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Objectives: To conduct an equivalency randomized controlled trial comparing occlusal splint (OS) and botulinum toxin-A (BTX-A) on jaw muscle pain in probable sleep bruxism., Methods: Sixty patients (≥18 years, probable sleep bruxism, and jaw muscle pain) were randomly allocated into groups. The primary outcome was the reduction of jaw muscle pain, assessed using the Graded Chronic Pain Scale (GCPS, v2.0). Secondary outcomes included: parameters of jaw opening and mandibular mobility; distribution of muscle pain; Jaw Functional Limitation Scale-20 (JFLS-20), Oral Behaviors Checklist (OBC); and Oral Health Impact Profile-14 (OHIP-14). Only the evaluator was blinded. Multilevel mixed-effects regression models were used., Results: Fifty-nine patients (30 received OS and 29 BTX-A) were analyzed at baseline, 3 and 6 months follow-up. One patient dropped out after receiving the intervention. No differences between the interventions were observed concerning the GCPS (p = 0.627), although a significant reduction was observed at 3 (OR=13.26, 95%CI[6.61-26.59]) and 6 months (OR=12.36, 95%CI[4.93-30.98]), regardless of the treatment. BTX-A showed a lower score reduction on JFLS-20 than OS (OR=0.29, 95%CI[0.11-0.82]). BTX-A presented inferior results for the parameters: opening without pain(p = 0.045), unassisted maximum opening(p = 0.024), assisted maximum opening(p = 0.041), and protrusion(p = 0.016). An improvement in OHIP-14 scores was observed at 3 (IRR=1.08, CI95%[1.02-1.14]) and 6 months (IRR=1.10, CI95%[1.04-1.16]), regardless of the intervention. BTX-A participants(n = 23;79,3%) reported mild discomfort during chewing., Conclusion: OS and BTX-A can effectively decrease the GCPS scores, improve OHRQoL, and enhance functional outcomes in sleep bruxist patients with jaw muscle pain. OS demonstrated slight advantages in specific parameters., Clinical Significance: Both occlusal splints and botulinum toxin-A effectively reduce jaw muscle pain in bruxist patients, improving quality of life and mandibular function. Clinically, occlusal splints may offer additional benefits in specific functional parameters. (NCT03456154)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes., Methods: The expression of the NPY/melanocortin receptors' levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system., Results: In this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the Lepr-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity., Conclusions: Our results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study examines the kinetics and thermodynamics of the inclusion complex (IC) formation between sodium dodecylbenzenesulfonate (SDBS) and amine-modified β-cyclodextrin (βCD-NH 2 ) using surface plasmon resonance (SPR) and theoretical analysis. We determined a binding constant of 10 3 L mol -1 for the thermodynamically stable complex ([βCD-NH 2 /SDBS]°) within the temperature range of 285.2-301.2 K. The thermodynamic analysis revealed a transition from entropy-driven to enthalpy-driven behavior with increasing temperature. The rate constant for IC formation was approximately 10 2 M -1 s -1 , with the residence time decreasing from 14.08 s at 285.2 K to 6.13 s at 301.2 K. We observed the formation of an activated complex ([βCD-NH 2 /SDBS] ‡ ), with energetic parameters indicating temperature dependence. At 285.2 K, the activated enthalpy change was positive, while at 301.2 K, it was negative. The dissociation energetic parameters remained temperature-independent. Additionally, increasing concentrations of the ionic liquid 1-butyl-3-methylimidazolium chloride influenced the SDBS tail's conformation and penetration into the βCD-NH 2 cavity at the activated state. These findings provide insights into the complexation mechanism and the effects of the temperature and ionic liquids on IC formation.

Background: Despite numerous clinical studies on bruxism management, critical evaluation parameters, including the impact of bruxism pain on quality of life and secondary issues like changes in craniocervical posture, are often disregarded., Research Question: Evaluate the effect of two treatments on the craniocervical posture of adult patients with myofascial pain., Methods: This parallel randomized clinical trial included 60 patients with myofascial pain due to probable bruxism that fulfilled the study requirements. A computer-generated random sequence was used to allocate treatments: botulinum toxin-A or occlusal appliance. Follow-up time was 3 and 6 months. Kyphosis angle (α) and head posture measurement by cervical radiograph were assessed using two-way repeated measures ANOVA (alpha = 0.05)., Results: Sixty patients were randomized (mean age 30 ± 7.6) and 6 were excluded from the analysis (did not attend follow-up). No statistically significant difference was observed for the head posture measure (p = 0.98) and kyphosis angle (p = 0.74). Mild pain was reported by one patient after botulinum toxin-A application., Significance: Results indicate that craniofacial posture does not seem to be influenced by the treatment of pain in bruxers. If a better posture is desired, this should probably be targeted with other therapies., Trial Registration: Clinical Trials NCT03456154., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Space, an extreme environment, poses significant challenges to human physiology, including adverse effects on oral health (e.g., increase of periodontitis prevalence, caries, tooth sensitivity). This study investigates the differences in oral health routines and oral manifestations among analog astronauts during their daily routines and simulated space missions conducted on Earth., Materials and Methods: This research focused on scientist-astronaut candidates of the International Institute for Astronautical Sciences (IIAS) and analog astronauts from other institutions. The study used a cross-sectional methodology with a descriptive component. A total of 16 participants, comprising individuals aged between 21 and 55 years, were invited to complete an online questionnaire. A comparison was made between the subjects' oral hygiene practices in everyday life (designated as Earth in this research) and their oral hygiene routines during their space analog missions., Results: (i) Toothbrushing duration was mostly "1-3 minutes" (n = 13; 81.30% on Earth; n = 11; 68.80% on a mission); (ii) "time spent" was the greatest difficulty in maintaining oral hygiene routine on a mission (n = 9; 53,6%); (iii) There were more experienced oral symptoms on Earth (n = 12; 75%) than on mission (n = 7; 43.80%); (iv) The most frequent frequency of oral check-ups was "> 12 months" (n = 6; 37,5%); (v) Oral health materials were scarce on the mission (n = 9; 56.30%); (vi) For the majority, personal oral hygiene was classified as "good" (n = 9; 56.30% on Earth; n = 7; 43.80% on the mission)., Conclusion and Clinical Relevance: This research contributes to increasing knowledge of oral hygiene measures in extreme environments, but further research is needed as this topic remains relatively understudied. This study represents an initial contribution to oral health in analog space missions, aiming to propose guidelines for future missions, including deep space missions and expeditions to extreme environments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Legumes are abundant sources of proteins, and white common bean proteins play an important role in air-water interface properties. This study aims to investigate the technical-functional properties of white common bean protein isolate (BPI) as a function of pH, protein concentration, and guar gum (GG) presence. BPI physicochemical properties were analyzed in terms of solubility, zeta potential, and mean particle diameter at pH ranging from 2 to 9, in addition to water-holding capacity (WHC), oil-holding capacity (OHC), and thermogravimetric analysis. Protein dispersions were evaluated in terms of dynamic, interfacial, and foam-forming properties. BPI showed higher solubility (>80 %) at pH 2 and above 7. Zeta potential and mean diameter ranged from 15.43 to -34.08 mV and from 129.55 to 139.90 nm, respectively. BPI exhibited WHC and OHC of 1.37 and 4.97 g/g, respectively. Thermograms indicated decomposition temperature (295.81 °C) and mass loss (64.73 %). Flow curves indicated pseudoplastic behavior, with higher η 100 values observed in treatments containing guar gum. The behavior was predominantly viscous (tg δ > 1) at lower frequencies, at all pH levels, shifting to predominantly elastic at higher frequencies. Equilibrium surface tension (γ eq ) ranged from 43.87 to 41.95 mN.m -1 and did not decrease with increasing protein concentration under all pH conditions. All treatments exhibited ϕ < 15°, indicating predominantly elastic surface films. Foaming properties were influenced by higher protein concentration and guar gum addition, and the potential formation of protein-polysaccharide complexes favored the kinetic stability of the system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sporotrichosis is a mycosis with zoonotic potential caused by species of Sporothrix . Once thought rare in northeastern Brazil, the disease has recently been spreading, leading to an emergency health issue. In this paper, we describe an outbreak of feline sporotrichosis in the Seventh Health District of Maceió-AL. We collected samples from 23 domiciled and non-domiciled felines without regard for age, breed, sex, and neutering state. Skin samples were analyzed cytologically under a light microscope and seeded onto Sabouraud dextrose agar at 25 °C for from 15 to 30 days. Fifteen of the twenty-three cats with suspected skin lesions were positive for Sporothrix spp. on either cytological or microbiological evaluation. Most of the infected cats were male, young adults, non-neutered, with free access to external areas, and living in environments with poor sanitation, a high population density, and an accumulation of garbage and organic matter. Three owners were bitten or scratched by infected cats and subsequently developed suspicious cutaneous lesions suggestive of sporotrichosis. The epidemiological features of feline sporotrichosis in the outbreaks of Maceió seemed to share similarities with the data obtained from outbreaks in current hyperendemic areas. Identifying geographical sites of infection and providing compulsory notification of the disease is essential for avoiding an epidemic in Alagoas.

