The Influence of Comorbidities, General Health Status, and Self-Care Self-Efficacy on COVID-19 Symptoms During the Omicron Wave.

Background The emergence of the less virulent COVID-19 strains such as Omicron and its subvariants shifted the paradigm of COVID-19 treatment from inpatient treatment to regular outpatient care. The individual health determinants affecting COVID-19 disease severity among vulnerable adults treated in outpatient settings are an under-researched area. Methods This study conducted in an outpatient COVID-19 antibody infusion center employed a cross-sectional survey design to explore the impact of comorbidities, general health status, and self-care self-efficacy on COVID-19 symptom severity. We recruited 120 COVID-19-positive participants over 40 years of age, of which 117 completed the study with 87 providing complete data. After the screening and consenting process, the participants completed the following surveys in a secure REDCap survey software (Vanderbilt University, Nashville, USA) on an iPad (Apple Inc., Cupertino, USA): 1) sociodemographic questionnaire, 2) Charlson Comorbidity Index (CCI) to capture comorbidities, 3) Medical Outcomes Study Short-Form (SF-12) to assess general health including physical (PCS) and mental (MCS) health subscales, 4) Self-Care Self-Efficacy Scale (SCSES) to measure self-care self-efficacy, and 5) the COVID-19 Symptom rating scale (COVID-19 SRS). Statistical analysis used were Chi-square and Pearson correlations.  Results As evidenced by CCI, the top five comorbidities were hypertension (42%), diabetes mellitus (31%), pulmonary disease (19%), depression (14%), and solid tumors (11%). Age was statistically significantly correlated to comorbidity burden (p<0.0001). Severe COVID-19 symptoms reported were fatigue, myalgia, cough, runny nose, and sore throat. The general health status measure (SF-12) subscales showed that the patient's mental component summary (MCS) was more statistically significant to COVID-19 symptom severity than the physical component summary (PCS). The MCS demonstrated a statistically significant correlation with fatigue and myalgia (p<0.0001), headache and breathing difficulties (p<0.001), nausea/vomiting (p<0.01), and abdominal pain/diarrhea (p<0.05). The PCS showed a lesser statistically significant correlation with fatigue, myalgia, headaches (p<0.01), fever/chills, cough, congestion/runny nose, night sweats, breathing difficulties, nausea/vomiting, and abdominal pain/diarrhea (p<0.05). Interestingly, the 'loss of smell' which is the hallmark symptom of COVID-19 was the only symptom that showed a statically significant correlation with the Charlson Comorbidity Index (p<0.05), and it did not show any association with either mental (SF-12 MCS) or physical (SF-12 PCS) health status. The SF-12 MCS also showed a statistically significant correlation with a diagnosis of depression (p< 0.01), validating it as a true measure of mental health among vulnerable adults. The SCSES was not correlated with any of the COVID-19 symptoms. Conclusions The patient's general health status, especially mental health was more statistically significant to COVID-19 symptoms. The COVID-19 hallmark symptom of 'loss of smell' was the only symptom that showed statistical significance with comorbidities. Within the limitations of a cross-sectional survey design and convenient sampling methods, this study calls to tailor general health status, especially mental health, and cumulative comorbidity burden to risk assessment/risk stratification of COVID-19 care.

Real-time heterogeneity of supramolecular assembly of amyloid precursor protein is modulated by an endocytic risk factor PICALM.

