Ability of Dental Students to Deliver Oxygen in a Medical Emergency

This study was conducted to evaluate the ability of dental students to administer emergency oxygen to a patient during a simulated emergency. Forty third‐year (D3) and fourth‐year (D4) dental students were recruited and asked to demonstrate their ability in managing a simulated angina attack. Students were tested on their knowledge related to emergency medical protocols, the time taken to obtain oxygen, and operation of the oxygen equipment. Of the subjects tested, 68 percent independently identified the need for oxygen and the correct location of the equipment in the dental school. Only 15 percent of the students completed the experiment within a predetermined optimal time frame, and 50 percent of all students did not successfully operate the tank regulator to administer oxygen correctly. Although most participants in the study were able to verbalize the proper protocol for managing medical emergencies, the chairside execution in this situation demonstrates room for improvement. Incorporation of periodic simulation exercises, in addition to classroom education, is likely to improve the ability of dental students to manage medical emergencies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153567/1/jddj002203372009734tb04721x.pd

The interleukin-6 receptor Asp358Ala single nucleotide polymorphism rs2228145 confers increased proteolytic conversion rates by ADAM proteases

The pleiotropic activities of Interleukin (IL-)6 are controlled by membrane-bound and soluble forms of the IL-6 receptor (IL-6R) in processes called classic and trans-signaling, respectively. The coding single nucleotide polymorphism (SNP) rs2228145 of the Interleukin 6 receptor (IL-6R Asp358Ala variant) is associated with a 2-fold increase in soluble IL-6R (sIL-6R) serum levels resulting in reduced IL-6-induced C-reactive protein (CRP) production and a reduced risk for coronary heart disease. It was suggested that the increased sIL-6R level leads to decreased IL-6 classic or increased IL-6 trans-signaling. Irrespective of the functional outcome of increased sIL-6R serum level, it is still under debate, whether the increased sIL-6R serum levels emerged from differential splicing or ectodomain shedding. Here we show that increased proteolytic ectodomain shedding mediated by the A Disintegrin and metalloproteinase domain (ADAM) proteases ADAM10 and ADAM17 caused increased sIL-6R serum level in vitro as well as in healthy volunteers homozygous for the IL-6R Asp358Ala allele. Differential splicing of the IL-6R appears to have only a minor effect on sIL-6R level. Increased ectodomain shedding resulted in reduced cell-surface expression of the IL-6R Asp358Ala variant compared to the common IL-6R variant. In conclusion, increased IL-6R ectodomain shedding is a mechanistic explanation for the increased serum IL-6R levels found in persons homozygous for the rs2228145 IL-6R Asp358Ala variant

"Activated" STAT Proteins: A Paradoxical Consequence of Inhibited JAK-STAT Signaling in Cytomegalovirus-Infected Cells

We have previously characterized mouse CMV (MCMV)–encoded immune-evasive IFN signaling inhibition and identified the viral protein pM27 as inducer of proteasomal degradation of STAT2. Extending our analysis to STAT1 and STAT3, we found that MCMV infection neither destabilizes STAT1 protein nor prevents STAT1 tyrosine Y701 phosphorylation, nuclear translocation, or the capability to bind g-activated sequence DNA-enhancer elements. Unexpectedly, the analysis of STAT3 revealed an induction of STAT3 Y705 phosphorylation by MCMV. In parallel, we found decreasing STAT3 protein amounts upon MCMV infection, although STAT3 expression normally is positive autoregulative. STAT3 phosphorylation depended on the duration of MCMV infection, the infectious dose, and MCMV gene expression but was independent of IFNAR1, IL-10, IL-6, and JAK2. Although STAT3 phosphorylation did not require MCMV immediate early 1, pM27, and late gene expression, it was restricted to MCMV- infected cells and not transmitted to bystander cells. Despite intact STAT1 Y701 phosphorylation, IFN-g–induced target gene transcription (e.g., IRF1 and suppressor of cytokine signaling [SOCS] 1) was strongly impaired. Likewise, the induction of STAT3 target genes (e.g., SOCS3) by IL-6 was also abolished, indicating that MCMV antagonizes STAT1 and STAT3 despite the occur- rence of tyrosine phosphorylation. Consistent with the lack of SOCS1 induction, STAT1 phosphorylation was prolonged upon IFN-g treatment. We conclude that the inhibition of canonical STAT1 and STAT3 target gene expression abrogates their intrinsic negative feedback loops, leading to accumulation of phospho–tyrosine-STAT3 and prolonged STAT1 phosphorylation. These findings challenge the generalization of tyrosine-phosphorylated STATs necessarily being transcriptional active and document antagonistic effects of MCMV on STAT1/3-dependent target gene expression

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis

Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT) its metabolic functions remain unclear. Herein, we address this critical gap in knowledge. Our transcriptomic analyses revealed that BMAT is distinct from WAT and BAT, with altered glucose metabolism and decreased insulin responsiveness. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake, while further in vivo studies showed that, compared to WAT, BMAT resists insulin-stimulated Akt phosphorylation. Thus, BMAT is functionally distinct from WAT and BAT. However, in humans basal glucose uptake in BMAT is greater than in axial bones or subcutaneous WAT and can be greater than that in skeletal muscle, underscoring the potential of BMAT to influence systemic glucose homeostasis. These PET/CT studies characterise BMAT function in vivo, establish new methods for BMAT analysis, and identify BMAT as a distinct, major adipose tissue subtype

