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Background/Objectives: Antifungal resistance to azoles, coupled with the increasing prevalence of Candida albicans infections, represents a significant public health challenge and has driven the search for new natural compounds that can act as alternatives or adjuvants to the current antifungals. Ellagic acid (EA) has demonstrated antifungal activity; however, its effects are not fully understood. In this study, we investigated the in vitro anti-Candida activity of EA and its ability to potentiate the effects of fluconazole (FLZ) on C. albicans. Methods: The Minimum Inhibitory Concentration (MIC) of EA was determined by broth microdilution and its interaction with FLZ was assessed using a checkerboard assay. Additionally, we examined the effects of EA on yeast-to-hypha transition, inhibition of biofilm formation, time–kill kinetics, hemolytic activity, and cytotoxicity in HeLa ATCC® CCL-2™ cells. Results: EA exhibited MIC values ranging from 250 to 2000 µg/mL and showed synergistic and additive interactions with FLZ, resulting in a marked reduction in the MIC values of FLZ (up to 32-fold) and EA (up to 16-fold). In the time–kill assay, the most effective combinations were 4× EA MIC, 2× EA MIC, and FIC EA + FLZ, which showed fungicidal activity. Furthermore, EA did not show hemolytic activity and demonstrated low and dose-dependent cytotoxicity in HeLa cells, with no cytotoxic effects observed in combination with FLZ. EA and the synergistic combination of EA and FLZ interfered with both the yeast-to-hypha transition process in C. albicans cells and biofilm formation. In addition to its antifungal efficacy, EA demonstrated a favorable safety profile at the concentrations used. Conclusions: This study presents promising results regarding the potential use of EA in combination with FLZ for the treatment of C. albicans infections. [ABSTRACT FROM AUTHOR]

Background/Objectives: Gastrointestinal functional disorders (GFDs), including irritable bowel syndrome (IBS), are imbalances in the gut–brain axis characterized by persistence of symptoms in the abdominal area. Probiotics are live microorganisms that provide benefits to the health of their hosts when administered in adequate amounts, while prebiotics are a substrate that is selectively used by host microorganisms. This narrative review aimed to evaluate the effectiveness of prebiotics and probiotics mostly in irritable bowel syndrome, particularly on issues such as the interaction between these products and the gut microbiota, the duration of supplementation and long-term effects, the definition of ideal dosages, and the regulation and quality control of these products. Methods: A bibliographic search was carried out in indexed databases and articles published within 10 years before the beginning of the study and publications in English language, which investigated the specific theme of the study were considered. Papers dealing with topics not covered by the research questions, or presenting errors related with the wrong population or the wrong methods, as well as experimental studies and case reviews were excluded. Fifty-five articles were selected, initially in isolation by the authors and, afterward, under consensus. Results: It was possible to observe the effectiveness mainly of probiotics, in improving specific symptoms of the respective disorder; however, the available data remain unclear due to limitations concerning samples and methods of the studies evaluated. Conclusions: Despite evidence suggestive of therapeutic efficacy, additional multicenter randomized controlled trials (RCTs) with better defined protocols are still necessary to fill in the gaps in this subject, define measures to ensure the safe administration of these products, and confirm their therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: Intranasal corticosteroids (INCS) are used for several conditions, including allergic rhinitis and sinusitis. Consequently, their safety profile needs continuous monitoring. This study aimed to analyse the adverse drug reactions (ADRs) of the INCS with market authorisation in Europe. Methods: A retrospective analysis of the ADR data from EudraVigilance in the period between the 1 January 2011 and 12 June 2023 was performed, with 2641 reports selected for analysis. ADRs were categorised by seriousness and evolution, with a focus on the most prevalent ADRs and their alignment with the Summary of Product Characteristics (SmPC). Results: The 18–64 age group, particularly females, was most affected. Mometasone was the most reported INCS, with predominantly non-serious ADRs, evolving towards resolution, which often were not listed in the SmPC. From the reported ADRs that were not described in the SmPC of the INCS studied, "Anosmia" and "Ageusia" were highlighted. Regarding the ADRs described in the SmPC, the most frequently reported were "Epistaxis" and "Headache". The ADRs belonging to the Designated Medical Event list were also analysed, with "Angioedema" as the most reported ADR, which was mainly associated with budesonide. Conclusions: These findings underscore the importance of continuous INCS monitoring to mitigate ADRs and safeguard public health. Further research is warranted to explore potential novel signs for safety arising from previously unreported ADRs. [ABSTRACT FROM AUTHOR]

