Ceramic surface relief gratings imprinted on an optical fiber tip.

We report on the fabrication, experimental measurement, and numerical simulation of sol-gel diffraction grating structures deposited on the end-face of a single mode optical fiber. Using the imprint method, we manufactured surface relief grating structures in four configurations with different grating-relative-to-fiber arrangements. We demonstrate the high quality of the fabricated structures based on atomic force microscopy imaging and their operational characteristics, presenting measured and simulated far-field intensity distributions. Using a numerical model, we simulated the diffraction patterns in the far-field. We obtained strong agreement between the results of the simulations and the experiments in terms of the angular positions of the diffraction peaks. We also investigated the tolerance of fabricated structures to high-power lasers. Among the proposed structures, the most intriguing is the grism fabricated on a fiber end-face using sol-gel imprint technology for the first time, to the best of our knowledge.

Diagnostic Criteria for Temporomandibular Disorders (DC/TMD): Polish assessment instruments.

The article presents the Polish version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), the process of document translation and cultural adaptation.

Acid ß-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter α-synuclein processing.

OBJECTIVE: Heterozygous mutations in the GBA1 gene elevate the risk of Parkinson disease and dementia with Lewy bodies; both disorders are characterized by misprocessing of α-synuclein (SNCA). A loss in lysosomal acid-ß-glucosidase enzyme (GCase) activity due to biallelic GBA1 mutations underlies Gaucher disease. We explored mechanisms for the gene's association with increased synucleinopathy risk. METHODS: We analyzed the effects of wild-type (WT) and several GBA mutants on SNCA in cellular and in vivo models using biochemical and immunohistochemical protocols. RESULTS: We observed that overexpression of all GBA mutants examined (N370S, L444P, D409H, D409V, E235A, and E340A) significantly raised human SNCA levels to 121 to 248% of vector control (p < 0.029) in neural MES23.5 and PC12 cells, but without altering GCase activity. Overexpression of WT GBA in neural and HEK293-SNCA cells increased GCase activity, as expected (ie, to 167% in MES-SNCA, 128% in PC12-SNCA, and 233% in HEK293-SNCA; p < 0.002), but had mixed effects on SNCA. Nevertheless, in HEK293-SNCA cells high GCase activity was associated with SNCA reduction by ≤32% (p = 0.009). Inhibition of cellular GCase activity (to 8-20% of WT; p < 0.0017) did not detectably alter SNCA levels. Mutant GBA-induced SNCA accumulation could be pharmacologically reversed in D409V-expressing PC12-SNCA cells by rapamycin, an autophagy-inducer (≤40%; 10µM; p < 0.02). Isofagomine, a GBA chaperone, showed a related trend. In mice expressing two D409Vgba knockin alleles without signs of Gaucher disease (residual GCase activity, ≥20%), we recorded an age-dependent rise of endogenous Snca in hippocampal membranes (125% vs WT at 52 weeks; p = 0.019). In young Gaucher disease mice (V394Lgba+/+//prosaposin[ps]-null//ps-transgene), which demonstrate neurological dysfunction after age 10 weeks (GCase activity, ≤10%), we recorded no significant change in endogenous Snca levels at 12 weeks of age. However, enhanced neuronal ubiquitin signals and axonal spheroid formation were already present. The latter changes were similar to those seen in three week-old cathepsin D-deficient mice. INTERPRETATION: Our results demonstrate that GBA mutants promote SNCA accumulation in a dose- and time-dependent manner, thereby identifying a biochemical link between GBA1 mutation carrier status and increased synucleinopathy risk. In cell culture models, this gain of toxic function effect can be mitigated by rapamycin. Loss in GCase activity did not immediately raise SNCA concentrations, but first led to neuronal ubiquitinopathy and axonal spheroids, a phenotype shared with other lysosomal storage disorders.

Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study.