Reduced Translocation of Cadmium from Roots Is Associated with Increased Production of Phytochelatins and Their Precursors

Cadmium (Cd) is a non-essential trace element and its environmental concentrations are approaching toxic levels, especially in some agricultural soils. Understanding how and where Cd is stored in plants is important for ensuring food safety. In this study, we examined two plant species that differ in the distribution of Cd among roots and leaves. Lettuce and barley were grown in nutrient solution under two conditions: chronic (4 weeks) exposure to a low, environmentally relevant concentration (1.0 μM) of Cd and acute (1 h) exposure to a high concentration (5.0 mM) of Cd. Seedlings grown in solution containing 1.0 μM CdCl2 did not show symptoms of toxicity and, at this concentration, 77% of the total Cd was translocated to leaves of lettuce, whereas only 24% of the total Cd was translocated to barley leaves. We tested the hypothesis that differential accumulation of Cd in roots and leaves is related to differential concentrations of phytochelatins (PCs), and its precursor peptides. The amounts of PCs and their precursor peptides in the roots and shoots were measured using HPLC. Each of PC2–4 was synthesized in the barley root upon chronic exposure to Cd and did not increase further upon acute exposure. In the case of lettuce, no PCs were detected in the root given either Cd treatment. The high amounts of PCs produced in barley root could have contributed to preferential retention of Cd in barley roots

Abnormal motor activity during anaesthesia in a dog: a case report

Seizures or convulsions that occur during anaesthesia in veterinary patients are infrequently reported in the literature. Consequently, the incidence of such events is unknown. Several drugs commonly used in clinical veterinary anaesthesia have been shown to induce epileptiform activity in both human clinical patients and experimental candidates. The present case report describes convulsions in a four-year old male Bernese mountain dog during maintenance of anaesthesia with isoflurane after premedication with acepromazine and methadone followed by co-induction with propofol and ketamine. The dog had no history of previous convulsions. The use of several sedative and anaesthetic drugs makes it difficult to find one single causative pharmaceutical

Obesity Reduces Bone Density Associated with Activation of PPARγ and Suppression of Wnt/β-Catenin in Rapidly Growing Male Rats

BACKGROUND: It is well established that excessive consumption of a high fat diet (HFD) results in obesity; however, the consequences of obesity on postnatal skeletal development have not been well studied. METHODOLOGY AND PRINCIPAL FINDINGS: Total enteral nutrition (TEN) was used to feed postnatal day 27 male rats intragastrically with a high 45% fat diet (HFD) for four weeks to induce obesity. Fat mass was increased compared to rats fed TEN diets containing 25% fat (medium fat diet, MFD) or a chow diet (low fat diet, LFD) fed ad libitum with matched body weight gains. Serum leptin and total non-esterified fatty acids (NEFA) were elevated in HFD rats, which also had reduced bone mass compared to LFD-fed animals. This was accompanied by decreases in bone formation, but increases in the bone resorption. Bone marrow adiposity and expression of adipogenic genes, PPARγ and aP2 were increased, whereas osteoblastogenic markers osteocalcin and Runx2 were decreased, in bone in HFD rats compared to LFD controls. The diversion of stromal cell differentiation in response to HFD stemmed from down-regulation of the key canonical Wnt signaling molecule β-catenin protein and reciprocal up-regulation of nuclear PPARγ expression in bone. In a set of in vitro studies using pluripotent ST2 bone marrow mesenchymal stromal cells treated with serum from rats on the different diets or using the free fatty acid composition of NEFA quantified in rat serum from HFD-fed animals by GC-MS, we were able to recapitulate our in vivo findings. CONCLUSIONS/SIGNIFICANCE: These observations strongly suggest that increased NEFA in serum from rats made obese by HFD-feeding impaired bone formation due to stimulation of bone marrow adipogenesis. These effects of obesity on bone in early life may result in impaired attainment of peak bone mass and therefore increase the prevalence of osteoporosis later on in life

Adenylyl Cyclase α and cAMP Signaling Mediate Plasmodium Sporozoite Apical Regulated Exocytosis and Hepatocyte Infection

Malaria starts with the infection of the liver of the host by Plasmodium sporozoites, the parasite form transmitted by infected mosquitoes. Sporozoites migrate through several hepatocytes by breaching their plasma membranes before finally infecting one with the formation of an internalization vacuole. Migration through host cells induces apical regulated exocytosis in sporozoites. Here we show that apical regulated exocytosis is induced by increases in cAMP in sporozoites of rodent (P. yoelii and P. berghei) and human (P. falciparum) Plasmodium species. We have generated P. berghei parasites deficient in adenylyl cyclase α (ACα), a gene containing regions with high homology to adenylyl cyclases. PbACα-deficient sporozoites do not exocytose in response to migration through host cells and present more than 50% impaired hepatocyte infectivity in vivo. These effects are specific to ACα, as re-introduction of ACα in deficient parasites resulted in complete recovery of exocytosis and infection. Our findings indicate that ACα and increases in cAMP levels are required for sporozoite apical regulated exocytosis, which is involved in sporozoite infection of hepatocytes