Antibacterial and anti-biofilm activities of new fluoroquinolone derivatives coupled with nitrogen-based heterocycles.

We report the design, synthesis, and antimicrobial evaluation of a series of ciprofloxacin (CP) conjugates coupled with nitrogen-containing heterocycles. In vitro screening of these new hybrid compounds (1-13) against a panel of planktonic bacterial strains highlighted thiazolyl homologs 6 and 7 as the most promising candidates for further investigation. These derivatives demonstrated potent growth-inhibitory activity against various standard and clinical isolates, with minimum inhibitory concentrations (MICs) ranging from 0.05 to 0.4 µg/ml, which are higher or comparable to the reference fluoroquinolone. Both compounds effectively inhibited biofilm formation by selected staphylococci across all tested concentrations (1-8 x MIC), displaying greater efficacy at higher doses compared to CP alone. Notably, conjugate 7 also significantly eradicated existing biofilms formed by S. aureus of various origin. Molecular docking studies revealed that conjugate 7 engages in a broader range of interactions with DNA gyrase and DNA topoisomerase IV than CP, suggesting stronger binding affinity and enhanced flexibility. This may contribute to its potential in overcoming bacterial resistance mechanisms. The above findings indicate compound 7 as a promising candidate for clinical development.

Infections caused by Slackia exigua: A single-center experience and literature review. / Infekcje wywolane przez Slackia exigua. Przeglad literatury i obserwacje wlasne.

Slackia exigua, originally classified as Eubacterium exiguum, is a Gram-positive, asaccharolytic, rod-shaped anaerobic bacterium. The virulence factors of S. exigua have not been accurately identified. The objective of the study is to evaluate the pathogenic potential of S. exigua by presenting the cases of infections diagnosed at our hospital laboratory. Additionally, we reviewed the literature to summarize the experience with S. exigua infections to clarify, in the light of current knowledge, the clinical picture, diagnostic, and therapeutic issues related to this anaerobic bacterium. We reported eleven severe human infections caused by S. exigua. All patients required hospitalization. Nine of the cases involved chronic infections in the stomatognathic system, in two patients, skin infections were diagnosed. As it is known, S. exigua is a component of the human microbiota; however, it can cause opportunistic infections, particularly in the case of translocation outside its natural habitat. A critical literature analysis revealed that S. exigua can be responsible for bacteremia, meningitis, tissue necrosis, periprosthetic joint infection, and osteomyelitis. Several studies have been published regarding the determination of drug susceptibility of S. exigua. The isolated strains were susceptible to most antibiotics used for the treatment of anaerobic infections. The interpretation of antimicrobial susceptibility testing for some slow-growing in vitro, infrequently causing infections anaerobic bacteria, such as S. exigua, is based on The European Committee on Antimicrobial Susceptibility Testing (EUCAST) additional guidance taking into account the determination of drug susceptibility for groups of microorganisms for which cut-off values have not been developed.

Focus on Pneumonia After Organ Transplantation: Is There a Need for Specific Medical Care in the Emergency Department?

BACKGROUND: Pneumonia is a major cause of hospitalization and has a substantial impact on health care costs. Diagnosis and treatment of pneumonia in solid organ transplant (SOT) patients remain a challenge for clinicians in the emergency department. This study aimed to evaluate demographic features, clinical patterns, history of hospitalization, and diagnosis of adult patients after organ(s) transplantation (liver, kidney, pancreas) with severe pneumonia requiring hospitalization. The aim is to determine whether patients undergoing SOT receive or require specific care and whether they need to be prioritized. METHOD: This was a single-center observational study of adult patients after SOT with severe pneumonia requiring hospitalization. The data set for the analysis included only patients with pneumonia as the main reason for hospitalization. The diagnosis of pneumonia was suspected based on the American Thoracic Society criteria. RESULTS: The study revealed that the standard of care for patients with a history of SOT did not significantly differ from care provided to the non-SOT patients with pneumonia admitted to the same hospital during a 94-week period. CONCLUSION: There were notable differences, such as post-transplant patients being transferred more quickly to the hospital ward, having longer hospital stays, and receiving antibiotics earlier than the non-SOT group.