Postmenopausal abnormal uterine bleeding is a common clinical problem addressed in gynaecological practice and should prompt clinical investigation due to the significant prevalence of malignant and premalignant lesions of the endometrium in this age group. Nevertheless, other causes should be considered, since its diagnostic and therapeutic management may differ considerably. Here, we present a case of a colouterine fistula due to chronic diverticulitis presenting with postmenopausal abnormal uterine bleeding. This is an infrequent occurrence and is caused by the rupture of a diverticular abscess into the uterine wall, resulting in an inflammatory adhesion of the colon and uterus, with necrosis and subsequent fistula formation. The clinical presentation is variable and may include abdominal pain, gastrointestinal tract symptoms, vaginal discharge, and abnormal uterine bleeding. The laboratory and imaging techniques may be not completely conclusive and definitive diagnosis can be made intraoperatively. There are different treatment options, with en bloc resection and primary anastomosis being used most often, allowing complete treatment. The prognosis for a colouterine fistula secondary to diverticulitis is excellent after surgery. This case highlights the importance of clinical suspicion of an unusual cause of uterine bleeding and an effective and multidisciplinary approach that allowed complete surgical treatment and patient recovery. [ABSTRACT FROM AUTHOR]

Falls are not always considered direct adverse drug reactions (ADRs). However, due to their mechanism of action, certain drugs increase the risk of falls. This retrospective study aimed to evaluate the association between drugs and the risk of falls. An analysis of ADR reports submitted to a national pharmacovigilance database from 1992 to 2021 was performed using terms from the MedDRA dictionary. This included the word "fall" and terms related to conditions potentially predisposing patients to falls. The analysis involved examining the sex and age distribution of the population. Reports were assessed for seriousness, the class of the suspected drug, and the characterisation of fall events when they occurred. Over this period, 2217 cases were reported, with the majority occurring among females (60.71%) and the age group of 18–64 years old (38.43%). Most reports were classified as serious across all age groups, and immunomodulators (16.78%) were the most frequently reported pharmacotherapeutic class of suspected drugs. Falls were reported as ADRs in 343 cases, with fractures being the most commonly reported injuries (24.45%). In conclusion, falls can pose a significant health problem. Therefore, continuously monitoring drugs is crucial to minimise fall-associated risk factors. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are a recent targeted therapy approved for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer. Abemaciclib, palbociclib and ribociclib demonstrated great efficacy and safety during clinical studies. However, differences in their adverse-event profiles have been observed. This work aims to describe the suspected adverse drug reactions (ADRs), such as leukopenia and thrombocytopenia, reported for each CDK4/6 inhibitor in the EudraVigilance (EV) database. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. Information on concomitant drug therapy, including fulvestrant, letrozole, anastrozole and exemestane, was also analyzed. A total of 1611 ICSRs were collected from the EV database. Most reports of palbociclib and ribociclib were classified as serious cases for both suspected leukopenia and thrombocytopenia ADRs. However, most patients had their leukopenia and thrombocytopenia recovered/resolved. On the contrary, reports of abemaciclib were mostly characterized as non-serious cases. Abemaciclib and palbociclib were often combined with fulvestrant, while ribociclib was generally associated with letrozole. Pharmacovigilance studies are crucial for the early identification of potential ADRs and to better differentiate the toxicity profile of the different CDK4/6 inhibitors, particularly in a real-world setting. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the potential of lactic acid bacteria (LAB) in developing alginate-based gel formulations to inhibit Staphylococcus aureus. Initially, the antagonistic actions of three lactic acid bacteria (LAB) (Lacticaseibacillus rhamnosus ATCC 10863, Lactiplantibacillus plantarum ATCC 14917, Limosilactobacillus fermentum ATCC 23271) were evaluated against S. aureus ATCC 25923. All tested LAB inhibited S. aureus, but the highest activity was observed for L. plantarum ATCC 14917 (p < 0.05). The antimicrobial effects of L. plantarum ATCC 14917 cell suspensions, sonicate cells extract, and cell-free supernatants (pH 5 or 7) were analyzed using a broth-based assay. The cell suspensions inhibited S. aureus at concentrations ≥ 10%, and these effects were confirmed by a time-kill assay. Alginate-based gels were formulated with cell suspensions, sonicate cells extract, and cell-free supernatant (pH 5). These formulations inhibited S. aureus growth. Based on the results, the alginate gel with cell suspensions at 10% was selected for further characterization. L. plantarum ATCC 14917 survived in the alginate-based gel, especially when stored at 5 °C. At this temperature, the L. plantarum-containing alginate gel was stable, and it was in compliance with microbiological standards. These findings suggest it can be a promising agent for the topical treatment of infections induced by S. aureus. [ABSTRACT FROM AUTHOR]

The first line medication for the treatment of type 2 diabetes is metformin. This study aims to investigate the safety profile of metformin and metformin combination medications in older adults using pharmacovigilance data. A literature search was used to identify published clinical studies reporting safety of metformin in older patients (age ≥ 65 years old), which were then thoroughly evaluated. Additionally, a deep analysis was performed, taking into account suspected adverse drug reaction (ADR) reports submitted to the Portuguese Pharmacovigilance System involving patients with 65 years old or older, with metformin or metformin combination as the suspected drug. The results suggest that metformin is safer when used in combination with other antidiabetics than when used in monotherapy. Metformin prolonged-release tablets have a lower incidence of adverse effects compared to treatment with immediate-release metformin tablets. The analysis of the reports showed that "gastrointestinal disorders" was one of the most common classes reported, and metformin alone was the drug most commonly associated with serious gastrointestinal reactions that resulted in hospitalization. In addition, it was the drug most commonly associated with the lactic acidosis ADR. Even though most ADRs in the reports were serious, the majority progressed to cure. According to the analysis performed, the results suggest that the patient's renal function should be considered in order to prevent ADRs associated with metformin, such as lactic acidosis. Therefore, monitoring the safety profile of metformin remains essential to prevent serious ADRs. [ABSTRACT FROM AUTHOR]

