The mandate of folic acid supplementation in grained products has reduced the occurrence of neural tube defects by one third in the U.S since its introduction by the Food and Drug Administration in ...1998. However, the advantages and possible mechanisms of action of using folic acid for peripheral nerve engineering and neurological diseases still remain largely elusive. Herein, folic acid is described as an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical translation. Our results suggest that folic acid-nerve guidance conduits may offer significant benefits as a low-cost, off-the-shelf product for reaching the functional recovery seen with autografts in large sciatic nerve defects. Consequently, folic acid holds great potential as a critical and convenient therapeutic intervention for neural engineering, regenerative medicine, medical prosthetics, and drug delivery.
Background Laparoscopic surgery for colon cancer has been demonstrated in clinical trials to have short-term benefits when compared to the open surgical approach. Guidelines of the National ...Comprehensive Cancer Network recommend that patients with stage III or high-risk stage II colon cancer undergo adjuvant chemotherapy. We hypothesized that laparoscopic colectomy is associated with increased compliance to recommendations for chemotherapy, a lesser time to start of chemotherapy, and increased overall survival. Methods The National Cancer Data Base was queried to identify patients with stage III or high-risk stage II colon cancer (T4, positive margins, <12 lymph nodes, or high tumor grade) diagnosed 2010–2012. Patients were divided into laparoscopic colectomy and open colectomy groups. Intent-to-treat analysis was used with converted cases included in the laparoscopic colectomy group. Rates of receiving adjuvant chemotherapy, time from diagnosis and date of operation to start of chemotherapy, and overall survival were compared. Results A total of 48,257 patients were included for analysis; 18,801 patients underwent laparoscopic colectomy and 29,456 underwent open colectomy. Laparoscopic colectomy patients received adjuvant chemotherapy at a somewhat greater rate than open colectomy (66.2% vs 59.4%, P < .01). Among patients who received chemotherapy, mean time to start of chemotherapy after definitive resection was somewhat less for laparoscopic colectomy than open colectomy (48.7 vs 52.7 days, P < .01). Two-year overall survival was greater for laparoscopic colectomy than open colectomy (81.9% vs 73.2%, P < .01). Conclusion Compared to open colectomy, laparoscopic colectomy is associated with somewhat greater rates of compliance with guidelines for adjuvant chemotherapy for stage III and high-risk stage II colon cancer, as well as a slightly lesser time to start of chemotherapy and improved overall survival.
Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms. However, the underlying mechanisms leading to the development of both ...phenotypes have not been elucidated. Here, we show that mouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternal inflammation were more susceptible to developing intestinal inflammation following challenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes, interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changes in the maternal gut microbiota that led to postnatal alterations in the chromatin landscape of naive CD4+ T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responses into germ-free dams produced immune-primed phenotypes in offspring. Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.
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•Mice prenatally exposed to maternal immune activation display immune-primed phenotypes•Maternal immune activation induces changes in the gut microbiota of pregnant mice•Altered microbiota promote immune priming by affecting T cells’ chromatin accessibility•Maternal IL-17A shapes the immune-primed phenotypes through changes in microbiota
Children with autism spectrum disorders often display dysregulated immune responses. Using a preclinical mouse model manifesting neurodevelopmental pathologies following exposure to maternal immune activation, Kim et al. revealed that changes in the gut microbiota of pregnant mice affect chromatin accessibility of naive CD4+ T cells in their offspring, leading to immune-primed phenotypes.
There is limited research on capacity building interventions that include theoretical foundations. The purpose of this systematic review is to identify underlying theories, models and frameworks used ...to support capacity building interventions relevant to public health practice. The aim is to inform and improve capacity building practices and services offered by public health organizations.
Four search strategies were used: 1) electronic database searching; 2) reference lists of included papers; 3) key informant consultation; and 4) grey literature searching. Inclusion and exclusion criteria are outlined with included papers focusing on capacity building, learning plans, professional development plans in combination with tools, resources, processes, procedures, steps, model, framework, guideline, described in a public health or healthcare setting, or non-government, government, or community organizations as they relate to healthcare, and explicitly or implicitly mention a theory, model and/or framework that grounds the type of capacity building approach developed. Quality assessment were performed on all included articles. Data analysis included a process for synthesizing, analyzing and presenting descriptive summaries, categorizing theoretical foundations according to which theory, model and/or framework was used and whether or not the theory, model or framework was implied or explicitly identified.
Nineteen articles were included in this review. A total of 28 theories, models and frameworks were identified. Of this number, two theories (Diffusion of Innovations and Transformational Learning), two models (Ecological and Interactive Systems Framework for Dissemination and Implementation) and one framework (Bloom's Taxonomy of Learning) were identified as the most frequently cited.
