Background/Objectives Vision-based speed of processing (VSOP) training is a promising cognitive intervention for older adults. However, it is unknown whether VSOP training can affect cognitive processing in individuals at high risk for dementia. Here, we examined cognitive and neural effects of VSOP training in older adults with amnestic mild cognitive impairment (aMCI) and contrasted those effects with an active control (mental leisure activities; MLA). Design A randomized single-blinded controlled pilot trial. Setting An academic medical center. Participants Twenty-one participants with aMCI. Intervention A 6-week computerized VSOP training. Measurements Multiple cognitive processing measures, instrumental activities of daily living (IADL), and two key resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN). Results We found that, compared to MLA control, VSOP training led to significant improvements in trained (processing speed and attention: F1,19 = 6.61, Partial η2 = 0.26, p = .019) and untrained cognitive domains (working memory: F1,19 = 7.33, Partial η2 = 0.28, p = .014; IADL: F1,19 = 5.16, Partial η2 = 0.21, p = .035), and protective maintenance in DMN (F1, 9 = 14.63, Partial η2 = 0.62, p = .004). Additionally, VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z = −2.37, p = .018). Conclusion We identified both target and transfer effects of VSOP training and revealed links between VSOP training and two key neural networks associated with aMCI. These findings highlight the potential of VSOP training to slow cognitive decline in aMCI. Further delineation of mechanisms underlying VSOP-induced plasticity is necessary to understand in what populations and conditions such training may be most effective.

IntroductionImpaired healing and non-union of skeletal fractures is a major public health problem, with morbidity exacerbated in patients with diabetes mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million US adults, with >90% having obesity-related type 2 DM (T2DM). While fracture healing in type 1 DM (T1DM) has been studied using animal models, an investigation into delayed healing in an animal model of T2DM has not yet been performed.MethodsMale C57BL/6J mice at 5 weeks of age were placed on either a control lean diet or an experimental high-fat diet (HFD) for 12 weeks. A mid-diaphyseal open tibia fracture was induced at 17 weeks of age and a spinal needle was used for intra-medullary fixation. Mice were sacrificed at days 7, 10, 14, 21, 28, and 35 for micro-computed tomography (μCT), histology-based histomorphometry and molecular analyses, and biomechanical testing.ResultsHFD-fed mice displayed increased body weight and impaired glucose tolerance, both characteristic of T2DM. Compared to control mice, HFD-fed mice with tibia fractures showed significantly (p<0.001) decreased woven bone at day 28 by histomorphometry and significantly (p<0.01) decreased callus bone volume at day 21 by μCT. Interestingly, fracture calluses contained markedly increased adiposity in HFD-fed mice at days 21, 28, and 35. HFD-fed mice also showed increased PPARγ immunohistochemical staining at day 14. Finally, calluses from HFD-fed mice at day 35 showed significantly (p<0.01) reduced torsional rigidity compared to controls.DiscussionOur murine model of T2DM demonstrated delayed fracture healing and weakened biomechanical properties, and was distinctly characterized by increased callus adiposity. This suggests altered mesenchymal stem cell fate determination with a shift to the adipocyte lineage at the expense of the osteoblast lineage. The up-regulation of PPARγ in fracture calluses of HFD-fed mice is likely involved in the proposed fate switching.

Although mucosal immune responses are critical for protection of hosts from clinical illness and even mortality caused by mucosal pathogens, the molecular mechanism of mucosal immunity, which is independent of systemic immunity, remains elusive. To explore the mechanistic basis of mucosal protective immunity, gene transcriptional profiling in mucosal tissues was evaluated after the primary and secondary immunization of animals with an attenuated avian infectious bronchitis virus (IBV), a prototype of Coronavirus and a well-characterized mucosal pathogen. Results showed that a number of innate immune factors including toll-like receptors (TLRs), retinoic-acid-inducible gene-1 (RIG-1), type I interferons (IFNs), complements, and interleukin-1 beta (IL-1beta) were activated locally after the primary immunization. This was accompanied or immediately followed by a potent Th1 adaptive immunity as evidenced by the activation of T-cell signaling molecules, surface markers, and effector molecules. A strong humoral immune response as supported by the significantly up-regulated immunoglobulin (Ig) gamma chain was observed in the absence of innate, Th1 adaptive immunity, or IgA up-regulation after the secondary immunization, indicating that the local memory response is dominated by IgG. Overall, the results provided the first detailed kinetics on the molecular basis underlying the development of primary and secondary mucosal immunity. The key molecular signatures identified may provide new opportunities for improved prophylactic and therapeutic strategies to combat mucosal infections.

Objective Illness uncertainty is a significant source of psychological distress that affects cancer patients' quality of life (QOL). Mishel's uncertainty in illness theory (UIT) proposes that illness uncertainty influences an individual's use of coping strategies, and directly and indirectly influences their QOL. This study tested the relationships depicted in the adapted UIT in cancer patients. Methods This cross‐sectional study is a secondary analysis of the baseline data from a randomized clinical trial (N = 263 prostate cancer patients). Patients were diagnosed with localized (64.6%), biochemical recurrent (12.6%), or advanced (22.8%) prostate cancer. Uncertainty, coping (avoidant and active coping strategies), and QOL (physical and mental well‐being) were measured using the Mishel's uncertainty of illness scale, Brief COPE, and the Medical Outcomes Study 12‐item short form (SF‐12), respectively. We used path analysis to achieve the research aim. Results Patients' illness uncertainty directly, negatively influenced their physical well‐being (P < .001) and mental well‐being (P < .05). Patients' illness uncertainty was positively related to their avoidant coping strategies (P < .001). Patients' active and avoidant coping strategies influenced their mental well‐being (P < .001). Uncertainty also negatively influenced mental well‐being through avoidant coping strategies. The model had excellent fit to the data. Conclusions Our findings have indicated the potential of improving QOL by decreasing illness uncertainty and reducing avoidant coping strategies. Future research is needed to better understand the complex relationships between illness uncertainty, coping strategies, and domains of QOL among patients with different types of cancer using longitudinal research.