Spherical Robots for Special Purposes: A Review on Current Possibilities.

The review discusses the possibilities of different driving mechanisms and sensors of spherical robots, and a special kind of mobile robots is introduced and discussed. The sensors discussed can expand robots' sensing capabilities which are typically very limited. Most spherical robots have holonomic characteristics and protect the inner environment using a shell. Today, there are a diversity of driving mechanisms. Therefore, this article provides a review of all of them and identifies their basic properties. Accordingly, many spherical robots have only inner sensors for moving, balancing, driving, etc. However, a few of them are also equipped with sensors that can measure environmental properties. Therefore, in this paper, we propose the possibility of using such sensors as cameras, LiDARs, thermocouples, and gas sensors, which can be used for special purposes underground, for example, in mines, underground tunnels, or road tunnels. After combining all components are combined, it is possible to design a special type of spherical robot designed for underground exploration, such as accidents in mines or road tunnels.

Nephrotoxicity of calcineurin inhibitors as a risk factor for BK polyomavirus replication after kidney transplantation.

BK polyomavirus-associated nephropathy (PyVAN) is responsible for a significant percentage of transplanted kidneys prematurely terminating their function. Its occurrence is closely related to the intensity of immunosuppressive therapy. In a group of 161 newly transplanted patients, we prospectively evaluated 457 protocol renal biopsies performed within the first year after transplantation. Using the calcineurin inhibitors (CI) nephrotoxicity score, the incidence of nephrotoxicity was monitored as a manifestation of excessive immunosuppression. Findings were correlated with clinical evidence of active BK polyomavirus (BKPyV) replication and PyVAN. Compared to the normal histology, nephrotoxicity was associated with more frequent BKPyV viremia and viruria (p = .01 and p < .01, respectively) and more common occurrence of PyVAN. The persistence of toxicity in the subsequent biopsy proved to be a negative risk factor of viremia and viruria (p = .03 and p < .01, respectively), independently of the initial BKPyV status. Toxicity could also be used as a predictor of viremia and viruria (p = .04 and p < .01, respectively) even in the absence of viral replication at the time of initial biopsy. The early histological manifestation of CI nephrotoxicity was associated with significant BKPyV reactivation in the risky first posttransplant year.

Enhanced Oral Bioavailability of 2-(Phosphonomethyl)-pentanedioic Acid (2-PMPA) from its (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl (ODOL)-Based Prodrugs.

2-(Phosphonomethyl)-pentanedioic acid (2-PMPA) is a potent (IC50 = 300 pM) and selective inhibitor of glutamate carboxypeptidase II (GCPII) with efficacy in multiple neurological and psychiatric disease preclinical models and more recently in models of inflammatory bowel disease (IBD) and cancer. 2-PMPA (1), however, has not been clinically developed due to its poor oral bioavailability (<1%) imparted by its four acidic functionalities (c Log P = -1.14). In an attempt to improve the oral bioavailability of 2-PMPA, we explored a prodrug approach using (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (ODOL), an FDA-approved promoiety, and systematically masked two (2), three (3), or all four (4) of its acidic groups. The prodrugs were evaluated for in vitro stability and in vivo pharmacokinetics in mice and dog. Prodrugs 2, 3, and 4 were found to be moderately stable at pH 7.4 in phosphate-buffered saline (57, 63, and 54% remaining at 1 h, respectively), but rapidly hydrolyzed in plasma and liver microsomes, across species. In vivo, in a single time-point screening study in mice, 10 mg/kg 2-PMPA equivalent doses of 2, 3, and 4 delivered significantly higher 2-PMPA plasma concentrations (3.65 ± 0.37, 3.56 ± 0.46, and 17.3 ± 5.03 nmol/mL, respectively) versus 2-PMPA (0.25 ± 0.02 nmol/mL). Given that prodrug 4 delivered the highest 2-PMPA levels, we next evaluated it in an extended time-course pharmacokinetic study in mice. 4 demonstrated an 80-fold enhancement in exposure versus oral 2-PMPA (AUC0-t: 52.1 ± 5.9 versus 0.65 ± 0.13 h*nmol/mL) with a calculated absolute oral bioavailability of 50%. In mouse brain, 4 showed similar exposures to that achieved with the IV route (1.2 ± 0.2 versus 1.6 ± 0.2 h*nmol/g). Further, in dogs, relative to orally administered 2-PMPA, 4 delivered a 44-fold enhanced 2-PMPA plasma exposure (AUC0-t for 4: 62.6 h*nmol/mL versus AUC0-t for 2-PMPA: 1.44 h*nmol/mL). These results suggest that ODOL promoieties can serve as a promising strategy for enhancing the oral bioavailability of multiply charged compounds, such as 2-PMPA, and enable its clinical translation.

