Clinical impact of allergy and pre-medication in CT studies with low-osmolality intravenous iodinated contrast media.

AIM: To evaluate the occurrence and severity of allergic reactions to iodinated contrast media (ICM), including associated risk factors and the impact of pre-medication. MATERIALS AND METHODS: Data on patients who had experienced allergic reactions during outpatient computed tomography (CT) examinations between January 2014 and September 2018 were analysed retrospectively. Response severity was assessed according to validated criteria. A control group was selected among individuals who underwent CT during the study period and did not experience allergic reactions. RESULTS: Screening of 36,920 CT studies revealed 74 (0.2%) individuals with systemic reactions to ICM. No significant differences in patient characteristics were found among patients who experienced mild (n=54), moderate (n=17), or severe (n=4) reactions. Previous ICM allergy was reported in 10 patients (13.3%). Patients with a history of ICM allergy had mild (9/10) or moderate (1/10) reactions, with one individual showing decreased intensity of the allergic response compared to a previous event. Within the control group, four patients (4%) had previous ICM allergy. In these individuals, lack of allergic reactions could not be attributed to pre-medication. All patients with severe reactions did not have a prior history of ICM allergy. CONCLUSION: Severe allergic reactions to ICM are rare, lack significant risk factors, and do not appear to be impacted by pre-medication. The findings presented herein highlight the need for prospective work that will re-evaluate the yield of pre-medication protocols.

Coenzyme Q10 in the Treatment of Heart Failure with Preserved Ejection Fraction: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation. RESULTS: A total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195). CONCLUSIONS: In this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels. TRIAL REGISTRATION: This trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634).

Association of Contemporary Statin Pretreatment Intensity and LDL-C Levels on the Incidence of STEMI Presentation.

Constituting hypolipidemic and pleiotropic effects, statins stabilize coronary artery plaque and may prevent STEMI events. This study investigated the association between contemporary statin pretreatment intensity, low-density lipoprotein cholesterol (LDL-C) levels, and the type of acute coronary syndrome (ACS) presentation: STEMI vs. NSTE-ACS. Data were drawn from the ACS Israeli Survey (ACSIS), a biennial prospective national survey that took place in 2008-2018. The rate of STEMI vs. NSTE-ACS was calculated by statin use, including statin intensity (high-intensity statin therapy (HIST) and low-intensity statin therapy (LIST) prior to the index ACS event. Among 5103 patients, 2839 (56%) were statin-naive, 1389 (27%) used LIST and 875 (17%) used HIST. Statin pretreated patients were older and had a higher rates of co-morbidities, cardiovascular disease history and pretreatment with evidence-based medications. STEMI vs. NSTE-ACS was lower among HIST vs. LIST vs. statin-naive patients (31.0%, 37.8%, and 54.0%, respectively, p for trend < 0.001). Multivariate analysis revealed that HIST was independently associated with lower STEMI presentation (ORadj 0.70; 95% CI 0.57-0.86), while LIST (ORadj 0.92; 95% CI 0.77-1.10) and LDL-C < 70 mg/dL (ORadj 0.96; 95% CI 0.82-1.14) were not. In conclusion, among patients admitted with ACS, pretreatment with HIST was independently associated with a lower probability of STEMI presentation, while LIST and LDL-C < 70 mg/dL were not.

γδT Cells Are Essential for Orthodontic Tooth Movement.

Sustained mechanical forces applied to tissue are known to shape local immunity. In the oral mucosa, mechanical stress, either naturally induced by masticatory forces or externally via mechanical loading during orthodontic tooth movement (OTM), is translated, in part, by T cells to alveolar bone resorption. Nevertheless, despite being considered critical for OTM, depletion of CD4+ and CD8+ T cells is reported to have no impact on tooth movement, thus questioning the function of αßT cells in OTM-associated bone resorption. To further address the role of T cells in OTM, we first characterized the leukocytes residing in the periodontal ligament (PDL), the tissue of interest during OTM, and compared it to the neighboring gingiva. Unlike the gingiva, monocytes and neutrophils represent the major leukocytes of the PDL. These myeloid cells were also the main leukocytes in the PDL of germ-free mice, although at lower levels than SPF mice. T lymphocytes were more enriched in the gingiva than the PDL, yet in both tissues, the relative fraction of the γδT cells was higher than the αß T cells. We thus sought to examine the role of γδT cells in OTM. γδT cells residing in the PDL were mainly Vγ6+ and produced interleukin (IL)-17A but not interferon-γ. Using Tcrd-GDL mice allowing conditional ablation of γδT cells in vivo, we demonstrate that OTM was greatly diminished in the absence of γδT cells. Further analysis revealed that ablation of γδT cells decreased early IL-17A expression, monocyte and neutrophil recruitment, and the expression of the osteoclastogenic molecule receptor activator of nuclear factor-κß ligand. This, eventually, resulted in reduced numbers of osteoclasts in the pressure site during OTM. Collectively, our data suggest that γδT cells are essential in OTM for translating orthodontic mechanical forces to bone resorption, required for relocating the tooth in the alveolar bone.

Cardiac arrhythmias amongst hospitalised Coronavirus 2019 (COVID-19) patients: Prevalence, characterisation, and clinical algorithm to classify arrhythmic risk.

OBJECTIVES: A significant proportion of COVID-19 patients may have cardiac involvement including arrhythmias. Although arrhythmia characterisation and possible predictors were previously reported, there are conflicting data regarding the exact prevalence of arrhythmias. Clinically applicable algorithms to classify COVID patients' arrhythmic risk are still lacking, and are the aim of our study. METHODS: We describe a single-centre cohort of hospitalised patients with a positive nasopharyngeal swab for COVID-19 during the initial Israeli outbreak between 1/2/2020 and 30/5/2020. The study's outcome was any documented arrhythmia during hospitalisation, based on daily physical examination, routine ECG's, periodic 24-hour Holter, and continuous monitoring. Multivariate analysis was used to find predictors for new arrhythmias and create classification trees for discriminating patients with high and low arrhythmic risk. RESULTS: Out of 390 COVID-19 patients included, 28 (7.2%) had documented arrhythmias during hospitalisation, including 23 atrial tachyarrhythmias, combined atrial fibrillation (AF), and ventricular fibrillation, ventricular tachycardia storm, and 3 bradyarrhythmias. Only 7/28 patients had previous arrhythmias. Our study showed a significant correlation between disease severity and arrhythmia prevalence (P < .001) with a low arrhythmic prevalence amongst mild disease patients (2%). Multivariate analysis revealed background heart failure (CHF) and disease severity are independently associated with overall arrhythmia while age, CHF, disease severity, and arrhythmic symptoms are associated with tachyarrhythmias. A novel decision tree using age, disease severity, CHF, and troponin levels was created to stratify patients into high and low risk for developing arrhythmia. CONCLUSIONS: Dominant arrhythmia amongst COVID-19 patients is AF. Arrhythmia prevalence is associated with age, disease severity, CHF, and troponin levels. A novel simple Classification tree, based on these parameters, can discriminate between high and low arrhythmic risk patients.

Exogenous interleukin-2 can rescue in-vitro T cell activation and proliferation in patients with a novel capping protein regulator and myosin 1 linker 2 mutation.

Capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is characterized by impaired T cell activation, which is attributed to defective CD28-mediated co-signaling. Herein, we aimed to analyze the effect of exogenous interleukin (IL)-2 on in-vitro T cell activation and proliferation in a family with CARMIL2 deficiency. This study included four children (one male and three females; aged 2·5-10 years at presentation). The patients presented with inflammatory bowel disease and recurrent viral infections. Genetic analysis revealed a novel homozygous 25-base pairs deletion in CARMIL2. Immunoblotting demonstrated the absence of CARMIL2 protein in all four patients and confirmed the diagnosis of CARMIL2 deficiency. T cells were activated in-vitro with the addition of IL-2 in different concentrations. CD25 and interferon (IFN)-γ levels were measured after 48 h and 5 days of activation. CD25 surface expression on activated CD8+ and CD4+ T cells was significantly diminished in all patients compared to healthy controls. Additionally, CD8+ T cells from all patients demonstrated significantly reduced IFN-γ production. When cells derived from CARMIL2-deficient patients were treated with IL-2, CD25 and IFN-γ production increased in a dose-dependent manner. T cell proliferation, as measured by Cell Trace Violet, was impaired in one patient and it was also rescued with IL-2. In conclusion, we found that IL-2 rescued T cell activation and proliferation in CARMIL2-deficient patients. Thus, IL-2 should be further studied as a potential therapeutic modality for these patients.

Alopecia areata in patients with systemic lupus erythematosus treated with belimumab: a plausible association.

Belimumab, an anti-B-lymphocyte stimulator monoclonal antibody, was recently approved for the treatment of systemic lupus erythematosus. Alopecia areata is characterized by an acute immune-mediated hair loss. Herein, we report on three adult systemic lupus erythematosus patients who developed alopecia areata in association with belimumab treatment. Alopecia areata was resolved in all three patients and belimumab was discontinued in two of them. Thus, in the current report, we explore the plausible link between alopecia areata and belimumab.

Sex-linked difference in blood oxygen saturation.

BACKGROUND: It is not known whether SpO2 in healthy volunteers is affected by sex. OBJECTIVE: To evaluate whether there are differences in SpO2 between young healthy adult males and females and to evaluate whether the differences are already present at birth. METHODS: We studied two cohorts of patients. The first one consisted of young adult volunteers (105 males and 102 females). In these patients, SpO2 was measured as well as selected anthropometric variables (height, weight), vital signs (respiratory rate, pulse rate and body temperature) and obtained data on menstrual cycle phase of the female participants. For the second cohort, we reanalyzed data from a previous prospective study that was performed to compare SpO2 of newborns infants born at different altitudes (sea level or 760 m above sea level). MEASUREMENTS AND MAIN RESULTS: In young male adults, mean SpO2 was 97.1% ± 1.2% versus 98.6% ± 1.0% in females (P < .001). This difference remained significant (P = .002) after correction for BMI, BSA and age, variables that were significantly different between sexes in univariate analysis. The SpO2 in females was unaffected by menstrual phase. In contrast to findings in adults, there were no significant differences in SpO2 measurements in newborn infants attributable to sex. CONCLUSIONS: Healthy young female adults have a higher (1.5%) SpO2 than their male counterparts. This difference is not yet present at birth. Further studies are needed to determine the timing of sex-differences, and to better define the mechanism(s) behind this observation.

Hydroxychloroquine desensitization, an effective method to overcome hypersensitivity-a multicenter experience.

Hydroxychloroquine (HCQ) is widely used to treat autoimmune/rheumatic diseases such as systemic lupus erythematosus (SLE). The immune modulation effects of HCQ have been highlighted as beneficial for maintaining remission of SLE as well as ameliorating skin, joint and other manifestations. Moreover, HCQ exposure for prolonged periods as well as during pregnancy is considered safe, therefore it is recommended for the vast majority of SLE patients. Although HCQ therapy requires follow-up by a specialist, its most common side effects are mild gastrointestinal disturbances, sensitivity to light and skin rashes. Of these side effects, hypersensitivity skin reactions have been suggested to play a role in reduced compliance to HCQ therapy. In the current study we present a two-stage HCQ desensitization protocol that was successfully implemented among 12 out of 13 patients. We exhibit that prolonged HCQ oral desensitization is an effective method for overcoming mild to moderate late hypersensitivity reactions and thoroughly address possible mechanisms of action.

Loss of lamin A function increases chromatin dynamics in the nuclear interior.

Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2α, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization.

Transgenic over-expression of mammalian heparanase delays prion disease onset and progression.

