Enhancing the antimycobacterial efficacy of pyridine-4-carbohydrazide: linkage to additional antimicrobial agents oxocarboxylic acids.

This study evaluates the antimycobacterial potential of novel "mutual" bioactive amides, combining pyridine-4-carbohydrazide (isoniazid, INH) with various antimicrobial agents (sulphonamides, 4-aminosalicylic acid, thiosemicarbazide, diphenyl (thio)ethers) oxocarboxylic acids. The aim was to enhance activity against both drug-susceptible and multidrug-resistant (MDR) and non-tuberculous strains, while overcoming drug resistance through dual-action mechanisms. Many derivatives exhibited potent antimycobacterial activity, with minimum inhibitory concentrations (MICs) as low as ≤0.

Novel pyrimidine-1,3,4-oxadiazole hybrids and their precursors as potential antimycobacterial agents.

Molecular hybridization and isostery are proven approaches in medicinal chemistry, and as such we used them to design novel compounds that we investigated as potential antimycobacterials to combat drug-resistant strains. Prepared -alkyl-2-(pyrimidine-5-carbonyl)hydrazine-1-carboxamides were cyclized to -alkyl-5-(pyrimidin-5-yl)-1,3,4-oxadiazol-2-amines along with their analogues. A total of 48 compounds were tested against  HRv, and , with oxadiazoles and C-C alkyls being the most effective from a concentration of 2 μM.

Improving the antimicrobial activity of old antibacterial drug mafenide: Schiff bases and their bioactivity targeting resistant pathogens.

Increasing rates of acquired resistance have justified the critical need for novel antimicrobial drugs. One viable concept is the modification of known drugs. 21 mafenide-based compounds were prepared via condensation reactions and screened for antimicrobial efficacy, which demonstrated promising activity against both Gram-positive and Gram-negative pathogens, pathogenic fungi and mycobacterial strains (minimum inhibitory concentrations from 3.

Epidemiology of dengue, chikungunya and Zika virus infections in travellers: A 16-year retrospective descriptive study at a tertiary care centre in Prague, Czech Republic.

Introduction: This study aims to describe the epidemiological characteristics of imported cases of dengue (DEN), chikungunya (CHIK), and Zika virus (ZIKV) infections in Czech travellers.

Materials And Methods: This single-centre descriptive study has retrospectively analysed data of patients with laboratory confirmed DEN, CHIK, and ZIKV infections diagnosed at the Department of Infectious, Parasitic and Tropical Diseases of the University Hospital Bulovka in Prague, Czech Republic from 2004 to 2019.

Results: The study included a total of 313 patients with DEN, 30 with CHIK, and 19 with ZIKV infections.

Synthesis and Antimycobacterial Activity of Isoniazid Derivatives Tethered with Aliphatic Amines.

Background: There is an urgent need for new antitubercular compounds. Modification of antimycobacterial isonicotinohydrazide at hydrazide N2 provided antimycobacterial active compounds.

Objective: Combining this scaffold with various aliphatic amines that are also frequently present in antitubercular compounds, we have designed, synthesized, and evaluated twenty-three N- (cyclo)alkyl-2-(2-isonicotinoylhydrazineylidene)propanamides and their analogues as potential antimycobacterial compounds.

Substituted N-phenylitaconamides as inhibitors of mycobacteria and mycobacterial isocitrate lyase.

Novel antimycobacterial drugs are needed, especially those with dual activity against both actively growing and non-replicating subpopulations of mycobacteria. Isocitrate lyase (ICL) is one of proposed targets and this enzyme is inhibited by itaconic acid. That is why we have designed and prepared sixteen amides of itaconic acid and various anilines and amine antimicrobial drugs to evaluate them as potential inhibitors of ICL and antimycobacterial agents.

Self-Reported Mental Health and Lifestyle Behaviour During the COVID-19 Pandemic in the Czech Population: Evidence From Two Cross-Sectional Surveys.

Evidence of the impact of COVID-19 pandemic on mental and physical health behaviours is limited. This study presents results of two cross-sectional surveys on mental health changes and its consequences on healthy and unhealthy lifestyle behaviours. An online survey was distributed during Spring 2020 ( = 9,168) and Autumn 2020 ( = 1,042) in the Czech Republic.

Combined Use of Presepsin and (1,3)-β-D-glucan as Biomarkers for Diagnosing Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients.

