Use of mobile technology to identify behavioral mechanisms linked to mental health outcomes in Kenya: protocol for development and validation of a predictive model.

OBJECTIVE: This study proposes to identify and validate weighted sensor stream signatures that predict near-term risk of a major depressive episode and future mood among healthcare workers in Kenya. APPROACH: The study will deploy a mobile application (app) platform and use novel data science analytic approaches (Artificial Intelligence and Machine Learning) to identifying predictors of mental health disorders among 500 randomly sampled healthcare workers from five healthcare facilities in Nairobi, Kenya. EXPECTATION: This study will lay the basis for creating agile and scalable systems for rapid diagnostics that could inform precise interventions for mitigating depression and ensure a healthy, resilient healthcare workforce to develop sustainable economic growth in Kenya, East Africa, and ultimately neighboring countries in sub-Saharan Africa. This protocol paper provides an opportunity to share the planned study implementation methods and approaches. CONCLUSION: A mobile technology platform that is scalable and can be used to understand and improve mental health outcomes is of critical importance.

Different gut microbiota in U.S. formula-fed infants consuming a meat vs. dairy-based complementary foods: A randomized controlled trial.

Objective: This project aimed to evaluate the impact of meat- vs. dairy-based complementary foods on gut microbiota and whether it relates to growth. Design: Full-term, formula-fed infants were recruited from the metro Denver area (Colorado, US) and randomized to a meat- or dairy-based complementary diet from 5 to 12 months of age. Infant's length and weight were measured, and stool samples were collected at 5, 10, and 12 months for 16S rRNA gene sequencing and short-chain fatty acids (SCFAs) quantification. Results: Sixty-four infants completed the dietary intervention (n = 32/group). Weight-for-age Z (WAZ) scores increased in both groups and length-for-age Z scores (LAZ) increased in the meat group only, which led to a significant group-by-time interaction (P = 0.02) of weight-for-length Z (WLZ) score. Microbiota composition (Beta-diversity) differed between groups at 12 months (weighted PERMANOVA P = 0.01) and had a group-by-time interaction of P = 0.09. Microbial community richness (Chao1) increased in the meat group only. Genus Akkermansia had a significant group-by-time interaction and increased in the dairy group and decreased in the meat group. A significant fold change of butyric acid from 5 to 12 months was found in the meat group (+1.75, P = 0.011) but not in the dairy group. Regression analysis showed that Chao1 had a negative association with WLZ and WAZ. Several genera also had significant associations with all growth Z scores. Conclusion: Complementary feeding not only impacts infant growth but also affects gut microbiota maturation. Complementary food choices can affect both the gut microbiota diversity and structures and these changes in gut microbiota are associated with infant growth.

Utilizing public health data to geotarget hepatitis C virus elimination approaches in urban and rural Michigan.

Using Michigan public health data, we assessed geographical access to specialist providers for hepatitis C virus (HCV) treatment in urban and rural areas in Michigan and explored correlates of HCV in these areas to help inform HCV elimination planning and resource allocations. We found higher HCV incidence in urban areas, lower treatment specialist access in rural areas, but few correlates of HCV across adult populations in both areas. State and local HCV elimination planning should include population-based screening among all adults and address geographical barriers to care.

Low-Intensity Vibration Improves Muscle Healing in a Mouse Model of Laceration Injury.

Recovery from traumatic muscle injuries is typically prolonged and incomplete, leading to impaired muscle and joint function. We sought to determine whether mechanical stimulation via whole-body low-intensity vibration (LIV) could (1) improve muscle regeneration and (2) reduce muscle fibrosis following traumatic injury. C57BL/6J mice were subjected to a laceration of the gastrocnemius muscle and were treated with LIV (0.2 g at 90 Hz or 0.4 g at 45 Hz for 30 min/day) or non-LIV sham treatment (controls) for seven or 14 days. Muscle regeneration and fibrosis were assessed in hematoxylin and eosin or Masson's trichrome stained muscle cryosections, respectively. Compared to non-LIV control mice, the myofiber cross-sectional area was larger in mice treated with each LIV protocol after 14 days of treatment. Minimum fiber diameter was also larger in mice treated with LIV of 90 Hz/0.2 g after 14 days of treatment. There was also a trend toward a reduction in collagen deposition after 14 days of treatment with 45 Hz/0.4 g (p = 0.059). These findings suggest that LIV may improve muscle healing by enhancing myofiber growth and reducing fibrosis. The LIV-induced improvements in muscle healing suggest that LIV may represent a novel therapeutic approach for improving the healing of traumatic muscle injuries.

Increased skin blood flow during low intensity vibration in human participants: Analysis of control mechanisms using short-time Fourier transform.