Recently, the localization of amyloid precursor protein (APP) into reversible nanoscale supramolecular assembly or "nanodomains" has been highlighted as crucial towards understanding the onset of the molecular pathology of Alzheimer's disease (AD). Surface expression of APP is regulated by proteins interacting with it, controlling its retention and lateral trafficking on the synaptic membrane. Here, we evaluated the involvement of a key risk factor for AD, PICALM, as a critical regulator of nanoscale dynamics of APP. Although it was enriched in the postsynaptic density, PICALM was also localized to the presynaptic active zone and the endocytic zone. PICALM colocalized with APP and formed nanodomains with distinct morphological properties in different subsynaptic regions. Next, we evaluated if this localization to subsynaptic compartments was regulated by the C-terminal sequences of APP, namely, the "Y682ENPTY687" domain. Towards this, we found that deletion of C-terminal regions of APP with partial or complete deletion of Y682ENPTY687, namely, APP-Δ9 and APP-Δ14, affected the lateral diffusion and nanoscale segregation of APP. Lateral diffusion of APP mutant APP-Δ14 sequence mimicked that of a detrimental Swedish mutant of APP, namely, APP-SWE, while APP-Δ9 diffused similar to wild-type APP. Interestingly, elevated expression of PICALM differentially altered the lateral diffusion of the APP C-terminal deletion mutants. These observations confirm that the C-terminal sequence of APP regulates its lateral diffusion and the formation of reversible nanoscale domains. Thus, when combined with autosomal dominant mutations, it generates distinct molecular patterns leading to onset of Alzheimer's disease (AD).

Coronavirus Disease 2019, Diabetes, and Inflammation: A Systemic Review.

People with cardiometabolic diseases [namely type 2 diabetes (T2D), obesity, or metabolic syndrome] are more susceptible to coronavirus disease 2019 (COVID-19) infection and endure more severe illness and poorer outcomes. Hyperinflammation has been suggested as a common pathway for both diseases. To examine the role of inflammatory biomarkers shared between COVID-19 and cardiometabolic diseases, we reviewed and evaluated published data using PubMed, SCOPUS, and World Health Organization COVID-19 databases for English articles from December 2019 to February 2022. Of 248 identified articles, 50 were selected and included. We found that people with diabetes or obesity have (i) increased risk of COVID-19 infection; (ii) increased risk of hospitalization (those with diabetes have a higher risk of intensive care unit admissions) and death; and (iii) heightened inflammatory and stress responses (hyperinflammation) to COVID-19, which worsen their prognosis. In addition, COVID-19-infected patients have a higher risk of developing T2D, especially if they have other comorbidities. Treatments controlling blood glucose levels and or ameliorating the inflammatory response may be valuable for improving clinical outcomes in these patient populations. In conclusion, it is critical for health care providers to clinically evaluate hyperinflammatory states to drive clinical decisions for COVID-19 patients.

Achieving nanoscale precision using neuromorphic localization microscopy.

Neuromorphic cameras are a new class of dynamic-vision-inspired sensors that encode the rate of change of intensity as events. They can asynchronously record intensity changes as spikes, independent of the other pixels in the receptive field, resulting in sparse measurements. This recording of such sparse events makes them ideal for imaging dynamic processes, such as the stochastic emission of isolated single molecules. Here we show the application of neuromorphic detection to localize nanoscale fluorescent objects below the diffraction limit, with a precision below 20 nm. We demonstrate a combination of neuromorphic detection with segmentation and deep learning approaches to localize and track fluorescent particles below 50 nm with millisecond temporal resolution. Furthermore, we show that combining information from events resulting from the rate of change of intensities improves the classical limit of centroid estimation of single fluorescent objects by nearly a factor of two. Additionally, we validate that using post-processed data from the neuromorphic detector at defined windows of temporal integration allows a better evaluation of the fractalized diffusion of single particle trajectories. Our observations and analysis is useful for event sensing by nonlinear neuromorphic devices to ameliorate real-time particle localization approaches at the nanoscale.

Nanoscale regulation of Ca2+ dependent phase transitions and real-time dynamics of SAP97/hDLG.

