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Aim:To evaluate the antifungal activity of amlodipine against strains of Candidaspp. and to its possible mechanism of action.Methods:Broth microdilution tests were used to determine the minimum inhibitory concentration, while the synergistic activity was evaluated by calculating the fractional inhibitory concentration index. The action of amlodipine against biofilms was determined using the MTT assay and its possible mechanism of action was investigated through flow cytometry tests.Results:Amlodipine showed MICs ranging from 62.5 to 250 μg/ml, in addition to action against pre-formed and forming biofilms, with reductions between 50 and 90%. Amlodipine increases the externalization of phosphatidylserine and reduces the cell viability of fungal cells, suggesting apoptosis.Conclusion:Amlodipine had good antifungal activity against planktonic cells and biofilms of Candidaspp., by leading the cells to apoptosis.

Purpose: Testosterone therapy represents the cornerstone of gender affirming hormone therapy (GAHT) among t-AFAB (transgender Assigned Female At Birth) people. Minoxidil is a vasodilator drug approved for topical use for the treatment of androgenetic alopecia. The aim of the present study was to evaluate the efficacy of topical minoxidil in enhancing beard growth in a group of t-AFAB people on GAHT. Methods: Sixteen t-AFAB individuals with an incomplete beard development, on GAHT for at least 6 months, were enrolled. Topical minoxidil was applied to the interested facial areas. Before starting (T0), after 3 (T3) and 6 (T6) months, we evaluated facial hair growth using the Ferriman-Gallwey modified score (FGm). Results: Subjects were 26 (2.7) years old and on GAHT for 18.5 [15–54] months; using a paired match evaluation, a statistically significant facial hair growth was observed over time, in particular at T6 (median upper lip FGm 3.5 [3–4] vs 2 [1–2] at T0 and chin FGm 4 [3.25–4] vs 1 [1–2] at T0; p ≤ 0.002). Comparing the minoxidil group with a control group (n = 16) matched for age and BMI who developed a full-grown beard only with GAHT, a logistic multivariable analysis identified hirsutism before GAHT was independently positively associated with the development of a full beard [OR 15.22 (95% CI 1.46–158.82); p = 0.023]. Conclusions: This is the first study demonstrating the efficacy of topical minoxidil in enhancing facial hair growth among t-AFAB people on GAHT. Further studies will be necessary to assess whether the obtained improvements will persist after discontinuing the medication.

Purpose: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. Methods: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). Results: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p< 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p< 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. Conclusions: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

This research highlights the efficacy of NaNbO3as a coating for P2-Na2/3Ni1/3Mn2/3O2cathodes in sodium-ion batteries. The coating enhances the kinetic behavior and cyclability of the electrochemical cells, as shown by electrochemical measurements. XRD analysis indicates that Nb does not incorporate into the cathode structure, implying a physical interaction between the coating and the cathode material. XRF analysis and EDX mapping confirm the actual composition and uniform dispersion of elements throughout the sample, while the electron micrographs evidence the occurrence of NaNbO3particles modifying the surface of the layered oxide. The Ni4+/Ni3+and Ni3+/Ni2+redox pairs, along with the partially reversible oxidation of oxide to peroxide anions, contribute significantly to cell capacity, as revealed by XPS spectra. This last effect and the appearance of a co-intercalated phase at high voltage are positive factors to provide fast kinetics. Cyclic voltammograms show that samples coated with 2–3% NaNbO3have superior rate capability, with high capacitive response and apparent diffusion coefficients. These samples also have low impedance at the electrode–electrolyte interface, which helps deliver a high capacity at 5C. Further cycling at 1C shows improved cyclability in the bare and 3% coated samples, due to their higher diffusion coefficients on charging. Notably, the 3% NaNbO3-coated sample exhibits excellent cyclability below 0 °C, making it a promising cathode material for sodium-ion batteries.

