Survival outcomes of patients with HER2/neu-positive breast cancer with germline BRCA mutations.

BACKGROUND: Breast cancer (BC) with germline BRCA1/2 mutations and their association with triple-negative BC has been thoroughly investigated. However, some carriers of BRCA1/2 mutations have human epidermal growth factor receptor 2 (HER2/neu)-positive BC, which has a different targeted therapy approach, and data are scarce for this patient population. The authors sought to characterize the clinical characteristics and outcomes of patients with HER2/neu-positive BC who had germline BRCA1/2 mutations. METHODS: This was a retrospective analysis of data from 1099 patients diagnosed with HER2/neu-positive BC who were screened for germline BRCA mutations between 1996 and 2022. Clinicopathologic features and survival rates were analyzed by BRCA mutation status. Univariate and multivariable Cox proportional hazards regression models were used to analyze the association between clinical variables and outcomes. RESULTS: Of 1099 patients with HER2/neu-positive BC, 73 (6.6%) tested positive for BRCA1/2 mutations. Age, race, and tumor characteristics did not differ between BRCA noncarriers and carriers. At a median follow-up of 78.6 months, the 5-year recurrence-free survival rate was 85% in BRCA carriers and 87% in noncarriers (p = .79), and the 5-year overall survival rate was 94% in BRCA carriers and 94% in noncarriers (p = .78). In a multivariable model, BRCA was not associated with recurrence-free survival (hazard ratio, 0.99; 95% confidence interval, 0.51-1.90; p = .96) or overall survival (hazard ratio, 0.83; 95% confidence interval, 0.33-2.07; p = .69). CONCLUSIONS: BRCA1/2 mutations occurred in 6.6% of patients with HER2/neu-positive BC and did not affect survival outcomes. Assessing the potential benefits of new treatment strategies, such as combining anti-HER2/neu therapies with poly(ADP-ribose) polymerase inhibitors, may lead to enhanced outcomes for these patients.

The Characterization of the Th1/Th2 Ratio in Moderate-Severe Alzheimer's Disease Patients and Its Response to an Aloe Polymannose-Based Dietary Supplement.

BACKGROUND: Alzheimer's disease (AD) is a leading killer of Americans, imparting a tremendous societal toll. Relationships between immune function and inflammation with cognition are well-established in AD, but the Th1/Th2 ratio of immune function is unknown. Describing the Th1/Th2 ratio and its relationship with cognition may shed light on the disease's clinical context. How the Th1/Th2 ratio responds to dietary supplementation is another unknown question in this population. OBJECTIVE: The objectives of the study were to: 1) characterize the Th1/Th2 ratio according to IL-2/IL-10, IFN-γ/IL-10, IL-2/IL-4, IFN-γ/IL-4, IL-2/TNF-α, and IFN-γ/TNF-α in subjects with moderate-to-severe AD and in comparison to healthy adults; 2) investigate the effect of an aloe polymannose multinutrient complex (APMC) dietary supplement on the Th1/Th2 ratios over 12 months; and 3) compare the changes in the Th1/Th2 ratios with the changes in cognition from baseline to 12 months. METHODS: Subjects consumed 2.5 g of the APMC four times per day for 12 months, and they were assessed on cognition and cytokines at baseline and 12 months. RESULTS: The Th1/Th2 ratios in AD patients were significantly higher than the healthy controls, and five of the six ratios decreased from baseline to 12 months follow-up (other than IL-2/TNF-α). Several significant relationships were noted between the changes in Th1/Th2 ratios with cognitive assessments. CONCLUSIONS: Our results showed an overall rebalancing of the Th1/Th2 ratio in response to APMC, these changes were related to improved cognition in subjects with moderate-to-severe AD, and the APMC supplement was safely tolerated.

Short-Term Biomarker Modulation Study of Dasatinib for Estrogen Receptor-Negative Breast Cancer Chemoprevention.

Objective: Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer. Materials and Methods: Women with a history of unilateral stage I, II, or III ER-negative breast cancer, having no active disease, and who completed all adjuvant therapies were eligible. Patients underwent baseline fine-needle aspiration (FNA) of the contralateral breast and serum collection for biomarker analysis and were randomized to receive either no treatment (control) or dasatinib at 40 or 80 mg/day for three months. After three months, serum collection and breast FNA were repeated. Planned biomarker analysis consisted of changes in cytology and Ki-67 on breast FNA, and changes in serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1, and IGF-binding protein 3. The primary objective was to evaluate changes in Ki-67 and secondary objective included changes in cytology in breast tissue and IGF-related serum biomarkers. Toxicity was also evaluated. Results: Twenty-three patients started their assigned treatments. Compliance during the study was high, with 86.9% (20/23) of patients completing their assigned doses. Dasatinib was well tolerated and no drug-related grade 3 and 4 adverse events were observed. Since only one patient met the adequacy criteria for the paired FNA sample, we could not evaluate Ki-67 level or cytological changes. No significant change in serum biomarkers was observed among the three groups. Conclusion: Dasatinib was well tolerated but did not induce any significant changes in serum biomarkers. The study could not fulfill its primary objective due to an inadequate number of paired FNA samples. Further, larger studies are needed to evaluate the effectiveness of Src inhibitors in breast cancer prevention.