Synapse associated protein-97/Human Disk Large (SAP97/hDLG) is a conserved, alternatively spliced, modular, scaffolding protein critical in regulating the molecular organization of cell-cell junctions in vertebrates. We confirm that the molecular determinants of first order phase transition of SAP97/hDLG is controlled by morpho-functional changes in its nanoscale organization. Furthermore, the nanoscale molecular signatures of these signalling islands and phase transitions are altered in response to changes in cytosolic Ca2+. Additionally, exchange kinetics of alternatively spliced isoforms of the intrinsically disordered region in SAP97/hDLG C-terminus shows differential sensitivities to Ca2+ bound Calmodulin, affirming that the molecular signatures of local phase transitions of SAP97/hDLG depends on their nanoscale heterogeneity and compositionality of isoforms.

Association between Caffeine Intake and All-Cause and Cause-Specific Mortality: An Analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014 Database.

Sixty-four percent of adults in America drink coffee daily, and caffeine is the main reason people tend to drink coffee habitually. Few studies have examined the association between caffeine and all-cause and cause-specific mortality. The objective of this study was to examine the association between caffeine and all-cause and cause-specific mortality using the National Health and Nutrition Examination Survey (NHANES) 1999-2014 database. The multivariate Cox proportional hazards regression model was used to examine 23,878 individuals 20 years and older. Daily caffeine intake was measured once at baseline. A total of 2206 deaths occurred, including 394 cardiovascular (CVD) deaths and 525 cancer deaths. Compared to those with a caffeine intake of <100 mg/day, the hazard ratios (HRs) for CVD mortality were significantly lower in the participants with a caffeine intake of 100-200 mg/day (HR, 0.63; 95% confidence interval [CI], 0.45-0.88), and those with a caffeine intake of >200 mg/day (HR, 0.67; 95% CI, 0.50-0.88) after adjusting for potential confounders. The HRs for all-cause mortality were significantly lower in the participants with a caffeine intake of 100-200 mg/day (HR, 0.78; 95% CI, 0.67-0.91), and those with a caffeine intake of >200 mg/day (HR, 0.68; 95% CI, 0.60-0.78). Subgroup analyses showed that caffeine may have different effects on all-cause mortality among different age and body mass index (BMI) groups. In conclusion, higher caffeine intake was associated with lower all-cause and CVD mortality.

Membrane Cholesterol Is a Critical Determinant for Hippocampal Neuronal Polarity.

Maintaining a normal cholesterol balance is crucial for the functioning of a healthy brain. Dysregulation in cholesterol metabolism and homeostasis in the brain have been correlated to various neurological disorders. The majority of previous studies in primary cultures focus on the role of cholesterol balance in neuronal development after polarity has been established. Here we have investigated how transient alteration of membrane lipids, specifically cholesterol, affects neuronal development and polarity in developing hippocampal neurons prior to polarity establishment, soon after initiation of neurite outgrowth. We observed that temporary cholesterol perturbation affects axonal and dendritic development differentially in an opposing manner. Transient membrane cholesterol deficiency increased neuronal population with a single neurite, simultaneously generating a second population of neurons with supernumerary axons. Brief replenishment of cholesterol immediately after cholesterol sequestering rescued neuronal development defects and restored polarity. The results showed a small window of cholesterol concentration to be complementing neurite outgrowth, polarity reestablishment, and in determining the normal neuronal morphology, emphasizing the critical role of precise membrane lipid balance in defining the neuronal architecture. Membrane cholesterol enhancement modified neurite outgrowth but did not significantly alter polarity. Cholesterol sequestering at later stages of development has shown to enhance neurite outgrowth, whereas distinct effects for neurite development and polarity were observed at early developmental stages, signifying the relevance of precise membrane cholesterol balance in altering neuronal physiology. Our results confirm cholesterol to be a key determinant for axo-dendritic specification and neuronal architecture and emphasize the possibility to reverse neuronal developmental defects caused by cholesterol deficiency by modulating membrane cholesterol during the early developmental stages.

Nanoscale organization of Nicastrin, the substrate receptor of the γ-secretase complex, as independent molecular domains.

