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Aim: To evaluate the clinical outcomes after subsequent implantation of a new intrastromal corneal ring segment (ICRS) model followed by an additional short-arc ICRS implant in keratoconus patients., Methods: This retrospective single-arm cohort study evaluated 25 eyes of 21 keratoconus patients implanted with the new ICRS followed by 140-arch length ICRS (140-ICRS) implantation. Uncorrected distance visual acuity (UDVA, logMAR), corrected distance visual acuity (CDVA, logMAR), sphere, astigmatism, keratometry, spherical equivalent (SE), and asphericity were compared preoperatively and postoperatively after both ICRS implantation., Results: The average follow-up time after 140-ICRS implantation was 6.40±2.20mo. The mean preoperative UDVA improved from 1.27±0.14 preoperative to 0.52±0.26 after both ICRS implantation ( P =0.03). The mean sphere value reduced from -5.34±2.74 preoperatively to -2.06±1.84 postoperatively ( P <0.001) after the first ICRS implantation and decreased to -0.59±1.54 postoperatively ( P <0.001) after 140-ICRS implantation. The mean preoperative astigmatism was -3.72±1.56 and improved to -2.82±1.08 after the first ICRS implantation, and following the 140-ICRS implantation, the mean astigmatism was -1.37±0.67 ( P =0.001). The SE and asphericity changes were statistically significant ( P <0.001). The researchers did not find intraoperative or postoperative complications for both procedures., Conclusion: The combination of 2 different ICRSs can efficiently regularize the cornea, reduce the SE, and improve visual acuity in selected keratoconus patients., Competing Interests: Conflicts of Interest: Coscarelli S, None; de Oliveira Sieiro R, None; Fernandes VM, None; Coscarelli SP, None; Torquetti L, None., (International Journal of Ophthalmology Press.)

Background: We tested the hypothesis that attenuation of the circulating insulin level in rats during early life can provide sustained protection against diet-induced obesity and metabolic dysfunction in adulthood. Methods: Male Wistar rats received intraperitoneal scopolamine butylbromide (SB) during the first 12 days of suckling, whereas control rats received 0.9% saline injections. The animals were weaned on day 21 and fed a normal chow diet. At 60 days of age, the control and SB groups were fed a normal chow diet (ND; 4.5% fat) or a high-fat diet (HF; 35% fat) until 90 days of age to induce obesity and metabolic dysfunction. Insulin secretion, food intake, and body weight were measured. Pancreatic islet function, autonomic nervous system function, and glucose homeostasis were evaluated at 90 days of age. Result: During lactation, the plasma insulin concentration was significantly lower in the SB groups than in the control group. SB rats also exhibited reduced body weight. The HF diet resulted in obesity, glucose intolerance, insulin resistance, disruption of insulin secretion, and vagal hyperactivity in adult control rats. Remarkably, SB-treated HF diet rats showed attenuated body weight and adiposity, and did not develop diet-induced glucose/insulin imbalance. Additionally, vagal activity and adequate pancreatic islet insulin secretion were preserved. Conclusion: Offspring exposed to SB during early life are provided with long-lasting protection against obesity and metabolic complications induced by an HF diet. An attenuated circulating insulin level in early life may have far-reaching consequences on metabolic programming.

This study aimed to evaluate the prevalence of thyroid, glycemic, lipid and metabolic bone disorders among adult patients with pulmonary arterial hypertension (PAH)., Methods: This was an observational cross-sectional clinical study with patients with PAH, matched by sex and age with a control group without PAH. All individuals were enrolled into a clinical assessment, metabolic workup, thyroid ultrasound, and bone densitometry protocol., Results: The PAH group included 35 participants (34 females, 46 ± 15.5 years), and the control group, 40 (39 females, 41.8 ± 13.1 years). There was no difference in body mass index (BMI) between PAH and control group (27.5 ± 5.9 and 26.9 ± 4.3 kg/m 2 , respectively; p = 0.63; 95% CI = -1.8, 2.94), neither in physical activity time per week (60.3 ± 103.3, 98.9 ±137.6, respectively; p = 0.17; 95% CI = -95.23, 18.06). Although there was no difference in the prevalence of insulin resistance between the PAH (51.4%) and the control group (47.5%), p=0.74, patients with PAH had a higher median of glycated hemoglobin (A1c) than the control group (6.1% and 5.57%, respectively), p=0.006; 95% CI = -0.14, 1.22. PAH group presented lower mean total cholesterol (170.46 ± 35.51 mg/dL) and median LDL-cholesterol [105 (46) mg/dL, median (interquartile range)] levels than the control group [192.1 ± 34.44 mg/dL, p = 0.009; 95% CI = -37.76, 5.52; 121.6 (35.02) mg/dL, p=0.012; 95% CI = -34.08, 0.77, respectively]. It was found a higher prevalence of hypothyroidism (22.9%) in PAH group than in control group (2.5%), p = 0.007. We found hyperparathyroidism (HPT) among 8 patients of PAH group (23%), but none in the control group. Considering bone mineral density disorders, 12 patients from PAH group presented low bone mass, osteopenia, or osteoporosis (34%), and 8 individuals in the control group (20%), p =0.032, which represented a 2.13 higher relative risk for those conditions for the former group. The patients with HPT presented a higher creatinine level (0.98 ± 0.12 mg/dL) than the PAH patients with normal parathyroid hormone (0.76 ± 0.14 mg/dL), p = 0.0004; 95% CI = 0.12, 0.33. The PAH group also presented lower total hip (-0.15 ± 1.25) and femoral neck (-0.14 ± 1.07) bone mineral density (BMD) Z-scores than the control group (0.50 ± 1.13, p = 0.021; 95% CI = -0.18, -0.027; 0.35 ± 0.94, p = 0.038; 95% CI = -0.16, -0.01, respectively)., Conclusion: In this cohort, the findings of higher A1c levels, hypothyroidism prevalence, lower LDL and total cholesterol levels, and a higher prevalence of hyperparathyroidism, as well as lower total hip and femoral neck BMD Z-scores in the PAH group, compared to the control group and highlighting the dysregulation of various metabolic pathways in patients with HAP, suggesting the need for targeted interventions to enhance patient care. Additionally, they underscore the importance of gaining a deeper understanding of the mechanisms driving these changes and their potential pathophysiological connections to the disease., 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 article., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The purpose of this study is to report the experience of a single Portuguese oncology center in the management of patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). Methods: This is a retrospective analysis of all patients with RCC and VTT surgically treated in our center between 2008 and 2023. Only patients with VTT up to level III (Mayo Clinic classification) were included. Patient, tumor characteristics and peri-operative outcome data were registered. Administration of systemic therapy was performed upon progression. Survival analysis was conducted with the collected data. Results: A total of 64 patients (n = 16 women) were included in this study. The mean age at diagnosis was 66.3 ± 10.7 years old. The VTT level was 0, I, II and III in 40 (62.5%), 12 (18.7%), 6 (9.4%) and 6 (9.4%) patients, respectively. Nine patients (14.1%) had distant metastasis at diagnosis. No peri-operative deaths occurred, and the major complication rate was 3.1%. Histology revealed 98.4% of clear cell RCC, with sarcomatoid differentiation present in 12.5% of the cases. A negative margin status was achieved in 54 (84.4%) patients. Systemic therapy was administered in 24 (37.5%) patients during follow-up. The median progression-free (PFS), cancer-specific (CSS) and overall (OS) survival were 23, 60 and 48 months, respectively. In multivariable analysis, significant predictors of CSS were tumor size, sarcomatoid differentiation and collecting system invasion. Conclusions: Radical nephrectomy with VTT excision up to level III is a feasible and safe procedure. Patients with large tumor size, sarcomatoid differentiation and collecting system invasion are at the highest risk and should be closely monitored.

Covering: 2013 to 2023In an era where antimicrobial resistance severely threatens our ability to treat infections, the discovery of new drugs that belong to different chemical classes and/or bear original modes of action is urgently needed. In this case, diterpenoids comprise a productive field with a proven track record in providing new anti-infectives to tackle bacterial infections and malaria. This review highlights the potential of both naturally occurring and semi-synthetic bi- and tricyclic diterpenoids to become leads in search of new drugs to treat infections caused by bacteria, fungi, viruses and protozoan parasites. The literature from the last decade (2013-2023) is covered, focusing on naturally occurring and semi-synthetic bicyclic (labdanes and labdane-type) and tricyclic (all classes) diterpenoids, detailing their relevant biological activities in the context of infection, which are explained through structure-activity relationships.

