Nitrogen, phosphorus, and potassium are the three most essential micronutrients which play major roles in plant survivability by being a structural or non-structural component of the cell. Plants acquire these nutrients from soil in the fixed (NO3 ̄, NH4+) and solubilized forms (K+, H2PO4- and HPO42-). In soil, the fixed and solubilized forms of nutrients are unavailable or available in bare minimum amounts; therefore, agrochemicals were introduced. Agrochemicals, mined from the deposits or chemically prepared, have been widely used in the agricultural farms over the decades for the sake of higher production of the crops. The excessive use of agrochemicals has been found to be deleterious for humans, as well as the environment. In the environment, agrochemical usage resulted in soil acidification, disturbance of microbial ecology, and eutrophication of aquatic and terrestrial ecosystems. A solution to such devastating agro-input was found to be substituted by macronutrients-availing microbiomes. Macronutrients-availing microbiomes solubilize and fix the insoluble form of nutrients and convert them into soluble forms without causing any significant harm to the environment. Microbes convert the insoluble form to the soluble form of macronutrients (nitrogen, phosphorus, and potassium) through different mechanisms such as fixation, solubilization, and chelation. The microbiomes having capability of fixing and solubilizing nutrients contain some specific genes which have been reported in diverse microbial species surviving in different niches. In the present review, the biodiversity, mechanism of action, and genomics of different macronutrients-availing microbiomes are presented.

• MeSH
• Bacteria * metabolismus   genetika   klasifikace   MeSH
• biodiverzita * MeSH
• biotechnologie * MeSH
• draslík metabolismus   MeSH
• dusík metabolismus   MeSH
• fosfor metabolismus   MeSH
• mikrobiota * MeSH
• půda chemie   MeSH
• půdní mikrobiologie MeSH
• zemědělské plodiny MeSH
• zemědělství MeSH
• živiny * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cyanobacteria are prokaryotic organisms characterised by their complex structures and a wide range of pigments. With their ability to fix CO2, cyanobacteria are interesting for white biotechnology as cell factories to produce various high-value metabolites such as polyhydroxyalkanoates, pigments, or proteins. White biotechnology is the industrial production and processing of chemicals, materials, and energy using microorganisms. It is known that exposing cyanobacteria to low levels of stressors can induce the production of secondary metabolites. Understanding of this phenomenon, known as hormesis, can involve the strategic application of controlled stressors to enhance the production of specific metabolites. Consequently, precise measurement of cyanobacterial viability becomes crucial for process control. However, there is no established reliable and quick viability assay protocol for cyanobacteria since the task is challenging due to strong interferences of autofluorescence signals of intercellular pigments and fluorescent viability probes when flow cytometry is used. We performed the screening of selected fluorescent viability probes used frequently in bacteria viability assays. The results of our investigation demonstrated the efficacy and reliability of three widely utilised types of viability probes for the assessment of the viability of Synechocystis strains. The developed technique can be possibly utilised for the evaluation of the importance of polyhydroxyalkanoates for cyanobacterial cultures with respect to selected stressor-repeated freezing and thawing. The results indicated that the presence of polyhydroxyalkanoate granules in cyanobacterial cells could hypothetically contribute to the survival of repeated freezing and thawing.

• MeSH
• fluorescence MeSH
• fluorescenční barviva * metabolismus   chemie   MeSH
• fyziologický stres * MeSH
• mikrobiální viabilita * MeSH
• polyhydroxyalkanoáty metabolismus   MeSH
• průtoková cytometrie * MeSH
• sinice metabolismus   fyziologie   MeSH
• Synechocystis * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) have a poor prognosis. The phase I/II NP30179 study (ClinicalTrials.gov identifier: NCT03075696) evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab. We present data for patients with R/R MCL. METHODS: Eligible patients with R/R MCL (at least one previous therapy) received Gpt (1,000 or 2,000 mg) 7 days before the first glofitamab dose (single dose or split over 2 days if required). Glofitamab step-up dosing was administered once a day on days 8 (2.5 mg) and 15 (10 mg) of cycle 1, with a target dose of 16 or 30 mg once every 3 weeks from cycle 2 day 1 onward, for 12 cycles. Efficacy end points included investigator-assessed complete response (CR) rate, overall response rate (ORR), and duration of CR. RESULTS: Of 61 enrolled patients, 60 were evaluable for safety and efficacy. Patients had received a median of two previous therapies (range, 1-5). CR rate and ORR were 78.3% (95% CI, 65.8 to 87.9) and 85.0% (95% CI, 73.4 to 92.9), respectively. In patients who had received previous treatment with a Bruton tyrosine kinase inhibitor (n = 31), CR rate was 71.0% (95% CI, 52.0 to 85.8) and ORR was 74.2% (95% CI, 55.4 to 88.1). CRS after glofitamab administration occurred in 70.0% of patients, with a lower incidence in the 2,000 mg (63.6% [grade ≥2, 22.7%]) versus 1,000 mg (87.5%; grade ≥2, 62.5%) Gpt cohort. Four adverse events led to glofitamab withdrawal (all infections). CONCLUSION: Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.

