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The ribosome, owing to its exceptional conservation, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate roles of the ribosomal protein fragments (rPeptides) within the ribosomal core. This research highlights the significance of rPeptides in stability and coacervation of two distinct protoribosomal evolutionary stages. The 617nt 'big' protoribosome model, which associates with rPeptides specifically, exhibits a structurally defined and rigid nature, further stabilized by the peptides. In contrast, the 136nt 'small' model, previously linked to peptidyltransferase activity, displays greater structural flexibility. While this construct interacts with rPeptides with lower specificity, they induce coacervation of the 'small' protoribosome across a wide concentration range, which is concomitantly dependent on the RNA sequence and structure. Moreover, these conditions protect RNA from degradation. This phenomenon suggests a significant evolutionary advantage in the RNA-protein interaction at the early stages of ribosome evolution. The distinct properties of the two protoribosomal stages suggest that rPeptides initially provided compartmentalization and prevented RNA degradation, preceding the emergence of specific RNA-protein interactions crucial for the ribosomal structural integrity., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Aims: Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis., Methods and Results: 3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = -0.49, P < 0.0001) than with 3D LV global circumferential strain (GCS, r = -0.38, P < 0.001) or 3D LVEF (r = -0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75-0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324)., Conclusion: 3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD., Competing Interests: Conflict of interest: D.R. reports consulting honoraria from Sanofi Genzyme. J.M. reports consulting honoraria from Sanofi Genzyme, Takeda, Amicus. G.D. reports consulting honoraria from Sanofi Genzyme, Takeda, Amicus, Protalix. A.L. reports consulting honoraria from Sanofi Genzyme, Takeda, Amicus, Avrobio., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Fabry disease (FD) is a rare X-linked disorder of glycosphingolipid metabolism caused by pathogenic variants within the alpha-galactosidase A (GLA) gene, often leading to neurological manifestations including stroke. Multiple screening programs seeking GLA variants among stroke survivors lacked detailed phenotype description, making the interpretation of the detected variant's pathogenicity difficult. Here, we describe detailed clinical characteristics of GLA variant carriers identified by a nationwide stroke screening program in the Czech Republic. A total of 23 individuals with 8 different GLA variants were included in the study. A comprehensive diagnostic workup was performed by a team of FD specialists. The investigation led to the suggestion of phenotype reclassification for the G325S mutation from late-onset to classical. A novel variant R30K was found and was classified as a variant of unknown significance (VUS). The typical manifestation in our FD patients was a stroke occurring in the posterior circulation with an accompanying pathological finding in the cerebrospinal fluid. Moreover, we confirmed that cornea verticillata is typically associated with classical variants. Our findings underline the importance of detailed phenotype description and data sharing in the correct identification of pathogenicity of gene variants detected by high-risk-population screening programs.

Aim: To report an overview of the most frequent tumors of the orbit, suggest diagnostic approach and possible solution according to experience with own cohort of patients., Material and Methods: From patients files from the Department of Ophthalmology and Department of Stomatology, First Medical Faculty, Charles University, and General Faculty Hospital in Prague, Czech Republic, there were selected patients, who underwent the surgery due to the suspicion of malignant development in the orbit during the period 2005 - 2019. From the surgical records we found information about 497 cases. At the Department of Stomatology, there were 282 surgeries under general anesthesia performed, and at the Department of Ophthalmology, there were 215 surgeries, mostly under local anesthesia performed., Results: The number of surgeries in men and women was equal; patients of all ages were present. The median of patients age operated on at the Department of Stomatology was 53 years, and at the Department of Ophthalmology 63 years. The most common primary benign tumor was the cavernous hemangioma (9 %), the most common non-tumorous expansion was the dermoid cyst (7 %); the most common malignant tumor was the lymphoma (17,5 %). The last mentioned tumor was the most common diagnosis in the whole cohort as well., Conclusion: Our cohort of patients is comparable with large cohorts published in the literature concerning age and gender distributions. Differences in frequencies of some lesions may be explained by that our cohort includes patients after the surgery only. The malignant lymphoma is the most common diagnosis indicated to surgical procedure, mostly biopsy. Comparing the two cohorts from our departments 20 years apart, the malignant lymphoma remains the most common indication for surgery, but the incidence of adenomas and adenocarcinomas of the lacrimal gland decreased. It is not the goal of this paper to evaluate all possible orbital affections. Suggested surgical approaches are just recommendations according to years of experience; however, in some situations, to choose an individual surgical approach is necessary.