Secreted novel AID/APOBEC-like deaminase 1 (SNAD1) - a new important player in fish immunology.

The AID/APOBECs are a group of zinc-dependent cytidine deaminases that catalyse the deamination of bases in nucleic acids, resulting in a cytidine to uridine transition. Secreted novel AID/APOBEC-like deaminases (SNADs), characterized by the presence of a signal peptide are unique among all of intracellular classical AID/APOBECs, which are the central part of antibody diversity and antiviral defense. To date, there is no available knowledge on SNADs including protein characterization, biochemical characteristics and catalytic activity. We used various in silico approaches to define the phylogeny of SNADs, their common structural features, and their potential structural variations in fish species. Our analysis provides strong evidence of the universal presence of SNAD1 proteins/transcripts in fish, in which expression commences after hatching and is highest in anatomical organs linked to the immune system. Moreover, we searched published fish data and identified previously, "uncharacterized proteins" and transcripts as SNAD1 sequences. Our review into immunological research suggests SNAD1 role in immune response to infection or immunization, and interactions with the intestinal microbiota. We also noted SNAD1 association with temperature acclimation, environmental pollution and sex-based expression differences, with females showing higher level. To validate in silico predictions we performed expression studies of several SNAD1 gene variants in carp, which revealed distinct patterns of responses under different conditions. Dual sensitivity to environmental and pathogenic stress highlights its importance in the fish and potentially enhancing thermotolerance and immune defense. Revealing the biological roles of SNADs represents an exciting new area of research related to the role of DNA and/or RNA editing in fish biology.

The use of SNP markers for cattle breed identification.

A potential application of single nucleotide polymorphisms (SNPs) in animal husbandry and production is identification of the animal breed. In this study, using chosen marker selection methods and genotypic data obtained with the use of Illumina Bovine SNP50 BeadChip for individuals belonging to ten cattle breeds, the reduced panels containing the most informative SNP markers were developed. The suitability of selected SNP panels for the effective and reliable assignment of the studied individuals to the breed of origin was checked by three allocation algorithms implemented in GeneClass 2. The studied breeds set included both Polish-native breeds under the genetic resources conservation programs and highly productive breeds with a global range. For all of the tested marker selection methods ("delta" and two FST-based variants), two separate methodological approaches of marker assortment were used and three marker panels were created with 96, 192, and 288 SNPs respectively, to determine the minimum number of markers required for effective differentiation of the studied breeds. Moreover, the usefulness of the most effective panels of markers to assess the population structure and genetic diversity of the analyzed breeds was examined. The conducted analyses showed the possibility of using SNP subsets from medium-density genotypic microarrays to distinguish breeds of cattle kept in Poland and to analyze their genetic structure.

Ulcerated skin evaluation by electrical impedance measurements.

In the presented study, the transdermal results from the areas surrounding the ulcerated skin areas were compared with those obtained from healthy skin tissue. The analysis of electrical parameters, such as the slope of the Nyquist plot, min. IM, min. RE, min. f, Imagine part index, Phase index, Real part index, and Magnitude index were conducted. Electrical parameters have been measured in the group without lower leg ulceration and in the group with lower leg ulcers. On the basis of the statistical analysis, it was determined that these parameters may be effective in the evaluation of the skin. In fact, the skin surrounding the ulceration was characterised by different values of electrical parameters as compared with healthy skin tissue. A statistically significant difference was found in the electrical parameters obtained for the healthy leg skin and the skin surrounding the ulceration. This study was to investigate the applicability of electrical parameters in the evaluation of the skin in lower leg ulcers. The electrical parameters can be used as an effective tool in assessing the condition of the skin, both healthy and surrounding the ulcerations. The most useful parameters in assessing skin condition using electrical parameters include min. IM, min. RE, min. f, Imagine part index, Phase index, and Magnitude index.