Intensity of Depression Symptoms Is Negatively Associated with Catalase Activity in Master Athletes.

BACKGROUND: This study examined associations between scores of depression (DEPs), thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), and catalase activity (CAT) in master athletes and untrained controls. METHODS: Participants were master sprinters (MS, n = 24; 50.31 ± 6.34 year), endurance runners (ER, n = 11; 51.35 ± 9.12 year), untrained middle-aged (CO, n = 13; 47.21 ± 8.61 year), and young untrained (YU, n = 15; 23.70 ± 4.02 year). CAT, SOD, and TBARS were measured in plasma using commercial kits. DEPs were measured by the Beck Depression Inventory-II. An ANOVA, Kruskal-Wallis, Pearson's, and Spearman's correlations were applied, with a significance level of p ≤ 0.05. RESULTS: The CATs of MS and YU [760.4 U·µL 1 ± 170.1 U·µL 1 and 729.9 U·µL 1 ± 186.9 U·µL 1] were higher than CO and ER. The SOD levels in the YU and ER [84.20 U·mL-1 ± 8.52 U·mL-1 and 78.24 U·mL-1 ± 6.59 U·mL-1 (p < 0.0001)] were higher than CO and MS. The TBARS in CO [11.97 nmol·L-1 ± 2.35 nmol·L-1 (p < 0.0001)] was higher than in YU, MS and ER. MS had lower DEPs compared to the YU [3.60 ± 3.66 vs. 12.27 ± 9.27 (p = 0.0002)]. A negative correlation was found between CAT and DEPs for master athletes [r = -0.3921 (p = 0.0240)] and a weak correlation [r = -0.3694 (p = 0.0344)] was found between DEPs and the CAT/TBARS ratio. CONCLUSIONS: In conclusion, the training model of master sprinters may be an effective strategy for increasing CAT and reducing DEPs.

The Effects of HSOP on Cognition, Depression, and Activities of Daily Living in Older Adults with Cognitive Issues.

Context: Worldwide, large numbers of people have Alzheimer's disease and other forms of dementia, Parkinson's disease, and multiple sclerosis. Unfortunately, approved medications are highly ineffective and have costly, untoward side effects. One alternative for neurodegenerative disorders may be use of plasmalogens, a type of phospholipid. Objective: The objective of the study was to assess the effectiveness of a unique extract of plasmalogen from scallops for older adults with concerns either about memory and cognition or some form of actual memory loss or cognitive dysfunction. Design: This pilot study was a 90-day intervention. Setting: The study took place in the homes of participants. Participants: Participants were nine older adults from South Florida. Intervention: Participants were randomly assigned to one of two groups taking different amounts of Hokkaido Scallop Oil Plasmalogen (HSOP) per day: (1) one 0.5-mg capsule-five participants or (2) two 0.5-mg capsules-four participants. Outcome Measures: The participants completed the assessments at baseline and postintervention. To determine if HSOP would have an effect on cognitive function, participants completed the Mini-Mental State Examination (MMSE). To evaluate issues with activities and depressive symptoms or disorders, participants completed assessments with the Activities of Daily Living (ADL) and Independent Activities of Daily Living (IADL) and the Center for Epidemiological Survey-Depression (CESD). The outcome measures were compared from baseline to postintervention, and the differences were assessed for statistical significance with paired-samples t tests. Correlation coefficients were assessed at baseline and postintervention between age and the outcome measures as well. Results: The average score of the MMSE at baseline was 19.1 (SD = 9.7), the average score at postintervention improved to 21.9 (SD = 10.2), and the difference from baseline to postintervention was statistically significant (t(6) = -2.7, P = .04). All other changes on the outcome measures were insignificant. For the MMSE, five subjects improved, one subject remained the same, and one subject worsened. For the CESD, one subject worsened, and five subjects improved. For the IADL and ADL, five subjects remained the same, and one subject improved. At baseline and as expected, age was inversely correlated with the MMSE (r = -0.88, P = .002), and the MMSE was inversely correlated with the ADL (r = -0.93, P = .002). No other correlations were significant. The correlations at postintervention showed a similar pattern to those at baseline. Conclusions: The pilot study showed that HSOP is safe to take and may provide some benefits for cognitive function and depressive symptoms, based on the clinically relevant changes in the MMSE and CESD over the 90-day period. Given the lack of efficacy of treatments for people with age-associated memory and cognitive dysfunction, HSOP may provide a natural and safe alternative for those faced with such challenges.