Objective: This article stresses an impact of appropriate management work up in the diagnosis of acute apendicitis in puerperium. Atypical clinical symptoms may cause doubts in diagnosis and may delay necessary surgical intervention., Design: Case report., Settings: Department of Gynecology and Obstetrics, 1st Faculty of Medicine, Charles University, and Hospital Na Bulovce, Prague., Methods: We present a case report describing an atypical presentation of acute apendicitis in early puerperium. Due to atypical course of the disease and atypical imaging locality and morphology, there were doubts about the diagnosis of acute apendicitis, patient was treated conservativelly and the disease later resulted in extensive surgical intervention., Conclusion: Acute appendicitis is the most common cause of non-urogenital morbidity in puerperium. Management of work up and timing of surgical intervention have key impact on maternal mortality and morbidity.

The authors found 220 reports focused on the treatment of chest trauma in available literature. From external fixations, the development of methods continued to internal fixations with sophisticated plates and screws. At the same time, the so-called pneumatic internal fixation (artificial lung ventilation) was abandoned for the benefit of osteosynthetic methods (ORIF). An active surgical approach to thoracic stabilization dates back to the beginning of the 20th century. After WWII the so-called period of the first renaissance began with the introduction of internal osteosynthesis. The period of the last ten years is called the second renaissance. Today, an active early complex surgical solution is preferred, which uses implants based on the principle of stable osteosynthesis.Key words: stabilisation of the thorax external fixation ORIF pneumatic internal fixation timing.

Ventricular outpouchings include acquired abnormalities (aneurysms and pseudoaneurysms) and congenital ventricular diverticula (CVD). CVD represent rare cardiac pathologies. Although CVD is often associated with other cardiac and extracardiac congenital anomalies, it can also be incidentally observed in otherwise healthy subjects. CVD may lead to significant morbidity and even have lethal consequences. We describe a case of arrhythmogenic left ventricle (LV) apical CVD revealed by cardiac magnetic resonance imaging (CMRI) after being initially overlooked by echocardiography. The paper includes the review of the literature also. This clinical case highlights the possible association of this pathology with recurrent ventricular tachycardia and stroke, and illustrates the importance of multimodal imaging approach in differential diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Magnetic resonance is becoming an increasingly used examination in cardiology, since it greatly improves the accuracy of diagnosing of many heart diseases. At present magnetic resonance is the gold standard in assessing the volumes of the heart chambers and the systolic function of both ventricles. The possibility of detecting tissue characteristics to refine the diagnostics of different types of myocardial pathology is of essential importance. The authors summarize in the article the present knowledge about the use of magnetic resonance of the heart in the field of myocardial disease, i.e. cardiomyopathy and myocarditis. The first part of the review gives a general introduction into the topic of magnetic resonance examination of myocardial diseases, which is followed by a detailed descrip-tion of the benefits of this imaging method in dilated cardiomyopathy and myocarditis,in hypertrophic cardio-myopathy, and arrhythmogenic right ventricular cardiomyopathy.Key words: fibrosis - cardiomyopathy - magnetic resonance - myocarditis - late contrast agent saturation.

Multiple myeloma has varied manifestations which resemble common patient complaints and that is why this disease is typically not diagnosed until it reaches an advanced stage. Spinal pains can be an expression of deformative and discogenous changes, but also a symptom of multiple myeloma. Pains in the long bones may result from the pain radiating from an arthrotic joint, but also from a large myelomatic osteolytic lesion which makes the bone prone to a spontaneous fracture. Pathological weariness may have many causes, multiple myeloma being one of them. Anemia may have a large number of causes and multiple myeloma is one of them. Raised creatinine levels and renal failure can also be due to many causes and again, multiple myeloma is one of them. Weakened immunity and frequent infections can also have many causes, among them multiple myeloma. Confusion and sleepiness may be due to psychiatric diagnosis, but also may result from hypercalcemia associated with multiple myeloma. The following text which is designed for non-hematology physicians therefore describes in detail the symptoms of multiple myeloma and diagnostic steps leading to establishing the diagnosis and it only briefly outlines the treatment related information. You can also visit www.myeloma.cz for details. This text aims to summarize the symptoms of multiple myeloma for physicians not specializing in hematology in order to facilitate earlier diagnosing of the disease.