Phenotypic and genotypic identification of carbapenem resistance in Bacteroides fragilis clinical strains.

Bacteroides fragilis is an important etiological agent of serious infections in humans. Rapid methods, readily adaptable to use in medical laboratories, are needed to detect antibiotic resistance and decrease the likelihood of therapy failure. The aim of this study was to determine the prevalence of B. fragilis cfiA-positive isolates. The second purpose was to investigate the carbapenemase activity in B. fragilis strains by Carba NP test. In the study, 5.2% of B. fragilis isolates are phenotypically resistant to meropenem. The cfiA gene was identified in 6.1% of B. fragilis isolates. The MICs of meropenem were significantly higher in cfiA-positive strains. The presence of the cfiA gene along with the IS1186 was detected in one B. fragilis strain which was resistant to meropenem (MIC 1.5 mg/L). The Carba NP test results were positive for all the cfiA-positive strains, including those susceptible to carbapenems based on their MIC values. A review of the literature revealed that the rate of B. fragilis with the cfiA gene varies from 7.6 to 38.9% worldwide. Presented results are in line with the other European studies. Phenotypic testing with the Carba NP test, it seems to be a viable alternative for the cfiA gene detection in B. fragilis isolates. The positive result obtained is of greater clinical importance than the detection of the gene cfiA.

New insights into posttranslational modifications of proteins during bull sperm capacitation.

BACKGROUND: Due to the unique nature of spermatozoa, which are transcriptionally and translationally silent, the regulation of capacitation is based on the formation of posttranslational modifications of proteins (PTMs). However, the interactions between different types of PTMs during the capacitation remain unclear. Therefore, we aimed to unravel the PTM-based regulation of sperm capacitation by considering the relationship between tyrosine phosphorylation and reversible oxidative PTMs (oxPTMs), i.e., S-nitrosylation and S-glutathionylation. Since reversible oxPTMs may be closely related to peroxyredoxin (PRDX) activity, the second aim was to verify the role of PRDXs in the PTM-based regulation of capacitation. METHODS: Cryopreserved bull sperm were capacitated in vitro with or without PRDX inhibitor. Qualitative parameters of sperm and symptoms characteristic of capacitation were analyzed. Posttranslational protein modifications (S-nitrosylation, S-glutathionylation, tyrosine phosphorylation) were investigated at the cellular level (flow cytometry, fluorescence microscopy) and at the proteomic level (fluorescent gel-based proteomic approach). RESULTS: Zona-pellucida binding proteins (ACRBP, SPAM1, ZAN, ZPBP1 and IZUMO4) were particularly rich in reversible oxPTMs. Moreover, numerous flagellar proteins were associated with all analyzed types of PTMs, which indicates that the direction of posttranslational modifications was integrated. Inhibition of PRDX activity during capacitation caused an increase in S-nitrosylation and S-glutathionylation and a decrease in tyrosine phosphorylation. Inhibition of PRDXs caused GAPDHS to undergo S-glutathionylation and the GSTO2 and SOD2 enzymes to undergo denitrosylation. Moreover, PRDX inhibition caused the AKAP proteins to be dephosphorylated. CONCLUSIONS: Our research provides evidence that crosstalk occurs between tyrosine phosphorylation and reversible oxPTMs during bull sperm capacitation. This study demonstrates that capacitation triggers S-nitrosylation and S-glutathionylation (and reverse reactions) of zona-pellucida binding proteins, which may be a new important mechanism that determines the interaction between sperms and oocytes. Moreover, TCA-related and flagellar proteins, which are particularly rich in PTMs, may play a key role in sperm capacitation. We propose that the deglutathionylation of ODFs and IZUMO4 proteins is a new hallmark of bull sperm capacitation. The obtained results indicate a relationship between PRDX activity and protein phosphorylation, S-glutathionylation and S-nitrosylation. The activity of PRDXs may be crucial for maintaining redox balance and for providing proper PKA-mediated protein phosphorylation during capacitation. Video Abstract.

