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The study reports the development of a thermal imaging method suitable for the screening and differentiation of joint inflammation in the rheumatoid foot of patients in comparison with the control group of healthy participants. The study included 81 patients, with rheumatoid arthritis (RA), and 39 healthy volunteers without any signs or symptoms of inflammation. The feet joints were examined by ultrasonography, and the surface temperature of the dorsal side of the foot was measured using a thermovision camera. Significant differences in mean temperatures between the study group and the control group were found. At the same time, there were no statistically significant differences between the mean temperatures in the left and right foot in any of the designated regions in the study and control group. The comparison of average temperatures of joints with or without inflammation, according to ultrasonography, did not show significance except for two joints. Despite the lack of statistical differences in the recorded temperatures, changes in the form of spikes, hot spots, and gradation of the temperatures during screening were observed. Screening analysis of the temperature distribution of the foot can aid in the diagnosis of RA and in the evaluation of the development of the disease. Additional studies must be conducted to confirm the results of this study.

The paper addresses the issue of fungal infections in the context of growing resistance to currently available antifungal agents and the development of new antimycotics. Fungal pathogens belonging to the genuses Candida, Aspergillus, Pneumocystis and Cryptococcus account for about 90% of all fungal infections. Candida albicans infections are a global clinical problem, and systemic candidiasis is considered one of the most severe fungal infections, with mortality rates of about 40% despite treatment. Currently, there are five classes of antimycotics available, of which only three (azoles, echinocandins and polyenes) are used for systemic infections. The limited variety of available therapies as well as their overuse in both therapy and prevention have contributed to the growing resistance among fungal pathogens. Many mechanisms of resistance to antimycotics have been identified. These include in particular: mutations in genes encoding target proteins, increase or decrease in target protein, protein pump activity, biofilm formation or activation of stress response. The growing incidence of fungal infections and the difficulty of their treatment have forced the search for alternative therapeutic agents with new mechanisms of action. Due to the eukaryotic nature of fungal cells, recent trends in literature imply that novel agents should specifically target virulence factors or stress response of the pathogen.

Background. Foot problems may have a substantial negative impact on rheumatoid arthritis (RA) patients’ mobility. They affect walking and the functional capacity to perform daily tasks. Methods. This study included 61 patients with RA and foot pain or swelling. The study group comprised 37 patients (aged 54.3 ± 9.5 years) with foot lesions, as demonstrated in an ultrasound, and the control group comprised 24 patients (aged 57.3 ± 11.5 years) without foot lesions. The patients’ health statuses were evaluated with the Foot Function Index-Revised Short Form (FFI-RS), the Polish version of the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Disease Activity Score 28 (DAS 28). Results. The FFI-RS showed significant differences between the study and control groups in total results, as well as in the pain and stiffness subscales. Subsequent analyses showed numerous significant correlations. The FFI-RS total results correlated with the HAQ’s standing up, walking, and total results. The FFI-RS pain results correlated with the social issues and HAQ’s total results. The FFI-RS difficulty results correlated with the disease’s duration. In the study group, there were significant correlations of the FFI-RS stiffness, difficulty, and social issues results with the HAQ’s standing up, walking, and total results, and also of the FFI-RS activity limitation results with the HAQ’s standing up results. In the control group, there were correlations of the FFI-RS stiffness, difficulty, and activity limitation results with the HAQ’s walking and total results. Finally, in the study group, we also found correlations of the FFI-RS total, pain, stiffness, difficulty, and social issues results with the Visual Analog Scale (VAS) results, as well as of the FFI-RS total results with the DAS 28 results. Conclusions. The FFI-RS is an effective tool for assessing RA patients’ functional status and can be used to evaluate treatment effects. The FFI-RS detected RA-related changes in the foot joint function in patients without foot lesions, as assessed by ultrasound.

