Younger and Rural Children are More Likely to be Hospitalized for SARS-CoV-2 Infections.

Purpose: To identify characteristics of SARS-CoV-2 infection that are associated with hospitalization in children initially evaluated in a Pediatric Emergency Department (ED). Methods: We identified cases of SARS-CoV-2 positive patients seen in the Arkansas Children's Hospital (ACH) ED or hospitalized between May 27, 2020, and April 28, 2022 using ICD-10 codes within the Pediatric Hospital Information System (PHIS) Database. We compared infection waves for differences in patient characteristics, and used logistic regressions to examine which characteristics led to a higher chance of hospitalization. Findings: We included 681 pre-Delta cases, 673 Delta cases, and 970 Omicron cases. Almost 17% of patients were admitted to the hospital. Compared to Omicron infected children, pre-Delta and Delta infected children were twice as likely to be hospitalized (OR=2.2 and 2.0, respectively; p<0.0001). Infants less than 1 year of age were >3 times as likely to be hospitalized than children ages 5-14 years regardless of wave (OR=3.42; 95%CI=2.36-4.94). Rural children were almost 3 times as likely than urban children to be hospitalized across all waves (OR=2.73; 95%CI=1.97-3.78). Finally, those with a complex condition had nearly a 15-fold increase in odds of admission (OR=14.6; 95%CI=10.6-20.0). Conclusions: Children diagnosed during the pre-Delta or Delta waves were more likely to be hospitalized than those diagnosed during the Omicron wave. Younger and rural patients were more likely to be hospitalized regardless of wave. We suspect lower vaccination rates and larger distances from medical care influenced higher hospitalization rates.

Micro-laparoscopic cholecystectomy: an alternative to single-port surgery.

INTRODUCTION: Recent advances in minimally invasive surgery aimed at diminishing incision size have led to the development of single-port surgery (SPS). SPS has an increased level of complexity and requires a higher level of surgical skill compared to traditional laparoscopy. We explored micro-laparoscopy as an alternative to routine laparoscopic cholecystectomy. METHODS: The study is a retrospective review of consecutive elective laparoscopic cholecystectomies performed by a single surgeon at a community teaching hospital over 24 months. All surgeries were performed using a 5-mm trocar for the umbilical port and 3-mm trocars for other ports in standard configuration. RESULTS: Seventy-nine cholecystectomies were performed by micro-laparoscopy during the 24-month period. Three cases required upgrade in trocar size for technical reasons, resulting in a completion rate of 96%. Intraoperative cholangiography was performed in 70 cases (89%). There were no conversions to open surgery. There were no intra- or postoperative complications, and all patients were discharged on the day of surgery. CONCLUSION: Micro-laparoscopic cholecystectomy is safe, feasible, and represents an alternative to other minimally invasive techniques. Future developments in surgical technology will allow the use of even smaller instruments, diminishing the surgical "footprint" even further and contributing to better cosmesis and decreased postoperative pain in cholecystectomy patients.

The non-excitable smooth muscle: calcium signaling and phenotypic switching during vascular disease.

Calcium (Ca(2+)) is a highly versatile second messenger that controls vascular smooth muscle cell (VSMC) contraction, proliferation, and migration. By means of Ca(2+) permeable channels, Ca(2+) pumps and channels conducting other ions such as potassium and chloride, VSMC keep intracellular Ca(2+) levels under tight control. In healthy quiescent contractile VSMC, two important components of the Ca(2+) signaling pathways that regulate VSMC contraction are the plasma membrane voltage-operated Ca(2+) channel of the high voltage-activated type (L-type) and the sarcoplasmic reticulum Ca(2+) release channel, Ryanodine Receptor (RyR). Injury to the vessel wall is accompanied by VSMC phenotype switch from a contractile quiescent to a proliferative motile phenotype (synthetic phenotype) and by alteration of many components of VSMC Ca(2+) signaling pathways. Specifically, this switch that culminates in a VSMC phenotype reminiscent of a non-excitable cell is characterized by loss of L-type channels expression and increased expression of the low voltage-activated (T-type) Ca(2+) channels and the canonical transient receptor potential (TRPC) channels. The expression levels of intracellular Ca(2+) release channels, pumps and Ca(2+)-activated proteins are also altered: the proliferative VSMC lose the RyR3 and the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase isoform 2a pump and reciprocally regulate isoforms of the ca(2+)/calmodulin-dependent protein kinase II. This review focuses on the changes in expression of Ca(2+) signaling proteins associated with VSMC proliferation both in vitro and in vivo. The physiological implications of the altered expression of these Ca(2+) signaling molecules, their contribution to VSMC dysfunction during vascular disease and their potential as targets for drug therapy will be discussed.

Sorghum extrusion increases bioavailability of catechins in weanling pigs.