Higher sirt1 is associated with a better body composition in master sprinters and untrained peers.

Sirt1 is an enzyme involved in several anti-aging pathways. Associations between Sirt1, age, and body fat (BF) were assessed in master sprinters (MS; n = 35; 50.25 ±5.93 yr.), untrained young non-athletes (UY; n = 32; 23.78 ±3.98 yr.), and untrained middle-aged (UMA; n = 24; 47.29 ±8.04 yr.). BF was assessed using a skinfold protocol, and Sirt1 was measured in plasma by using commercial kits. Sirt1 of MS (17.18 ±4.77 ng/mL) was higher than UMA (6.36 ±2.29 ng/mL; p<0.0001) and did not differ from UY (20.26 ±6.20 ng/mL). Relative BF of MS was lower than UMA (12.71 ±4.07% vs. 22.13 ±4.18%; p<0.0001). Sirt1 was negatively correlated with chronological age (r = -0.735; p<0.0001) when combining UY and UMA in the analysis. However, when Sirt1 of MS and UY was analyzed together, no significant relationship between Sirt1 and chronological age was observed (r = -0.243; p = 0.083). Sirt1 correlated inversely with BF (r = -0.743; p<0.0001) for UY and UMA. Stepwise multiple regression revealed that being either a young or master athlete and body adiposity are possible predictors of Sirt1 levels. MS and UY were associated with higher levels of Sirt1, while UMA and increased BF were associated with lower levels of this enzyme. The relationships among Sirt1, BF, and chronological age of young and middle-aged non-athletes were not statistically significant when the middle-aged participants were MS. These findings suggest possible links between Sirt1 and body composition, which may play roles in the rate of biological aging.HighlightsLower levels of Sirt1 are associated with higher body fat.Master athlete lifestyle seems to promote higher Sirt1 Levels.

The Effects of a Nutrition Education Program on Dietary Intake and Biomarkers in HIV+ Adults.

Background. People living with HIV (PLWH) have increased risk of cardiovascular disease (CVD). Dietary behavior modification may assist in the treatment of CVD, but the optimal dose of nutrition education is unknown. The current aim was to determine if a weekly 1-hour nutrition education program would improve multiple outcomes among PLWH. Methods. Participants (n = 62) were assessed on dietary intake, serum biomarkers, and physical characteristics at baseline and 3 months, and percent change was calculated. Participants were grouped into 3 attendance categories of the classes: none, fair, or good. Analyses of covariance were performed on the outcomes. Results. Calories, protein, fat, saturated fat, carbohydrate, sugar, added sugar, and glycemic load were significantly different (all P values <.05). Those who attended no class typically had increases in these variables versus those with fair or good attendance. High-density lipoprotein cholesterol (HDL-C; P = .006) and total cholesterol/HDL-C ratio (P = .083) were different, as those who attended no class or had fair attendance worsened, but those with good attendance improved. Conclusions. Several outcomes improved more so among those with good class attendance versus those with either fair or no attendance. Thus, an interactive nutrition education program may be an effective tool to help improve the health of PLWH.

Minimal sensor arrays for localizing objects using an electric sense.

Weakly electric fish encode perturbations in a self-generated electric field to sense their environment. Localizing objects using this electric sense requires that distance be decoded from a two-dimensionalelectric imageof the field perturbations on their skin. Many studies of object localization by weakly electric fish, and by electric sensing in a generic context, have focused on extracting location information from different features of the electric image. Some of these studies have also considered the additional information gained from sampling the electric image at different times, and from different viewpoints. Here, we take a different perspective and instead consider the information available at asinglepoint in space (i.e. a single sensor or receptor) at a single point in time (i.e. constant field). By combining the information from multiple receptors, we show that an object's distance can be unambiguously encoded by as few as four receptors at specific locations on a sensing surface in a manner that is relatively robust to environmental noise. This provides a lower bound on the information (i.e. receptor array size) required to decode the three-dimensional location of an object using an electric sense.

Are Physical Fitness and CRP Related to Framingham Risk Score in HIV+ Adults?

