Loneliness prevention and the role of the Public Health system.

AIMS: To evaluate evidence on loneliness interventions that have been assessed and found effective, both for remediation and addressing fundamental causes of loneliness; to consider why population-level primary prevention strategies targeting fundamental causes are necessary, and determine areas for future research; and to outline an integrated approach to prevention considering roles for the Public Health system. METHOD: We conducted a review of systematic reviews to identify effective loneliness interventions and classified them in our Population-Prevention Matrix according to public health impact, amount of individual effort required, and level of prevention. We also highlighted emerging interventions that have yet to be formally evaluated. RESULTS: We identified a range of preventive or therapeutic approaches, and a dearth of population-level primary prevention interventions targeting fundamental causes of loneliness. Filling this gap will be essential in addressing the loneliness epidemic, and we provided emerging examples of population-level primary prevention interventions that may inform future efforts. CONCLUSION: Based on evidence to date, we suggest an integrated approach to prevention with significant roles for the US Public Health system, including its function as Chief Health Strategist to lead and guide multisystem approaches to loneliness prevention, with a particular focus on population-level primary prevention strategies.

Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).

Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followed seminal research in 1990, whereby, Blum's group identified the first genetic association with severe alcoholism published in JAMA. While it is true that no one to date has provided adequate RDS free controls there have been many studies using case -controls whereby SUD has been eliminated. We argue that this deficiency needs to be addressed in the field and if adopted appropriately many spurious results would be eliminated reducing confusion regarding the role of genetics in addiction. However, an estimation, based on these previous literature results provided herein, while not representative of all association studies known to date, this sampling of case- control studies displays significant associations between alcohol and drug risk. In fact, we present a total of 110,241 cases and 122,525 controls derived from the current literature. We strongly suggest that while we may take argument concerning many of these so-called controls (e.g. blood donors) it is quite remarkable that there are a plethora of case -control studies indicating selective association of these risk alleles ( measured in GARS) for the most part indicating a hypodopaminergia. The paper presents the detailed methodology of the GARS. Data collection procedures, instrumentation, and the analytical approach used to obtain GARS and subsequent research objectives are described. Can we combat SUD through early genetic risk screening in the addiction field enabling early intervention by the induction of dopamine homeostasis? It is envisaged that GARS type of screening will provide a novel opportunity to help identify causal pathways and associated mechanisms of genetic factors, psychological characteristics, and addictions awaiting additional scientific evidence including a future meta- analysis of all available data -a work in progress.

Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

Relationship of Physical Frailty to Phosphocreatine Recovery in Muscle after Mild Exercise Stress in the Oldest-Old Women.

BACKGROUND: Physical frailty is a clinical syndrome associated with aging and manifesting as slowness, weakness, reduced physical activity, weight loss, and/or exhaustion. Frail older adults often report that their major problem is "low energy", and there is indirect evidence to support the hypothesis that frailty is a syndrome of dysregulated energetics. We hypothesized that altered cellular energy production underlies compromised response to stressors in the frail. METHODS: We conducted a pilot study to assess muscle energetics in response to a mild isometric exercise challenge in women (n=30) ages 84-93 years. The frailty status was assessed by a validated physical frailty instrument. Localized phosphorus (P31) magnetic resonance spectroscopy with a 1.5T magnet was used to assess the kinetics of Phosphocreatine recovery in the tibialis anterior muscle following maximal isometric contraction for 30 seconds. RESULTS: Phosphocreatine recovery following exertion, age-adjusted, was slowest in the frail group (mean=189 sec; 95%CI: 150,228) compared to pre-frail (mean=152 sec; 95%CI: 107,197) and nonfrail subjects (mean=132 sec; 95%CI: 40,224). The pre-frail and frail groups had 20 sec (95%CI: -49,89) and 57 sec (95%CI: -31,147) slower phosphocreatine recovery, respectively, than the non-frail. This response was paralleled by dysregulation in glucose recovery in response to oral glucose tolerance test in women from the same study population. CONCLUSIONS: Impaired muscle energetics and energy metabolism might be implicated in the physical frailty syndrome.

Detonation synthesis of carbon nano-onions via liquid carbon condensation.