Cochlear Implantation.

Historically, cochlear implants are the first substitute for a sensory modality, hearing. In past decades, they have become a standard method of a compensation for a hearing loss, both for children and adults. Because of restored hearing by cochlear implants, people were able to keep their jobs, marriages and other social ties. Many children born deaf could attend standard schools from basic education to universities, together with their hearing peers, the fact which had influenced greatly their future lives. Unfortunately, not all suitable candidates for cochlear implants get them. Paradoxically, not due to insufficient financing as before or in undeveloped countries nowadays, but due to lack of a correct information and a lack of interest both in patients and specialists. In our contribution, a principle of the cochlear implant is explained, together with proper indications, modes of application and results of its usage. Because of a limited text span, a history of development of cochlear implants is skipped completely. Nevertheless, we believe that the information proper will reach all those, who could benefit from it.

Exposure criteria for evaluating lumbar spine load.

OBJECTIVE: As a part of regular revision of the List of Occupational Diseases in the Czech Republic, efforts have been made to add a new item so that lumbar spine disease caused by overload may be recognized as occupational one, with adherence to the valid national rules, that is, clinical criteria are met and objective assessment confirms working conditions under which, according to recent scientific knowledge, such an occupational disease develops. The aim is to provide information on the use of a proposed method for working condition assessment in a real setting, based on the initial experiences gained from a pilot study carried out to validate the method. METHODS: Working conditions were assessed in 55 individuals with chronic low back pain (25 males, 30 females; mean age 45.6 years; mean length of employment 15.6 years). The assessment was based on estimating compressive force on the L4/L5 intervertebral disc when performing potentially high-risk work tasks which were entered into four types of checklists throughout their work shifts. The compression values were calculated using a special module that was developed. RESULTS: In 24 cases comprehensive assessment of all tasks performed showed fulfillment of the proposed criteria of working conditions needed for recognition of occupational disease. Those included healthcare, foundry and forest workers, production operators, cabinetmakers, locksmiths, bricklayers, etc. In all the cases, lumbar spine overload was associated with work tasks requiring combinations of manual handling of objects and trunk rotation or bending. The criteria were not met in 31 subjects. The mean length of employment was 15.4 and 15.8 years in patients who met and did not meet the proposed criteria, respectively. CONCLUSION: The proposed method proved to be applicable in occupational hygiene evaluation in a real setting.

A New Approach to the Evaluation of Local Muscular Load while Typing on a Keyboard.

OBJECTIVE: The aim of this study was to assess the contribution of using keystroke dynamics (KD) in combination with integrated electromyography (iEMG) for the objective evaluation of local muscular load of hands and forearms while typing on a computer keyboard and to compare it with results of the commonly used method. METHOD: Study was performed on 12 subjects. Data were collected using our own application for capturing KD data and using EMG Holter for detecting electromyographic potentials to determine local muscular load. RESULTS: The results of our study revealed that currently used methods for assessment of the workload while typing on a computer keyboard are not entirely accurate. In particular, the real total number of keystrokes performed during processing of a text is significantly higher than the count of characters the text is consisting of. In addition to this count, also the so-called invisible keys, keyboard shortcuts, and especially corrections in the typed text must be taken into consideration. CONCLUSIONS: The results indicated that all probands in our study exceeded the valid hygienic limits for the total amount of the small repetitive movements of the hands and forearms and the total amount of the keyboard typing movements. Most of the probands in our study also exceeded the valid hygienic limit for the highest average time-weighted value of the percent maximum voluntary contraction (%MVC). This implies that the keystroke dynamics method has a great potential to increase the accuracy of evaluation of local muscular load when using the keyboard and thus to improve the existing methodology for investigation of occupational diseases resulting from overload while working on the computer.