The distribution of pulmonary blood flow is uneven and can be described as a three-zone model, the West zones: zone 1 occurs whenever alveolar pressure exceeds arterial pressure; zone 2 when the arterial pressure is greater than alveolar but the alveolar pressure exceeds the venous pressure; and finally zone 3 when both arterial and venous pressures exceed alveolar pressure. Consequently, the blood flow is almost determined by the difference between the arterial and venous pressures in zone 3 and between arterial and alveolar pressures in zone 2 and ceases in zone 1. The understanding of this subject may be difficult to some medical students. Therefore, to improve the learning of this topic in our physiology course, we used a didactic model to demonstrate the core concept of flow down gradients and its application to pulmonary blood flow. We modeled a Starling resistor by placing a collapsible tube inside a hermetic chamber of variable pressure. Transparent turbine flowmeters were connected to the upstream and downstream extremities of the Starling resistor, and we generated a constant airflow with a brushless motor. By maintaining the input (arterial) pressure constant and varying the chamber (alveolar) pressure, we could simulate the three zones and demonstrate the resulting flow through the turbines. In conclusion, our demonstration using a Starling resistor model combined with visible turbine flowmeters can be used to facilitate comprehension of important concepts in physiology involving flow down gradients, such as pulmonary blood flow. NEW & NOTEWORTHY The understanding of respiratory physiology is a challenge to medical students. To improve the learning of pulmonary blood flow distribution through lung vessels in our physiology course, we modeled a Starling resistor model combined with visible turbine flowmeters. Our model can significantly improve the core concept of flow down gradients teaching and its application to West zones.

With the emergence of multidrug-resistant microorganisms, microbial agents have become a serious global threat, affecting human health and various plants. Therefore, new therapeutic alternatives, such as chitin-binding proteins, are necessary. Chitin is an essential component of the fungal cell wall, and chitin-binding proteins exhibit antifungal activity. In the present study, chitin-binding peptides isolated from Capsicum chinense seeds were characterized and evaluated for their in vitro antimicrobial effect against the growth of Candida and Fusarium fungi. Proteins were extracted from the seeds and subsequently the chitin-binding proteins were separated by chitin affinity chromatography. After chromatography, two fractions, Cc-F1 (not retained on the column) and Cc-F2 (retained on the column), were obtained. Electrophoresis revealed major protein bands between 6.5 and 26.6 kDa for Cc-F1 and only a ~ 6.5 kDa protein band for Cc-F2, which was subsequently subjected to mass spectrometry. The protein showed similarity with hevein-like and endochitinase and was then named Cc-Hev. Data are available via ProteomeXchange with identifier PXD054607. Next, we predicted the three-dimensional structure of the peptides and performed a peptide docking with (NAG) 3 . Subsequently, growth inhibition assays were performed to evaluate the ability of the peptides to inhibit microorganism growth. Cc-Hev inhibited the growth of C. albicans (up to 75% inhibition) and C. tropicalis (100% inhibition) and induced a 65% decrease in cell viability for C. albicans and 100% for C. tropicalis. Based on these results, new techniques to combat fungal diseases could be developed through biotechnological applications; therefore, further studies are needed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Oral squamous cell carcinoma (OSCC) is the prevalent type of oral cavity cancer, requiring precise, accurate, and affordable diagnosis to identify the disease in early stages, Comprehending the differences in lipid profiles between healthy and cancerous tissues encompasses great relevance in identifying biomarker candidates and enhancing the odds of successful cancer treatment. Therefore, the present study evaluates the analytical performance of simultaneous mRNA and lipid extraction in gingiva tissue from healthy patients and patients diagnosed with OSCC preserved in TRIzol reagent. The data was analyzed by partial least-squares discriminant analysis (PLS-DA) and confirmed via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The lipid extraction in TRIzol solution was linear in a range from 330 to 2000 ng mL -1 , r 2 > 0.99, intra and interday precision and accuracy <15%, and absolute recovery values ranging from 90 to 110%. The most important lipids for tumor classification were evaluated by MALDI-MSI, revealing that the lipids responsible for distinguishing the OSCC group are more prevalent in the cancerous tissue in contrast to the healthy group. The results exhibit the possibilities to do transcriptomic and lipidomic analyses in the same sample and point out important candidates related to the presence of OSCC.

The emergence of resistant microorganisms has reduced the effectiveness of currently available antimicrobials, necessitating the development of new strategies. Plant antimicrobial peptides (AMPs) are promising candidates for novel drug development. In this study, we aimed to isolate, characterize, and evaluate the antimicrobial activities of AMPs isolated from Capsicum annuum. The antifungal potential was tested against Candida species. Three AMPs from C. annuum leaves were isolated and characterized: a protease inhibitor, a defensin-like protein, and a lipid transporter protein, respectively named CaCPin-II, CaCDef-like, and CaCLTP2. All three peptides had a molecular mass between 3.5 and 6.5 kDa and caused morphological and physiological changes in four different species of the genus Candida, such as pseudohyphae formation, cell swelling and agglutination, growth inhibition, reduced cell viability, oxidative stress, membrane permeabilization, and metacaspase activation. Except for CaCPin-II, the peptides showed low or no hemolytic activity at the concentrations used in the yeast assays. CaCPin-II inhibited α-amylase activity. Together, these results suggest that these peptides have the potential as antimicrobial agents against species of the genus Candida and can serve as scaffolds for the development of synthetic peptides for this purpose., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Faced with the emergence of multiresistant microorganisms that affect human health, microbial agents have become a serious global threat, affecting human health and plant crops. Antimicrobial peptides have attracted significant attention in research for the development of new microbial control agents. This work's goal was the structural characterization and analysis of antifungal activity of chitin-binding peptides from Capsicum baccatum and Capsicum frutescens seeds on the growth of Candida and Fusarium species. Proteins were initially submitted to extraction in phosphate buffer pH 5.4 and subjected to chitin column chromatography. Posteriorly, two fractions were obtained for each species, Cb -F1 and Cf -F1 and Cb -F2 and Cf -F2, respectively. The Cb -F1 ( C. baccatum ) and Cf -F1 ( C. frutescens ) fractions did not bind to the chitin column. The electrophoresis results obtained after chromatography showed two major protein bands between 3.4 and 14.2 kDa for Cb -F2. For Cf -F2, three major bands were identified between 6.5 and 14.2 kDa. One band from each species was subjected to mass spectrometry, and both bands showed similarity to nonspecific lipid transfer protein. Candida albicans and Candida tropicalis had their growth inhibited by Cb -F2. Cf -F2 inhibited the development of C. albicans but did not inhibit the growth of C. tropicalis . Both fractions were unable to inhibit the growth of Fusarium species. The toxicity of the fractions was tested in vivo on Galleria mellonella larvae, and both showed a low toxicity rate at high concentrations. As a result, the fractions have enormous promise for the creation of novel antifungal compounds.

