Pilot test of cooperative learning format for training mental health researchers and black community leaders in partnership skills

To support reduction of racial disparities in mental health diagnosis and treatment, mental health researchers and black community-based organization (CBO) leaders need training on how to engage in collaborative research partnerships. In this study, we pilot tested a series of partnership skills training modules for researchers and CBO leaders in a collaborative learning format. Two different sets of three modules, designed for separate training of researchers and CBO leaders, covered considering, establishing and managing mental health research partnerships and included instructions for self-directed activities and discussions. Eight CBO leaders participated in 10 sessions, and six researchers participated in eight sessions. The effectiveness of the training content and format was evaluated through standardized observations, focus group discussions, participant evaluation forms and retrospective pre-/posttests to measure perceived gains in knowledge. Participants generally were satisfied with the training experience and gained new partnership knowledge and skills. Although the CBO leaders were more engaged in the cooperative learning process, this training format appealed to both audiences. Pilot testing demonstrated that: 1) our modules can equip researchers and CBO leaders with new partnership knowledge and skills and 2) the cooperative learning format is a well-received and suitable option for mental health research partnership training.     

Induction of organ-selective CD4+ regulatory T cell homing

Compelling evidence suggests that Foxp3⁺CD25⁺CD4⁺ Treg play a fundamental role in immunoregulation. We have previously demonstrated that Treg have to enter peripheral tissues to suppress ongoing inflammation. However, relatively little is known about how Treg acquire the expression of homing receptors required for tissue‐ or inflammation‐specific migration. Migratory properties of conventional naïve T cells are shaped by the tissue microenvironment and organ‐specific dendritic cells during priming. Here, we show that this basic concept also holds true for CD25⁺CD4⁺ Treg: Priming of Treg within peripheral LN led to the expression of selectin ligands, which facilitate migration into inflamed skin, whereas activation within mesenteric LN led to induction of the integrin α₄β₇, which is required for migration into mucosal tissues. Furthermore, we could establish in vitro culture systems containing either dendritic cells from mesenteric and peripheral LN, or retinoic acid and IL‐12 as polarizing compounds to induce mucosa‐ and skin‐seeking Treg, respectively. Together, our results demonstrate that Treg, similarly to conventional T cells, can be configured with organ‐selective homing properties allowing efficient targeting into distinct tissues.     

Involvement of prefrontal cortex in visual search

Visual search for target items embedded within a set of distracting items has consistently been shown to engage regions of occipital and parietal cortex, but the contribution of different regions of prefrontal cortex remains unclear. Here, we used fMRI to compare brain activity in 12 healthy participants performing efficient and inefficient search tasks in which target discriminability and the number of distractor items were manipulated. Matched baseline conditions were incorporated to control for visual and motor components of the tasks, allowing cortical activity associated with each type of search to be isolated. Region of interest analysis was applied to critical regions of prefrontal cortex to determine whether their involvement was common to both efficient and inefficient search, or unique to inefficient search alone. We found regions of the inferior and middle frontal cortex were only active during inefficient search, whereas an area in the superior frontal cortex (in the region of FEF) was active for both efficient and inefficient search. Thus, regions of ventral as well as dorsal prefrontal cortex are recruited during inefficient search, and we propose that this activity is related to processes that guide, control and monitor the allocation of selective attention.     

gyrA and parC Mutations and associated quinolone resistance in Vibrio anguillarum serotype O2b strains isolated from farmed Atlantic cod (Gadus morhua) in Norway

MIC testing of Vibrio anguillarum isolates recovered from diseased farmed Atlantic cod revealed oxolinic acid MICs of < or =0.001, 0.06, and 16 microg ml(-1). Single gyrA Ser-Ile substitutions were identified at position 83 of the intermediate and resistant strains, while a parC Ser-Leu substitution at position 85 was found only in the resistant strain.     

Antibacterial activity and mechanism of action of a novel anilinouracil-fluoroquinolone hybrid compound

The anilinouracils (AUs) such as 6-(3-ethyl-4-methylanilino)uracil (EMAU) are a novel class of gram-positive, selective, bactericidal antibacterials which inhibit pol IIIC, the gram-positive-specific replicative DNA polymerase. We have linked various fluoroquinolones (FQs) to the N-3 position of EMAU to generate a variety of AU-FQ "hybrids" offering the potential for targeting two distinct steps in DNA replication. In this study, the properties of a hybrid, "251D," were compared with those of representative AUs and FQs in a variety of in vitro assays, including pol IIIC and topoisomerase/gyrase enzyme assays, antibacterial, bactericidal, and mammalian cytotoxicity assays. Compound 251D potently inhibited pol IIIC and topoisomerase/gyrase, displayed gram-positive antibacterial potency at least 15 times that of the corresponding AU compound, and as expected, acted selectively on bacterial DNA synthesis. Compound 251D was active against a broad panel of antibiotic-resistant gram-positive pathogens as well as several gram-negative organisms and was also active against both AU- and FQ-resistant gram-positive organisms, demonstrating its capacity for attacking both of its potential targets in the bacterium. 251D also was bactericidal for gram-positive organisms and lacked toxicity in vitro. Although we obtained strains of Staphylococcus aureus resistant to the individual parent compounds, spontaneous resistance to 251D was not observed. We obtained 251D resistance in multiple-passage experiments, but resistance developed at a pace comparable to those for the parent compounds. This class of AU-FQ hybrids provides a promising new pharmacophore with an unusual dual mechanism of action and potent activity against antibiotic-sensitive and -resistant gram-positive pathogens.