Can Assessment of Rheological Properties of Whole Blood and Plasma Be Useful in the Diagnosis of Tinnitus? A Pilot Study.

Tinnitus is a sensation of ringing in the ears in the absence of any physical source in the environment. Between 9-35% of adults experience some form of tinnitus. Common causes of tinnitus include noise, head injury, ototoxic substances, as well as disorders of blood and blood vessels. Vascular causes include: head-neck tumours, turbulent blood flow, problems with blood supply and inner ear cell damage. The aspect of rheology in terms of tinnitus has not been described yet. In the present study, which comprised 12 patients aged 30 to 74 years presenting with tinnitus, rheological properties of whole blood and plasma were assessed. All the subjects underwent audiological and neurological evaluation. The Quemada model was used to describe the variability of red blood cell shape, as well as their tendency to form aggregates. On the basis of the experimental study, statistically different results of haemorheological measurements were observed in the evaluated group in comparison to a reference group.

Body Balance Analysis in the Visually Impaired Individuals Aged 18-24 Years.

BACKGROUND: Proper body balance is maintained by both sensory, i.e., vision, hearing, vestibular, and proprioception, and motor nervous systems. Visual control facilitates balance both in a static position, as well as during movement. Visual dysfunctions can adversely affect balance and stability control. METHODS: The study comprised a group of 30 individuals visually impaired from birth aged 18-24 years. The control group consisted of 50 persons in the same age range as the study group. The trial was performed as four separate tests: two on a stable surface platform, and two on an unstable surface platform. RESULTS: No statistically significant differences were found in the posturography test on the stable platform between the study groups. When tested on an unstable ground surface, the visually impaired subjects obtained showed worse performance than the sighted persons. Statistically significant differences were observed in the majority of the analyzed results. CONCLUSIONS: Visually impaired individuals present a poorer ability to maintain balance under dynamic conditions. Tests conducted on the unstable surface platform seem to be more relevant and applicable in the diagnosis of the subjects with visual impairment, as they differentiate the subjects to a greater extent.

Evolution of Influenza Viruses-Drug Resistance, Treatment Options, and Prospects.

Viral evolution refers to the genetic changes that a virus accumulates during its lifetime which can arise from adaptations in response to environmental changes or the immune response of the host. Influenza A virus is one of the most rapidly evolving microorganisms. Its genetic instability may lead to large changes in its biological properties, including changes in virulence, adaptation to new hosts, and even the emergence of infectious diseases with a previously unknown clinical course. Genetic variability makes it difficult to implement effective prophylactic programs, such as vaccinations, and may be responsible for resistance to antiviral drugs. The aim of the review was to describe the consequences of the variability of influenza viruses, mutations, and recombination, which allow viruses to overcome species barriers, causing epidemics and pandemics. Another consequence of influenza virus evolution is the risk of the resistance to antiviral drugs. Thus far, one class of drugs, M2 protein inhibitors, has been excluded from use because of mutations in strains isolated in many regions of the world from humans and animals. Therefore, the effectiveness of anti-influenza drugs should be continuously monitored in reference centers representing particular regions of the world as a part of epidemiological surveillance.

Venous leg ulcers treated with fish collagen gel in a 12-week randomized single-centre study.