New biomarker panel was developed and validated on 165 critically ill adult patients to enable a more accurate invasive candidiasis (IC) diagnosis. Serum levels of the panfungal biomarker (1,3)-β-D-glucan (BDG) and the inflammatory biomarkers C-reactive protein, presepsin (PSEP), and procalcitonin (PCT) were correlated with culture-confirmed candidemia or bacteremia in 58 and 107 patients, respectively. The diagnostic utility was evaluated in sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Design and Synthesis of Highly Active Antimycobacterial Mutual Esters of 2-(2-Isonicotinoylhydrazineylidene)propanoic Acid.

The combination of two active scaffolds into one molecule represents a proven approach in drug design to overcome microbial drug resistance. We designed and synthesized more lipophilic esters of 2-(2-isonicotinoylhydrazineylidene)propanoic acid, obtained from antitubercular drug isoniazid, with various alcohols, phenols and thiols, including several drugs, using carbodiimide-mediated coupling. Nineteen new esters were evaluated as potential antimycobacterial agents against drug-sensitive (.

Evaluation of Fine and Ultrafine Particles Proportion in Airborne Dust in an Industrial Area.

The health impacts of suspended particulate matter (SPM) are significantly associated with size-the smaller the aerosol particles, the stronger the biological effect. Quantitative evaluation of fine and ultrafine particles (FP and UFP) is, therefore, an integral part of ongoing epidemiological studies. The mass concentrations of SPM fractions (especially PM, PM, PM) were measured in an industrial area using cascade personal samplers and a gravimetric method, and their mass ratio was determined.

Design and synthesis of 2-(2-isonicotinoylhydrazineylidene)propanamides as InhA inhibitors with high antitubercular activity.

Based on successful antitubercular isoniazid scaffold we have designed its "mee-too" analogues by a combination of this drug linked with substituted anilines through pyruvic acid as a bridge. Lipophilicity important for passive diffusion through impenetrable mycobacterial cell wall was increased by halogen substitution on the aniline. We prepared twenty new 2-(2-isonicotinoylhydrazineylidene)propanamides that were assayed against susceptible Mycobacterium tuberculosis HRv, nontuberculous mycobacteria, and also multidrug-resistant tuberculous strains (MDR-TB).

Comparison of lung cancer risk in black-coal miners based on mortality and incidence.

Background: Cancer risk (especially as regards lung cancer) in black-coal miners is mainly analyzed on the basis of mortality. The risk calculated based on mortality may differ from the values based on incidence. The aim of the study was to compare cancer risk in black-coal miners with and without coal workers' pneumoconiosis (CWP), based on data on mortality and the incidence of lung cancer in the Czech Republic in 1992-2013.

-Alkyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides and Their Analogues: Synthesis and Multitarget Biological Activity.

Based on the isosterism concept, we have designed and synthesized homologous -alkyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamides (from C to C) as potential antimicrobial agents and enzyme inhibitors. They were obtained from 4-(trifluoromethyl)benzohydrazide by three synthetic approaches and characterized by spectral methods. The derivatives were screened for their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) via Ellman's method.

4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents.

4-aminobenzoic acid (PABA), an essential nutrient for many human pathogens, but dispensable for humans, and its derivatives have exhibited various biological activities. In this study, we combined two pharmacophores using a molecular hybridization approach: this vitamin-like molecule and various aromatic aldehydes, including salicylaldehydes and 5-nitrofurfural, via imine bond in one-step reaction. Resulting Schiff bases were screened as potential antimicrobial and cytotoxic agents.

Phenolic N-monosubstituted carbamates: Antitubercular and toxicity evaluation of multi-targeting compounds.

The research of novel antimycobacterial drugs represents a cutting-edge topic. Thirty phenolic N-monosubstituted carbamates, derivatives of salicylanilides and 4-chlorophenol, were investigated against Mycobacterium tuberculosis HRa, HRv including multidrug- and extensively drug-resistant strains, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium aurum and Mycobacterium smegmatis as representatives of nontuberculous mycobacteria (NTM) and for their cytotoxic and cytostatic properties in HepG2 cells. Since salicylanilides are multi-targeting compounds, we determined also inhibition of mycobacterial isocitrate lyase, an enzyme involved in the maintenance of persistent tuberculous infection.

Silver/Chitosan Antimicrobial Nanocomposites Coating for Medical Devices: Comparison of Nanofiller Effect Prepared via Chemical Reduction and Biosynthesis.

