The Development of Social Media Guidelines for Psychologists and for Regulatory Use.

The Association of State and Provincial Psychology Boards, the national organization representing psychology regulatory/licensing boards in Canada and the USA, recently developed social media guidelines that are being recommended for use by its member boards. The purposes of the guidelines were to provide guidance to psychology regulatory boards both countries in identifying and communicating what are considered appropriate and inappropriate uses of social media and to promote consistency and clarity about this across jurisdictions. The process involved reviewing the professional literature, relevant guidelines, standards, current laws, and regulations. The guidelines developed include guidelines about confidentiality, informed consent, risk management, competence, multiple relationships, professional conduct, security of information, personal use of social media, and regulatory board use of social media. Major challenges and limitations in accomplishing this task are identified and discussed.

Reading Comprehension Instruction for Young Students with Autism: Forming Contextual Connections.

Central coherence is the ability to perceive and connect salient information in a context such as a narrative text. Individuals with autism exhibit a detail-focused cognitive style of processing information that overlooks connections and shows weak central coherence. A six-session instructional intervention to foster coherence processing was administered to first and second graders (N = 10) while a control group (N = 10) received an irrelevant treatment, mean age 7.06 years, 18 males and 2 females. Results showed that the instruction benefited children's comprehension of narrative text. The intervention improved children's ability to retell a narrative text and improved first graders' use of sequence words to retell a story compared to control students. Findings carry implications for designing reading instruction for this special population.

The Significance of Preoperative Computed Tomography for Predicting Optimal Cytoreduction in Advanced Ovarian Cancer.

Introduction Optimal cytoreduction is the most important prognostic factor in advanced ovarian cancer. Although staging and assessment of operability are made by exploratory surgery, preoperative computed tomography (CT) of the abdomen is regarded as standard. The aim of this study was to examine various CT parameters with regard to prediction of optimal cytoreduction. Patients and Methods The retrospective study included 131 patients with ovarian cancer newly diagnosed between 2010 and 2014. Of these, n = 36 with FIGO stage I to IIB were excluded from the study. A preoperative abdominal CT was available for n = 75 of the 95 patients with FIGO stage IIC to IV. The CT scans underwent blinded review. The 11 evaluated CT parameters were examined by means of χ 2 test and logistic regression analysis with regard to the endpoints of macroscopic residual tumour and residual tumour > 1 cm. Survival analyses used the Kaplan-Meier method and log rank test. Results Of 75 patients, 28 (37.3%) had complete tumour resection and 26 (34.7%) had residual tumour ≤ 1 cm. Residual tumours > 1 cm were found in 21 (28%) patients, five of which were not resectable. Overall survival with residual tumour > 1 cm differed significantly from the group with no macroscopic residual tumour (p = 0.003) and with residual tumour ≤ 1 cm (p = 0.04). The CT parameters tumour foci in the diaphragm, mesocolon, greater omentum and peritoneum as well as ascites correlated with macroscopic residual tumour. In the multivariate logistic regression analysis only the CT parameter intraparenchymal liver metastasis was statistically significant with regard to prediction of suboptimal tumour resection (> 1 cm) (OR 8.04; 95% CI 1.57 - 42.4; p = 0.0134). The sensitivity, specificity, PPV and NPV were 37.5, 89.7, 66.7 and 72.2%. Conclusion Although risk parameters for suboptimal tumour reduction can be identified by CT of the abdomen, surgical exploration with histological confirmation of the diagnosis is essential because of the poor diagnostic accuracy.

Profiles and service utilization for children accessing a mental health walk-in clinic versus usual care.

