Serum anticholinergicity is associated with reduced prefrontal brain function in early course schizophrenia.

Increased anticholinergic activity resulting from pharmacotherapies used to treat schizophrenia is associated with poorer cognition. However the neural mechanisms underlying this effect are unknown. In this study of 39 early course schizophrenia outpatients, we demonstrate that increased serum anticholinergic activity is associated with reduced activation across the prefrontal cortex, including the dorsolateral, anterior, and medial prefrontal cortices, during two tasks of cognitive control. Lower activation in the dorsolateral and anterior prefrontal cortices mediated the association between increased anticholinergicity and poorer neurocognitive function. Such findings provide preliminary insight into how anticholinergic medications may impact cognition through reduced prefrontal cortical function in schizophrenia.

Single-use membrane adsorbers for endotoxin removal and purification of endogenous polysialic acid from Escherichia coli K1.

Polysialic acid (polySia) is a promising molecule for various medical applications (e.g., treatment of inflammatory neurodegenerative diseases). In this study a complete production process for human-identical α-(2,8)-linked polySia was developed using a disposable bioreactor for cultivation of Escherichia coli K1 and single-use membrane adsorbers for downstream processing (DSP). The cultivation process was optimized to minimize complex media components and a maturation process after cultivation was established. The maturation led to further product release from the cell surface into the supernatant. Afterwards DSP was established using sodium hydroxide treatment combined with anion exchange membrane adsorbers for endotoxin and DNA depletion. After downstream processing the final product had neither detectable protein nor DNA contamination. Endotoxin content was below 3 EU mg-1. Investigation of the maximal chain length showed no effect of the harsh sodium hydroxide treatment during DSP on the stability of the polySia. Maximal chain length was ∼98 degree of polymerization.

Continuous purification of Candida antarctica lipase B using 3-membrane adsorber periodic counter-current chromatography.

Batch chromatography has several disadvantages, such as insufficient utilization of the capacity of the resin, high buffer consumption and discontinuity. Considering the high costs for downstream processing, a continuously working chromatographic system with three membrane adsorber units was designed, tested and put into operation. The basic principle of the setup is periodic counter-current chromatography (PCCC). The PCCC system was used for capturing and purifying Candida antarctica lipase B (CalB) directly from cell lysate in one single unit operation. The best purification result was achieved by means of anion-exchange chromatography. The dynamic binding capacity with Sartobind® Q 75 amounted to 4.2 mg (56 g/cm2). After transferring the method to the 3MA-PCCC, 0.22 g CalB (73 U/mg) were obtained from 0.9 L E. coli lysate within 6 h and a recovery of 80%. Compared to the batch process, the productivity could be increased by 36% and the buffer consumption could be reduced by about 20%. Although the purification of CalB from lysate by means of anion-exchange chromatography was not selective and quantitative using the 3MA-PCCC device, it could be shown that the concept of the system was successfully implemented and led to a significant improvement of CalB purification.

New application of depth filters for the immobilization of Candida antarctica lipase B.

The objective of this study was to use for the first time depth filters, which are usually intended for clarification of cell culture broth, as a direct immobilization support/matrix for industrially relevant enzymes. With this method, it is not only possible to immobilize pure enzymes; it can be also used for capturing recombinant enzymes directly out of culture supernatant. Therefore, the depth filters were coated with different anionic and cationic polymer layers by Layer-by-Layer (LbL) technology. The immobilization behavior of the model enzyme Candida antarctica lipase B (CalB) was examined. Optimal conditions for lipase immobilization were found for anionic surfaces with Poly (allylamin hydrochlorid) (PAH)/Poly (sodium-4-styrene sulfonate) (PSS) coating in 20 mM acetate buffer pH 4. Stability studies showed that immobilized CalB is 1.7-fold more stable when storage is carried out in buffer at 4 °C, compared to storage in buffer at room temperature or storage after drying at 30 °C for 24 h. The calculated half-life period is 108 days until half of the activity was lost. Furthermore, the possibility of direct capture of the CalB either from sonicated culture broth (Escherichia coli) or from cell-free supernatant was tested. Filter blocking prevented the immobilization of lipase from sonicated culture broth, but immobilization from cell-free supernatant could be performed successfully at moderate biomass content (OD600 = 7.0).

Social Relationships of Dually Diagnosed Homeless Adults Following Enrollment in Housing First or Traditional Treatment Services.

OBJECTIVE: Strong and effective social support is a critical element of mental health recovery, yet social support is often lacking for adults experiencing homelessness. This study examines differences in the social networks of participants newly enrolled in programs that use either a Housing First (HF) approach (i.e., provides immediate access to permanent housing with ongoing consumer-driven support services) or a treatment first (TF) approach (i.e., traditional clinician-driven staircse model that requires temporary or transitional housing and treatment placements before accessing permanent housing). METHOD: We use a mixed-methods social network analysis approach to assess group differences of 75 individuals based on program type (HF or TF) and program retention. RESULTS: Quantitative results show that compared with TF, HF participants have a greater proportion of staff members in their network. TF participants are more likely than HF participants to maintain mixed-quality relationships (i.e., relationships with elements of support and conflict). As compared with participants who remain in a program, those who disengage from programs have a greater proportion of mixed relationships and relationships that grow distant. Qualitative analyses suggest that HF participants regard housing as providing a stable foundation from which to reconnect or restore broken relationships. However, HF participants are guarded about close relationships for fear of being exploited due to their newly acquired apartments. TF participants report that they are less inclined to develop new relationships with peers or staff members due to the time-limited nature of the TF programs. CONCLUSIONS: These findings suggest that HF participants are not more socially isolated than those in traditional care. Implications for practice, policy and future research are discussed.