Background. People living with HIV (PLWH) have increased risk of cardiovascular disease (CVD). The Framingham Risk Score (FRS) predicts a 10-year CVD risk. Its relationships to physical fitness and C-reactive protein (CRP) are not well established. The current aim is to determine the links between FRS, physical fitness, and CRP in PLWH. Methods. Participants (n = 87) were assessed on multiple biomarkers. The FRS was calculated with the respective variables. Other variables that correlated significantly with FRS were entered into a regression equation to determine their relationship to FRS. Results. The FRS for men was more than twice that for women (12.8 vs 6.0, P < .001). Men were more fit than women, but most participants were not fit. Aerobic capacity was predictive of FRS in men, but not in women, and muscular strength was not predictive of FRS. Women had more than double the CRP compared with men (7.9 vs 3.5 mg/L, P < .01), and it was unrelated to FRS. Conclusions. In men, aerobic capacity was significantly predictive of FRS, but muscular strength and CRP were unrelated to FRS in both genders. These results do not conclusively demonstrate that physical fitness and CRP are related to FRS in PLWH.

Telomere Length, SIRT1, and Insulin in Male Master Athletes: The Path to Healthy Longevity?

Lower SIRT1 and insulin resistance are associated with accelerated telomere shortening. This study investigated whether the lifestyle of master athletes can attenuate these age-related changes and thereby slow aging. We compared insulin, SIRT1, and telomere length in highly trained male master athletes (n=52; aged 49.9±7.2 yrs) and age-matched non-athletes (n=19; aged 47.3±8.9 yrs). This is a cross-sectional study, in which all data were collected in one visit. Overnight fasted SIRT1 and insulin levels in whole blood were assessed using commercial kits. Relative telomere length was determined in leukocytes through qPCR analyses. Master athletes had higher SIRT1, lower insulin, and longer telomere length than age-matched non-athletes (p<0.05 for all). Insulin was inversely associated with SIRT1 (r=-0.38; p=0.001). Telomere length correlated positively with SIRT1 (r=0.65; p=0.001), whereas telomere length and insulin were not correlated (r=0.03; p=0.87). In conclusion, master athletes have higher SIRT1, lower insulin, and longer telomeres than age-matched non-athletes. Furthermore, SIRT1 was negatively associated with insulin and positively associated with telomere length. These findings suggest that in this sample of middle-aged participants reduced insulin, increased SIRT1 activity, and attenuation of biological aging are connected.

The effects of twenty-one nutrients and phytonutrients on cognitive function: A narrative review.

BACKGROUND AND AIM: Brain health is becoming more important to the average person as the number of people with cognitive impairments, such as Alzheimer's disease (AD), is rising significantly. The current Food and Drug Administration-approved pharmacotherapeutics for dementia neither cure nor halt cognitive decline; they just delay the worsening cognitive impairment. This narrative review summarizes the effects of nutrients and phytonutrients on cognitive function. METHODS: A comprehensive literature search of PubMed was performed to find clinical trials in humans that assessed the effects of nutrients and phytonutrients on cognitive function published in English between 2000 and 2021. Six independent reviewers evaluated the articles for inclusion in this review. RESULTS: Ninety-six articles were summarized in this narrative review. In total 21 categories of nutrients and phytonutrients were included, i.e., α-lipoic acid, Bacopa monnieri, B vitamins, cholinergic precursors, vitamin D, vitamin E, Ginkgo biloba, ginseng, lion's mane mushroom, N-acetyl cysteine, omega-3 fatty acids, aloe polysaccharides, Rhodiola rosea, rosemary, saffron, tart cherries, turmeric, wild yam, Withania somnifera, xanthines, and zinc. Particular noteworthy effects on cognition included memory, recollection, attention, intelligence, vocabulary, recognition, response inhibition, arousal, performance enhancement, planning, creative thinking, reaction time, vigilance, task switching, orientation to time, place, and person, reading, writing, comprehension, accuracy, learning, information processing speed, executive function, mental flexibility, daily functioning, decrease in mental fatigue, and freedom from distractibility. Some nutrients and phytonutrients also improved mood and contentedness and reduced anxiety and the need for caregiving. These effects are not completely consistent or ubiquitous across all patient populations or health statuses. Adverse effects were minimal or nonexistent. CONCLUSION: Due to the growing population of people with cognitive impairment and the lack of effective pharmacotherapeutics, it is prudent for those afflicted or their caregivers to find alternative treatments. Our narrative review shows that many of these nutrients and phytonutrients may be promising for treating some aspects of cognitive impairment, especially for people afflicted with AD. RELEVANCE FOR PATIENTS: As demonstrated in a number of clinical trials, healthy adults and patients with various health challenges (e.g., AD, mild cognitive impairment, multiple sclerosis, and Parkinson's disease) exhibiting a wide range of severity in cognitive defects would be best served to consider multiple nutrients and phytonutrients to improve aspects of their cognitive function.