Catechins and procyanidins are beneficial for human health; however, their bioavailability is low. The effect of food processing on catechin bioavailability from sources containing predominantly procyanidins has not been studied. The sumac sorghum mixture (50% whole grain+50% bran) used in this study contained catechins, procyanidins dimers, and polymers at 0.08, 0.6, and 26.4 mg/g, respectively. Extrusion decreased the polymeric procyanidins by 48% to 22 mg/g while increasing catechins (50%) and dimers (64%) to 0.12 and 1.0 mg/g, respectively. Six weanling pigs (8.9+/-1.1 kg) received a single dose by gavage of the sorghum mixture (7 g/kg0.75), the sorghum mixture extrudate, or white sorghum (50% whole grain+50% bran) in a randomized crossover design. Treatments were separated by a 7-day washout period. Blood was drawn at 0, 1, 2, and 4 h. Plasma catechin, 3'-O-methylcatechin, 4'-O-methylcatechin, epicatechin, 3'-O-methylepicatechin, and 4'-O-methylepicatechin peaked at 1 h and were 18, 43, 1, 0.7, 0.7, and 0.3 nmol/L for pigs receiving sorghum, respectively. Plasma levels in pigs receiving extruded sorghum were 66, 110, 2, 16, 8, and 11 nmol/L, respectively. Plasma levels of catechin, 3'-O-methylcatechin, and the total catechins were higher in pigs fed extruded sorghum at 1, 2, and 4 h postdose (P

CaMKII-delta isoform regulation of neointima formation after vascular injury.

OBJECTIVE: The purpose of this study was to test the function of the calcium/calmodulin-dependent protein kinase II delta2 isoform (CaMKIIdelta2) in regulating vascular smooth muscle (VSM) cell proliferation and migration in response to vascular injury. METHODS AND RESULTS: CaMKII isoform content was assessed in rat carotid arteries after balloon angioplasty-induced injury by Western blotting with isoform specific antibodies. Within 3 days after injury, a significant increase in CaMKIIdelta2 and decrease in CaMKIIgamma isoform content was observed in both medial smooth muscle and adventitial fibroblasts. Neointimal VSM cells expressed primarily the delta2 isoform. Incubation of the injured vessel with adenovirus encoding siRNA targeting CaMKIIdelta isoforms prevented upregulation of the delta2 isoform in the media and adventitia; inhibited cell proliferation assessed by PCNA expression in both layers and markedly inhibited neointima formation and adventitial thickening. CONCLUSIONS: CaMKIIdelta2 is specifically induced in VSM and adventitial fibroblasts during the response of an artery to injury and is a positive regulator of proliferation and migration in the vessel wall contributing to neointima formation and vascular remodeling. This provides a potential mechanism for Ca2+-dependent regulation of VSM and myofibroblast proliferation and migration in response to vascular injury or disease.

Sorghum bran in the diet dose dependently increased the excretion of catechins and microbial-derived phenolic acids in female rats.

Sorghum bran is concentrated with procyanidins (predominately polymers), which may be beneficial for health in humans; however, the bioavailability of procyanidins is not well-understood. Female Sprague-Dawley rats were fed an AIN93G diet containing 0, 5, 10, 20, or 40% Hi-tannin sorghum bran (n = 5-7 for each group) for 50 days. Sorghum bran contained 23.3 mg/g of procyanidins. The urinary excretions of catechin, epicatechin, methylated catechins, and phenolic acids were analyzed using liquid chromatography-tandem mass spectrometry. Sorghum bran dose dependently increased the urinary excretion of catechin (0-2.2 nmol/day) and 3'-O-methylcatechin (0-9.5 nmol/day). Their serum concentrations also increased with dose (range of 0-14 nM for 3'-O-methylcatechin). Among the 14 phenolic acids analyzed, 3,4-dihydroxybenzoic acid, 3-methoxy-4-hydroxybenzoic acid, and 4-hydroxyphenylacetic acid dominated in the serum (1.8-8 micromol/L). In the urine, 3-methoxy-4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, and 3-hydroxyphenylpropionic acid dominated and their excretion increased significantly with the level of sorghum bran in the diet. The summed phenolic acid excretion was 0.8 micromol/day in the control group and increased to 23 micromol/day for 40% sorghum bran group. The hippuric acid excretion ranged from 2.2 to 16.2 micromol/day and peaked in the 10% sorghum bran group. On the basis of chromic oxide, a nonabsorbable marker, total procyanidins and polymers disappeared progressively, and significant degradation occurred in the cecum and colon. Catechins and procyanidins in sorghum were bioavailable; however, bacteria-derived phenolic acids were the predominant metabolites of procyanidins. Procyanidins degraded in the gastrointestinal tract. Depolymerization was not observed.

Calcium/calmodulin-dependent protein kinase II-delta isoform regulation of vascular smooth muscle cell proliferation.

