Demographic Profile, Health, and Associated Factors of Family Caregivers and Functionality of Hospitalized Older Adults: Cross-Sectional, Exploratory, and Descriptive Study.

BACKGROUND: The longevity of the world population can contribute to an increase in hospitalizations and, consequently, to the emergence of functional limitations, resulting in the need for family caregivers. Hospitalized older adults may become dependent and require more care, increasing the burden on family caregivers. Thus, the nursing team in the hospital environment faces a new situation: an increase in the number of older adults occupying hospital beds and the presence of their family caregivers. OBJECTIVE: We aimed to analyze the association between the demographic variables of interest and the self-rated health of family caregivers and to describe the functionality of older adults hospitalized in a university hospital in the Amazonian context. METHODS: This cross-sectional, quantitative, exploratory, and descriptive study was carried out through individual interviews with 98 interviewees, divided into 49 family caregivers and 49 older adults hospitalized in the surgical clinic sector of a university hospital in Brazil between February and March 2023. Demographic data and health conditions were collected from family caregivers, and to describe the functionality of hospitalized older adults, the Barthel Index was applied. Descriptive (frequency and percentage) and inferential analyses were used, and the student t test was applied. The significance level of 5% was adopted. RESULTS: Among the 49 family caregivers, the majority were women (n=40, 81.6%) with an average age of 46.9 (SD 13.3) years. Most were single (n=28, 57.1%) and had completed an average level of education (n=26, 53.1%). Additionally, 25 (51%) caregivers were caring for their parents. Regarding health conditions, respondents self-assessed their health as good (25/49, 51%; P=.01), and they considered that their health status was not affected by the provision of care (36/49, 73.5%; P=.01). There was a significant association between demographic variables (ie, gender, age, and education) and self-assessment of family caregivers (P=.01, P=.01, and P=.04, respectively). Of the 49 older adults hospitalized, the majority (n=31, 63.2%) were men, with a mean age of 69.2 (SD 7.12) years. Regarding the assessment of functionality, most older adults were classified as having mild dependence on care (n=23, 46.9%), specifically in the age group between 60 and 69 years (21/49, 67.8%). CONCLUSIONS: The data revealed that female gender, age, and education of family caregivers contributed favorably to the provision of care to hospitalized older adults with a lower degree of functional dependence. It is important to emphasize that during the older adult's hospitalization, the family caregiver should not be seen as a delegation of responsibilities or as a complement of human resources to assist in their recovery. Health professionals need to implement assertive interventions so that the family caregiver functions as a therapeutic resource.

Integration of Electrochemical Sensing and Machine Learning to Detect Tuberculosis via Methyl Nicotinate in Patient Breath.

Tuberculosis (TB) remains a significant global health issue; making early, accurate, and inexpensive point-of-care detection critical for effective treatment. This paper presents a clinical demonstration of an electrochemical sensor that detects methyl-nicotinate (MN), a volatile organic biomarker associated with active pulmonary tuberculosis. The sensor was initially tested on a patient cohort comprised of 57 adults in Kampala, Uganda, of whom 42 were microbiologically confirmed TB-positive and 15 TB-negative. The sensor employed a copper(II) liquid metal salt solution with a square wave voltammetry method tailored for MN detection using commercially available screen-printed electrodes. An exploratory machine learning analysis was performed using XGBOOST. Utilizing this approach, the sensor was 78% accurate with 71% sensitivity and 100% specificity. These initial results suggest the sensing methodology is effective in identifying TB from complex breath samples, providing a promising tool for non-invasive and rapid TB detection in clinical settings.

The effects of mango consumption on vascular health and immune function.