Sulfate radical-based advanced oxidation processes (SR-AOPs) are renowned for their exceptional capacity to degrade refractory organic pollutants due to their wide applicability, cost-effectiveness, and swift mineralization and oxidation rates. The primary sources of radicals in AOPs are persulfate (PS) and peroxymonosulfate (PMS) ions, sparking significant interest in their mechanistic and catalytic aspects. To develop a novel nanocatalyst for SR-AOPs, particularly for PMS activation, we synthesized carbon-coated FeCo nanoparticles (NPs) using solvothermal methods based on the polyol approach. Various synthesis conditions were investigated, and the NPs were thoroughly characterized regarding their structure, morphology, magnetic properties, and catalytic efficiency. The FeCo phase was primarily obtained at [OH - ] / [Metal] = 26 and [Fe] / [Co] = 2 ratios. Moreover, as the [Fe]/[Co] ratio increased, the degree of xylose carbonization to form a carbon coating (hydrochar) on the NPs also increased. The NPs exhibited a spherical morphology with agglomerates of varying sizes. Vibrating-sample magnetometer analysis (VSM) indicated that a higher proportion of iron resulted in NPs with higher saturation magnetization (up to 167.8 emu g -1 ), attributed to a larger proportion of FeCo bcc phase in the nanocomposite. The best catalytic conditions for degrading 100 ppm Rhodamine B (RhB) included 0.05 g L -1 of NPs, 2 mM PMS, pH 7.0, and a 20-min reaction at 25 °C. Notably, singlet oxygen was the predominant specie formed in the experiments in the SR-AOP, followed by sulfate and hydroxyl radicals. The catalyst could be reused for up to five cycles, retaining over 98% RhB degradation, albeit with increased metal leaching. Even in the first use, dissolved Fe and Co concentrations were 0.8 ± 0.3 and 4.0 ± 0.5 mg L -1 , respectively. The FeCo catalyst proved to be effective in dye degradation and offers the potential for further refinement to minimize Co 2+ leaching., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the present study, we identified and characterized two defensin-like peptides in an antifungal fraction obtained from Capsicum chinense pepper fruits and inhibited the growth of Colletotrichum scovillei, which causes anthracnose. AMPs were extracted from the pericarp of C. chinense peppers and subjected to ion exchange, molecular exclusion, and reversed-phase in a high-performance liquid chromatography system. We investigated the endogenous increase in reactive oxygen species (ROS), the loss of mitochondrial functioning, and the ultrastructure of hyphae. The peptides obtained from the G3 fraction through molecular exclusion chromatography were subsequently fractionated using reverse-phase chromatography, resulting in the isolation of fractions F1, F2, F3, F4, and F5. The F1-Fraction suppressed C. scovillei growth by 90, 70.4, and 44% at 100, 50, and 25 μg mL -1 , respectively. At 24 h, the IC 50 and minimum inhibitory concentration were 21.5 μg mL -1 and 200 μg mL -1 , respectively. We found an increase in ROS, which may have resulted in an oxidative burst, loss of mitochondrial functioning, and cytoplasm retraction, as well as an increase in autophagic vacuoles. MS/MS analysis of the F1-Fraction indicated the presence of two defensin-like proteins, and we were able to identify the expression of three defensin sequences in our C. chinense fruit extract. The F1-Fraction was also found to inhibit the activity of insect α-amylases. In summary, the F1-Fraction of C. chinense exhibits antifungal activity against a major pepper pathogen that causes anthracnose. These defensin-like compounds are promising prospects for further research into antifungal and insecticide biotechnology applications. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background and Objectives: Limited evidence exists for endovascular first-line treatment of Spetzler-Martin (SM) grade III brain arteriovenous malformations (AVMs). In this article, we sought to evaluate advanced endovascular techniques for treating SM III AVMs across different sizes, eloquence, and patterns of venous drainage., Methods: Data from AVMs SM III treated between January 2010 and January 2022 were collected: size (S), eloquence (E), drainage (V), angioarchitecture features (arterial and venous aneurysms, venous drainage, and venous stenosis), treatment strategy (single arterial, double arterial, venous, both arterial and venous, and transvenous endovascular embolization with selective temporary flow arrest [TFATVE]), neoadjuvant treatment, and number of previous embolization sessions. AVMs were classified according to the modified SM grade as follows: small (S1V1E1/III-), medium/deep (S2V1E0/III), medium/eloquent (S2V0E1/III+), and large (S3V0E0). Treatment complications (hemorrhagic and ischemic), clinical discharge and 6-month outcomes (modified Rankin Scale 0-2, mRS), and angiographic occlusion rates were recorded., Results: A total of 91 AVMs (62.6% ruptured, 72.5% S1V1E1, 7% S2V1E0, 19.7% S2V0E1, and 0% S3V0E0) in 91 patients (mean age 37 ± 15.8 years) were included. Treatment techniques included single arterial approach (28.6%), double arterial technique (30.8%), single venous strategy (9.9%), TFATVE (10.9%), and arterial and venous combined (19.8%). The angiographic occlusion rate was 91.2% (90.9% S1V1E1, 100% S2V1E0, and 88.9% S2V0E1) for all techniques, and 100% for the transvenous technique, isolated or combined with transarterial embolization. Minor complication (mRS 0-2), major complication (mRS >2), and mortality rate were 16.5%, 2.2%, and 3.4%, respectively. Overall, treatment morbimortality (mRS >2) was 3% (2/66) for S1V1E1, 0% for S2V1E0, and 16.7% (3/18) for S2V0E1., Conclusion: Although morbidity is non-negligible, endovascular treatment of SM grade III lesions with advanced techniques offers up to 100% rates of cure, which is of high interest, especially for ruptured deep-seated eloquent AVMs with high reruptured rates, and less amenable to microsurgery techniques., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

The aim of this study was to assess the surface and tissue quality of keratinized mucosa grafts (KMG) obtained using the conventional scalpel and mucotome techniques. This was an experimental in vitro/ex vivo study involving six porcine hemi-mandibles. Specimens were harvested using both the mucotome and conventional scalpel techniques, with randomization determining the choice of technique for tissue removal. The specimens were prepared following predefined laboratory protocols and subsequently subjected to optical microscopy for evaluating epithelial and connective tissue and scanning electron microscopy for topographical and 3D profilometry analysis. Tissues harvested using the mucotome exhibited a linear base and uniform thickness, along with the presence of submucosa and fibrous connective tissue, all of which are ideal for graft success. Differences in the surface characteristics of specimens obtained through the two techniques were observed during a comparative analysis of images obtained through both microscopy types. KMG obtained using the mucotome technique displayed greater uniformity and reduced undesirable cell presence compared to the scalpel technique, thereby enhancing the likelihood of success in soft tissue graft surgical procedures. This study provides valuable insights to oral healthcare professionals and may contribute to future research aimed at achieving more successful surgeries, shorter postoperative recovery times, reduced discomfort, and an overall more positive patient experience., (© 2024. The Author(s).)