• MeSH
• dospělí MeSH
• humanizované monoklonální protilátky aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• lymfom z plášťových buněk * farmakoterapie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH

Při nutnosti řešit středně silnou a silnou bolest je téměř nemožné se obejít bez silných opioidů. Nové opioidní léčivé přípravky (atypické opioidy – buprenorfin, transdermální nebo transmukózní lékové formy) pomáhají zlepšit léčbu různých typů nádorové i nenádorové bolesti a zároveň snižují nežádoucí účinky silných opioidů, zejména zácpu. Fixní kombinace oxykodonu s naloxonem v poměru 2 : 1 zachovává výborný analgetický účinek silného opioidu oxykodonu a zároveň díky obsahu naloxonu předchází vzniku zácpy vyvolané opioidy.

When it is necessary to manage moderate to severe pain, it is nearly impossible to do so without the use of strong opioids. New opioid medications - referred to as atypical opioids, such as buprenorphine in transdermal or transmucosal formulations - contribute to improved treatment of various types of both cancer-related and non-cancer-related pain. At the same time, they help reduce the adverse effects commonly associated with strong opioids, particularly constipation. A fixed combination of oxycodone and naloxone in a 2:1 ratio maintains the excellent analgesic effect of the potent opioid oxycodone, while the inclusion of naloxone effectively prevents opioid-induced constipation.

Úvod: U idiopatické retroperitoneální fibrózy dominuje zavzetí ureterů do retroperitoneální fibrotické masy (zejména ve střední části ureterů), což vede k rozvoji (dolicho-) megaureterů s následnou progredující renální insuficiencí. Levá strana bývá postižena dříve. Řešením je ovlivnění etiopatogeneze onemocnění (zejména kortikoidní léčba) a derivace horních cest močových. Je možné provést buď trvalý stenting obou ureterů se všemi svými nevýhodami, či jejich deliberaci, která se historicky prováděla otevřeně ze střední laparotomie, nověji miniinvazivně. V práci hodnotíme výsledky miniinvazivní (laparoskopické, resp. roboticky asistované) deliberace a prezentujeme video robotické varianty. Soubor: V období 2001–2024 bylo k oboustranné deliberaci indikováno devět nemocných – tři muži (33 %) a šest žen; průměrný věk 58,5 ± 6,9 (48,8–69,6) roků; body mass index (BMI) 28,9 ± 5,8 (19,5–38,1). První čtyři řešení laparoskopicky, pět poté roboticky asistovaně. U dvou (22,2 %) nemocných nebylo možno uretery z těžkých fibrotických změn uvolnit (jeden z laparoskopie ponechán na stentech, druhý řešený roboticky asistovaně, provedena otevřená nefrektomie u ledviny s 8,6 % funkce a otevřená druhostranná deliberace – ze střední laparotomie). Doba operace obou stran (bez otevřeného výkonu) byla 154,0 ± 33,5 (100–201) min. Video: Ukazuje deliberaci obou ureterů roboticky asistovaně. Je užit čtyřramenný systém da Vinci Xi, poloha na boku 70°. Začínáme postiženější levou stranou. S Veres jehlou vytvořeno kapnoperitoneum tlakem 12 mm Hg, pupkem zaveden asistentský port 11 mm, za kontroly zraku zavedeny čtyři robotické 8mm porty. Kamera 30°, ProGraspTM, bipolární grasper MarylandTM, monopolární nůžky. Otevřeno parakolicky peritoneum, nalezen ureter a deliberován od dolního pólu ledviny až pod ilické cévy. Pod deliberovaný močovod vloženo mediální peritoneum a fixováno k laterálnímu okraji stehem či Hem-o-lok® L klipy. Ponechán port v pupku, změněna poloha a identicky proveden výkon i vpravo. Dutina břišní nedrénována. Ureterální stenty odstraněny za 3–6 týdnů. Výsledky: U 8 nemocných, kde bylo možno uretery deliberovat (15 močovodů, z toho 1 otevřeně), je známo dlouhodobé sledování všech 15 močovodů, u nich není nutný další stenting ureterů, horní cesty močové jsou sonograficky bez dilatace a nedochází k rozvoji renální insuficience. Doba sledování je v průměru 63,9 ± 64,3 (1–158) měsíců. U 8 kombinováno s kortikoidní terapií, která vedla vždy k výrazné regresi fibrotických hmot. Závěr: Deliberace močovodů při morbus Ormond je proveditelná miniinvazivně (laparoskopicky či roboticky asistovaně) u 77,8 % s překvapivě dobrými dlouhodobými výsledky umožňujícími uchránit horní cesty močové a vyhnout se dlouhodobému stentingu (ve 100 %). Robotické variantě dáváme nyní jednoznačně přednost.