Objectives: Heart disease, caused by atherosclerosis, is the leading cause of death. Maintaining vascular integrity is crucial to reducing atherosclerosis risk. Mangos are rich in fiber, vitamins, minerals, and phytochemicals that may offer cardioprotective and immune-boosting benefits. However, their effects on the vasculature and immune system in adults with overweight and obesity remain unclear. The objective of this study was to investigate the effects of mango consumption on vascular health and immune function in adults with overweight and obesity. Methods: In a 12-week, crossover study, 27 overweight and obese participants consumed either 100 kcals of mangos daily or isocaloric low-fat cookies daily. Fasting blood samples were collected at baseline, week 4, and week 12 and analyzed for vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin, sCD4, sCD8, sCD3E, and sCD45, tumor necrosis factor-alpha (TNF-α), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Results: Mango consumption significantly decreased VCAM-1 between baseline and week 4 (P = 0.046) and week 12 (P = 0.004). CAT increased between baseline and week 12 (P = 0.035) with mango consumption. GPx increased at week 12 compared to baseline and week 4 (P < 0.05). At week 12, SOD was higher after mango consumption compared to low-fat cookie consumption (P = 0.046). There were no significant differences in ICAM-1, P-selectin, E-selectin, sCD4, sCD8, sCD3E, sCD45 or TNF-α concentrations (P > 0.05 for all non-significant results). Conclusions: This study suggests that 100 kcals of mangos may benefit the integrity of the vasculature by reducing VCAM-1 and increasing SOD, CAT, and GPx levels. Mangos can be an alternative snack for improving atherosclerosis and oxidative stress risk factors.

Long-Term Outcomes of Hyperadrenergic Orthostatic Hypotension.

Purpose: Hyperadrenergic orthostatic hypotension is a subtype of orthostatic hypotension associated with elevated norepinephrine levels upon standing. Our previous study found that this subtype is characterized by less severe autonomic impairment compared to orthostatic hypotension with normal or low norepinephrine levels. However, long-term outcomes have not been determined. Thus, the purpose of this study was to evaluate the all-cause mortality and phenoconversion over 7 years. Methods: In this prospective observational study, 92 patients with orthostatic hypotension were recruited from the Vanderbilt Autonomic Dysfunction Center. 34 patients with upright norepinephrine levels above 600 pg/mL were included in the hyperadrenergic cohort and 58 composed the orthostatic hypotension cohort. Both cohorts were followed for 7 years while assessing all-cause mortality and phenoconversion to neurodegenerative autonomic disorders. Results: Hyperadrenergic patients showed an exaggerated orthostatic increase in norepinephrine to 938 ± 305 pg/mL upon head up tilt despite presenting with impaired autonomic reflexes. The 7-year mortality rate was 35% in the hyperadrenergic cohort compared to 22% in orthostatic hypotension (p = 0.01). The hyperadrenergic cohort had a greater phenoconversion rate to multiple system atrophy (p = 0.04), whereas the orthostatic hypotension cohort had greater phenoconversion to Parkinson's disease and dementia with Lewy bodies. Conclusions: Despite having less severe autonomic impairment, our data suggests that hyperadrenergic orthostatic hypotension has worse clinical outcomes than neurogenic orthostatic hypotension. Patients with hyperadrenergic orthostatic hypotension require careful monitoring, given that this condition may be associated with negative outcomes.

Effects of mixed nut consumption on LDL cholesterol, lipoprotein(a), and other cardiometabolic risk factors in overweight and obese adults.

BACKGROUND AND AIMS: Elevated LDL-C, lipoprotein(a) [Lp(a)], and inflammation are associated with greater risk for atherosclerotic cardiovascular events. Consumption of individual nut types decreases these risk factors but knowledge about the effect of mixed nuts on Lp(a) is limited. The objective of this study was to determine the effects of consuming 42.5 g/day of mixed nuts on LDL-C, Lp(a), and inflammatory markers in individuals with overweight or obesity. METHODS AND RESULTS: In a 16-week randomized control trial, 29 participants with overweight or obesity (BMI 25-40 kg/m2) consumed either 42.5 g/day of mixed nuts (cashews, almonds, macadamia nuts, Brazil nuts, pecans, pistachios, walnuts, and peanuts) or 69 g/day isocaloric pretzels. Blood samples were collected at baseline, week 8, and week 16 for analysis on total cholesterol (TC), LDL-C, Lp(a), inflammation markers, glucose, insulin, adiponectin and liver function enzymes. No significant differences were seen in TC, LDL-C, HDL-C, Lp(a), or liver function enzymes between the two groups. Participants consuming mixed nuts had significantly lower body fat percentage and diastolic blood pressure, and higher adiponectin (all P ≤ 0.05). C-reactive protein (CRP) and 8-oxo-deoxyguanosis (8-oxodG) showed non-significant decreasing trends and total antioxidant capacity (TAC) had a non-significant increasing trend in the mixed nut group. CONCLUSION: Consumption of mixed nuts had no evidence of an effect on LDL-C or Lp(a) throughout the intervention. Notably, mixed nut consumption lowered body fat percentage without significant changes in body weight or BMI. Future studies with larger sample sizes investigating the changing trends of CRP, 8-oxodG, and TAC are warranted. CLINICAL TRIAL REGISTER: NCT03375866.