Many children and adolescents with mental health problems do not receive the treatment they need. Unmet need raises questions about specific barriers that may prevent service use, and/or the characteristics of children and families who are less likely to receive care. Brief interventions or single-session psychotherapy delivered in a highly accessible manner are methods of addressing the problems associated with waitlists and limited access to care. In the current study the authors offer an exploratory evaluation of the West End Walk-In Counseling Centre for children and youth with psychosocial problems. Children 4 to 18 years of age who accessed the Walk-In Counseling Centre and a comparison group of clients who accessed usual care were assessed at intake, post-treatment, and 3-month follow-up on demographic characteristics, behavioral/emotional adjustment and functioning, client satisfaction, and service use. Children in the walk-in group had more severe behavioral/emotional adjustment and functioning than usual care clients at baseline. At post-treatment, walk-in clients had lower scores on Total Mental Health Problems and Internalizing Behaviors, and exhibited fewer problems across all scales at follow-up. Walk-in clients found the wait time for service more reasonable and at follow-up, felt the service addressed concerns and had higher regard for counselor availability and cultural sensitivity of the service than usual care clients. Service utilization, assessed at post-treatment and 3-month follow-up, showed that both groups were more likely to access mental health and education services rather than health or child welfare services, and were more likely to have used services in the 12 months prior to service than the 3 months following service completion. Walk-in clients had steeper rates of improvement compared to usual care clients despite equivalence in psychosocial functioning at baseline. The walk-in model may be an effective alternative to usual care, particularly for those clients only willing to wait up to 2 weeks for service.

Adenosine transport by plasma membrane monoamine transporter: reinvestigation and comparison with organic cations.

The plasma membrane monoamine transporter (PMAT) belongs to the equilibrative nucleoside transporter family (solute carrier 29) and was alternatively named equilibrative nucleoside transporter 4. Previous studies from our laboratory characterized PMAT as a polyspecific organic cation transporter that minimally interacts with nucleosides. Recently, PMAT-mediated uptake of adenosine (a purine nucleoside) was reported, and the transporter was proposed to function as a dual nucleoside/organic cation transporter. To clarify the substrate specificity of PMAT, we comprehensively analyzed the transport activity of human PMAT toward nucleosides, nucleobases, and organic cations in heterologous expression systems under well controlled conditions. Among 12 naturally occurring nucleosides and nucleobases, only adenosine was significantly transported by PMAT. PMAT-mediated adenosine transport is saturable, pH-dependent, and membrane-potential sensitive. Under both neutral (pH 7.4) and acidic (pH 6.6) conditions, adenosine is transported by PMAT at an efficiency (V(max)/K(m)) at least 10-fold lower than that of the organic cation substrates 1-methyl-4-phenylpyridinium and serotonin. PMAT-mediated adenosine uptake rate was significantly enhanced by an acidic extracellular pH. However, the effect of acidic pH was not adenosine-specific but was common to organic cation substrates as well. Our results demonstrated that although PMAT transports adenosine, the transporter kinetically prefers organic cation substrates. Functionally, PMAT should be viewed as a polyspecific organic cation transporter rather than an archetypical nucleoside transporter.

Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function.

To determine specific molecular features of endothelial cells (ECs) relevant to the physiological process of penile erection we compared gene expression of human EC derived from corpus cavernosum of men with and without erectile dysfunction (HCCEC) to coronary artery (HCAEC) and umbilical vein (HUVEC) using Affymetrix GeneChip microarrays and GeneSifter software. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. A total of 190 genes/transcripts were highly expressed only in HCCEC. Gene Ontology classification indicated cavernosal enrichment in genes related to cell adhesion, extracellular matrix, pattern specification and organogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed high expression of genes relating to ECM-receptor interaction, focal adhesions, and cytokine-cytokine receptor interaction. Real-time PCR confirmed expression differences in cadherins 2 and 11, claudin 11 (CLDN11), desmoplakin, and versican. CLDN11, a component of tight junctions not previously described in ECs, was highly expressed only in HCCEC and its knockdown by siRNA significantly reduced transendothelial electrical resistance in HCCEC. Overall, cavernosal ECs exhibited a transcriptional profile encoding matrix and adhesion proteins that regulate structural and functional characteristics of blood vessels. Contribution of the tight junction protein CLDN11 to barrier function in endothelial cells is novel and may reflect hemodynamic requirements of the corpus cavernosum.

Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells.