The effects of twenty-four nutrients and phytonutrients on immune system function and inflammation: A narrative review.

BACKGROUND AND AIM: Recently, optimal immune function has become a primary focus of worldwide attention not only in the prevention of chronic disease but also as one strategy to reduce the severity of acute illness. Inflammation, a process largely controlled by the immune system, has long been studied and recognized for its role in chronic disease. Optimizing immune function or managing inflammation using individual nutrients and phytonutrients is not well understood by the average person. Thus, this narrative literature review summarizes many of the more recent findings about how certain nutrients and phytonutrients affect immune function and inflammation, and how they may best be utilized considering the growing worldwide interest in this topic. METHODS: A comprehensive literature search of PubMed was performed to find clinical trials in humans that assessed the effect of nutrients and phytonutrients on immune function and inflammation, in individuals with acute and chronic health conditions, published in English between 2000 and 2020. Two independent reviewers evaluated the articles for their inclusion. RESULTS: Eighty-seven articles were summarized in this narrative review. In total 24 nutrients and phytonutrients were included in the study, that is, acetyl-L-carnitine, Aloe vera polysaccharides, beta-glucans, bilberry, black seed oil, coenzyme Q10, curcumin (turmeric), frankincense, garlic, ginger, hydrolyzed rice bran, isoflavones, lipoic acid, mistletoe, N-acetyl cysteine, omega-3 fatty acids, resveratrol, selenium, shiitake mushroom and its derivatives, Vitamin B12, Vitamin C, Vitamin D3 (cholecalciferol), Vitamin E (d-alpha- and gamma-tocopherol), and zinc. Some of the noteworthy immune function and anti-inflammatory responses to these interventions included modulation of nuclear factor-Kappa B, tumor necrosis factor-a, interferon-g, interleukin-6, and CD4+ T cells, among others. These findings are not completely consistent or ubiquitous across all patient populations or health status. CONCLUSIONS: Based on this review, many nutrients and phytonutrients are capable of significantly modulating immune function and reducing inflammation, according to multiple biomarkers in clinical trials in different populations of adults with varying health statuses. Thus, dietary supplementation may serve as an adjunct to conventional pharmaceutical or medical therapies, but evaluation of risks and benefits for each person and health status is necessary. Additional larger studies are also needed to investigate the safety and efficacy of nutritional compounds in various health conditions, with emphases on potential drug-supplement interactions and clinical endpoints. RELEVANCE FOR PATIENTS: As demonstrated in the reviewed clinical trials, patients of various health challenges with a wide range of severity may benefit from select nutrients and phytonutrients to improve their immune function and reduce inflammation.

The Relationship between HIV Duration, Insulin Resistance and Diabetes Risk.

The risk of developing Type 2 Diabetes Mellitus in people living with HIV (PLWH) can be four times greater and can occur at an earlier age and even without the presence of obesity compared to those without HIV. Therefore, the purpose of this analytical cross-sectional study was to determine the relationship between HIV duration and glucose metabolism among PLWH. Eighty-two PLWH were categorized into shorter (≤15 years) or longer HIV duration (≥16 years) and then compared for differences in demographics, physical and clinical characteristics, biomarkers, and dietary intake. Compared to those with shorter HIV duration (n = 34), those with longer HIV duration (n = 48) were on average older (p = 0.02), reported lower consumption of alcohol (p = 0.05), had higher levels of homeostasis model assessment of insulin resistance (HOMA-IR, p = 0.02), were also more likely to be a woman (p = 0.06), and have higher levels of fasting insulin (p = 0.06). When adjusted for age and body weight, the levels of HOMA-IR and fasting insulin were higher (p = 0.02 and p = 0.04) with longer compared to shorter HIV duration, respectively. Longer exposure to HIV infection is associated with impaired insulin sensitivity. Continuing research aimed at the long-term effects of HIV infection and (antiretroviral therapy) is required.

The effectiveness of a community-based exercise program on depression symptoms among people living with HIV.