Cellular heparan sulfate (HS) has a dual role in scrapie pathogenesis; it is required for PrP(Sc) (scrapie prion protein) formation and facilitates infection of cells, mediating cellular uptake of prions. We examined the involvement of heparanase, a mammalian endoglycosidase degrading HS, in scrapie infection. In cultured cells, heparanase treatment or over-expression resulted in a profound decrease in PrP(Sc). Moreover, disease onset and progression were dramatically delayed in scrapie infected transgenic mice over-expressing heparanase. Together, our results provide direct in vivo evidence for the involvement of intact HS in the pathogenesis of prion disease and the protective role of heparanase both in terms of susceptibility to infection and disease progression.

Retained placental tissue as an emerging cause for malpractice claims.

BACKGROUND: Removal of retained placental tissue postpartum and retained products of conception (RPOC) abortion is done by uterine curettage or hysteroscopy. Trauma to the endometrium from surgical procedures, primarily curettage, can cause intrauterine adhesions (Asherman's syndrome) and subsequent infertility. The incidence of malpractice claims relating to intrauterine adhesions is rising, justifying reevaluation of the optimal way of handling these complications. OBJECTIVES: To review malpractice claims regarding intrauterine adhesions, and to explore the clinical approach that might reduce those claims or improve their medical and legal outcomes. METHODS: We examined 42 Asherman's syndrome claims handled by MCI, the largest professional liability insurer in Israel. The clinical chart of each case was reviewed and analyzed by the event preceding the adhesion formations, timing and mode of diagnosis, and outcome. We also assessed whether the adverse outcome was caused by substandard care and it it could have been avoided by different clinical practice. The legal outcome was also evaluated. RESULTS: Forty-seven percent of the cases occurred following vaginal delivery, 19% followed cesarean section, 28% were RPOC following a first-trimester pregnancy termination, and 2% followed a second-trimester pregnancy termination. CONCLUSIONS: It is apparent that due to the lack of an accepted management protocol for cases of RPOC, it is difficult to legally defend those cases when the complication of Asherman syndrome develops.

Newborn oxygen saturation at mild altitude versus sea level: implications for neonatal screening for critical congenital heart disease.

AIM: To determine the normal SpO2 in healthy term newborns at mild altitude (MA, 780 metres) compared with sea level (SL), within the context of universal screening for critical congenital heart disease (CCHD). METHODS: We studied 199 (119 at MA and 80 at SL) consecutively born healthy newborns. SpO2 recordings were at 24-72 h using Masimo SET Radical-7 on the right hand and left foot. RESULTS: Mean SpO2 was lower at MA compared with SL in the right hand (97.86 ± 1.58 vs 98.28 ± 1.41, p = 0.05) and left foot (98.49 ± 1.35 vs 98.90 ± 1.16, p = 0.03). No infant with SpO2 <95% had CCHD. Extrapolating with predicted regression lines set at 95% CI, a SpO2 cut-off of 95% would result in up to 3.5 times more false-positive screens at MA compared with SL. CONCLUSIONS: At MA, SpO2 is approximately 0.4% lower compared with SL. Our study supports the AAP recommendation suggesting algorithm cut-offs may need adjustment in high-altitude nurseries and suggest broadening it to MA as well.

Transient anomalous diffusion of telomeres in the nucleus of mammalian cells.

We measured individual trajectories of fluorescently labeled telomeres in the nucleus of eukaryotic cells in the time range of 10(-2)-10(4)sec by combining a few acquisition methods. At short times the motion is subdiffusive with r2 approximately talpha and it changes to normal diffusion at longer times. The short times diffusion may be explained by the reptation model and the transient diffusion is consistent with a model of telomeres that are subject to a local binding mechanism with a wide but finite distribution of waiting times. These findings have important biological implications with respect to the genome organization in the nucleus.

Goal orientations in negotiations: the influence of goal orientations on fixed-pie perceptions and bargaining outcomes.