Purpose of the Study: The primary objective of the study was to find out in-hospital mortality in patients undergoing surgery for proximal femoral fracture. The secondary objective was to identify independent predictors of in-hospital mortality., Material and Methods: A retrospective single-centre observational study PROXIMORT of patients operated on for isolated proximal femoral fracture at the University Hospital (FN) Brno in the years 2011 and 2012. The 30-day and overall one-year mortality in the study group and the impact of observed parameters on mortality were also assessed. The observed parameters were: patient age and sex, ASA score, time from injury to surgery (hr), daily (7-20 hr) or night (20-7 hr) time of surgery, type of anaesthesia (general vs spinal), initial haemoglobin and haematocrit levels, intra-operative administration of blood products and vasopressors, and erudition of the anaesthesiologist and surgeon. To evaluate the relationship of in-hospital mortality to the observed characteristics, we used univariate logistic regression modelling and odds ratio, using SPSS 22 software (IBM, USA)., Results: Data were obtained from 414 patients and 369 patients were included (male, n = 91; female, n = 278). Due to exclusion criteria, 45 patients were excluded (not an isolated injury). In-hospital mortality was 6.5% (n = 24), 30-day mortality was 8.4% (n = 31) and total mortality of the study group was 35.8% (n = 132). Statistically significant effects on in-hospital mortality included: older age of the patient (p = 0.013), ASA score of 3 or more (p = 0.002) and general anaesthesia administration (p = 0.043). For 30-day mortality, this was older age (p = 0.012), ASA score of 3 and more (p < 0.001), general anaesthesia administration (p < 0.001), lower weight (p = 0.028), lower BMI (p = 0.006) and intra-operative administration of vasopressors (p = 0.023). The influence of other observed parameters on post-operative mortality was not statistically significant., Discussion: In-hospital mortality in the PROXIMORT study was 6.5% (95% confidence interval (CI) 4.2 to 9.5%), which was significantly higher than in-hospital mortality in unselected surgically treated patients in the Czech Republic, as reported in the EuSOS study (2.3% with 95% CI 0.9 to 3.7%). Administration of general anaesthesia was determined as an independent predictor of in-hospital and 30-day mortality, which was concordant with the results of meta-analysis published by Rodgers et al. and Barbosa et al in 2013. Postponing surgery for perioperative optimisation had no effect on mortality according to the PROXIMORT study. Patorn et al. have supported this conclusion by the results of a selected group of patients with surgery delayed for more than 24 hours; the patients mortality, regardless of anaesthesia, was up to 2.5%., Conclusions: The PROXIMORT study identified the higher patient age, ASA score of 3 and more and general anaesthesia administration as independent predictors of in-hospital mortality.

We have used the method of irreversible electroporation (IRE) twice to treat central non-small cell lung tumours. Both tumours obstructed the right main stem bronchus. Due to a high risk of right-sided pneumonectomy we chose to apply the tissue sparing device called NanoKnife and an alternative IRE method. The first surgery was performed in August 2011 and the second one in June 2012. The first case was an epidermoid carcinoma, 3 cm in size, which completely obstructed the right main stem bronchus on the boundary line with the upper lobar bronchus and caused lung atelectasis. The second case was a carcinoid, 2 cm in size, which grew from the main stem bronchus to the carina. Pneumonectomy was contraindicated due to lung function in the first case, and the other patient preferred the IRE method to radical but risky resection with bronchoplasty. IRE was performed through open thoracotomy. No complications were detected after the surgery in both cases. The first patient was discharged on the 12th postoperative day and the second one on the 5th postoperative day. 98% regression of the tumour was detected by CT scan in the first patient, and complete regression occurred in the case of the second one. 100% apoptosis and "disparition" of the carcinoma in the first case was verified by bronchoscopy and cytology after 6 months. Both patients remain in follow-up after surgery using the IRE method and are without subjective or objective complaints and without any signs of tumour recurrence. NanoKnife and IRE without lung resection resulted in the destruction of lung tumours while preserving the lung parenchyma and pulmonary functions.

Background: Adrenal venous sampling serves as a discrimination between uni- and bilateral forms of primary aldosteronism (PA). Even correctly performed adrenal venous sampling may lead to non-diagnostic results in some cases., Results: We describe 7 subjects with PA in whom correct cannulation of adrenal veins (high selectivity index defined as cortisol((adrenal))/cortisol((periphery)) ratio) was associated with aldosterone (ALDO) suppression (ALDO/cortisol((adrenal))/ALDO/cortisol((periphery)) ratio <1) in the left adrenal gland and in whom all subjects underwent a successful adrenalectomy on the right side. In 3 subjects, samples from the right side with lower selectivity indexes (1.11-1.7) compared to those samples with a higher index of selectivity (10.4-44.9) pointed to lateralization. Next, 2 subjects were operated because of relatively large adrenal masses in the right adrenal gland on CT despite ALDO suppression on this side. One subject presented with high selectivity indexes from the right side (19.5 and 37.6), but only one sample showed ALDO secretion. Patient 7 was treated with right-sided adrenalectomy despite a low lateralization index (ALDO/cortisol((right))/ALDO/cortisol((left)) 1.78)., Conclusions: Our results document some uncertainties in interpreting results of adrenal venous sampling in subjects with PA which may result from deep catheter insertion, anomalous venous drainage, or fluctuations in ALDO secretion., (Copyright © 2012 S. Karger AG, Basel.)