Antibiotics' action, once a 'magic bullet', is now hindered by widespread microbial resistance, creating a global antimicrobial resistance (AMR) crisis. A primary driver of AMR is the selective pressure from antimicrobial use. Between 2000 and 2015, antibiotic consumption increased by 65%, reaching 34.8 billion tons, 73% of which was used in animals. In the dairy cattle sector, antibiotics are crucial for treating diseases like mastitis, posing risks to humans, animals and potentially leading to environmental contamination. To address AMR, strategies like selective dry cow therapy, alternative treatments (nanoparticles, phages) and waste management innovations are emerging. However, most solutions are in development, emphasizing the urgent need for further research to tackle AMR in dairy farms.

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC 50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC 50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Water pollution is a major environmental challenge. Due to the inefficiency of conventional wastewater treatment plants in degrading many organic complex compounds, these recalcitrant pollutants end up in rivers, lakes, oceans and other bodies of water, affecting the environment and human health. Semiconductor photocatalysis is considered an efficient complement to conventional methods, and the use of various nanomaterials for this purpose has been widely explored, with a particular focus on improving their activity under visible light. This work focuses on developing magnetic and photoactive zinc/magnesium mixed ferrites (Zn 0.5 Mg 0.5 Fe 2 O 4 ) by sol-gel and solvothermal synthesis methods, which are two of the most important and efficient methods used for the synthesis of ferrite nanoparticles. The nanoparticles (NPs) synthesized by the sol-gel method exhibited an average size of 14.7 nm, while those synthesized by the solvothermal method had an average size of 17.4 nm. Both types possessed a predominantly cubic structure and demonstrated superparamagnetic behavior, reaching a magnetization saturation value of 60.2 emu g -1 . Due to the high recombination rate of electrons/holes, which is an intrinsic feature of ferrites, surface functionalization with silver was carried out to enhance charge separation. The results demonstrated a strong influence of adsorption and of the deposition of silver. Several optimization steps were performed during synthesis, allowing us to create efficient catalysts, as proved by the almost full removal of the dye malachite green attaining 95.0% (at a rate constant of 0.091 min -1 ) and 87.6% (at a rate constant of 0.017 min -1 ) using NPs obtained by the sol-gel and solvothermal methods, respectively. Adsorption in the dark accounted for 89.2% of the dye removal for nanoparticles prepared by sol-gel and 82.8% for the ones obtained by the solvothermal method. These results make mixed zinc/magnesium ferrites highly promising for potential industrial application in effluent photoremediation using visible light.

Histoplasma capsulatum causes a fungal respiratory disease. Some studies suggest that the fungus requires zinc to consolidate the infection. This study aimed to investigate the influence of zinc and the metal chelator TPEN on the growth of Histoplasma in planktonic and biofilm forms. The results showed that zinc increased the metabolic activity, cell density, and cell viability of planktonic growth. Similarly, there was an increase in biofilm metabolic activity but no increase in biomass or extracellular matrix production. N'-N,N,N,N-tetrakis-2-pyridylmethylethane-1,2 diamine (TPEN) dramatically reduced the same parameters in the planktonic form and resulted in a decrease in metabolic activity, biomass, and extracellular matrix production for the biofilm form. Therefore, the unprecedented observations in this study highlight the importance of zinc ions for the growth, development, and proliferation of H. capsulatum cells and provide new insights into the role of metal ions for biofilm formation in the dimorphic fungus Histoplasma , which could be a potential therapeutic strategy.

The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat's therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.

The main goal of this work was to elucidate the potential relevance of (radio)metal chelates of 99m Tc and Re targeting G-quadruplex structures for the design of new tools for cancer theranostics. 99m Tc provides the complexes with the ability to perform single-photon-emission computed tomography imaging studies, while the Re complexes should act as anticancer agents upon interaction with specific G4 DNA or RNA structures present in tumor tissues. Towards this goal, we have developed isostructural 99m Tc(I) and Re(I) tricarbonyl complexes anchored by a pyrazolyl-diamine (Pz) chelator carrying a pendant pyridostatin (PDS) fragment as the G4-binding motif. The interaction of the PDF-Pz-Re (8) complex with different G4-forming oligonucleotides was studied by circular dichroism, fluorescence spectroscopy and FRET-melting assays. The results showed that the Re complex retained the ability to bind and stabilize G4-structures from different DNA or RNA sequences, namely those present on the SRC proto-oncogene and telomeric RNA (TERRA sequence). PDF-Pz-Re (8) showed low to moderate cytotoxicity in PC3 and MCF-7 cancer cell lines, as typically observed for G4-binders. Biodistribution studies of the congener PDF-Pz- 99m Tc (12) in normal mice showed that the complex undergoes a fast blood clearance with a predominant hepatobiliary excretion, pointing also for a high in vitro stability., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The present study aimed to investigate the contextual inequalities of specialized public dental care (SPDC) in Brazil. The outcome was the trajectory of dental specialized production in municipalities with SPDC (from 2015 to 2017) obtained by group-based trajectory modeling. A Poisson regression model was used to analyze the factors associated with the high trajectory of SPDC production. The inequality indicators for SPDC production were the slope index and the concentration index according to contextual factors. The study included 954 SPDC units distributed across 893 municipalities. Among the municipalities evaluated, 62.9% had a low trajectory of SPDC. Large-sized municipalities had the highest production (IRR = 2.84, 95%CI: 1.94-4.14) and the southern region had the lowest production (IRR = 0.73, 95%CI: 0.58-0.92). Municipalities presenting a very high human development index (HDI) showed the greatest SPDC production (IRR = 3.34, 95%CI: 1.09-10.24), as well as municipalities with the highest tertile of schooling rate (IRR = 1.23, 95%CI: 1.00-1.50). The absolute inequality was 52.1 percentage points for the average monthly wage (p < 0.001), 61.0 percentage points for the HDI (p < 0.001), -22.1 for infant mortality rate (p <0.001), and 14.8 for the schooling rate (p = 0.012). Thus, there are contextual inequalities in the Brazilian SPDC. Higher scores for social indicators were associated with better SPDC performance.

The significant attention drawn to Ir III -complexes in recent years has boosted the development of new compounds with advantageous photophysical features. However, obtaining Ir III deep-red-emitting complexes with long lived excited state, high colour purity and high quantum yield ( Φ ) remains a challenging task. To address this issue, this study reports the synthesis and photophysical investigation of three novel zwitterionic complexes, [Ir(C^N) 2 bqdc ] (C^N = ppy , phq , and bzq ), with ppy = 2-phenylpyridine (Ir-pb), phq = 2-phenylquinoline (Ir-qb), bzq = benzo[ h ]quinoline (Ir-bb), and bqdc = potassium 2,2'-biquinoline-4,4'-dicarboxylate. These complexes exhibit high quantum yields and long emission lifetimes with high colour purity in the deep-red region. The structural characterisation carried out by usual spectroscopic measurements supports the proposed structures, while the photophysical study unveiled the high contribution of the 3 MLCT state to the hybrid emitter state, as endorsed by theoretical investigations. The desired correspondence between the calculations and the experimental data set affirmed the accuracy of the theoretical analysis, which enabled us to establish a relationship between the ground-to-excited-state geometry distortion and the lifetime through the nonradiative decay ( k nr ). Furthermore, these newly synthesized complexes exhibit quenching in the presence of molecular oxygen. In deoxygenated DMSO solution the k nr values halve, increasing the quantum yields (34.0, 10.6, and 26.6%) and the lifetimes (1.13, 1.11, and 1.72 μs), while leading to quite pure deep-red emission - CIE coordinates: (0.67, 0.33), (0.60, 0.40;), (0.65, 0.35) for Ir-pb, Ir-qb, and Ir-bb, respectively. These complexes display considerable potential for a wide range of applications, such as photodynamic therapy, due to their attractive photophysical properties, and are among the deep-red-emitting complexes reported in the literature with longer lifetimes and higher Φ .

Biogenic amines (BAs) are biologically active nitrogen-containing compounds formed during the food spoilage process and are often related as key markers of food quality, safety, and freshness. Because their presence in foods at high levels can cause significant health problems, researchers have been focused on developing novel strategies and methods for early detection and capture of these analytes. Herein, water-soluble sulfonated calix[ n ]arene macrocycles (SC4, SC6, and SC8) and a pH-sensitive dye (4'-hydroxy-10-methylpyranoflavylium) were investigated as host-guest systems for BA sensing. The hosts were able to bind the flavylium cation of the dye with association constants of 10 3 to 10 4 M -1 . The dye complexation also allowed tuning its p K a from 6.72 (free) toward high values: 7.68 (SC4), 7.79 (SC6), and 8.45 (SC8). These data were crucial to optimize the host-guest complexes as optical sensing systems for putrescine/tyramine (pH 7.2-7.6), yielding a colorimetric redshift from yellow to red. The BA sensing was also demonstrated by fluorescence quenching for the calix[ n ]arene/dye complexes and fluorescence recovery after the addition of BAs. 1 H NMR spectroscopy was used to demonstrate the interaction mode, confirming an encapsulation-driven mechanism. Overall, these host-guest systems demonstrated great potential for the detection of BAs, one of the main key markers of food spoilage.

Automatic Milking System (AMS) installations are increasing in the USA despite the higher investment cost than conventional systems. Surveys on AMSs conducted outside the USA focused on small-medium herds, specific regions, or aspects of AMS milking. This study described farmers' perceptions about the decision-making process of adopting an AMS in the USA's large dairies (≥7 AMS boxes) regarding changes in technology, housing, management practices, labor, herd performance, and health. After being contacted, 27 of 55 farmers from large AMS herds completed the survey. The main reasons for adopting an AMS were labor costs, cows' welfare, and herd performance. Most farms constructed new barns, used a free-flow traffic system, and changed their feed management. Increases in water and energy use were perceived by 42% and 62% of farmers, respectively. Farmers estimated decreases in labor costs of over 21%, and AMS employees worked 40-60 h/week. Milk production increases were reported by 58%, with 32% observing higher milk fat and protein content. Easier sick cow detection, better mastitis management, and improvements in pregnancy rates were reported. Thus, farmers transitioning to AMSs perceived altered resource utilization, labor cost savings, and improvements in employee quality of life, animal welfare, and farm management. While 54% of respondents would recommend an AMS to other farms, 38% suggested considering additional aspects prior to adoption.

