Ru(II)-Catalyzed Asymmetric Transfer Hydrogenation of α-Alkyl-ß-Ketoaldehydes via Dynamic Kinetic Resolution.

The (R,R)-Teth-TsDPEN-Ru(II) complex promoted the one-pot double C=O reduction of α-alkyl-ß-ketoaldehydes through asymmetric transfer hydrogenation/dynamic kinetic resolution (ATH-DKR) under mild conditions. In this process, ten anti-2-benzyl-1-phenylpropane-1,3-diols (85:15 to 92:8 dr) were obtained in good yields (41-87%) and excellent enantioselectivities (>99% ee for all compounds). Notably, the preferential reduction of the aldehyde moiety led to the in situ formation of 2-benzyl-3-hydroxy-1-phenylpropan-1-one intermediates. These intermediates played a crucial role in enhancing both reactivity and stereoselectivity through hydrogen bonding.

Deciphering Rind Color Heterogeneity of Smear-Ripened Munster Cheese and Its Association with Microbiota.

Color is one of the first criteria to assess the quality of cheese. However, very limited data are available on the color heterogeneity of the rind and its relationship with microbial community structure. In this study, the color of a wide range of smear-ripened Munster cheeses from various origins was monitored during storage by photographic imaging and data analysis in the CIELAB color space using luminance, chroma, and hue angle as descriptors. Different levels of inter- and intra-cheese heterogeneity were observed. The most heterogeneous Munster cheeses were the darkest with orange-red colors. The most homogeneous were the brightest with yellow-orange. K-means clustering revealed three clusters distinguished by their color heterogeneity. Color analysis coupled with metabarcoding showed that rinds with heterogeneous color exhibited higher microbial diversity associated with important changes in their microbial community structure during storage. In addition, intra-cheese community structure fluctuations were associated with heterogeneity in rind color. The species Glutamicibacter arilaitensis and Psychrobacter nivimaris/piscatorii were found to be positively associated with the presence of undesirable brown patches. This study highlights the close relationship between the heterogeneity of the cheese rind and its microbiota.

C1-C2 Transarticular Anterior Fixation for the Treatment of Atlantoaxial Traumatic Dislocation: A Clinical Case.

Fractures of the odontoid apophysis are one of the most frequent lesions in the elderly population, and an increasingly preponderant problem with the progressive aging of the world population. In the present work, we report a clinical case of an 88-year-old male patient who suffered a fall resulting in a type-II fracture of the odontoid apophysis on the Anderson-D'Alonzo classification. Given the age and comorbidities of the patient, we decided to perform osteosynthesis of the fracture through anterior fixation with a transarticular screw in combination with fixation with an odontoid screw. This technique enables the necessary stability for the consolidation of Anderson-D'Alonzo's type II odontoid apophysis fracture, with the advantage of the lower levels of dissection of the cervical extensor musculature and hemorrhage resulting from this aggression when compared with the posterior approach; moreover, it is a readily-available technique that yields clear benefits in the treatment of this pathology in the geriatric population.

Prospective, Randomized, Controlled Pivotal Trial of Biodegradable Balloon Rectal Spacer for Prostate Radiation Therapy.

PURPOSE/OBJECTIVES: Rectal spacers have been shown to reduce rectal side effects in patients receiving prostate radiation. However, concerns remain regarding precise and reproducible gel injection. We evaluated efficacy and safety of a novel rectoprostatic spacer balloon which allows potential for controlled, adaptable deployment. This study tested co-primary hypotheses: 1) Balloon spacer would result in ≥ 25% reduction of rectal V70 in > 75% of subjects, and 2) Implantation procedure-related and rectal ≥ Grade 1 adverse events within 6 months (duration ≥ 2 days, CTCAE 4.0) would be non-inferior in balloon vs control subjects. MATERIALS/METHODS: 222 subjects were enrolled at 16 centers. All patients had T1-T3 prostate cancer without MRI evidence of posterior extraprostatic invasion. Randomization was 2:1 (balloon: control) and subject-blinded. Patients underwent transperineal TRUS-guided fiducial placement +/- balloon, followed by IMRT (81 Gy in 1.8 Gy fractions or biologically equivalent hypofractionated dose). For efficacy comparisons, plans were generated by a central core lab on pre- and post-implant CT scans. RESULTS: The primary efficacy endpoint was met, with 97.9% of balloon subjects (139/142) having rectal V70 reduction >25% (p<0.001). Mean V70 was 7.0 % pre- vs 1.1% post- implant. The primary safety endpoint was met with balloon subjects experiencing fewer ≥ Grade 1 events, 18% vs 23% (p < 0.001 for non-inferiority). On pre-defined secondary endpoint of ≥ Grade 2 events, rates trended lower in balloon subjects (4.3% vs 6.5%, p=0.527). Mean perirectal spacing was 19 ±3.7mm and maintained through radiation treatment (18 ±3.9mm). Balloon resorption was observed on 6-month CT in 98.5% (133/135) of subjects. The EPIC QOL instrument was collected throughout study, and did not differ statistically between the study arms. CONCLUSIONS: Biodegradable rectal spacer balloon was effective in significantly reducing dose to rectum, and associated with decreased cumulative rectal plus implantation-related adverse events. Balloon resorption was consistently observed by 6 months.

