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Acute beetroot juice reduces blood pressure in young Black and White males but not females.
Grosicki, GJ, Flatt, AA, Cross, BL, Vondrasek, JD, Blumenburg, WT, Lincoln, ZR, Chall, A, Bryan, A, Patel, RP, Ricart, K, et al
Redox biology. 2023;63:102718
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Cardiovascular (CV) disease is the leading cause of death in the United States. Out of all ethnic groups, CV disease is particularly common in black Americans. High blood pressure (BP) is one of the main contributors to CV disease, and black Americans exhibit a disproportionally higher incident rate of high BP when compared to other ethnic groups. Partly this is due to genetic and physiological differences, yet is also influenced by social, socioeconomic, and environmental factors. One physiological difference that may contribute to higher BP in black adults appears to be a reduced availability of nitric oxide (NO). NO is a gas that is abundant in the human body. It regulates vascular tone and elasticity of the arteries, and therefore helps to manage blood pressure. Nitrates that occur in foods can be converted to NO and thus contribute to NO levels in the body. Beetroot juice (BRJ) is rich in nitrates. This study examined whether BRJ supplementation can reduce resting BP and cardiovascular reactivity in adults. The randomized, placebo-controlled, crossover-design study was completed by 18 black and 20 white young adults, male and female, with an average age of 21. The study monitored heart rate, BP and arterial stiffness in a variety of settings. The study also assessed socioeconomic status, perceived discrimination, sleep and dietary intake. The main findings from this investigation were that despite young black adults having higher resting BP, acute BRJ supplementation reduced the pressure to a similar extent in young black and white adults, but primarily in males. This reduction correlated with increased levels of circulating nitrites. However, acute BRJ supplementation did not influence resting arterial stiffness. The result also highlighted previously seen racial differences relating to social determinants of health and lifestyle, which may contribute to the elevated BP values seen in black participants. The study demonstrated that dietary nitrate from beetroot juice has the potential to be a cost-effective blood pressure-lowering strategy for young black and white males. Yet the findings also highlighted the complex interplay of social, lifestyle, and underlying physiological factors that influence racial differences when it comes to CV health
Abstract
A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.
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Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation.
Mitchell, CM, Ma, N, Mitchell, AJ, Wu, MC, Valint, DJ, Proll, S, Reed, SD, Guthrie, KA, Lacroix, AZ, Larson, JC, et al
American journal of obstetrics and gynecology. 2021;225(2):159.e1-159.e15
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Close to half of postmenopausal women report bothersome symptoms of vulvar, vaginal or urinary discomfort collectively referred to as genitourinary syndrome of menopause. These are associated with negative impacts on sexual function and quality of life. The study’s hypothesis is that vaginal microbiota and inflammatory markers (i.e. increased Lactobacillus abundance and decreased inflammation) would differ significantly between women with the largest reductions in most bothersome symptom (MBS) severity compared to those women with smaller reductions, regardless of treatment arm. This study is a sub-study (secondary analysis of samples collected) of the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Vaginal Health Trial. Of 302 women randomised in the parent trial, 120 were enrolled in this sub-study. Results did not show significant associations between change in MBS severity and vaginal microbiota composition, Lactobacillus dominance, soluble immune markers, vaginal maturation index or vaginal fluid metabolites. Authors conclude that efforts to change superficial features of the vaginal microenvironment, such as pH or Lactobacillus colonization, may not address the primary underlying mechanism that leads to postmenopausal vaginal discomfort and is unlikely to be effective in relieving moderate to severe bothersome symptoms.
Abstract
BACKGROUND Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. OBJECTIVE To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve. STUDY DESIGN This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm. RESULTS Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm. CONCLUSION Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.
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Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 at a Tertiary Care Medical Center in New York City.
Chao, JY, Derespina, KR, Herold, BC, Goldman, DL, Aldrich, M, Weingarten, J, Ushay, HM, Cabana, MD, Medar, SS
The Journal of pediatrics. 2020;223:14-19.e2
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Epidemiologic studies have consistently demonstrated that children are at lower risk of developing severe symptoms or critical illness compared with adults. The aim of this study was to describe the clinical profiles and risk factors for critical illness in hospitalised children and adolescents with COVID-19. The study is a retrospective review of 67 children aged between 1 month to 21 years with COVID-19 from a single tertiary care children’s hospital. Out of the 44 children who tested positive, 33 (72%) were admitted to the general paediatric medical unit and 13 (28%) to the paediatric intensive care unit (PICU). Results showed that patients admitted to the PICU were noted to have more severe symptoms and markers of inflammatory response. The most common symptoms at admission were cough (63%) and fever (60.9%). Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. Authors conclude that their study showed a higher rate of PICU admission per hospitalization (28.2%), which they believe may be a reflection of a variety of social determinants that influence health outcomes.