Solving the electronic Schrodinger equation for strongly correlated ground states is a long-standing challenge. We present quantum algorithms for the variational optimization of wave functions correlated by products of unitary operators, such as Local Unitary Cluster Jastrow (LUCJ) ansatzes, using stochastic reconfiguration (SR) and the linear method (LM). While an implementation on classical computing hardware would require exponentially growing compute cost, the cost (number of circuits and shots) of our quantum algorithms is polynomial in system size. We find that classical simulations of optimization with the linear method consistently find lower energy solutions than with the L-BFGS-B optimizer across the dissociation curves of the notoriously difficult N2and C2dimers; LUCJ predictions of the ground-state energies deviate from exact diagonalization by 1 kcal/mol or less at all points on the potential energy curve. While we do characterize the effect of shot noise on the LM optimization, these noiseless results highlight the critical but often overlooked role that optimization techniques must play in attacking the electronic structure problem (on both classical and quantum hardware), for which even mean-field optimization is formally NP hard. We also discuss the challenge of obtaining smooth curves in these strongly correlated regimes, and propose a number of quantum-friendly solutions ranging from symmetry-projected ansatz forms to a symmetry-constrained optimization algorithm.

There is an urgent need for animal models of meibomian gland dysfunction (MGD) and evaporative dry eye disease (EDED) to understand their pathophysiology and investigate novel therapeutics. This study sought to further define the acyl-CoA: wax alcohol acyltransferase 2knockout (Awat2KO) mouse as a model of EDED using a combination of novel clinical, biochemical, and biophysical endpoints.

Magnetically responsive soft biomaterials are at the forefront of bioengineering and biorobotics. We have created a magnetic hybrid material by coupling silk fibroin─i.e., a natural biopolymer with an optimal combination of biocompatibility and mechanical robustness─with the FeCo alloy, the ferromagnetic material with the highest saturation magnetization. The material is in the form of a 6 μm-thick silk fibroin film, coated with a FeCo layer (nominal thickness: 10 nm) grown by magnetron sputtering deposition. The sputtering deposition technique is versatile and eco-friendly and proves effective for growing the magnetic layer on the biopolymer substrate, also allowing one to select the area to be decorated. The hybrid material is biocompatible, lightweight, flexible, robust, and water-resistant. Electrical, structural, mechanical, and magnetic characterization of the material, both as-prepared and after being soaked in water, have provided information on the adhesion between the silk fibroin substrate and the FeCo layer and on the state of internal mechanical stresses. The hybrid film exhibits a high magnetic bending response under a magnetic field gradient, thanks to an ultralow fraction of the FeCo component (less than 0.1 vol %, i.e., well below 1 wt %). This reduces the risk of adverse health effects and makes the material suitable for bioactuation applications.

The study of foam injection dynamics into porous media holds numerous applications, with its primary use being the optimization of the oil extraction process. Additionally, it finds utility in various other domains, including soil decontamination techniques. This study focuses on evaluating foam injection through low-cost experiments and computational models. The model integrates a classic two-phase immiscible fluid flow in a porous media framework, augmented by a mobility reduction factor to simulate foam’s impact on gas phase mobility. Simple experiments were conducted to assess water displacement using both gas and gas-foam injection methods. Results revealed that while gas injection tends to form preferential paths rapidly, leading to gas disruption, foam injection generates a more compact front, enhancing sweep efficiency by mitigating preferential path formation. The computational model successfully reproduced the experimental findings qualitatively. This research introduces a cost-effective experiment suitable for didactic purposes, illustrating complex concepts and underscoring the complementary nature of experimental and computational methodologies in advancing engineering techniques.