Plasma membrane monoamine transporter (PMAT) is a novel membrane transporter recently cloned and characterized in our laboratory. We previously demonstrated that PMAT functions as a polyspecific organic cation transporter and efficiently transports many organic cations such as monoamine neurotransmitters and 1-methyl-4-phenylpyridinium (MPP(+)). In this study, we explored the role of PMAT in the renal handling of organic cations. Using a polyclonal antibody generated toward the NH(2)-terminal 66 amino acid residues of human PMAT, we showed that the PMAT protein (approximately 55 kDa) is expressed in the human kidney and is primarily targeted to the apical membranes when expressed in polarized Madin-Darby canine kidney (MDCK) cells. Using MDCK cells stably expressing human PMAT, we showed that PMAT-mediated MPP(+) uptake is strongly dependent on extracellular pH. Lowering extracellular pH from 7.4 to 6.6 greatly stimulated PMAT-mediated MPP(+) uptake, whereas elevating extracellular pH to 8.2 abolished transporter activity. Kinetic analysis revealed that the apparent V(max) at pH 6.6 is about fourfold higher than that at pH 7.4, whereas the apparent K(m) values were not statistically different at these two conditions. Under acidic conditions (pH 6.6), the proton ionophore, carbonyl cyanide p-trifluormethoxyphenylhydrazone, drastically reduced PMAT-mediated MPP(+) uptake, suggesting that the stimulatory effect of proton may be due to transporter coupling with a proton gradient. Taken together, our data suggest that PMAT is expressed on the apical membranes of renal epithelial cells and may use luminal proton gradient to drive organic cation reabsorption in the kidney.

Evidence for significant contribution of a newly identified monoamine transporter (PMAT) to serotonin uptake in the human brain.

The high affinity serotonin transporter (SERT) constitutes the principal pathway for removal of serotonin (5-HT) from extracellular fluid of brain, but evidence indicates that other transporters may also be involved in this process. We recently reported the cloning of a novel plasma membrane monoamine transporter (PMAT), which is abundantly expressed in the human brain and avidly transports 5-HT [Engel K, Zhou M, Wang J. Identification and characterization of a novel monoamine transporter in the human brain. J Biol Chem 2004;279:50042-9]. In this study, we evaluated whether PMAT contributes to total human brain uptake of 5-HT using a hybrid depletion approach in Xenopus laevis oocytes. We also examined whether PMAT interacts with selective serotonin reuptake inhibitors (SSRIs) using MDCK cells stably expressing recombinant human PMAT. Microinjection of total human brain poly(A)(+) mRNA into oocytes elicited approximately 2.5-3-fold increase in 5-HT uptake. Pre-hybridization of poly(A)(+) mRNA with PMAT or SERT antisense oligonucleotides significantly reduced mRNA-induced 5-HT uptake. An additive inhibitory effect was observed when poly(A)(+) mRNA was co-hybridized with both PMAT and SERT antisense oligonucleotides. In contrast, mRNA-induced 5-HT uptake was not affected by pre-hybridization with sense oligonucleotides. These data suggest that functional transcripts of PMAT are present in the human brain, and the PMAT transporter may be significantly involved in brain uptake of 5-HT. All five tested SSRIs inhibited PMAT with IC(50) values ranging from 11 to 116 microM, which are much greater than clinically encountered concentrations, suggesting that PMAT activity is minimally affected by SSRI therapies.

Molecular determinants of substrate selectivity of a novel organic cation transporter (PMAT) in the SLC29 family.