There has been a rapid development in studies of nature-based solutions (NbS) worldwide, which reveals the potential of this type of solution and the high level of interest in its implementation to improve the resilience of cities. Much relevant information and many important results are being published, and it is now possible to see their diverse benefits and complexity. Several authors highlight their role in urban areas not just in temperature control, but also in human health, ecosystem development and water management. However, in the current reality of cities, where water use is being (and will be) constantly challenged, analyzing NbS advantages for the urban water cycle is crucial. This study performed an intense review of the NbS literature from 2000 to 2021, to identify their contributions to the improvement of urban water cycle management and thus provide a solid information base for distinct entities (public institutions, private investors and the urban population in general) to disseminate, apply and justify their implementation. In general terms, the urban water cycle embraces not only the abstraction of water for urban consumption, but also its return to nature and all the stages in between, including water reuse and stormwater management. This review will highlight the important benefits that NbS in general, and green roofs in particular, provide to urban stormwater control, a key factor that contributes to urban sustainability and resilience in order to face future climate challenges. The novelty of the present review paper falls within the conclusions regarding the crucial role that NbS develop in urban water management and the main features that must be tested and technically enhanced to improve their functioning. [ABSTRACT FROM AUTHOR]

Poly (ADP-Ribose) polymerase inhibitors (PARPi) have emerged as a targeted therapy in cancer treatment with promising results in various types of cancer. This work aims to investigate the profile of adverse drug reactions (ADRs) associated with PARPi through the reports provided by the Eudravigilance (EV) database. We also intend to analyze the potential association of peripheral neuropathy to PARPi. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. A total of 12,762 ICSRs were collected from the EV database. Serious cases of nervous system disorders were analyzed providing strong evidence that peripheral neuropathy was reported in a higher frequency in patients treated with niraparib. Most cases reported a not recovered/not resolved outcome and involved drug withdrawal. However, several studies suggest that PARPi attenuate chemotherapy-induced painful neuropathy. Unexpected ADRs such as peripheral neuropathy may also occur, mostly in patients taking niraparib. Further pharmacovigilance studies should be conducted in this area to clarify with more precision the toxicity profile of these drugs. [ABSTRACT FROM AUTHOR]

Stormwater runoff in green roofs (GRs) is represented by the runoff coefficient, which is fundamental to assess their hydraulic performance and to design the drainage systems downstream. Runoff coefficient values in newly installed GR systems should be estimated by models that must be feasible and reproduce the retention behavior as realistically as possible, being thus adjusted to each season and climate region. In this study, the suitability of a previously developed model for runoff coefficient determination is assessed using experimental data, and registered over a 1 year period. Results showed that the previously developed model does not quite fit the experimental data obtained in the present study, which was developed in a distinct year with different climate conditions, revealing the need to develop a new model with a better adjustment, and taking into consideration other variables besides temperature and precipitation (e.g., early-stage moisture conditions of the GR matrix and climate of the study area). Runoff coefficient values were also determined with different time periods (monthly, weekly, and per rain event) to assess the most adequate approach, considering the practical uses of this coefficient. The monthly determination approach resulted in lower runoff coefficient values (0–0.46) than the weekly or per rain event (0.017–0.764) determination. When applied to a long-term performance analysis, this study showed no significant differences when using the monthly, weekly, or per rain event runoff, resulting on a variation of only 0.9 m3 of annual runoff. This indicates that the use of monthly values for runoff coefficient, although not suitable for sizing drainage systems, might be used to estimate their long-term performance. Overall, this pilot extensive GR of 0.4 m2 presented an annual retention volume of 469.3 L, corresponding to a retention rate of 89.6%, in a year with a total precipitation of 1089 mm. The assessment of different time scales for runoff coefficient determination is a major contribution for future GR performance assessments, and a fundamental decision support tool. [ABSTRACT FROM AUTHOR]