HIV is a worldwide public health issue affecting millions of individuals, and people living with HIV (PLWH) are often affected by depression. Nonetheless, exercise can prevent and treat depression among PLWH. The aim of the present study was to investigate the effect of exercise on depression symptoms in PLWH. Using a prospective single-arm trial, a semi-supervised community-based exercise intervention was offered 3 times/week for 12 weeks to PLWH (n = 52; age: 49 ± 6 years; HIV diagnosis: 19 ± 15 years). Participants were divided into compliant (≥1 exercise session/week) and non-compliant (<1 exercise session/week) groups according to their attendance in the intervention. Depression symptoms were assessed using the Beck Depression Inventory (BDI), and the change in BDI from baseline to post-intervention was assessed with an analysis of covariance, adjusted for demographics. The post-intervention BDI score was significantly lower (p = 0.027) for the compliant group compared to the non-compliant group, and the rate of improvement from moderate/severe symptoms of depression to minimal symptoms of depression was four times greater in the compliant group. In conclusion, a community-based exercise program may be effective in reducing depression symptoms among PLWH.

Low-Fat, High-Fiber Diet Reduces Markers of Inflammation and Dysbiosis and Improves Quality of Life in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: A high-fat diet has been associated with an increased risk of ulcerative colitis (UC). We studied the effects of a low-fat, high-fiber diet (LFD) vs an improved standard American diet (iSAD, included higher quantities of fruits, vegetables, and fiber than a typical SAD). We collected data on quality of life, markers of inflammation, and fecal markers of intestinal dysbiosis in patients with UC. METHODS: We analyzed data from a parallel-group, cross-over study of 17 patients with UC in remission or with mild disease (with a flare within the past 18 mo), from February 25, 2015, through September 11, 2018. Participants were assigned randomly to 2 groups and received a LFD (10% of calories from fat) or an iSAD (35%-40% of calories from fat) for the first 4-week period, followed by a 2-week washout period, and then switched to the other diet for 4 weeks. All diets were catered and delivered to patients' homes, and each participant served as her or his own control. Serum and stool samples were collected at baseline and week 4 of each diet and analyzed for markers of inflammation. We performed 16s ribosomal RNA sequencing and untargeted and targeted metabolomic analyses on stool samples. The primary outcome was quality of life, which was measured by the short inflammatory bowel disease (IBD) questionnaire at baseline and week 4 of the diets. Secondary outcomes included changes in the Short-Form 36 health survey, partial Mayo score, markers of inflammation, microbiome and metabolome analysis, and adherence to the diet. RESULTS: Participants' baseline diets were unhealthier than either study diet. All patients remained in remission throughout the study period. Compared with baseline, the iSAD and LFD each increased quality of life, based on the short IBD questionnaire and Short-Form 36 health survey scores (baseline short IBD questionnaire score, 4.98; iSAD, 5.55; LFD, 5.77; baseline vs iSAD, P = .02; baseline vs LFD, P = .001). Serum amyloid A decreased significantly from 7.99 mg/L at baseline to 4.50 mg/L after LFD (P = .02), but did not decrease significantly compared with iSAD (7.20 mg/L; iSAD vs LFD, P = .07). The serum level of C-reactive protein decreased numerically from 3.23 mg/L at baseline to 2.51 mg/L after LFD (P = .07). The relative abundance of Actinobacteria in fecal samples decreased from 13.69% at baseline to 7.82% after LFD (P = .017), whereas the relative abundance of Bacteroidetes increased from 14.6% at baseline to 24.02% on LFD (P = .015). The relative abundance of Faecalibacterium prausnitzii was higher after 4 weeks on the LFD (7.20%) compared with iSAD (5.37%; P = .04). Fecal levels of acetate (an anti-inflammatory metabolite) increased from a relative abundance of 40.37 at baseline to 42.52 on the iSAD and 53.98 on the LFD (baseline vs LFD, P = .05; iSAD vs LFD, P = .09). The fecal level of tryptophan decreased from a relative abundance of 1.33 at baseline to 1.08 on the iSAD (P = .43), but increased to a relative abundance of 2.27 on the LFD (baseline vs LFD, P = .04; iSAD vs LFD, P = .08); fecal levels of lauric acid decreased after LFD (baseline, 203.4; iSAD, 381.4; LFD, 29.91; baseline vs LFD, P = .04; iSAD vs LFD, P = .02). CONCLUSIONS: In a cross-over study of patients with UC in remission, we found that a catered LFD or iSAD were each well tolerated and increased quality of life. However, the LFD decreased markers of inflammation and reduced intestinal dysbiosis in fecal samples. Dietary interventions therefore might benefit patients with UC in remission. ClinicalTrials.gov no: NCT04147598.

RETRACTED ARTICLE: The Novel Effects of a Hydrolyzed Polysaccharide Dietary Supplement on Immune, Hepatic, and Renal Function in Adults with HIV in a Randomized, Double-Blind Placebo-Control Trial.