AIM: Investigate the immediate effect of low intensity vibration on skin blood flow and its underlying control mechanisms in healthy human participants. MATERIALS AND METHODS: One-group pre-post design in a university laboratory setting. Nine adults underwent two bouts of 10-minute vibration (30Hz, peak acceleration 0.4g). Outcome measures include skin blood flow, and skin temperature on the right foot. To examine the control mechanisms underlying the vibration-induced blood flow response, SHORT-TIME Fourier analyses were computed to obtain the spectral densities for three frequency bands: metabolic (0.0095-0.02Hz), neurogenic (0.02-0.06Hz), and myogenic (0.06-0.15Hz). Non-parametric Friedman's tests were computed to compare changes of the outcome measures and control mechanisms over the course of vibration. RESULTS: Vibration increased skin blood flow during both bouts of vibration, however the effect did not last after vibration was terminated. Myogenic spectral density increased during both bouts of vibration, whereas the metabolic and neurogenic spectral densities increased only during the 2nd bout of vibration. Interestingly, only the metabolic spectral density remained elevated after vibration ended. CONCLUSION: Low intensity vibration produced acute increases in skin blood flow mediated in part by vascular control mechanisms of myogenic origin. Further investigation is warranted to determine whether low intensity vibration induces similar increases in skin blood flow in populations prone to developing chronic non-healing wounds, such as spinal cord injury and diabetes.

Whey Protein Supplementation and Higher Total Protein Intake Do Not Influence Bone Quantity in Overweight and Obese Adults Following a 36-Week Exercise and Diet Intervention.

BACKGROUND: Controversy exists concerning the effects of higher total protein intake (TPro) on bone health, which may be associated with reduced bone mineral density (BMD). However, whey protein (WP) may induce bone formation because of its basic component, milk basic protein. OBJECTIVE: This study assessed the effects of WP supplementation, TPro, and change in TPro (postsupplementation - presupplementation) on BMD and bone mineral content (BMC; total body, lumbar spine, total femur, and femoral neck) in overweight and class I obese middle-aged adults following an exercise intervention. METHODS: This analysis used data from a double-blind, randomized, placebo-controlled 36-wk WP supplementation trial, wherein participants consumed a 1.7-MJ (400-kcal) supplement (0, 20, 40, or 60 g WP/d) along with their otherwise unrestricted diet while participating in a resistance and aerobic exercise intervention (3 d/wk). TPro was the summation of WP and habitual dietary intakes (4-d food record). Statistical analyses for WP were based on group and bone data [n = 186, 108 women; mean ± SD age: 49 ± 8 y; body mass index (BMI; in kg/m2): 30.1 ± 2.8], whereas TPro was based on dietary and bone data (n = 113, 70 women; age 50 ± 8 y; BMI 30.1 ± 2.9). RESULTS: WP supplementation, regardless of dose, did not influence BMD or BMC following the intervention. By using a multiple linear regression model, TPro (expressed as g/d or g · kg-1 · d-1) and change in TPro (expressed as g/d) were not associated with responses over time in total or regional BMD or BMC. By using a cluster analysis approach [<1.0 (n = 41), 1.0-1.2 (n = 28), and ≥1.2 g · kg-1 · d-1 (n = 44)], TPro was also not associated with responses in total or regional BMD or BMC over time. CONCLUSION: WP supplementation and total dietary protein intake did not negatively or beneficially influence bone quantity in overweight and obese adults during a 9-mo exercise intervention. This trial was registered at clinicaltrials.gov as NCT00812409.

Low-intensity vibrations accelerate proliferation and alter macrophage phenotype in vitro.

Macrophages are essential for the efficient healing of various tissues. Although many biochemical signaling pathways have been well characterized in macrophages, their sensitivity to mechanical signals is largely unexplored. Here, we applied low-intensity vibrations (LIV) to macrophages to determine whether macrophages could directly transduce LIV signals into changes in the expression of genes and proteins involved in tissue repair. Two different LIV signal frequencies (30Hz or 100Hz) were combined with two acceleration magnitudes (0.15g or 1g) to generate four distinct LIV signals that were applied to cultured murine macrophages. All four LIV signals significantly increased macrophage number after 3 days of stimulation with the combination of the smallest acceleration and the highest frequency (0.15g at 100Hz) generating the largest response. Compared to non-LIV controls, gene expression of the pro-healing growth factors VEGF and TGF-ß increased with all four LIV signals (Day 1). LIV also decreased protein levels of the pro-inflammatory cytokines IL-6, IFN-γ, and TNF-α (Days 1 and 3). These data demonstrate the sensitivity of macrophages to high-frequency oscillations applied at low intensities and may suggest that the benefit of LIV for tissue repair may be based on reducing inflammation and promoting a pro-healing macrophage phenotype.

Thyroid status, insulin sensitivity and glucose tolerance in overweight and obese adults before and after 36 weeks of whey protein supplementation and exercise training.