Background: Dust mites are the leading cause of respiratory allergic diseases worldwide. Allergy to storage mites (SMs) has mostly been related to occupational exposures. However, recent studies have shown that sensitisation to SM, such as Lepidoglyphus destructor (Lep d), is of considerable importance also in urban populations, with high prevalence in dust samples of domestic environments. Co-sensitisation between house dust mites (HDMs) and SM is now regarded as very frequent in some regions, and cross-reactivity between them seems to be narrow. Therefore, SM allergenic capacity is increasingly a subject of study. The nasal provocation test (NPT), as an in vivo technique, could be considered the gold standard for the clinical relevance assessment of an allergen, in polysensitised rhinitis patients., Objective: The objective of this study was to analyse the clinical relevance of the SM Lep d, by assessing the relationship between in vivo sensitisation and expression of allergic respiratory disease in an urban setting., Patients and Methods: In our study, we enrolled a total of 32 allergic patients with rhinitis (with or without asthma) with proven sensitisation by skin prick test (SPT) and specific IgE (sIgE) to HDMs and/or SM. Patients underwent NPT with Lep d using subjective (Lebel Symptom Score Scale) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal response., Results: Most of the patients with positive SPT and sIgE to Lep d had a positive NPT (24/27; 89%). True Lep d allergy, assessed by a positive NPT, could be predicted by a SPT wheal size &gt;9.7 mm and a sIgE &gt;0.42 kUA/L, with 100%/95.7% sensitivity and 75.0%/83.3% specificity, respectively. Co-sensitisation between Lep d and Der p was high, 75.0%. Asthma was more frequent in the positive Lep d NPT group (54 vs. 12%, p &lt; 0.05). Significantly more patients from this group reported physical exercise, nonspecific irritants, and respiratory infections as relevant triggers of respiratory symptoms (p &lt; 0.01-p &lt; 0.05)., Conclusions: To our knowledge, this is the first study to show that sensitisation to Lep d may have clinical relevance in a non-occupational setting. In this group, there seems to be a relationship between allergy to Lep d and severity of respiratory disease, with more bronchial inflammation, when comparing with mite-allergic patients sensitised only to HDM. Therefore, the authors consider that sensitisation to Lep d should be considered when assessing and treating allergic respiratory disease in urban environments., (© 2024 S. Karger AG, Basel.)

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival ( p < 0.05) and progression-free survival ( p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene ( RB1 ). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Effectively, RB patients present a higher risk of SMN incidence compared to other oncology patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. Over the decades, some studies have been performed to better understand this subject, evaluating the risk of the development of SMNs in RB patients. Furthermore, this risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB. This review aims to clarify the effect of ionizing radiation in RB patients and to understand the association between the risk of SMN incidence in patients that underwent radiation therapy, especially in hereditary RB individuals.

In the study of fungal pathogenesis, alternative methods have gained prominence due to recent global legislation restricting the use of mammalian animals in research. The principle of the 3 Rs (replacement, reduction, and refinement) is integrated into regulations and guidelines governing animal experimentation in nearly all countries. This principle advocates substituting vertebrate animals with other invertebrate organisms, embryos, microorganisms, or cell cultures. This review addresses host-fungus interactions by employing three-dimensional (3D) cultures, which offer more faithful replication of the in vivo environment, and by utilizing alternative animal models to replace traditional mammals. Among these alternative models, species like Caenorhabditis elegans and Danio rerio share approximately 75% of their genes with humans. Furthermore, models such as Galleria mellonella and Tenebrio molitor demonstrate similarities in their innate immune systems as well as anatomical and physiological barriers, resembling those found in mammalian organisms.

Background Establishing surgical criteria for aortic valve replacement (AVR) in severe aortic regurgitation in young adults is challenging due to the lack of evidence-based recommendations. We studied indications for AVR in young adults with severe aortic regurgitation and their outcomes, as well as the relationship between presurgical echocardiographic parameters and postoperative left ventricular (LV) size, function, clinical events, and valve-related complications. Methods and Results Data were collected retrospectively on 172 consecutive adult patients who underwent AVR or repair for severe aortic regurgitation between 2005 and 2019 in a tertiary cardiac center (age at surgery 29 [22-41] years, 81% male). One-third underwent surgery before meeting guideline indications. Postsurgery, 65% achieved LV size and function normalization. LV ejection fraction showed no significant change from baseline. A higher presurgical LV end-systolic diameter correlated with a lack of LV normalization (odds ratio per 1-cm increase 2.81, P <0.01). The baseline LV end-systolic diameter cut-off for predicting lack of LV normalization was 43 mm. Pre- and postoperative LV dimensions and postoperative LV ejection fraction predicted clinical events during follow-up. Prosthetic valve-related complications occurred in 20.3% during an average 5.6-year follow-up. Freedom from aortic reintervention was 98%, 96.5%, and 85.4% at 1, 5, and 10 years, respectively. Conclusions Young adult patients with increased baseline LV end-systolic diameter or prior cardiac surgery are less likely to achieve LV normalization after AVR. Clinicians should carefully balance the long-term benefits of AVR against procedural risks and future interventions, especially in younger patients. Evidence-based criteria for AVR in severe aortic regurgitation in young adults are crucial to improve outcomes.

Guanidines are fascinating small nitrogen-rich organic compounds, which have been frequently associated with a wide range of biological activities. This is mainly due to their interesting chemical features. For these reasons, for the past decades, researchers have been synthesizing and evaluating guanidine derivatives. In fact, there are currently on the market several guanidine-bearing drugs. Given the broad panoply of pharmacological activities displayed by guanidine compounds, in this review, we chose to focus on antitumor, antibacterial, antiviral, antifungal, and antiprotozoal activities presented by several natural and synthetic guanidine derivatives, which are undergoing preclinical and clinical studies from January 2010 to January 2023. Moreover, we also present guanidine-containing drugs currently in the market for the treatment of cancer and several infectious diseases. In the preclinical and clinical setting, most of the synthesized and natural guanidine derivatives are being evaluated as antitumor and antibacterial agents. Even though DNA is the most known target of this type of compounds, their cytotoxicity also involves several other different mechanisms, such as interference with bacterial cell membranes, reactive oxygen species (ROS) formation, mitochondrial-mediated apoptosis, mediated-Rac1 inhibition, among others. As for the compounds already used as pharmacological drugs, their main application is in the treatment of different types of cancer, such as breast, lung, prostate, and leukemia. Guanidine-containing drugs are also being used for the treatment of bacterial, antiprotozoal, antiviral infections and, recently, have been proposed for the treatment of COVID-19. To conclude, the guanidine group is a privileged scaffold in drug design. Its remarkable cytotoxic activities, especially in the field of oncology, still make it suitable for a deeper investigation to afford more efficient and target-specific drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Doxorubicin (Dox) is a chemotherapeutic agent widely used in the clinic, whose side effects include cardiotoxicity, associated with decreased antioxidant defenses and increased oxidative stress. The association of Dox with natural antioxidants can extend its use if not interfering with its pharmacological potential. In this study, we aimed to understand the effects and mechanisms of the aqueous extract of Acrocomia aculeata leaves (EA-Aa) in cancer cells and the co-treatment with Dox, in in vitro and in vivo models. It was found that EA-Aa showed a relevant decrease in the viability of cancer cells (K562 and MCF-7) and increased apoptosis and death. The Dox cytotoxic effect in co-treatment with EA-Aa was increased in cancer cells. The therapeutic association also promoted a change in cell death, leading to a higher rate of apoptosis compared to the Dox group, which induced necrosis. In addition, in non-cancer cells, EA-Aa enhanced red blood cell (RBC) redox state with lower hemolysis and malondialdehyde (MDA) content and had no in vitro nor in vivo toxicity. Furthermore, EA-Aa showed antioxidant protection against Dox-induced cytotoxicity in H9c2 cells (cardiomyoblast), partially mediated by the NRF2 pathway. In vivo , EA-Aa treatment showed a relevant decrease in MDA levels in the heart, kidney, and brain, evaluated in C57Bl/6 mice induced to cardiotoxicity by Dox. Together, our results proved the effectiveness of EA-Aa in potentiating Dox anticancer effects, with antioxidant and cardioprotective activity, suggesting EA-Aa as a potential Dox pharmacological adjuvant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Monteiro-Alfredo, dos Santos, Antunes, Cunha, da Silva Baldivia, Pires, Marques, Abrantes, Botelho, Monteiro, Gonçalves, Botelho, Paula de Araújo Boleti, Cabral, Oliveira, Lucas dos Santos, Matafome and de Picoli Souza.)