STUDY OBJECTIVES: The relative risks and benefits of strategies of rate control vs rhythm control in patients with atrial fibrillation (AF) remain to be fully explored. DESIGN: The How to Treat Chronic Atrial Fibrillation (HOT CAFE) Polish trial was designed to evaluate in a randomized, multicenter, and prospective manner the feasibility and long-term outcomes of rate control vs rhythm control strategies in patients with persistent AF. PATIENTS: Our study population comprised 205 patients (134 men and 71 women; mean [+/- SD] age, 60.8 +/- 11.2 years) with a mean AF duration of 273.7 +/- 112.4 days. The mean observation period was 1.7 +/- 0.4 years. One hundred one patients were randomly assigned to the rate control group and received rate-slowing therapy guided by repeated 24-h Holter monitoring. Direct current cardioversion and atrioventricular junctional ablation with pacemaker placement were alternative nonpharmacologic strategies for patients with tachycardia that was resistant to medical therapy. One hundred four patients were randomized to sinus rhythm restoration and maintenance using serial cardioversion supported by a predefined stepwise antiarrhythmic drug regimen (ie, disopyramide, propafenone, sotalol, and amiodarone). In both groups, thromboembolic prophylaxis followed current guidelines. MEASUREMENTS AND RESULTS: At the end of follow-up, 63.5% of patients in the rhythm control arm remained in sinus rhythm. No significant differences in the composite end point (ie, all-cause mortality, number of thromboembolic events, or major bleeding) were found between the rate control group and the rhythm control group (odds ratio, 1.98; 95% confidence interval, 0.28 to 22.3; p > 0.71). The incidence of hospital admissions was much lower in the rate control arm (12% vs 74%, respectively; p < 0.001). New York Heart Association functional class improved in both study groups, while mean exercise tolerance, as measured by the maximal treadmill workload, improved only in the rhythm control group (5.2 +/- 5.1 vs 7.6 +/- 3.3 metabolic equivalents, respectively; p < 0.001). The rhythm control strategy led to an increased mean left ventricular fractional shortening (29 +/- 7% vs 31 +/- 7%, respectively; p < 0.01). One episode of pulmonary embolism occurred in the rate control group despite oral anticoagulation therapy, while three patients in the rhythm control arm of the study experienced ischemic strokes (not significant). CONCLUSIONS: The Polish HOT CAFE study revealed no significant differences in major end points between the rate control group and the rhythm control group.

Rhythm control versus rate control in patients with persistent atrial fibrillation. Results of the HOT CAFE Polish Study.

BACKGROUND: Patients with atrial fibrillation (AF) can be managed either by maintaining sinus rhythm using antiarrhythmic drugs and/or electrical cardioversion, or by leaving patients in AF and controlling ventricular rate without attempts to restore sinus rhythm. Which of these two strategies is superior, has not yet been definitively established. AIM: HOT CAFE Polish Study (How To Treat Chronic Atrial Fibrillation) was designed to evaluate in a randomised, multicentre and prospective manner the risks and advantages of two therapeutical strategies - rate control or rhythm control, in patients with persistent AF. METHODS: The study group consisted of 205 patients (71 females and 134 males; mean age 60.8+/-11.2 years) with a mean time of AF duration of 273.7+/-112.4 days; 101 patients were randomly assigned to rate control (Group I) whereas 104 patients were randomised to sinus rhythm (SR) restoration by DC cardioversion (CV) and subsequent antiarrhythmic drug treatment (Group II). At the end of follow-up (12 months) SR was present in 75% of patients. RESULTS: The incidence of hospital admissions was higher in group II in comparison to group I (12% vs 74%; p<0.001). Mortality was similar in both groups (1.0% versus 2.9%, NS). In both groups a significant improvement of heart failure symptoms was observed during the first 2 months (p<0.02 and p<0.001). In group II exercise tolerability measured by maximal workload during treadmill test significantly improved compared with baseline (5.2+/-5.1 vs 7.6+/-3.3 MET; p<0.0001). In patients in whom SR was restored, the left ventricular function improved and an increase in the shortening fraction was observed (29+/-7% vs 31+/-7%; p<0.01). No thromboembolic complications were observed in patients left with AF. Three patients from group II suffered ischaemic stroke; in two cases stroke was associated with CV whereas in the third patient - with late AF recurrence. CONCLUSIONS: The HOT CAFE Polish Study did not reveal significant differences in mortality between the two treatment strategies in patients with persistent AF. Although patients with SR had better improvement in some haemodynamical parameters, the hospitalisation rate was higher and the incidence of stroke was not reduced compared with the rate control group.

