Symptoms of advanced heart failure—A case for radiofrequency catheter ablation?

A sixty-year-old man with previous history of coronary artery disease was admitted due to progressive worsening of dyspnoea at exertion (NYHA III functional class) and no angina. Coronary angiography confirmed occlusion of the right coronary artery which was naturally bypassed by homocollaterals with TIMI 3 flow to the peripheral branches. The lesion was not technically suitable for percutaneous angioplasty. The left coronary artery was without stenosis. On echocardiography, both the left ventricle and the left atrium were dilated and hemodynamically significant mitral regurgitation was present. Surface ECG showed a left bundle branch block with repeated runs of monomorphic ventricular ectopic beats (PVC). Radiofrequency catheter ablation of the focus in the posteroseptal region of the left ventricle underneath the mitral valve was performed using electroanatomical mapping system. After the procedure, mitral regurgitation decreased and reverse remodeling of the left ventricle and the left atrium occurred with concomitant significant clinical improvement of the patient. The authors discuss several treatment strategies: mitral valve repair surgery combined with revascularization, implantation of a biventricular ICD system or elimination of the focus of monomorphic VT runs by radiofrequency catheter ablation as a possible causal approach in the treatment of PVC-induced cardiomyopathy.     

ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones

AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.METHODS:Mutational analysis of ABCB4,screening for copy number variations by multiplex ligation-dependent probe amplification,genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome(LPAC,OMIM#600803)and in 5young females with suspected LPAC and their families(5 probands,15 additional family members).The probands came to medical attention for contraceptiveassociated intrahepatic cholestasis.RESULTS:A possibly pathogenic variant of ABCB4was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4.Among these 16,however,none developed gallstones in childhood.In 5index patients,all young females carrying at least one pathogenic mutation in one allele of ABCB4,manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives.Variants ABCB11c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.CONCLUSION:Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied topediatric patients with idiopathic gallstones.Sexual immaturity even prevents manifestation of LPAC.     

Parameter Identification of Cutting Forces in Crankshaft Grinding Using Artificial Neural Networks

The intensifying of the manufacturing process and increasing the efficiency of production planning of precise and non-rigid parts, mainly crankshafts, are the first-priority task in modern manufacturing. The use of various methods for controlling the cutting force under cylindrical infeed grinding and studying its impact on crankpin machining quality and accuracy can improve machining efficiency. The paper deals with developing a comprehensive scientific and methodological approach for determining the experimental dependence parameters’ quantitative values for cutting-force calculation in cylindrical infeed grinding. The main stages of creating a method for conducting a virtual experiment to determine the cutting force depending on the array of defining parameters obtained from experimental studies are outlined. It will make it possible to get recommendations for the formation of a valid route for crankpin machining. The research’s scientific novelty lies in the developed scientific and methodological approach for determining the cutting force, based on the integrated application of an artificial neural network (ANN) and multi-parametric quasi-linear regression analysis. In particular, on production conditions, the proposed method allows the rapid and accurate assessment of the technological parameters’ influence on the power characteristics for the cutting process. A numerical experiment was conducted to study the cutting force and evaluate its value’s primary indicators based on the proposed method. The study’s practical value lies in studying how to improve the grinding performance of the main bearing and connecting rod journals by intensifying cutting modes and optimizing the structure of machining cycles.     

Chemical Removal of Lead Corrosion Products

Restoration treatment, specimen preparation or mass loss measurements on coupons made of lead require a reliable process of dissolution of corrosion products. In this study, several types of model corrosion products with compositions representative of those found on real objects were prepared and characterized. Ten solutions were then thoroughly tested in interval cleaning experiments, regarding the efficiency of removal of the corrosion products, corrosivity towards bare lead, and remnants left on the surface. The solution recommended in the current version of the ISO 8470 standard was found to be improper for the cleaning of both historical artefacts and corrosion coupons due to its inability to remove sulfide corrosion products and the risk of surface contamination and staining. A solution of 20% hydrochloric acid is the best choice for the preparation of lead coupons before exposure or for evaluation of mass loss of exposed samples because its somewhat higher corrosivity towards metallic lead is tolerable for these applications. Rochelle salt solution was found to be optimal for the cleaning of historical artefacts free of sulfide corrosion products due to the lowest corrosivity. None of these alternative solutions leave remnants on the surface and they are efficient at laboratory temperature.     