Since candidiasis is so difficult to eradicate with an antifungal treatment and the existing antimycotics display many limitations, hopefully new sulfone derivatives may overcome these deficiencies. It is pertinent to study new strategies such as sulfone derivatives targeting the virulence attributes of C. albicans that differentiate them from the host. During infections, the pathogenic potential of C. albicans relies on the virulence factors as follows: hydrolytic enzymes, transcriptional factors, adhesion, and development of biofilms. In the article we explored how the above-presented C. albicans fitness and virulence attributes provided a robust response to the environmental stress exerted by sulfones upon C. albicans; C. albicans fitness and virulence attributes are fungal properties whose inactivation attenuates virulence. Our understanding of how these mechanisms and factors are inhibited by sulfones has increased over the last years. As lack of toxicity is a prerequisite for medical approaches, sulfones (non-toxic as assessed in vitro and in vivo) may prove to be useful for reducing C. albicans pathogenesis in humans. The antifungal activity of sulfones dealing with these multiple virulence factors and fitness attributes is discussed.

Introduction: Increasing occurrence of fungal infections raises the need to develop novel antifungal agents. In this context, an inhibition of morphological switch may provide an alternative approach to find compounds with a potential to control the Candida albicans infections. Methods: A series of 17 sulfone and sulfanyl derivatives was synthesized and evaluated for activity against the C. albicans wild type (SC5314, ATCC) and SAP-deficient mutant strains using the broth microdilution method M27-A3. Afterwards, phase-contrast microscopy was applied to evaluate the inhibition of fungal morphogenesis under the influence of randomly selected active compounds: 1, 5 and 6. Results: By in vitro susceptibility testing of C. albicans, we identified the effective antifungal agents displaying moderate-to-good activity. Newly synthesized sulfanyl and sulfone derivatives strongly inhibited the C. albicans morphogenetic transition under the hyphae inducing conditions. Conclusions: The leading compound 6 has the potential to be used as a base structure in antifungal drug development, however further structural optimalization and toxicity studies are required.

Since our study showed that sulfone derivatives’ action mode creates a lesser risk of inducing widespread resistance among Candida spp., we continued verifying sulfones’ antifungal activity using the following newly synthesized derivatives: bromodichloromethy-4-hydrazinyl-3-nitrophenyl sulfone (S1), difluoroiodomethyl-4-hydrazinyl-3-nitrophenyl sulfone (S2), and chlorodifluoromethyl-4-hydrazinyl-3-nitrophenyl sulfone (S3). As the mechanism by which sulfones gain access to the cytoplasm has not been elucidated yet, in order to track S1-3, we coupled their hydrazine group with BODIPY (final S1-3 BODIPY-labelled were named SB1-3). This approach allowed us to follow the vital internalization and endocytic routing of SB1-3, while BODIPY interacts primarily with fungal surfaces, thus confirming that S1-3 and their counterparts SB1-2 behaved as non-typical agents by damaging the cell membrane and wall after being endocytosed (SB1-3 fluorescence visible inside the unlysed sessile cells). Thus greatly decreasing the likelihood of the appearance of strains resistance. Core sulfones S1-3 are a promising alternative not only to treat planktonic C. albicans but also biofilm-embedded cells. In the flow cytometric analysis, the planktonic cell surface was digested by S1-3, which made the externalized PS accessible to AnnexinV binding and PI input (accidental cell death ACD). The occurrence of ACD as well as apoptosis (crescent-shaped nuclei) and anoikis of sessile cells (regulated cell death by 100%-reduction in attachment to epithelium) was assessed through monitoring the AO/PI/HO342 markers. CLSM revealed the invasion of S1-3 and SB1-3 in C. albicans without inducing cell lysis. This was a novel approach in which QCM-D was used for real-time in situ detection of viscoelastic changes in the C. albicans biofilm, and its interaction with S1 as a representative of the sulfones tested. S1 (not toxic in vivo) is a potent fungicidal agent against C. albicans and could be administered to treat invasive candidiasis as a monotherapy or in combination with antifungal agents of reference to treat C. albicans infections.