[Iatrogenic left lateral thoracic artery injury during pacemaker implantation successfully treated with stentgraft implantation]. / Jatrogenne uszkodzenie tetnicy piersiowej bocznej lewej podczas zabiegu implantacji stymulatora serca skutecznie leczone implantacja stentgraftu.

Left lateral thoracic artery iatrogenic injury is a rare complication during pacemaker implantation procedure. We present a case, where this complication occurred and was followed with massive tissue and pleural haemorrhage. The injury was successfully sealed with stentgraft device without any complications.

Characteristics of the heart failure population in Poland: ZOPAN, a multicentre national programme.

BACKGROUND: It is difficult to define the optimal management of elderly heart failure (HF) patients with complex comorbidities. Thus, comprehensive characterisation of HF patients constitutes a crucial pre-condition for the successful management of this fragile population. AIM: To analyse the 'real life' HF patients, including the evaluation of their health conditions, management and their use of public health resources. METHODS AND RESULTS: We examined 822 consecutive patients diagnosed with HF in NYHA classes II-IV in primary care practices. The mean age was 68.5 years, and 56% were male. Only 23% of the patients who were of pre-retirement age remained professionally active. Ischaemic or hypertension aetiology was found in 90% of participants. Nearly all patients had multiple comorbidities. Most patients received converting enzyme inhibitors (88%) and beta-blockers (77%), 60% of them both, although dosing was frequently inadequate. During the six months preceding the study, 31% had cardiovascular hospitalisation and 66% required unscheduled surgery visits. CONCLUSIONS: The real life HF population differs from trial populations. Most of the real life patients who had not yet reached retirement age were professionally inactive, mainly due to a disability caused by cardiovascular conditions. Moreover, extremely few participants were free from any comorbidity. Compared to 20th century Polish data, there has been an improvement in the overall quality of HF-recommended pharmacotherapy. It must be stressed, however, that the percentage of those on optimal dosage remains unsatisfactory.

Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo.

BACKGROUND: Elevated SNCA gene expression and intracellular accumulation of the encoded alpha-synuclein (aSyn) protein are associated with the development of Parkinson disease (PD). To date, few enzymes have been examined for their ability to degrade aSyn. Here, we explore the effects of CTSD gene expression, which encodes the lysosomal protease cathepsin D (CathD), on aSyn processing. RESULTS: Over-expression of human CTSD cDNA in dopaminergic MES23.5 cell cultures induced the marked proteolysis of exogenously expressed aSyn proteins in a dose-dependent manner. Unexpectedly, brain extractions, Western blotting and ELISA quantification revealed evidence for reduced levels of soluble endogenous aSyn in ctsd knock-out mice. However, these CathD-deficient mice also contained elevated levels of insoluble, oligomeric aSyn species, as detected by formic acid extraction. In accordance, immunohistochemical studies of ctsd-mutant brain from mice, sheep and humans revealed selective synucleinopathy-like changes that varied slightly among the three species. These changes included intracellular aSyn accumulation and formation of ubiquitin-positive inclusions. Furthermore, using an established Drosophila model of human synucleinopathy, we observed markedly enhanced retinal toxicity in ctsd-null flies. CONCLUSION: We conclude from these complementary investigations that: one, CathD can effectively degrade excess aSyn in dopaminergic cells; two, ctsd gene mutations result in a lysosomal storage disorder that includes microscopic and biochemical evidence of aSyn misprocessing; and three, CathD deficiency facilitates aSyn toxicity. We therefore postulate that CathD promotes 'synucleinase' activity, and that enhancing its function may lower aSyn concentrations in vivo.

FAK/src-family dependent activation of the Ste20-like kinase SLK is required for microtubule-dependent focal adhesion turnover and cell migration.

Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal.