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.

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.

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.

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.

Tooth caries detection by curve fitting of laser-induced fluorescence emission: a comparative evaluation with reflectance spectroscopy.

BACKGROUND AND OBJECTIVES: Nitrogen laser-induced fluorescence (LIF) spectra of sound tooth consists of two broad bands centered at 440 and 490 nm, with two apparent side bands on either side. In order to locate the exact peak position of these bands and to effectively utilize the LIF spectral signatures for detection of tooth caries, the LIF spectra were curve-fitted using Gaussian spectral functions and the results were compared with those from diffuse reflectance spectral measurements. STUDY DESIGN/MATERIALS AND METHODS: The excitation light at 337.1 nm was guided to the sound and caries-affected tooth samples through the central fiber of the fiber-optic probe of a laser-induced fluorescence reflectance spectroscopy (LIFRS) system. Six surrounding fibers of the probe collect tooth fluorescence or diffuse reflectance from the lesion and direct it to a miniature spectrometer. The in vitro spectra were obtained from healthy enamel, dentin, and pulp level tooth caries. RESULTS: As compared to sound tooth, the caries tooth showed lower fluorescence and reflectance intensities in the 350-700 nm region. The deconvoluted peaks in the LIF spectra of sound tooth were found centered at 403.80, 434.20, 486.88, and 522.45 nm, whereas in the case of pulp level caries, a new peak was observed at 636.78 nm. Curve-fitted parameters, such as peak center, Gaussian curve area, full width at half intensity maximum (FWHM), and their ratios, were also found to vary with the stage of tooth caries. The ratios involving the 435 nm band, such as F405/F435, F435/F490, and F435/F525 ratios derived from curve-fitted areas and amplitudes, were found to be sensitive to discriminate between sound, dentin, and pulp level caries. Among the various diffuse reflectance spectral intensity ratios, the R500/R700 was found to be most sensitive to distinguish between pulp and dentin level caries. CONCLUSIONS: Nitrogen laser-excited fluorescence spectral studies were found to be more suited for detection of caries lesions. The LIF measurement with spectral analysis, done by curve fitting, outscores the diffuse reflectance methodology and shows the potential to screen different levels of tooth decay in a clinical setting.