Transit through the carbon liquid phase has significant consequences for the subsequent formation of solid nanocarbon detonation products. We report dynamic measurements of liquid carbon condensation and solidification into nano-onions over ∽200 ns by analysis of time-resolved, small-angle X-ray scattering data acquired during detonation of a hydrogen-free explosive, DNTF (3,4-bis(3-nitrofurazan-4-yl)furoxan). Further, thermochemical modeling predicts a direct liquid to solid graphite phase transition for DNTF products ~200 ns post-detonation. Solid detonation products were collected and characterized by high-resolution electron microscopy to confirm the abundance of carbon nano-onions with an average diameter of ∽10 nm, matching the dynamic measurements. We analyze other carbon-rich explosives by similar methods to systematically explore different regions of the carbon phase diagram traversed during detonation. Our results suggest a potential pathway to the efficient production of carbon nano-onions, while offering insight into the phase transformation kinetics of liquid carbon under extreme pressures and temperatures.

Relevance of heat stress and dehydration to chronic kidney disease (CKDu) in Sri Lanka.

Chronic kidney disease in the absence of hypertension and diabetes is a growing problem among agricultural laborers in tropical and subtropical regions. It is unclear if heat stress and dehydration are risk factors for this form of chronic kidney disease (CKDu). To investigate this relationship, agricultural workers in four villages (n = 261) in North Central Province, Sri Lanka completed the US National Institute for Occupational Safety and Health (NIOSH) health hazard evaluation of heat stress, translated into Sinhalese (July 2017). We constructed a heat stress/dehydration index based on the frequency of 16 symptoms (range 0-32; reliability, 0.84). Workers provided a urine sample for dipstick assessment of urine albumin-creatinine ratio (ACR) and refractometer analysis of urine concentration. Of 261 respondents, 41 participants reported diabetes or chronic kidney disease. They scored higher on the heat stress-dehydration index (10.78 vs. 8.03, p < .01) and were more likely to have ACR > 30 (85.4% vs. 69.4%, p < .05). Among 216 non-pregnant agricultural workers without diabetes or kidney disease (mean age, 46.6; 37% male), villagers in the high-CKDu prevalence area were more likely to show signs of dehydration (for example, greater urine concentration, 1.015 vs. 1.012, p < .05, among males); however, the heat stress-dehydration index overall was not associated with ACR or urine concentration. Because an elevated ACR (proteinuria) is not a reliable marker of early CKDu, additional studies are needed to assess the association between heat stress-dehydration symptoms and risk of CKDu.

Use of remote monitoring with continuous glucose monitoring in young children with Type 1 diabetes: the parents' perspective.

AIM: Remote monitoring with continuous glucose monitoring (CGM) in children with Type 1 diabetes mellitus has recently become available, but little is known about caregivers' experiences of its use, particularly in younger children. The aim of this study was to explore parents' everyday experiences of using this technology. METHODS: The parents of children with Type 1 diabetes diagnosed for > 1 year, aged 2-12 years were invited to participate in a semi-structured interview. Interviews were the second phase of a randomized cross-over study using standard insulin therapy with or without CGM and remote monitoring for two 3-month periods. Open-ended questions were used to explore parents' real-life experiences of the remote monitoring and CGM system. Interviews were analysed using thematic analysis. RESULTS: Five themes related to remote monitoring emerged: (i) impact on sleep quality for the parents, (ii) peace of mind, (iii) impact on anxiety, (iv) freedom and confidence for the parents and children, and (v) impact on relationships. Furthermore, parents reported on themes related to CGM in general, such as better understanding of how to manage and control their child's diabetes and experiences related to physical or technical aspects. CONCLUSION: Overall, parents of primary school children reported that using remote monitoring and CGM was a mostly beneficial experience. However, negative aspects within the themes were also reported. These findings will help to provide a structure to discuss parent and child expectations and provide targeted education at the start of using remote monitoring and CGM.

Understanding the Scientific Basis of Post-traumatic Stress Disorder (PTSD): Precision Behavioral Management Overrides Stigmatization.

Post-traumatic stress disorder (PTSD) is a severe polygenic disorder triggered by environmental factors. Many polymorphic genes, particularly the genetic determinants of hypodopaminergia (low dopamine function), associate with a predisposition to PTSD as well as substance use disorder. Support from the National Institutes of Health for neuroimaging research and molecular, genetic applied technologies has improved understanding of brain reward circuitry functions that have inspired the development of new innovative approaches to their early diagnosis and treatment of some PTSD symptomatology and addiction. This review presents psychosocial and genetic evidence that vulnerability or resilience to PTSD can theoretically be impacted by dopamine regulation. From a neuroscience perspective, dopamine is widely accepted as a major neurotransmitter. Questions about how to modulate dopamine clinically in order to treat and prevent PTSD and other types of reward deficiency disorders remain. Identification of genetic variations associated with the relevant genotype-phenotype relationships can be characterized using the Genetic Addiction Risk Score (GARS®) and psychosocial tools. Development of an advanced genetic panel is under study and will be based on a new array of genes linked to PTSD. However, for now, the recommendation is that enlistees for military duty be given the opportunity to voluntarily pre-test for risk of PTSD with GARS, before exposure to environmental triggers or upon return from deployment as part of PTSD management. Dopamine homeostasis may be achieved via customization of neuronutrient supplementation "Precision Behavioral Management" (PBM™) based on GARS test values and other pro-dopamine regulation interventions like exercise, mindfulness, biosensor tracking, and meditation.

"Pro-dopamine regulation (KB220Z™)" as a long-term therapeutic modality to overcome reduced resting state dopamine tone in opiate/opioid epidemic in America.

Since it is known that relapse, morality, and hospitalizations have been tied to the presence of the Dopamine D2 Receptor A1 allele, as one example, and carriers of this gene variant have a proclivity to favor amino-acid therapy, it seems intuitive that the incorporation of modalities to provide a balance and or restoration of hypodopaminergia should be considered as a front-line tactic to overcome the current American opiate/opioid epidemic, saving millions from death and unwanted locked-in-addiction. If we continue down the prim road path of fighting addiction to narcotics with narcotics, we are doomed to fail. This lesson can also have global interest.

The association of neighborhood characteristics with obesity and metabolic conditions in older women.

OBJECTIVE: Previous studies exploring the relationship of neighborhood characteristics with metabolic conditions have focused on middle-aged adults but none have comprehensively investigated associations in older adults, a potentially vulnerable population. The aim was to explore the relationship of neighborhood characteristics with metabolic conditions in older women. DESIGN: Cross-sectional analysis. SETTING/PARTICIPANTS: We studied 384 women aged 70-79 years, representing the two-thirds least disabled women in the community, enrolled in the Women's Health and Aging Study II at baseline. Neighborhood scores were calculated from census-derived data on median household income, median house value, percent earning interest income, percent completing high school, percent completing college, and percent with managerial or executive occupation. Participants were categorized by quartile of neighborhood score with a higher quartile representing relative neighborhood advantage. Logistic regression models were created to assess the association of neighborhood quartiles to outcomes, adjusting for key covariates. MEASUREMENTS: Primary outcomes included metabolic conditions: obesity, diabetes, hypertension, and hyperlipidemia. Secondary outcomes included BMI, HbA1c, blood pressure and lipids. RESULTS: Higher neighborhood quartile score was associated with a lower prevalence of obesity (highest quartile=13.5% versus lowest quartile=36.5%; p<0.001 for trend). A lower prevalence of diabetes was also observed in highest (6.3%) versus lowest (14.4%) neighborhood quartiles, but was not significantly different (p= 0.24 for trend). Highest versus lowest neighborhood quartile was associated with lower HbA1c (-0.31%, p=0.02) in unadjusted models. Women in the highest versus lowest neighborhood quartile had lower BMI (-2.01 kg/m2, p=0.001) and higher HDL-cholesterol (+6.09 mg/dL, p=0.01) after accounting for age, race, inflammation, and smoking. CONCLUSION: Worse neighborhood characteristics are associated with adiposity, hyperglycemia, and low HDL. Further longitudinal studies are needed and can inform future interventions to improve metabolic status in older adults.

Clinical study on cholesterol-lowering effect of RYR Cholestin among Americans with moderate hy-percholesterolemia / 上海预防医学

[Objective] To evaluate lipid -lowering efficacy and safety of RYR Cholestin , or Monascus purpureus (Red Yeast) Rice, in Americans with moderate hypercholesterolemia. [Methods] This study was an open-label, self-control, and multi-center clinical trial.A total of 187 subjects were entered into this trial (serum LDL-Cholesterol 3.50~4.92 mmol/L,total cholesterol 5.18~7.25 mmol/L, male:female=116∶71) , of whom 162 completed the study .Subjects were placed on the NCEP Step I Diet throughout the study and RYR Cholestin (2.4 g/day) was administered for 8 weeks following initial 4-week diet control . [ Results] Being on the diet alone for 4 weeks resulted in no significant changes in serum lipids .RYR Cholestin treatment for 8 weeks reduced serum total cholesterol , LDL-Cholesterol and triglycerides by 16 .6%, 24 .0%, and 25 .2%, respectively , and increased HDL-Cholesterol by 14 .3%( all P<0 .001 ) .There were 97 .5% of patients having ≥10% improvement in at least one of lipid risk factors, and 79.0%having ≥20% improvement.Discontinuation of RYR Cholestin intervention for 14 d led to a return of serum lipids to baseline of pre -study .And 29 possible product -related mild adverse re-actions were reported . [ Conclusion] RYR Cholestin is well tolerated and effective in reducing total and LDL-Cholesterol, and triglycerides, as well as in increasing HDL-Cholesterol in hypercholesterolemic patients, but those indicators return to the beginning baseline when the treatment is discontinued .

