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Abstract Management of congenital coronary artery anomalies (CAA) is not standardized due to the variety of conditions included and their rare prevalence. Detection of CAA during myocardial infarction with non‐obstructive coronary arteries (MINOCA) may induce clinicians to address the patient for surgery as CAA is not included in any algorithm1,2 for the management of MINOCA and American Association for Thoracic Surgery evidence‐based guidelines suggest surgical repair for patients with anomalous aortic origin of a coronary artery and symptoms compatible with myocardial ischaemia.3 We present the case of a 35‐year‐old man with an anomalous origin of left coronary artery from right Valsalva sinus with pre‐pulmonic course detected during urgent coronary angiography for suspected myocardial infarction. Stress cardiac magnetic resonance did not show signs of ischaemia at high‐dose dobutamine but did reveal a recent myocarditis. This clinical case highlights the need for accurate risk stratification in CAA especially when confounding clinical scenarios co‐exist.

Abstract This systematic review consists of two parts. Part I seeks to synthesise evidence from primary or secondary research studies examining the implementation and effectiveness of case management tools and approaches currently being used to counter radicalisation to violence. Part II is an ‘overview of reviews’ that seeks to identify relevant and transferable lessons from systematic reviews and meta‐analyses of case management tools and approaches used in the broader field of violence prevention that could be applied to counter‐radicalisation practice.

Abstract Aim Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. Methods and results The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA‐R) will collect data from ACHD evaluated or listed for heart or heart‐combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989–2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All‐cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. Conclusion The ARTORIA‐R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

ABSTRACT Three protocols (Ketamine–Medetomidine, Ketamine–Xylazine and Ketamine–Medetomidine–Midazolam) were used to immobilize 2 sympatric wild cat species, the critically endangered Andean cat (Leopardus jacobita), and the relatively more common Pampas cat (L. colocolo), in the high Andes Mountains of Argentina between September 2011 and May 2016. Based on 8 Andean cat capture events and 9 Pampas cat capture events, we determined that the ketamine–medetomidine combination safely induced 45 minutes of anesthesia at a dosage range of ketamine: 6–9 mg/kg, medetomidine: 0.05–0.08 mg/kg for field immobilization. Heart rate, respiratory rate, and oxygen saturation remained within acceptable limits during all captures, but we had cases of hyperthermia in animals captured during the day. There was no evidence of a decline in the health condition of any animals recaptured 148–1,290 days post–initial capture. © 2020 The Wildlife Society.

Background Tricuspid regurgitation (TR) is a common finding in adults with congenital heart disease referred for pulmonary valve replacement (PVR). However, indications for combined valve surgery remain controversial. This study aimed to evaluate early results of concomitant tricuspid valve intervention (TVI) at the time of PVR. Methods and Results Observational studies comparing TVI+PVR and isolated PVR were identified by a systematic search of published research. Random‐effects meta‐analysis was performed, comparing outcomes between the 2 groups. Six studies involving 749 patients (TVI+PVR, 278 patients; PVR, 471 patients) met the eligibility criteria. In the pooled analysis, both TVI+PVR and PVR reduced TR grade, pulmonary regurgitation grade, right ventricular end‐diastolic volume, and right ventricular end‐systolic volumes. TVI+PVR, but not PVR, was associated with a decrease in tricuspid valve annulus size (mean difference, −6.43 mm, 95% CI, −10.59 to −2.27; P=0.010). Furthermore, TVI+PVR was associated with a larger reduction in TR grade compared with PVR (mean difference, −0.40; 95% CI, −0.75 to −0.05; P=0.031). No evidence could be established for an effect of either treatment on right ventricular ejection fraction or echocardiographic assessment of right ventricular dilatation and dysfunction. There was no evidence for a difference in hospital mortality or reoperation for TR. Conclusions While both strategies are effective in reducing TR and right ventricular volumes, routine TVI+PVR can reduce TR grade to a larger extent than isolated PVR. Further studies are needed to identify the subgroups of patients who might benefit most from combined valve surgery.

ABSTRACT We assessed chemical immobilization and success of trapping devices on a little‐known South American mustelid, the lesser grison (Galictis cuja). From December 1998 to June 2006, we live‐trapped (n = 23) and radiomarked (n = 9) free‐ranging lesser grisons in 2 areas of the Pampas grasslands of Argentina. Both box‐traps and rubber‐padded leg‐hold traps allowed us to capture lesser grisons. However, leg‐hold traps had greater capture efficiency. Although the liberation time was longer with tiletamine–zolazepam than ketamine–xylazine, field immobilization of lesser grisons with both drug combinations was effective and safe. The high frequency of thermal regulation problems suggests that body temperatures of chemically restrained lesser grisons should be routinely monitored. Neither collars nor backpack harnesses were effective methods for attachment of radiotransmitters. Trapped individuals showed male‐skewed sexual size dimorphism and sex ratio. Capture times suggest that lesser grisons are largely diurnal. Most of the data presented in this study are the first published on the lesser grison and provide baseline information for future research and conservation. © 2016 The Wildlife Society.