There is accumulating evidence that Ca(2+)-dependent signaling pathways regulate proliferation and migration of vascular smooth muscle (VSM) cells, contributing to the intimal accumulation of VSM that is a hallmark of many vascular diseases. In this study we investigated the role of the multifunctional serine/threonine kinase, calmodulin (CaM)-dependent protein kinase II (CaMKII), as a mediator of Ca(2+) signals regulating VSM cell proliferation. Differentiated VSM cells acutely isolated from rat aortic media express primarily CaMKIIgamma gene products, whereas passaged primary cultures of de-differentiated VSM cells express primarily CaMKIIdelta(2), a splice variant of the delta gene. Experiments examining the time course of CaMKII isoform modulation revealed the process was rapid in onset following initial dispersion and primary culture of aortic VSM with a significant increase in CaMKIIdelta(2) protein and a significant decrease in CaMKIIgamma protein within 30 h, coinciding with the onset of DNA synthesis and cell proliferation. Attenuating the initial upregulation of CaMKIIdelta(2) in primary cultured cells using small-interfering RNA (siRNA) resulted in decreased serum-stimulated DNA synthesis and cell proliferation in primary culture. In passaged VSM cells, suppression of CaMKIIdelta(2) activity by overexpression of a kinase-negative mutant, or suppression of endogenous CaMKII content using multiple siRNAs, significantly attenuated serum-stimulated DNA synthesis and cell proliferation. Cell cycle analysis following either inhibitory approach indicated decreased proportion of cells in G1, an increase in proportion of cells in G2/M, and an increase in polyploidy, corresponding with accumulation of multinucleated cells. These results indicate that CaMKIIdelta(2) is specifically induced during modulation of VSM cells to the synthetic phenotypic and is a positive regulator of serum-stimulated proliferation.

Procyanidin and catechin contents and antioxidant capacity of cocoa and chocolate products.

Cocoa and chocolate products from major brands were analyzed blind for total antioxidant capacity (AOC) (lipophilic and hydrophilic ORAC(FL)), catechins, and procyanidins (monomer through polymers). Accuracy of analyses was ascertained by comparing analyses on a NIST standard reference chocolate with NIST certified values. Procyanidin (PC) content was related to the nonfat cocoa solid (NFCS) content. The natural cocoa powders (average 87% of NFCS) contained the highest levels of AOC (826 +/- 103 micromol of TE/g) and PCs (40.8 +/- 8.3 mg/g). Alkalized cocoa (Dutched powders, average 80% NFCS) contained lower AOC (402 +/- 6 micromol of TE /g) and PCs (8.9 +/- 2.7 mg/g). Unsweetened chocolates or chocolate liquor (50% NFCS) contained 496 +/- 40 micromol of TE /g of AOC and 22.3 +/- 2.9 mg/g of PCs. Milk chocolates, which contain the least amount of NFCS (7.1%), had the lowest concentrations of AOC (80 +/- 10 micromol of TE /g) and PCs (2.7 +/- 0.5 mg/g). One serving of cocoa (5 g) or chocolate (15 or 40 g, depending upon the type of chocolate) provides 2000-9100 micromol of TE of AOC and 45-517 mg of PCs, amounts that exceed the amount in a serving of the majority of foods consumed in America. The monomers through trimers, which are thought to be directly bioavailable, contributed 30% of the total PCs in chocolates. Hydrophilic antioxidant capacity contributed >90% of AOC in all products. The correlation coefficient between AOC and PCs in chocolates was 0.92, suggesting that PCs are the dominant antioxidants in cocoa and chocolates. These results indicate that NFCS is correlated with AOC and PC in cocoa and chocolate products. Alkalizing dramatically decreased both the procyanidin content and antioxidant capacity, although not to the same extent.

Metabolic phenotype of isoflavones differ among female rats, pigs, monkeys, and women.

Various physiologic effects of soy food consumption have been attributed to the estrogenic actions of isoflavones. The order of estrogen receptor binding potency of soy-derived isoflavone aglycones is equol > genistein > daidzein, and their conjugates are less potent. Because the metabolic profile may be an important determinant of bioactivity after soy intake, we studied the serum and urine isoflavone concentrations in 3 animal models and compared them with isoflavone profiles in women. Female Sprague-Dawley rats, Hampshire/Duroc Cross pigs, cynomolgus monkeys, and women were fed diets containing soy protein isolate. Isoflavones and their metabolites were measured by LC-MS or electrochemical detection. Equol represented approximately 77 and 52% (molar ratio) of summed serum isoflavones (isoflavones plus metabolites) in rats and cynomolgus monkeys, respectively. Equol was undetectable in pig serum and human plasma, but daidzein and genistein contributed >88% of summed circulating isoflavones. Monkey and rat urine contained high levels of aglycones (>85% and >32%, respectively), whereas pigs and women excreted isoflavone mainly in the form of glucuronides (>80%), with <10% as aglycones. Isoflavones in human plasma were predominantly glucuronides (75%) with 24% as sulfates and <1% as aglycones; in monkey serum, however, 64% of isoflavones were sulfates, 30% glucuronides, and 6% aglycones. Equol was also a major serum metabolite of 6-mo-old rhesus monkeys (80% of summed isoflavones). Thus, there were significant interspecies differences in isoflavone metabolism, and the overall metabolic profile of pigs was closer to that of women than that of rats or monkeys.