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Background: The DNA mismatch repair (MMR) system serves as a sophisticated guardian of the precise functioning of the human genome. Dysregulation within this system is linked to the oncogenesis process. Reduced expression of MMR system proteins identified in salivary gland tumors (SGTs) suggests an increased risk of tumoral occurrence. This study aims to analyze the expression of MMR proteins in SGTs and discuss the relevance of this association to the development of these neoplasms. Material and Methods: This review was conducted following the PRISMA guidelines and was registered in PROSPERO (CRD42023465590). A comprehensive search of the PubMed/MEDLINE, Web of Science, Scopus, Embase, and ProQuest (non-peer reviewed platform) was performed to answer the question "Do DNA MMR system proteins exhibit expression in SGTs?". The methodological quality of the selected studies was assessed using the JBI's Critical Appraisal Tool. Results: A total of 142 patients with benign SGTs and 84 with malignant SGTs were included in this review. The literature analysis showed a notable reduction in the expression of DNA MMR system proteins (hHMS2, hMLH1, hMSH3 and hMSH6) in the percentage of marked cells. Conclusions: The reduction in the expression of the DNA MMR system proteins suggests an interesting correlation with the development of malignant and benign SGTs. Nevertheless, further investigations are warranted to better clarify the precision of measuring biomarker protein expression. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia(S. maltophilia) is an intrinsically drug-resistant and biofilm-forming bacteria causing infections in immunocompromised humans. This study reports the isolation of five S. maltophiliastrains from saliva and gingival crevicular fluid (GCF) of AIDS patients with periodontitis in São Paulo, Brazil, showing resistance to ceftazidime, strong biofilm formation capacity and a close genetic relationship. The presence of S. maltophiliastrains in saliva and CGF of patients with AIDS and periodontitis is a concern for the presence and persistence of intrinsically resistant bacteria in the oral environment, enhancing the risk for the development of severe infections in immunocompromised patients.

Aortic graft infection (AGI) is a life-threatening complication that can result in death, amputation, sepsis, aorto-enteric fistula, and pseudoaneurysm formation. After explantation of the infected graft, options for reconstruction include extra-anatomic bypass or in-line reconstruction using antibiotic-coated prosthetic graft, cryopreserved allograft, or a neo-aortoiliac system (NAIS) using autogenous femoral veins. While the NAIS procedure has shown promising results, there is relatively limited clinical experience due the magnitude and morbidity of the surgery. In this study, we reviewed our single-center experience using the NAIS procedure and performed a systematic review of the contemporary literature more than the past decade.

Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension.

ABSTRACTIntroductionTelemedicine has shown promising results, allowing specialists to provide rapid and effective care in remote locations. However, to our knowledge, current evidence is not robust enough to prove the effectiveness of this tool. This cluster-randomized trial (CRT) aimed to evaluate the impact of telemedicine on clinical care indicators in pediatric intensive care units (PICUs).MethodsAn open-label CRT was conducted in 16 PICUs within the Brazilian public health system. The trial took place from August 2022 to December 2023 and compared an intervention group, which received telemedicine support, with a control group, which received usual PICU care. The primary outcome was the PICU length of stay. The main secondary outcomes were mortality rate and ventilator-free days.ResultsA total of 1393 participants were included, 657 in the control group and 736 in the intervention group. The mean PICU length of stay was 10.42 (SD, 10.71) days for the control group and 11.52 (SD, 10.80) days for the intervention group. The overall mean of ventilator-free days was 6.82 (SD, 7.71) days. Regarding mortality, 7.54% of participants died in total. No significant difference was found in the outcomes between the groups.ConclusionDespite the potential benefits of telemedicine, its effective implementation in the Brazilian public health system faces considerable challenges, highlighting the continued importance of investigating and improving the role of telemedicine in pediatric critical care.Clinical trial registrationClinicalTrials.gov NCT05260710 and ReBEC – RBR-7×j4wyp.

The reliable measurement of the inorganic carbon content of soils and its changes resulting from land management practices and amendments is crucial for precisely quantifying carbon stocks as part of monitoring, reporting, and verification schemes. While various methods are available for evaluating the carbonate content in soils, the most direct approach is calcimetry, which involves the dissolution of solid-phase carbonates and the evolution of gas-phase CO2through acid-initiated reactions. Despite being a well-established method, uncertainties about how reliable calcimetry is to measure small changes in soil inorganic carbon (SIC) or how its measurement may be affected by potentially interfering reactions, sample size, and solid–liquid contact call for a dedicated investigation of these effects. The present study demonstrates the reliability of the calcimetry method and its limits through a parametric analysis that investigated the effect of the solid-to-liquid ratio, the presence of unweathered silicate phases, and the presence of copious amounts of organic matter. The results point to the reliable performance of calcimetry within the range of soil conditions that can be expected to be encountered during activities involving enhanced rock weathering and other best management practices that aim to boost the global soil carbon stocks as a climate change mitigation strategy.