Plasma membrane monoamine transporter (PMAT or ENT4) is a newly cloned transporter assigned to the equilibrative nucleoside transporter (ENT) family (SLC29). Unlike ENT1-3, PMAT mainly functions as a polyspecific organic cation transporter. In this study, we investigated the molecular mechanisms underlying the unique substrate selectivity of PMAT. By constructing chimeras between human PMAT and ENT1, we showed that a chimera consisting of transmembrane domains (TM) 1-6 of PMAT and TM7-11 of hENT1 behaved like PMAT, transporting 1-methyl-4-phenylpyridinium (MPP+, an organic cation) but not uridine (a nucleoside), suggesting that TM1-6 contains critical domains responsible for substrate recognition. To identify residues important for the cation selectivity of PMAT, 10 negatively charged residues were chosen and substituted with alanine. Five of the alanine mutants retained PMAT activity, and four were non-functional due to impaired targeting to the plasma membrane. However, alanine substitution at Glu(206) in TM5 abolished PMAT activity without affecting cell surface expression. Eliminating the charge at Glu(206) (E206Q) resulted in loss of organic cation transport activity, whereas conserving the negative charge (E206D) restored transporter function. Interestingly, mutant E206Q, which possesses the equivalent residue in ENT1, gained uridine transport activity. Thr(220), another residue in TM5, also showed an effect on PMAT activity. Helical wheel analysis of TM5 revealed a distinct amphipathic pattern with Glu(206) and Thr(220) clustered in the center of the hydrophilic face. In summary, our results suggest that Glu(206) functions as a critical charge sensor for cationic substrates and TM5 forms part of the substrate permeation pathway in PMAT.

Fluid shear stress-induced nitric oxide production in human cavernosal endothelial cells: inhibition by hyperglycaemia.

OBJECTIVE: To investigate whether fluid shear stress (FSS) induces endothelial nitric oxide synthase (eNOS) activity and NO production in isolated human corpus cavernosal endothelial cells (HCCECs), and whether this response is altered during hyperglycaemia in vitro, as haemodynamic signalling during penile erection induces eNOS-mediated NO production in vivo. MATERIALS AND METHODS: ECs were cultured from HCC and characterized by the uptake of acetylated low-density lipoprotein and the expression of von Willebrand factor, VE-cadherin, CD31 and eNOS. HCCECs were exposed to FSS (1.2 Pa (12 dynes/cm2), 5 min) using a cone-and-plate viscometer in the presence or absence of high glucose (30 mm, 48 h). The phosphorylation of ser1177 on eNOS and total eNOS protein expression after FSS was examined by Western blot. NO in the conditioned media was assessed by measuring nitrate and nitrite levels. RESULTS: Compared to static conditions, FSS induced a significant increase in the phosphorylation of eNOS on ser1177 in HCCECs, and the release of NO to the conditioned media. Treatment of HCCECs with high glucose levels did not alter the ratio FSS-induced phosphorylated eNOS/total eNOS, but did result in the down-regulation of total eNOS and significantly attenuated FSS-induced NO release. CONCLUSION: These in vitro data suggest that FSS contributes to eNOS activation and NO release in HCCECs, and supports in vivo reports suggesting a role for haemodynamic signalling in the erectile response. Treatment with high glucose levels prevented FSS-induced NO release, suggesting a mechanism that may contribute to decreased erectile function associated with diabetes.

Interaction of organic cations with a newly identified plasma membrane monoamine transporter.

Many endogenous compounds and xenobiotics are organic cations that rely on polyspecific organic cation transporters (OCTs) to traverse cell membranes. We recently cloned a novel human plasma membrane monoamine transporter (PMAT) that belongs to the equillibrative nucleoside transporter (ENT) family. We have reported previously that, unlike other ENTs, PMAT (also known as ENT4) is a Na+-independent and membrane potential-sensitive transporter that transports monoamine neurotransmitters and the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). These compounds are the known substrates for OCTs, which raises the possibility that PMAT functions as a polyspecific transporter like the OCTs. In the present study, we analyzed the interaction of PMAT with a series of structurally diverse organic cations using MDCK cells stably expressing human PMAT. Our study showed that PMAT interacts with many organic cations that have heterogeneous chemical structures. PMAT transports classic OCT substrates, such as tetraethylammonium, guanidine, and histamine. Prototype OCT inhibitors, including cimetidine, and type II cations (e.g., quinidine, quinine, verapamil, and rhodamine123) are also PMAT inhibitors. An analysis of molecular structures and apparent binding affinities revealed that charge and hydrophobicity are the principal determinants for transporter-substrate/inhibitor interaction. A planar aromatic mass seems to be important for high affinity interaction. trans-Stimulation and efflux studies demonstrate that PMAT is able to mediate bidirectional transport. These functional properties of PMAT are strikingly similar to those of the OCTs. We therefore conclude that PMAT can function as a polyspecific organic cation transporter, which may play a role in organic cation transport in vivo.