Medical devices have an essential part in healthcare system in recent years, such as usage of heart valves, several types of stents and implants devices in patients. However, bacterial infection of medical devices causes critical issues for patients due to attachment of bacteria and formation of biofilm onto the medical devices. Therefore, finding an effective antibacterial coating to prevent biofilm formation and infection is our goal.

Polyethylene/Organo-Inorgano Vermiculites and Their Antimicrobial Properties.

Clay mineral vermiculite was treated with silver and copper nitrate solutions and samples were subsequently modified with organic compound (dodecylamine) via solid-solid melt intercalation. Prepared organo-inorgano vermiculites were used as nanofillers to the polyethylene matrix. Mixtures of polyethylene with vermiculite nanofillers, prepared by melt compounding technique, were pressed into thin plates.

Successful surgical excision of cerebral abscess caused by Fonsecaea monophora in an immunocompetent patient and review of literature.

Cerebral abscesses caused by dark-pigmented Fonsecaea fungi are rare, especially in otherwise healthy individuals. In this case report, we present a 61-year-old man from Moldova, living in the Czech Republic, who had worked as a locksmith on oil platforms in Turkmenistan, Kazakhstan, Sudan, and Iraq since 1999, and was admitted to a neurology ward for a sudden motion disorder of the right leg, dysarthria, and hypomimia. Imaging revealed presence of expansive focus around the left lateral ventricle of the brain and a pronounced peripheral edema.

Fluorescence & bioluminescence in the quest for imaging, probing & analysis of mycobacterial infections.

Mycobacterioses represent a global health problem and rapid diagnostic improvements are urgently required. Mycobacteria-specific fluorescence and bioluminescence phenomena have been found to be useful for a wide range of mycobacteria-focused research. Here, we present a critical survey of the most promising techniques in this field and the potential of new methods under investigation.

New lipophilic isoniazid derivatives and their 1,3,4-oxadiazole analogues: Synthesis, antimycobacterial activity and investigation of their mechanism of action.

The development of novel drugs is essential for the treatment of tuberculosis and other mycobacterial infections in future. A series of N-alkyl-2-isonicotinoylhydrazine-1-carboxamides was synthesized from isoniazid (INH) and then cyclized to N-alkyl-5-(pyridin-4-yl)-1,3,4-oxadiazole-2-amines. All derivatives were characterised spectroscopically.

Diagnostic value of serum galactomannan, (1,3)-β-d-glucan, and Aspergillus fumigatus-specific IgA and IgG assays for invasive pulmonary aspergillosis in non-neutropenic patients.

Detection of serum galactomannan (GM) and (1,3)-β-d-glucan (BG) is considered useful for non-culture diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Only few studies evaluated these seromarkers in non-neutropenic patients suspected of having IPA. The aim of this study was to evaluate both tests together with the Aspergillus fumigatus-specific serum IgG and IgA (IgAG) test for serological IPA diagnosis in non-neutropenic patients.

Synthesis and biological evolution of hydrazones derived from 4-(trifluoromethyl)benzohydrazide.

Reflecting the known biological activity of isoniazid-based hydrazones, seventeen hydrazones of 4-(trifluoromethyl)benzohydrazide as their bioisosters were synthesized from various benzaldehydes and aliphatic ketones. The compounds were screened for their in vitro activity against Mycobacterium tuberculosis, nontuberculous mycobacteria (M. avium, M.

Sulfadiazine Salicylaldehyde-Based Schiff Bases: Synthesis, Antimicrobial Activity and Cytotoxicity.

The resistance among microbes has brought an urgent need for new drugs. Thus, we synthesized a series of Schiff bases derived from the sulfa drug sulfadiazine and various salicylaldehydes. The resulting 4-[(2-hydroxybenzylidene)amino]--(pyrimidin-2-yl)benzene-sulfonamides were characterized and evaluated against Gram-positive and Gram-negative bacteria, yeasts, moulds, , nontuberculous mycobacteria (, ) and their cytotoxicity was determined.

Associations between air pollution in the industrial and suburban parts of Ostrava city and their use.

Selecting the locations and numbers of air quality monitoring stations is challenging as these are expensive to operate. Representative concentrations of pollutants in certain areas are usually determined by measuring. If there are significant correlations with concentrations of other pollutants or with other monitoring sites, however, concentrations could also be computed, partly reducing the costs.