Psychological impact of life events in systemic lupus erythematosus patients - Differences between flares and remission.

BACKGROUND: Stress has been linked to worsening symptoms and increased disease activity in patients with Systemic lupus erythematosus (SLE). Life-events are individual stress points, and there is conflicting evidence regarding their role in SLE activity and disease perception. METHODS: Adult SLE patients were recruited for the study. Clinical and laboratory features of SLE were recorded, and previous diagnosis of anxiety or depression were retrieved from patients' electronic charts. Flares were defined by the Systemic Lupus Erythematosus Disease Activity (SLEDAI) flare Index, and flares during the previous year were documented. During a routine visit, they completed validated Portuguese translations of the 10-item Perceived Stress Scale (PSS-10), Hospital Anxiety and Depression Scale (HADS) and Life Experience Survey (LES) for the previous year. RESULTS: A total of 47 female SLE patients were recruited. Ten patients (21.3%) had experienced recent flares. Patients with recent flares reported fewer life events, with lower positive, negative, and total weightings sums compared to those without recent flares. Although 42.2% of patients perceived pathological levels of stress in the previous month, 48.9% had anxiety symptoms, and 34% were at high risk for an anxiety disorder, these psychometric measures did not differ significantly between the recent flare and no-flare groups. CONCLUSIONS: There is a high prevalence of pathological levels of stress among SLE patients. SLE patients with recent flares report less psychological impact from life events, both positive and negative, independent of other psychological or pharmacological factors.

Vascular access specialist teams versus standard practice for catheter insertion and prevention of failure: a systematic review.

OBJECTIVE: Billions of vascular access devices (VADs) are inserted annually for intravenous therapy worldwide. However, their use is not without challenges. Facilitating the process and enhancing results, hospital authorities have created vascular access specialist teams (VASTs) with advanced competencies in the evaluation, insertion, care and management of VADs. The objective is to compare the effectiveness of VASTs versus standard practice regarding cannulation success and vascular access maintenance in hospitalised adults. DESIGN: Systematic review, using the Mixed Methods Appraisal Tool. DATA SOURCES: We conducted a structured data search on Cochrane Library, MEDLINE, Web of Science, Scopus and EBSCOhost up to 31 May 2023. We did not impose a time limit regarding the date of publication. ELIGIBILITY CRITERIA: Studies were eligible for inclusion in the review if they were randomised and non-randomised trials and observational studies. DATA EXTRACTION AND SYNTHESIS: We included studies that described or evaluated the activity of VASTs compared with clinical practitioners. The outcomes analysed were the success of the cannulation and the incidence of associated adverse effects. RESULTS: The search strategy produced 3053 papers published between 1984 and 2020, from which 12 were selected for analysis. VASTs are heterogeneously described among these studies, which mainly focus on insertions, frequently for patients with difficult intravenous access. Some patients presented with specific needs or requirement for specific insertion technique or catheter type. Compared with usual practice, these studies indicate that the involvement of a VAST is associated with a higher effectiveness in terms of first attempt insertions and insertion success rates, and a reduction in catheter-associated adverse events. However, meta-analyses confirming this trend are not currently possible. CONCLUSIONS: It seems apparent that VASTS contribute to improving the health of patients during the administration of intravenous. VASTs seem to increase the effectiveness of VAD insertion and care and reduce complications. PROSPERO REGISTRATION NUMBER: CRD42021231259.

International External Validation of Risk Prediction Model of 90-Day Mortality after Gastrectomy for Cancer Using Machine Learning.

BACKGROUND: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. METHODS: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. RESULTS: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. CONCLUSION: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice.