[30 years of the cochlear implantations in the Czech Republic]. / 30 let kochleárních implantací v Ceské republice.

Cochlear implant is the unique sensory neuroprosthesis and still the only one used in clinical praxis. The function of the inner ear is replaced with direct electrical stimulation of the cochlear nerve. It is 30 years since the first cochlear implantation has been performed with the Czech single-channel cochlear neuroprosthesis. There are more than one thousand users of cochlear implants in the Czech Republic nowadays. Cochlear implants have become a standard of care of patients with severe hearing loss. It allows user inclusion to the society with only a minimum of obstacles.Key words: cochlear implant, history, neuroprosthesis, severe hearing loss.

Evaluation of Lumbar Spine Load by Computational Method in Order to Acknowledge Low-back Disorders as Occupational Diseases.

AIM: The aim of the study was to develop a computational module for the prediction of compressive force on the L4/L5 disc suitable for use in field settings. METHOD: The value of compressive force is intended to be used as a proxy measure of the mechanical burden of low-back when performing work activities. The compressive force predicted by the module in a particular worker should be compared with the NIOSH limit value of 3,400 N for the assessment of lumbar spine load during manual lifting tasks. Exceeding the limit will be considered as the fulfilment of "hygienic criterion" that should be met to acknowledge low-back disorder as an occupational disease. To develop the computational module we used the ergonomic software TECNOMATIX Classic Jack taking into account the anthropometric parameters of a worker and ergonomic parameters of his/her work activity. RESULTS: We calculated compressive forces on the L4/L5 disc in about 1,300 simulated combinations of various factors influencing compressive force. Parameters which turned out to be crucial for the compression of L4/L5 disc were included in the computational algorithm. CONCLUSION: Our study was primarily aimed at the assessment of lumbar disorders as occupational diseases. Moreover, the study can contribute to the recommendation of preventive measures to decrease health risks in occupations associated with the overload of low-back region. The graphic maps generated by the computational module enable a fast and exact analysis of particular job.

Primitive neuroectodermal tumor (PNET) of the lung in an adult woman.

Primary primitive neuroectodermal tumors (PNETs) are extremely rare in the lung and especially in adult women. We describe a case of PNET of the lung with aggressive behavior in 31-year-old woman. Diagnosis was based on histopathological and immunohistochemical studies, and confirmed by molecular genetic analysis of chromosome rearrangements in the EWSR1 gene region. Clinical follow-up, post-mortem findings, and differential diagnosis are also discussed.

[Closed pleural biopsy in the diagnostics of malignant pleural involvement]. / Necílená biopsie pleury v diagnostice maligního pleurálního výpotku - nase zkusenosti za posledních 15 let.

INTRODUCTION: Pleural effusion is a frequent reason for a pulmonologist´s investigation. The cornerstone is to distinguish transudative pleural effusion from exudative pleural effusion. In the case of the exudative pleural effusion the next step is detection of malignant etiology of pleural effusion. We have a variety of any non-invasive or invasive examinations. The pleural biopsy is one of the most important methods for diagnostics of malignant pleural effusion. MATERIAL AND METHODS: Two hundred and twenty-two closed pleural biopsies (CPB) were performed in 208 patients with pleural effusion, where the cytologic examination of pleural fluid was negative. The authors evaluated the value of CPB for the diagnosis of malignant pleural involvement. RESULTS AND CONCLUSION: Total sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 63.1%, 100%, 73.9%, 100% and 52.8%, but in the group of mesotheliomas these results were 59.1%, 100%, 79.4%, 100% and 70.7%. The incidence of complications and representative sampling of the pleura was mentioned. The authors compared the diagnostic value and the incidence of complications of various diagnostic methods in malignant pleural involvement by data in the literature.