Introduction: In idiopathic retroperitoneal fibrosis, ureteral involvement of the retroperitoneal fibrotic mass (especially in the middle part of the ureters) dominates, leading to the development of (dolicho-) megaureters with subsequent progressive renal insufficiency. The left side tends to be affected earlier. The solution is to influence the etiopathogenesis of the disease (especially corticoid treatment) and diversion of the upper urinary tract. Either permanent stenting of both ureters with all its disadvantages or ureterolysis. Historically open via midline laparotomy, more recently minimally invasive. In this paper we evaluate the results of minimally invasive (laparoscopic or robotic assisted) ureterolysis. Abstract: Between 2001 and 2024, nine patients were indicated for bilateral ureterolysis. Three men (33%) and six women. Mean age 58.5±6.9 (48.8-69.6) years. Body mass index (BMI) 28.9±5.8 (19.5-38.1). First four laparoscopically, subsequent five robotic assisted. In two (22.2%) patients ureters could not be released from severe fibrotic changes (one laparoscopy left with stents, the other robotically assisted open nephrectomy in a kidney with 8.6% function and open secondary ureterolysis - via midline laparotomy). The bilateral operation time (without open surgery) was 154.0±33.5 (100-201) min. Video: Shows the robotic-assisted bilateral ureterolysis. The 4-arm daVinci Xi system is used, 70° lateral position. Starting with the more affected left side. With Veres needle, capnoperitonum pressure of 12 mmHg created, 11 mm assisted port inserted through umbilicus, four robotic 8mm introduced under visual control. Camera 30°, ProGraspTM, bipolar grasper MarylandTM, monopolar scissors. Paracolic peritoneum opened, ureter found and liberated from the lower pole of the kidney to below the iliac vessels. Medial peritoneum inserted under the deliberated ureter and fixed to the lateral margin with suture or Hem-o-lok® L clips. The port in the umbilicus was left, the position was changed and the procedure was performed identically on the right side. The abdominal cavity was not drained. Ureteral stents removed in 3-6 weeks. Results: In the eight patients where ureters could be liberated (15 ureters, 1 open), long-term follow-up is known for all 15 ureters, no further ureteral stenting is required, the upper urinary tract is sonographically free of dilatation and no renal insufficiency developed. The mean follow-up time is 63.9±64.3 (1-158) months. In eight cases, combined corticosteroid therapy always resulted in significant regression of fibrotic masses. Conclusion: Liberation of ureters in morbus Ormond is feasible minimally invasively (laparoscopically or robotically assisted) in 77.8% with surprisingly good long-term results allowing preservation of the upper urinary tract and avoiding long-term stenting (in 100%). The robotic option is now clearly preferred.