Introduction: Venous ulcers are difficult to heal chronic wounds. Most challenging are the non-healing and recurrent ulcers, because of which we are seeking for therapies that stimulate and support their healing. Aim: To assess the efficacy of fish collagen and its impact on the process of healing of venous leg ulcers. Material and methods: This 12-week randomized single-centre study included a total of 97 adults with venous leg ulcer, randomized into two groups: the study group (n = 48) and the control group (n = 49). All patients received specialist medical care including skin and limb care, wound development according to the TIME scheme (tissue debridement, infection and inflammation control, moisture balance, edge) and short-stretch bandage compression (compression class II). In addition, the study group received tropocollagen gel applied to the skin around the wound. Every 2 weeks we evaluated the wound surface and temperature distribution on the shin (average temperature, median, minimum and maximum) - symmetrically on the sick and healthy limb. Results: We observed a greater number of complete ulcer healing in the study group (week 12: 29.2% vs. 22.4%; week 24: 52.1% vs. 36.7%). Faster healing time in the study group was observed in both big and small ulcers. The thermographic analysis showed statistically significant reduction in periwound inflammation among patients from the study group (p < 0.05). Statistically significant reduction in mean as well as maximum values of limb temperature occurred only in the study group (Tx: R = 0.37, p < 0.001; Tmax: R = 0.40, p < 0.001). Conclusions: Thermographic analysis showed better wound healing effects in the group using tropocollagen. Significant impact of collagen on the healing process was observed only after 8 weeks of application.

The effects of acoustic and optokinetic stimulus on the postural stability.

Objectives: This article addresses the question of whether the simultaneous auditory and optokinetic stimulation affects the postural stability differently than only the stimulation with a single auditory or optokinetic stimulus. Methods: The study involved 30 volunteers. The postural stability was evaluated by means of the posturography platform, which allows for both stable and dynamic posturography tests as well as for applying optokinetic stimulus. Three series of measurements were performed in each patient: measurements on an only with the optokinetic stimulus, measurements using only the acoustic stimulus, and finally measurements with both stimuli applied simultaneously. Results: The results indicate that there are statistically significant differences in the findings obtained with the simultaneous auditory and visual stimulation and the observed results with only one of the stimuli on the dynamic platform. Hence, on the basis of the results obtained, it is possible to conclude that the acoustic stimulus has the potential to help maintain a stable posture. However, this process is not sufficiently compensated with the optokinetic stimulation alone. Conclusion: The sense of sight may be essential for the maintenance of a stable posture. The presence of a sound stimulus improves the postural stability, although this improvement does not compensate for the disturbance caused by the optokinetic stimulus. Hence, functioning of auditory and visual system can influence patients posture. Level of Evidence: 4.

Change for the Better: Severe Pneumonia at the Emergency Department.

This is a single-centre observational study of adult patients with severe pneumonia requiring hospitalization conducted at the emergency department. During the observation period (94 weeks), 398 patients were diagnosed with severe pneumonia and required further treatment at the hospital. The median age of patients was 73 years. About 65% of patients had at least one chronic comorbidity. Almost 30% of patients had cardiovascular disorders, and 13% had diabetes mellitus. The average Emergency Department length of stay was 3.56 days. The average length of hospitalization was 15.8 days. Overall, 94% of patients treated for pneumonia received a beta-lactam antibiotic. The median time from ED admission to the administration of the first dose of antimicrobial agent was less than 6 h. Microbiology test samples were obtained from 48.7% patients. Gram-positive cocci were isolated most commonly (52.9%) from blood samples. Biological material from the lower respiratory tract was collected from 8.3% of patients, and from 47.2% of positive samples, fungi were cultured. The urine samples were obtained from 35.9% patients, and Gram-negative rods (76%) were isolated most commonly. Overall, 16.1% of patients died during the hospitalization. The mean age of patients who died was 79 years. This observational study is the first single-centre study conducted as part of the Polish Emergency Department Research Organization (PEDRO) project. It aims to provide up-to-date information about patients with pneumonia in order to improve medical care and develop local diagnostic and therapeutic recommendations.

Effect of Raw Chickpea in the Broiler Chicken Diet on Intestinal Histomorphology and Intestinal Microbial Populations.