The primary objective of the study was to evaluate the effects of a hydrolyzed polysaccharide, rice bran arabinoxylan compound (RBAC), on immune, hepatic, and renal function in HIV + individuals. A six-month randomized double-blind placebo-controlled trial was utilized to conduct the intervention. Forty-seven HIV + participants on stable antiretroviral therapy were enrolled and randomly assigned to one of the two study conditions (n = 22 RBAC and n = 25 placebo) and consumed 3 gram/day of either compound for six months. Participants were assessed at baseline and 3 and 6 months follow-up for CD4+ and CD8+, liver enzymes, and kidney function. No side effects were reported, and liver and kidney markers nearly remained completely within normal limits. The percentage change in CD4+ was similar for the placebo (+2.2%) and RBAC (+3.1%) groups at 6 months follow-up. The percentage change in CD8+ count significantly decreased from baseline to 6 months in the RBAC group (-5.2%), whereas it increased in the placebo group (+57.8%; p = 0.04). The CD4+/CD8+ ratio improved clinically in the RBAC group from 0.95 (SD =0.62) at baseline to 1.07 (SD =0.11) at 6 months, whereas it declined in the placebo group from 0.96 (SD =0.80) at baseline to 0.72 (SD =0.59) at 6 months. Our results showed a statistically significant decrease in CD8+ count and a clinically significant increase in CD4+/CD8+ ratio for the RBAC group compared to the placebo group. Thus, the results of this study suggest that the immunomodulatory and antisenescent activities of RBAC are promising for the HIV population.

Dynamics of a neuronal pacemaker in the weakly electric fish Apteronotus.

The precise timing of neuronal activity is critical for normal brain function. In weakly electric fish, the medullary pacemaker network (PN) sets the timing for an oscillating electric organ discharge (EOD) used for electric sensing. This network is the most precise biological oscillator known, with sub-microsecond variation in oscillator period. The PN consists of two principle sets of neurons, pacemaker and relay cells, that are connected by gap junctions and normally fire in synchrony, one-to-one with each EOD cycle. However, the degree of gap junctional connectivity between these cells appears insufficient to provide the population averaging required for the observed temporal precision of the EOD. This has led to the hypothesis that individual cells themselves fire with high precision, but little is known about the oscillatory dynamics of these pacemaker cells. As a first step towards testing this hypothesis, we have developed a biophysical model of a pacemaker neuron action potential based on experimental recordings. We validated the model by comparing the changes in oscillatory dynamics produced by different experimental manipulations. Our results suggest that this relatively simple model can capture a large range of channel dynamics exhibited by pacemaker cells, and will thus provide a basis for future work on network synchrony and precision.

Cardiovascular, endothelial function, and immune markers in response to treatment with a polysaccharide in HIV+ adults in a randomized, double-blind placebo-controlled trial.

BACKGROUND AND AIM: Given the ongoing problems of hypertension and endothelial dysfunction in the HIV population, the primary objective of the study was to assess the cardiovascular, endothelial function, and immune markers in response to rice bran arabinoxylan compound (RBAC) treatment in a sample of HIV+ adults on antiretroviral therapy (ART). STUDY DESIGN: A randomized, double-blind placebo-controlled trial of 6 months was used to execute the study. MATERIALS AND METHODS: Forty-seven subjects were enrolled and randomly assigned to one of two study conditions (n=22 RBAC and n=25 placebo) for 6 months with assessments at baseline and 3 and 6 months. A multivariate repeated measures analysis of variance model was used to assess the differences between RBAC and placebo groups in cardiovascular (systolic blood pressure), endothelial function (skin blood flow in response to nitric oxide), and immune (CD4+ cell count) markers from baseline to 6 months. RESULTS: The effect of treatment (RBAC versus placebo) was significant (Wilks' λ=0.92, F[3, 102]=3.07, P=0.03). The effect of time was significant (Wilks' λ=0.10, F[2, 103]=474.6, P<0.001). The overall interaction between treatment and time was significant (Wilks' λ=0.92, F[2, 103]=4.58, P=0.01). Time contrasts showed that a difference in the overall dependent variable did not occur from baseline to 3 months (F[1, 104]=2.7, P=0.10), marginally occurred from baseline to 6 months (F[1, 104]=3.2, P=0.08), and was significant from 3 to 6 months (F[1, 104]=6.43, P=0.01). CONCLUSIONS: The overall significant interaction suggests varying responses in the dependent variables between RBAC and placebo over time, which is being driven by systolic blood pressure, as it decreased in the RBAC group, but increased in the placebo group. In addition, CD4+ manifested a non-significant increase from baseline to 3 months then decreased from 3 to 6 months in the RBAC group, whereas it decreased at 3 months followed by a slight increase at 6 months in the placebo group. Skin blood flow in response to nitric oxide improved non-significantly overall in both groups, but worsened from 3 to 6 months in the placebo group. Thus, RBAC treatment may contribute to modest short-term improvements in systolic blood pressure, endothelial function, and CD4+ cell count, which could help improve the overall health profile of HIV+ adults. RELEVANCE FOR PATIENTS: Persons with HIV on ART suffer disproportionately from hypertension and endothelial dysfunction compared to the non-infected population, and conventional medical therapy does not alleviate these issues. RBAC is a safe, low-risk alternative that may help to improve the overall quality of life of these patients through modest improvements in these biomarkers plus CD4+ cell count.