[Bortezomib-based therapy in patients with light chain deposition disease]. / Lécba bortezomibem u pacientu s onemocnením z depozice lehkých retezcu imunoglobulinu.

Light chain deposition disease (LCDD) is a rare systemic condition caused by monoclonal proliferation of terminally differentiated B-lymphocytes with production of free light chains and their deposition in kidneys or other organs. The aim of our study is to show the pitfalls of the diagnostics, and to demonstrate the effect of bortezomib-based therapy on a series of 4 patients with LCDD, from the point of hematological and organ therapeutic response. We include that bortezomib based treatment provides rapid and effective hematological response. It is, however, often accompanied by adverse events, especially within intensive treatment schedules. The most serious adverse effects includes peripheral neuropathy, which might be dose or treatment-limiting. Less intensive regimens ("bortezomib weekly") suggest an alternative with expectation of lower incidence of adverse effects. Autologous stem cell transplantation is a recommended and relatively safe approach in convenient candidates. Organ response is significantly delayed after hematological response, and organ damage by light chain deposits might not be fully reversible.

[Giant cell interstitial pneumonia without exposure to hard metals]. / Obrovskobunecná intersticiální pneumonie bez souvislosti s expozicí tvrdokovum.

We describe the case of a 58-year-old woman with giant cell interstitial pneumonia without any history of exposure to hard metals. Giant cell interstitial pneumonia (GIP) is a rare interstitial lung disease characterized by the presence of numerous multinucleated giant cells in the alveolar spaces. Currently GIP is regarded as secondary interstitial pneumonia. While it has become almost synonymous with hard metal lung disease (cobalt pneumonitis), the literature has also included sporadic cases of GIP without exposure to hard metals. This fact undermines the synonymical relationship between GIP and hard metal lung disease. The alteration of lung tissue in GIP is immunologically mediated. In our patient we found a classical histological picture of GIP with lymphoid hyperplasia. At the time of diagnosis she was being treated for Hashimoto´s thyreoiditis. Later, autoimmune hemolytic anemia and bronchial asthma developed. We suggest that our case supports the hypothesis of the autoimmune ethiology of idiopathic GIPs.

Neoadjuvant nivolumab and cabozantinib in advanced renal cell carcinoma in a horseshoe kidney - how to achieve a safe and radical resection? a case report and review of the literature.

Introduction: Neoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting. Methods: We report a case of a 52-year old male who presented with a large inoperable tumor of the horseshoe kidney and achieved major partial radiologic response after neoadjuvant therapy with nivolumab and cabozantinib leading to radical resection of the tumor. The patient remains tumor free on the subsequent follow-up and his renal function is only mildly decreased. The systemic treatment was complicated by hepatotoxicity leading to early nivolumab withdrawal. Results: Currently, the combination therapy based on immune checkpoint inhibitors and tyrosine kinase inhibitors represents the treatment of choice in treatment-naïve patients with metastatic renal cell carcinoma in any prognostic group. The neoadjuvant treatment approach is being tested in prospective clinical trials and results are eagerly awaited. Renal cell carcinoma in a horseshoe kidney is an uncommon finding that is always challenging. Additionally, management guidance in this patient population is lacking. In some patients neoadjuvant therapy could be the only way to preserve kidney function. The initial treatment strategy should be individualized to patient needs aiming at the radical resection of the primary tumor as the only chance of getting the tumor under control in the long term. Conclusion: Herein, we highlight the feasibility of neoadjuvant systemic therapy with nivolumab and cabozantinib allowing the subsequent performance of radical tumor resection with negative margins in a patient with advanced renal cell carcinoma in a horseshoe kidney, removing the primary tumor while sparing the patient from lifelong dialysis.