This study aimed to develop a hydroxyethyl cellulose-based topical formulation containing probiotics and to evaluate its antimicrobial action using in vivo and ex vivo models. Initially, the antagonistic effects of Lacticaseibacillus rhamnosus ATCC 10863, Limosilactobacillus fermentum ATCC 23271, Lactiplantibacillus plantarum ATCC 8014 and Lactiplantibacillus plantarum LP-G18-A11 were analyzed against Enterococcus faecalis ATCC 29212, Klebsiella pneumoniae ATCC 700603, Staphylococcus aureus ATCC 27853 and Pseudomonas aeruginosa ATCC 2785. The best action was seen for L. plantarum LP-G18-A11, which presented high inhibition against S. aureus and P. aeruginosa. Then, lactobacilli strains were incorporated into hydroxyethyl cellulose-based gels (natrosol); however, only the LP-G18-A11-incorporated gels (5% and 3%) showed antimicrobial effects. The LP-G18-A11 gel (5%) maintained its antimicrobial effects and viability up to 14 and 90 days at 25 °C and 4 °C, respectively. In the ex vivo assay using porcine skin, the LP-G18-A11 gel (5%) significantly reduced the skin loads of S. aureus and P. aeruginosa after 24 h, while only P. aeruginosa was reduced after 72 h. Moreover, the LP-G18-A11 gel (5%) showed stability in the preliminary and accelerated assays. Taken together, the results show the antimicrobial potential of L. plantarum LP-G18-A11, which may be applied in the development of new dressings for the treatment of infected wounds. [ABSTRACT FROM AUTHOR]

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous vegetables, is an antimicrobial with yet controversial activities and mechanisms on fungi. Herein, the in silico and antifungal activities of SFN against C. albicans were investigated. In silico analyzes for the prediction of the biological activities and oral bioavailability of SFN, its possible toxicity and pharmacokinetic parameters, as well as the estimates of its gastrointestinal absorption, permeability to the blood-brain barrier and skin, and similarities to drugs, were performed by using different software. SFN in vitro anti-Candida activities alone and in combination with fluconazole (FLZ) were determined by the broth microdilution method and the checkerboard, biofilm and hyphae formation tests. Amongst the identified probable biological activities of SFN, nine indicated an antimicrobial potential. SFN was predicted to be highly absorbable by the gastrointestinal tract, to present good oral availability, and not to be irritant and/or hepatotoxic. SFN presented antifungal activity against C. albicans and prevented both biofilm and hyphae formation by this microorganism. SFN was additive/synergistic to FLZ. Overall, the data highlights the anti-Candida activity of SFN and its potential to be used as an adjuvant therapy to FLZ in clinical settings. [ABSTRACT FROM AUTHOR]

In folk medicine, Vismia guianensis is used to treat skin diseases and mycoses in the Amazon region. We evaluated the anti-Candida activity of the hydroalcoholic extract from the leaves of Vismia guianensis (EHVG). HPLC-PDA and FIA-ESI-IT-MSn were used to chemically characterize EHVG. The anti-Candida activity was determined in vitro by the minimum inhibitory concentrations (MIC) against Candida glabrata (ATCC-2001); Candida albicans (ATCC-90028, ATCC-14053, and ATCC-SC5314), and C. albicans clinical isolates. EHVG effects on adhesion, growth, and biofilm formation were also determined. Molecular docking was used to predict targets for EHVG compounds. The main compounds identified included anthraquinone, vismione D, kaempferol, quercetin, and vitexin. EHVG was fungicidal against all tested strains. C. albicans ATCC 14053 and C. glabrata ATCC 2001 were the most sensitive strains, as the extract inhibited their virulence factors. In silico analysis indicated that vismione D presented the best antifungal activity, since it was the most effective in inhibiting CaCYP51, and may act as anti-inflammatory and antioxidant agent, according to the online PASS prediction. Overall, the data demonstrate that EHVG has an anti-Candida effect by inhibiting virulence factors of the fungi. This activity may be related to its vismione D content, indicating this compound may represent a new perspective for treating diseases caused by Candida sp. [ABSTRACT FROM AUTHOR]

Candida albicans is a human pathogen that is part of the healthy microbiome. However, it is often associated with opportunistic fungal infections. The treatment of these infections is challenging because prolonged exposure to antifungal drugs can culminate in fungal resistance during therapy, and there is a limited number of available drugs. Therefore, this study investigated the antifungal activity of ononin by in silico and in vitro assays, and in Tenebrio molitor as an alternative in vivo model of infection caused by C. albicans. Ononin is an isoflavone glycoside derived from formononetin that has various biological activities. According in silico evaluation, ononin showed the best electron affinity in molecular docking with CaCYP51, with a binding free energy of −10.89 kcal/mol, superior to that of the antifungal drugs fluconazole and posaconazole. The ononin + CaCYP51 complex formed hydrogen bonds with Tyr132, Ser378, Phe380, and Met508, as well as hydrophobic connections with Tyr118, Leu121, Phe126, Leu131, Ile304, and Leu309, and interactions with the heme group. Ononin exerted anti-Candida albicans activity, with MIC between 3.9 and 7.8 µg/mL, and inhibited young and mature biofilms, with a reduction in cell density and metabolic activity of 50 to 80%. The compound was not cytotoxic to sheep red blood cells at concentrations up to 1000 µg/mL. Larvae of the mealworm T. molitor were used as an alternative in vivo model of C. albicans infection. Ononin was able to prolong larval survival at concentrations of 0.5, 1, and 5 mg/kg, and was not toxic up to a concentration of 20 mg/kg. Moreover, ononin reduced the fungal charge in treated animals. In conclusion, our results suggest that ononin has anti-Candida albicans activity and is a potential candidate for the development of new therapeutic alternatives. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 is an acute respiratory disease caused by the severe acute respiratory syndrome coronavirus 2. As the virus spreads rapidly, it has become a major public health emergency, which has led to rapid vaccines development. However, vaccines can present harmful and unintended responses, which must be notified to the National Pharmacovigilance System. The aim of this study is to characterize the adverse drug reactions (ADRs) of these vaccines notified in the region covered by the Regional Pharmacovigilance Unit (RPU) of Beira Interior, in Portugal, between 1 and 31 December 2020. During this period, 4 vaccines were administered: Comirnaty®, Spikevax®, Vaxzevria® and Jcovden®. The RPU of Beira Interior received 2134 notifications corresponding to 5685 ADRs, of which 20.34% (n = 434) of the notifications were considered serious reactions. Of these, 9.52% (n = 42) resulted in hospitalization and 0.45% (n = 2) resulted in death. Among the ADRs notified, reactions at or around the injection site, myalgia, headaches and pyrexia were the most commonly notified. Most ADRs were resolved within a few hours or days without sequelae. These ADRs are in accordance with clinical trials, the summary of product characteristics (SmPC) of each vaccine and ADR notifications from other countries. However, further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Simple Summary: This study compared muscle strength and power indicators in resistance-trained men by evaluating associations between phase angle and performance, while controlling for body composition. We evaluated dynamic muscle strength in bench press and back squat, and muscle power using the Wingate test and countermovement jump. Participants with higher phase angle displayed superior muscle strength of the upper limbs and greater muscle power of the lower limbs. Regarding countermovement jump and bench press, phase angle showed moderate association with performance, even after controlling for body composition. Still, lean soft tissue was the most important predictor of muscle strength and power. This study aimed to compare muscle strength and power indicators according to bioimpedance spectroscopy's phase angle (PhA) values, in resistance-trained (RT) men, while exploring associations between PhA and performance. Forty-four men aged 18–45 years, engaged in RT, were allocated according to PhA tertiles. Lean soft tissue (LST) and fat mass (%FM) were assessed using dual-energy x-ray absorptiometry; dynamic muscle strength using 1 repetition maximum (1RM) of bench press (BP) and back squat (BS) and muscle power using Wingate test (WT) and countermovement jump (CMJ). For WT and CMJ, the 3rd tertile was significantly higher than the 1st tertile (p = 0.027 and p = 0.018, respectively). Regarding BP 1RM, the 3rd tertile was significantly higher than the 2nd tertile (p = 0.037). LST better explained the variability in the WT, BS and BP (p =< 0.001), while %FM better accounted for jump height in CMJ (p =< 0.001). PhA was a predictor of performance in both CMJ (p = 0.040) and BP (p = 0.012), independently of LST and %FM. Participants with higher PhA also displayed superior muscle strength of the upper limbs and greater muscle power of the lower limbs. PhA displayed significant moderate associations with performance in CMJ and BP, even after controlling for body composition. Still, LST was the most important predictor of muscle strength and power. [ABSTRACT FROM AUTHOR]

Failures in endodontic treatments are mostly associated with the difficulty in eradicating microbes of the root canal system, highlighting the need to develop novel effective antimicrobials. Punica granatum (pomegranate) leaf hydroalcoholic extract may be a potential alternative in canal dressing, owing to its antimicrobial properties. The objective of this study was to evaluate the antimicrobial activity of hydroalcoholic leaf extract of Punica granatum (HEPg) alone or in combination with calcium hydroxide (Ca(OH)2) against Enterococcus faecalis and Candida albicans in isolation and in mono- and polymicrobial biofilms. Microdilution tests in broth and assays for inhibition of biofilm formation were carried out to evaluate the antimicrobial properties of HEPg and HEPg + Ca(OH)2 against Enterococcus faecalis and Candida albicans. The cytotoxicity of HEPg in HaCaT cells was evaluated by MTT assay. HEPg and HEPg + Ca(OH)2 exerted significant antimicrobial activity against planktonic cells and mono- and polymicrobial biofilms. The combination of Punica granatum extract with Ca(OH)2 appears to be a promising alternative in endodontic treatments, which could be tested in vivo to confirm the efficacy of this mixture in disinfecting root canal systems. [ABSTRACT FROM AUTHOR]

