Vitamin D Deficiency and Long-Term Cognitive Impairment Among Older Adult Emergency Department Patients

Introduction: Approximately 16% of acutely ill older adults develop new, long-term cognitive impairment (LTCI), many of whom initially seek care in the emergency department (ED). Currently, no effective interventions exist to prevent LTCI after an acute illness. Identifying early and modifiable risk factors for LTCI is the first step toward effective therapy. We hypothesized that Vitamin D deficiency at ED presentation was associated with LTCI in older adults.Methods: This was an observational analysis of a prospective cohort study that enrolled ED patients ≥ 65 years old who were admitted to the hospital for an acute illness. All patients were enrolled within four hours of ED presentation. Serum Vitamin D was measured at enrollment and Vitamin D deficiency was defined as serum concentrations <20 mg/dL. We measured pre-illness and six-month cognition using the short form Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), which ranges from 1 to 5 (severe cognitive impairment). Multiple linear regression was performed to determine whether Vitamin D deficiency was associated with poorer six-month cognition adjusted for pre-illness IQCODE and other confounders. We incorporated a two-factor interaction into the regression model to determine whether the relationship between Vitamin D deficiency and six-month cognition was modified by pre-illness cognition.Results: We included a total of 134 older ED patients; the median (interquartile range [IQR]) age was 74 (69, 81) years old, 61 (46%) were female, and 14 (10%) were nonwhite race. The median (IQR) vitamin D level at enrollment was 25 (18, 33) milligrams per deciliter and 41 (31%) of enrolled patients met criteria for vitamin D deficiency. Seventy-seven patients survived and had a six-month IQCODE. In patients with intact pre-illness cognition (IQCODE of 3.13), Vitamin D deficiency was significantly associated with worsening six-month cognition (β-coefficient: 0.43, 95% CI, 0.07 to 0.78, p = 0.02) after adjusting for pre-illness IQCODE and other confounders. Among patients with pre-illness dementia (IQCODE of 4.31), no association with Vitamin D deficiency was observed (β-coefficient: -0.1;, 95% CI, [-0.50-0.27], p = 0.56).Conclusion: Vitamin D deficiency was associated with poorer six-month cognition in acutely ill older adult ED patients who were cognitively intact at baseline. Future studies should determine whether early Vitamin D repletion in the ED improves cognitive outcomes in acutely ill older patients.

Toward the rational design of non-precious transition metal oxides for oxygen electrocatalysis

In this Review, we discuss the state-of-the-art understanding of non-precious transition metal oxides that catalyze the oxygen reduction and evolution reactions. Understanding and mastering the kinetics of oxygen electrocatalysis is instrumental to making use of photosynthesis, advancing solar fuels, fuel cells, electrolyzers, and metal–air batteries. We first present key insights, assumptions and limitations of well-known activity descriptors and reaction mechanisms in the past four decades. The turnover frequency of crystalline oxides as promising catalysts is also put into perspective with amorphous oxides and photosystem II. Particular attention is paid to electronic structure parameters that can potentially govern the adsorbate binding strength and thus provide simple rationales and design principles to predict new catalyst chemistries with enhanced activity. We share new perspective synthesizing mechanism and electronic descriptors developed from both molecular orbital and solid state band structure principles. We conclude with an outlook on the opportunities in future research within this rapidly developing field.National Science Foundation (U.S.) (DMR - 0819762)National Science Foundation (U.S.) (DGE-1122374

Delirium and mortality risk prediction: a story in evolution

Contains fulltext : 88249.pdf (publisher's version ) (Open Access

INTEGRATE: Gene fusion discovery using whole genome and transcriptome data

While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use

Convenience stores are the key food environment influence on nutrients available from household food supplies in Texas Border Colonias

BACKGROUND: Few studies have focused on the relationship between the retail food environment and household food supplies. This study examines spatial access to retail food stores, food shopping habits, and nutrients available in household food supplies among 50 Mexican-origin families residing in Texas border colonias. METHODS: The design was cross-sectional; data were collected in the home March to June 2010 by promotora-researchers. Ground-truthed methods enumerated traditional (supercenters, supermarkets, grocery stores), convenience (convenience stores and food marts), and non-traditional (dollar stores, discount stores) retail food stores. Spatial access was computed using the network distance from each participant’s residence to each food store. Data included survey data and two household food inventories (HFI) of the presence and amount of food items in the home. The Spanish language interviewer-administered survey included demographics, transportation access, food purchasing, food and nutrition assistance program participation, and the 18-item Core Food Security Module. Nutrition Data Systems for Research (NDS-R) was used to calculate HFI nutrients. Adult equivalent adjustment constants (AE), based on age and gender calorie needs, were calculated based on the age- and gender composition of each household and used to adjust HFI nutrients for household composition. Data were analyzed using bivariate analysis and linear regression models to determine the association of independent variables with the availability of each AE-adjusted nutrient. RESULTS: Regression models showed that households in which the child independently purchased food from a convenience store at least once a week had foods and beverages with increased amounts of total energy, total fat, and saturated fat. A greater distance to the nearest convenience store was associated with reduced amounts of total energy, vitamin D, total sugar, added sugar, total fat, and saturated fat. Participation in the National School Lunch Program (NSLP) was associated with lower household levels of total energy, calcium, vitamin C, sodium, vitamin D, and saturated fat. Spatial access and utilization of supermarkets and dollar stores were not associated with nutrient availability. CONCLUSIONS: Although household members frequently purchased food items from supermarkets or dollar stores, it was spatial access to and frequent utilization of convenience food stores that influenced the amount of nutrients present in Texas border colonia households. These findings also suggest that households which participate in NSLP have reduced AE-adjusted nutrients available in the home. The next step will target changes within convenience stores to improve in-store marketing of foods and beverages to children and adults