Alterations in the canonical processing of Amyloid Precursor Protein generate proteoforms that contribute to the onset of Alzheimer's Disease. Modified composition of γ-secretase or mutations in its subunits has been directly linked to altered generation of Amyloid beta. Despite biochemical evidence about the role of γ-secretase in the generation of APP, the molecular origin of how spatial heterogeneity in the generation of proteoforms arises is not well understood. Here, we evaluated the localization of Nicastrin, a γ-secretase subunit, at nanometer sized functional zones of the synapse. With the help of super resolution microscopy, we confirm that Nicastrin is organized into nanodomains of high molecular density within an excitatory synapse. A similar nanoorganization was also observed for APP and the catalytic subunit of γ-secretase, Presenilin 1, that were discretely associated with Nicastrin nanodomains. Though Nicastrin is a functional subunit of γ-secretase, the Nicastrin and Presenilin1 nanodomains were either colocalized or localized independent of each other. The Nicastrin and Presenilin domains highlight a potential independent regulation of these molecules different from their canonical secretase function. The collisions between secretases and substrate molecules decide the probability and rate of product formation for transmembrane proteolysis. Our observations of secretase nanodomains indicate a spatial difference in the confinement of substrate and secretases, affecting the local probability of product formation by increasing their molecular availability, resulting in differential generation of proteoforms even within single synapses.

Optogenetic modulation of real-time nanoscale dynamics of HCN channels using photoactivated adenylyl cyclases.

Adenosine 3',5'-cyclic monophosphate (cAMP) is a key second messenger that activates several signal transduction pathways in eukaryotic cells. Alteration of basal levels of cAMP is known to activate protein kinases, regulate phosphodiesterases and modulate the activity of ion channels such as Hyper polarization-activated cyclic nucleotide gated channels (HCN). Recent advances in optogenetics have resulted in the availability of novel genetically encoded molecules with the capability to alter cytoplasmic profiles of cAMP with unprecedented spatial and temporal precision. Using single molecule based super-resolution microscopy and different optogenetic modulators of cellular cAMP in both live and fixed cells, we illustrate a novel paradigm to report alteration in nanoscale confinement of ectopically expressed HCN channels. We characterized the efficacy of cAMP generation using ensemble photoactivation of different optogenetic modulators. Then we demonstrate that local modulation of cAMP alters the exchange of membrane bound HCN channels with its nanoenvironment. Additionally, using high density single particle tracking in combination with both acute and chronic optogenetic elevation of cAMP in the cytoplasm, we show that HCN channels are confined to sub 100 nm sized functional domains on the plasma membrane. The nanoscale properties of these domains along with the exchange kinetics of HCN channels in and out of these molecular zones are altered upon temporal changes in the cytoplasmic cAMP. Using HCN2 point mutants and a truncated construct of HCN2 with altered sensitivity to cAMP, we confirmed these alterations in lateral organization of HCN2 to be specific to cAMP binding. Thus, combining these advanced non-invasive paradigms, we report a cAMP dependent ensemble and single particle behavior of HCN channels mediated by its cyclic nucleotide binding domain, opening innovative ways to dissect biochemical pathways at the nanoscale and real-time in living cells.

Health determinants and risk factors for coronary artery disease among older Filipinos in rural communities.

AIMS: Lifestyle modifications and healthy behavioural regimens are critical in preventing coronary artery disease (CAD) and other important health conditions. Little is known about the risk for CAD and health behaviour among older adults (>60 years) living in rural areas in the Philippines. Compare risk profiles and health behaviours of Filipinos at low- vs. moderate-to-high-risk for CAD and examine the association between demographic variables, risk profiles, and health behaviours. METHODS AND RESULTS: A comparative, cross-sectional study was conducted using a convenient sample of 427 Filipinos (≥60 years old). Data on sociodemographic characteristics, risk profiles, and health behaviours (e.g. diet, physical activity, smoking status, and alcohol use) were collected. Ten-year CAD risk was estimated using the non-laboratory-based Framingham algorithm. Of the 427 participants [mean age was 69.2 ± 6.7 years, primarily women (65%), married (52.8%)], 319 (75%) were at low risk, and 108 (25%) were at moderate-to-high-risk for CAD. Filipinos at moderate to high risk were more likely to have cardiometabolic diseases (e.g. hypertension, hyperlipidaemia, diabetes, and obesity, all P's < 0.001). Health behaviours did not differ between the two groups except for the consumption of ≥5 servings of fruit, higher in the low-risk group. CONCLUSION: Data showed highly consistent and convergent evidence among older Filipinos living in rural areas at high risk for CAD and other health conditions. These findings underscore the need for culturally sensitive guidance to improve CAD outcomes for moderate to high-risk older adults living in rural areas, including education and counselling on risk and risk-reducing strategies.

Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease.

Despite intuitive insights into differential proteolysis of amyloid precursor protein (APP), the stochasticity behind local product formation through amyloidogenic pathway at individual synapses remain unclear. Here, we show that the major components of amyloidogenic machinery namely, APP and secretases are discretely organized into nanodomains of high local concentration compared to their immediate environment in functional zones of the synapse. Additionally, with the aid of multiple models of Alzheimer's disease (AD), we confirm that this discrete nanoscale chemical map of amyloidogenic machinery is altered at excitatory synapses. Furthermore, we provide realistic models of amyloidogenic processing in unitary vesicles originating from the endocytic zone of excitatory synapses. Thus, we show how an alteration in the stochasticity of synaptic nanoscale organization contributes to the dynamic range of C-terminal fragments ß (CTFß) production, defining the heterogeneity of amyloidogenic processing at individual synapses, leading to long-term synaptic deficits as seen in AD.

High-protein vs. standard-protein diets in overweight and obese patients with heart failure and diabetes mellitus: findings of the Pro-HEART trial.

AIMS: The intermediate-term effects of dietary protein on cardiometabolic risk factors in overweight and obese patients with heart failure and diabetes mellitus are unknown. We compared the effect of two calorie-restricted diets on cardiometabolic risk factors in this population. METHODS AND RESULTS: In this randomized controlled study, 76 overweight and obese (mean weight, 107.8 ± 20.8 kg) patients aged 57.7 ± 9.7 years, 72.4% male, were randomized to a high-protein (30% protein, 40% carbohydrates, and 30% fat) or standard-protein diet (15% protein, 55% carbohydrates, and 30% fat) for 3 months. Reductions in weight and cardiometabolic risks were evaluated at 3 months. Both diets were equally effective in reducing weight (3.6 vs. 2.9 kg) and waist circumference (1.9 vs. 1.3 cm), but the high-protein diet decreased to a greater extent glycosylated haemoglobin levels (0.7% vs. 0.1%, P = 0.002), cholesterol (16.8 vs. 0.9 mg/dL, P = 0.031), and triglyceride (25.7 vs. 5.7 mg/dL, P = 0.032), when compared with the standard-protein diet. The high-protein diet also significantly improved both systolic and diastolic blood pressure than the standard-protein diet (P < 0.001 and P = 0.040, respectively). CONCLUSIONS: Both energy-restricted diets reduced weight and visceral fat. However, the high-protein diet resulted in greater reductions in cardiometabolic risks relative to a standard-protein diet. These results suggest that a high-protein diet may be more effective in reducing cardiometabolic risk in this population, but further trials of longer duration are needed.

Real-time nanoscale organization of amyloid precursor protein.