Simple Summary: Bioelectrical and body composition proprieties are linked to health status and physical performance. The bioelectrical impedance vector analysis (BIVA) is a valid approach for qualitatively and timely assessing body components in sports practice. However, it is still unclear, if bioimpedance vector patterns can provide relevant information regarding the aerobic power. For the first time, this study shows that BIVA is useful in discriminating professional futsal players according to their VO2max. In addition, fat mass and bioelectrical phase angle were identified as valid predictors for aerobic power. Aims: The present study aimed to assess the ability of bioelectrical impedance vector analysis (BIVA) in discriminating fitness levels in futsal players, exploring the association of body composition and bioelectrical parameters with aerobic power. Methods: Forty-eight professional futsal players (age 23.8 ± 5.3 years) were involved in a cross-sectional study during their pre-season phase. Fat mass (FM) and muscle mass were determined by dual-energy X-ray absorptiometry. VO2max was obtained by indirect calorimetry through a graded exercise test performed on a treadmill. Bioelectrical resistance (R), reactance (Xc), and phase angle (PhA) were directly measured using a foot-to-hand bioimpedance technology at a 50 kHz frequency. Bioelectric R and Xc were standardized for the participants' height and used to plot the bioimpedance vector in the R-Xc graph according to the BIVA approach. Results: The participants divided into groups of VO2max limited by tertiles showed significant differences in mean vector position in the R-Xc graph (p < 0.001), where a higher VO2max resulted in a longer vector and upper positioning. FM, muscle mass, and PhA differed (p < 0.01) among the athletes grouped by tertiles of VO2max, where athletes with a greater aerobic power showed a lower percentage of FM and a higher percentage of muscle mass and PhA. FM and PhA were associated with VO2max (FM: r = −0.658, p < 0.001; PhA: r = 0.493, p < 0.001). These relationships remained significant after adjusting for age and body mass (FM: ß = −0.335, p = 0.046; PhA: ß = 0.351, p = 0.003). Conclusions: Bioelectrical impedance vectors positioned on the lower pole of the R-Xc graph identified futsal players with a lower VO2max, while longer vectors corresponded to a greater aerobic power. Additionally, PhA, that describes the vector direction, was positively associated with VO2max, while a higher FM negatively affected VO2max in the futsal players. BIVA and PhA evaluation may represent a valid support for screening the aerobic fitness level in professional futsal players, when more sophisticated assessment methods are not available. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a pathology with increasing frequency in society, being one of the main causes of death worldwide. For this reason, new therapeutic targets have been studied over the years. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme responsible for reducing cortisone to its active form cortisol, which can lead to metabolic changes such as insulin resistance and hyperglycemia. Therefore, 11β-HSD1 inhibition may offer a new therapeutic approach for type 2 diabetes mellitus. This work intends to systematically review the available scientific evidence on this subject. For this, a search was conducted in three databases and 15 clinical and in vivo preclinical studies were included in this review. Despite the high inhibitory and selectivity levels achieved with several molecules and the demonstrated clinical efficacy in diabetes treatment, no phase III clinical trials have yet been conducted. This is important because the long-term effects of 11β-HSD1 inhibitors including the consequences in hypothalamic-pituitary-adrenal axis must be evaluated. However, this enzyme remains a promising target for drug development, including due to its effectiveness in controlling various factors that constitute the metabolic syndrome and its potential for multiple indications in patients with diabetes, including wound healing and weight loss. [ABSTRACT FROM AUTHOR]

Candidiasis is the most common fungal infection among immunocompromised patients. Its treatment includes the use of antifungals, which poses limitations such as toxicity and fungal resistance. Plant-derived extracts, such as Punica granatum, have been reported to have antimicrobial activity, but their antifungal effects are still unknown. We aimed to evaluate the antifungal and antiviral potential of the ethyl acetate fraction of P. granatum (PgEA) and its isolated compound galloyl-hexahydroxydiphenoyl-glucose (G-HHDP-G) against Candida spp. In silico analyses predicted the biological activity of G-HHDP-G. The minimum inhibitory concentrations (MIC) of PgEA and G-HHDP-G, and their effects on biofilm formation, preformed biofilms, and phospholipase production were determined. In silico analysis showed that G-HHDP-G has antifungal and hepatoprotective effects. An in vitro assay confirmed the antifungal effects of PgEA and G-HHDP-G, with MIC in the ranges of 31.25–250 μg/mL and 31.25 ≥ 500 μg/mL, respectively. G-HHDP-G and PgEA synergistically worked with fluconazole against planktonic cells. The substances showed antibiofilm action, alone or in combination with fluconazole, and interfered with phospholipase production. The antifungal and antibiofilm actions of PgEA and G-HHDP-G, alone or in combination with fluconazole, in addition to their effects on reducing Candida phospholipase production, identify them as promising candidates for therapeutics. [ABSTRACT FROM AUTHOR]

