Association of dexmedetomidine use with haemodynamics, postoperative recovery, and cost in paediatric anaesthesia: a hospital registry study.

BACKGROUND: Dexmedetomidine utilisation in paediatric patients is increasing. We hypothesised that intraoperative use of dexmedetomidine in children is associated with longer postanaesthesia care unit length of stay, higher healthcare costs, and side-effects. METHODS: We analysed data from paediatric patients (aged 0-12 yr) between 2016 and 2021 in the Bronx, NY, USA. We matched our cohort with the Healthcare Cost and Utilization Project-Kids' Inpatient Database (HCUP-KID). RESULTS: Among 18 104 paediatric patients, intraoperative dexmedetomidine utilisation increased from 51.7% to 85.7% between 2016 and 2021 (P<0.001). Dexmedetomidine was dose-dependently associated with a longer postanaesthesia care unit length of stay (adjusted absolute difference [ADadj] 19.7 min; 95% confidence interval [CI]: 18.0-21.4 min; P<0.001, median length of stay of 122 vs 98 min). The association was magnified in children aged ≤2 yr undergoing short (≤60 min) ambulatory procedures (ADadj 33.3 min; 95% CI: 26.3-40.7 min; P<0.001; P-for-interaction <0.001). Dexmedetomidine was associated with higher total hospital costs of USD 1311 (95% CI: USD 835-1800), higher odds of intraoperative mean arterial blood pressure below 55 mm Hg (adjusted odds ratio [ORadj] 1.27; 95% CI: 1.16-1.39; P<0.001), and higher odds of heart rate below 100 beats min-1 (ORadj 1.32; 95% CI: 1.21-1.45; P<0.001), with no preventive effects on emergence delirium requiring postanaesthesia i.v. sedatives (ORadj 1.67; 95% CI: 1.04-2.68; P=0.034). CONCLUSIONS: Intraoperative use of dexmedetomidine is associated with unwarranted haemodynamic effects, longer postanaesthesia care unit length of stay, and higher costs, without preventive effects on emergence delirium.

Energy window optimization in bremsstrahlung imaging after Yttrium-90 microsphere therapy.

In imaging of Yttrium-90 patients treated hepatic primary and metastatic cancers, bremsstrahlung photons produced in a wide energy range is used. However, the image quality depends on acquisition energy window. This research aimed energy window optimization for Yttrium-90 bremsstrahlung imaging and 48 patients with various types of cancer received radioembolization therapy were investigated. Patients were imaged using a GE Healthcare Optima NM/CT 640 series gamma camera system with a medium energy general-purpose (MEGP) collimator and planar images were acquired with 8 different energy windows in the 55-400 keV energy range. The data set, formed with the % FOV, contrast, and spatial resolution of image quality parameters calculated from these images, was statistically examined with ANOVA and Tukey tests. According to the visual evaluations and ANOVA/Tukey test results, it was statistically concluded that energy window of 90-110 keV is the optimal energy window while 60-400 keV energy ranges show the lowest image quality for Y-90 bremsstrahlung imaging.

The relationship between social achievement goals and self-esteem, depression and anxiety among medical school students.

Background: Social achievement goals such as the desire to receive positive feedback from the social environment or avoid negative feedback are situations that affect an individual's quality of life and predispose them to mental disorders. Aim: The aim of this study is to investigate the relationship between social achievement goals and self-esteem, depression, and anxiety in medical school students. Materials and Methods: 400 participants, 201 of whom were female volunteers, between the ages of 18-30, studying at the Faculty of Medicine were evaluated. Sociodemographic Data Form, Social Achievement Goal Orientation Scale, Beck Anxiety Inventory, Beck Depression Inventory, and Rosenberg Self-Esteem Inventory Sub-Scale were applied to the participants. Results: A negative correlation between social development goals and depression (rs = -0.218, P < 0.001) and anxiety (rs = -0.188, P < 0.001), and a positive correlation with self-esteem (P = 0.002) were found. A statistically significant and positive correlation between social performance-avoidance goals and depression (rs = 0.233, P < 0.001) and anxiety (rs = 0.245, P < 0.001), and still statistically significant, and negative relationship with self-esteem (P = 0.001) were found. While social performance-approach goals were positively correlated with anxiety (rs = 0.192, P < 0.001) and depression (rs = 0.108, P = 0.03), no statistically significant correlation was found with self-esteem (P = 0.129). Conclusion: It has been seen that our study generally supports the other studies in the literature concerning the relations between social achievement goal subgroups and self-esteem, depression, and anxiety in university students. It will be possible to contribute to the findings with studies encompassing university students from different cities and departments and studies with a large number of participants other than students.