Despite an intuitive understanding of the role of APP in health and disease, there exist few attempts to dissect its molecular localization at excitatory synapses. Though the biochemistry involved in the enzymatic processing of APP is well understood, there is a void in understanding the nonuniformity of the product formation in vivo. Here, we employed multiple paradigms of single molecules and ensemble based nanoscopic imaging to reveal that APP molecules are organized into regulatory nanodomains that are differentially compartmentalized in the functional zones of an excitatory synapse. Furthermore, with the aid of high density single particle tracking, we show that the lateral diffusion of APP in live cells dictates an equilibrium between these nanodomains and their nano-environment, which is affected in a detrimental variant of APP. Additionally, we incorporate this spatio-temporal detail 'in silico' to generate a realistic nanoscale topography of APP in dendrites and synapses. This approach uncovers a nanoscale heterogeneity in the molecular organization of APP, depicting a locus for differential APP processing. This holistic paradigm, to decipher the real-time heterogeneity of the substrate molecules on the nanoscale, could enable us to better evaluate the molecular constraints overcoming the ensemble approaches used traditionally to understand the kinetics of product formation.

Differential Scaling of Synaptic Molecules within Functional Zones of an Excitatory Synapse during Homeostatic Plasticity.

Homeostatic scaling is a form of synaptic plasticity where individual synapses scale their strengths to compensate for global suppression or elevation of neuronal activity. This process can be studied by measuring miniature EPSP (mEPSP) amplitudes and frequencies following the regulation of activity in neuronal cultures. Here, we demonstrate a quantitative approach to characterize multiplicative synaptic scaling using immunolabelling of hippocampal neuronal cultures treated with tetrodotoxin (TTX) or bicuculline to extract scaling factors for various synaptic proteins. This approach allowed us to directly examine the scaling of presynaptic and postsynaptic scaffolding molecules along with neurotransmitter receptors in primary cultures from mouse and rat hippocampal neurons. We show robust multiplicative scaling of synaptic scaffolding molecules namely, Shank2, PSD95, Bassoon, and AMPA receptor subunits and quantify their scaling factors. We use super-resolution microscopy to calculate scaling factors of surface expressed GluA2 within functional zones of the synapse and show that there is differential and correlated scaling of GluA2 levels within the spine, the postsynaptic density (PSD), and the perisynaptic regions. Our method opens a novel paradigm to quantify relative molecular changes of synaptic proteins within distinct subsynaptic compartments from a large number of synapses in response to alteration of neuronal activity, providing anatomic insights into the intricacies of variability in strength of individual synapses.

Characterization of Nanoscale Organization of F-Actin in Morphologically Distinct Dendritic Spines In Vitro Using Supervised Learning.

The cytoarchitecture of a neuron is very important in defining morphology and ultrastructure. Although there is a wealth of information on the molecular components that make and regulate these ultrastructures, there is a dearth of understanding of how these changes occur or how they affect neurons in health and disease. Recent advances in nanoscale imaging which resolve cellular structures at the scale of tens of nanometers below the limit of diffraction enable us to understand these structures in fine detail. However, automated analysis of these images is still in its infancy. Towards this goal, attempts have been made to automate the detection and analysis of the cytoskeletal organization of microtubules. To date, evaluation of the nanoscale organization of filamentous actin (F-actin) in neuronal compartments remains challenging. Here, we present an objective paradigm for analysis which adopts supervised learning of nanoscale images of F-actin network in excitatory synapses, obtained by single molecule based super-resolution light microscopy. We have used the proposed analysis to understand the heterogeneity in the organization of F-actin in dendritic spines of primary neuronal cultures from rodents. Our results were validated using ultrastructural data obtained from platinum replica electron microscopy (PREM). The automated analysis approach was used to differentiate the heterogeneity in the nanoscale organization of F-actin in primary neuronal cultures from wild-type (WT) and a transgenic mouse model of Alzheimer's disease (APPSwe/PS1ΔE9).

Live cell super resolution imaging by radial fluctuations using fluorogen binding tags.

Fluorescence-Activating and absorption-Shifting Tag (FAST) is a novel genetically encoded optical highlighter probe. Since the fluorescence of FAST originates from the stochastic and reversible diffusive association of a fluorogenic ligand, we investigate the application of FAST using Super-Resolution Radial Fluctuations (SRRF) to achieve routine imaging below the diffraction limit in a widefield epifluorescence microscope. We show that intensity fluctuation analysis like SRRF allows the imaging of FAST-tagged proteins with sub - 100 nm resolution in live cells. FAST co-labeled with conventional fluorophores enables real time multicolour 2D and 3D super-resolution imaging, indicating that FAST can be used for the observation of sub-diffraction limited structures in both living and fixed samples.