UNLABELLED: Research suggests that subclinical hypothyroidism (SHT) influences insulin sensitivity and glucose tolerance. Reductions in thyroid stimulating hormone (TSH) concentrations are associated with exercise training (ExTr), which improves insulin sensitivity and glucose uptake. PURPOSE: A secondary analysis of previously published data was conducted to examine the relationship between SHT, TSH and glucose homeostatic control at baseline and to assess the impact of ExTr on thyroid status and how SHT affects changes in insulin sensitivity after ExTr. MATERIALS AND METHODS: Data were obtained from a 36-week ExTr and whey protein supplementation intervention trial. Subjects (n = 304, 48 ± 7 years, females = 186) were randomized to a specific whey protein group (0, 20, 40, or 60 g per day) and all subjects participated in a resistance (2 d/wk) and aerobic (1 d/wk) training program. Testing was conducted at baseline and post-intervention. RESULTS: At baseline, 36% (n = 110) and 12% (n = 35) of subjects were classified with SHT based on the TSH ≥ 3 µIU/L or TSH ≥ 4.5 µIU/L cut-offs, respectively. No association was found between baseline TSH and baseline measures of glucose homeostatic control. Whey protein supplementation did not influence intervention outcomes. Post-intervention (n = 164), no change was observed in TSH. SHT did not affect changes in insulin sensitivity following ExTr. CONCLUSION: These results support that the health benefits of ExTr for the management of insulin resistance (IR) are not blunted by SHT.

The Apparent Relation between Plasma 25-Hydroxyvitamin D and Insulin Resistance is Largely Attributable to Central Adiposity in Overweight and Obese Adults.

BACKGROUND: Research indicates that plasma 25-hydroxyvitamin D [25(OH)D] is associated with insulin resistance, but whether regional adiposity confounds this association is unclear. OBJECTIVE: This study assessed the potential influence of adiposity and its anatomical distribution on the relation between plasma 25(OH)D and insulin resistance. METHODS: A secondary analysis of data from middle-aged overweight and obese healthy adults [n = 336: 213 women and 123 men; mean ± SD (range); age: 48 ± 8 y (35-65 y); body mass index (BMI; in kg/m2): 30.3 ± 2.7 (26-35)] from West Lafayette, Indiana (40.4 °N), were used for this cross-sectional analysis. Multiple linear regression analyses that controlled for multiple covariates were used as the primary statistical model. RESULTS: Of all participants, 8.6% and 20.5% displayed moderate [20.1-37.5 nmol/L plasma 25(OH)D] to mild (37.6-49.9 nmol/L) vitamin D insufficiency, respectively. A regression analysis controlling for age, sex, race, plasma parathyroid hormone concentration, season of year, and supplement use showed that 25(OH)D was negatively associated with fasting insulin (P = 0.021). Additional regression analyses showed that total and central adiposity but not peripheral adiposity predicted low plasma 25(OH)D [total fat mass index (FMI): P = 0.018; android FMI: P = 0.052; gynoid FMI: P = 0.15; appendicular FMI: P = 0.07) and insulin resistance (homeostasis model assessment of insulin resistance: total and android FMI, P <0.0001; gynoid FMI, P = 0.94; appendicular FMI, P = 0.86). The associations of total and central adiposity with insulin resistance remained significant after adjusting for plasma 25(OH)D. However, adjusting for central adiposity but not other anatomical measures of fat distribution eliminated the association between plasma 25(OH)D and insulin resistance. CONCLUSION: Central adiposity drives the association between plasma 25(OH)D and insulin resistance in overweight and obese adults. The trial was registered at clinicaltrials.gov as NCT00812409.

Higher Total Protein Intake and Change in Total Protein Intake Affect Body Composition but Not Metabolic Syndrome Indexes in Middle-Aged Overweight and Obese Adults Who Perform Resistance and Aerobic Exercise for 36 Weeks.