Abstract
OBJECTIVE To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with coronavirus disease 2019 (COVID-19). STUDY DESIGN Children 1 month to 21 years of age with COVID-19 from a single tertiary care children's hospital between March 15 and April 13, 2020 were included. Demographic and clinical data were collected. RESULTS In total, 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (P = .99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (P < .05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (P = .0001) and were more likely to have received Remdesivir through compassionate release (P < .05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) patients in the PICU. Acute respiratory distress syndrome was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.
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The COVID-19 Pandemic: a Call to Action to Identify and Address Racial and Ethnic Disparities.
Laurencin, CT, McClinton, A
Journal of racial and ethnic health disparities. 2020;7(3):398-402
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The severe acute respiratory syndrome coronavirus 2 virus was first identified in late 2019 in Wuhan, China. Various unsubstantiated reports emerged declaring that the genetic constitution of Blacks or even the presence of melanin rendered Blacks immune to the virus. This study is a call of action which reviews preliminary data on race and ethnicity in the peer-reviewed literature for citizens in America affected by COVID-19. Findings demonstrate that communities of colour (Blacks) have a higher rate of infection and death in comparison to their population percentage in the state of Connecticut. However, authors are unable to draw conclusions since race and ethnicity data is missing and the data in this paper is the earliest data available. Therefore, the authors call for action to identify and address racial and ethnic health disparities in the COVID-19 crisis.
Abstract
The Coronavirus disease 2019 (COVID-19) pandemic has significantly impacted and devastated the world. As the infection spreads, the projected mortality and economic devastation are unprecedented. In particular, racial and ethnic minorities may be at a particular disadvantage as many already assume the status of a marginalized group. Black Americans have a long-standing history of disadvantage and are in a vulnerable position to experience the impact of this crisis and the myth of Black immunity to COVID-19 is detrimental to promoting and maintaining preventative measures. We are the first to present the earliest available data in the peer-reviewed literature on the racial and ethnic distribution of COVID-19-confirmed cases and fatalities in the state of Connecticut. We also seek to explode the myth of Black immunity to the virus. Finally, we call for a National Commission on COVID-19 Racial and Ethnic Health Disparities to further explore and respond to the unique challenges that the crisis presents for Black and Brown communities.
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A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring.
Alpert, A, Pickman, Y, Leipold, M, Rosenberg-Hasson, Y, Ji, X, Gaujoux, R, Rabani, H, Starosvetsky, E, Kveler, K, Schaffert, S, et al
Nature medicine. 2019;25(3):487-495
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The human immune system changes with age, ultimately leading to a clinically evident, profound deterioration resulting in high morbidity and mortality rates attributed to infectious and chronic diseases. The aim of this study was to assess at high resolution the dynamics of older adults’ immune systems. The study uses multiple ‘omics’ technologies in a cohort of 135 adults (63 young adults and 72 older adults) of different ages who were sampled longitudinally over the course of 9 years to comprehensively capture population- and individual-level changes in the immune system over time. Results indicate that immune-cell frequencies changed at substantially different rates; some cell subsets show no directionality of change yet differ between young and old individuals, whereas other cell subsets continued changing (either increasing or decreasing) throughout the course of the study. Authors postulate that an individual’s immune age is a function of life history, namely environmental exposure coupled with genetic background. Thus, immune modulators may one day be identified that affect the position of an individual’s immune system along the immunological landscape.
Abstract
Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual's immune age. Here, we use multiple 'omics' technologies to capture population- and individual-level changes in the human immune system of 135 healthy adult individuals of different ages sampled longitudinally over a nine-year period. We observed high inter-individual variability in the rates of change of cellular frequencies that was dictated by their baseline values, allowing identification of steady-state levels toward which a cell subset converged and the ordered convergence of multiple cell subsets toward an older adult homeostasis. These data form a high-dimensional trajectory of immune aging (IMM-AGE) that describes a person's immune status better than chronological age. We show that the IMM-AGE score predicted all-cause mortality beyond well-established risk factors in the Framingham Heart Study, establishing its potential use in clinics for identification of patients at risk.