The aim of the study was to determine the effect of partial replacement of SBM protein with CPR-derived protein in the broiler rearing period from 22 to 42 days of age on the intestinal histomorphology and the composition of the intestinal microbial population. Male broiler chicks aged 1 day were assigned to two groups with different nutrition schemes (n = 100 in each, 5 cages of 20 chicks in each). The chickens were reared for 42 days. All birds were fed isonitrogenous and isoenergetic diets: starter (1 to 21 d), grower (22 to 35 d), and finisher (36 to 42 d). From rearing day 22, different diets were provided to the birds: the SBM group received feed with 100% soybean meal protein, and the diet of the CPR group the protein originated from soybean meal was replaced by 50% chickpea protein. The study results indicated a significant impact of the inclusion of CPR in the diet on the basic intestinal structures (thickness of myenteron: submucosa, jejunum and duodenum mucosa, and jejunum transversal lamina). The addition of CPR led to shortening of intestinal villi, an increase in villus thickness, and reduced intestine absorptive surface in the duodenum and jejunum. The CPR group exhibited a significantly lower villus length-to-crypt depth ratio in the jejunum (p < 0.001). The inclusion of chickpeas in the diet increased the total count of mesophilic bacteria and coliforms in the intestinal contents (p < 0.05). In summary, it has been demonstrated that the inclusion of CPR in the diet induced considerable disturbances in metabolism and intestinal structure. Although CPR is a cheap protein source, its use in poultry diet does not ensure development of the intestinal structure comparable to that in the case of an SBM-only diet.

Application of two-dimensional difference gel electrophoresis to identify protein changes between center, margin, and adjacent non-tumor tissues obtained from non-small-cell lung cancer with adenocarcinoma or squamous cell carcinoma subtype.

Lung cancer is responsible for the most cancer-related mortality worldwide and the mechanism of its development is poorly understood. Proteomics has become a powerful tool offering vital knowledge related to cancer development. Using a two-dimensional difference gel electrophoresis (2D-DIGE) approach, we sought to compare tissue samples from non-small-cell lung cancer (NSCLC) patients taken from the tumor center and tumor margin. Two subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were compared. Data are available via ProteomeXchange with identifier PXD032736 and PXD032962 for ADC and SCC, respectively. For ADC proteins, 26 significant canonical pathways were identified, including Rho signaling pathways, a semaphorin neuronal repulsive signaling pathway, and epithelial adherens junction signaling. For SCC proteins, nine significant canonical pathways were identified, including hypoxia-inducible factor-1α signaling, thyroid hormone biosynthesis, and phagosome maturation. Proteins differentiating the tumor center and tumor margin were linked to cancer invasion and progression, including cell migration, adhesion and invasion, cytoskeletal structure, protein folding, anaerobic metabolism, tumor angiogenesis, EMC transition, epithelial adherens junctions, and inflammatory responses. In conclusion, we identified several proteins that are important for the better characterization of tumor development and molecular specificity of both lung cancer subtypes. We also identified proteins that may be important as biomarkers and/or targets for anticancer therapy.

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

Herpes simplex virus types 1 and 2 HSV1 and 2, namely varicella-zoster VZV and cytomegalovirus CMV, are among the most common pathogens worldwide. They remain in the host body for life. The course of infection with these viruses is often asymptomatic or mild and self-limiting, but in immunocompromised patients, such as solid organ or bone marrow transplant recipients, the course can be very severe or even life-threatening. Unfortunately, in the latter group, the highest percentage of infections with strains resistant to routinely used drugs is observed. On the other hand, frequent recurrences of genital herpes can be a problem even in people with normal immunity. Genital herpes also increases the risk of acquiring sexually transmitted diseases, including HIV infection and, if present in pregnant women, poses a risk to the fetus and newborn. Even more frequently than herpes simplex, congenital infections can be caused by cytomegalovirus. We present the most important anti-herpesviral agents, the mechanisms of resistance to these drugs, and the associated mutations in the viral genome. Special emphasis was placed on newly introduced drugs such as maribavir and brincidofovir. We also briefly discuss the most promising substances in preclinical testing as well as immunotherapy options and vaccines currently in use and under investigation.