Herb-induced liver injury (HILI) can be caused by supplements containing herbs, natural products, and products used in traditional medicine. Herbal products' most common adverse reaction is hepatotoxicity. Almost every plant part can be used to make herbal products, and these products can come in many different forms, such as teas, powders, oils, creams, capsules, and injectables. HILI incidence and prevalence are hard to estimate and vary from study to study because of insufficient large-scale prospective studies. The diagnosis of HILI is a challenging process that requires not only insight but also a high degree of suspicion by the clinician. HILI presents with unspecific symptoms and is a diagnosis of exclusion. For diagnosis, it is necessary to make a causality assessment; the Council for International Organizations of Medical Sciences assessment is the preferred method worldwide. The most effective treatment is the suspension of the use of the suspected herbal product and close monitoring of liver function. The objective of this review is to highlight the necessary steps for the clinician to follow to reach a correct diagnosis of herb-induced liver injury. Further studies of HILI are needed to better understand its complexity and prevent increased morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Drug induced liver injury (DILI) is an adverse drug reaction that causes liver damage in a predictable (dose-dependent) or an unpredictable (idiosyncratic) fashion. We performed an assessment of DILI in Portugal, by analyzing the reports, sent to the Portuguese Pharmacovigilance System (PPS). Methods: A search was performed on the PPS database, in a 10-year time frame, from 1 January 2010 to 31 December 2019. Results: There was not a prevalence of either sex in any age group. Most reports (n = 1120, 55.0%) belonged to patients in the age group 19–64 years old. Hepatitis (n = 626, 26.7%) was the most common adverse drug reaction in our study. Hepatotoxicity (n = 362, 15.5%) and hepatitis (n = 333, 14.2%) were more frequent in age group 19–64 years old. Cholestasis was more prevalent in adults independently of age. Hepatic fibrosis and encephalopathy were more common in the elderly. Most patients consumed between one and four suspected drugs (n = 1867, 92%). Most patients in our study evolved to "cure" (n = 796; 39%). Hepatotoxicity (n = 23; 13.8%) and hepatitis (n = 610; 25.9%) had a female predominancy while choluria (n = 8; 4.8%) and splenomegaly (n = 8; 4.8%) were of male predominance. Conclusions: DILI is rare but can be fatal. As such, an active search of DILI is necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: The ability of specific bioelectrical impedance vector analysis (BIVA) to classify subjects according to the percentage of fat mass has been recognized in different cross-sectional studies, but no longitudinal designs have yet been applied. The results of this investigations showed that specific BIVA can be used as a practical solution for assessing body composition management in former overweight/obese athletes. In particular, reductions in bioelectrical vector length adjusted according to the specific BIVA procedure were found to be associated with reductions in percentage of fat mass. Background: specific bioelectrical impedance vector analysis (BIVA) has been proposed as an alternative bioimpedance method for evaluating body composition. This investigation aimed to verify the ability of specific BIVA in identifying changes in fat mass after a 16-week lifestyle program in former athletes. Methods: The 94 participants included in the Champ4life project (clinicaltrials.gov: NCT03031951) were randomized into intervention (n = 49) and control (n = 45) groups, from which 82 athletes completed the intervention (age 43.9 ± 9.2 y; body mass index 31.1 ± 4.6 kg/m2). Fat mass was estimated by dual-energy X-ray absorptiometry. Bioelectric resistance, reactance, phase angle, and vector length were assessed by bioelectric impedance spectroscopy, and the BIVA procedure was applied. Results: A significant (p < 0.05) group x time interaction for fat mass, specific resistance, reactance, and vector length was found. Fat mass and vector length significantly (p < 0.05) decreased in the intervention group, while no change was measured in the control group. Considering the participants as a whole group, changes in vector length were associated with changes in fat mass percentage (r2 = 0.246; β = 0.33; p < 0.001) even after adjusting for age, sex, and group (R2 = 0.373; β = 0.23; p = 0.002). Conclusions: The specific BIVA approach is suitable to track fat mass changes during an intervention program aimed to reduce body fat in former athletes. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis is a common fungal infection in women. In this study, Platonia insignis hydroalcoholic extract (PiHE) and its fractions were evaluated for antifungal and antivirulence activities against vaginal Candida species. Dichloromethane (DCMF) and ethyl acetate fractions (EAF) obtained from PiHE effectively inhibited the pathogen. Electrospray ionization mass spectrometry was used for identifying the main compounds in extracts. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined by a broth microdilution assay. Furthermore, we evaluated the effect of the extract and fractions on the virulence properties of Candida albicans, and their cytotoxicity effect was determined on RAW 264.7 cells. Compounds found in extracts were flavonoid glycosides, mainly derivatives of quercetin and myricetin. Extracts showed antifungal potential, with the lowest MIC value for EAF (1.3 mg/mL) and inhibited Candida adherence and biofilm formation. EAF disrupted 48 h biofilms with an inhibition rate of more than 90%. The extract and its fractions exhibited no cytotoxicity. The antifungal effects were attributed to the ability of these extracts to alter the mitochondrial membrane potential for the release of pro-apoptotic factors in the cytosol. In conclusion, our data suggest that PiHE and EAF could act as novel candidates for the development of new therapeutic treatments against fungal infections. [ABSTRACT FROM AUTHOR]

