittent users for all the tobacco product groups. Among single product users, exposure to TSNAs differed by sex, age, race/ethnicity, and education. Urinary TSNAs and nicotine metabolite biomarkers were also highly correlated. CONCLUSIONS: We have provided PATH Study estimates of TSNA exposure among US adult users of a variety of tobacco products. These data can inform future tobacco product and human exposure evaluations and related regulatory activities.

[Dosage of presurgical cefazolin in obese and non-obese patients. Does weight matter?] / Dosificación de cefazolina prequirúrgica en pacientes obesos y no obesos. ¿Importa el peso?

OBJECTIVE: Evaluation of the effectiveness of a standard dose of cefalozin 2 grams for surgical site infection (SSI) prevention in obese patients compared to non-obese patients. There is no still controversy surrounding which is the best dosage of this antibiotic in obese patients for surgical prophylaxis. METHODS: Retrospective review of men who received prophylactic cefazolin between January 1st, 2019 and June 30th, 2019 in a traumatology department of a university hospital. Patients were stratified into 2 groups: obese (≥ 100 kg and body mass index (BMI)> 30 kg / m2) and non-obese. Patients without a 90 days follow-up after surgery and/or with an active infection at the time of surgery and/or treated with immunosuppressants were excluded. Demographic data, height, real weight, smoking, diabetes, concomitant use of immunosuppressants, surgery data and presence of infection until day 90 were collected. RESULTS: A total of 57 patients underwent traumatic surgery with prophylactic cefazolin, 26 non-obese and 23 obese, were studied. Both groups presented statistically significant differences in weight, BMI and post-surgery use of cefazolin. No significant differences were observed in the other variables. Two obese (8.7%) and two non-obese (7.7%) patients developed SSIs after 63 days post-surgery on average, following the difference between the groups being statistically non-significant. CONCLUSIONS: This study shows that there is no significant difference in SSI with a standard prophylactic dose of two grams of cefazolin between obese and non-obese patients.

Long-term response control in a patient with metastatic squamous cell lung cancer after treatment with nivolumab: a case report.

INTRODUCTION: Nivolumab is a fully human programmed death control immune point 1 immune checkpoint inhibitor antibody which promotes antitumor immunity. Cutaneous toxicity associated with nivolumab, immune system related, could be linked to a more durable response in patients with squamous cell lung cancer. CASE REPORT: We present the case of a 62-year-old male diagnosed with metastatic squamous cell lung cancer, who was treated with nivolumab after cytotoxic chemotherapy. After treatment discontinuation, due to grade 2 cutaneous toxicity, the patient is maintaining with durable partial response for more than one year with close follow-up. MANAGEMENT AND OUTCOME: Cumulative doses of nivolumab could cause immunological toxicities that may prolong survival of these patients even after discontinuation of treatment. DISCUSSION: Nivolumab was approved by European Medicines Agency (EMA), as second-line therapeutic, for the treatment of squamous cell lung cancer, showing a median of 9.23 months of overall survival. The development of immune-related skin toxicities has been associated with greater clinical benefit in patients with lung cancer. When cutaneous toxicity forces to nivolumab suspension, in certain cases, the option of not starting again and closely following up the patient may appear reasonable, even though there are no survival data in this context. Suspension of treatment with close monitoring of these patients until progression may be an alternative, since immune-related skin toxicities could be related to a greater clinical benefit and a durable response to nivolumab.

Cardiolipin and phosphatidylethanolamine role in dibucaine interaction with the mitochondrial membrane.