TEMPy: a toolkit for the modeling of weighted tissue equivalent material in diagnostic imaging.

Objective.Accurate simulation of human tissues is imperative for advancements in diagnostic imaging, particularly in the fields of dosimetry and image quality evaluation. Developing Tissue Equivalent Materials (TEMs) with radiological characteristics akin to those of human tissues is essential for ensuring the reliability and relevance of imaging studies. This study presents the development of a mathematical model and a new toolkit (TEMPy) for obtaining the best composition of materials that mimic the radiological characteristics of human tissues. The model and the toolkit are described, along with an example showcasing its application to obtain desired TEMs.Approach.The methodology consisted of fitting volume fractions of the components of TEM in order to determine its linear attenuation coefficient as close as possible to the linear attenuation coefficient of the reference material. The fitting procedure adopted a modified Least Square Method including a weight function. This function reflects the contribution of the x-ray spectra in the suitable energy range of interest. TEMPy can also be used to estimate the effective atomic number and electron density of the resulting TEM.Main results.TEMPy was used to obtain the chemical composition of materials equivalent to water and soft tissue, in the energy range used in x-ray imaging (10 -150 keV) and for breast tissue using the energy range (5-40 keV). The maximum relative difference between the linear attenuation coefficients of the developed and reference materials was ±5% in the considered energy ranges.Significance.TEMPy facilitates the formulation of TEMs with radiological properties closely mimicking those of real tissues, aiding in the preparation of physical anthropomorphic or geometric phantoms for various applications. The toolkit is freely available to interested readers.

Unlocking the nutraceutical potential of Corylus avellana L. shells: microwave-assisted extraction of phytochemicals with antiradical and anti-diabetic properties.

BACKGROUND: In recent years, the demand for high-quality natural extracts to be included in nutraceutical formulations has increased sharply. Hazelnut (Corylus avellana L.) shells (HZS) are underrated agricultural by-products that could be exploited as a source of active ingredients with pro-healthy properties. In the present study, a fully green microwave-assisted extraction (MAE) method was established for the first time aiming to recover bioactive constituents from HZS with significant nutraceutical value. Key MAE parameters, including ethanol in water concentration, microwave power, irradiation time and solvent-to-powder ratio, were optimized through response surface methodology utilizing a Box-Behnken design to achieve the highest total phenolic content and antioxidant/antiradical activities in the final extract. RESULTS: The optimal MAE conditions (28% v/v ethanol/water, 270 s, 670 W, and 37 mL g-1) yielded an extract with significant scavenging capacity against reactive oxygen species and remarkable inhibitory activity towards both α-amylase (IC50 = 7.73 µg mL-1) and α-glucosidase (IC50 = 49.44 µg mL-1), demonstrating stronger hypoglycaemic properties than the anti-diabetic drug acarbose. Additionally, fluorescence spectroscopy results highlighted the ability of the optimized extract from HZS (OHS-E) to counteract advanced glycation end-product formation throughout the glycation cascade in a dose-dependent manner. Liquid chromatography/electrospray ionization-tandem mass spectrometry profiling unveiled the presence of fatty acids and phenolic compounds, including lignans, flavonoids, gallic acid derivatives and diarylheptanoids. Lastly, the biocompatibility of OHS-E was attested on HT29-MTX and Caco-2 intestinal cells. CONCLUSION: Altogether, these findings encourage the potential application of OHS-E as an effective nutraceutical component against type 2 diabetes mellitus and oxidative stress. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Click Chemistry in Polymersome Technology.

Polymersomes, self-assembled nanoparticles composed of amphiphilic block copolymers, have emerged as promising versatile nanovesicles with various applications, such as drug delivery, medical imaging, and diagnostics. The integration of click chemistry reactions, specifically the copper [I]-catalysed azide-alkyne cycloaddition (CuAAC), has greatly expanded the functionalisation and bioconjugation capabilities of polymersomes and new drugs, being this synergistic combination explored in this review. It also provides up-to-date examples of previous incorporations of click-compatible moieties (azide and alkyne functional groups) into polymer building blocks, enabling the "click" attachment of various functional groups and ligands, delving into the diverse range of click reactions that have been reported and employed for polymersome copolymer synthesis and the modification of polymersome surfaces, including ligand conjugation and surface modification. Overall, this review explores the current state-of-the-art of the combinatory usage, in recent years, of polymersomes with the click chemistry reaction, highlighting examples of studies of their synthesis and functionalisation strategies.