Frailty status and altered dynamics of circulating energy metabolism hormones after oral glucose in older women.

OBJECTIVES: Frailty status is associated with altered glucose-insulin dynamics. Here, we sought to investigate whether alteration in the dynamics of other circulating energy metabolism hormones after oral glucose is associated with frailty status. DESIGN: Substudy of older women in a prospective cohort. SETTING: Baltimore, Maryland. PARTICIPANTS: Seventy-three community-dwelling women aged 84-95 years without a diagnosis of diabetes who were enrolled in the Women's Health and Aging Study II. MEASUREMENTS: We examined stimulus-response dynamics of free fatty acids (FFA), gut- (ghrelin,GLP-1) and adipocyte-derived hormones (leptin, adiponectin, resistin), growth hormone (GH), insulin-like growth factor 1 (IGF-1), and interleukin-6 (IL-6) at 0, 30, 60, 120, and 180-minutes after a 75-g glucose challenge according to frailty status (non-frail, pre-frail, or frail). RESULTS: On average, frail women had higher fasting levels of glucose-raising hormones (FFA, resistin, GH, and IL-6) and lower fasting levels of glucose-lowering hormones (ghrelin, adiponectin, GLP-1 and IGF-1) versus non-frail women but these results were not statistically significant. Frail women also had higher fasting levels of leptin with relative adiposity compared to their counterparts, suggestive of leptin-resistance. Integrated area under the curve (AUC) values for each hormone followed similar trends by frailty status. After age and BMI adjustment, frail versus non-frail women were more likely to be in the lowest tertile of fasting ghrelin levels and 120-min ghrelin levels (both p<0.05) in logistic regression analyses. No large differences were found for other hormones in adjusted models. CONCLUSIONS: Our findings suggest dysregulation of the orexigenic hormone ghrelin in the frailty syndrome. Further studies are needed to explore the role of ghrelin dysregulation in the clinical manifestation of frailty.

Diet quality and social support: factors associated with serum carotenoid concentrations among older disabled women (the Women's Health and Aging Study).

PURPOSE: This study investigated the relationship between social support (including instrumental support, emotional support, social interaction, social space, and family networks) and diet quality, as indicated by serum carotenoid levels. DESIGN AND METHODS: The sample consisted of participants in the Women's Health and Aging Study with longitudinal carotenoid data (n=325). We performed regression analyses using baseline indicators of social support and changes in social support to determine whether baseline levels and/or change in levels of social support predict changes in serum carotenoid levels. Social support changes were measured over 1 year from baseline to follow-up round 1. Carotenoid level changes were established from follow-up round 1 to round 2. To determine whether or not regression to the mean was driving these results, we performed an analysis that included baseline and change levels of social support indicators. RESULTS: At baseline, the frequency of leaving one's home was associated with a decrease in carotenoid levels. Leaving one's home more frequently predicted an increase in carotenoid levels and attending fewer activities predicted a decrease in carotenoid levels. IMPLICATIONS: In older, community-resident disabled women, baseline levels of social support did not consistently predict diet quality. However, change in social support predicted both positive and negative change in diet quality and thus provides supportive evidence that social activity and family interaction may play meaningful roles in the maintenance of diet quality among functionally compromised older women. Further research is necessary to more fully understand the impact of multiple forms of social supports on the diet quality of older adults.

Serum carotenoids and pulmonary function in older community-dwelling women.