Evaluation of arterial stiffness and serum endocan levels in patients with primary aldosteronism with new-onset hypertension and long-term hypertension.

PURPOSE: There is growing evidence that prolonged exposure to high serum aldosterone concentrations results in target organ damage to the heart, kidney, and arterial wall, and that primary aldosteronism (PA) is associated with increased cardiovascular risk. In this study, we aimed to evaluate cardiovascular disease (CVD) risk indicators such as arterial stiffness [with pulse wave velocity (PWV) measurement] in PA patients and endocan levels, which is a biomarker of endothelial dysfunction. METHODS: 28 patients with PA were included in our study. As the control group, 14 patients with essential hypertension (EHT) and 28 normotensive healthy volunteers were included. Height, weight, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum fasting glucose, insulin, hemoglobin A1c (HbA1c), C-reactive protein (CRP), lipids and endocan levels of all subjects in the PA, EHT and control groups were measured. PWV measurements were performed to assess arterial stiffness. RESULTS: In the PA group, PWV levels were similar to the EHT group, and endocan levels were lower than the EHT group. In the PA group, PWV levels were higher than the control group, and endocan levels were lower than the control group. When we compared the PA group with new-onset HT with the PA group with long-term HT, PWV levels were higher in the PA group with long-term HT. When we compared the long-term HT group with the EHT group, PWV levels were higher in the long-term HT PA group and endocan levels were higher in the EHT group. When we compared the PA group with long-term HT with the control group, PWV levels were higher in the PA group with long-term HT, and endocan levels were similar in both groups. CONCLUSIONS: In our study, it was determined that arterial stiffness increased in PA cases with long-term HT compared to PA cases with new-onset HT, EHT cases and normotensive healthy cases. We found that endocan levels in PA patients were also lower than both EHT patients and healthy controls.

NEW BIOMARKERS TO PREDICT CARDIOVASCULAR RISK IN PATIENTS WITH ADRENAL INCIDENTALOMA; IRISIN AND NESFATIN-1.

Objective: In our study, we aimed to investigate the levels of irisin, nesfatin-1 and the relationship between levels of these relatively new molecules with cardiometabolic risk markers; carotid intima-media thickness (CIMT), epicardial adipose tissue (EAT) thickness in patients with nonfunctional adrenal incidentaloma (NFAI). Materials and Methods: Patients with NFAI (n=59) and age, sex and body mass index-matched healthy control subjects (n=59) were enrolled in this study. Serum glucose, insulin, C-reactive protein (CRP), lipid, irisin and nesfatin-1 levels and echocardiographic CIMT and EAT thickness measurements were performed in patients and controls. Results: The irisin level was 17.58 ± 4.38 pg/mL in the NFAI group, significantly higher (p<0.001) than 14.03 ± 4.03 pg/mL in the control group. Nesfatin-1 level was significantly lower in the NFAI group 194.98 ± 119.15 pg/mL ((p < 0.001)) versus 303.48 ± 200.78 pg/mL in the control group. A positive correlation was found between irisin and nesfatin-1 levels and CIMT and EAT thickness in the NFAI group. Conclusions: In our study, we found that irisin level was higher and nesfatin-1 level was lower in patients with NFAI, and both irisin and nesfatin-1 levels were associated with CIMT and EAT thickness in NFAI patients.

Human NK cells confer protection against HIV-1 infection in humanized mice.