Knowledge, Attitude and Practice Regarding Staphylococcus pettenkoferi.

Staphylococcus pettenkoferi is a coagulase-negative staphylococcus, first described in 2002. Using medical databases, i.e., Scopus, Web of Science, Pubmed, and Embase, we identified and analysed research, reports, and opinions dealing with S. pettenkoferi. Published data allow us to conclude that S. pettenkoferi is a human commensal, opportunistic bacterium and may be isolated from the environment and animals. The involvement of S. pettenkoferi in bloodstream infection and osteomyelitis has been described, but its clinical relevance is not fully understood, so far. This work summarizes knowledge about S. pettenkoferi and reveals the difficulties and rules for interpreting the results of microbiological tests, when S. pettenkoferi has been identified in the blood sample. Clinical and laboratory criteria, recommended by Centers for Disease Control and Prevention (CDC) and the third international consensus definitions of sepsis and septic shock (Sepsis-3), are important to determine whether the presence of bacteria in the sample is a consequence of an infection, contamination from the environment, or translocation of the bacteria outside the place of its natural existence. The precise identification of bacteria from the blood sample and recognizing the true bacteraemia are critical to implement the appropriate procedures and make decisions concerning the patient's medical care.

Favipiravir in the Battle with Respiratory Viruses.

Among antiviral drugs, the vast majority targets only one or two related viruses. The conventional model, one virus - one drug, significantly limits therapeutic options. Therefore, in the strategy of controlling viral infections, there is a necessity to develop compounds with pleiotropic effects. Favipiravir (FPV) emerged as a strong candidate to become such a drug. The aim of the study is to present up-to-date information on the role of favipiravir in the treatment of viral respiratory infections. The anti-influenza activity of favipiravir has been confirmed in cell culture experiments, animal models, and clinical trials. Thoroughly different - from the previously registered drugs - mechanism of action suggests that FVP can be used as a countermeasure for the novel or re-emerging influenza virus infections. In recent months, favipiravir has been broadly investigated due to its potential efficacy in the treatment of COVID-19. Based on preclinical and clinical studies and a recently published meta-analysis it seems that favipiravir may be a promising antiviral drug in the treatment of patients with COVID-19. FPV is also effective against other RNA respiratory viruses and may be a candidate for the treatment of serious infections caused by human rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza viruses and hantavirus pulmonary syndrome.

Pandemic resilient cities: Possibilities of repairing Polish towns and cities during COVID-19 pandemic.

Cities, due to population density and the complexity of human interactions, experience specific problems arising from their functioning in the era of the Covid-19 pandemic. Many scientists who publish their findings in contemporary literature agree on the need to shape pandemic resilient cities by making changes to the functional-spatial structure and preparing cities for rapid revitalization [regeneration] in the post-pandemic period. The main objective of the research is to identify the most important problems regarding service infrastructure deficiencies in the nine medium-sized Polish cities selected for research located in the Warsaw agglomeration, which are well connected with Warsaw. The research was based on: analysis of selected GIS spatial data, demographic data from the Polish Central Statistical Office, surveys among residents, on their needs during pandemic constraints. The focus was on three important aspects of development in the era of the pandemic: access to first-need services, access to greenery and active recreation areas, accessibility and transport efficiency problems. The research revealed changes in the way people travel and do their essential shopping, inadequate cycling infrastructure and problems with the availability of essential services close to where they live. The research programme varies, although the diagnosis and the possibility of transforming the functional-spatial structure of the cities studied as typical medium-sized cities in the impact zone of a large centre dominate. The conclusions provide examples of proposals for tactical urbanism planning solutions that could rapidly improve the quality of residence in a low-budget way. Finally, the proposals and guidelines for creating sustainable pandemic resilient cities are described. The article investigates the aspect of urban resilience related to transport, services, relaxation, while using the method of tactical urbanism as a remedy for cities' pandemic problems.