Mononuclear gold(iii) complexes with diazanaphthalenes: the influence of the position of nitrogen atoms in the aromatic rings on the complex crystalline properties

A series of mononuclear gold(iii) complexes of the general formula [AuCl₃(diazanaphthalene)], where diazanaphthalene is quinazoline (qz, 1), phthalazine (phtz, 2), 1,5-naphthyridine (1,5-naph, 3), 1,6-naphthyridine (1,6-naph, 4) or 1,8-naphthyridine (1,8-naph, 5), were prepared and fully characterized. The complexes 1–5 consist of discrete monomeric species with the Au(iii) cation in a square planar coordination geometry surrounded by three chloride anions and one diazanaphthalene ligand. Crystallographic studies indicate the presence of an extended 4 + 1 or 4 + 2 geometry around the square planar [AuCl₃(diazanaphthalene)] center due to Au⋯Cl and Au⋯N interactions. The crystal structures of these complexes are controlled by a variety of intermolecular interactions that utilize the amphiphilic properties of the coordinated chloride anions and involve C–H groups, π-electrons, and an uncoordinated nitrogen atom of the diazanaphthalene ligand. The usual offset π-stacking between the N-heteroaromatic ligands appears to be completely hindered between the 1,5-naph fragments and significantly weakened between the 1,6-naph and 1,8-naph in their respective complexes 3, 4 and 5, for which the average molecular polarizability (α) values are the lowest in the series. It is remarkable that the [AuCl₃(benzodiazine)] complexes 1 and 2 form centrosymmetric crystals, but the [AuCl₃(naphthyridine)] complexes 3–5 assemble into non-centrosymmetric aggregates, making them potential alternatives to the previously studied systems for application in various fields by taking advantage of their polarity.

The [AuCl₃(benzodiazine)] complexes form centrosymmetric crystals, while the [AuCl₃(naphthyridine)] complexes assemble into non-centrosymmetric aggregates, making them potential alternatives for advanced nonlinear optical materials due to their polarity.     

Sleep disturbances in women with polycystic ovary syndrome

Sleep disturbances in women with Polycystic Ovary Syndrome (PCOS) have been reported in recent years. The majority of published studies are related to Obstructive Sleep Apnea (OSA) while not many researches have analyzed any other causes of sleep disturbances. A group of ninety five women with Polycystic Ovary Syndrome were enrolled into the study. Sleep disturbances were assessed using validated questionnaires. On the grounds of Athens Insomnia Scale (AIS) evaluation a clinically significant insomnia was ascertained in 12.6% of women with PCOS, while according to Insomnia Severity Index (ISI) in 10.5%. Clinically significant insomnia according to both AIS and ISI, occurred significantly more often in women with PCOS than in women without PCOS based on the chi-square test. The Mann–Whitney U test revealed statistically significant difference between women with and without PCOS based on total values of ISI. An excessive daytime sleepiness occurred at 7.4% of women with PCOS. Statistically significant dependance between: clinically significant insomnia in both AIS and ISI and excessive daytime sleepiness indicated by Epworth Sleepiness Scale (ESS) was observed. Sleep disorders are common in women with PCOS. Screening assessment of sleep disturbances should be a part of medical diagnostics in women with PCOS.     

Influence of reciprocating tachycardia on the development of atrial fibrillation in patients with preexcitation syndrome

BACKGROUND: We sought to evaluate the influence of atrio-ventricular reentrant tachycardia (AVRT) on atrial pressures during tachycardia and the presence of atrial fibrillation (AF) in patients with preexcitation syndrome. METHODS: The study population consisted of 88 patients (37 females, mean age 37.3 years) with left-sided accessory pathway and AVRT induced during electrophysiologic study. The AF-inducible group consisted of 32 patients with sustained episodes of AF provoked during electrophysiologic study, whereas the noninducible group comprised 56 patients without AF. RESULTS: We found significantly higher values of maximal and mean left (LAP) and right (RAP) atrial pressures in the AF group compared with noninducible group: LAP max 32.0 versus 20.8, LAP mean 21.6 versus 13.2, RAP max 15.2 versus 11.5, RAP mean 8.2 versus 6.2 respectively (P < 0.001). When analyzing the effect of AVRT on atrial pressures, we found a significant (P < 0.001) negative correlation between anterograde conduction times during tachycardia and LAP max and LAP mean in the whole population, but a significant positive correlation between retrograde conduction time and left atrial pressures. Similar effects of AVRT on the right atrial pressures were found. CONCLUSIONS: Atrial pressures during AVRT, which depend on the electrophysiological features of tachycardia, play an important role in the genesis of atrial fibrillation in patients with preexcitation syndrome.     