A founder COL4A4 pathogenic variant resulting in autosomal recessive Alport syndrome accounts for most genetic kidney failure in Romani people.

Introduction: Romani people have a high prevalence of kidney failure. This study examined a Romani cohort for pathogenic variants in the COL4A3, COL4A4, and COL4A5 genes that are affected in Alport syndrome (AS), a common cause of genetic kidney disease, characterized by hematuria, proteinuria, end-stage kidney failure, hearing loss, and eye anomalies. Materials and methods: The study included 57 Romani from different families with clinical features that suggested AS who underwent next-generation sequencing (NGS) of the COL4A3, COL4A4, and COL4A5 genes, and 83 family members. Results: In total, 27 Romani (19%) had autosomal recessive AS caused by a homozygous pathogenic c.1598G>A, p.Gly533Asp variant in COL4A4 (n = 20) or a homozygous c.415G>C, p.Gly139Arg variant in COL4A3 (n = 7). For p.Gly533Asp, 12 (80%) had macroscopic hematuria, 12 (63%) developed end-stage kidney failure at a median age of 22 years, and 13 (67%) had hearing loss. For p.Gly139Arg, none had macroscopic hematuria (p = 0.023), three (50%) had end-stage kidney failure by a median age of 42 years (p = 0.653), and five (83%) had hearing loss (p = 0.367). The p.Gly533Asp variant was associated with a more severe phenotype than p.Gly139Arg, with an earlier age at end-stage kidney failure and more macroscopic hematuria. Microscopic hematuria was very common in heterozygotes with both p.Gly533Asp (91%) and p.Gly139Arg (92%). Conclusion: These two founder variants contribute to the high prevalence of kidney failure in Czech Romani. The estimated population frequency of autosomal recessive AS from these variants and consanguinity by descent is at least 1:11,000 in Czech Romani. This corresponds to a population frequency of autosomal dominant AS from these two variants alone of 1%. Romani with persistent hematuria should be offered genetic testing.

Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis as a Complication of Home Parenteral Nutrition.

Patients on long-term home parenteral nutrition (HPN) occasionally develop glomerulonephritis due to chronic central venous catheter (CVC)-related infection. Most previously reported cases were membranoproliferative glomerulonephritis (MPGN). This is a case report of a 16-year-old girl receiving HPN for short bowel syndrome. After 11 years on HPN, she developed acute kidney injury with macroscopic hematuria, nephrotic-range proteinuria, and a reduced glomerular filtration rate (GFR). Initially, MPGN associated with chronic bacteremia was suspected with the assumption that the condition would be treated with antibiotics and CVC replacement. However, her kidney biopsy revealed antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAG). This was consistent with the fact that the patient tested positive for proteinase 3-ANCA. Immunosuppressive therapy with methylprednisolone pulses (followed by oral prednisone) and rituximab led to remission. Her GFR and protein excretion returned to normal. Chronic bacteremia as a complication of long-term HPN may cause various types of glomerulonephritis including, rarely, AAG requiring immunosuppressive therapy.

Current Status, Prevention and Treatment of BK Virus Nephropathy.

All renal transplant recipients should undergo a regular screening for BK viral (BKV) viremia. Gradual reduction of immunosuppression is recommended in patients with persistent plasma BKV viremia for 3 weeks after the first detection, reflecting the presence of probable or suspected BKV-associated nephropathy. Reduction of immunosuppression is also a primary intervention in biopsy proven nephropathy associated with BKV (BKVN). Thus, allograft biopsy is not required to treat patients with BKV viremia with stabilized graft function. There is a lack of proper randomised clinical trials recommending treatment in the form of switching from tacrolimus to cyclosporin-A, from mycophenolate to mTOR inhibitors or leflunomide, or the additive use of intravenous immunoglobulins, leflunomide or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. There are on-going studies to evaluate the possibility of using a multi-epitope anti-BKV vaccine, administration of BKV-specific T cell immunotherapy, BKV-specific human monoclonal antibody and RNA antisense oligonucleotides. Retransplantation after allograft loss due to BKVN can be successful if BKV viremia is definitively removed, regardless of allograft nephrectomy.