Mitochondrial membranes are pointed out as the site of cardiotoxic action of local anaesthetics. Its three main phospholipids components are phosphatidylcholine, phosphatidylethanolamine and cardiolipin. Cardiolipins, in eukaryotes, are only found in mitochondria and are essential for the maintenance of its integrity and dynamics. Fluorescence and nuclear magnetic resonance spectroscopy were used to study the interactions of a local anaesthetics, Dibucaine (DBC), with different mitochondrial membrane models constituted by combinations of its three main lipid components in which cardiolipin was a natural extract (CLmix). Both CLmix presence/absence and its percentage in the model membranes were evaluated. Fluorescence spectroscopy showed that DBC lowered the transition temperature of all membrane models understudy. DBC partition showed to be dependent of CLmix presence and phosphatidylethanolamine:CL ratio. Furthermore, the maximum emission wavelength (λmax) exhibited a notorious decreased with increasing phospholipid to DBC ratio, in all the membrane models containing CLmix. Nevertheless, it remained approximately the same in the membrane without CLmix. This indicates a differential membrane localization of the anaesthetics, dependent on the membrane models used. NMR results showed that DBC interaction and location in the membrane models is mainly influenced by CLmix presence, and DBC can significant alter lipid systems properties e.g. percentage and type of lipid phase present. Taken all together it was shown that DBC interaction and location are largely dependent on the membrane model system. Furthermore, DBC is able to produce significant changes in the lipidic systems which might help to explain its high toxicity.

A cognitive versus behavioral approach to emotion regulation training for externalizing behavior problems in adolescence: Study protocol of a randomized controlled trial.

BACKGROUND: Interventions for adolescents with externalizing behavior problems are generally found to be only moderately effective, and treatment responsiveness is variable. Therefore, this study aims to increase intervention effectiveness by examining effective approaches to train emotion regulation, which is considered to be a crucial mechanism involved in the development of externalizing behavior problems. Specifically, we aim to disentangle a cognitive and behavioral approach to emotion regulation training. METHODS: A randomized controlled parallel-group study with two arms will be used. Participants are adolescents between 12 and 16 years old, with elevated levels of externalizing behavior problems. Participants will be randomly assigned to either the control condition or the intervention condition. Participants in the intervention condition receive both a cognitive and behavioral emotion regulation module, but in different sequences. Primary outcome measures are emotion regulation skills, emotion regulation strategies, and externalizing behavior problems. Questionnaires will be completed at pre-test, in-between modules, and post-test. Moreover, intensive longitudinal data is collected, as adolescents will complete weekly and daily measures. DISCUSSION: Gaining insight into which approaches to emotion regulation training are more effective, and for whom, is important because it may lead to the adaptation of effective intervention programs for adolescents with externalizing behavior problems. Eventually, this could lead to individually tailored evidence-based interventions. TRIAL REGISTRATION: The trial is registered at the Central Committee on Research Involving Human Subjects ( NL61104.041.17 , September 20th, 2017) and the Dutch Trial Register ( NTR7334 , July 10th, 2018).

Revealing cardiolipins influence in the construction of a significant mitochondrial membrane model.

Cardiolipins are essential for the integrity and the dynamics of the mitochondria membrane, where they exclusively exist in eukaryotes. Changes in cardiolipins membrane levels have been related to several cardiac health disorders. To evaluate cardiolipins impact on membrane properties a physico-chemical study was conducted using steady-state fluorescence anisotropy, dynamic light scattering and Nuclear Magnetic Resonance (1H and 31P NMR). Different binary and ternary mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and a natural extract of bovine heart cardiolipin were used as models of mitochondrial membrane. The main transition temperatures, obtained by the first two techniques, revealed to be cardiolipins dependent. Cardiolipins also showed to act as a bidirectional regulator of membrane fluidity. 1H and 31P NMR results revealed that cardiolipins affects the conformation, mobility and structural order of the phospholipid molecules. According to 1H NMR results, cardiolipins disturbs the overall structure and packing order of membrane demonstrated with the decrease of the line broadening and shift of all resonances. The 31P NMR line shape analysis confirmed that, at distinct temperatures, different lipid phases coexist in the systems, and their type and quantitative distribution are cardiolipins dependent. In summary, cardiolipins presence/absence dramatically changes the membrane properties and has a major impact in the construction of a mitochondrial membrane model.

The influence of functional groups on the permeation and distribution of antimycobacterial rhodamine chelators.