Background: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 × data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function., Results: We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU&#95;Cfam&#95;GSD&#95;1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection., Conclusions: We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In the present study, we compared mucus and gut-associated prokaryotic communities from seven nudibranch species with sediment and seawater from Thai coral reefs using high-throughput 16S rRNA gene sequencing. The nudibranch species were identified as Doriprismatica atromarginata (family Chromodorididae), Jorunna funebris (family Discodorididae), Phyllidiella nigra, Phyllidiella pustulosa, Phyllidia carlsonhoffi, Phyllidia elegans, and Phyllidia picta (all family Phyllidiidae). The most abundant bacterial phyla in the dataset were Proteobacteria, Tenericutes, Chloroflexi, Thaumarchaeota, and Cyanobacteria. Mucus and gut-associated communities differed from one another and from sediment and seawater communities. Host phylogeny was, furthermore, a significant predictor of differences in mucus and gut-associated prokaryotic community composition. With respect to higher taxon abundance, the order Rhizobiales (Proteobacteria) was more abundant in Phyllidia species (mucus and gut), whereas the order Mycoplasmatales (Tenericutes) was more abundant in D. atromarginata and J. funebris. Mucus samples were, furthermore, associated with greater abundances of certain phyla including Chloroflexi, Poribacteria, and Gemmatimonadetes, taxa considered to be indicators for high microbial abundance (HMA) sponge species. Overall, our results indicated that nudibranch microbiomes consisted of a number of abundant prokaryotic members with high sequence similarities to organisms previously detected in sponges., (© 2023. The Author(s).)

Background: Microorganisms and their by-products are responsible for establishing pulpal and periapical diseases. Healing is compromised in patients under bisphosphonate therapy, and the presence of periapical infections can potentially lead to the development of medication-related osteonecrosis of the jaw (MRONJ). This work aimed to evaluate if bisphosphonate therapy is a risk factor for MRONJ development in the presence of periapical lesions., Methods: Two groups of 10 female Wistar rats were used. The experimental group received zoledronate (0.1 mg/kg) intraperitoneally, and the control received a saline solution, three times a week for three weeks. One week after the last injection, apical periodontitis was induced through pulpal exposure in the mandibular first molars. Twenty-one days later, the animals were intravenously injected with 99m Tc-HMDP, and the radioactivity uptake by mandibular specimens was counted. In addition, sample radiographs and a histological examination were performed., Results: The bone loss was higher in the control group when compared to the experimental group ( p = 0.027). 99m Tc-HMDP uptake in the control was reduced compared with the experimental group, although without statistical significance., Conclusions: In the presence of zoledronate therapy, apical periodontitis does not increase the risk of MRONJ development, and periapical lesions have lower bone resorption when compared to the control group.

Background: Impairment of the heart valves can occur due to many diseases that cause deterioration of the contractile function and harm the body, making it necessary for the heart valves to be transplanted. This study's objective was to analyze families' refusal to donate heart valves between 2001 and 2020., Methods: This was a cross-sectional study conducted in accordance with the Terms of Family Authorization for Donation of Organs and Tissues from patients diagnosed with brain death by an Organ Procurement Organization in the state of São Paulo. The variables analyzed were sex, age, cause of death, hospital type (private or public), and refusal to donate heart valves. Data analysis was performed using Stata software version 15.0  (StataCorp, LLC, College Station, Tex, United States) in a descriptive and inferential way., Results: A total of 236 people (9.65%) refused to specifically donate heart valves of their relatives, the majority of whom were between 41 and 59 years old. Most potential donors had suffered a stroke and had been in a private hospital. From 2001 to 2009, there was a decreasing trend in males and the age group from 0 to 11 years old, whereas there was an increasing trend in those aged 60 years or older and in the general population. Between 2010 and 2020, there was a downward trend in the 41- to 59-year-old age group and the general population., Conclusions: The specific refusal to donate heart valves was associated with age, diagnosis, and whether the institution was public or private., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Maghreb is a key region for understanding the dynamics of cattle dispersal and admixture with local aurochs following their earliest domestication in the Fertile Crescent more than 10,000 years ago. Here, we present data on autosomal genomes and mitogenomes obtained for four archaeological specimens of Iron Age (∼2,800 cal BP-2,000 cal BP) domestic cattle from the Eastern Maghreb, i.e. Althiburos (El Kef, Tunisia). D - loop sequences were obtained for an additional eight cattle specimens from this site. Maternal lineages were assigned to the elusive R and ubiquitous African-T1 haplogroups found in two and ten Althiburos specimens, respectively. Our results can be explained by post-domestication hybridization of Althiburos cattle with local aurochs. However, we cannot rule out an independent domestication in North Africa considering the shared ancestry of Althiburos cattle with the pre-domestic Moroccan aurochs and present-day African taurine cattle., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Luminescent Ln III complexes incorporated in polymeric films exhibit narrow emission bands and absorption within the near-UV/blue spectral range, and enhanced phostability, which qualify them to be explored for solid-state lighting. Herein, (C 26 H 56 N)[Eu(dbm) 4 ] and Na[Tb(acac) 4 ], (C 26 H 56 N + = didodecyldimethylammonium, dbm - =1,3-diphenyl-1,3-propanedionate, acac - = acetylacetonate), were dispersed in PMMA or PVDF films to protect them from degradation, and the obtained blends were applied as downshifting coatings on near-UV emitter LEDs. Upon such excitation, both Eu III and Tb III complexes emit red or green light with absolute emission quantum yields of 6.4 and 99%, respectively. The complex amount within films influences the photophysical parameters due to multiphotonic deactivation, and formation of agglomerates. For the PMMA-based LED prototypes, the Ln III emission is well-observed while for the PVDF ones, only a poor Ln III emission is detected due to their opacity. Therefore, the PMMA-based systems are better candidates to be used as luminescent coatings of near-UV LEDs for solid-state lighting.

This review aimed to investigate the use of the Cambridge Neuropsychological Automated Testing Battery (CANTAB) for people at risk of cognitive impairment, especially those born with Down syndrome and those born preterm. Six databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, in addition to the bibliography index listed in the CANTAB site. Twenty four studies regarding Down syndrome and 17 regarding prematurity were reviewed and are here described. Both cognitive profiles were described, and their performance was compared on specific tasks and CANTAB tests. In this battery of tests, people with Down syndrome usually present impaired key cognitive domains, such as episodic memory and recognition memory. Results were presented considering general aspects described in the studies, specific findings such as dementia, the role of genetics, and cognitive profile, among other descriptions. Comparability between both populations in future studies is discussed.