BACKGROUND AND OBJECTIVES: Deterioration in pulmonary function is associated with greater disability and mortality in older adults. Dietary antioxidants are implicated in lung health, but the relationship between major dietary antioxidants, such as serum carotenoids, and pulmonary function have not been well characterized. Serum carotenoids are considered the most reliable indicator of fruit and vegetable intake. SUBJECTS AND METHODS: We examined the relationship between serum α-carotene, ß-carotene, ß-cryptoxanthin, lutein/zeaxanthin, and lycopene with pulmonary function (forced expiratory volume in one second [FEV1] and forced vital capacity [FVC]) in a population-based sample of 631 moderately to severely disabled community-dwelling older women (Women's Health and Aging Study I) in Baltimore, Maryland, USA. RESULTS: Higher serum α-carotene and ß-carotene concentrations were positively associated with both FEV1 and FVC, respectively (all P < 0.05), in separate multivariate linear regression models adjusting for age, race, education, cognition, anemia, inflammation, and chronic diseases. Total serum carotenoids were associated with FEV1 (P = 0.08) and FVC (P = 0.06), respectively, in similar models. No association was found between ß-cryptoxanthin, lutein/zeaxanthin, and lycopene, and FEV1 or FVC. CONCLUSIONS: Higher serum α-carotene and ß-carotene concentrations, which reflect greater intake of orange and dark green leafy fruits and vegetables, were associated with better pulmonary function among older community-dwelling women.function may lead to food avoidance and to a higher incidence of digestive complaints.

The association of genetic variants in interleukin-1 genes with cognition: findings from the cardiovascular health study.

The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer's, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta=0.47, 95%CI=0.09, 0.85, p=0.016; rs4251961: beta=-0.36, 95%CI=-0.13,-0.60, p=0.0027; rs931471: beta=0.39, 95%CI=0.13, 0.65, p=0.0032), and the IL1B gene for African Americans (rs1143627: beta=1.6, 95%CI=0.48, 2.8; p=0.006 and rs1143634: beta=2.09, 95%CI=0.39, 3.8; p=0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.

Temporal patterns in overweight and obesity in Type 1 diabetes.

AIMS: Time trends in overweight and obesity in the general population have been well documented; however, temporal patterns in Type 1 diabetes (T1DM) have not been thoroughly investigated. We therefore assessed temporal patterns in overweight and obesity and predictors of weight change in 589 individuals from the Pittsburgh Epidemiology of Diabetes Complications Study, a cohort of childhood-onset T1DM. METHODS: Participants were first seen in 1986-1988, when mean age and diabetes duration were 29 and 20 years, respectively, and biennially thereafter for 18 years. Overweight was defined as 25.0or=30.0 kg/m2. RESULTS: At baseline, the prevalence of overweight and obesity were 28.6% and 3.4%, respectively. After 18 years' follow-up, the prevalence of overweight increased by 47% while the prevalence of obesity increased sevenfold. Seven per cent were on intensive insulin therapy (>or=3 insulin injections per day or on insulin pump) at baseline; by 2004-2007, this was 82%. Predictors of weight change were a higher baseline HbA1c, symptomatic autonomic neuropathy (inversely), overt nephropathy (inversely), and going onto intensive insulin therapy during follow-up. CONCLUSIONS: These data demonstrate dramatic weight gain in T1DM and underscore the complexity of weight change in this disease.

Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty.

OBJECTIVE: This project was designed to follow-up prior evidence that demonstrated a significant association between vitamin B12 transport and metabolism and the frailty syndrome in community-dwelling older women. The cross-sectional relationship between genetic variants within six candidate genes along this pathway with serum methylmalonic acid (MMA) levels and frailty was evaluated in this same population of older women. METHODS: Baseline measures were collected prior to folate fortification from 326 women in the Women's Health and Aging Studies I and II. Odds ratios and statistical tests were estimated for single SNP and haplotype via linear regression models for serum MMA, a marker for available vitamin B12, and in logistic regression models for frailty. RESULTS: Fifty-six SNPs from CBS, MTHFR, MTR, MTRR, TCN1 and TCN2 genes were genotyped. Several SNPs in MTHFR, MTR and MTRR demonstrated a modest association to elevated MMA, while SNPs in TCN2 showed significant association to the frailty syndrome. TCN2 polymorphisms, particularly one SNP reported to be in perfect LD with functional variant Pro259Arg, were significantly associated with increased odds of frailty, after adjustment for age, presence of cardiovascular disease and elevated MMA (OR = 2.25, p-value = 0.009). CONCLUSIONS: Using MMA as a marker for vitamin B12, these results suggest that TCN2 gene variants may lead to decreased vitamin B12 availability, leading to reduced energy metabolism, ultimately contributing to frailty pathology. Further studies to determine the biological role of functional TCN2 polymorphisms in frailty are needed.