Self-injurious behaviours in children and adults with autism spectrum disorder (ASD).

BACKGROUND: Self-injurious behaviours (SIB) are concerning, maladaptive behaviours that commonly occur in people with neurodevelopmental conditions and delays but seem to be particularly prevalent in children and adults with autism spectrum disorder (ASD). There has been increasing research examining the risk markers associated with the presence of SIB in people with ASD. Some of the factors associated with SIB have included cognitive abilities, adaptive functioning deficits and behaviour regulation impairments (e.g. impulsivity and repetitive behaviours). However, many of the findings in the literature are mixed and only explain a small proportion of the variance contributing to SIB. Limitations in the previous literature have centred on lack of availability of large and diverse samples, restricted age ranges and constraints of measurement. METHOD: This study characterises a clinic-referred sample of children and adults currently presenting with and without SIB using a range of standardised and parent-report measures. The sample includes 144 individuals with ASD between the ages of 2.5 and 60.1 years. RESULTS: After adjusting for multiple tests, none of the variables maintained statistical significance between the group of individuals with and without SIB, but medium to large effect sizes were noted. These variables include parent-reported early motor and toileting delays and perinatal risk, and current cognitive and social impairment. The remaining variables, including current autism severity levels, early ASD symptomatology, impulsivity, executive functioning impairments, adaptive functioning, mood and anxiety, did not differ between those with and without current engagement in SIB. CONCLUSIONS: Utilising a diverse clinic-referred sample and standardised diagnostic tools, this study explored retrospective and current correlate risk markers of SIB in individuals with ASD. In addition to impairments in current functioning, specific early developmental delays and perinatal risk factors were preliminarily associated with the presence of SIB in individuals with ASD. Together these findings suggest that a set of specific characteristics may be related to both early risk and concurrent manifestation of SIB. Identifying this set of characteristics in early development may lead to faster identification and better intervention services, but future work utilising longitudinal design and multivariate analysis is warranted.

Developing nonpoint-source suspended solids control strategies using multimedia watershed management modeling.

Kaoping River Basin is the largest and most intensively used river basin in Taiwan. In this study, 14 types of land-use patterns in the basin are classified with the aid of the Erdas Imagine process (Erdas, Inc., Atlanta, Georgia) and ArcView geographic information system (GIS) (ESRI, Redlands, California). Results from GIS identification and field verification indicate that orchard gardens, rice paddies, and sugarcane fields dominate the farmland areas in the basin. Investigation results indicate that nonpoint-source (NPS) pollution has significant contributions to the suspended solids load to the Kaoping River during the wet season. The average suspended solids concentrations increased from below 64 mg/ L in dry seasons to more than 1700 mg/L in wet seasons. The Integrated Watershed Management Model (Systech Engineering, Inc., San Ramon, California) was applied to simulate the water quality and evaluate the NPS suspended solids load to the river. Modeling results show that forestation and land-use management are feasible best management practices for NPS suspended solids reduction.

Using a constructed wetland for non-point source pollution control and river water quality purification: a case study in Taiwan.

The Kaoping River Rail Bridge Constructed Wetland, which was commissioned in 2004, is one of the largest constructed wetlands in Taiwan. This multi-function wetland has been designed for the purposes of non-point source (NPS) pollutant removal, wastewater treatment, wildlife habitat, recreation, and education. The major influents of this wetland came from the local drainage trench containing domestic, agricultural, and industrial wastewaters, and effluents from the wastewater treatment plant of a paper mill. Based on the quarterly investigation results from 2007 to 2009, more than 96% of total coliforms (TC), 48% of biochemical oxygen demand (BOD), and 40% of nutrients (e.g. total nitrogen, total phosphorus) were removed via the constructed wetland system. Thus, the wetland system has a significant effect on water quality improvement and is capable of removing most of the pollutants from the local drainage system before they are discharged into the downgradient water body. Other accomplishments of this constructed wetland system include the following: providing more green areas along the riversides, offering more water assessable eco-ponds and eco-gardens for the public, and rehabilitating the natural ecosystem. The Kaoping River Rail Bridge Constructed Wetland has become one of the most successful multi-function constructed wetlands in Taiwan. The experience obtained from this study will be helpful in designing similar natural treatment systems for river water quality improvement and wastewater treatment.

