Background:Diabetic neuropathy is a common and often debilitating condition for which available treatments are limited. Because a low-fat plant-based diet has been shown to improve glycemic control in individuals with type 2 diabetes, we hypothesized that such a diet would reduce painful symptoms of diabetic neuropathy.Methods:In this 20-week pilot study, individuals with type 2 diabetes and painful diabetic neuropathy were randomly assigned to two groups. The intervention group was asked to follow a low-fat, plant-based diet, with weekly classes for support in following the prescribed diet, and to take a vitamin B12 supplement. The control group was asked to take the same vitamin B12 supplement, but received no other intervention. At baseline, midpoint and 20 weeks, clinical, laboratory and questionnaire data were collected. Questionnaires included an analog ‘worst pain' scale, Michigan Neuropathy Screening Instrument, global impression scale, Short Form McGill Pain Questionnaire, Neuropathy Total Symptom Score, a weekly pain diary and Norfolk Quality of Life Questionnaire.Results:After 20 weeks, body weight change with the intervention was −6.4 kg (95% confidence interval (CI) −9.4 to −3.4, P<0.001) in an effect size analysis. Electrochemical skin conductance in the foot improved by an average of 12.4 microseimens (95% CI 1.2–23.6, P=0.03) with the intervention in an effect size analysis. The between-group difference in change in pain, as measured by the McGill pain questionnaire, was −8.2 points (95% CI −16.1 to −0.3, P=0.04). Michigan Neuropathy Screening Instrument questionnaire score change was −1.6 points (95% CI −3.0 to −0.2, P=0.03).Conclusions:Improvements were seen in some clinical and pain measures. This pilot study suggests the potential value of a plant-based diet intervention, including weekly support classes, for treating painful diabetic neuropathy.
Ribosomes are self-assembling macromolecular machines that translate DNA into proteins, and an understanding of ribosome biogenesis is central to cellular physiology. Previous studies on the E. coli 30S subunit suggest that ribosome assembly occurs via multiple, parallel pathways rather than through a single rate-limiting step, but little mechanistic information is known about this process. Discovery Single-particle Profiling (DSP), an application of time resolved electron microscopy, was used to obtain over 1 million snapshots of assembling 30S subunits, identify and visualize the structures of 14 assembly intermediates, and monitor the population flux of these intermediates over time. DSP results were integrated with mass spectrometry data to construct the first ribosome assembly mechanism that incorporates binding dependencies, rate constants, and structural characterization of populated intermediates.
Increased prevalence of traumatic brain injury (TBI) has been associated with service members and veterans who completed combat deployments in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Management of persistent post-concussive symptoms (PCS) has been a challenge to healthcare providers throughout the Military and Veterans Healthcare Systems, as well as civilian healthcare providers, due in part to the chronic nature of symptoms, co-occurrence of behavioral health disorders such as depression, Posttraumatic Stress Disorder (PTSD), and substance use disorders, and fear of a potential stigma associated with psychiatric diagnoses and behavioral health treatment(s). This systematic review examined non-pharmacologic behavioral health interventions and cognitive rehabilitation interventions for PCS in military service members and veterans with a history of mild TBI (mTBI). Six electronic databases were searched with specific term limitations, identifying 121 citations. Ultimately, 19 articles met criteria for inclusion in this systematic review. Studies were broadly categorized into four subtypes: psychoeducational interventions, cognitive rehabilitation, psychotherapeutic approaches, and integrated behavioral health interventions for PCS and PTSD. The review provides an update of the empirical evidence for these four types of interventions for PCS in active duty service members and veterans. Recommendations for future research are discussed, including the need to expand and improve the limited evidence basis on how to manage persistent post-concussive symptoms in this population.
Cognitive disorders of later life are potentially devastating. To estimate the relationship between saturated and trans fat intake and risk of cognitive disorders. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies reporting saturated or trans fat intake and incident dementia, Alzheimer's disease (AD), or mild cognitive impairment (MCI) or cognitive decline. Only observational studies met the inclusion criteria: 4 for AD or other dementias, 4 for MCI, and 4 for cognitive decline. Saturated fat intake was positively associated with AD risk in 3 of 4 studies, whereas the fourth suggested an inverse relationship. Saturated fat intake was also positively associated with total dementia in 1 of 2 studies, with MCI in 1 of 4 studies, and with cognitive decline in 2 of 4 studies. Relationships between trans fat intake and dementia were examined in 3 reports with mixed results. Several, although not all, prospective studies indicate relationships between saturated and trans fat intake and risk of cognitive disorders.
Quantitative proteomic mass spectrometry involves comparison of the amplitudes of peaks resulting from different isotope labeling patterns, including fractional atomic labeling and fractional residue labeling. We have developed a general and flexible analytical treatment of the complex isotope distributions that arise in these experiments, using Fourier transform convolution to calculate labeled isotope distributions and least-squares for quantitative comparison with experimental peaks. The degree of fractional atomic and fractional residue labeling can be determined from experimental peaks at the same time as the integrated intensity of all of the isotopomers in the isotope distribution. The approach is illustrated using data with fractional 15 N-labeling and fractional 13 C-isoleucine labeling. The least-squares Fourier transform convolution approach can be applied to many types of quantitive proteomic data, including data from stable isotope labeling by amino acids in cell culture and pulse labeling experiments.Stable isotope labeling in cells coupled with mass spectrometry has many important applications in the analysis of protein expression, modification, turnover, and metabolism. 1 Cells and organisms can be isotopically labeled by supplying labeled precursors in the form of nutrients such as amino acids, glucose, and ammonia. These labeled precursors are incorporated into proteins, whose resulting isotope labeling patterns reflect their abundance and the dynamics of protein synthesis and turnover. The era of quantitative proteomics began with experiments where mixtures of unlabeled control cells and 15 N-labeled or isotope depleted test cells were quantitatively analyzed to determine protein expression and phosphorylation levels. 2,3 More recently, the SILAC technique was developed based on specific amino acid labeling of cells for quantitative analysis of protein expression, modification, and turnover. 4-6The two basic classes of quantitative metabolic labeling approaches are the stable isotope labeling by amino acids in cell culture (SILAC) experiments and pulse labeling experiments, both of which have been implemented in a variety of ways. 7 In the SILAC method, independent samples are prepared with different labeling patterns that are mixed prior to mass spectrometry analysis. For pulse labeling experiments, labels that are added to the growth medium are taken up to metabolically label the proteome, which generates fractionally enriched proteins from a
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