Parkinson's disease (PD) is a debilitating condition that can cause locomotor problems in affected patients, such as tremors and body rigidity. PD therapy often includes the use of monoamine oxidase B (MAOB) inhibitors, particularly phenylhalogen compounds and coumarin-based semi-synthetic compounds. The objective of this study was to analyze the structural, pharmacokinetic, and pharmacodynamic profile of a series of Triazolo Thiadiazepine-fused Coumarin Derivatives (TDCDs) against MAOB, in comparison with the inhibitor safinamide. To achieve this goal, we utilized structure-based virtual screening techniques, including target prediction and absorption, distribution, metabolism, and excretion (ADME) prediction based on multi-parameter optimization (MPO) topological analysis, as well as ligand-based virtual screening techniques, such as docking and molecular dynamics. The findings indicate that the TDCDs exhibit structural similarity to other bioactive compounds containing coumarin and MAOB-binding azoles, which are present in the ChEMBL database. The topological analyses suggest that TDCD3 has the best ADME profile, particularly due to the alignment between low lipophilicity and high polarity. The coumarin and triazole portions make a strong contribution to this profile, resulting in a permeability with P app estimated at 2.15 × 10 -5  cm/s, indicating high cell viability. The substance is predicted to be metabolically stable. It is important to note that this is an objective evaluation based on the available data. Molecular docking simulations showed that the ligand has an affinity energy of - 8.075 kcal/mol with MAOB and interacts with biological substrate residues such as Pro102 and Phe103. The results suggest that the compound has a safe profile in relation to the MAOB model, making it a promising active ingredient for the treatment of PD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is a growing imperative for research into alternative compounds for the treatment of the fungal infections. Thus, many studies have focused on the analysis of antifungal proteins and peptides from different plant sources. Among these molecules are protease inhibitors (PIs). Previously, PIs present in the peptide-rich fractions called PEF1, PEF2 and PEF3 were identified from Capsicum chinense seeds, which have strong activity against phytopathogenic fungi. The aim of this study was to evaluate the mechanism of action and antimicrobial activity of PIs from PEF2 and PEF3 on the growth of yeasts of the genus Candida. In this work, analyses of their antimicrobial activity and cell viability were carried out. Subsequently, the mechanism of action by which the PIs cause the death of the yeasts was evaluated. Cytotoxicity was assessed in vitro by erythrocytes lysis and in vivo in Galleria mellonella larvae. PEF2 and PEF3 caused 100% of the growth inhibition of C. tropicalis and C. buinensis. For C. albicans inhibition was approximately 60% for both fractions. The PEF2 and PEF3 caused a reduction in mitochondrial functionality of 54% and 46% for C. albicans, 26% and 30% for C. tropicalis, and 71% and 68% for C. buinensis, respectively. These fractions induced morphological alterations, led to membrane permeabilization, elevated ROS levels, and resulted in necrotic cell death in C. tropicalis, whilst demonstrating low toxicity toward host cells. From the results obtained here, we intend to contribute to the understanding of the action of PIs in the control of fungal diseases of medical importance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Extracts from Mangifera indica leaves and its main component, mangiferin, have proven antidiabetic activity. In this study, mangiferin and its natural derivatives Homomangiferin (HMF), Isomangiferin (IMF), Neomangiferin (NMF), Glucomangiferin (GMF), Mangiferin 6'-gallate (MFG), and Norathyriol (NRT) were compared regarding their action on Diabetes mellitus (DM), employing docking and molecular dynamics (MD) simulations to analyze interactions with the aldose reductase enzyme, the precursor to the conversion of glucose into sorbitol. Notably, HMF showed significant affinity to residues in the active site of the enzyme, including Trp 79, His 110, Trp 111, Phe 122, and Phe 300, with an energy of - 7.2 kcal/mol, observed in the molecular docking simulations. MD reinforced the formation of stable complexes for HMF and MFG with the aldose reductase, with interaction potential energies (IPE) in the order of - 300.812 ± 52 kJ/mol and - 304.812 ± 52 kJ/mol, respectively. The drug-likeness assessment, by multiparameter optimization (MPO), highlighted that HMF and IMF have similarities with polyphenols and glycosidic flavonoids recently patented as antidiabetics, revealing that high polarity (TPSA > 180 Å 2 ) is a favorable property for subcutaneous administration, especially because of the gradual passive cell permeability values in biological tissues, with P app values estimated at < 10 × 10 -6 cm/s. These compounds are metabolically stable against metabolic enzymes, resulting in a low toxic incidence by metabolic activation, corroborating with a lethal dose (LD 50 ) greater than 2000 mg/kg. In this way, HMF showed a systematic alignment between predicted pharmacokinetics and pharmacodynamics, characterizing it as the most favorable substance for inhibiting aldose reductase., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03978-9., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: The present study aimed to evaluate the association between muscle mass variation, estimated by different equations, during hospitalization with the energy and protein intake and clinical and nutrition outcomes of patients using nutrition support., Methods: A prospective observational study with patients older than 18 years in use of enteral and/or parenteral nutrition therapy and monitored by the Nutritional Therapy Committee between December 14, 2021, and December 14, 2022. Data were collected from the electronic records and were applied in 11 equations to estimate the four different portions of muscle mass of patients receiving nutrition support at the beginning and the end of hospitalization., Results: A total of 261 patients were evaluated, with a median age of 61.0 (49.0-69.75) years, and 106 were women (40.6%). According to the nutrition diagnosis, several participants had severe malnutrition (39.5%). The most muscle mass estimation equations indicated a reduction of muscle mass during hospitalization. All patients presented negative energy and protein balances during hospitalization, but greater protein intake increased the lean soft tissue. Also, the greater the number of infections, metabolic complications, and scheduled diet interruption, the greater was the chance of losing muscle mass., Conclusion: There can be an association between the variation in muscle mass and energy and protein intake during hospitalization of patients using nutrition support. In addition, variation in muscle mass was associated with complications from nutrition support. The results emphasize the importance of anthropometric measurements to estimate muscle mass when other methods are not available., (© 2024 American Society for Parenteral and Enteral Nutrition.)

The characterization of colleters in Rubiaceae is crucial for understanding their role in plant function. Analyzing colleters in Palicourea tetraphylla and Palicourea rudgeoides aims to deepen the understanding of these structures morphoanatomical and functional characteristics. The study reveals colleters with palisade epidermis and a parenchymatic central axis, classified as standard type, featuring vascularization and crystals. Colleter secretion, abundant in acidic mucopolysaccharides, proteins, and phenolic compounds, protects against desiccation. The ontogenesis, development, and senescence of the colleters are quite rapid and fulfill their role well in biotic and abiotic protection because these structures are present at different stages of development in the same stipule. Pronounced protrusions on the colleters surface, coupled with the accumulation of secretion in the intercellular and subcuticular spaces, suggest that the secretory process occurs through the wall, driven by pressure resulting from the accumulation of secretion. The microorganisms in the colleters' secretion, especially in microbiota-rich environments such as the Atlantic Forest, provide valuable information about plant-microorganism interactions, such as resistance to other pathogens and organisms and ecological balance. This enhanced understanding of colleters contributes to the role of these structures in the plant and enriches knowledge about biological interactions within specific ecosystems and the family taxonomy.

The management of fungal diseases imposes an urgent need for the development of effective antifungal drugs. Among new drug candidates are the antimicrobial peptides, and especially their derivatives. Here, we investigated the molecular mechanism of action of three bioinspired peptides against the opportunistic yeasts Candida tropicalis and Candida albicans. We assessed morphological changes, mitochondrial functionality, chromatin condensation, ROS production, activation of metacaspases, and the occurrence of cell death. Our results indicated that the peptides induced sharply contrasting death kinetics, of 6 h for RR and 3 h for D-RR to C. tropicalis and 1 h for WR to C. albicans. Both peptide-treated yeasts exhibited increased ROS levels, mitochondrial hyperpolarization, cell size reduction, and chromatin condensation. RR and WR induced necrosis in C. tropicalis and C. albicans, but not D-RR in C. tropicalis. The antioxidant ascorbic acid reverted the toxic effect of RR and D-RR, but not WR, suggesting that instead of ROS there is a second signal triggered that leads to yeast death. Our data suggest that RR induced a regulated accidental cell death in C. tropicalis, D-RR induced a programmed cell death metacaspase-independent in C. tropicalis, while WR induced an accidental cell death in C. albicans. Our results were obtained with the LD 100 and within the time that the peptides induce the yeast death. Within this temporal frame, our results allow us to gain clarity on the events triggered by the peptide-cell interaction and their temporal order, providing a better understanding of the death process induced by them., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Several epidemiological, clinical and experimental studies in recent decades have shown the relationship between exposure to stressors during development and health outcomes later in life. The characterization of these susceptible phases, such as preconception, gestation, lactation and adolescence, and the understanding of factors that influence the risk of an adult individual for developing obesity, metabolic and cardiovascular diseases, is the focus of the DOHaD (Developmental Origins of Health and Disease) research line. In this sense, advancements in molecular biology techniques have contributed significantly to the understanding of the mechanisms underlying the observed phenotypes, their morphological and physiological alterations, having as a main driving factor the epigenetic modifications and their consequent modulation of gene expression. The present narrative review aimed to characterize the different susceptible phases of development and associated epigenetic modifications, and their implication in the development of non-communicable diseases. Additionally, we provide useful insights into interventions during development to counteract or prevent long-term programming for disease susceptibility., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: to compare the parameters of pain, oedema, temperature, and soft tissue closure in dental sockets that received two different photobiomodulation (PBM) protocols following extractions., Materials and Methods: Thirty-one participants had their teeth 38 and 48 extracted. Subsequently, one of the dental sockets received PBM at a wavelength (WL) of 808 nanometers (808 group- nm) and the other dental socket received the PBM at WLs of 808 nm and 660 nm, simultaneously (808 + 660 group). The PBM was applied immediately after the surgical procedure and on the 3rd and 7th days., Results: The mean of Visual Analogue Scale (VAS) values for pain were 1.45 for the 3rd day and 0.52 for the 7th day in the 808 + 660 and 808 group, respectively. The mean the pogonion-tragus measurement, used to assess facial oedema on the 3rd day, was 15.38 cm (range 13.5-17.5) in the 808 + 660 group and 15.48 cm (range 14.0-17.5) in the 808 group. The mean facial temperatures in the 808 + 660 group were 34.9 degrees Celsius (ºC) (range 33.5-36.4) on the 3rd day and 35 ºC (range 33.4-36.4) on the 7th day. In the 808 group, the mean temperatures were 34.9 ºC (range 33.9-36.2) on the 3rd day and 34.9 ºC (33.7-36.2) on the 7th day. Regarding the dimensions of the dental socket, the mean were similar for both groups. Significant differences between the groups were only observed in the pain parameter and only on the 7th day, being greater for the 808 + 660 group (p = 0.031)., Conclusions: The association of the 660 nm with 808 nm, and the increase in energy did not showed more benefits in pain reduction oedema, or acceleration of the closure of the soft tissues of the dental sockets of lower third molars, in the protocols used here., Clinical Relevance: There is no need to combine lasers at wavelengths of 660 and 808 nm to reduce oedema, pain and repair of soft tissues after extraction of lower third molars., Clinical Trial Registration: This trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the following code: RBR-66pyrh8, on 29th December, 2022., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Leishmaniasis is a complex group of infectious and parasitic diseases that afflict many thousands of individuals across five continents. Leishmaniasis treatment remains a challenge because it relies on drugsknown for their high toxicity and limited efficacy, making itimperative to identify new molecules that offer greater effectiveness and safety. This study sought to explore the impact of seven synthetic guanidine derivatives (LQOF-G1, LQOF-G2, LQOF-G6, LQOF-G7, LQOF-G32, LQOF-G35 and LQOF-G36) onthe parasite Leishmania (Viannia) braziliensis and in vitro macrophage infection by this parasite, as well as cytotoxic approaches in vitro models of mammalian host cells and tissues. The synthesized compounds showed purity ≥ 99.65% and effectively inhibited parasite growth. LQOF-G1 proved the most potent, yielding the best half-maximal inhibitory concentration (IC 50 ) values against promastigotes (4.62 μmol/L), axenic amastigotes (4.27 μmol/L), and intracellular amastigotes (3.65 μmol/L). Notably, the antileishmanial activity of LQOF-G1, LQOF-G2, and LQOF-G6 was related to immunomodulatory effects, evidenced by alterations in TNF-α, IL-12, IL-10, nitric oxide (NO), and reactive oxygen species (ROS) levels in the supernatant of culture macrophages infected with L. (V.) braziliensis and coincubated with these compounds. LQOF-G2 and LQOF-G36 compounds exhibited vasodilator and spasmolytic effects at higher concentrations (≥100 μmol/L). Generally, LQOF-G1, LQOF-G2, and LQOF-G32 compounds were found to be nontoxic to assessed organs and cells. No toxic effects were observed in human cell lines, such as HEK-293, CaCo-2 and A549, at concentrations ≥ 500 μmol/L. Collectively, data have shown unequivocal evidence of the effectiveness of these compounds against L. (V.) braziliensis parasite, one of the causative agents of Tegumentary Leishmaniasis and Mucocutaneous Leishmaniasis in America.