The well-known phenomenon of phase separation in synthetic polymers and proteins has become a major topic in biophysics because it has been invoked as a mechanism of compartment formation in cells, without the need for membranes. Most of the coacervates (or condensates) are composed of Intrinsically Disordered Proteins (IDPs) or regions that are structureless, often in interaction with RNA and DNA. One of the more intriguing IDPs is the 526-residue RNA-binding protein, Fused in Sarcoma (FUS), whose monomer conformations and condensates exhibit unusual behavior that are sensitive to solution conditions. By focussing principally on the N-terminus low-complexity domain (FUS-LC comprising residues 1-214) and other truncations, we rationalize the findings of solid-state NMR experiments, which show that FUS-LC adopts a non-polymorphic fibril structure (core-1) involving residues 39-95, flanked by fuzzy coats on both the N- and C-terminal ends. An alternate structure (core-2), whose free energy is comparable to core-1, emerges only in the truncated construct (residues 110-214). Both core-1 and core-2 fibrils are stabilized by a Tyrosine ladder as well as hydrophilic interactions. The morphologies (gels, fibrils, and glass-like) adopted by FUS seem to vary greatly, depending on the experimental conditions. The effect of phosphorylation is site-specific. Simulations show that phosphorylation of residues within the fibril has a greater destabilization effect than residues that are outside the fibril region, which accords well with experiments. Many of the peculiarities associated with FUS may also be shared by other IDPs, such as TDP43 and hnRNPA2. We outline a number of problems for which there is no clear molecular explanation., (© 2023 Wiley Periodicals LLC.)

Pentoxifylline is a synthetic xanthine derivative and is hepatically cleared. The natural dimethylxanthines theobromine and theophylline have been shown to have enhanced metabolism in smokers when compared with nonsmokers. Subsequently, the effect of smoking on pentoxifylline plasma concentrations was investigated. Twenty healthy volunteers (10 smokers and 10 nonsmokers) received pentoxifylline 400 mg as a controlled-release tablet every 8 hours for 17 doses. Several blood samples were collected for 8 hours after the final dose. These samples were assayed for pentoxifylline and its metabolites. The mean values of the smokers were compared with those of the nonsmokers. With respect to pentoxifylline, no statistically significant differences in maximum concentration and time of maximum concentration were observed between the two groups. Although no statistical differences in plasma concentrations and area-under-the-curve at steady state (AUCss) were observed, the oral clearance of pentoxifylline among the smokers (.22 +/- .08 L/minute/kg) was significantly greater (P < .05) than that among the nonsmokers (0.15 +/- 0.06 L/minute/kg) when corrected for body weight. With respect to the pentoxifylline metabolite 1-(5-hydroxy-hexyl)-3,7-dimethylxanthine (MI), the maximum concentration and AUCss of the smokers were significantly decreased when compared with the nonsmokers. The AUCss of the smokers was 1438 +/- 819 ng.hour/mL and of the nonsmokers was 2864 +/- 1375 ng.hour/mL (P < .02). The results of this trial suggest that smoking tends to reduce pentoxifylline plasma concentrations and significantly reduces MI plasma concentrations.

The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect.

Pentoxifylline, recently approved for the treatment of intermittent claudication, is hepatically cleared with a high degree of first-pass metabolism. Subsequently, the effect of cimetidine on pentoxifylline pharmacokinetics was studied in humans. Ten healthy subjects received, in random cross-over fashion, pentoxifylline 400 mg as a controlled-release tablet every 8 hours with and without cimetidine 300 mg four times a day for 7 days. Pentoxifylline and metabolite plasma concentrations over one dosing interval were measured on day 7 of each phase. The unavailability of an immediate-release pentoxifylline dosage form prevented a single dose trial. Cimetidine significantly increased (P less than .05) pentoxifylline area under the curve at steady state 26.2% from 675 +/- 97 (mean +/- SEM) to 852 +/- 108 ng. hr/mL. The average steady-state plasma concentration increased 27.4% from 84 +/- 12 to 107 +/- 14 ng/mL (P less than .05). Apparent oral clearance decreased 21.5% from 1309 +/- 304 to 1027 +/- 244 mL/min (P less than .02). Significant alterations in pentoxifylline metabolite concentrations were also observed. The results of this trial suggest cimetidine elevates pentoxifylline plasma concentrations, presumably by decreasing apparent oral clearance, although a reduction in total body clearance or an increase in gastric absorption could not be ruled out.