Annulotrema (Monogenea: Dactylogyridae) from Hydrocynus brevis (Characiformes: Alestidae) in Senegal,with descriptions of two new species and remarks on Annulotrema pikei

Two new species of Annulotrema Paperna & Thurston, 1969 were collected from the gills of the African tiger fish, Hydrocynus brevis, from the Gambia River basin in the Niokolo-Koba National Park, Senegal. Annulotrema besalis n. sp. is characterized by having a male copulatory organ (MCO) composed of an arcuate copulatory tube articulated to an eight-shaped accessory piece with terminal claw. The new species resembles Annulotrema pikei (Price, Peebles & Bamford, 1969) in having morphologically similar types of haptoral sclerites and MCO. As a result of the differential diagnosis made for A. besalis n. sp., new information on taxonomically important features of A. pikei is provided based on illustrations of the sclerotized parts of the holotype from Hydrocynus vittatus. The report of A. pikei on the gills of Hydrocynus forskahlii by Paperna in 1979 is shown to be erroneous. Annulotrema uncata n. sp. is similar to Annulotrema alestesimberi Paperna, 1973 in its possession of a coiled copulatory tube with about two and a half rings. Features distinguishing the new species include the sharply curved shaft of the ventral anchor, the base of the copulatory tube extending to a sock-like structure and a leech-shaped vagina. The necessity of emending the generic diagnosis of Annulotrema is briefly discussed.     

Mutation Screening of the HGD Gene Identifies a Novel Alkaptonuria Mutation with Significant Founder Effect and High Prevalence

Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2‐dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16 positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU‐causing mutation was not identified in these patients. This result indicates that the founder effect and high degree of consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2. The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin.     

Correlation of creatinine‐ and specific gravity‐normalized free and glucuronidated urine cannabinoid concentrations following smoked,vaporized, and oral cannabis in frequent and occasional cannabis users

Variability in urine dilution complicates urine cannabinoid test interpretation. Normalizing urine cannabinoid concentrations to specific gravity (SG) or creatinine was proposed to account for donors' hydration states. In this study, all urine voids were individually collected from eight frequent and eight occasional cannabis users for up to 85 hours after each received on separate occasions 50.6 mg Δ9‐tetrahydrocannabinol (THC) by smoking, vaporization, and oral ingestion in a randomized, within‐subject, double‐blind, double‐dummy, placebo‐controlled protocol. Each urine void was analyzed for 11 cannabinoids and phase I and II metabolites by liquid chromatography?tandem mass spectrometry (LC–MS/MS), SG, and creatinine. Normalized urine concentrations were log₁₀ transformed to create normal distributions, and Pearson correlation coefficients determined the degree of association between the two normalization methods. Repeated‐measures linear regression determined if the degree of association differed by frequent or occasional cannabis use, or route of administration after adjusting for gender and time since dosing. Of 1880 urine samples examined, only 11‐nor‐9‐carboxy‐THC (THCCOOH), THCCOOH‐glucuronide, THC‐glucuronide, and 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabivarin (THCVCOOH) were greater than the method's limits of quantification (LOQs). Associations between SG‐ and creatinine‐normalized concentrations exceeded 0.90. Repeated‐measures regression analysis found small but statistically significant differences in the degree of association between normalization methods for THCCOOH and THCCOOH‐glucuronide in frequent vs occasional smokers, and in THCVCOOH and THC‐glucuronide by route of administration. For the first time, SG‐ and creatinine‐normalized urine cannabinoid concentrations were evaluated in frequent and occasional cannabis users and following oral, smoked, and inhaled cannabis. Both normalization methods reduced variability, improving the interpretation of urine cannabinoid concentrations and methods were strongly correlated.     

Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study

Aims/hypothesis

The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes.

Methods

We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR >?3.4 mg/mmol) or an estimated (eGFR) <?60 ml min^?1 1.73 m^?2. CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability.

Results

Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (?9.0?±?17.8% vs ?3.3?±?10.3%, p?=?0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β?=??3.5, p?=?0.03). Spectral analysis variables were also independent predictors of eGFR decline.

Conclusions/interpretation

CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.     

Direct evidence for a magnetic f-electron–mediated pairing mechanism of heavy-fermion superconductivity in CeCoIn5

To identify the microscopic mechanism of heavy-fermion Cooper pairing is an unresolved challenge in quantum matter studies; it may also relate closely to finding the pairing mechanism of high-temperature superconductivity. Magnetically mediated Cooper pairing has long been the conjectured basis of heavy-fermion superconductivity but no direct verification of this hypothesis was achievable. Here, we use a novel approach based on precision measurements of the heavy-fermion band structure using quasiparticle interference imaging to reveal quantitatively the momentum space (k-space) structure of the f-electron magnetic interactions of CeCoIn₅. Then, by solving the superconducting gap equations on the two heavy-fermion bands Ekα,β with these magnetic interactions as mediators of the Cooper pairing, we derive a series of quantitative predictions about the superconductive state. The agreement found between these diverse predictions and the measured characteristics of superconducting CeCoIn₅ then provides direct evidence that the heavy-fermion Cooper pairing is indeed mediated by f-electron magnetism.Superconductivity of heavy fermions is of abiding interest, both in its own right (1–7) and because it could exemplify the unconventional Cooper pairing mechanism of high-temperature superconductors (8–11). Heavy-fermion compounds are intermetallics containing magnetic ions in the 4f- or 5f-electronic state within each unit cell. At high temperatures, each f-electron is localized at a magnetic ion (Fig. 1A). At low temperatures, interactions between f-electron spins (red arrows Fig. 1A) lead to the formation of a narrow but the subtly curved f-electron band εkf near the chemical potential (red curve, Fig. 1B), and Kondo screening hybridizes this band with the conventional c-electron band εkc of the metal (black curve, Fig. 1B). As a result, two new heavy-fermion bands Ekα,β (Fig. 1C) appear within a few millielectron volts of the Fermi energy. Their electronic structure is controlled by the hybridization matrix element s_k for interconversion of conduction c-electrons to f-electrons and vice-versa, such thatEkα,β=εkc+εkf2±(εkc−εkf2)2+sk2.[1]The momentum structure of the narrow bands of hybridized electronic states (Eq. 1 and Fig. 1C, blue curves at left) near the Fermi surface then directly reflects the form of magnetic interactions encoded within the parent f-electron band εkf. It is these interactions that are conjectured to drive the Cooper pairing (1–5) and thus the opening up of a superconducting energy gap (Fig. 1C, yellow curves at right).Open in a separate windowFig. 1.Effects of f-electron magnetism in a heavy-fermion material. (A) The magnetic subsystem of CeCoIn₅ consists of almost localized magnetic f-electrons (red arrows) with a weak hopping matrix element yielding a very narrow band with strong magnetic interactions between the f-electron spins. (B) The heavy f-electron band is shown schematically in red and the light c-electron band in black. (C) On the left, schematic of the result of hybridizing the c- and f-electrons in B into new composite electronic states referred to as heavy fermions (blue). On the right, the opening of a superconducting energy gap is schematically shown by back-bending bands near the chemical potential. The microscopic interactions driving Cooper pairing of these states, and thus of heavy-fermion superconductivity, have not been identified unambiguously for any heavy-fermion compound.