Antifungal resistance poses a significant challenge to disease management, necessitating the development of novel drugs. Antimicrobial peptides offer potential solutions. This study focused on extraction and characterization of peptides from Adenanthera pavonina seeds with activity against Candida species, Mycobacterium tuberculosis, proteases, and α-amylases. Peptides were extracted in phosphate buffer and heated at 90°C for 10 min to create a peptide rich heated fraction (PRHF). After confirming antimicrobial activity and the presence of peptides, the PRHF underwent ion exchange chromatography, yielding retained and non-retained fractions. These fractions were evaluated for antimicrobial activity and cytotoxicity against murine macrophages. The least toxic and most active fraction underwent reversed-phase chromatography, resulting in ten fractions. These fractions were tested for peptides and antimicrobial activity. The most active fraction was rechromatographed on a reversed-phase column, resulting in two fractions that were assessed for antimicrobial activity. The most active fraction revealed a single band of approximately 6 kDa and was tested for inhibitory effects on proteases and α-amylases. Thermal stability experiments were conducted on the 6 kDa peptide at different temperatures followed by reassessment of antifungal activity and circular dichroism. The 6 kDa peptide inhibited yeasts, M. tuberculosis, human salivary and Tenebrio molitor larvae intestine α-amylases, and proteolytic activity from fungal extracts, and thus named ApPI. Remarkably, ApPI retained antifungal activity and conformation after heating and is primarily composed of α-helices. ApPI is a thermally stable serine protease/α-amylase inhibitor from A. pavonina seeds, offering promise as a foundational molecule for innovative therapeutic agents against fungal infections and tuberculosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Bone quality of non-ambulatory patients with cerebral palsy (CP) is a matter of concern for proximal femoral varus derotational osteotomies (VDRO). Locking plates (LCP) have been designed to compensate this biological downfall. Little data exist comparing the LCP with the conventional femoral blade plate., Methods: We retrospectively studied 32 patients submitted to VDRO (40 hips), operated with blade plates or LCP. Groups were matched, and the minimal follow-up was 36 months. Clinical (age at surgery, sex, GMFCS class, CP patterns) and radiological characteristics (neck shaft angle [NSA], acetabular index [AI], Reimers migration index [MP] and time until bone healing), as well as postoperative complications and the cost of treatment, were evaluated., Results: Preoperative clinical characteristics and radiographic measurements were comparable, except for a higher AI in the BP group (p < 0.01). Mean follow-up was longer in the LCP group (57.35 vs 34.6 months). Mean NSA, AI and MP had comparable correction with surgery (p < 0.01). At final follow-up, dislocation recurrence speed was higher in BP group although not statistically significant (0.56% vs 0.35%/month; p = 0.29). The complication rate was similar in both groups (p > 0.05). Finally, the cost of the treatment was 62% higher in the LCP group (p = 0.01)., Conclusion: Our cohorts showed LCP or BP equivalence clinically and radiographically in mid-term follow-up, with the former increasing the cost of treatment by a mean of 62%. This may raise a question on the real necessity of locked implants for these operations., Level of Evidence: Level III-Retrospective comparative study., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

12-Thiazole abietanes are highly selective reversible inhibitors of hABHD16A that could potentially alleviate neuroinflammation. In this study, we used synthetic chemistry, competitive activity-based protein profiling, and computational methodologies to try to establish relevant structural determinants of activity and selectivity of this class of compounds for inhibiting ABHD16A over ABHD12. Five compounds significantly inhibited hABHD16A but also very efficiently discriminated between inhibition of hABHD16A and hABHD12, with compound 35 being the most effective, at 100 μM (55.1 ± 8.7%; p < 0.0001). However, an outstanding switch in the selectivity toward ABHD12 was observed in the presence of a ring A ester, if the C2' position of the thiazole ring possessed a 1-hydroxyethyl group, as in compound 28 . Although our data were inconclusive as to whether the observed enzyme inhibition is allosteric or not, we anticipate that the structure-activity relationships presented herein will inspire future drug discovery efforts in this field., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), challenged public health systems worldwide. Individuals in low-income countries/regions are still at individual and community risk concerning inequality, sanitation, and economic conditions. Besides, during the pandemic, the transmission in municipalities and communities in the countryside and less developed regions kept viral spread and required structured and strengthened clinical and laboratory surveillance. Here, we present an observational, analytic, cross-sectional study conducted using secondary data from the Laboratório de Farmacogenômica e Epidemiologia Molecular (LAFEM)-Universidade Estadual de Santa Cruz (UESC), to evaluate individual and community factors associated to SARS-CoV-2 infection in outpatients from different cities from Southern Region of Bahia State, in Brazil. The data were collected between June 2021 and May 2022. The SARS-CoV-2 positivity by RT-qPCR was correlated with low socio-economic indicators, including the Human development index ( HDI c ) and Average worker salary ( AWSc ). Besides, in general, females were less likely to test positive for SARS-CoV-2 (OR = 0.752; CI 95% 0.663-0.853; p < 0.0001), while brown individuals had more positivity for infection ( p < 0.0001). In addition, those who had clinical symptoms were more likely to test positive for SARS-CoV-2 (OR = 6.000; CI 95% 4.932-7.299; p < 0.0001). Although dry cough, headache, and fever were the most frequent, loss of taste (OR = 5.574; CI 95% 4.334-7.186) and loss of smell (OR = 6.327; CI 95% 4.899-8.144) presented higher odds ratio to be positive to SARS-CoV-2 by RT-qPCR. Nonetheless, the distribution of these characteristics was not homogenous among the different cities, especially for age and gender. The dynamic of SARS-CoV-2 positivity differed between cities and the total population and reinforces the hypothesis that control strategies for prevention needed to be developed based on both individual and community risk levels to mitigate harm to individuals and the health system.

Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.