Identification and characterization of a novel monoamine transporter in the human brain.

Precise control of monoamine neurotransmitter levels in the extracellular fluids of the brain is critical in maintaining efficient and robust neurotransmission. High affinity transporters in the solute carrier SLC6A family function in removing monoamines from the neurosynaptic cleft. Emerging evidence suggests that these transporters are only one part of a system of transporters that work in concert to maintain brain homeostasis of monoamines. Here we report the cloning and characterization of a new human plasma membrane monoamine transporter, PMAT. The PMAT cDNA encodes a protein of 530 amino acid residues with 10-12 transmembrane segments. PMAT is not homologous to known neurotransmitter transporters but exhibits low homology to members of the equilibrative nucleoside transporter family. When expressed in Madin-Darby canine kidney cells and Xenopus laevis oocytes, PMAT efficiently transports serotonin (K(m) = 114 mum), dopamine (K(m) = 329 mum), and the neurotoxin 1-methyl-4-phenylpyridinium (K(m) = 33 mum). In contrast, there is no significant interaction of PMAT with nucleosides or nucleobases. PMAT-mediated monoamine transport does not require Na(+) or Cl(-) but appears to be sensitive to changes in membrane potential. Northern blot analysis showed that PMAT is predominantly expressed in the human brain and widely distributed in the central nervous system. These studies demonstrate that PMAT may be a novel low affinity transporter for biogenic amines, which, under certain conditions, might supplement the role of the high affinity transporters in the brain.

Mammalian nucleoside transporters.

Nucleoside transporters mediate cellular uptake of physiologic nucleosides for nucleic acid synthesis in the salvage pathways in many cell types. These transporters also play an important role in in vivo disposition and intracellular targeting of many nucleoside analogs used in anticancer and antiviral drug therapy. In mammalian cells, there are two major nucleoside transporter gene families: the equilibrative nucleoside transporters (ENTs) and the concentrative nucleoside transporters (CNTs). The ENTs are facilitated carrier proteins and the CNTs are Na(+)-dependent secondary active transporters. Recent molecular cloning of a number of ENT and CNT transporters has greatly advanced our understanding of the molecular and cellular mechanisms by which nucleosides and nucleoside analogs are transported across biological membranes. In this manuscript, we review the structure, function, tissue distribution, and cellular localization of various cloned mammalian nucleoside transporters. Information on transporter interaction with various nucleoside drugs and analogs is presented. Current knowledge on the regulation of nucleoside transporters in various cell types and tissues is reviewed. The therapeutic significance of nucleoside transporters is discussed along with emerging data from recent clinical studies.

Management of acute superior mesenteric artery occlusion.

BACKGROUND: This review examines the surgical management of acute superior mesenteric artery (SMA) occlusion and the impact of interventional radiology techniques. METHODS: Eight consecutive patients with SMA occlusion were treated at the Lismore Base Hospital, Lismore, NSW, Australia, from 1996 through to 2001 and of these, one patient was managed successfully with catheter-directed lytic therapy. The study group included five male and three female patients with a mean age of 71.3 (range 57-88) years. The records of these patients were reviewed to determine demographic characteristics, clinical features, predisposing factors and the duration of symptoms before intervention, management details and final outcome. RESULTS: Embolic phenomena due to atrial fibrillation were the most frequently identifiable cause of acute SMA occlusion, present in six of eight patients. Seven patients were managed with open surgery in the first instance and of these, four died. Three patients remain alive and well at a mean 2.8 years follow-up. Patient number eight developed acute SMA occlusion from embolism secondary to atrial fibrillation and was managed initially with SMA urokinase thrombolysis. This patient's pain was relieved 1 h after initiation of the procedure. Delayed films after 18 h from initiation of thrombolysis demonstrated re-opening of all the ileo-colic branches and at 6 weeks' follow-up the patient remains well with normal bowel function. CONCLUSIONS: There is a role for selective SMA cannulation and urokinase thrombolysis in the management of patients with acute SMA thrombosis.