Objective: Intensive care unit-acquired muscle weakness (ICUAW) in critically ill patients is frequent and associated with negative outcomes. Early rehabilitation is a strategy to improve outcomes. The aim was to assess the effects of a rehabilitation nursing programme at discharge from intensive care unit., Methods: Quasi-experimental study with the comparison between two groups: one enrolled in a systematized nursing rehabilitation program and the other with usual nursing rehabilitation care. A non-probabilistic sample, sequential, of 42 critically ill ventilated patients, 21 patients in the control group and 21 patients the intervention group (June 2017 to June 2019), in three intensive care units of one large Portuguese teaching hospital. Mann-Whitney test was performed to compare Medical Research Council Sum Score (MRC-SS) values between groups., Results: Patients undergoing the rehabilitation program had a decrease in ICUAW (at ICU discharge mean MRC-SS = 38 vs. mean MRC-SS = 42.7, p = 0.043, U = 152,5). There was a decrease in severe muscle weakness (9.5% vs. 28.6%) and significant muscle weakness (42.9% vs. 52.4%) and an increase without muscle weakness (47,6% vs. 19%)., Conclusions: The systematic rehabilitation nursing program can improve muscle strength and reduce functional disability at the time of discharge from intensive care., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Introduction: Pulmonary arterial hypertension (PAH) is defined as a mean pulmonary artery pressure >20 mmHg and pulmonary vascular resistance >2 Wood Units (WU) on right-heart catheterization. Pregnancy is generally contraindicated in PAH, it is associated with high maternal mortality. Despite current recommendations, the number of women with PAH wishing to become pregnant is increasing. Specialist care is essential for preconception counseling, and the management of pregnancy and delivery in such patients., Areas Covered: We cover the physiology of pregnancy, and its effects on the cardiovascular system in PAH. We also discuss optimal management based on available evidence and guidance., Expert Opinion: Pregnancy should be avoided in most patients with PAH. Counseling on appropriate contraception should be offered routinely. Education of women with childbearing potential is essential and should start at the time of diagnosis of PAH, or the time of transition from pediatric to adult services in patients developing PAH in childhood. Women wishing to become pregnant should receive individualized risk assessment and optimization of PAH therapies via a dedicated specialist pre-pregnancy counseling service, to minimize risk and improve outcomes. Pregnant PAH patients should receive expert multidisciplinary management in a PH center, including close monitoring and early initiation of therapies.

The last 18 years have brought an increasing interest in the therapeutic use of perinatal derivatives (PnD). Preclinical studies used to assess the potential of PnD therapy include a broad range of study designs. The COST SPRINT Action (CA17116) aims to provide systematic and comprehensive reviews of preclinical studies for the understanding of the therapeutic potential and mechanisms of PnD in diseases and injuries that benefit from PnD therapy. Here we describe the publication search and data mining, extraction, and synthesis strategies employed to collect and prepare the published data selected for meta-analyses and reviews of the efficacy of PnD therapies for different diseases and injuries. A coordinated effort was made to prepare the data suitable to make statements for the treatment efficacy of the different types of PnD, routes, time points, and frequencies of administration, and the dosage based on clinically relevant effects resulting in clear increase, recovery or amelioration of the specific tissue or organ function. According to recently proposed guidelines, the harmonization of the nomenclature of PnD types will allow for the assessment of the most efficient treatments in various disease models. Experts within the COST SPRINT Action (CA17116), together with external collaborators, are doing the meta-analyses and reviews using the data prepared with the strategies presented here in the relevant disease or research fields. Our final aim is to provide standards to assess the safety and clinical benefit of PnD and to minimize redundancy in the use of animal models following the 3R principles for animal experimentation.

Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (Mg 0.75 Ca 0.25 Fe 2 O 4 ) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The Mg 0.75 Ca 0.25 Fe 2 O 4 calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.

Steroids and their derivatives have been the subject of extensive research among investigators due to their wide range of pharmacological properties, in which steroidal oximes are included. Oximes are a chemical group with the general formula R 1 R 2 C=N-OH and they exist as colorless crystals and are poorly soluble in water. Oximes can be easily obtained through the condensation of aldehydes or ketones with various amine derivatives, making them a very interesting chemical group in medicinal chemistry for the design of drugs as potential treatments for several diseases. In this review, we will focus on the different biological activities displayed by steroidal oximes such as anticancer, anti-inflammatory, antibacterial, antifungal and antiviral, among others, as well as their respective mechanisms of action. An overview of the chemistry of oximes will also be reported, and several steroidal oximes that are in clinical trials or already used as drugs are described. An extensive literature search was performed on three main databases-PubMed, Web of Science, and Google Scholar.

Objective To systematically review the literature and assess the effectiveness of perioperative systemic and nonsystemic therapies in reducing edema after orthognathic surgery. Study Design Four databases (PubMed, Web of Science, Bireme, and Scopus) were searched. Only randomized clinical trials were included and assessed using the RoB 2.0 software (Cochrane Collaboration, London, UK). Studies were grouped into time of assessment and systemic/nonsystemic therapy. Results Eighteen studies were included in this review (8 in the meta-analysis, n = 349). The qualitative assessment of systemic (enzyme therapy, dexamethasone, betamethasone, and Venoplant) and nonsystemic therapies (thermotherapy and K-Taping) appear to reduce edema. Manual lymphatic drainage (MLD) after 72 hours (CI: -1.03 to 2.31; P = .45), and 30 days (CI: -1.53 to 0.49; P = .49), and laser after 24 hours (CI: -1.36 to 1.48; P = .93), 72 hours (CI: -4.81 to 2.92; P = .63), 30 days (CI: -3.44 to 0.99; P = .28), and 90 days (CI: -1.83 to 0.96; P = .54) showed no significance. Thermotherapy reduced edema after 48 hours (CI: -48.47 to -13.31; P = .0006) and 30 days (CI: -14.73 to -1.98; P = .01). Conclusion The Grading of Recommendations, Assessment, Development and Evaluations tool showed moderate evidence for thermotherapy (significant reduction of edema), whereas the MLD and laser results were rated as high certainty of evidence (no reduction of edema)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