Introduction: Ubiquitin-specific protease 7 (USP7) also known as herpesvirus-associated ubiquitin-specific protease (HAUSP) is a well-characterized cysteine protease that belongs to the largest subfamily of deubiquitinating enzymes (DUBs). It is involved in multiple signaling pathways, some of them dysregulated in malignant tumors. USP7 inhibition can lead to cell growth arrest and apoptosis through inhibition of tumor promoters and stabilization of tumor suppressors, making it a promising druggable target for cancer therapy., Areas Covered: This review covers the structure of USP7, its function in multiple signaling pathways and relevance in cancer, as well as recent advances and future perspectives in the development of USP7 inhibitors for cancer therapy., Expert Opinion: Literature reports display the multiple antitumor activities of USP7 inhibitors, both in vitro and in vivo. Nonetheless, none have entered clinical trials so far, highlighting the need to delve into a deeper understanding of USP7 binding sites and the development of more accurate compound screening methods. Despite these challenges, further development of USP7 inhibitors is promising as a valuable new approach for cancer treatment, including the ability to address chemoresistance.

Plant fungal diseases cause major problems for the global economy. Antimicrobial peptides have aroused great interest in the control of phytopathogens, as they are natural molecules and have a broad spectrum of inhibitory activity. Herein, we have tried to identify and characterize antimicrobial peptides present in fruits of Capsicum chinense and to evaluate their enzymatic and antifungal activities. The retained fraction obtained in the anion exchange chromatography with strong antifungal activity was subjected to molecular exclusion chromatography and obtained four fractions named G1, G2, G3, and G4. The 6.0-kDa protein band of G2 showed similarity with protease inhibitors type II, and it was able to inhibit 100% of trypsin and α-amylase activities. The protein band with approximately 6.5 kDa of G3 showed similarity with sequences of protease inhibitors from genus Capsicum and showed growth inhibition of 48% for Colletotrichum lindemuthianum, 49% for Fusarium lateritium, and 51% for F. solani and F. oxysporum. Additionally, G3 causes morphological changes, membrane permeabilization, and ROS increase in F. oxysporum cells. The 9-kDa protein band of G4 fraction was similar to a nsLTP type 1, and a protein band of 6.5 kDa was similar to a nsLTP type 2. The G4 fraction was able to inhibit 100% of the activities of glycosidases tested and showed growth inhibition of 35 and 50% of F. oxysporum and C. lindemuthianum, respectively. C. chinense fruits have peptides with antifungal activity and enzyme inhibition with biotechnological potential., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The COVID-19 pandemic put healthcare professionals, including residents (postgraduate trainees of health professions), under intense physical and psychological stress, hence at risk for mental disorders. We evaluated the prevalence of mental disorders among healthcare residents during the pandemic., Methods: From July to September 2020, residents in medicine and other healthcare specialties in Brazil were recruited. The participants completed electronic forms with validated questionnaires (DASS-21, PHQ-9, BRCS) to screen for depression, anxiety, and stress, and to evaluate resilience. Data on potential predisposing factors for mental disorders were also collected. Descriptive statistics, chi-squared, students t, correlation and logistic regression models were applied. The study received ethical approval, and all participants provided informed consent., Results: We included 1313 participants (51.3% medical; 48.7% nonmedical) from 135 Brazilian hospitals; mean (SD) age: 27.8 (4.4) years; 78.2% females; 59.3% white race. Of all participants, 51.3%, 53.4% and 52.6% presented symptoms consistent with depression, anxiety, and stress, respectively; 61.9% showed low resilience. Nonmedical residents exhibited higher anxiety compared to medical residents (DASS-21 anxiety score, mean difference: 2.26; 95% CI: 1.15-3.37; p < 0.001). In multivariate analyses, having any pre-existent, nonpsychiatric chronic disease was associated with higher prevalence of symptoms indicative of depression (odds ratio, OR: 2.05; 95% CI: 1.47-2.85, on DASS-21 | OR: 2.26; 95% CI: 1.59-3.20, on PHQ-9), anxiety (OR: 2.07; 95% CI: 1.51-2.83, on DASS-21), and stress (OR: 1.53; 95% CI: 1.12-2.09, on DASS-21); other predisposing factors were identified; by contrast, high resilience (BRCS score) was protective against symptoms of depression (OR 0.82; 95% CI: 0.79-0.85, on DASS-21 | OR 0.85; 95% CI: 0.82-0.88, on PHQ-9), anxiety (OR 0.90; 95% CI: 0.87-0.93, on DASS-21), and stress (OR 0.88; 95% CI: 0.85-0.91, on DASS-21); p < 0.05 for all outcomes., Conclusions: We found a high prevalence of mental disorder symptoms among healthcare residents during COVID-19 pandemic in Brazil. Nonmedical residents exhibited higher levels of anxiety than medical ones. Some predisposing factors for depression, anxiety and stress among residents were identified., (© 2023. The Author(s).)

Objective: To assess the accuracy of cone-beam computed tomography (CBCT) for determining gingival thickness., Material and Methods: Searches were undertaken in PubMed/MEDLINE, EMBASE, LILACS, Web of Science, Scopus, LIVIVO, and gray literature (Google Scholar and ProQuest) for studies considered eligible according to the following criteria: cross-sectional observational studies, which compared CBCT accuracy with that of transgingival probing when determining gingival thickness, in adult patients with good periodontal health. No language or time restrictions were applied in this systematic review. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for analytical cross-sectional studies., Results: Six articles were included for qualitative synthesis, involving a pooled sample of 132 patients with a mean age of 29 years (18-51 years). Of these 6 studies, 5 were eligible for quantitative analysis. The meta-analysis showed no statistically significant difference between CBCT and transgingival probing measures of gingival tissue (mean difference of 0.10 (95% CI-0.17-0.38). No significant level of heterogeneity was detected (Tau 2 -P = 0.0662; I 2 = 0%; H 2 -P = 1.000; Q-P = 1.134). According to the GRADE criterion, confidence in the cumulative evidence was considered low., Conclusions: CBCT is an accurate method for determining gingival tissue thickness, comparable to the reference standard (transgingival probing)., Clinical Relevance: CBCT could be considered for gingival thickness measurement when bone thickness is also needed, and thereby aid in the assessment of gingival biotype without the discomfort and anesthesia needed in transgingival probing., Trial Registration: This protocol was registered at the PROSPERO database (International Prospective Register of Systematic Review) under registration number CRD42022326970. Available from: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42022326970 ., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to develop films of chitosan (CSF) associated with pentoxifylline (PTX) for healing cutaneous wounds. These films were prepared at two concentrations, F1 (2.0 mg/mL) and F2 (4.0 mg/mL), and the interactions between the materials, structural characteristics, in vitro release, and morphometric aspects of skin wounds in vivo were evaluated. The formation of the CSF film with acetic acid modifies the polymeric structure, and the PTX demonstrates interaction with the CSF, in a semi-crystalline structure, for all concentrations. The release for all films was proportional to the concentration, with two phases: a fast one of ≤2 h and a slow one of >2 h, releasing 82.72 and 88.46% of the drug after 72 h, being governed by the Fickian diffusion mechanism. The wounds of the mice demonstrate a reduction of up to 60% in the area on day 2 for F2 when compared to CSF, F1, and positive control, and this characteristic of faster healing speed for F2 continues until the ninth day with wound reduction of 85%, 82%, and 90% for CSF, F1, and F2, respectively. Therefore, the combination of CSF and PTX is effective in their formation and incorporation, demonstrating that a higher concentration of PTX accelerates skin-wound reduction.

Citrus leprosis (CL) is the main viral disease affecting the Brazilian citriculture. Sweet orange ( Citrus sinensis L. Osbeck) trees affected by CL were identified in small orchards in Southern Brazil. Rod-like particles of 40 × 100 nm and electron lucent viroplasm were observed in the nucleus of infected cells in symptomatic tissues. RNA extracts from three plants, which proved negative by RT-PCR for known CL-causing viruses, were analyzed by high throughput sequencing and Sanger sequencing after RT-PCR. The genomes of bi-segmented ss(-)RNA viruses, with ORFs in a typical organization of members of the genus Dichorhavirus , were recovered. These genomes shared 98-99% nt sequence identity among them but <73% with those of known dichorhavirids, a value below the threshold for new species demarcation within that genus. Phylogenetically, the three haplotypes of the new virus called citrus bright spot virus (CiBSV) are clustered with citrus leprosis virus N, which is a dichorhavirus transmitted by Brevipalpus phoenicis sensu stricto. In CiBSV-infected citrus plants, B. papayensis and B. azores were found, but the virus could only be transmitted to Arabidopsis plants by B. azores. The study provides the first evidence of the role of B. azores as a viral vector and supports the assignment of CiBSV to the tentative new species Dichorhavirus australis .

Myxobolus spp. are parasites of wide diversity and distribution in fish, both in the natural environment and in freshwater or marine farming systems around the world and are sometimes associated with severe disease in their hosts (Schmahl et al. 1989; Lom and Dyková, 1995; Eiras et al. 2021). The white mullet Mugil curema Valenciennes, 1836 is a pelagic fish of the Mugilidae family widely distributed in the Atlantic Ocean (Froese & Pauly 2022). Recently, Myxobolus curemae Vieira, Agostinho, Negrelli, Silva, Azevedo and Abdallah, 2022 was described from white mullets Mugil curema Valenciennes, 1836 in Brazil (Vieira et al. 2022). In the current work, Myxobolus sp. was identified with the same biological and morphological characteristic features of M. curemae from white mullets from the Jacarepaguá Lagoon Complex in the State of Rio de Janeiro, Brazil, in addition to being 100% identical for a genic region of the nuclear small subunit ribosomal DNA. However, this Myxobolus sp. was also similar to Myxobolus hani Faye, Kpatcha, Diebakate, Fall and Toguebaye, 1999, which was described from white mullets in Senegal, Africa, without molecular identification (Faye et al. 1999). Therefore, this current work makes observations on these Myxobolus spp. which are morphologically and biologically similar, and that could establish M. curemae as a junior synonymy of M. hani.

Background: Protease inhibitors (PIs) have attracted attention due to their important roles in plant defense., Objective: The objective of this work was to characterize and evaluate the antimicrobial activity of the peptides of a family of serine PIs from Capsicum chinense Jacq. seeds., Methods: Initially, PIs were extracted from the seeds and subjected to purification by chromatography, resulting in three different peptide enriched fractions (PEFs) termed PEF1, PEF2 and PEF3. Subsequently, the PEF3 was subjected to trypsin inhibition assays, α-amylase activity assays, antimicrobial activity assays on phytopathogenic fungi, and assays to determine the likely mechanisms of action., Results: The PEF3 was composed of three protein bands with molecular masses ranging between 6 and 14 kDa. The amino acid residues of the ~6 kDa band showed high similarity with serine PIs. PEF3 inhibited the activity of the enzymes trypsin, human salivary α-amylase, and Tenebrio molitor larval α-amylase and inhibited the growth of phytopathogenic fungi, showing 83.7% loss of viability in Fusarium oxysporum. PEF3 induced reactive oxygen species in Colletotrichum lindemuthianum and F. oxysporum to dissipate their mitochondrial membrane potential and activated caspases in C. lindemuthianum., Conclusion: Our results reinforce the importance of PIs in plant defense mechanisms against phytopathogenic fungi as well as in their biotechnological applications for the control of plant pathogens., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Since the beginning of the COVID-19 pandemic, health professionals have been working under extreme conditions, increasing the risk of physical and mental illness. We evaluated the prevalence of burnout and its associated factors among postgraduate student residents in health professions during the global health crisis., Methods: Healthcare residents were recruited from all across Brazil between July and September 2020 through digital forms containing instruments for assessing burnout (Oldenburg Burnout Inventory (OLBI)), resilience (brief resilient coping scale (BRCS)) and anxiety, stress and depression (depression, anxiety and stress scale (DASS-21) and Patient Health Questionnaire (PHQ-9)). Additionally, the relationships between burnout and chronic diseases, autonomy and educational adequacy in the residency programme, personal protective equipment (PPE), workload and care for patients with COVID-19 were evaluated. The chi-square test, Student's t test, Pearson's correlation test and logistic regression were performed., Results: A total of 1,313 participants were included: mean (standard deviation) age, 27.8 (4.4) years; female gender, 78.1%; white race, 59.3%; and physicians, 51.3%. The overall prevalence of burnout was 33.4%. The odds (odds ratio [95% confidence interval]) of burnout were higher in the presence of pre-existing diseases (1.76 [1.26-2.47]) and weekly work > 60 h (1.36 [1.03-1.79]) and were lower in the presence of high resilience (0.84 [0.81-0.88]), autonomy (0.87 [0.81-0.93]), and educational structure (0.77 [0.73-0.82]), adequate availability of PPE (0.72 [0.63-0.83]) and non-white race (0.63 [0.47-0.83]). Burnout was correlated with anxiety (r = 0.47; p < 0.05), stress (r: 0.58; p < 0.05) and depression (r: 0.65; p < 0.05)., Conclusions: We observed a high prevalence of burnout among residents during the COVID-19 pandemic. Individual characteristics and conditions related to the work environment were associated with a higher or lower occurrence of the syndrome., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Pinho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Maternal circadian eating time and frequency are associated with altered glucose metabolism during pregnancy in humans. Research on long maternal fasting intervals is inconclusive, and little is known about the effect of maternal time feeding on offspring health. Therefore, the aim of the present study is to determine whether maternal time feeding influences the metabolic status of both male and female offspring., Methods: Pregnant rats were provided ad libitum access to chow diet or fed during either the light phase (LP) or dark phase (DP) during embryonic development. At the age of 150 days, glucose tolerance, lipid concentrations, and insulin secretion were determined in adult male and female offspring., Results: Both male and female offspring of LP and DP dams exhibited alterations in the lipid profile, and female offspring were glucose intolerant. Glucose-stimulated insulin secretion decreased in male and female offspring of LP and DP dams. Acetylcholine increased insulin secretion in male and female offspring. Islets from male and female offspring of DP dams exhibited less pronounced inhibition of insulin secretion by epinephrine, suggesting alterations in the cholinergic and adrenergic pathways in these animals., Conclusions: Our data suggest that a time-restricted feeding regimen during embryonic development could program rat offspring for metabolic dysfunction during adulthood., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Antimicrobial peptides, natural or synthetic, appear as promising molecules for antimicrobial therapy because of their both broad antimicrobial activity and mechanism of action. Herein, we determine the anti-Candida and antimycobacterial activities, mechanism of action on yeasts, and cytotoxicity on mammalian cells in the presence of the bioinspired peptide CaDef2.1 G27-K44 ., Methods: CaDef2.1 G27-K44 was designed to attain the following criteria: high positive net charge; low molecular weight (<3000 Da); Boman index ≤2.5; and total hydrophobic ratio ≥ 40%. The mechanism of action was studied by growth inhibition, plasma membrane permeabilization, ROS induction, mitochondrial functionality, and metacaspase activity assays. The cytotoxicity on macrophages, monocytes, and erythrocytes were also determined., Results: CaDef2.1 G27-K44 showed inhibitory activity against Candida spp. with MIC 100 values ranging from 25 to 50 μM and the standard and clinical isolate of Mycobacterium tuberculosis with MIC 50 of 33.2 and 55.4 μM, respectively. We demonstrate that CaDef2.1 G27-K44 is active against yeasts at different salt concentrations, induced morphological alterations, caused membrane permeabilization, increased ROS, causes loss of mitochondrial functionality, and activation of metacaspases. CaDef2.1 G27-K44 has low cytotoxicity against mammalian cells., Conclusions: The results obtained showed that CaDef2.1 G27-K44 has great antimicrobial activity against Candida spp. and M. tuberculosis with low toxicity to host cells. For Candida spp., the treatment with CaDef2.1 G27-K44 induces a process of regulated cell death with apoptosis-like features., General Significance: We show a new AMP bioinspired with physicochemical characteristics important for selectivity and antimicrobial activity, which is a promising candidate for drug development, mainly to control Candida infections., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This work aimed to investigate the effects of early progeny exposure to methylglyoxal (MG), programming for metabolic dysfunction and diabetes-like complications later in life. At delivery (PN1), the animals were separated into two groups: control group (CO), treated with saline, and MG group, treated with MG (20 mg/kg of BW; i.p.) during the first 2 weeks of the lactation period. In vivo experiments and tissue collection were done at PN90. Early MG exposure decreased body weight, adipose tissue, liver and kidney weight at adulthood. On the other hand, MG group showed increased relative food intake, blood fructosamine, blood insulin and HOMA-IR, which is correlated with insulin resistance. Besides, MG-treated animals presented dyslipidaemia, increased oxidative stress and inflammation. Likewise, MG group showed steatosis and perivascular fibrosis in the liver, pancreatic islet hypertrophy, increased glomerular area and pericapsular fibrosis, but reduced capsular space. This study shows that early postnatal exposure to MG induces oxidative stress, inflammation and fibrosis markers in pancreas, liver and kidney, which are related to metabolic dysfunction features. Thus, nutritional disruptors during lactation period may be an important risk factor for metabolic alterations at adulthood.