The role of formulation approaches in presenting targeting ligands on lipid nanoparticles.

Aims: The density of functional ligands on lipid nanoparticles (LNPs) greatly determined its capability of postfunctionalization and targetability for the applications of personalized nanomedicine and drug/gene delivery. This work is to investigate whether and how formulation methods influence the presentation of surface ligands. Methods: Biotin-modified LNPs as a functional LNP model were synthesized by four different formulation methods. The biotin ligand density and targetability of biotin-LNPs were evaluated and compared. Results: Both the ligand density and targetability of biotin-LNPs formulated by four different formulation methods exhibited a similar trend: homogenization > extrusion > wave-shaped micromixer ≈ Y-shaped micromixer. Conclusion: Formulation methods could modulate the presentation of targeting ligands on LNPs, which could guide future formulation screening and nanomedicine engineering.

The effects of fresh mango consumption on gut health and microbiome - Randomized controlled trial.

Some individual fruits have been widely researched for their effects on overall health and correlations with chronic diseases. The beneficial effects of mango supplementation on metabolic diseases have been detected. However, research into mango consumption on gut health, including the microbiome, is limited to processed mango preparations or peels. Our goal was to examine the effects of fresh mango consumption on the gut microbiome, gut permeability proteins, and bowel movement habits in overweight/obese individuals. In a 12-week crossover design study, 27 participants consumed 100 kcal/day of either mangos or low-fat cookies with a washout period of 4 weeks. The mango intervention showed higher Shannon-Wiener and Simpson alpha diversity indices of the microbiome than the low-fat cookie intervention in week 4. Significant differences in beta diversity of the microbiome were found between diet interventions at week 12. Mango consumption increased the abundance of Prevotella maculosa, Corynebacterium pyruviciproducens, and Mogibacterium timidum while it decreased Prevotella copri. Low-fat cookie intake increased Cyanobacterium aponinum and Desulfovibrio butyratiphilus and reduced Alloscardovia omnicolens. There were no significant differences in circulating gut permeability protein (ZO-1, claudin-2, and occludin) levels. There was a slight increase in the amount of bowel movement with mango consumption, but no significant findings for frequency, consistency, strain, pain, and constipation in bowel movement between trials. Given these results, it can be concluded that consumption of mango may have positive effects on the gut health, which may yield possible health benefits for chronic disease that deserve further study.

Neonatal abstinence syndrome and mother's own milk at discharge.

OBJECTIVE: To describe factors impacting receipt of mother's own milk (MOM) at discharge among California infants diagnosed with neonatal abstinence syndrome (NAS). STUDY DESIGN: Cohort study of the California Perinatal Quality Care Collaborative's Maternal Substance Exposure Database for infants with NAS and gestational age ≥ 34 weeks from 2019 to 2020. RESULT: 245 infants with NAS were identified. Variables with an increased likelihood of being discharged on MOM included maternal medication assisted treatment (p = 0.001), use of maternal addiction services (p < 0.001), receiving donor human milk (p = 0.001), being treated in the well baby unit (p < 0.001), rooming-in (p < 0.001), and kangaroo care (p < 0.001). Among infants with NAS for whom MOM was recommended (n = 84), rooming-in was the only factor associated with being discharged on MOM (p = 0.002); receiving formula was the only inversely associated factor (p < 0.001). CONCLUSION: Results suggest supporting the mother-infant dyad and using non-pharmacologic treatment methods, such as rooming-in, increase receipt of MOM at discharge.