We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of a set of rhodamine labelled iron chelators is improved via the rhodamine fluorophore which enhances the chelators' permeation properties through membranes. To validate our hypothesis in a cellular context and to understand the influence of the structure of the fluorophore on the chelator's uptake and distribution within macrophages we now report comparative confocal microscopy studies performed with a set of rhodamine labelled chelators. We identify the functional groups of the chelator's framework that favor uptake by macrophages and conclude that the antimycobacterial effect is strongly related with the capacity of the chelator to distribute within the host cell and its compartments, a property that is closely related with the chelators' ability to interact with membranes. The quantification of the chelators' interaction with membranes was assessed through measurement of the corresponding partition constants in liposomes. The overall results support that the compounds which are preferentially taken up are the most efficient antimycobacterial chelators and for that reason we infer that the biological activity is modulated by the structural features of the fluorophore.

Smoking Behavior and Exposure: Results of a Menthol Cigarette Cross-over Study.

OBJECTIVE: Our objective was to improve understanding of the differences in use behavior and exposure when smoking menthol and non-menthol cigarettes using a 2-part cross-over design. METHODS: Adult daily smokers were assigned randomly to alternate between 2 weeks of exclusively smoking a menthol test cigarette or a non-menthol test cigarette. Urine and saliva were collected for biomarker measurements; carbon monoxide (CO) was measured, and participants smoked test cigarettes through a CreSS® smoking topography device during 3 clinic visits. Participants turned in their cigarette butts from the test periods for determination of mouth level nicotine and completed subjective questionnaires related to the test cigarettes. RESULTS: Regardless of cigarette preference, participants had higher salivary cotinine when smoking the non-menthol test cigarette, but there were no significant differences detected in urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol between the 2 test cigarettes. Mouth level nicotine, puff volume, and puff duration were significantly higher when smoking the menthol brand. Both menthol and non-menthol smokers reported significantly lower enjoyment and satisfaction scores for test cigarettes compared with their brand of choice. CONCLUSIONS: Our results suggest that mentholation has an effect on measures of smoking behavior and that mouth level nicotine is a useful indicator of between-brand smoke exposure.

Effectiveness of a brief school-based intervention on depression, anxiety, hyperactivity, and delinquency: a cluster randomized controlled trial.

Problematic substance use and mental health problems often co-occur in adolescents. Effective school-based interventions that are brief and target multiple problems are promising in the field of health promotion. Preventure is a brief, school-based, selective preventive intervention, tailored to four personality profiles. Preventure has already proved effective on alcohol outcomes. Previous trials also reveal effects on several mental health outcomes, yet the evidence for these outcomes is limited. This study presents the results of the Dutch Preventure Trial, on a range of mental health outcomes. In a cluster RCT, including 699 high risk students (mean age 14 years), the intervention effects on mental health problems at 2, 6, and 12 months post intervention were tested in the total high risk population and in four specific personality groups. No significant intervention effects were found on 22 from the 24 tests. A positive intervention effect on anxiety was found in the anxiety sensitivity personality group at 12-month follow-up, and a negative intervention effect on depression was found at 12-month follow-up in the negative thinking group. In post hoc growth curve analyses these effects were not found. This study found no convincing evidence for the effectiveness of Preventure in The Netherlands on mental health problems. This finding is not in line with the results of an earlier effectiveness study in the UK. This highlights the need for more research into the knowledge transfer model of interventions, to ensure that interventions are effective in a variety of circumstances.

Risk factor for death in hematopoietic stem cell transplantation: are biomarkers useful to foresee the prognosis in this population of patients?