The role of NK cells against HIV-1 infections remains to be elucidated in vivo. While humanized mouse models potentially could be used to directly evaluate human NK cell responses during HIV-1 infection, improved functional development of human NK cells in these hosts is needed. Here, we report the humanized MISTRG-6-15 mouse model, in which NK cells were quick to expand and exhibit degranulation, cytotoxicity, and proinflammatory cytokine production in nonlymphoid organs upon HIV-1 infection but had reduced functionality in lymphoid organs. Although HIV-1 infection induced functional impairment of NK cells, antiretroviral therapy reinvigorated NK cells in response to HIV-1 rebound after analytic treatment interruption. Moreover, a broadly neutralizing antibody, PGT121, enhanced NK cell function in vivo, consistent with antibody-dependent cellular cytotoxicity. Monoclonal antibody depletion of NK cells resulted in higher viral loads in multiple nonlymphoid organs. Overall, our results in humanized MISTRG-6-15 mice demonstrated that NK cells provided direct anti-HIV-1 responses in vivo but were limited in their responses in lymphoid organs.

Zinc Metalloprotease ProA from Legionella pneumophila Inhibits the Pro-Inflammatory Host Response by Degradation of Bacterial Flagellin.

The environmental bacterium Legionella pneumophila is an intracellular pathogen of various protozoan hosts and able to cause Legionnaires' disease, a severe pneumonia in humans. By encoding a wide selection of virulence factors, the infectious agent possesses several strategies to manipulate its host cells and evade immune detection. In the present study, we demonstrate that the L. pneumophila zinc metalloprotease ProA functions as a modulator of flagellin-mediated TLR5 stimulation and subsequent activation of the pro-inflammatory NF-κB pathway. We found ProA to be capable of directly degrading immunogenic FlaA monomers but not the polymeric form of bacterial flagella. These results indicate a role of the protease in antagonizing immune stimulation, which was further substantiated in HEK-BlueTM hTLR5 Detection assays. Addition of purified proteins, bacterial suspensions of L. pneumophila mutant strains as well as supernatants of human lung tissue explant infection to this reporter cell line demonstrated that ProA specifically decreases the TLR5 response via FlaA degradation. Conclusively, the zinc metalloprotease ProA serves as a powerful regulator of exogenous flagellin and presumably creates an important advantage for L. pneumophila proliferation in mammalian hosts by promoting immune evasion.

Macroanatomical and morphometric study on the skull bones of Aksaray Malakli dogs.

BACKGROUND: The skull is an important anatomical structure to discern dog breeds and wolves from dogs. For this purpose, skull morphology and some morphometric measurements of Malakli dogs, a local breed in the Aksaray region, were examined. MATERIALS AND METHODS: Thirty-two distances were measured and seven ratios calculated in nine skulls of adult dogs. In our study, different morphological features and statistical findings that were not revealed by taking measurements from 32 distinct anatomical points of Aksaray Malakli dog skull bones were determined in accordance with the literature. RESULTS: Processus zygomaticus was found to be long and pointed in the Aksaray Malakli dogs. The results of morphometric analysis were as follows: facial index value 107.68 ± 4.98, nasal index value 19.61 ± 3.25, cranial index value 56.17 ± 2.52, basal index value 30.57 ± 1.30, skull index 54.68 ± 3.01, palatal index I value 56.76 ± 1.89 and palatal index II value 59.83 ± 2.23. CONCLUSIONS: It can be concluded form the present investigation that the neurocranium length, facial index, cranial index, basal index, skull index, and palatal index values were statistically different from other dog breeds.

GRANULYSIN PEPTIDE AND GENE POLYMORPHISM IN THE PATHOGENESIS OF HASHIMOTO THYROIDITIS.

Background: Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Aim: Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. Material and Methods: 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. Results: There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. Conclusion: In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

Sustained Remission in Rheumatoid Arthritis: Time to Withdraw Treatment?

With increasing numbers of patients with rheumatoid arthritis achieving sustained remission, medication withdrawal is an important consideration to reduce polypharmacy and associated adverse events. An article from the journal Arthritis & Rheumatology (1) explores the treatment withdrawal options for patients on etanercept and methotrexate combination therapies and suggests methotrexate withdrawal has the least impact on disease worsening. There are limitations in the study, including the use of only one disease activity score and no assessment of radiographic progression, but, overall, the article provides a good framework for future studies on treatment withdrawal options and the possibility of medication reduction for patients.