Candida albicans represents an interesting microorganism to study complex host-pathogen interactions and for the development of effective antifungals. Our goal was to assess the efficacy of 4-chloro-3-nitrophenyldifluoroiodomethyl sulfone (named Sulfone) against the C. albicans infections in the Galleria mellonella host model. We assessed invasiveness of CAI4 parental strain and mutants: kex2Δ/KEX2 and kex2Δ/kex2Δ in G. mellonella treated with Sulfone. We determined that KEX2 expression was altered following Sulfone treatment in G. mellonella-C. albicans infection model. Infection with kex2Δ/kex2Δ induced decreased inflammation and minimal fault in fitness of larvae vs CAI4. Fifty percent of larvae died within 4–5 days (P value

Candida albicans CNB1 plays a role in the response in vitro and in vivo to stress generated by PB-WUT-01, namely 1,3-dimethyl-7-(2-((1-(3-(perbromo-2H-benzo[d][1,2,3]triazol-2-yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)propyl)-1H-purine-2,6(3H,7H)-dione. The antifungal mechanism involved the calcineurin pathway-regulated genes SAP9-10. Galleria mellonella treated with PB-WUT-01 (at 0.64 µg/mg) showed limited candidiasis and remained within the highest survival rates. The molecular mode of action of PB-WUT-01 was rationalized by in silico docking studies toward both human and C. albicans calcineurin A (CNA) and calcineurin B (CNB) complexes, respectively. PB-WUT-01 acting as a calcineurin inhibitor in the C. albicans cells enhances the cells’ susceptibility. Therefore it could be a suitable alternative treatment in patients with candidiasis.

The increase of opportunistic fungal infections raises the need for design and synthesis of new antifungal agents. Taking into account that tetrazole derivatives exhibit antifungal activity, and some of them are in the phase of clinical trials, new tetrazole derivatives bearing pyrrolidine moiety were synthesized in order to present their action mode against C. albicans. The target compounds were obtained by N-alkylation of various 2-arylpyrrolidines with several 1-(3-chloropropyl)-5-aryl-2H-tetrazoles. Regardless of the substituents at tetrazole or pyrrolidine rings reactions took place in 48 h and with satisfactory yields ranging from 53 to 70%. We performed screen of the synthesized compounds to identify these nontoxic inhibiting the C. albicans planktonic and sessile cells, and conducted a series of follow up studies to examine the in vitro and in vivo activity of the most potent antifungals. The leading antifungal inhibitor: 2-{3-[2-(3-Methylphenyl)pyrrolidin-1-yl]propyl}-5-phenyl-2H-tetrazole (3aC) and the randomly selected ones: 5-phenyl-2-[3-(2-phenylpyrrolidin-1-yl)propyl]-2H-tetrazole (3aA), 5-(4-chlorophenyl)-2-{3-[2-(4-fluorophenyl)pyrrolidin-1-yl]propyl}-2H-tetrazole (3cD), and 5-(4-chlorophenyl)-2-{3-[2-(4-chlorophenyl)pyrrolidin-1-yl]propyl}-2H-tetrazole (3cE) showed little to no toxicity against the Vero cell line and Galleria mellonella. 3aC and 3aD, the most active against biofilm in vitro, demonstrated in vivo activity in the invertebrate model of disseminated candidiasis. Flow cytometry analysis showed that necrotic cell death was generated under 3aC due to its interactions with the fungal membrane; this confirmed by the mitochondrial damage (XTT assay) and reduced adhesion to the TR-146 cell line at 46.05 μM. Flow cytometry was used to directly measure the redox state of the treated cells with the fluorescent DCFH probe. Pro-necrotic tetrazole derivatives (3aA, 3aC, 3cD) are unable to induce ROS production in the C. albicans cells. Moreover, CLSM analyses revealed that the tetrazole derivatives (principally 3aC, 3aD, and 3aE) inhibit C. albicans' ability to neutralize macrophages; a more effective phagosomes organisation was observed. 3aC's and 3aD's activity reflected in an attenuation of virulence in disseminated candidiasis in vivo.

Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (lg R ≥ 3 at conc. of 31, 36 and 20 μM, respectively) however not against normal mammalian Vero cell line in vitro (IC50 ≥ 280 μM) and Galleria mellonella in vivo. These compounds also displayed moderate antineoplastic activity against human breast adenocarcinoma (MCF-7) cell line (EC50 = 80 μM) and high against peripheral blood T lymphoblast (CCRF-CEM) (EC50 = 6.3–6.5 μM). In addition, 6 and 42 exerted: (1) dual activity against fungal adhesion and damage mature biofilm; (2) necrosis of planktonic cells due to loss of membrane function and of structural integrity; (3) biochemical (inhibition of sessile cell respiration) and morphological changes in cell wall polysaccharide contents. Therefore, leading proxyphylline derivatives can be employed to prevent cancer-associated biofilm Candida infections.