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Exposure to glyphosate-based herbicides and risk for non-Hodgkin lymphoma: A meta-analysis and supporting evidence.
Zhang, L, Rana, I, Shaffer, RM, Taioli, E, Sheppard, L
Mutation research. Reviews in mutation research. 2019;781:186-206
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Glyphosate is a highly effective broad-spectrum herbicide that is typically applied in mixtures known as glyphosate-based herbicides (GBHs). Glyphosate and its metabolites persist in food, water, and dust, potentially indicating that everyone may be exposed ubiquitously. The objective of this study was to focus on an a priori hypothesis - the highest biologically relevant exposure to GBHs, i.e., higher levels, longer durations and/or with sufficient lag and latency, will lead to increased risk of non-Hodgkin lymphoma (NHL) in humans. This study is a meta-analysis of six studies (one cohort and five case-control control studies) with almost 65,000 participants. Results demonstrated a significantly increased NHL risk in highly GBH-exposed individuals. Authors conclude that the overall evidence from human, animal, and mechanistic studies presented in this study, supports a compelling link between exposures to GBHs and increased risk for NHL.
Abstract
Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that includes the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% confidence interval, CI: 1.13-1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we calculated a meta-RR for NHL of 1.45 (95% CI: 1.11-1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed publicly available animal and mechanistic studies related to lymphoma. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between glyphosate / GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL or lymphomagenesis. Overall, in accordance with findings from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL.
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Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary.
Richman, S, Morris, MC, Broderick, G, Craddock, TJA, Klimas, NG, Fletcher, MA
Clinical therapeutics. 2019;41(5):798-805
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Myalgic encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/ CFS), is a disease characterized by an inability to exert oneself physically, often coupled with a combination of other symptoms, including sleep disorders, severe unpredictable pain, and compromised cognitive abilities. The aim of this review was to delineate a number of the more prominent treatments for ME/CFS into different categories and evaluate the methods and results of corresponding drug trials. Results indicate that: • antiviral drugs appear to show limited efficacy in treating ME/CFS over a broad demographic. • there is a lack of clinical research focusing on the use of specific cyclooxygenase-2 inhibitors [analgesic] to treat ME/CFS. • antidepressants may be of use in delivering improvements in the quality of life of patients with ME/CFS. • recalibration of endocrine-immune regulation may be involved in supporting the persistence of ME/CFS and may be responsible at least in part for its resistance to single agent interventions. Authors conclude that there is a great need for larger, longitudinal studies focused on a more clearly defined subset of ME/CFS as well as a greater consideration of potential synergies between interventions and the suitability of combination therapies.
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by prolonged periods of fatigue, chronic pain, depression, and a complex constellation of other symptoms. Currently, ME/CFS has no known cause, nor are the mechanisms of illness well understood. Therefore, with few exceptions, attempts to treat ME/CFS have been directed mainly toward symptom management. These treatments include antivirals, pain relievers, antidepressants, and oncologic agents as well as other single-intervention treatments. Results of these trials have been largely inconclusive and, in some cases, contradictory. Contributing factors include a lack of well-designed and -executed studies and the highly heterogeneous nature of ME/CFS, which has made a single etiology difficult to define. Because the majority of single-intervention treatments have shown little efficacy, it may instead be beneficial to explore broader-acting combination therapies in which a more focused precision-medicine approach is supported by a systems-level analysis of endocrine and immune co-regulation.
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Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Nagy-Szakal, D, Williams, BL, Mishra, N, Che, X, Lee, B, Bateman, L, Klimas, NG, Komaroff, AL, Levine, S, Montoya, JG, et al
Microbiome. 2017;5(1):44
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, swollen lymph glands and irritable bowel syndrome (IBS). It is associated with gut bacterial dysbiosis, systemic inflammation and both gastro intestinal (GI) and neurological disturbances. The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. This experiment looked at fecal bacterial samples and metabolic pathway markers in 50 ME/CFS patients and 50 healthy controls. In ME/CFS subgroups, measures of symptom severity including pain, fatigue, and reduced motivation were correlated with the amounts and types of gut bacteria and certain metabolic pathways. Future prospective studies should consider more detailed exploration of IBS subtypes, associated GI symptoms, and their relationship to ME/CFS dysbiosis. This may enable more accurate diagnosis and the development of specific therapeutic strategies.
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.