BACKGROUND: The morbidity and mortality in hematopoietic stem cell transplantation (HSCT) occur due to infectious complications and constitute the major clinical problems in HSCT recipients. The role of the use of biomarkers in post-HSCT patients is still controversial. OBJECTIVES: To assess the serum values of biomarkers interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) and risk factors for post-HSCT death. PATIENTS AND METHODS: Prospective study conducted in patients submitted to HSCT at a university hospital. Biomarkers (IL-6, PCT and CRP) were assessed on the day afebrile neutropenia was detected, in the febrile event, 24 and 72 h after fever onset and 48 h or 5 days if fever persisted. Patients were compared as to the death outcome within 30 days from the HSCT. Variables with p < 0.15 were included in the multivariate analysis model (MVA) that were performed for all patients included in the study and separated for autologous and allogeneic HSCT patients. RESULTS: 296 patients with ages ranging between 15 and 70 years, neutropenic, submitted to HSCT, being 216 (73%) autologous and 80 (20%) allogeneic were assessed. One hundred and ninety (64.2%) patients presented fever after the transplantation and infection microbiologically controlled in 78 (26.4%). Twenty-three cases (7.8%) evolved to death. The risk factors associated with death in the bivariate analysis were age, allogeneic transplantation, unrelated transplantation, GVHD, bloodstream infection by Gram-negative, IL-6 >140 pg/mL and CRP ≥ 120 mg/L and the protective ones were lymphoma and hospital outpatient support. The independent variables in the MVA associated with death were allogeneic and unrelated transplantation, blood stream infection (BSI) by Gram-negative, LDH ≥ 390 UI/L, urea ≥ 25 mg/dL and CRP ≥ 120 mg/L for HSCT transplanted patients and BSI due to Gram-negative and CRP ≥ 120 mg/L for allogeneic HSCT, however, CRP ≥ 120 mg/L did not remain in the model when urea ≥ 25 mg/L was included. No independent risk factor was found for autologous patients. CONCLUSIONS: Out of the biomarkers assessed, only CRP ≥ 120 mg/L was independently associated with death. Other risk factors found were: type of transplantation (allogeneic and unrelated), bloodstream infection by Gram-negative, LDH ≥ 390 UI/L and urea ≥ 25 mg/dL. For allogeneic patients only CRP ≥ 120 mg/L and BSI due to Gram-negative were risk factors for death; however, CRP did not remain in the model when urea ≥ 25 mg/L was included.

[Which characteristics of adolescents with behavioural problems are associated with the completion of residential treatment]. / Kenmerken van jongeren met gedragsproblemen en samenhang met het voltooien van een residentiële behandeling.

BACKGROUND: Many adolescents who have a combination of psychiatric disorders and behavioural problems fail to complete their course of treatment and therefore do not get the treatment they need. AIM: To investigate whether gender and the severity of symptoms at the start of treatment can predict whether patients will complete their course of treatment. METHOD: By means of questionnaires ( SCL-90, YSR and CBCL) we attempted to find out if the gender and symptoms of 127 male adolescent patients beginning their treatment in a psychiatric institution could 'predict' whether the patients would complete their treatment or terminate it prematurely. For the purpose of our research, specific definitions of the terms drop out, push out and treatment success were formulated. RESULTS: The inter rater reliability of the definitions of drop out and treatment success ranged from adequate to good, whereas the reliability of the definition of push out was only moderate. CONCLUSION: The questionnaire was not able to predict accurately whether patients would complete their treatment. Apparently, adolescent males whose treatment was predicted to have a more favourable outcome had obtained higher scores on the ( SCL-90) Hostility subscale at the beginning of treatment and more girls than boys were judged to have improved.

Long-term in vitro reactivity for human leukocyte antigen antibodies and comparison of detection using serum versus plasma.