Preliminary identification of watershed management strategies for the Houjing river in Taiwan.

The Houjing River watershed is one of the three major river watersheds in the Kaohsiung City, Taiwan. Based on the recent water quality analysis, the Houjing River is heavily polluted. Both point and non-point source (NPS) pollutants are the major causes of the poor water quality in the Houjing River. Investigation results demonstrate that the main point pollution sources included municipal, agricultural, and industrial wastewaters. In this study, land use identification in the Houjing River watershed was performed by integrating the skills of geographic information system (GIS) and global positioning system (GPS). Results show that the major land-use patterns in the upper catchment of the Houjing River watershed were farmlands, and land-use patterns in the mid to lower catchment were residential and industrial areas. An integrated watershed management model (IWMM) and Enhanced Stream Water Quality Model (QUAL2K) were applied for the hydrology and water quality modeling, watershed management, and carrying capacity calculation. Modeling results show that the calculated NH3-N carrying capacity of the Houjing River was only 31 kg/day. Thus, more than 10,518 kg/day of NH3-N needs to be reduced to meet the proposed water quality standard (0.3 mg/L). To improve the river water quality, the following remedial strategies have been developed to minimize the impacts of NPS and point source pollution on the river water quality: (1) application of BMPs [e.g. source (fertilizer) reduction, construction of grassy buffer zone, and land use management] for NPS pollution control; (2) application of river management scenarios (e.g. construction of the intercepting and sewer systems) for point source pollution control; (3) institutional control (enforcement of the industrial wastewater discharge standards), and (4) application of on-site wastewater treatment systems for the polishment of treated wastewater for water reuse.

Application of integrated GIS and multimedia modeling on NPS pollution evaluation.

In Taiwan, nonpoint source (NPS) pollution is one of the major causes of the impairment of surface waters. I-Liao Creek, located in southern Taiwan, flows approximately 90 km and drains toward the Kaoping River. Field investigation results indicate that NPS pollution from agricultural activities is one of the main water pollution sources in the I-Liao Creek Basin. Assessing the potential of NPS pollution to assist in the planning of best management practice (BMP) is significant for improving pollution prevention and control in the I-Liao Creek Basin. In this study, land use identification in the I-Liao Creek Basin was performed by properly integrating the skills of geographic information system (GIS) and global positioning system (GPS). In this analysis, 35 types of land use patterns in the watershed area of the basin are classified with the aid of Erdas Imagine process system and ArcView GIS system. Results indicate that betel palm farms, orchard farms, and tea gardens dominate the farmland areas in the basin, and are scattered around on both sides of the river corridor. An integrated watershed management model (IWMM) was applied for simulating the water quality and evaluating NPS pollutant loads to the I-Liao Creek. The model was calibrated and verified with collected water quality and soil data, and was used to investigate potential NPS pollution management plans. Simulated results indicate that NPS pollution has significant contributions to the nutrient loads to the I-Liao Creek during the wet season. Results also reveal that NPS pollution plays an important role in the deterioration of downstream water quality and caused significant increase in nutrient loads into the basin's water bodies. Simulated results show that source control, land use management, and grassy buffer strip are applicable and feasible BMPs for NPS nutrient loads reduction. GIS system is an important method for land use identification and waste load estimation in the basin. Linking the information of land utilization with the NPS pollution simulation model may further provide essential information of potential NPS pollution for all subregions in the river basin. Results and experience obtained from this study will be helpful in designing the watershed management and NPS pollution control strategies for other similar river basins.

Application of immobilized cells to the treatment of cyanide wastewater.