As is the case for other achievement situations, people may approach negotiations emphasizing outcome and/or process goals. This paper examines the effects of process goal orientation (PGO) and outcome goal orientation (OGO) on individuals' fixed-pie perceptions and the negotiation of joint outcomes. Process and outcome goal orientations are associated with different personal beliefs about the world. We hypothesized that persons who are primarily oriented toward outcome goals, based on their fixed-entity perception of the world, would mainly concentrate on the final results or on the outcomes of the negotiation. They would tend to perceive negotiations as fixed, zero-sum, competitive situations, which have to be "won" by one of the parties at the expense of the other. On the other hand, we predicted that people who are strongly process-oriented, based on their malleable-entity perception of the world, would focus mainly on formulating and mastering the best strategies that lead to successful resolution of the negotiation. They would perceive positions to be "malleable" and, hence, would tend to perceive the negotiation as a non zero-sum situation. Additionally, the interaction between the two types of goal orientations and its effect on the parties' joint negotiation outcomes was examined. Results of two empirical studies indicated that OGO was significantly positively associated with fixed-pie bias (Study 1). The significant interaction between PGO and OGO (Study 2) demonstrated that a strong OGO combined with a strong PGO led to the best joint negotiation outcomes. Implications for goal orientation and negotiation theories are discussed.

A rare complication of a common operation: hepatic artery pseudo aneurysm following cholecystectomy report of a case.

BACKGROUND: Vascular injuries following cholecystectomy are a known entity though the incidence is low. More frequently we are seeing cases of right hepatic artery pseudo aneurysm post cholecystectomy after the advent of the laparoscopic approach. METHODS: We report a case of multiple right hepatic artery aneurysms as a complication of cholecystectomy in a 71-year-old patient. RESULTS: The diagnosis was confirmed by angiogram, and the patient was treated successfully with coil embolisation. CONCLUSION: Though it is a rare complication, early diagnosis and treatment of postoperative pseudo aneurysm is essential to prevent life threatening bleeding.

Nitrate removal in aquariums by immobilized pseudomonas.

Biological denitrification of nitrate to nitrogen gas was examined in a freshwater and a marine aquarium. Nitrate removal in the aquarium water was accomplished with denitrifiers immobilized in a freeze-dried, alginate-starch matrix. Starch served as a bacterial carbon source and cellular matrix-strengthening filler. Freeze-dried beads were placed in canisters through which nitrate-rich aquarium water was recirculated. The freshwater aquarium (100 L) contained goldfish (Carassius auratus) at a total biomass of 390 g, whereas cichlids (Oreochromis mossambicus) were kept at a similar stocking density in the marine aquarium. Denitrification resulted in low ambient nitrate concentrations in both aquariums. The specific nitrate removal rate of the freshwater beads was significantly higher (50 microg of NO(3)-N/bead/day) than that of seawater beads (5 microg of NO(3)-N/bead/day). Differences in ambient nitrate concentrations between both aquariums and diffusion limitation of nitrate to the active denitrification sites within the beads might explain these observed differences.

At first glance: social meanings of dental appearance.

OBJECTIVES: An important factor in social interaction is physical appearance. Major elements in the evaluation of physical appearance are the mouth and teeth. The purpose of this study was to evaluate the effect of tooth appearance on the development of a first impression of the other person, with regard to the sex of both the respondent and the target. METHODS: Eight facial photographs of individuals with intact upper teeth were manipulated: one set was left untouched and the other was professionally altered so that the front anterior teeth appeared decayed. The photographs were randomly aligned in sets of eight, each set consisting of four individuals with an original, intact dentition and four other individuals with a "decayed" dentition. The sets of photographs were then presented to 115 respondents (65 males and 50 females). Evaluations were made according to three categories of traits--esthetic, social, and professional. RESULTS: For all three evaluation categories, the difference in scores between decayed and intact dentition given to targets were significantly higher when participants of one sex evaluated targets of the opposite sex, as compared to evaluating targets of their own sex. CONCLUSIONS: The effect of tooth appearance on the physical attractiveness stereotype is more evident when males evaluate females and vice versa, rather than when evaluating their own sex.