Lead Screening for Chronic Obstructive Pulmonary Disease of IKK2 Inhibited by Traditional Chinese Medicine

Chronic obstructive pulmonary disease (COPD) is a chronic obstructive lung disease and is frequently found in well-developed countries due to the issue of aging populations. Not all forms of medical treatment are unable to return a patient's limited pulmonary function back to normal and eventually they could require a lung transplant. At this time, COPD is the leading cause of death in the world. Studies surveying I-kappa-B-kinase beta (IKK2) are very relevant to the occurrence and deterioration of the condition COPD. The sinapic acid-4-O-sulfate, kaempferol, and alpha-terpineol were found to be IKK2 inhibitors and helped prevent COPD occurrence and worsening according to a screening of the traditional Chinese medicine (TCM) database. The protein-ligand interaction of these three compounds with regard to IKK2 was also done by molecular dynamics. The docking poses, hydrogen bond variation, and hydrophobic interactions found Asp103 and Lys106 are crucial to IKK2 binding areas for IKK2 inhibition. Finally, we found the three compounds that have an equally strong effect in terms of IKK2 binding proven by the TCM database and perhaps these may be an alternative treatment for COPD in the future

Investigation of Anti-Infection Mechanism of Lactoferricin and Splunc-1

The innate immune system is the first line in the defense system and prevents the body from further bacteria, virus, or fungal infections. Most of the innate immune system is relevant to mucosa immunity. Lactotransferrin is secreted from the human mammal breast duct epithelial tissue and strengthens infant immunity to defense with regard to outward pathogens. Splunc-1 is also an innate material secreted from the soft palate, lung, nasal cavity epithelium, and mucosa. It helps with mucosa defense against bacterial, virus, and even fungus. LPS is the main etiology of Gram-negative bacilla infection source. And studies of lactoferricin and slpunc-1 both can combine with LPS and subsequently cause insults to the mucosa. Although, we know that both of them partake in an important role in innate immunity, we do not know the effects when they work together. In this study, we just overview silicon stimulation to examine the combination of Lactoferricin and Splunc-1 and the effect with regard to LPS

Excitatory Motor Neurons are Local Central Pattern Generators in an Anatomically Compressed Motor Circuit for Reverse Locomotion [preprint]

Central pattern generators are cell- or network-driven oscillators that underlie motor rhythmicity. The existence and identity of C. elegans CPGs remain unknown. Through cell ablation, electrophysiology, and calcium imaging, we identified oscillators for reverse locomotion. We show that the cholinergic and excitatory class A motor neurons exhibit intrinsic and oscillatory activity, and such an activity can drive reverse locomotion without premotor interneurons. Regulation of their oscillatory activity, either through effecting an endogenous constituent of oscillation, the P/Q/N high voltage-activated calcium channel UNC-2, or, via dual regulation, inhibition and activation, by the descending premotor interneurons AVA, determines the propensity, velocity, and sustention of reverse locomotion. Thus, the reversal motor executors themselves serve as oscillators; regulation of their intrinsic activity controls the reversal motor state. These findings exemplify anatomic and functional compression: motor executors integrate the role of rhythm generation in a locomotor network that is constrained by small cell numbers

Excitatory motor neurons are local oscillators for backward locomotion

Cell- or network-driven oscillators underlie motor rhythmicity. The identity of C. elegans oscillators remains unknown. Through cell ablation, electrophysiology, and calcium imaging, we show: (1) forward and backward locomotion is driven by different oscillators; (2) the cholinergic and excitatory A-class motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive backward locomotion in the absence of premotor interneurons; (3) the UNC-2 P/Q/N high-voltage-activated calcium current underlies A motor neuron\u27s oscillation; (4) descending premotor interneurons AVA, via an evolutionarily conserved, mixed gap junction and chemical synapse configuration, exert state-dependent inhibition and potentiation of A motor neuron\u27s intrinsic activity to regulate backward locomotion. Thus, motor neurons themselves derive rhythms, which are dually regulated by the descending interneurons to control the reversal motor state. These and previous findings exemplify compression: essential circuit properties are conserved but executed by fewer numbers and layers of neurons in a small locomotor network