Randomized Trial of Combined Aerobic, Resistance, and Cognitive Training to Improve Recovery From Stroke: Feasibility and Safety.

Background Physical exercise and cognitive training have been recommended to improve cognitive outcomes poststroke, but a multifaceted strategy including aerobic, resistance, and cognitive training to facilitate poststroke recovery has not been investigated. We aimed to assess the feasibility, adherence, and safety of a combined aerobic, resistance, and cognitive training intervention (CARET+CTI) after stroke. Methods and Results We prospectively randomized patients presenting with recent stroke to a comparison of a supervised 12-week CARET+CTI program and a control group receiving sham CARET+CTI. Participants were scheduled for 3 weekly CARET and CTI sessions. All participants underwent pre- and postintervention assessments of strength, endurance, and cognition. The primary outcomes were feasibility and adherence, defined as the ratio of scheduled and observed visits, and safety. We enrolled 131 participants, of whom 37 withdrew from the study. There were 17 (20%) withdrawals in the CARET+CTI and 20 (44%) in the control group. The observed-over-expected visit ratio was significantly higher in the intervention than in the control group (0.74±0.30 versus 0.54±0.38; P=0.003). A total of 99 adverse events were reported by 59 participants, none of which were serious and related to the intervention. Greater gains in physical, cognitive, and mood outcomes were found in the CARET+CTI group than in the control group, but were not statistically significant after adjustments. Conclusions A CARET+CTI intervention, after stroke, is safe, feasible, and has satisfactory participant adherence over 12 weeks. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT02272426.

Relationship between brain-derived neurotrophic factor and immune function during dietary supplement treatment of elderly with Alzheimer's dementia.

BACKGROUND AND AIM: The objective of the present study was to investigate the relationships among pro-brain-derived neurotrophic factor (BDNF) and mature BDNF and immune functioning during aloe polymannose multinutrient complex (APMC) treatment in persons with moderate to severe Alzheimer's dementia (AD). MATERIALS AND METHODS: An open-label trial of 12 months was used to execute the study. Thirty-four adults with AD were enrolled and consumed four teaspoons/day of APMC for 12 months. Subjects were assessed at baseline and 12 months follow-up for proBDNF and BDNF and cytokines, growth factors, T-cell and B-cell subsets, and complete blood count to measure immune functioning. All biomarkers were intercorrelated. RESULTS: Several relationships were identified between proBDNF, BDNF, and BDNF/proBDNF ratio and immune function at 12 months, particularly BDNF with vascular endothelial growth factor (VEGF) (r=0.55, P=0.03), epidermal growth factor (EGF) (r=0.74, P=0.001), and CD95+CD3+ (%) (r=-0.64, P=0.03) and proBDNF with VEGF (r=0.64, P=0.02), EGF (r=0.86, P<0.001), and CD16+56+ (%) (r=-0.78, P<0.01). Other correlations were noted for various immune function variables with BDNF, proBDNF, and/or BDNF/proBDNF ratio at baseline and 12 months. Dichotomizing subjects on BDNF above and below 5000 pg/mL revealed additional relationships with platelets and neutrophils. CONCLUSIONS: The associations between BDNF and proBDNF and various immune markers, such as VEGF, EGF, and CD95+CD3+ ratio, provide insight into the link between neurological function and the immune system. These relationships were even stronger in response to APMC treatment, which lends support to previous findings showing improved immune function after dietary supplementation. RELEVANCE FOR PATIENTS: AD patients have conventional treatment options with limited efficacy for counteracting the deleterious effects of the disease on neurological function. The link between neurological and immune function has been understudied in this population. Overall, our results showed a significant beneficial relationship between immune and neurological function, particularly in response to 12 months of treatment with an all-natural polysaccharide-based dietary supplement that is a known immunomodulator. Thus, the use of this dietary supplement may benefit these patients by simultaneously improving immune and neurological function.