Purpose of the Study: The aim was to evaluate subjective and objective criteria of wrist, hand and arm function in a group of patients with acute static scapholunate dissociation treated by acute suture or ligament reinsertion, and in a group of patients with chronic static scapholunate dissociation treated by ligament reconstruction using ligamentoplasty., Material and Methods: Of a total number of 70 patients treated surgically for scapholunate instability at the Department of Trauma Surgery, University Hospital in Olomouc and the Department of Trauma Surgery, University Hospital in Brno, from 2002 till the end of 2008, 37 patients with acute or chronic static scapholunate dissociation treated by suture, ligament reinsertion or ligamentoplasty were selected. Of them, 17 patients with chronic scapholunate dissociation and 10 patients with acute scapholunate dissociation appeared at the final follow-up. The assessment of subjective criteria was based on the Disabilities of the Arm, Shoulder and Hand Score, the Wrightington Wrist Function Score and the Visual Analogue Scale. The objective criteria included range of motion and grip strength, and radiographic parameters, such as scapholunate gap and scapholunate and scaphocapitate angles. Satisfaction of the patients and their return to work were also evaluated. The results were statistically analysed using the Chi-square, Mann-Whitney-U and Wilcoxon tests, with the level of significance a=0.05., Results: In the group with acute static scapholunate dissociation, the objective criteria showed an improved range of flexion- extension. The range of radial and ulnar bending and grip strength were almost identical with those of the healthy wrist. In both evaluated groups the self-rated criteria had almost the same values in all three rating systems used. No statistically significant difference in any of the values compared was recorded., Discussion: The results of subjective and objective assessments were comparable in the two groups. Paradoxically, some items of the subjective evaluation were better in the patients undergoing ligament reconstruction - ligamentoplasty. This can probably be explained by different subjective comparison of pre- and post-operative conditions in each group. Even though the subjective assessment was almost identical in both groups, we definitely find an advantage in acute treatment of a scapholunate ligament tear by suture. A technically easier procedure, a shorter period of restricted hand and arm function for the patient, no degenerative changes due to instability and a lower risk of complications - they all give support to this technique. Later conversion to another type of stabilisation if ligamentoplasty fails may bring problems and give much worse results than a failure of acute sutures, Conclusions: An acute operative treatment of scapholunate ligament injury is regarded as a more suitable method for scapholunate dissociation. Ligamentoplasty, because of technical demands and risk of post-operative complications, can be used as a method of choice if the acute sutures of a torn scapholunate ligament fail or scapholunate dissociation is diagnosed at a late stage.

Re-evaluation of all functions of baroreflex by means of a simple mathematical model of circulation was the aim of the present study. The following states are modelled: 1. Rest. 2. Immediately after baroreceptor denervation. 3. Several days after denervation. 4. Physical exercise before denervation. 5. Physical exercise several days after denervation. Despite the same cardiac contractility and the same vasodilatation in working muscles as before denervation the cardiac output is by one third lower after baroreceptor denervation. In conclusion, a model simulation revealed the common regulation of blood pressure and blood volume by baroreflex and kidneys as a primary function of baroreflex.

The relationship between age and circadian blood pressure (BP) variation was the aim of the present study. One hundred and eighty-seven subjects (130 males, 57 females), 20-77 years old, were recruited for seven-day BP monitoring. Colin medical instruments (Komaki, Japan) were used for ambulatory BP monitoring (oscillation method, 30-minute interval between measurements). A sinusoidal curve was fitted (minimum square method) and the mean value and amplitude of the curve (double amplitude corresponds to the night-day difference) were evaluated on every day of monitoring. The average 7-day values of the mean (M) and of double amplitude (2A) for systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) were determined in each subject. The mean values of M (+/-SD) for the whole group were: SBP- 127+/-8, DBP - 79+/-6 mmHg, HR - 70+/-6 bpm; of 2A: SBP - 21+/-7, DBP - 15+/-5 mmHg, HR - 15+/-6 bpm. A linear relationship between M of SBP and age (r=0.341, p< 0.001) and DBP and age (r=0.384, p<0.001) was found (difference between 20 and 77 years: SBP - 16, DBP - 12 mmHg). 2A of SBP and DBP was increasing with age up to 35 years, then the curve remained relatively flat up to 55 years (maximum at 45 years), and then it decreased again (difference between 45 and 77 years: SBP - 13mmHg, DBP - 12 mmHg). Heart rate M and 2A were age-independent. The mean values of SBP and DBP were increasing with age up to 75 years, but the night-day difference of SBP and DBP reached its maximum value at 45 years and then decreased.