Cyanide is highly toxic to living organisms, particularly in inactivating the respiration system by tightly binding to terminal oxidase. To protect the environment and water bodies, wastewater containing cyanide must be treated before discharging into the environment. Biological treatment is a cost-effective and environmentally acceptable method for cyanide removal compared with the other techniques currently in use. Klebsiella oxytoca (K. oxytoca), isolated from cyanide-containing industrial wastewater, has been shown to be able to biodegrade cyanide to non-toxic end products. The technology of immobilized cells can be applied in biological treatment to enhance the efficiency and effectiveness of biodegradation. In this study, potassium cyanide (KCN) was used as the target compound and both alginate (AL) and cellulose triacetate (CTA) techniques were applied for the preparation of immobilized cells. Results from this study show that KCN can be utilized as the sole nitrogen source by K. oxytoca. The free suspension systems reveal that the cell viability was highly affected by initial KCN concentration, pH, and temperature. Results show that immobilized cell systems could tolerate a higher level of KCN concentration and wider ranges of pH and temperature, especially in the system with CTA gel beads. Results show that a longer incubation period was required for KCN degradation using immobilized cells compared to the free suspended systems. This might be due to internal mass transfer limitations. Results also indicate that immobilized systems can support a higher biomass concentration. Complete KCN degradation was observed after the operation of four consecutive degradation experiments with the same batch of immobilized cells. This suggests that the activity of the immobilized cells can be maintained and KCN can be used as the nitrogen source throughout KCN degradation experiments. Results reveal that the application of immobilized cells of K. oxytoca is advantageous to the maintenance of KCN degradation efficiency. Thus, it is conceivable that the immobilized cells of K. oxytoca would be applicable to the treatment of cyanide-containing wastewaters.

Synthesis and kappa-opioid antagonist selectivity of a norbinaltorphimine congener. Identification of the address moiety required for kappa-antagonist activity.

Compound 2, which represents a structurally simplified congener of norbinaltorphimine 1a, was synthesized in order to evaluate the role of its second basic nitrogen in conferring kappa-opioid receptor antagonist selectivity. Congener 2 was found to be at least twice as selective as 1a as a kappa antagonist, while its N-carbobenzoxy derivative (3) was inactive at kappa-receptors. This study establishes the importance of the second basic nitrogen of 1a for kappa-receptor recognition. It is proposed that this basic group mimics the guanidinium moiety of Arg7, which may be the key kappa-address component of dynorphin.

Structure-activity relationship of N17'-substituted norbinaltorphimine congeners. Role of the N17' basic group in the interaction with a putative address subsite on the kappa opioid receptor.

A series of norbinaltorphimine congeners (2-12) which contain different groups at the N17'-position have been synthesized in order to evaluate the role of N17' in conferring kappa opioid antagonist selectivity at opioid receptor sites. The compounds that contain a basic N17' nitrogen (2-9) were found to be selective kappa antagonists. Amidation of N17' afforded congeners 10-12 with feeble kappa antagonist potency and low selectivity. The fact that potent antagonism and selectivity were observed only when members of the series contain a basic N17' nitrogen suggests that it interacts with extracellular domains of the kappa receptor that contain acidic amino acid residues. The N-terminal domain and extracellular loop 2, both of which contain acidic residues, are candidates for this interaction and may be components of the kappa address subsite of the receptor.

Role of spacer and address components in peptidomimetic delta opioid receptor antagonists related to naltrindole.

A series of heterocyclic analogues 2-5 related to naltrindole (1) (NTI) and 6-arylnaltrexone derivatives 6-8 were synthesized in order to determine the role of the spacer and the address moieties in conferring delta opioid receptor antagonist activity. The benzofuran (NTB), quinoxaline, and quinoline analogues (2, 3, and 4, respectively) were delta-selective opioid antagonists in vitro and bound selectively to delta receptors. The tetrahydroindole derivative 5, while delta-selective, was considerably less potent than its indole analogue 13. The data for 2-4 indicate that heterocycles other than pyrrole can serve as a spacer for the delta address moiety. Moreover, the lower delta antagonist potency of 5 illustrates the importance of the aromatic address component. Molecular dynamics simulations of enkephalin using a zipper binding model are consistent with a delta address subsite that may accommodate the benzene moiety of NTI or the Phe4 phenyl group of leucine enkephalin. The considerably lower delta opioid receptor antagonist potencies of the 6-aryl derivatives 6-8 are consistent with the conformational mobility of the aryl group and its location in the molecule.

Synthesis and siderophore activity of albomycin-like peptides derived from N5-acetyl-N5-hydroxy-L-ornithine.

N5-Acetyl-N5-hydroxy-L-ornithine (1), the key constituent of several microbial siderophores, has been synthesized in 23% yield overall from N-Cbz-L-glutamic acid 1-tert-butyl ester (6) derived from L-glutamic acid. Reduction of 6 to 7 and treatment with N-[(trichloroethoxy)carbonyl]-O-benzylhydroxylamine (8), and diethyl azodicarboxylate and triphenylphosphine followed by deprotection produced the protected N5-acetyl-N5-hydroxy-L-ornithine derivatives 11 and 12 in large quantities (10-20 g). Following alpha-amino and alpha-carboxyl deprotections of 11 and 12, EEDQ [2-ethoxy-N-(ethoxycarbonyl)-1,2-dihydroquinoline] mediated peptide coupling and final deprotection provided amino acid 1 and six albomycin-like peptides (20, 23, 25, 28, 35, and 36). The growth-promoting ability of each was evaluated with the siderophore biosynthesis mutant Shigella flexneri SA240 (SA 100 iucD:Tn5). These results indicate that substantial modification of the framework of peptide-based siderophores can be tolerated by microbial iron-transport systems.

Synthesis and siderophore and antibacterial activity of N5-acetyl-N5-hydroxy-L-ornithine-derived siderophore-beta-lactam conjugates: iron-transport-mediated drug delivery.

N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acety l- N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a "carrier" substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthesized protected version of this tripeptide (14) was coupled with various beta-lactam analogues 17, 19, 24, and 25 to give protected conjugates 21, 22, 26, and 27. Final deprotection by hydrogenolysis provided the deprotected siderophore-beta-lactam antibiotic conjugates 1-4. The growth-promoting ability of each has been evaluated using either the siderophore-deficient mutant Shigella flexneri SA 100 or S. flexneri SA240 (SA 100 iucD:Tn5). Measurement of the growth-promoting activity using two isogenic Escherichia coli strains differing only in the presence or absence of fhuA (hydroxamate ferrichrome receptor) suggests uptake by the hydroxamate iron-transport system. The antibacterial activity of these conjugates has been investigated, and the potential for use of the ferrichrome iron-transport system as a means of drug delivery is discussed.

Role of the spacer in conferring kappa opioid receptor selectivity to bivalent ligands related to norbinaltorphimine.

The thiophene 2 and pyran 3 analogues of the kappa-selective opioid antagonist norbinaltorphimine (1a, norBNI) were synthesized and tested in an effort to determine the contribution of the spacer to the interaction of bivalent ligands at different opioid receptor types. Both 2 and 3 were found to be selective kappa opioid receptor antagonists in smooth muscle preparations, and they bound selectively to kappa-recognition sites. The thiophene analogue 2 displayed binding selectivity that was of the same order of magnitude as that of 1a, while 3 was considerably less selective for kappa site. This is consistent with the fact that the second pharmacophore in 1a and 2 displayed a greater degree of superposition than 1a and 3. The results of this study suggest that the pyrrole moiety of norBNI functions primarily as an inert spacer to rigidly hold the basic nitrogen in the second pharmacophore at an "address" subsite that is unique for the kappa opioid receptor.

Migration behavior and separation of benzenediamines, aminophenols and benzenediols by capillary zone electrophoresis.

The migration behavior and separation of five benzendiamines, five aminophenols and three benzenediols were investigated in capillary zone electrophoresis. The results indicate that benzendiamines and aminophenols are optimally separated with a phosphate buffer at pH 5, whereas benzenediol isomers are best separated at pH about 12. The addition of surfactant monomers of tetradecyltrimethylammonium bromide to a phosphate buffer at pH 5 under the conditions of reversed electroosmotic flow is effective for separating these dye intermediates, except for the separation of 1,2-benzenediol from 1,3-benzenediol. The addition of sodium tetraborate as an electrolyte modifier is effective in the separation of 1,2-benzenediol from 1,3-benzenediol, but the latter comigrates with the 1,4-benzenediol isomer at pH 5.0. The electrophoretic mobility of ionized analytes can be described with Offord's equation, and the migration order depends on their ratios of charge to mass. In addition, the pKa values of these analytes in 50 mM phosphate buffer are reported.

Migration behavior and separation of tetracycline antibiotics by micellar electrokinetic chromatography.

The migration behavior and separation of six tetracyclines (TCs) were investigated by micellar electrokinetic chromatography (MEKC) in the pH range 5.0-9.0 using ammonium acetate buffer with the addition of sodium dodecyl sulfate (SDS). Mixed SDS-Brij 35, sodium cholate (SC) and tetradecyltrimethylammonium bromide (TTAB) were also used as surfactants. The influences of surfactant concentration and buffer pH on the separation of TCs were examined and the separations of TCs were optimized. Complete separation of six TCs was achieved within 8 min with 15 mM ammonium acetate buffer containing 20 mM SDS, with or without the addition of Brij 35 (0.135%, w/v), at pH 6.5 using a fused-silica capillary (42 cm x 75 microns I.D.) at 15 kV. In general, good linear correlations of the logarithm of migration factor (log k') versus the logarithm of octanol-water partition coefficient (log P(ow)) in these micellar systems, except for the TTAB-MEKC system, were obtained. The results indicate that the migration of TCs in MEKC is mainly based on hydrophobic interactions. However, hydrogen bonding interactions also play a significant role in influencing the chemical selectivity of TCs. In addition, the micelle-water partition coefficients (Pmw) of TCs, which are pH-dependent in the SDS-MEKC micellar system, are reported.

Separation and selectivity of benzophenones in micellar electrokinetic chromatography using sodium dodecyl sulfate micelles or sodium cholate modified mixed micelles.

The separation and selectivity of nine benzophenones in micellar electrokinetic chromatography (MEKC) using sodium dodecyl sulfate (SDS) micelles or sodium cholate (SC) modified mixed micelles were investigated in the pH range 6.5-8.0. The results indicate that the combined effects of buffer pH and SC concentration can greatly affect the separation and selectivity of benzophenones, particularly for benzophenones possessing a hydroxyl substituent at the 4-position of the aromatic ring with respect to the carbonyl moiety when using SDS-SC mixed micelles. Better separability can be obtained with SDS-SC mixed micelles than with SDS micelles. Complete separation of nine benzophenones in MEKC can be achieved with an appropriate choice of buffer pH and the concentration of SDS micelles or SC modified mixed micelles. The dependence of the migration order of those benzophenones based on their structures and solute-micelle interactions is discussed.

Enantioseparation of phenothiazines in capillary zone electrophoresis using cyclodextrins as chiral selectors.

In this study, enantioseparations of five phenothiazines, including promethazine, ethopropazine, trimeprazine, methotrimeprazine, and thioridazine, in cyclodextrin (CD)-modified capillary zone electrophoresis were investigated using a phosphate buffer (40 mM) at pH 3.0. We focussed on the separation of phenothiazines with the use of CDs at low concentrations. Three different CDs, including beta-CD, hydroxypropyl-beta-CD (HP-beta-CD) and gamma-CD, were chosen as chiral selectors. The results indicate that effective enantioseparation of phenothiazines, except for methotrimeprazine, is simultaneously achievable with addition of gamma-CD at a concentration of 2.5-6.0 mM. The enantiomers of ethopropazine and trimeprazine are effectively separated with addition of HP-beta-CD at low concentrations, in the range 0.4-6.0 mM, whereas those of promethazine and trimeprazine are baseline resolved with beta-CD at much lower concentrations (0.02-3.0 mM) than with HP-beta-CD. The results also confirm that the separation window is greatly enlarged at low CD concentrations. Moreover, the drastic variations of the electrophoretic mobility of phenothiazines as a function of CD concentration reveal that phenothiazines interact very strongly with CDs in the order gamma-CD

A capillary electrophoresis study on the influence of beta-cyclodextrin on the critical micelle concentration of sodium dodecyl sulfate.