As the effects of global warming become increasingly complex and difficult to manage, the conservation and sustainable use of locally adapted sheep breeds are gaining ground. Portuguese native sheep breeds are important reservoirs of genetic diversity, highly adapted to harsh environments and reared in low input production systems. Genomic data that would describe the breeds in detail and accelerate the selection of more resilient animals to be able to cope with climatic challenges are still lacking. Here, we sequenced the genomes of 37 animals from four Portuguese native sheep breeds (Campaniça, Bordaleira Serra da Estrela, Merino Branco and Merino Preto) and 19 crossbred sheep to make inferences on their genomic diversity and population structure. Mean genomic diversities were very similar across these breeds (.30 ≤ H o ≤ .34; .30 ≤ H e ≤ .35; 1.7 × 10 -3 ≤ π ≤ 3.1 × 10 -3 ) and the levels of inbreeding were negligible (.005 ≤ F IS ≤ .038). The Principal Components, Bayesian clustering and Treemix analyses split the Portuguese breeds in two main groups which are consistent with historical records: one comprising Campaniça and Serra da Estrela together with other European and transboundary dairy breeds; and another of the well-differentiated multi-purpose Merino and Merino-related breeds. Runs of homozygosity analyses yielded 1,690 ROH segments covering an average of 2.27 Gb across the genome in all individuals. The overall genome covered by ROH segments varied from 27,75 Mb in Serra da Estrela to 61,29 Mb in Campaniça. The phylogenetic analysis of sheep mitogenomes grouped the Portuguese native breeds within sub-haplogroup B1a along with two animals of the Akkaraman breed from Turkey. This result provides additional support to a direct influence of Southwest Asian sheep in local breeds from the Iberian Peninsula. Our study is a first step pertaining to the genomic characterization of Portuguese sheep breeds and the results emphasize the potential of genomic data as a valid tool to guide conservation efforts in locally adapted sheep breeds. In addition, the genomic data we generated can be used to identify markers for breed assignment and traceability of certified breed-products., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gaspar, Usié, Leão, Guimarães, Pires, Matos, Ramos and Ginja.)

Natural pigments are bioactive compounds that can present health-promoting bioactivities in the human body. Due to their strong coloring properties, these compounds have been widely used as color additives as an alternative to artificial colorants. However, since these pigments are unstable under certain conditions, such as the presence of light, oxygen, and heat, the use of complexation and encapsulation techniques with biopolymers is in demand. Moreover, some functional properties can be achieved by using natural pigments-biopolymers complexes in food matrices. The complexation and encapsulation of natural pigments with biopolymers consist of forming a complex with the aim to make these compounds less susceptible to oxidative and degrading agents, and can also be used to improve their solubility in different media. This review aims to discuss different techniques that have been used over the last years to create natural pigment-biopolymers complexes, as well as the recent advances, limitations, effects, and possible applications of these complexes in foods. Moreover, the understanding of thermodynamic parameters between natural pigments and biopolymers is very important regarding the complex formation and their use in food systems. In this sense, thermodynamic techniques that can be used to determine binding parameters between natural pigments and potential wall materials, as well as their applications, advantages, and limitations are presented in this work. Several studies have shown an improvement in many aspects regarding the use of these complexes, including increased thermal and storage stability. Nonetheless, data regarding the biological effects on the human body and the sensory acceptance of natural pigments-biopolymers complexes in food systems are scarce in the literature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The death of a partner is a critical life event in later life, which requires grief work as well as the development of a new perspective for the future. Cognitive behavioral web-based self-help interventions for coping with prolonged grief have established their efficacy in decreasing symptoms of grief, depression, and loneliness. However, no study has tested the efficacy for reducing grief after losses occurring less than 6 months ago and the role of self-tailoring of the content., Objective: This study aims to evaluate the clinical efficacy and acceptance of a web-based self-help intervention to support the grief process of older adults who have lost their partner. It will compare the outcomes, adherence, and working alliance in a standardized format with those in a self-tailored delivery format and investigate the effects of age, time since loss, and severity of grief at baseline as predictors. Focus groups to understand user experience and a cost-effectiveness analysis will complement the study., Methods: The study includes 3 different randomized control trials. The trial in Switzerland comprises a waitlist control group and 2 active arms consisting of 2 delivery formats, standardized and self-tailored. In the Netherlands and in Portugal, the trials follow a 2-arm design that will be, respectively, complemented with focus groups on technology acceptance and cost-effectiveness analysis. The main target group will consist of adults aged >60 years from the general population in Switzerland (n≥85), the Netherlands (n≥40), and Portugal (n≥80) who lost their partner and seek help for coping with grief symptoms, psychological distress, and adaptation problems in daily life. The trials will test the intervention's clinical efficacy for reducing grief (primary outcome) and depression symptoms and loneliness (secondary outcomes) after the intervention. Measurements will take place at baseline (week 0), after the intervention (week 10), and at follow-up (week 20)., Results: The trials started in March 2022 and are expected to end in December 2022 or when the needed sample size is achieved. The first results are expected by January 2023., Conclusions: The trials will provide insights into the efficacy and acceptance of a web-based self-help intervention among older adults who have recently lost a partner. Results will extend the knowledge on the role of self-tailoring, working alliance, and satisfaction in the effects of the intervention. Finally, the study will suggest adaptations to improve the acceptance of web-based self-help interventions for older mourners and explore the cost-effectiveness of this intervention. Limitations include a self-selective sample and the lack of cross-cultural comparisons., Trial Registration: Switzerland: ClinicalTrials.gov NCT05280041; https://clinicaltrials.gov/ct2/show/NCT05280041; Portugal: ClinicalTrials.gov NCT05156346; https://clinicaltrials.gov/ct2/show/NCT05156346., International Registered Report Identifier (irrid): PRR1-10.2196/37827., (©Jeannette Brodbeck, Sofia Jacinto, Afonso Gouveia, Nuno Mendonça, Sarah Madörin, Lena Brandl, Lotte Schokking, Ana Maria Rodrigues, Judite Gonçalves, Bettina Mooser, Marta M. Marques, Joana Isaac, Vasco Nogueira, Ana Matos Pires, Lex van Velsen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.11.2022.)

Background: Schizophrenia is a chronic psychiatric disorder with a significant impact worldwide. The early onset and its relapsing nature pose a significant challenge to patients and caregivers. The PSIPROSPER study aimed to characterize the real-world context of schizophrenia treatment in Portugal and to measure the impact of including paliperidone palmitate 1-month formulation (PP1M) in the clinical outcomes (relapses and hospitalizations) and healthcare resource utilization, in a context in which payment scheme in Portugal allows for patients to receive free antipsychotics if prescribed at public hospitals., Methods: This was a multicenter, retrospective, observational study. Male and female adults with a diagnosis of schizophrenia who initiated treatment with PP1M after a minimum of 12 months on an Oral Antipsychotic (OAP), and with complete medical charts, were consecutively included. A mirror-image design over 24 months allowed the comparison of outcomes before and after the PP1M introduction., Results: Out of the 51 patients included, 80.4% were male, with a mean age of 34 (±9.8) years. Around 92% of patients were being treated with PP1M at inclusion. Lack of adherence to previous OAP was the main driver for PP1M initiation. Only 9.8% of patients were hospitalized during the PP1M period vs. 64.7% during the OAP period ( p < 0.0001). The mean number of hospitalizations (0.1) was significantly lower during the PP1M period ( p < 0.0001). Type of treatment was the only variable found to be significant in predicting a lower hospitalization rate and a lower risk of hospitalization. Relapses were significantly lower ( p < 0.0001) in PP1M (21.6%) vs. OAP (83.7%). Similarly, the mean change in the number of relapses ( p < 0.0001) showed significantly better outcomes in PP1M., Conclusion: This study supports PP1M as part of schizophrenia treatment in Portugal. Given the lower number of relapses and hospitalizations observed in schizophrenia patients treated with PP1M when compared to OAP-treated patients, this real-world study seems to provide further evidence to support the use of PP1M to treat this condition, in line with previous research. In the context of scarce public resources, these benefits should be carefully considered by healthcare decision-makers to ensure optimal value-based treatment strategies., Competing Interests: GA and AP were employed by Janssen-Cilag Farmacêutica, Portugal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marques-Teixeira, Amorim and Pires.)