BACKGROUND: Human leukocyte antigen (HLA) antibodies are a possible cause of transfusion-related acute lung injury (TRALI), and fluorescent bead assays are often used for antibody detection. Serum is the manufacturer's recommended sample, but plasma may be easier to obtain for studies of HLA antibody prevalence and TRALI case investigations. STUDY DESIGN AND METHODS: Specimens were obtained from 44 multiparous females positive for the presence of HLA antibodies by lymphocytotoxicity testing at least 13 years prior and from 1000 contemporary blood donors. Screening tests were performed using a multiplex bead-based assay. In addition to comparing results obtained with paired plasma and serum samples, the effects of storage at 4 degrees C for 1 week and of multiple freeze-thaw cycles were evaluated. RESULTS: Of 42 evaluable subjects with HLA antibodies documented more than 13 years earlier, only 1 showed loss of detectable antibodies, with 39 (93%) positive in the screening assay for HLA Class I and 24 (57%) positive in the screening assay for HLA Class II antibodies. In 968 evaluable contemporary donors, 291 screened positive for the presence of HLA Class I and 206 for HLA Class II antibodies using a low assay cutoff. Screening test concordance using paired plasma and serum samples was high, particularly for subjects with higher-level antibodies. Refrigeration of samples for 1 week did not significantly affect assay results, while repeated freeze-thaw cycles caused a decrement in signal level. CONCLUSION: Serum and plasma samples gave concordant results in the majority of cases, particularly for specimens with higher-level antibodies. High-level HLA antibodies were present in most individuals for more than 13 years.

Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice.

Storage of acetylcholine in synaptic vesicles plays a key role in maintaining cholinergic function. Here we used mice with a targeted mutation in the vesicular acetylcholine transporter (VAChT) gene that reduces transporter expression by 40% to investigate cognitive processing under conditions of VAChT deficiency. Motor skill learning in the rotarod revealed that VAChT mutant mice were slower to learn this task, but once they reached maximum performance they were indistinguishable from wild-type mice. Interestingly, motor skill performance maintenance after 10 days was unaffected in these mutant mice. We also tested whether reduced VAChT levels affected learning in an object recognition memory task. We found that VAChT mutant mice presented a deficit in memory encoding necessary for the temporal order version of the object recognition memory, but showed no alteration in spatial working memory, or spatial memory in general when tested in the Morris water maze test. The memory deficit in object recognition memory observed in VAChT mutant mice could be reversed by cholinesterase inhibitors, suggesting that learning deficits caused by reduced VAChT expression can be ameliorated by restoring ACh levels in the synapse. These data indicate an important role for cholinergic tone in motor learning and object recognition memory.

Impulse control and aggressive response generation as predictors of aggressive behaviour in children with mild intellectual disabilities and borderline intelligence.

BACKGROUND: A growing interest exists in mechanisms involved in behaviour problems in children with mild intellectual disabilities and borderline intelligence (MID/BI). Social problem solving difficulties have been found to be an explanatory mechanism for aggressive behaviour in these children. However, recently a discrepancy was found between automatic and reflective responding in social situations. We hypothesise that low impulse control and aggressive social problem solving strategies together may explain mechanisms involved in aggressive behaviour by children with MID/BI. METHOD: In a clinical sample of 130 children with MID/BI receiving intramural treatment, main, moderating and mediating effects of impulse control and aggressive response generation on aggressive behaviour were examined by conducting hierarchical linear multiple regression analyses. RESULTS: Independent main effects of both impulse control and aggressive response generation on aggressive behaviour were found. Results indicated that low impulse control and aggressive response generation each explain unique variance in aggressive behaviour. CONCLUSIONS: As this study is the first that has shown both impulse control and aggressive response generation to be important predictors for aggressive behaviour in children with MID/BI, future research should further examine the nature of relations between low impulse control and social problem solving.

Anchoring of a [Mn(salen)Cl] complex onto mesoporous carbon xerogels.

Carbon xerogels were synthesized by the conventional sol-gel approach using formaldehyde and resorcinol. The wet gel was dried by two different procedures followed by carbonization, leading to mesoporous carbon xerogels with considerably different pore size distributions. The materials were subsequently oxidized with air, in order to introduce functional groups on the surface, in particular phenols, anhydrides and carbonyls. The capacity of the carbon xerogels for direct immobilization of metal complexes was tested with a manganese(III) salen complex which possesses an extended ligand pi system and two reactive hydroxyl groups on the aldehyde fragment. The manganese loadings of the various samples indicate that larger amounts of Mn(III) complex were immobilized in the oxidized carbon xerogels when compared with the parent unactivated materials, suggesting that complex immobilization took place preferably by covalent bond between the surface oxygen functional groups and the ligand reactive groups, rather than by pi-pi interactions. The size and shape of the carbon xerogel pores were also shown to play an important role in the final loading of the manganese(III) salen complex.