ABSTRACTIntroductionOncogenic tyrosine kinases (TK) are enzymes that play a key role in cell growth and proliferation and their mutations can lead to uncontrolled cell growth and development of aggressive cancer. This knowledge has led to the development of new classes of drugs, Tyrosine kinase inhibitors (TKI). They target oncogenic kinases who are associated with advanced radioactive iodine (RAI) refractory TC, which is not able to uptake RAI anymore and/or still grows between consecutive treatments with Iodine 131 (I131).Areas coveredSince Lenvatinib and Sorafenib approval, several other molecular inhibitors have been studied and then introduced for the treatment of aggressive and refractory thyroid cancer (TC), and, although the development of adverse effects or tumor resistance mechanisms, more and more compounds are still under investigation. The literature search was executed in PubMed and ClinicalTrials.gov to identify relevant articles and clinical trials published until December 2023.Expert opinionIn the context of clinical trials, driven by the presence of specific molecular mutations or even in the absence of both conditions, systemic therapy TKIs are valuable weapons to be used in patients affected by aggressive forms of TC, waiting for further expansion of the treatment landscape with more efficacious and safer drugs.

The decrease in species richness toward higher latitudes is an expected biogeographical pattern. This pattern could be related to particular environmental constraints and the evolutionary history of clades. However, species richness does not fully represent the evolutionary history of the clades behind their distributions. Phylogenetic diversity better clarifies the role of historical factors in biogeographical patterns. We analyzed environmental and historical drivers related to latitudinal variation in species richness and phylogenetic diversity of Atlantic Forest endemic snakes. We implemented species distribution models, from voucher-based locality points, to map the snake ranges and diversity. We used generalized additive mixed models to evaluate the relationships among the diversity metrics and area, topographical roughness, and past climate change velocity since the Last Maximum Glacial in the Atlantic Forest latitudinal gradient. Contrary to the expected general pattern, species richness was higher toward higher latitudes, being positively related to past climatic stability. Species richness also increased with total area and higher topographical roughness. Phylogenetic diversity, on the other hand, showed opposite relationships related to the same factors. Phylogenetic diversity increased with lower climatic stability in lower latitudes. Thus, dimensions of diversity were affected in different ways by historical and environmental constraints in this unique and threatened biodiversity hotspot.

Le onde d’urto a bassa intensità (LI-ESWT) emergono come un trattamento promettente per la disfunzione erettile (DE). Questa terapia non invasiva, che sfrutta l’utilizzo di onde acustiche, migliora il flusso sanguigno penieno con effetti positivi sulla funzionalità erettile. In letteratura sono emerse sempre maggiori evidenze rispetto all’efficacia delle LI-ESWT. I principali vantaggi di tale metodica includono la non invasività, i minimi effetti collaterali e la procedura eseguibile in setting ambulatoriale. Tuttavia, i costi della metodica, la necessità di sedute multiple e l’efficacia non garantita a tutte le classi di pazienti con DE rappresentano alcune limitazioni. Inoltre, sono ancora dubbi i benefici a lungo termine di tale terapia ed è ancora in fase di definizione un profilo chiaro dei pazienti che potrebbero trarne maggior vantaggio.