We aimed to evaluate the incidence of unstable non-acid milk (UNAM) in cows fed either sugarcane or corn silage. Second, we aimed to evaluate the effect of daily variation (d 1 to 4) and alcohol grades (72, 78, and 80%) on UNAM incidence. The experiment was conducted as a split-plot crossover design, with 2 periods and 2 roughage types (sugarcane or corn silage). Thirteen multiparous Holstein cows with an average of 281 ± 29 d in milk were randomly distributed into 2 diets. Individual blood (analysis of total proteins, albumin, urea, calcium, phosphorus, magnesium, iron, chloride, glucose, and lactate) and milk samples (analysis of protein, fat, lactose and total solids, somatic cell count, and characterization of the protein profile) were collected during the last 4 d of each period. For UNAM identification, the alcohol test was conducted in milk samples at 4°C; specifically, if the sample presented the formation of clots, this would be noted as positive for UNAM. In addition, the Dornic acidity analysis was performed in the same samples to evaluate the true milk acidity. The use of sugarcane and higher degrees of alcohol were associated with increased UNAM. We observed no daily variation in UNAM. Nevertheless, we found no roughage type effect on the variables most commonly associated with UNAM, such as changes in salts in the casein micelle and, consequently, the zeta potential and the κ-casein (CN) fraction. The Pearson correlation analysis showed that the zeta potential and the concentrations of α S2 -CN, blood ionic calcium, lactate, and glucose increased as the incidence of UNAM increased, showing a positive correlation among these variables. In contrast, the concentrations of lactose, phosphorus, and potassium decreased as UNAM increased, presenting a negative correlation. This study brought important discoveries to unveil why cows manifest UNAM. For instance, higher alcohol grades and cows fed with sugarcane had increased the incidence of UNAM. Additionally, animals with a higher incidence of UNAM (sugarcane-fed cows) were related to increased ionic calcium and glucose and changes in milk protein profile, with lower levels of BSA, β-CN, and α-lactalbumin and greater α S1 -CN content, all of which were correlated with UNAM. Nonetheless, this trial also provides evidence for the need for further studies to better understand the physiological mechanisms that directly affect the stability of milk protein., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Recent studies have demonstrated that blocking the PI3Kδ signalling enzyme (by administering a small molecule inhibitor, PI-3065) can potently improve the anti-tumour T-cell response through direct inhibition of Tregs. This treatment also has a negative impact on MDSC numbers but the primary mechanism driving this effect has remained unclear., Methods: The 4T1 breast cancer mouse model was used in combination with PI-3065 to gain insights into the effect of PI3Kδ inhibition on MDSCs., Results: PI-3065 treatment resulted in a concomitant reduction in MDSC expansion and tumour size. However, targeting Tregs independent of PI-3065 was also associated with reduced tumour volume and MDSC numbers. Surgical removal of tumours resulted in a rapid and significant decline in MDSC numbers, whilst ex vivo studies using cells from PI-3065-treated mice demonstrated no direct effect of the inhibitor on MDSC activity., Conclusions: Our data suggest that MDSCs are not inhibited directly by PI-3065 treatment but that their reduced recruitment and immunosuppression within the tumour microenvironment is an indirect consequence of PI3Kδ-inhibition-driven tumour control. This indicates that PI3Kδ inhibition drives tumour immunity by breaking down multiple immunosuppressive pathways through both direct mechanisms (on Treg) and indirect mechanisms, secondary to tumour control (on MDSCs)., (© 2022. The Author(s).)

Although toxic and dangerous, Phenylmethane (PhM) dyes have a variety of medicinal functions. To optimize the use of these dyes, it is essential to understand their interaction mechanism with proteins. Through surface plasmon resonance, we investigated the kinetics and thermodynamics of interaction between bovine lactoferrin (BLF) and PhM dyes at pH 7.4, which allowed elucidate the effect of the dyes' functional groups on the binding process. Negative ΔG° revealed that at thermodynamic equilibrium the formed [BLF-PhM]° complex was more stable than the free BLF and PhM molecules. The increase in the number of methyl groups in the PhM structure led to an increase in the rates of association (k a ) and dissociation (k d ) and the binding constant (K b ). A similar effect was observed when comparing methyl violet B (MVB) and methyl violet 6 B (MV6B), in which the charged MV6B structure promoted an increase in the k a , k d , and K b values. By contrast, an increase in the number of phenyl groups (2-3 rings) led to a decrease in the K b values. The [BLF-PhM]° formation was entropically driven, indicating that hydrophobic interactions are critical for stabilizing these complexes These results are beneficial for understanding the molecular dynamics of protein-dye interactions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The Covid-19 pandemic has strongly impacted people's lives and the food industry. In this sense, food products claiming nutritional and health-promoting benefits due to the presence of bioactive peptides and probiotics, such as Greek-style yogurt, have been in demand. The objective of this work was to investigate, through word association, the perception of the consumers regarding the seven concepts related to Greek-style yogurt (traditional, ultra-creamy, zero fat, high content proteins, zero lactose, light and with no added sugars), in the context of social isolation due to Covid-19. In this online survey, 346 participants completed a questionnaire. The participants were divided according to health concerns (increased, not changed, or decreased) and eating habits (improved, not changed, or worsened) during the Covid-19 pandemic. Chi-square and prototypical analysis were used as statistical tests. During the Covid-19 pandemic, based on self-report, around 66% of the participants had their eating habits and their concerns about health changed. The general associations were related to the categories pleasure, health, creamy, pleasant texture, food restriction, and loss of sensory quality. 'Health' and 'pleasure' were negatively associated with the conceptualization of Greek-style yogurt. For the zero-fat, light, and sugar-free Greek-style yogurts, the terms creamy and ultra-creamy are sensory appealing to the consumers. In general, the price and concerns about health are factors that strongly influence the purchase intention of Greek-style yogurts. The yogurts were associated with sensory and non-sensory characteristics, which can be useful for marketing strategies for of different product concepts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)