Effect of long-term administration of ranitidine,a histamine H2 receptor antagonist,on bone metabolism in young growing rats

Background

Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones.

Mining Knowledge of Respiratory Rate Quantification and Abnormal Pattern Prediction

The described application of granular computing is motivated because cardiovascular disease (CVD) remains a major killer globally. There is increasing evidence that abnormal respiratory patterns might contribute to the development and progression of CVD. Consequently, a method that would support a physician in respiratory pattern evaluation should be developed. Group decision-making, tri-way reasoning, and rough set–based analysis were applied to granular computing. Signal attributes and anthropomorphic parameters were explored to develop prediction models to determine the percentage contribution of periodic-like, intermediate, and normal breathing patterns in the analyzed signals. The proposed methodology was validated employing k-nearest neighbor (k-NN) and UMAP (uniform manifold approximation and projection). The presented approach applied to respiratory pattern evaluation shows that median accuracies in a considerable number of cases exceeded 0.75. Overall, parameters related to signal analysis are indicated as more important than anthropomorphic features. It was also found that obesity characterized by a high WHR (waist-to-hip ratio) and male sex were predisposing factors for the occurrence of periodic-like or intermediate patterns of respiration. It may be among the essential findings derived from this study. Based on classification measures, it may be observed that a physician may use such a methodology as a respiratory pattern evaluation-aided method.

     

Disinfection of contaminated metal implants with an Er:YAG laser

Infections related to orthopedic procedures are considered particularly severe when implantation materials are used, because effective treatments for biofilm removal are lacking. In this study, the relatively new approach for infection control by using an erbium:yttrium-aluminum-garnet (Er:YAG) laser was tested. This laser vaporizes all water containing cells in a very effective, precise, and predictable manner and results in only minimal thermal damage. For preliminary testing, 42 steel plates and 42 pins were seeded with mixed cultures. First, the minimally necessary laser energy for biofilm removal was determined. Subsequently, the effectiveness of biofilm removal with the Er:YAG laser and the cleansing of the metal implants with octenidine-soaked gauze was compared. Then, we compared the effectiveness of biofilm removal on 207 steel pins from 41 patients directly after explantation. Sonication and scanning electron microscopy were used for analysis. Laser fluences exceeding 2.8 J/cm² caused a complete extinction of all living cells by a single-laser impulse. Cleansing with octenidine-soaked gauze and irradiation with the Er:YAG laser are both thoroughly effective when applied to seeded pins. In contrast, when explanted pins with fully developed biofilms were analyzed, we found a significant advantage of the laser procedure. The Er:YAG laser offers a secure, complete, and nontoxic eradication of all kinds of pathogens from metal implants without damaging the implant and without the possible development of resistance. The precise noncontact removal of adjacent tissue is a decisive advantage over conventional disinfectants. Therefore, laser irradiation could become a valuable method in every debridement, antibiotics, and implant retention procedure.     

The influence of CYP3A,PPARA, and POR genetic variants on the pharmacokinetics of tacrolimus and cyclosporine in renal transplant recipients

Purpose

Tacrolimus (Tac) and cyclosporine (CsA) are mainly metabolized by CYP3A4 and CYP3A5. Several studies have demonstrated an association between the CYP3A5 genotype and Tac dose requirements. Recently, CYP3A4, PPARA, and POR gene variants have been shown to influence CYP3A metabolism. The present study investigated potential associations between CYP3A5*3, CYP3A4*22, PPARA c.209-1003G>A and c.208?+?3819A>G, and POR*28 alleles and dose-adjusted concentrations (C/D) of Tac and CsA in 177 renal transplant patients early post-transplant.

Methods

All patients (n?=?177) were genotyped for CYP3A4*22, CYP3A5*3, POR*28, PPARA c.209-1003G>A, and PPARA c.208?+?3819A>G using real-time polymerase chain reaction (PCR) and melting curve analysis with allele-specific hybridization probes or PCR restriction fragment length polymorphisms (RFLP) methods. Drug concentrations and administered doses were retrospectively collected from patient charts at Oslo University Hospital, Rikshospitalet, Norway. One steady-state concentration was collected for each patient.

Results

We confirmed a significant impact of the CYP3A5*3 allele on Tac exposure. Patients with POR*28 and PPARA variant alleles demonstrated 15 % lower (P?=?0.04) and 19 % higher (P?=?0.01) Tac C₀/D respectively. CsA C₂/D was 53 % higher among CYP3A4*22 carriers (P?=?0.03).

Conclusion

The results support the use of pre-transplant CYP3A5 genotyping to improve initial dosing of Tac, and suggest that Tac dosing may be further individualized by additional POR and PPARA genotyping. Furthermore, initial CsA dosing may be improved by pre-transplant CYP3A4*22 determination.