Assessing Perceptions of Broad Consent Concerning Biological Specimen Collection in a Cohort of Young Sexual Minority Men.

The use of broad consent to store human biospecimens to be used in future research studies has increased over the years. However, it is currently unknown how young sexual minority men (YSMM) perceive broad consent in these specific types of studies. Therefore, in this study we aimed to determine the extent to which YSMM are comfortable with providing broad consent concerning their identifiable biological specimens to a variety of entities, including external researchers and pharmaceutical companies and to examine the relationship between mistrust based on racial/ethnic identity or sexual orientation and attitudes toward broad consent. YSMM (N = 239) ages 24-27 years were recruited from a prospective cohort study in New York City in 2018 to complete a survey assessing attitudes about the use of broad consent concerning biospecimens for secondary research. We found that YSMM were most willing to provide broad consent to the researcher from the study they were enrolled in (85.3%), other researchers within the same university (82.4%), and researchers at other universities (74.5%). Participants were least willing to provide broad consent to government organizations (64.4%) and pharmaceutical companies (53.8%). Further, we found that medical mistrust based on racial/ethnic identity or sexual orientation was associated with attitudes toward the use of broad consent. Research institutions should consider modifying consent procedures around the use of broad consent in order to maximize recruitment and retention, especially among minority populations.

Interrelationship of Seasons with Inflammation, Red Meat, Fruit, and Vegetable Intakes, Cardio-Metabolic Health, and Smoking Status among Breast Cancer Survivors.

Seasons can affect human inflammatory status and the occurrence of diseases, and foods may also have differential impacts on inflammation across seasons; however, few studies have investigated whether there are independent and joint impacts of seasons and red meat, fruit and vegetable intakes on inflammation in breast cancer survivors. We conducted a cross-sectional study by leveraging a large cohort, the Women's Healthy Eating and Living (WHEL) study. The WHEL study comprised primarily early stage breast cancer survivors and collected blood samples, dietary intake, demographic, and health status information at baseline. We selected 2919 participants who provided baseline dietary information and had measurement of C-reactive protein (CRP), a general marker of inflammation. In our multivariable-adjusted analyses, we found that red meat intakes were positively associated, while fruit and vegetable intakes were inversely associated with CRP; blood collected in the winter season was associated with lower CRP when compared to summer; and increased smoking intensity and body mass index (BMI) as well as having cardio-metabolic conditions (such as heart disease or diabetes) were positively associated with CRP. Furthermore, we examined the joint associations of food intakes and the season of blood draw with CRP in different subgroups. We found that moderate intakes of red meat were associated with a reduction of CRP in winter but not in other seasons; increased intakes of fruit and vegetables were associated with reduced inflammation in most seasons except winter. These associations were observed in most subgroups except past smokers with pack-years ≥ 15, in whom we observed no benefit of red meat intakes in winter. Our study provides valuable evidence for considering seasonal impacts on inflammation and seasonal food impacts in different subgroups among breast cancer survivors. The results of our study are in line with one of the emphases of the current NIH 2020-2030 nutrition strategy plan-namely, pay attention to what, when, and who should eat.

Neonatal abstinence syndrome management in California birth hospitals: results of a statewide survey.

OBJECTIVE: Assess management of neonatal abstinence syndrome (NAS) in California hospitals to identify potential opportunities to expand the use of best practices. STUDY DESIGN: We fielded an internet-based survey of 37 questions to medical directors or nurse managers at 145 birth hospitals in California. RESULTS: Seventy-five participants (52%) responded. Most respondents reported having at least one written protocol for managing NAS, but gaps included protocols for pharmacologic management. Newer tools for assessing NAS severity were not commonly used. About half reported usually or always using nonpharmacologic strategies; there is scope for increasing breastfeeding when recommended, skin-to-skin care, and rooming-in. CONCLUSIONS: We found systematic gaps in care for infants with NAS in a sample of California birth hospitals, as well as opportunities to spread best practices. Adoption of new approaches will vary across hospitals. A concerted statewide effort to facilitate such implementation has strong potential to increase access to evidence-based treatment for infants and mothers.