• MeSH
• lidé MeSH
• miniinvazivní chirurgické výkony MeSH
• obstrukce močovodu chirurgie   MeSH
• retroperitoneální fibróza * komplikace   MeSH
• roboticky asistované výkony MeSH
• urologické chirurgické výkony MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• audiovizuální média MeSH

Prevalence bronchiálního astmatu vzrůstá a těžké astma, které není pod kontrolou ani při optimální terapii vysokou dávkou inhalačního kortikosteroidu v kombinaci s dlouhodobě působícím β2-mimetikem, trápí až 10 % astmatiků. Těžké astma je spojeno s vyšším rizikem vzniku fixované bronchiální obstrukce, akutních exacerbací, zhoršenou kvalitou života i finanční zátěží zdravotnického systému. Přídatná biologická léčba astmatu by měla být zvážena u všech pacientů, kteří i přes optimální léčbu astmatu a případných komorbidit prodělávají akutní exacerbace či mají z indikace astmatu nasazenou systémovou kortikoterapii. V současné době máme v České republice k dispozici pět preparátů, kterými léčíme pacienty s těžkým astmatem. Tato biologika jsou zaměřena proti cytokinům uplatňujícím se v patogenezi eozinofilního zánětu (interleukin 4, 5 a 13), thymickému stromálnímu lymfopoetinu či proti imunoglobulinu E. Tento přehledový článek stručně a přehledně pojednává o základech současných možností a indikacích biologické léčby těžkého bronchiálního astmatu.

The prevalence of bronchial asthma is increasing and severe asthma, which is not controlled even with optimal therapy with a high dose of inhaled corticosteroid in combination with a long-acting β2-mimetic, affects up to 10 % of asthmatics. Severe asthma is associated with a higher risk of fixed bronchial obstruction, acute exacerbations, impaired quality of life and financial burden on the healthcare system. Biological treatment of asthma should be considered in all patients who, despite optimal treatment of asthma and its comorbidities, experience acute exacerbations or use chronic systemic corticotherapy due to asthma. Currently, we have five agents available in the Czech Republic to treat patients with severe asthma. These biologics are directed against cytokines involved in the pathogenesis of eosinophilic inflammation (interleukin 4, 5 and 13), against immunoglobulin E or against thymic stromal lymphopoietin. This review article briefly and clearly discusses the basics of current options and indications for biologic treatment of severe bronchial asthma.

• Klíčová slova
• těžké astma,
• MeSH
• biologická terapie MeSH
• bronchiální astma * farmakoterapie   MeSH
• lidé MeSH
• monoklonální protilátky farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) patients is correlated with the efficacy of immune checkpoint blockade therapy (ICB) targeting programmed cell death ligand 1 (PD-L1) or its cognate receptor (PD-1) on cancer cells or infiltrating immune cells. Analysis of PD-L1/PD-1 expression in tumor tissue represents a crucial step before PD-L1/PD-1 blocker usage. METHODS: We used directed evolution of protein variants derived from a 13 kDa Myomedin loop-type combinatorial library with 12 randomized amino acid residues to select high-affinity binders of human PD-L1 (hPD-L1). After the ribosome display, individual clones were screened by ELISA. Detailed analysis of binding affinity and kinetics was performed using LigandTracer. The specificity of Myomedins was assessed using fluorescent microscopy on HEK293T-transfected cells and cultured cancer cells in vitro, formalin-fixed paraffin-embedded (FFPE) sections of human tonsils, and FFPE tumor samples of NSCLC patients. RESULTS: Seven identified PD-L1 binders, called MLE, showed positive staining for hPD-L1 on transfected HEK293T cells and cultured MCF-7 cells. MLE031, MLE105, MLE249, and MLE309 exhibited high affinity to both human and mouse PD-L1-transfected HEK293T cells measured with LigandTracer. The diagnostic potential of MLE variants was tested on human tonsillitis tissue and compared with diagnostic anti-PD-L1 antibody DAKO 28-8 and PD-L1 IHC 22C3 pharmDx antibody. MLE249 and MLE309 exhibited an excellent overlap with diagnostic DAKO 28-8 (Pearson ́s coefficient (r) = 0.836 and 0.731, respectively) on human tonsils on which MLE309 exhibited also excellent overlap with diagnostic 22C3 antibody (r = 0.876). Using three NSCLC tissues, MLE249 staining overlaps with 28-8 antibody (r = 0.455-0.883), and MLE309 exhibited overlap with 22C3 antibody (r = 0.534-0.619). Three MLE proteins fused with Fc fragments of rabbit IgG, MLE249-rFc, MLE309-rFc and MLE031-rFc, exhibited very good overlap with anti-PD-L1 antibody 28-8 on tonsil tissue (r = 0.691, 0.610, and 0.667, respectively). Finally, MLE249-rFc, MLE309-rFc and MLE031-rFc exhibited higher sensitivity in comparison to IHC 22C3 antibody using routine immunohistochemistry staining system Ventana, which is one of gold standards for PD-L1 diagnosis. CONCLUSIONS: We demonstrated the development of MLE Myomedins specifically recognizing hPD-L1 that may serve as a refinement tool for clinical PD-L1 detection.