Quantitative and qualitative evaluation of microorganism profile identified in bioburden analysis in a biopharmaceutical facility in Brazil: Criteria for classification and management of results.

Microbiological contamination may cause microbial proliferation and consequently additional problems for pharmaceutical companies through production stoppage, product contamination, investigations of process deviations, out-of-specification results and product disposal. This is one of the major concerns of the regulatory health agencies. Microbiological load (bioburden) may represent a potential risk for patients if the sterilization process is not effective and/or due to the production of toxins. Although bioburden can be eliminated by terminal sterilization or filtration processes, it is important to monitor the amount and determine the identity and characteristics of the microorganisms present prior to final processing. The application of microorganism identification systems is crucial for identifying the type of contamination, which can be extremely useful for investigating. The aim of this study was to evaluate the profiles of microorganisms identified in bioburden assays from solutions, culture medias, and products (SCP) from a pharmaceutical industry facility. From 2018-2020, a total of 1,078 samples from 857 different lots of SCP were analyzed and isolated microorganisms were identified. A prefiltering step was included after March 2020, in order to reduce the bioburden before sterilizing filtration. Criteria for the definition and management of microorganisms identified were evaluated after an integrative bibliographic review, and three groups were proposed (critical, objectionable, and nonobjectionable microorganisms). For the samples that did not include prefiltering (n=636), 227 (35.7%) presented microbial growth. For those that included prefiltering, before prefiltering (n=221), 60.6% presented microbial growth, and after prefiltering, this value was reduced to 4.1%, which can be attributed to a contamination during the sampling or a wrong filtering. From the samples that presented microbial growth, 678 microorganisms were identified as bacteria and 59 as molds and yeasts. A total of 120 microorganisms (56 and 27 Gram-positive and negative bacteria, respectively, 31 yeasts, and six filamentous molds) could not be identified, and the remaining microorganisms were classified as objectionable (n=507; 82.2%), nonobjectionable (n=103; 16.7%) and critical (n=7; 1.1%). Most of the bioburden species (>80.0%) were considered objectionable microorganisms. A process for classification and management of bioburden analysis results based on a literature review of pathogenic and physiological characteristics of the microorganisms was proposed.

Prevalence and clinico-pathology of PSOROPTIC mange in buffaloes of the Amazon region.

Scabies is an important skin disease in several species of domestic and wild animals; however, few reports in Brazil have emphasized its occurrence in buffaloes. This article describes the epidemiological, clinical and pathological aspects and diagnosis of psoroptic mange in buffaloes in a property in the municipality of Castanhal, PA, Amazon region. Of the 41 buffaloes examined, 38 males and females of the Murrah, Baio, Mediterranean and Carabao breeds and their crossbreeds, aged between 2 and 20 years, had a history of pruritus. Clinical examination was performed to map the lesions, skin scrapings were collected to identify the mites, and a biopsy was performed for histopathological examination. Clinical signs, from mild to severe intensity, varied according to the system of creation and handling of the animals and were more severe in buffaloes raised in bays than those raised under a collective regime (pastures and collective troughs). The characteristic clinical signs were intense itching, extensive areas of alopecia, periocular edema, and thickening of the epidermis with exudative crusts covering the face, chamfer, neck, scapular region, back, base of the horn, thoracic and pelvic limbs and chest. The behavior of rubbing the affected regions of the body against structures (troughs, fence posts, gates) or with the horns was frequently observed and provided relief from itching. In the most severe cases, mites were also noted in the crusts, which were identified as Psoroptes natalensis. Histological skin lesions exhibited alterations consistent with immune-mediated dermatitis, which is typical of hypersensitivity to mite-derived allergens.

Translation, cultural adaptation, and validation of the Nurse Self-Concept Questionnaire (NSCQ) for Portuguese nursing students.