Coccidian protozoan species recorded from flycatchers are few, but they have been described with a certain frequency in recent years. In this context, the present study describes a new Isospora sp. from sepia-capped flycatchers Leptopogon amaurocephalus Tschudi, 1846 captured in the Itatiaia National Park and in a reforestation area which is about 60 km away from the park boundaries, in addition to providing a molecular identification via sequencing of the mitochondrial cytochrome c oxidase subunit 1 gene. Isospora leptopogoni n. sp. has oöcysts that are subspheroidal to ovoidal, measuring on average 22.0 × 19.7 μm, with a smooth, bi-layered wall, c.1.7 μm thick. The micropyle is delicate or inconspicuous. Oöcyst residuum is absent, but one to three polar granules are present. Sporocysts are lemon-shaped, measuring on average 14.7 × 9.3 μm, with a knob-like Stieda body and a rectangular to rounded sub-Stieda body. Sporocyst residuum is present, consisting of compactly bounded granules. Sporozoites are vermiform, with refractile bodies and nucleus. Isospora leptopogoni is different from other Isospora spp. mainly due to its lemon-shaped sporocysts, the presence of micropyle and details of Stieda and sub-Stieda bodies. Phylogenetic analysis placed I. leptopogoni close to other Isospora spp. recorded from phylogenetically related hosts and from the same biogeographic region. Finally, the recurrent finding of this coccidian species in the same L. amaurocephalus specimen in a specific locality in the Itatiaia National Park suggests that the dispersion of I. leptopogoni needs continuous transmissions between susceptible passerines as the area of movement of each L. amaurocephalus specimen appears to be quite small., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Eimeria spp. are coccidian protozoan parasites of domestic and wild animals. Pelecaniform birds are hosts of some Eimeria spp., however, from the family Threskiornithidae only one eimerian species is recorded, Eimeria bazi Chauhan et Bhatia, 1970 which was described from red-naped ibises Pseudibis papillosa (Temminck, 1824) in India. In this study, in turn, this species is morphologically and molecularly identified from buff-necked ibises Theristicus caudatus (Boddaert, 1783) in Brazil., Purpose: This study aimed to report E. bazi from buff-necked ibises T. caudatus in southeastern Brazil, revealing the worldwide distribution of this coccidian species, in addition to providing preliminary genotypic identification via sequencing of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene., Methods: A total of 73 fecal samples were collected from a flock of buff-necked ibises, which remained on the campus of the Federal Rural University of Rio de Janeiro (Universidade Federal Rural do Rio de Janeiro-UFRRJ) from March 2019 to August 2020. Fecal samples were processed by the Sheather's method to recover oocysts. The morphological and morphometrical studies of the oocysts were performed using an optical microscope and graphic editing software. Molecular analysis was performed by sequencing of the COI gene, and the phylogenetic analysis was based in the neighbor-joining and maximum likelihood estimates., Results: Forty-five fecal samples were positive for oocysts identified as E. bazi. This oocysts are ovoidal, 26.2 × 18.9 μm, with smooth to slightly rough wall, c.1.7 μm thick. Micropyle robust and protruding, sometimes with a polar body attached. Oocyst residuum absent, but one or two small polar granules are present. Sporocysts ovoidal to lemon-shaped, 14.2 × 8.7 μm. The Stieda body is knob-like to rounded and sub-Stieda body is absent or vestigial. Sporocyst residuum is composed of granules often membrane-bound. Sporozoites are vermiform, with refractile bodies. This morphology was consistent with the original description of E. bazi from P. papillosa in India. Molecular analysis at the COI gene exhibited low similarity with coccidians sequenced for the same genic region deposited in GenBank, sitting E. bazi separately on the cladogram., Conclusions: The morphological and molecular studies support the identification of E. bazi from T. caudatus in South America, thus revealing the wide distribution of this eimerian species in the world provided by migratory birds and/or with intercontinental distribution., (© 2022. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

Background: Kidney transplant patients frequently suffer from Chronic Kidney Disease associated with Mineral Bone Disease (CKD-MBD), a complex condition that affects mainly kidney transplant patients. Post-transplantation bone disease is complex, especially in patients with pre-existing metabolic bone disorders that are further affected by immunosuppressive medications and changes in renal allograft function. Main biochemical abnormalities of mineral metabolism in kidney transplantation (KTx) include hypophosphatemia, hyperparathyroidism (HPTH), insufficiency or deficiency of vitamin D, and hypercalcemia., Objective: This review aims to summarize the pathophysiology and main biomarkers of CKD-MBD in KTx., Methods: A comprehensive and non-systematic search in PubMed was independently made, emphasizing biomarkers in mineral bone disease in KTx., Results: CKD-MBD can be associated with numerous factors, including secondary HPTH, metabolic dysregulations before KTx, and glucocorticoid therapy in post-transplant subjects. Fibroblast growth factor 23 (FGF23) reaches normal levels after KTx with good allograft function, while calcium, vitamin D, and phosphorus, ultimately result in hypercalcemia, persistent vitamin D insufficiency, and hypophosphatemia, respectively. As for PTH levels, there is an initial tendency of a significant decrease, followed by a rise due to secondary or tertiary HPTH. In regard to sclerostin levels, there is no consensus in the literature., Conclusion: KTx patients should be continuously evaluated for mineral homeostasis and bone status, both in cases with successful kidney transplantation and those with reduced functionality. Additional research on CKD-MBD pathophysiology, diagnosis, and management is essential to guarantee long-term graft function, better prognosis, good quality of life, and reduced mortality for KTx patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Guillian Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy often associated with previous exposure to infectious agents., Methods: A clinical cohort of 41 patients with GBS admitted to the Base Hospital Institute of the Federal District between May 2017 and April 2019 was followed up for 1 year. Serological tests for arbovirus detection and amplification of nucleic acids using polymerase chain reaction for zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV) were performed., Results: The cohort consisted of 61% men with a median age of 40 years, and 83% had GBS-triggering events. A total of 54% had Grade 4 disability, 17% had Grade 3, 12% had Grade 2, 10% had Grade 5, and 7% had Grade 1. The classic form occurred in 83% of patients. Nerve conduction evaluations revealed acute demyelinating inflammatory polyneuropathy (51%), acute motor axonal neuropathy (17%), acute sensory-motor neuropathy (15%), and indeterminate forms (17%). Four patients were seropositive for DENV. There was no laboratory detection of ZIKV or CHIKV infection. Ninety percent of patients received human immunoglobulin. Intensive care unit admission occurred in 17.1% of the patients, and mechanical ventilation was used in 14.6%. One patient died of Bickerstaff's encephalitis. Most patients showed an improvement in disability at 10 weeks of follow-up., Conclusions: GBS in the Federal District showed a variable clinical spectrum, and it was possible to detect recent exposure to DENV.

The present study identifies three Isospora spp. recorded from faecal samples of green-winged saltators Saltator similis d'Orbigny & Lafresnaye kept in captivity in the surroundings of the Itatiaia National Park, which is a Conservation Unit with a high degree of vulnerability located in the Serra da Mantiqueira on the border of the States of Rio de Janeiro and Minas Gerais. Isospora saltatori Berto, Balthazar, Flausino & Lopes, 2008, Isospora trincaferri Berto, Balthazar, Flausino & Lopes, 2008 and Isospora similisi Coelho, Berto, Neves, Oliveira, Flausino & Lopes, 2013 were compatible in all characteristic features with their respective original descriptions, despite some divergences that are discussed in this study. In addition to the preliminary morphological identification, this study provided a preliminary genotypic identification of these three Isospora spp. via sequencing of the mitochondrial cytochrome c oxidase subunit 1 gene, which was suitable for the genotypic differentiation of these three coccidians, but was inconclusive in the phylogenetic analysis. Finally, this study discusses the environmental risks of these coccidians in captivity of green-winged saltators in the surroundings of the Itatiaia National Park., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)