May Measurement Month 2017: an analysis of blood pressure screening in the Philippines-South-East Asia and Australasia.

Cardiovascular diseases remain the Philippines' leading cause of mortality, with hypertension as a prevalent contributory risk factor. We took part in May Measurement Month 2017 (MMM17), a global initiative to raise awareness of high blood pressure (BP) and to serve as a temporary solution to the lack of screening programs worldwide. Following the standard MMM protocol, data for 271 604 screened individuals were submitted from the Philippines. After multiple imputation, 91 994 (34.3%) were hypertensive; 28 662 out of 205 158 participants (14.0%) not receiving treatment had hypertension; and of the 60 370 receiving treatment, 25 144 (41.6%) had uncontrolled BP. Blood pressures were significantly higher in the overweight and obese, current smokers, in participants receiving antihypertensive medication, those with previous myocardial infarction or stroke. The BP measurements were relatively lower when taken on the left arm, and in pregnant women. A slightly higher systolic BP was noted in participants who reported no alcohol intake. Blood pressures recorded during the weekends were highest, and the lowest readings were obtained on Tuesdays. MMM17 was the largest BP screening campaign conducted in the Philippines. Opportunistic BP screening, harnessing volunteers, are a cost-effective public health measure to improve awareness and treatment rates of raised BP. These may help provide additional information that can guide medical practitioners and health officials in drafting preventive and therapeutic measures to improve control rates and long-term outcomes of hypertensive individuals in the population.

Role of Oral Mucosal Fluid and Electrolyte Absorption and Secretion in Dry Mouth.

Dry mouth is induced by dehydration of the oral mucosa, resulting from an imbalance of fluid supply and clearance within the oral cavity. Saliva is the major source of oral mucosal fluid, whereas oral fluid clearance includes evaporation and swallowing. Oral mucosal fluid absorption has been suggested to play a critical role in oral fluid clearance; over-absorption of water and ions across the oral mucosa under certain conditions may be a major component for oral fluid imbalance, leading to mucosal dehydration. While numerous studies have confirmed that the oral mucosa absorbs fluid and electrolytes, the pathways and mechanisms mediating the absorption remain undefined. The transcellular pathway regulating oral mucosal epithelial absorption includes aquaporins, epithelial Na+ channel and/or Na+/H+ exchanger, whereas the paracellular transport is likely to be mediated by tight junctions. The regulatory mechanisms of these pathways require further elucidation. It remains unclear whether the oral mucosa also secretes fluid and ions into the oral cavity. Although intercellular lipids secreted by epithelial cells form the major barrier to paracellular water and ion transport, the role and regulation of these lipids in oral mucosal hydration in physiological and pathological conditions need further investigation. Delineation of these mechanisms will be conducive to the development of preventive and therapeutic interventions for dry mouth.

The Joint Admission Medical Program: a statewide approach to expanding medical education and career opportunities for disadvantaged students.

In 2003, Texas initiated an experiment to address enrollment disparities in its medical schools. With bipartisan support from key Texas legislators, funding was allocated in 2002 to establish the Joint Admission Medical Program (JAMP). Texas' then eight medical schools created, through JAMP, a partnership with the state's 31 public and 34 private undergraduate colleges and universities. Cognizant of legal prohibitions against reliance solely on race or ethnicity in promoting diversity, JAMP is designed to enhance opportunities for economically disadvantaged students from across the state, including those from (1) rural and remote areas of the state, and (2) institutions that have historically sent few students to medical school. Now in its seventh year of operation, JAMP is overseen by a council with representatives from all nine Texas medical schools. For the six years-2003 to 2008-for which data are available, indicators of JAMP performance can be seen in (1) the numbers of applicants to JAMP (1,230 applicants in the first six years), (2) levels of JAMP participation (480 participants), and (3) matriculation of JAMP participants into medical schools (164 of 288 of those accepted into the program in the years 2003-2006).The authors provide a brief history of JAMP, describe its structure and operation, summarize objective performance data, and identify some of the challenges still faced. These include increasing the participation of students from underrepresented minority groups within the legal structure for the program, and fostering substantive participation in JAMP by all of Texas' undergraduate institutions. A focused effort is under way to strengthen the evaluative aspects of JAMP so that more comprehensive data, including subjective evaluation data from participants, can be shared with colleagues in the future.