Copy number variants (CNVs) represent the genetic cause of about 15–20% of neurodevelopmental disorders (NDDs). We identified a ~67 kb de novo intragenic deletion on chromosome 2q22.3 in a female individual showing a developmental encephalopathy characterised by epilepsy, severe intellectual disability, speech delay, microcephaly, and thin corpus callosum with facial dysmorphisms. The microdeletion involved exons 5-6 of GTDC1, encoding a putative glycosyltransferase, whose expression is particularly enriched in the nervous system. In a previous study, a balanced de novo translocation encompassing GTDC1was reported in a male child with global developmental delay and delayed speech and language development. Based on these premises, we explored the transcriptomic profile of our proband to evaluate the functional consequences of the novel GTDC1de novo intragenic deletion in relation to the observed neurodevelopmental phenotype. RNA-seq on the proband’s lymphoblastoid cell line (LCL) showed expression changes of glycine/serine and cytokine/chemokine signalling pathways, which are related to neurodevelopment and epileptogenesis. Subsequent analysis by ELISA (enzyme-linked immunosorbent assay) and HPLC (high-performance liquid chromatography) revealed increased levels of glycine in the proband’s LCL and serum compared to matched controls. Given that an increased level of glycine has been observed in the plasma samples of individuals with Rett syndrome, a condition sharing epilepsy, microcephaly, and intellectual disability with our proband, we proposed that the GTDC1downregulation is implicated in neurodevelopmental impairment by altering glycine metabolism. Furthermore, our findings expanded the phenotypic spectrum of the novel GTDC1-related condition, including microcephaly and epilepsy among relevant clinical features.

Sequential infiltration synthesis (SIS) is a scalable and valuable technique for the synthesis of organic–inorganic materials with several potential applications at the industrial level. Despite the increasing interest for this technique, a clear picture of the fundamental physicochemical phenomena governing the SIS process is still missing. In this work, infiltration of Al2O3into thin poly(methyl methacrylate) (PMMA) films using trimethyl aluminum (TMA) and H2O as precursors is investigated by operando dynamic spectroscopic ellipsometry (SE) analysis. The TMA diffusion coefficient values at temperatures ranging from 70 to 100 °C are determined, and the activation energy for the TMA diffusion process in PMMA is found to be Ea= 2.51 ± 0.03 eV. Additionally, systematic data about reactivity of TMA molecules with the PMMA matrix as a function of temperature are obtained. These results provide important information, paving the way to the development of a comprehensive theory for the modeling of the SIS process.

Wheat porridge contributes to the intake of micronutrients but can also be a route of the toxic heavy metal, cadmium. This study aimed to determine the effect of processing on micronutrients, cadmium dialyzability, and cellular bioaccessibility. Cadmium (0.21%), magnesium (0.19%), iron (0.17%), and zinc (0.07%) presented low bioaccessibility from raw whole wheat flour. Boiling and germination reduced phytic acid content (p< .001) but failed to improve mineral bioaccessibility compared to raw flour. Fermentation increased the bioaccessibility of cadmium (2.3‐fold), magnesium (8.3‐fold), iron (2.2‐fold), and zinc (10.4‐fold) (p< .001). Dialyzability only presented a valid correlation with bioaccessibility for cadmium (r= 0.68; p< .001). Food processing did not decrease cadmium bioaccessibility from wheat porridge. Dialyzability was a suitable method to estimate the cellular bioaccessibility of cadmium, but not other beneficial elements. Strategies to decrease cadmium bioaccessibility from foods are still needed. However, based on these results, the dialyzability assay reported here could allow the rapid screening of wheat‐based foods for their cadmium bioaccessibility.

Neonatal hypoxic-ischemic encephalopathy after perinatal asphyxia causes neurolinguistic disturbances in children without disabilities. Poor academic performance appears as a long-term result. Language intervention is sought to reduce harmful effects on children. The aim of this study is showing the relationship between clinical conditions of hypoxic-ischemic-encephalopathy (HIE) and language disorders in children without disabilities. This cross-sectional study with a neurolinguistic approach was carried out in patients with perinatal asphyxia during childbirth, at the ZH Sikder Women's Medical College Hospital, Bangladesh. Respondents between 4 and 12 years, 76% underwent cranial computed tomography (CT); 82% underwent magnetic resonance imaging (MRI); and 70% underwent electroencephalogram (EEG). Among them were found positive results for neonatal hypoxia ischemic encephalopathy (EHI). These results are related to the following language disorders: reception/perception disorder (64%), sociolinguistic disorders (84%); metalinguistic competence disorder (66%); 86% of children had poor peer relationships and 72% had reading and writing disorders. Concluding, school-age children after perinatal asphyxia who developed Hypoxic-Ischemic Encephalopathy (HIE) had language disorders and poor school performance. There are still challenges to be overcome, as this is the first neurolinguistic approach in Bangladesh. More large-scale studies are needed.

The adaptation of traditional roads (tRoads) into electrified roads (eRoads) generally requires the inclusion of a charging unit (CU) in the pavement. In this study, the structural behaviour of a conductive eRoad is assessed using 2-D FEM simulations, and compared to the behaviour of a tRoad. Thermal and mechanical loadings representative of field configurations were applied and the relaxation response of the bituminous mixtures was calculated. Resulted strain and stress fields indicated a differential thermomechanical behaviour of the eRoad components. Strain and stress concentrations due to daily temperature fluctuations were pronounced near the interface with the CU. Traditional parameters obtained at the bottom of the bituminous layer were found similar for tRoad and eRoad. It is concluded that the development of new failure criteria is necessary to predict the service life of eRoads, in order to consider the thermally-induced strain and the impact of the volumetric rearrangement of the CU.

Green’s function methods lead to ab initio, systematically improvable simulations of molecules and materials while providing access to multiple experimentally observable properties such as the density of states and the spectral function. The calculation of the exact one-particle Green’s function remains a significant challenge for classical computers and was attempted only on very small systems. Here, we present a hybrid quantum-classical algorithm to calculate the imaginary-time one-particle Green’s function. The proposed algorithm combines the variational quantum eigensolver and the quantum subspace expansion methods to calculate Green’s function in Lehmann’s representation. We demonstrate the validity of this algorithm by simulating H2and H4on quantum simulators and on IBM’s quantum devices.

Chemical doping is an important approach to manipulating charge-carrier concentration and transport in organic semiconductors (OSCs)1–3and ultimately enhances device performance4–7. However, conventional doping strategies often rely on the use of highly reactive (strong) dopants8–10, which are consumed during the doping process. Achieving efficient doping with weak and/or widely accessible dopants under mild conditions remains a considerable challenge. Here, we report a previously undescribed concept for the photocatalytic doping of OSCs that uses air as a weak oxidant (p-dopant) and operates at room temperature. This is a general approach that can be applied to various OSCs and photocatalysts, yielding electrical conductivities that exceed 3,000 S cm–1. We also demonstrate the successful photocatalytic reduction (n-doping) and simultaneous p-doping and n-doping of OSCs in which the organic salt used to maintain charge neutrality is the only chemical consumed. Our photocatalytic doping method offers great potential for advancing OSC doping and developing next-generation organic electronic devices.

ABSTRACTIntroductionThe oral cavity harbors an extensive array of over 700 microorganisms, forming the most complex biome of the entire human body, with bacterial species being the most abundant. Oral diseases, e.g.periodontitis and caries, are strictly associated with bacterial dysbiosis. Porphyromonas gingivalisand Streptococcus mutansstand out among bacteria colonizing the oral cavity.Areas coveredAfter a brief overview of the bacterial populations in the oral cavity and their roles in regulating (flora) oral cavity or causing diseases like periodontal and cariogenic pathogens, we focused our attention on P.gingivalisand S.mutans, searching for the last-5-year patents dealing with the proposal of new strategies to fight their infections. Following the PRISMA protocol, we filtered the results and analyzed over 100 applied/granted patents, to provide an in-depth insight into this R&D scenario.Expert opinionSeveral antibacterial proposals have been patented in this period, from both chemical – peptides and small molecules – and biological – probiotics and antibodies – sources, along with natural extracts, polymers, and drug delivery systems. Most of the inventors are from China and Korea and their studies also investigated anti-inflammatory and antioxidant effects, being beneficial to oral health through a prophylactic, protective, or curative effect.