No abstract

Peer-delivered mental health models may hold important benefits for family members, yet their prevalence, components, and outcomes are unknown. We conducted a review of peer-delivered services for families of children and adults with mental health problems. Randomized studies of interventions published between 1990-2014 were included if the intervention contained a component for family members and examined familial outcomes. Of 77 studies that were assessed for their eligibility, six met criteria. Familial components included coping and parenting skills, knowledge about mental health, and emotional support. Outcomes were uneven, although significant improvements in family functioning, knowledge about mental illness, parental concerns about their child, and parenting skills were associated with the intervention. Peer-delivered services for family members may have important benefits to family members and individuals with mental health problems; however, the research base remains thin. A research agenda to develop and examine these models is discussed.

Private tuberculosis care providers were less compliant with CDC-ATS guidelines than public tuberculosis care providers. Because providers did not follow the recommended treatment guidelines universally, it is advised that all tuberculosis care providers in Virginia would benefit from increased education regarding adequate treatment regimens for tuberculosis and the prevention of multidrug-resistant tuberculosis.

Macrocycles have several advantages over small-molecule drugs when it comes to addressing specific protein-protein interactions as therapeutic targets. Herein we report the synthesis of seven new cyclic peptide molecules and their biological activity. These macrocycles were designed to understand how moving an N-methyl moiety around the peptide backbone impacts biological activity. Because the lead non-methylated structure inhibits the oncogenic regulator heat-shock protein 90 (Hsp90), two of the most potent analogues were evaluated for their Hsp90 inhibitory activity. We show that incorporating an N-methyl moiety controls the conformation of the macrocycle, which dramatically impacts cytotoxicity and binding affinity for Hsp90. Thus, the placement of an N-methylated amino acid within a macrocycle generates an unpredictable change to the compound's conformation and hence biological activity.

Histone deacetylase enzymes (HDACs) are potential targets for the treatment of cancer and other diseases, but it is challenging to design isoform-selective agents. In this work, we created new analogs of two established but non-selective HDAC inhibitors. We decorated the central linker chains of the molecules with specifically positioned fluorine atoms in order to control the molecular conformations. The fluorinated analogs were screened against a panel of 11 HDAC isoforms, and minor differences in isoform selectivity patterns were observed.