Hemostatic consequences of a non-fresh or reconstituted whole blood small volume cardiopulmonary bypass prime in neonates and infants.

OBJECTIVES: Despite aggressive measures to miniaturize the cardiopulmonary bypass (CPB) circuit in neonates and infants, the CPB prime volume is often at least as large as the patients' blood volume. We conducted an observational study to characterize the hemostatic consequences of a CPB prime consisting of either non-fresh or reconstituted whole blood. METHODS: Hematocrit, fibrinogen, platelet count, plasminogen, anti-thrombin III (AT-III), and factors (F) II, V, VII, IX, and X of 30 neonates and infants undergoing cardiac surgery with CPB utilizing either a non-fresh or reconstituted whole blood prime were prospectively evaluated at eight time points. Following protamine administration, microvascular bleeding was treated by protocol. RESULTS: The hemostatic composition of the CPB prime was the same following the use of either non-fresh or reconstituted whole blood. The CPB prime platelet count (mean +/- SD) was 5.87 +/- 2.84 x 10(3) microl(-1) when compared to a preoperative platelet count of 298 +/- 142 x 10(3) microl(-1) (P < 0.0001). Twenty patients received 17.3 +/- 9.2 ml x kg(-1) (0.86 +/- 0.46 units x kg(-1)) of platelets with significant improvement in platelet count. Nine patients received 16.7 +/- 13.4 ml x kg(-1) (0.84 +/- 0.67 units x kg(-1)) of cryoprecipitate with significant improvements in FVIII and fibrinogen. CONCLUSIONS: Non-fresh or reconstituted whole blood as a component of a small volume CPB prime in neonates and infants induces clinically significant dilutional thrombocytopenia in conjunction with less significant reductions in fibrinogen, FII, FV, FVII, FVIII, FIX, FX, plasminogen, and AT-III.

The effect of milrinone on platelet activation as determined by TEG platelet mapping.

BACKGROUND: Milrinone is a phosphodiesterase III inhibitor that increases intracellular cyclic adenosine monophosphate resulting in improved ventricular function and vasodilation. Increased intracellular levels of cyclic adenosine monophosphate also inhibit adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation. We hypothesized that inhibition of ADP and AA-induced platelet activation by therapeutic blood concentrations of milrinone could be quantified using TEG Platelet Mapping. METHODS: Blood was taken from 15 healthy adults who had not been taking antiplatelet medications. Milrinone was added to whole blood in three clinically relevant concentrations (30, 100, and 300 ng/mL). Conventional thromboelastography (TEG) and TEG Platelet Mapping were performed on whole blood without milrinone and at each of these three concentrations. RESULTS: Increased blood concentrations of milrinone were associated with increased inhibition of ADP and AA-induced platelet activation (P < 0.0001). Milrinone at a blood concentration of 300 ng/mL markedly impaired the platelet activation response to ADP and AA. CONCLUSIONS: Therapeutic blood concentrations of milrinone exhibit a significant inhibitory effect on ADP and AA-induced platelet activation as determined by TEG Platelet Mapping, without affecting the conventional kaolin-activated TEG. We suggest that TEG Platelet Mapping results be interpreted with caution in patients being treated with milrinone, and other drugs that modify platelet cyclic nucleotide concentrations.

Prospective longitudinal study of coagulation profiles in children with hypoplastic left heart syndrome from stage I through Fontan completion.

