Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer.

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

The role of microglia in 67NR mammary tumor-induced suppression of brain responses to immune challenges in female mice.

It is poorly understood how solid peripheral tumors affect brain neuroimmune responses despite the various brain-mediated side effects and higher rates of infection reported in cancer patients. We hypothesized that chronic low-grade peripheral tumor-induced inflammation conditions microglia to drive suppression of neuroinflammatory responses to a subsequent peripheral immune challenge. Here, Balb/c murine mammary tumors attenuated the microglial inflammatory gene expression responses to lipopolysaccharide (LPS) and live Escherichia coli (E. coli) challenges and the fatigue response to an E. coli infection. In contrast, the inflammatory gene expression in response to LPS or a toll-like receptor 2 agonist of Percoll-enriched primary microglia cultures was comparable between tumor-bearing and -free mice, as were the neuroinflammatory and sickness behavioral responses to an intracerebroventricular interleukin (IL)-1ß injection. These data led to the hypothesis that Balb/c mammary tumors blunt the neuroinflammatory responses to an immune challenge via a mechanism involving tumor suppression of the peripheral humoral response. Balb/c mammary tumors modestly attenuated select circulating cytokine responses to LPS and E. coli challenges. Further, a second mammary tumor/mouse strain model (E0771 tumors in C57Bl/6 mice) displayed mildly elevated inflammatory responses to an immune challenge. Taken together, these data indicate that tumor-induced suppression of neuroinflammation and sickness behaviors may be driven by a blunted microglial phenotype, partly because of an attenuated peripheral signal to the brain, which may contribute to infection responses and behavioral side effects reported in cancer patients. Finally, these neuroimmune effects likely vary based on tumor type and/or host immune phenotype.

Electrical and memory properties of Si3N4 MIS structures with embedded Si nanocrystals.

Memory structures with an embedded sheet of separated Si nanocrystals were prepared by low pressure chemical vapour deposition using a Si3N4 control layer and different Si2O2 or Si3N4 tunnel layers. It was obtained that Si nanocrystals improve the charging behaviour of the MNOS structures. Memory window width of 1.3 V and 2.0 V were obtained for pulse amplitudes of +/-9 V and +/-10 V, 100 ms, respectively. The extrapolated memory window after 10 years is about 15% of its initial value.

Formation of ge nanocrystals in SiO2 by electron beam evaporation.

Ge nanocrystals were formed by electron beam evaporation on SiO2 covered Si substrates. The size and distribution of the nanocrystals were studied by atomic force microscopy, scanning electron microscopy and cross-sectional transmission electron microscopy. Dependencies of the nanocrystal size, of the nanocrystal surface coverage, and sheet resistance obtained by van der Pauw method of the Ge layer have been found on the evaporation time. The suggested growth mechanism for the formation of nanocrystals is the Volmer-Weber type. The sheet resistance exhibited a power dependence on the nanocrystal size.

Feasibility of gait training for acute stroke patients using FNS with implanted electrodes.

Following stroke, many patients do not regain a normal, safe gait pattern even after receiving conventional physical therapy. One promising technique is functional neuromuscular stimulation (FNS) with intramuscular (IM) electrodes (FNS-IM). Five subjects were admitted into the study at 3 weeks to 3 months following the stroke. For each subject, electrodes were placed intramuscularly at the motor point of up to seven lower extremity paretic muscles. Subjects were treated for 6 months, twice weekly with FNS-IM for exercise and gait training. The stimulator and software provided individualized stimulation patterns, with flexible stimulus parameters and activation timings of multiple muscles. Outcome measures were active joint movement, coordination (Fugl-Meyer scale), balance (Tinetti scale), gait (Tinetti scale), activities of daily living (functional independence measure), and therapist and subject satisfaction (survey instrument). Subjects tolerated well the placement of IM electrodes with no adverse effects, and subjects lost no conventional rehabilitation time. Therapists and subjects were satisfied with the FNS-IM system as a rehabilitation tool. Post treatment, subjects demonstrated improvements in impairment and disability in active joint movement, coordination, balance, gait and activities of daily living. Considered together with prior research for chronic stroke subjects, this research suggests that FNS-IM can be successfully and efficaciously utilized for gait training for those with acute stroke.

Neuromuscular stimulation for upper extremity motor and functional recovery in acute hemiplegia.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the efficacy of neuromuscular stimulation in enhancing the upper extremity motor and functional recovery of acute stroke survivors. METHODS: Forty-six stroke survivors admitted to an inpatient rehabilitation unit were randomly assigned to receive either neuromuscular stimulation or placebo. Twenty-eight subjects completed the study. The treatment group received surface neuromuscular stimulation to produce wrist and finger extension exercises. The control group received placebo stimulation over the paretic forearm. All subjects were treated 1 hour per day, for a total of 15 sessions. Outcomes were assessed in a blinded manner with the upper extremity component of the Fugl-Meyer Motor Assessment and the self-care component of the Functional Independence Measure at pretreatment, after treatment, and at 4 and 12 weeks after treatment. RESULTS: The treatment subjects and control subjects had comparable baseline characteristics. Parametric analyses revealed significantly greater gains in Fugl-Meyer scores for the treatment group after treatment (13.1 versus 6.5; P=0.05), at 4 weeks after treatment (17.9 versus 9.7; P=0.05), and at 12 weeks after treatment (20.6 versus 11.2; P=0.06). Functional Independence Measure scores were not different between groups at any of the time periods (P>0.10). CONCLUSIONS: Data suggest that neuromuscular stimulation enhances the upper extremity motor recovery of acute stroke survivors. However, the sample size in this study was too small to detect any significant effect of neuromuscular stimulation on self-care function.