BACKGROUND: Studies assessing the effects of protein supplementation on changes in body composition (BC) and health rarely consider the impact of total protein intake (TPro) or the change in TPro (CTPro) from participants' usual diets. OBJECTIVE: This secondary data analysis assessed the impact of TPro and CTPro on changes in BC and metabolic syndrome (MetS) indexes in overweight and obese middle-aged adults who participated in an exercise training program. METHODS: Men and women [n = 117; age: 50 ± 0.7 y, body mass index (BMI; in kg/m(2)): 30.1 ± 0.3; means ± SEs] performed resistance exercise 2 d/wk and aerobic exercise 1 d/wk and consumed an unrestricted diet along with 200-kcal supplements (0, 10, 20, or 30 g whey protein) twice daily for 36 wk. Protein intake was assessed via 4-d food records. Multiple linear regression model and stratified analysis were applied for data analyses. RESULTS: Among all subjects, TPro and CTPro were inversely associated (P < 0.05) with changes in body mass, fat mass (FM), and BMI. Changes in BC were different (P < 0.05) among groups that consumed <1.0 (n = 43) vs. ≥1.0 to <1.2 (n = 29) vs. ≥1.2 g · kg(-1) · d(-1) (n = 45). The TPro group with ≥1.0 to <1.2 g ·: kg(-1) ·: d(-1) reduced FM and %FM and increased percentage of LM (%LM) compared with the lowest TPro group, whereas the TPro group with ≥1.2 g ·: kg(-1) ·: d(-1) presented intermediate responses on changes in FM, %FM, and %LM. The gain in LM was not different among groups. In addition, MetS indexes were not influenced by TPro and CTPro. CONCLUSIONS: In conjunction with exercise training, higher TPro promoted positive changes in BC but not in MetS indexes in overweight and obese middle-aged adults. Changes in TPro from before to during the intervention also influenced BC responses and should be considered in future research when different TPro is achieved via diet or supplements. This trial was registered at clinicaltrials.gov as NCT00812409.

Nod-like receptor protein-3 inflammasome plays an important role during early stages of wound healing.

The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1ß pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1ß and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1ß partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1ß production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1ß treated wounds, suggesting that IL-1ß has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1ß-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing.

Low-intensity vibration improves angiogenesis and wound healing in diabetic mice.

Chronic wounds represent a significant health problem, especially in diabetic patients. In the current study, we investigated a novel therapeutic approach to wound healing--whole body low-intensity vibration (LIV). LIV is anabolic for bone, by stimulating the release of growth factors, and modulating stem cell proliferation and differentiation. We hypothesized that LIV improves the delayed wound healing in diabetic mice by promoting a pro-healing wound environment. Diabetic db/db mice received excisional cutaneous wounds and were subjected to LIV (0.4 g at 45 Hz) for 30 min/d or a non-vibrated sham treatment (controls). Wound tissue was collected at 7 and 15 d post-wounding and wound healing, angiogenesis, growth factor levels and wound cell phenotypes were assessed. LIV increased angiogenesis and granulation tissue formation at day 7, and accelerated wound closure and re-epithelialization over days 7 and 15. LIV also reduced neutrophil accumulation and increased macrophage accumulation. In addition, LIV increased expression of pro-healing growth factors and chemokines (insulin-like growth factor-1, vascular endothelial growth factor and monocyte chemotactic protein-1) in wounds. Despite no evidence of a change in the phenotype of CD11b+ macrophages in wounds, LIV resulted in trends towards a less inflammatory phenotype in the CD11b- cells. Our findings indicate that LIV may exert beneficial effects on wound healing by enhancing angiogenesis and granulation tissue formation, and these changes are associated with increases in pro-angiogenic growth factors.

Sustained inflammasome activity in macrophages impairs wound healing in type 2 diabetic humans and mice.

The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound-conditioned medium activates caspase-1 and induces release of interleukin (IL)-1ß and IL-18 in cultured Mp via a reactive oxygen species-mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from proinflammatory to healing-associated Mp phenotypes, and increased levels of prohealing growth factors. Furthermore, data generated from bone marrow-transfer experiments from NLRP-3 or caspase-1 knockout to db/db mice indicated that blocking inflammasome activity in bone marrow cells is sufficient to improve healing. Our findings indicate that sustained inflammasome activity in wound Mp contributes to impaired early healing responses of diabetic wounds and that the inflammasome may represent a new therapeutic target for improving healing in diabetic individuals.

Macrophage activation and skeletal muscle healing following traumatic injury.

Following injury to different tissues, macrophages can contribute to both regenerative and fibrotic healing. These seemingly contradictory roles of macrophages may be related to the markedly different phenotypes that macrophages can assume upon exposure to different stimuli. We hypothesized that fibrotic healing after traumatic muscle injury would be dominated by a pro-fibrotic M2a macrophage phenotype, with M1 activation limited to the very early stages of repair. We found that macrophages accumulated in lacerated mouse muscle for at least 21 days, accompanied by limited myofibre regeneration and persistent collagen deposition. However, muscle macrophages did not exhibit either of the canonical M1 or M2a phenotypes, but instead up-regulated both M1- and M2a-associated genes early after injury, followed by down-regulation of most markers examined. Particularly, IL-10 mRNA and protein were markedly elevated in macrophages from 3-day injured muscle. Additionally, though flow cytometry identified distinct subpopulations of macrophages based on high or low expression of TNFα, these subpopulations did not clearly correspond to M1 or M2a phenotypes. Importantly, cell therapy with exogenous M1 macrophages but not non-activated macrophages reduced fibrosis and enhanced muscle fibre regeneration in lacerated muscles. These data indicate that manipulation of macrophage function has potential to improve healing following traumatic injury.