Candida yeasts are generally found in the vaginal microbiota; however, disruption of the balance maintained by host factors and microorganisms results in vulvovaginal candidiasis (VVC). This study evaluated the antagonistic activity of vaginal Lactobacillus spp. on Candida albicans to verify whether active compounds of Lactobacillus spp. had antifungal and antivirulence activity. The antagonism assay showed that 15 out of 20 Lactobacillus strains had an inhibitory effect on C. albicans. Biosurfactants displayed surface-tension-reducing activity, with the best value obtained for Lactobacillus gasseri 1. Lactobacillus rhamnosus ATCC 9595, Lactobacillus acidophilus ATCC 4356, and Lactobacillus paracasei 11 produced biosurfactants that decreased C. albicans adhesion and disrupted biofilm formation. The best results were obtained in the pre-incubation assay for L. gasseri 1 and L. paracasei 11. Overall, Lactobacillus strains showed significant anti-Candida activity, and their biosurfactants exhibited considerable anti-adhesion and antibiofilm activity against C. albicans. To be considered safe for use in vivo, the safety of biosurfactant (BS) should be investigated using cytotoxicity assays. [ABSTRACT FROM AUTHOR]

The occurrence of damage on bacterial DNA (mediated by antibiotics, for example) is intimately associated with the activation of the SOS system. This pathway is related to the development of mutations that might result in the acquisition and spread of resistance and virulence factors. The inhibition of the SOS response has been highlighted as an emerging resource, in order to reduce the emergence of drug resistance and tolerance. Herein, we evaluated the ability of betulinic acid (BA), a plant-derived triterpenoid, to reduce the activation of the SOS response and its associated phenotypic alterations, induced by ciprofloxacin in Staphylococcus aureus. BA did not show antimicrobial activity against S. aureus (MIC > 5000 µg/mL), however, it (at 100 and 200 µg/mL) was able to reduce the expression of recA induced by ciprofloxacin. This effect was accompanied by an enhancement of the ciprofloxacin antimicrobial action and reduction of S. aureus cell volume (as seen by flow cytometry and fluorescence microscopy). BA could also increase the hyperpolarization of the S. aureus membrane, related to the ciprofloxacin action. Furthermore, BA inhibited the progress of tolerance and the mutagenesis induced by this drug. Taken together, these findings indicate that the betulinic acid is a promising lead molecule in the development helper drugs. These compounds may be able to reduce the S. aureus mutagenicity associated with antibiotic therapies. [ABSTRACT FROM AUTHOR]

This cross-sectional study aimed to explore specific online behaviours and their association with a range of underlying psychological and other behavioural factors during the COVID-19 pandemic. Eight countries (Italy, Spain, the United Kingdom, Lithuania, Portugal, Japan, Hungary, and Brazil) participated in an international investigation involving 2223 participants ( M = 33 years old; SD = 11), 70% of whom were females. Participants were surveyed for specific type of Internet use severity, appearance anxiety, self-compassion, and image and use of performance-enhancing drugs (IPEDs). Results were compared cross-culturally. The mean time spent online was 5 h ( SD = ±3) of daily browsing during the pandemic. The most commonly performed activities included social networking, streaming, and general surfing. A strong association between these online behaviours and appearance anxiety, self-compassion, and IPEDs use was found after adjustment for possible confounders, with higher scores being associated with specific online activities. Significant cross-cultural differences also emerged in terms of the amount of time spent online during the initial stages of the COVID-19 pandemic.

Background and objective: For a high level athlete, it is essential to ensure optimal energy as well as macro- and micro-nutrient and fluid intakes, in order to improve their performance during training and competition. Protein intake should be 1.2⁻2.1 g/kg/d, whereas the requirements for carbohydrate and fat intakes should be >5g/kg/d and 20⁻35% of energy, respectively. The micronutrient and fluid intakes in athletes were compared to the Dietary Reference Intake (DRI) and European Food Safety Authority (EFSA) recommendations, respectively. This study aimed to characterize and compare the nutritional habits of athletes at the preparatory and competitive phase, and to test if their nutritional intakes were in accordance with the recommendations. Materials and methods: A total of 276 professional athletes were assessed. To evaluate their nutritional intake, the athletes completed a 7 days food record. Under reporting was defined using a ratio of energy intake to basal metabolic rate (BMR) of 1.1. Body composition was assessed using dual energy X-ray absorptiometry (DXA). Results: Almost half (49%) of the athletes from the final sample reported lower measured intakes of carbohydrates and 27% reported a higher consumption of proteins than what was recommended. In both the preparatory and competitive phases, the micronutrients with a higher mismatch between the actual and recommended intakes were vitamins D and E, magnesium, folate, calcium, and zinc for both sexes, and iron intake for females. A large proportion of athletes reported a lower water intake. Compared to the recommendations, males reported a higher intake of carbohydrates, lipids, vitamins E, calcium, and magnesium ( p <0.05) in the competitive phase, while females reported a lower ingestion of water, vitamins A and D, and calcium ( p <0.05) in the preparatory phase. Conclusions: Overall, in the preparatory and competitive phases of the season, athletes reported a macro- and micro-nutrient intake below the recommendations, especially in the female athletic population. Dietary intakes in athletes need to be optimized and adjusted to their requirements, according to sex and sport, so as to avoid compromising health and performance.