BACKGROUND: The professional self-concept of nursing students significantly influences their attitude and identity within the profession, ultimately impacting their mental health and overall well-being. Recent evidence underscores the importance of assessing students' professional self-concept to prevent adverse outcomes such as burnout and stress. Since there are currently no validated instruments available in Portugal for this purpose, our objective was to translate, adapt, and validate the Nurse Self-Concept Questionnaire (NSCQ) with nursing students in Portugal. METHODS: A two-phase research study with a non-probabilistic sample of 216 undergraduate nursing students, using the QualtricsXM electronic platform for data collection. An exploratory factor analysis was performed to verify the validity of the theoretical construct and its internal consistency. Cronbach's alpha was calculated, and a confirmatory factor analysis was performed to assess the model fit. RESULTS: The final instrument, designated as Questionário de Autoconceito dos/as Enfermeiros/as (Pt - NSCQ), is composed of 24 items distributed across five dimensions: "General self-concept", "Staff relations", "Leadership", "Communication-care" and "Knowledge", which explain 67.71% of the total variance. All dimensions and the global scale revealed good internal consistency values, ranging from 0.775 to 0.927. The resulting factorial structure is coherent with the theoretical framework. CONCLUSION: The Pt - NSCQ proved to be a valid and reliable instrument to assess Portuguese nursing students' professional self-concept. Future studies should be carried out on larger samples and different educational contexts, aligned with the importance to ensure the continuity of the psychometric analysis of the instrument.

Integrating Cosmic Microwave Background Readings with Celestial Navigation to Enhance Deep Space Navigation.

This research unveils a cutting-edge navigation system for deep space missions that utilizes cosmic microwave background (CMB) sensor readings to enhance spacecraft positioning and velocity estimation accuracy significantly. By exploiting the Doppler-shifted CMB spectrum and integrating it with optical measurements for celestial navigation, this approach employs advanced data processing through the Unscented Kalman Filter (UKF), enabling precise navigation amid the complexities of space travel. The simulation results confirm the system's exceptional precision and resilience in deep space missions, marking a significant advancement in astronautics and paving the way for future space exploration endeavors.

Treatment of Two-column Acetabular Fractures by Double Extrapelvic Approach: Three Clinical Cases.

Fractures of two columns of the acetabulum according to the Letournel classification are among the most common in frequency, indication and surgical complexity. These are mainly the result of lateral compression mechanisms and are characterized by originating a disconnected acetabulum from the axial skeleton. Its surgical treatment may include: isolated anterior or posterior approach; combined, at the same surgical time or not; or broad approaches. The authors present another surgical option with association of the Kocher-Langenbeck pathway with the iliac crest approach simultaneously and in the same positioning (lateral decubitus) based on the first three clinical cases performed and their clinical and imaging results. In addition to the presentation of the cases, a description of the three characteristic fragments of this type of acetabular fractures, the approach pathway, and the reduction sequence performed are made. From the results obtained and the associated advantages, the authors believe that the addition of the iliac crest approach to the Kocher-Langenbeck pathway may be a very attractive option to consider in the surgical treatment of properly selected fractures of two columns of the acetabula.

Optimization of the molecular detection assay of Salmonella (MDS®) for drag swab samples of aviaries.

Detection of Salmonella sp. is important for the broiler chicken production chain because it is one microorganisms involved in food-borne diseases. Thus, this study performed the optimization of a technique of Loop-mediated isothermal DNA amplification (LAMP) through the 3MTM Molecular Detection Assay 2: Salmonella (MDS®), in accordance with Ordinance number 126 of the Ministry of Agriculture, for the detection of Salmonella sp. in drag swab. The methodology followed ISO 16140-2: 2016, with the analysis naturally contaminated drag swab samples collected from broiler aviaries and artificially contaminated with salmonella ATCCs. Of the 300 samples processed in protocol A (pre-enrichment tetrathionate broth (TT)), 45 were positive for Salmonella sp., 242 negative, one false-positive, and 12 false-negative, while of the 300 samples analyzed in protocol B (pre-enrichment brain-heart infusion broth (BHI)), 40 were positive, 256 negative, one false-positive, and three false-negative. The result for protocol A was a sensitivity of 79%, specificity of 99.6%, Positive Predictive Value (PPV) of 98%, and Negative Predictive Value (NPV) of 95%; and for protocol B, 93% sensitivity, 99.6% specificity, 98% PPV, and 99% NPV. Both protocols were associated with the reference method (p>0.05), concluding that the MDS® can be used for the qualitative detection of Salmonella sp.

Nursing Students' Perceptions of a Novel Education Approach to Prevention and Control of Healthcare-Associated Infections: Insights from PrevInf Pilot Study.