This review identifies specific theories, models and frameworks to support capacity building interventions relevant to public health organizations. It provides public health practitioners with a menu of potentially usable theories, models and frameworks to support capacity building efforts. The findings also support the need for the use of theories, models or frameworks to be intentional, explicitly identified, referenced and for it to be clearly outlined how they were applied to the capacity building intervention.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Childhood neglect and/or abuse can induce mental health conditions with unknown mechanisms. Here, we identified stress hormones as strong inducers of astrocyte-mediated synapse phagocytosis. Using ...in vitro, in vivo, and human brain organoid experiments, we showed that stress hormones increased the expression of the Mertk phagocytic receptor in astrocytes through glucocorticoid receptor (GR). In post-natal mice, exposure to early social deprivation (ESD) specifically activated the GR-MERTK pathway in astrocytes, but not in microglia. The excitatory post-synaptic density in cortical regions was reduced in ESD mice, and there was an increase in the astrocytic engulfment of these synapses. The loss of excitatory synapses, abnormal neuronal network activities, and behavioral abnormalities in ESD mice were largely prevented by ablating GR or MERTK in astrocytes. Our work reveals the critical roles of astrocytic GR-MERTK activation in evoking stress-induced abnormal behaviors in mice, suggesting GR-MERTK signaling as a therapeutic target for stress-induced mental health conditions.
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•Stress hormones induce astrocyte-mediated phagocytosis through GR-MERTK activation•Astrocytic GR-MERTK activation induces excitatory synapse loss in ESD model mice•ESD model mice show abnormal behaviors with increased cortical neuronal firing•Ablating GR-MERTK in astrocytes prevents ESD-evoked synapse loss and behavior symptoms
Early social deprivation induces synaptic and behavioral deficits by unknown mechanisms. Byun et al. reveal that stress hormones induce excessive excitatory synapse elimination via the astrocytic GR-MERTK pathway. Ablating GR-MERTK from astrocytes prevents the loss of excitatory synapses, abnormal neuronal firing, and behavioral symptoms in ESD mice, emphasizing the critical roles of astrocytic phagocytosis in brain physiology and animal behavior.
OBJECTIVE: Iron deficiency has been reported to elevate A1C levels apart from glycemia. We examined the influence of iron deficiency on A1C distribution among adults without diabetes. RESEARCH DESIGN ...AND METHODS: Participants included adults without self-reported diabetes or chronic kidney disease in the National Health and Nutrition Examination Survey 1999-2006 who were aged ≥18 years of age and had complete blood counts, iron studies, and A1C levels. Iron deficiency was defined as at least two abnormalities including free erythrocyte protoporphyrin >70 μg/dl erythrocytes, transferrin saturation <16%, or serum ferritin less-than or equal to15 μg/l. Anemia was defined as hemoglobin <13.5 g/dl in men and <12.0 g/dl in women. RESULTS: Among women (n = 6,666), 13.7% had iron deficiency and 4.0% had iron deficiency anemia. Whereas 316 women with iron deficiency had A1C ≥5.5%, only 32 women with iron deficiency had A1C ≥6.5%. Among men (n = 3,869), only 13 had iron deficiency and A1C ≥5.5%, and only 1 had iron deficiency and A1C ≥6.5%. Among women, iron deficiency was associated with a greater odds of A1C ≥5.5% (odds ratio 1.39 95% CI 1.11-1.73) after adjustment for age, race/ethnicity, and waist circumference but not with a greater odds of A1C ≥6.5% (0.79 0.33-1.85). CONCLUSIONS: Iron deficiency is common among women and is associated with shifts in A1C distribution from <5.5 to ≥5.5%. Further research is needed to examine whether iron deficiency is associated with shifts at higher A1C levels.
Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed ...along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-γ-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3',4'-dihydroxyphenyl)-γ-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-γ-valerolactone-sulfate (3',4' isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the "gut-brain axis".
The most powerful country on the planet was not expected to fall so easily to a virus. Yet 13 months after the outbreak of COVID-19, the United States continues to display some of the worst outcomes ...in the world: more than 23 million cases and 390 000 deaths.1 Despite having more time to prepare- thanks to lessons learned from our European and Asian counterparts-we have struggled with poor communication, mismanaged information, and inconsistent response coordination. In some regions of the United States, pandemic mortality varies widely within a 15-minute driving distance, magnifying long-standing inequities in life expectancy and access to care. These disparities persist when stratified by neighborhood income, overcrowding, work environment, and other barriers. Meanwhile, in smaller, less powerful countries, including Taiwan and New Zealand, the virus is all but contained.2So why the difference?One answer lies in precision public health: the best response for a specific population at a given point in time.3 Precision public health addresses disparities in morbidity and mortality and is particularly relevant, as COVID-19 exacerbates health inequities (Figure A, available as a supplement to the online version ofthis article at http://www.ajph. org) and unearths political and social divides.3
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