Evaluation of retinal microvascular changes in patients with prediabetes.

AIM: Diabetic retinopathy is a chronic progressive complication with neuronal cell and retinal microvascular involvement and is closely associated with blood sugar and blood pressure levels. Studies have shown that retinal neural dysfunction takes place before the microvascular changes in patients with Type 2 diabetes mellitus. The aim of this study is to compare the retinal microvascular changes of patients who are at the prediabetes stage and healthy volunteers. METHOD: Our study included 41 patients with prediabetes who were referred to the internal medicine outpatient clinic and 47 healthy volunteers. All patients underwent ophthalmologic examinations, including best visual acuity, intraocular pressure measurement, slit-lamp examination, and dilated fundus examination. Refractive error measurements were performed with the same automatic refractor-keratometer device. Typically, 3 × 3 mm macular images centered on foveola were obtained by using XR Avanti Optical Coherence Tomography Angiography with AngioVue (RTVue XR AVANTI, Optovue, Fremont, CA, USA) device. In the statistical analysis of the measurements, it was examined by Kolmogorov Smirnov test. Conditions expressed as IFG or IGT are considered as prediabetes; IFG is defined as fasting blood sugar to be between 100 and 125 mg/dL, while IGT is the condition in which the second hour value of the oral glucose tolerance test is 140-199 mg/dL. RESULTS: There was no statistically significant difference between the control and pre-DM groups in terms of mean age. The distribution of males and females between groups was statistically similar (P = 0.087). In the pre-DM group, 24 (58.6%) patients had IFG, 16 (39.0%) had IFG + IGT, and 1 (2.4%) had IGT. There were no statistically significant differences between the groups for the nonflow area (NFA) and the foveal avascular zone (FAZ) area (P > 0.05). The mean values of superficial and deep capillary plexus (DCP) density were not statistically significant differences between the groups. No statistically significant difference was found between the control group and pre-DM group in terms of the mean measurements of clinical ocular findings (P > 0.05). Retinal thicknesses were also not statistically significant differences between the groups (P > 0.05). CONCLUSION: All of the retinal measurements of both patients with prediabetes and healthy volunteers are similar. We did not find any difference between prediabetes and control groups. The ophthalmologic examinations which contain best-visual acuity, intraocular pressure measurement, slit-lamp examination, and dilated fundus examination are similar.

Loss of CASK Accelerates Heart Failure Development.

[Figure: see text].

Zinc metalloprotease ProA of Legionella pneumophila increases alveolar septal thickness in human lung tissue explants by collagen IV degradation.

ProA is a secreted zinc metalloprotease of Legionella pneumophila causing lung damage in animal models of Legionnaires' disease. Here we demonstrate that ProA promotes infection of human lung tissue explants (HLTEs) and dissect the contribution to cell type specific replication and extracellular virulence mechanisms. For the first time, we reveal that co-incubation of HLTEs with purified ProA causes a significant increase of the alveolar septal thickness. This destruction of connective tissue fibres was further substantiated by collagen IV degradation assays. The moderate attenuation of a proA-negative mutant in A549 epithelial cells and THP-1 macrophages suggests that effects of ProA in tissue mainly result from extracellular activity. Correspondingly, ProA contributes to dissemination and serum resistance of the pathogen, which further expands the versatile substrate spectrum of this thermolysin-like protease. The crystal structure of ProA at 1.48 Å resolution showed high congruence to pseudolysin of Pseudomonas aeruginosa, but revealed deviations in flexible loops, the substrate binding pocket S1 ' and the repertoire of cofactors, by which ProA can be distinguished from respective homologues. In sum, this work specified virulence features of ProA at different organisational levels by zooming in from histopathological effects in human lung tissue to atomic details of the protease substrate determination.

SnoopLigase-Mediated Peptide-Peptide Conjugation and Purification.