Phosphatidylserine and GTPase activation control Cdc42 nanoclustering to counter dissipative diffusion.

The anisotropic organization of plasma membrane constituents is indicative of mechanisms that drive the membrane away from equilibrium. However, defining these mechanisms is challenging due to the short spatiotemporal scales at which diffusion operates. Here, we use high-density single protein tracking combined with photoactivation localization microscopy (sptPALM) to monitor Cdc42 in budding yeast, a system in which Cdc42 exhibits anisotropic organization. Cdc42 exhibited reduced mobility at the cell pole, where it was organized in nanoclusters. The Cdc42 nanoclusters were larger at the cell pole than those observed elsewhere in the cell. These features were exacerbated in cells expressing Cdc42-GTP, and were dependent on the scaffold Bem1, which contributed to the range of mobility and nanocluster size exhibited by Cdc42. The lipid environment, in particular phosphatidylserine levels, also played a role in regulating Cdc42 nanoclustering. These studies reveal how the mobility of a Rho GTPase is controlled to counter the depletive effects of diffusion, thus stabilizing Cdc42 on the plasma membrane and sustaining cell polarity.

A quantitative imaging-based screen reveals the exocyst as a network hub connecting endocytosis and exocytosis.

The coupling of endocytosis and exocytosis underlies fundamental biological processes ranging from fertilization to neuronal activity and cellular polarity. However, the mechanisms governing the spatial organization of endocytosis and exocytosis require clarification. Using a quantitative imaging-based screen in budding yeast, we identified 89 mutants displaying defects in the localization of either one or both pathways. High-resolution single-vesicle tracking revealed that the endocytic and exocytic mutants she4∆ and bud6∆ alter post-Golgi vesicle dynamics in opposite ways. The endocytic and exocytic pathways display strong interdependence during polarity establishment while being more independent during polarity maintenance. Systems analysis identified the exocyst complex as a key network hub, rich in genetic interactions with endocytic and exocytic components. Exocyst mutants displayed altered endocytic and post-Golgi vesicle dynamics and interspersed endocytic and exocytic domains compared with control cells. These data are consistent with an important role for the exocyst in coordinating endocytosis and exocytosis.

Educational competencies and technologies for disaster preparedness in undergraduate nursing education: an integrative review.

OBJECTIVES: This integrative review of literature was conducted to determine (1) what are the suitable disaster preparedness competencies for undergraduate nursing curriculum? and (2) what are the suitable methods of instruction to deliver disaster preparedness content? DATA SOURCES AND REVIEW METHOD: A literature search was conducted on three major electronic databases: Ovid MEDLINE, PubMed and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) using the keywords; Disaster Preparedness, Disaster and nursing education; disaster response and nursing education. Limiters used were published within the last 10 years and in nursing field. Out of the 190 articles retrieved, eight were research articles that met the inclusion criteria. These articles were carefully reviewed and the results are summarized in two sections to answer the research questions. RESULTS AND FINDINGS: There was no uniformity of intended competencies among the studies, though all studies used resources from reputed national and international organizations. All the studies reviewed adhered to a systematic approach in delivering content and used eclectic methods including multiple technologies to enhance the educational outcomes. Most of the studies had incorporated simulation in different ways involving low to high fidelity simulators, virtual simulation and live actors. Content and length of the programs were greatly varied but stayed focused on the general principles of disaster management and appropriate for the level of the students within the programs. DISCUSSION AND CONCLUSION: More rigorous research is needed in this area since all published articles had deficiencies in the methodologies, especially in data collection and analysis. Disaster preparedness education was found to be a suitable activity for interprofessional education.