Do social information-processing models explain aggressive behaviour by children with mild intellectual disabilities in residential care?

BACKGROUND: This study aimed to examine whether the social information-processing model (SIP model) applies to aggressive behaviour by children with mild intellectual disabilities (MID). The response-decision element of SIP was expected to be unnecessary to explain aggressive behaviour in these children, and SIP was expected to mediate the relation between social schemata and aggressive behaviour. METHOD: SIP and aggressive behaviour of 130 10- to 14-year-old children with MID in residential care were assessed. The fit of various SIP models was tested with structural equation modelling. RESULTS: The response-decision process was found not to be necessary to explain aggressive behaviour. Social schemata were indirectly related to aggressive behaviour with aggressive response generation as mediating variable. CONCLUSIONS: Implications for SIP theory and intervention are discussed.

Do children do what they say? Responses to hypothetical and real-life social problems in children with mild intellectual disabilities and behaviour problems.

BACKGROUND: Most research on children's social problem-solving skills is based on responses to hypothetical vignettes. Just how these responses relate to actual behaviour in real-life social situations is, however, unclear, particularly for children with mild intellectual disabilities (MID). METHOD: In the present study, the spontaneous and selected responses of 56 children with MID to hypothetical situations from the Social Problem-Solving Test for children with MID (SPT-MID) were compared to their actual behaviour in comparable staged standardized real-life conflict situations. Correlations to externalizing behaviour problems were assessed using the Teacher's Report Form (TRF). RESULTS: The results show children with MID and accompanying externalizing behaviour problems to behave more aggressively in the staged real-life conflicts and provide more spontaneous aggressive responses to the hypothetical vignettes than children with MID and no accompanying externalizing behaviour problems; they did not, however, select more aggressive responses from the hypothetical options provided. A moderate correlation was found between the aggressiveness of the spontaneous responses in the hypothetical situations and actual behaviour in the staged real-life situations. In addition, both the spontaneous aggressive responses under hypothetical circumstances and the actual aggressive behaviour under staged real-life circumstances were related to teacher-rated aggressive behaviour in the classroom. CONCLUSIONS: It is concluded that the hypothetical vignettes from the SPT-MID do provide information on both the actual behaviour and knowledge of social problem-solving skills of children with MID.

Derivative spectrophotometry as a tool for the determination of drug partition coefficients in water/dimyristoyl-L-alpha-phosphatidylglycerol (DMPG) liposomes.

The partition coefficients (K(p)) between lipid bilayers of dimyristoyl-L-alpha-phosphatidylglycerol (DMPG) unilamellar liposomes and water were determined using derivative spectrophotometry for chlordiazepoxide (benzodiazepine), isoniazid and rifampicin (tuberculostatic drugs) and dibucaine (local anaesthetic). A comparison of the K(p) values in water/DMPG with those in water/DMPC (dimyristoyl-L-alpha-phosphatidylcholine) revealed that for chlordiazepoxide and isoniazid, neutral drugs at physiological pH, the partition coefficients are similar in anionic (DMPG) and zwitterionic (DMPC) liposomes. However, for ionised drugs at physiological pH, the electrostatic interactions are different with DMPG and DMPC, with the cationic dibucaine having a stronger interaction with DMPG, and the anionic rifampicin having a much larger K(p) in zwitterionic DMPC. These results show that liposomes are a better model membrane than an isotropic two-phase solvent system, such as water-octanol, to predict drug-membrane partition coefficients, as they mimic better the hydrophobic part and the outer polar charged surface of the phospholipids of natural membranes.