A series of novel tetrazole derivatives was synthetized using N-alkylation or Michael-type addition reactions, and screened for their fungistatic potential against Candida albicans (the lack of endpoint = 100%). Among them, the selected compounds 2d, 4b, and 6a differing in substituents at the tetrazole ring were non-toxic to Galleria mellonella larvae in vivo and exerted slight toxicity against Caco-2 in vitro (CC50 at 256 μg/mL). An antagonistic effect of tetrazole derivatives 2d, 4b, and 6a respectively in combination with Fluconazole was shown using the checker board and colorimetric methods (fractional inhibitory concentration indexes FICIs >1). The most active 2d and 6a displayed an inverse relation between MICs in the presence of exogenous ergosterol, the effect was opposite to Itraconazole and Amphotericin B. The differences between 6a's and 2d's action mode were noted. Combining both flow cytometry and fluorescence image analyses respectively showed the complexity of planktonic and biofilm cell demise mode under the tetrazole derivatives tested. The following evidences for 6a's interaction with fungal membrane were noted: necrosis-like programmed cell death (97.03 ± 0.88), DNA denaturation (no laddering), mitochondrial damage (XTT assay), reduced adhesion to human epithelium (>50% at 0.0313 μg/mL, p ≤ .05), irregular deposit of chitin, and attenuated morphogenesis in mature biofilm. The treatment with 6a reduced pathogenicity of C. albicans during infection in G. mellonella. Contrariwise, 2d enhancing fungal adhesion displayed mechanism targeted to the cell wall (due to the presence of 3-chloropropyl clubbed with aryltetrazole) in the presence of osmotic protector. Under 2d, the accidental cell death (88.60% ± 4.81) was observed. In conclusion, all tetrazole derivatives were obtained in satisfactory yields (60–95%) using efficient, simple and not expensive methods. Fungistatic and slightly anticancer tetrazole derivatives with the novel action mode can circumvent an appearance of antifungal-resistant strains. These results indicate that they are worthy of further studies.

We conducted a thermovisual comparison of mean hand surface temperature changes upon local heating with two different IR sources. Sixty-six patients with rheumatoid arthritis (47 women and 19 men; average age, 56.1 ± 8.6 years) were subjected to topical heat therapy for one hand with either the standard IR radiator (SIR) or the water filter IRA (wIRA). The surface temperature of the dorsal side of both hands was measured, and thermal images were taken before and up to 2 h after treatment. At 1 min after treatment, SIR application increased the surface skin temperature of the heated hand from 31.5 ± 1.9 to 35.0 ± 1.9°C (P

We conducted a thermovisual comparison of mean hand surface temperature changes upon local heating with two different IR sources. Sixty-six patients with rheumatoid arthritis (47 women and 19 men; average age, 56.1 ± 8.6 years) were subjected to topical heat therapy for one hand with either the standard IR radiator (SIR) or the water filter IRA (wIRA). The surface temperature of the dorsal side of both hands was measured, and thermal images were taken before and up to 2 h after treatment. At 1 min after treatment, SIR application increased the surface skin temperature of the heated hand from 31.5 ± 1.9 to 35.0 ± 1.9 °C (P0.05), while wIRA increased it from 32.1 ± 1.6 to 34.2 ± 1.1 °C (P0.05). Constant decline in temperature was observed immediately after treatment, with the temperatures reaching baseline in about 30 and 120 min after wIRA and SIR treatment, respectively. Similar temperature changes were observed in the heated hands for wIRA and SIR, except at 1 min after treatment. Changes in the untreated hands indicated contralateral reaction. The temperature of the warmed hand showed a correlation to the body mass index.