New prodrugs of Adefovir and Cidofovir.

New Adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl or decyloxyethyl chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared starting from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The activity of the prodrugs was evaluated in vitro against different virus families. A loss in the antiviral activities of the hydroxylated decyl or decyloxyethyl esters and hexaethyleneglycol esters of PMEA against human immunodeficiency virus (HIV) and herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (CMV)] occurred in comparison with the parent compound. On the other hand, the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of PMEA showed significant activities against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anti-cytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir.

Mathematical Modelling of Temperature Distribution in Selected Parts of FFF Printer during 3D Printing Process.

This work presented an FEM (finite element method) mathematical model that describes the temperature distribution in different parts of a 3D printer based on additive manufacturing process using filament extrusion during its operation. Variation in properties also originate from inconsistent choices of process parameters employed by individual manufacturers. Therefore, a mathematical model that calculates temperature changes in the filament (and the resulting print) during an FFF (fused filament fabrication) process was deemed useful, as it can estimate otherwise immeasurable properties (such as the internal temperature of the filament during the printing). Two variants of the model (both static and dynamic) were presented in this work. They can provide the user with the material's thermal history during the print. Such knowledge may be used in further analyses of the resulting prints. Thanks to the dynamic model, the cooling of the material on the printing bed can be traced for various printing speeds. Both variants simulate the printing of a PLA (Polylactic acid) filament with the nozzle temperature of 220 °C, bed temperature of 60 °C, and printing speed of 5, 10, and 15 m/s, respectively.

Para-hydrogenated glucose derivatives as potential 13C-hyperpolarized probes for magnetic resonance imaging.

A set of molecules in which a glucose moiety is bound to a hydrogenable synthon has been synthesized and evaluated for hydrogenation reactions and for the corresponding para-hydrogen-induced polarization (PHIP) effects, in order to select suitable candidates for an in vivo magnetic resonance imaging (MRI) method for the assessment of glucose cellular uptake. It has been found that amidic derivatives do not yield any polarization enhancement, probably due to singlet-triplet state mixing along the reaction pathway. In contrast, ester derivatives are hydrogenated in high yield and afford enhanced (1)H and (13)C NMR spectra after para-hydrogenation. The obtained PHIP patterns are discussed and explained on the basis of the calculated spin level populations in the para-hydrogenated products. These molecules may find interesting applications in (13)C MRI as hyperpolarized probes for assessing the activity of glucose transporters in cells.

Subclinical toxicity of calcineurin inhibitors in repeated protocol biopsies: an independent risk factor for chronic kidney allograft damage.

The purpose of the prospective study was to determine the prevalence of subclinical toxicity of calcineurin inhibitors (CI) in repeated protocol renal allograft biopsies and to assess its impact on the development of chronic graft changes. A total of 424 biopsies were conducted in a cohort of 158 patients; of these biopsies, 158 were in the third week, 142 were in the third month and 124 were in the first year after transplantation. Histological signs of toxicity occurred in the third week in 33 (20.1%) patients, with persistence after CI dose reduction in the third month in 27 (19.0%) and in the first year in 23 (18.5%) patients. Of the toxic changes, 52% were clinically silent. At the end of the one-year follow-up, both subclinical and clinically manifest toxicity resulted in a similar progression of chronic changes quantified by Banff chronicity score and they significantly differed from the control group (P < 0.05). Subclinical toxicity affects a significant percentage of grafts; it occurs independently of dosage, blood level and type of applied CI. It is associated with the progression of chronic changes as early as in the first year after transplantation and represents an independent risk factor for chronic allograft damage. We report here our clinical approach to toxicity.