Covalently linking together different proteins can enhance functionality for a range of applications. We have developed the SnoopLigase peptide-peptide conjugation method to easily and specifically link proteins fused to the peptides SnoopTagJr or DogTag via an isopeptide bond. SnoopLigase conjugation has been applied for enhancing enzyme resilience and for antigen oligomerization to enhance vaccine efficacy. Following conjugation, SnoopLigase and unreacted substrates can be removed by solid-phase immobilization of SnoopLigase, yielding purified protein-protein conjugates. Here, we describe procedures for designing tag-fused proteins, SnoopLigase purification, and ligation of SnoopTagJr and DogTag. We further define steps for the purification of the ligated product and quantification of ligation success.

Fuzzy-based self organizing aggregation method for swarm robots.

Fuzzy-based self-organizing aggregation method was suggested in the present study for swarm robots. In the suggested method, Swarm robots evaluate their limited sensor input via rules of fuzzy logic and display aggregation behavior with the suggested aggregation method. In the meantime, swarm robots also have the ability to escape the obstacles in a bounded arena with this method. Swarm robots perceive the neighboring robots with this method, make individual decisions and display aggregation behaviors. Different from the traditional self-organizing aggregation methods, the suggested approach utilizes fuzzy logic controllers to evaluate limited sensor data. Systematic experiments were applied on different number of swarm robots with different detection areas in arenas of different sizes. Moreover, noise was applied on the sensor inputs for examining the performance of the fuzzy logic based self-organizing aggregation method. The scalability and flexibility of the self-organizing aggregation behaviors of swarm robots were evaluated by way of systematic experiments. The swarm robots displayed aggregation behavior during the systematic experiments applied despite the changes in the number of robots and detection distances.

Development of a Larval Zebrafish Infection Model for Clostridioides difficile.

Clostridioides difficile infection (CDI) is considered to be one of the most common healthcare-associated gastrointestinal infections in the United States. The innate immune response against C. difficile has been described, but the exact roles of neutrophils and macrophages in CDI are less understood. In the current study, Danio rerio (zebrafish) larvae are used to establish a C. difficile infection model for imaging the behavior and cooperation of these innate immune cells in vivo. To monitor C. difficile, a labeling protocol using a fluorescent dye has been established. A localized infection is achieved by microinjecting labeled C. difficile, which actively grows in the zebrafish intestinal tract and mimics the intestinal epithelial damage in CDI. However, this direct infection protocol is invasive and causes microscopic wounds, which can affect experimental results. Hence, a more noninvasive microgavage protocol is described here. The method involves delivery of C. difficile cells directly into the intestine of zebrafish larvae by intubation through the open mouth. This infection method closely mimics the natural infection route of C. difficile.

SnoopLigase peptide-peptide conjugation enables modular vaccine assembly.

For many infectious diseases there is still no vaccine, even though potential protective antigens have been identified. Suitable platforms and conjugation routes are urgently needed to convert the promise of such antigens into broadly protective and scalable vaccines. Here we apply a newly established peptide-peptide ligation approach, SnoopLigase, for specific and irreversible coupling of antigens onto an oligomerization platform. SnoopLigase was engineered from a Streptococcus pneumoniae adhesin and enables isopeptide bond formation between two peptide tags: DogTag and SnoopTagJr. We expressed in bacteria DogTag linked to the self-assembling coiled-coil nanoparticle IMX313. This platform was stable over months at 37 °C when lyophilized, remaining reactive even after boiling. IMX-DogTag was efficiently coupled to two blood-stage malarial proteins (from PfEMP1 or CyRPA), with SnoopTagJr fused at the N- or C-terminus. We also showed SnoopLigase-mediated coupling of a telomerase peptide relevant to cancer immunotherapy. SnoopLigase-mediated nanoassembly enhanced the antibody response to both malaria antigens in a prime-boost model. Including or depleting SnoopLigase from the conjugate had little effect on the antibody response to the malarial antigens. SnoopLigase decoration represents a promising and accessible strategy for modular plug-and-display vaccine assembly, as well as providing opportunities for robust nanoconstruction in synthetic biology.