OBJECTIVE: The risk for thrombosis is increased after the Fontan operation. It is unknown whether children with univentricular heart disease have an intrinsic coagulation anomaly or acquire a defect in coagulation during the course of the staged repair. This prospective, longitudinal study evaluated changes in coagulation profiles in a cohort of patients with hypoplastic left heart syndrome from stage I palliation through completion of the Fontan operation. METHODS: Thirty-seven patients with hypoplastic left heart syndrome were enrolled prospectively, and the concentration of factors II, V, VII, VIII, IX, X, proteins C and S, fibrinogen, antithrombin, serum albumin, and liver enzymes were measured before stage I palliation (mean age 4 +/- 2 days), before bidirectional Glenn (mean age 5.9 +/- 1.8 months), before the Fontan procedure (mean age 27.1 +/- 6.6 months), and after the Fontan procedure (mean age 49 +/- 17.6 months). Healthy children were used as age-matched controls for coagulation factors. Demographic, hemodynamic variables, and elapsed time after the Fontan procedure were evaluated as possible predictors of coagulation abnormalities. RESULTS: Significantly lower levels of both procoagulation and anticoagulation factors were demonstrated through to completion of the Fontan procedure. After the Fontan procedure, there was a significantly higher factor VIII level (P < .005) but no correlation with hemodynamic variables or liver function. CONCLUSION: This longitudinal study in patients with identical cardiac disease and staged surgical procedures confirms the increase in factor VIII level after the Fontan procedure. This is an acquired defect, and although the cause remains to be determined, monitoring factor VIII levels after the Fontan operation could indicate a subset of patients at risk for thrombosis.

Regulation of epithelial Na+ channel (ENaC) in the salivary cell line SMG-C6.

Glucocorticoids and mineralocorticoids modulate Na+ transport via epithelial Na+ channels (ENaC). The rat submandibular epithelial cell line, SMG-C6, expresses alpha-ENaC mRNA and protein and exhibits amiloride-sensitive Na+ transport when grown in low-serum (2.5%) defined medium, therefore, we examined the effects of altering the composition of the SMG-C6 cell growth medium on ENaC expression and function. No differences in basal or amiloride-sensitive short-circuit current (Isc) were measured across SMG-C6 monolayers grown in the absence of thyroid hormone, insulin, transferrin, or EGF. In the absence of hydrocortisone, basal and amiloride-sensitive Isc significantly decreased. Similarly, monolayers grown in 10% serum-supplemented medium had lower basal Isc and no response to amiloride. Adding hydrocortisone (1.1 microM) to either the low or 10% serum medium increased basal and amiloride-sensitive Isc, which was blocked by RU486, the glucocorticoid and progesterone receptor antagonist. Aldosterone also induced an increase in alpha-ENaC expression and Na+ transport, which was also blocked by RU486 but not by the mineralocorticoid receptor antagonist spironolactone. Thus, in the SMG-C6 cell line, hydrocortisone and aldosterone increased ENaC expression and basal epithelial Na+ transport. The absence of endogenous ENaC expression in culture conditions devoid of steroids makes the properties of this cell line an excellent model for investigating pathways regulating ENaC expression and Na+ transport.

Induction of serum- and glucocorticoid-induced kinase-1 (SGK1) by cAMP regulates increases in alpha-ENaC.

Alpha-ENaC expression and activity is regulated by a variety of hormones including beta-adrenergic agonists via the second messenger cAMP. We evaluated the early intermediate pathways involved in the up-regulation of SGK1 by DbcAMP and whether SGK1 is a prerequisite for induction of alpha-ENaC expression. Submandibular gland epithelial (SMG-C6) cells treated with DbcAMP (1 mM) induced both SGK1 mRNA and protein expression. DbcAMP-stimulated SGK1 mRNA expression was decreased by actinomycin D and mRNA and protein expressions were attenuated by PKA inhibitors (H-89 and KT5720). Inhibition of PI3-K with either LY294002 or dominant negative PI3-K reduced DbcAMP-stimulated SGK1 protein and mRNA levels, attenuated the phosphorylation of CREB (a cAMP-activated transcription factor) and decreased alpha-ENaC protein levels and Na(+) transport. In addition, the combination of PKA inhibitors with dominant negative PI3-K synergistically inhibited DbcAMP-induced Na(+) transport. Inhibition of SGK1 expression by siRNA decreased but did not obliterate DbcAMP-induced alpha-ENaC expression. Thus, in a cell line which endogenously exhibits minimal alpha-ENaC expression, induction of SGK1 by DbcAMP occurs via the PI3-K and PKA pathways. Increased alpha-ENaC levels and function are partly dependent upon the early induction of SGK1 expression.