BACKGROUND: Healthcare-associated infections (HAIs) pose a significant global threat, particularly in developing regions such as Southeast Asia. International bodies emphasize the role of formal undergraduate training in the prevention and control of HAIs. To address this, we aimed to explore the perceptions of Southeast Asian nursing students regarding a novel educational approach developed by a European-Southeast Asian project consortium. METHODS: A pilot study was conducted in four nursing higher education institutions from Cambodia and Vietnam. First, local nursing educators conducted a 2 h classroom-based training session. Then, students were invited to participate for the first time in one of twelve evidence-based simulation scenarios developed by the research team, covering a range of nursing care situations related to the prevention and control of HAIs. After attending both components, students were asked to complete a paper-based questionnaire and rate their agreement with a set of statements on the appropriateness and meaningfulness of both components. RESULTS: A total of 430 nursing students enrolled in the pilot study; 77.4% were female, with an average age of 19.8 years. The PrevInf educational intervention received positive feedback from participating students across settings, with strong agreement on the importance of proactiveness in competency development (M = 5.9, SD = 1.4). Notable differences between Cambodian and Vietnamese students were observed in terms of their receptiveness to the pre-selected teaching materials (p = 0.001) and strategies (p = 0.01) used by the nursing educators during their experience with the simulation scenarios. CONCLUSIONS: The PrevInf educational intervention shows promise in engaging Southeast Asian nursing students and fostering a deeper understanding of the prevention and control of HAIs. Further studies are warranted to refine the learning content and standardize the pedagogical strategies used by nursing educators across settings. This study was not registered.

Synthesis, Activity, Toxicity, and In Silico Studies of New Antimycobacterial N-Alkyl Nitrobenzamides.

Tuberculosis (TB) is a disease that plagues the frailest members of society. We have developed a family of N-alkyl nitrobenzamides that exhibit promising antitubercular activities and can be considered a structural simplification of known inhibitors of decaprenylphosphoryl-ß-D-ribofuranose 2'-oxidase (DprE1), an essential Mycobacterium tuberculosis (Mtb) enzyme and an emergent antitubercular target. Hereby, we report the development of these compounds via a simple synthetic methodology as well as their stability, cytotoxicity, and antitubercular activity. Studying their in vitro activity revealed that the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives were the most active, and within these, the derivatives with intermediate lipophilicities presented the best activities (MIC of 16 ng/mL). Additionally, in an ex vivo macrophage model of infection, the derivatives with chain lengths of six and twelve carbon atoms presented the best results, exhibiting activity profiles comparable to isoniazid. Although the proof is not definite, the assessment of susceptibility over multiple mycobacterial species, together with the structure similarities with known inhibitors of this enzyme, support DprE1 as a likely target of action for the compounds. This idea is also reinforced by the docking studies, where the fit of our more active compounds to the DprE1 binding pocket is very similar to what was observed for known inhibitors like DNB1.

Advances in the synthesis of rearranged homoisoflavonoids.

Rearranged homoisoflavonoids constitute a unique group of natural products, renowned for their structural diversity and complexity. These compounds, derived from modifications in the 3-benzylchroman skeleton, are categorized into four subclasses: brazilin, caesalpin, protosappanin, and scillascillin homoisoflavonoids. This review examines the advancements in the total synthesis of these complex structures, aiming to highlight the challenges and opportunities encountered. A comparative analysis of the strategies employed thus far to synthesize these compounds provides a comprehensive understanding of the progress in this field.

Synergistic activity between conventional antifungals and chalcone-derived compound against dermatophyte fungi and Candida spp.

The scarce antifungal arsenal, changes in the susceptibility profile of fungal agents, and lack of adherence to treatment have contributed to the increase of cases of dermatomycoses. In this context, new antimicrobial substances have gained importance. Chalcones are precursors of the flavonoid family that have multiple biological activities, have high tolerability by humans, and easy synthesis. In this study, we evaluated the in vitro antifungal activity, alone and in combination with conventional antifungal drugs, of the VS02-4'ethyl chalcone-derived compound against dermatophytes and Candida spp. Susceptibility testing was carried out by broth microdilution. Experiments for determination of the target of the compound on the fungal cell, time-kill kinetics, and toxicity tests in Galleria mellonella model were also performed. Combinatory effects were evaluated by the checkerboard method. Results showed high activity of the compound VS02-4'ethyl against dermatophytes (MIC of 7.81-31.25 µg/ml). The compound targeted the cell membrane, and the time-kill test showed the compound continues to exert gradual activity after 5 days on dermatophytes, but no significant activity on Candida. Low toxicity was observed at 250 mg/kg. Excellent results were observed in the combinatory test, where VS02-4'ethyl showed synergistic interactions with itraconazole, fluconazole, terbinafine, and griseofulvin, against all isolates tested. Although further investigation is needed, these results revealed the great potential of chalcone-derived compounds against fungal infections for which treatments are long and laborious.