The influence of beta-cyclodextrin (beta-CD) on the critical micelle concentration (CMC) of sodium dodecyl sulfate (SDS) was investigated by capillary electrophoresis using anionic chlorophenols as probe molecules at pH 7.0. The variations of the electrophoretic mobility of probe molecules as a function of surfactant concentration in both premicellar and micellar regions in the absence and presence of beta-CD was analyzed. The results indicate that, as a consequence of a strong inclusion complexation between beta-CD and SDS, the encapsulation of beta-CD with probe molecules is greatly diminished, or even vanished, in the presence of SDS. The complexes formed between beta-CD and SDS monomers exist predominantly in the form of a 1:1 stoichiometry, while the complexes with a 2:1 stoichiometry reported previously in the literature as a minor component may exist by less than 10%. The elevation of the CMC value of SDS depends not only on the concentration of beta-CD in the buffer electrolyte but also on methanol content in the sample solution. The binding constants of probe molecules to beta-CD, to surfactant molecules, and to the complexes formed between beta-CD and SDS are reported.

Optimization of separation and migration behavior of cephalosporins in capillary zone electrophoresis.

The influences of buffer pH, buffer concentration and buffer electrolyte on the migration behavior and separation of 12 cephalosporin antibiotics in capillary zone electrophoresis using three different types of buffer electrolyte, including phosphate, citrate, and 2-(N-morpholino)ethanesulfonate (MES), were investigated. The results indicate that, although buffer pH is a crucial parameter, buffer concentration also plays an important role in the separation of cephalosporins, particularly when cefuroxime and cefazolin, cephalexin and cefaclor, or cefotaxime and cephapirin are present as analytes at the same time. The electrophoretic mobility of cephalosporins and electroosmotic mobility measured in citrate and MES buffers are remarkably different from those measured in phosphate buffer. With citrate buffer, optimum buffer concentration is confined to a small range (35-40 mM), whereas buffer concentrations up to 300 mM can be used with MES buffer. Complete separations of 12 cephalosporins could be satisfactorily achieved with these three buffers under various optimum conditions. However, the separability of 12 cephalosporins with citrate or MES buffer is better than that with phosphate buffer. As a consequence of a greater electrophoretic mobility of cephalosporins than the electroosmotic mobility with citrate buffer at pH below about 5, some cephalosporins are not detectable. The cloudiness of the peak identification and of the magnitudes of the electrophoretic mobility of cefotaxime and cefuroxime reported previously are clarified. In addition, the pKa values of cephradine, cephalexin, cefaclor, and cephapirin attributed to the deprotonation of either an amino group or a pyridinium group are reported, and the migration behavior of these cephalosporins in the pH range studied is quantitatively described.

Migration behavior and separation of sulfonamides in capillary zone electrophoresis. I. Influence of buffer pH and electrolyte modifier.

The influence of buffer pH and electrolyte modifier on the migration behavior and separation of thirteen sulfonamides was investigated by capillary zone electrophoresis. The results indicate that precise optimization of buffer pH is crucial in improving the separation of some closely migrating sulfonamides. On the addition of either an appropriate amount of an organic modifier (methanol or acetonitrile) or a low concentration of beta-cyclodextrin (beta-CD, 0.5 mM) to a phosphate-borate buffer at pH 6.85 and an applied voltage of 20 kV, the resolution of peaks between sulfathiazole and sulfamethoxypyridarine is markedly enhanced and effective separations of thirteen sulfonamides are achieved within a relatively short time. Methanol gives better resolution than acetonitrile as an organic modifier. Weak inclusion complexation occurs between beta-CD and sulfonamides, with the exception of sulfathiazole. The formation constants of thirteen sulfonamides with beta-CD are reported.