Aerozoloterapia należy do najczęściej wybieranych metod w postępowaniu leczniczym wielu chorób pul‑ monologicznych wieku rozwojowego. W aerozoloterapii – jest to jej podstawowa zaleta – leki są bezpośred‑ nio kierowane do chorych obszarów płuc, gwarantując szybszy efekt terapeutyczny oraz możliwość stoso‑ wania mniejszych dawek leku. Efekty inhalowania zależą od budowy anatomicznej układu oddechowego dziecka i jego funkcjonowania, właściwie dobranego leku, wielkości cząsteczek oraz zastosowanej aparatury. Integralną częścią aerozoloterapii jest także dobrze przeprowadzona edukacja w wieku rozwojowym. Sposób podawania aerozolu powinien być skoncentrowany na inhalatorach najłatwiejszych w użyciu, pra‑ widłowo dobranych do różnych grup wiekowych oraz niewymagających wielokrotnych szkoleń w zakresie obsługi. Systemy aerozoloterapii różnią się pod względem budowy, sposobu wytwarzania chmury aerozolu, techniki optymalnej inhalacji i trudności w obsłudze. W aerozoloterapii pediatrycznej w celu wdychania leków najczęściej stosowane są cztery systemy: indywidualne inhalatory ciśnieniowe pMDI (pressurized metered‑dose inhaler), pMDI ze spejserem, inhalatory suchego proszku DPI (dry powder inhaler) i nebuli‑ zatory. U małych dzieci, zwykle oddychających przez nos, problemem może być nawiązanie współpracy, dlatego stosuje się u nich maski twarzowe. Bez względu na wybór inhalatora najważniejsza jest poprawna i wielokrotna edukacja poprzez demonstrację techniki oddychania i nadzorowanie wykonania inhalacji. Ważnym elementem dobrze przeprowadzonej inhalacji jest również analiza indywidualnych potrzeb dziecka ze zmianami pulmonologicznymi.

Wstęp: W procesie usprawniania osób z chorobami reumatycznymi wykorzystuje się wiele zabiegów z zakresu ciepłolecznictwai krioterapii. W dostępnym piśmiennictwie niewiele jest opisówbadań dotyczących efektów termicznych występujących w tkankachw wyniku stosowania takich zabiegów w obrębie ręki reumatoidalnej.Z tego powodu autorzy podjęli próbę określenia przebiegudynamiki zmian temperatury po zastosowaniu powszechniestosowanych u pacjentów z reumatoidalnym zapaleniem stawów(RZS) zabiegów z zakresu termoterapii, w aspekcie zmian zachodzącychw mikrokrążeniu podczas 120 minut obserwacji.Materiały i metody: Do dwóch grup przydzielono 27 pacjentówz rozpoznanym RZS (średni wiek badanych 57 ±7,9 roku): I grupaliczyła 14 osób, u których naświetlano jedną rękę promiennikiempodczerwieni IR-A, -B oraz -C, II grupa – 13 osób, u których wykonanozabieg nadmuchu jednej ręki zimnym powietrzem (–30°C).Analizy rozkładu temperatury dokonano na podstawie 120-minutowejobserwacji zmian temperatury powierzchniowej obu rąk, dozapisu której użyto kamery termowizyjnej. U każdej osoby wykonano8 zdjęć termowizyjnych w określonych odstępach czasu:przed zabiegiem, zaraz po zabiegu oraz 5, 15, 30, 45, 60 i 120 minutpo zabiegu.Wyniki: Istotne różnice temperatur mierzonych w kolejnych odstępachczasu zaobserwowano we wszystkich grupach tylko podczas wynopierwszych5 minut po zabiegu (p < 0,05). Maksymalny wzrost temperaturyodnotowany zaraz po zabiegu IR-A, -B, -C wynosił 3,5°C. Ponadmuchu zimnym powietrzem (–30°C) maksymalne obniżenietemperatury mierzonej zaraz po zabiegu wynosiło 6,4°C (ryc. 1 i 2).Wnioski: Istotne zmiany temperatury powierzchniowej rąk obserwowanow ciągu pierwszych 5 minut po zabiegu, zarówno ponaświetlaniu IR-A, -B, -C, jak i nadmuchu zimnym powietrzemo temperaturze ok. –30°C. W przypadku zabiegu cieplnego wartośćtemperatury w ciągu tego czasu pozostawała powyżej wartościwyjściowej, natomiast w przypadku krioterapii pozostawała poniżejwartości spoczynkowych.