• MeSH
• antigeny CD274 * metabolismus   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory plic * diagnóza   metabolismus   patologie   MeSH
• nemalobuněčný karcinom plic * diagnóza   metabolismus   patologie   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

IMPORTANCE: Progression independent of relapse activity (PIRA) is a significant contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (MS). Prior studies have used varying PIRA definitions, hampering the comparability of study results. OBJECTIVE: To compare various definitions of PIRA. DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved a retrospective analysis of prospectively collected data from the MSBase registry from July 2004 to July 2023. The participants were patients with MS from 186 centers across 43 countries who had clinically definite relapsing-remitting MS, a complete minimal dataset, and 3 or more documented Expanded Disability Status Scale (EDSS) assessments. EXPOSURE: Three-hundred sixty definitions of PIRA as combinations of the following criteria: baseline disability (fixed baseline with re-baselining after PIRA, or plus re-baselining after relapses, or plus re-baselining after improvements), minimum confirmation period (6, 12, or 24 months), confirmation magnitude (EDSS score at/above worsening score or at/above threshold compared with baseline), freedom from relapse at EDSS score worsening (90 days prior, 90 days prior and 30 days after, 180 days prior and after, since previous EDSS assessment, or since baseline), and freedom from relapse at confirmation (30 days prior, 90 days prior, 30 days before and after, or between worsening and confirmation). MAIN OUTCOME AND MEASURE: For each definition, we quantified PIRA incidence and persistence (ie, absence of a 3-month confirmed EDSS improvement over ≥5 years). RESULTS: Among 87 239 patients with MS, 33 303 patients fulfilled the inclusion criteria; 24 152 (72.5%) were female and 9151 (27.5%) were male. At the first visits, the mean (SD) age was 36.4 (10.9) years; 28 052 patients (84.2%) had relapsing-remitting MS, and the median (IQR) EDSS score was 2.0 (1.0-3.0). Participants had a mean (SD) 15.1 (11.9) visits over 8.9 (5.2) years. PIRA incidence ranged from 0.141 to 0.658 events per decade and persistence from 0.753 to 0.919, depending on the definition. In particular, the baseline and confirmation period influenced PIRA detection. The following definition yielded balanced incidence and persistence: a significant disability worsening compared with a baseline (reset after each PIRA event, relapse, and EDSS score improvement), in absence of relapses since the last EDSS assessment, confirmed with EDSS scores (not preceded by relapses within 30 days) that remained above the worsening threshold for at least 12 months. CONCLUSION AND RELEVANCE: Incidence and persistence of PIRA are determined by the definition used. The proposed standardized definition aims to enhance comparability among studies.

• MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• posuzování pracovní neschopnosti MeSH
• progrese nemoci * MeSH
• recidiva MeSH
• registrace MeSH
• relabující-remitující roztroušená skleróza * diagnóza   patofyziologie   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, a well-established event in prostate carcinogenesis. This study investigates whether LPL deletion represents a biologically relevant event or occurs merely as a bystander to NKX3.1 loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed LPL deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of NKX3.1 and LPL in 54 patients. Notably, NKX3.1 loss without accompanying LPL deletion was observed in eight additional cases. These findings suggest that LPL deletion is a passenger event secondary to NKX3.1 loss and underscore the importance of cautious interpretation of cytogenetic findings involving the LPL locus.

• MeSH
• delece genu * MeSH
• homeodoménové proteiny * genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty * genetika   patologie   metabolismus   MeSH
• progrese nemoci MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• transkripční faktory * genetika   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• fixní ortodontický aparát * MeSH
• fotografie zubní metody   MeSH
• kefalometrie metody   MeSH
• lebka růst a vývoj   MeSH
• lidé MeSH
• malokluze - Angleova II. třída * terapie   MeSH
• mladiství MeSH
• muskuloskeletální vývoj MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH