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Eggplant (Solanum melongena) is consumed extensively in Brazil. It has been believed that infusion of a powdered preparation of the fruit may reduce serum cholesterol. However, there are few documented reports on its effects on cholesterol metabolism and its possible hypocholesterolemic effect has not been proved by well-controlled studies. The aim of the present study was to observe the effects of S. melongena on the serum cholesterol and triglycerides of 38 hypercholesterolemic human volunteers ingesting S. melongena infusion for five weeks. Thirty-eight hypercholesterolemic subjects receiving either S. melongena infusion (N = 19) or placebo (N = 19) participated in two clinical experiments in which the effect of S. melongena infusion was studied with (N = 16) or without (N = 38) dietary orientation. Total cholesterol and its fractions, triglycerides, and apolipoproteins A and B were measured in blood at the beginning of the experiment and three and five weeks thereafter. No differences were observed compared to control. Intraindividual analysis showed that S. melongena infusion significantly reduced the blood levels of total and LDL cholesterol and of apolipoprotein B. After dietary orientation, no intra- or intergroup differences were seen for any of the parameters analyzed. The results suggest that S. melongena infusion had a modest and transitory effect, which was not different from that obtained with standard orientation for dyslipidemia patients (diet and physical activities).

Abstract: Background: Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs−), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation‐associated compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation. Methods: The distribution of different maturation‐associated subsets of BM and PB CD34+ HPC from 64 newly diagnosed (KIT‐mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS‐purified PB cell compartments were also investigated for the KIT mutation. Results: ISM patients showed higher percentages of both BM and PB MC‐committed CD34+ HPC vs controls, particularly among ISM cases with MC‐restricted KIT mutation (ISMMC); this was associated with progressive blockade of maturation of CD34+ HPC to the neutrophil lineage from ISMMC to multilineage KIT‐mutated cases (ISMML). Regarding the frequency of KIT‐mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT‐mutated PB CD34+ HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs−MC and ISMs+MC to ISMML patients. Conclusion: The presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34+ HPC and multiple myeloid cell subpopulations, KIT‐mutated PB CD34+ HPC potentially contributing to early dissemination of the disease. [ABSTRACT FROM AUTHOR]

Amblyomma sculptum ( Ixodida: Ixodidae) Berlese, 1888, a member of the Amblyomma cajennense complex, is the major vector of Brazilian spotted fever ( BSF) in southeastern Brazil. In this study, the genetic diversity of A. sculptum populations in the state of Rio de Janeiro ( RJ), Brazil, was investigated because genetic variability in tick populations may be related to vector competence. Samples of A. sculptum from 19 municipalities in 7 regions of RJ were subjected to DNA extraction, amplification and sequencing of D-loop, cytochrome oxidase II and 12S rDNA mitochondrial genes. These sequences were used to map the genetic diversity of this tick. Amblyomma sculptum populations are genetically diverse in RJ, especially in the South Centre and Highland regions. Few unique haplotypes were observed in all populations, and the majority of genetic variation found was among ticks within each population. Phylogenetic reconstruction reinforced the assumption that all the haplotypes identified in RJ belong to A. sculptum. However, some RJ haplotypes are closer to A. sculptum from Argentina than to A. sculptum from elsewhere in Brazil. In RJ, A. sculptum has high genetic diversity, although little genetic differentiation. Observations also indicated a high level of gene flow among the studied populations and no evidence of population structure according to region in RJ. [ABSTRACT FROM AUTHOR]

Cacajao calvus ucayalii (Thomas, 1928) (Primates: Pitheciidae), a subspecies endemic to the Peruvian Amazon, occurs in patchy and sometimes isolated populations in north-eastern Peru and is in a vulnerable situation, mainly due to habitat loss and hunting. This rareness and remote distribution means that, until now, parasitical studies have been limited. Based on optical and scanning electron microscopy of specimens of both sexes, we report two new species of Trypanoxyuris pinworms occurring in the large intestine of the Peruvian red uakari, namely Trypanoxyuris (Trypanoxyuris) cacajao and Trypanoxyuris (Trypanoxyuris) ucayalii. Both species showed a distinct morphology of the lips and cephalic structure. Sexual dimorphism in the lateral alae was observed in both male and the female worms, with ventral ornamentation being shown in the oesophageal teeth. The finding of these new pinworm species highlights the possibility of discovering other species. [ABSTRACT FROM AUTHOR]

Health-care workers (HCWs) on the frontlines of the 2019 Coronavirus Disease 2019 (COVID-19) have a high risk of acquiring and dying from the disease. Brazil is a country with high morbimortality and ranks highest in general mortality from COVID-19. A large proportion of medical doctors (MDs) is dying, impacting in the workforce. As part of the research by Fiocruz on working conditions among HCWs, we have conducted this study of death among MDs. We analyzed data from Federal Council of Medicine, the only national platform with details about deaths in MDs. A broad search of other sources, including the Ministry of Health, was done, but unfortunately, the data does not exist. A total of 622 MDs died from March 2020 to March 2021: 87.6% male and 75% over age 60. The Southeast had the highest percentage (34.7%), followed by the Northeast (27.2%), and rankings by state showed Rio de Janeiro (15.8%), followed by São Paulo, Pará, Paraná and Paraíba, totalizing 50.1%. The specialties with highest mortality were gynecology (12.2%), pediatrics (10.0%), internal medicine (9.3%), general surgery (7.8%) and cardiology (7.6%). May 2020 was the month of worst mortality (16.9%) followed by July and June. A slow decline was observed until October, when Brazil begun to experience the ‘‘second wave’’. The vaccination of MDs began at the end of January 2021 and has not been sufficient time to evaluate the impact on morbimortality. The results of a study of 50 professional categories are under analysis and will be published soon as well as a study of ‘‘invisible’’ HCWs, who do not have specific training but are essential to supporting health care system, from primary care units to high-complexity hospitals. We hope that the results of these studies will improve links among managers, those who define public policies, and union leaders, achieving better workplace and living conditions, minimizing health and socioeconomic disparities. Key messages: This study is about death by COVID-19 among medical doctors in Brazil, as part of a large one on professional categories, essentials to supporting health care system, conducted by FIOCRUZ. This stdy is part of a large one on professional categories, essentials to supporting health care system, conducted by FIOCRUZ. [ABSTRACT FROM AUTHOR]

Health-care workers (HCWs) on the frontlines have a high risk of acquiring and dying from covid-19. Nursing professionals (NP) represent over half of HCWs in Brazil, a country with high morbidity and mortality from covid-19, above all in 2021. The absenteeism and death of nursing professionals due to covid-19 have a major impact on the workforce. As part of the research by Fiocruz on working conditions among HCWs, including those considered ‘‘invisible,’’ we have conducted this study of death among graduated nurses. Although they represent 4 out of 5 members of nursing teams in Brazil, the technicians and assistant nurses remains largely unseen and are covered by the ‘‘invisible’’ HCW study. We analyzed data from Federal Council of Nurses, publicized at the website Observatorio da Enfermagem. The sociodemographic profile, professional category and timeline of nursing professional deaths were considered. The time period of the study was from March 2020 to March 2021. A total of 670 professionals of the nursing team died, 200 of these were nurses. Among nurses: 59.5% were female and 81.5% were up to 60 years old. Our study registers a concentration of deaths in the North region. Despite having fewer registered professionals, it had the highest number of deaths (29.5%), and the Southeast had the second highest percentage (26.5%). A slow decline was observed until December, when Brazil experienced a ‘‘second wave’’ of Covid-19. Vaccination of Nurses began in late January 2021; therefore, there was not enough time to assess the impact on morbidity and mortality. The results of a study of almost 50 professional categories are under analysis and will be published shortly. Key messages: This study is about death by COVID-19 among nurses in Brazil. This study is part of a large one on professional categories, essentials to supporting health care system, conducted by FIOCRUZ. [ABSTRACT FROM AUTHOR]

Abstract: The properties of granite powders—a granite manufacturing waste product—were analyzed to assess their potential use as amendments and fertilizers on acid soils. Two types of powders were characterized: one produced during cutting of granite with a diamond-edged disc saw, comprising only rock powder, the other produced during cutting with a multi-blade bandsaw, containing calcium hydroxide and metal filings added during the cutting procedure. The acid neutralizing capacity of the granite powders was assessed in short- (2–3h) and medium-term (1–30d) experiments. The powders showed a buffering capacity at around pH 8, which corresponded to the rapid dissolution of basic cations, and another buffering effect at pH<4.5, attributable to the dissolution of Fe and Al. The acid neutralizing capacity (ANC) determined in the short-term experiments, to a final pH of 4.5, varied between 5 and 61cmolH+ kg−1 powder. The ANC to pH 4.5 obtained in the medium-term experiments was much higher than that obtained in the short-term experiments, reaching a maximum ANC value of 200cmolH+ kg−1 powder. There was no great difference in the neutralizing capacity determined at between 1 and 30d. The most abundant elements in acid solutions obtained at the end of medium-term experiments were Mg and Ca for disc saw powders, whereas Ca and Fe (at pH<5) were the most soluble elements in the bandsaw powders. The rapid release of these cations suggests the possible effective use of the granite powders as a source of nutrients on being added to acid soils. [Copyright &y& Elsevier]

In humans, insulin resistance is a physiological response to infections developed to supply sufficient energy to the activated immune system. This metabolic adaptation facilitates the immune response but usually persists after the recovery period of the infection and predisposes the hosts to type 2 diabetes and vascular injury. In patients with diabetes, superimposed insulin resistance worsens metabolic control and promotes diabetic ketoacidosis. Pathogenic mechanisms underlying insulin resistance during microbial invasions remain to be fully defined. However, interferons cause insulin resistance in healthy subjects and other population groups, and their production is increased during infections, suggesting that this group of molecules may contribute to reduced insulin sensitivity. In agreement with this notion, gene expression profiles [transcriptomes] from patients with insulin resistance show a robust overexpression of interferon-stimulated genes [interferon signature]. In addition, serum levels of interferon and surrogates for interferon activity are elevated in patients with insulin resistance. Circulating levels of interferon-γ-inducible protein-10, neopterin, and apolipoprotein L1 correlate with insulin resistance manifestations, such as hypertriglyceridemia, reduced HDL-c, visceral fat, and homeostasis model assessment-insulin resistance. Furthermore, interferon downregulation improves insulin resistance. Antimalarials such as hydroxychloroquine reduce interferon production and improve insulin resistance, reducing the risk for type 2 diabetes and cardiovascular disease. In addition, diverse clinical conditions that feature interferon upregulation are associated with insulin resistance, suggesting that interferon may be a common factor promoting this adaptive response. Among these conditions are systemic lupus erythematosus, sarcoidosis, and infections with severe acute respiratory syndrome-coronavirus-2, human immunodeficiency virus, hepatitis C virus, and Mycobacterium tuberculosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The risk for metabolic and cardiovascular complications of obesity is defined by body fat distribution rather than global adiposity. Unlike subcutaneous fat, visceral fat (including hepatic steatosis) reflects insulin resistance and predicts type 2 diabetes and cardiovascular disease. In humans, available evidence indicates that the ability to store triglycerides in the subcutaneous adipose tissue reflects enhanced insulin sensitivity. Prospective studies document an association between larger subcutaneous fat mass at baseline and reduced incidence of impaired glucose tolerance. Case-control studies reveal an association between genetic predisposition to insulin resistance and a lower amount of subcutaneous adipose tissue. Human peroxisome proliferator-activated receptorgamma (PPAR-γ) promotes subcutaneous adipocyte differentiation and subcutaneous fat deposition, improving insulin resistance and reducing visceral fat. Thiazolidinediones reproduce the effects of PPAR-γ activation and therefore increase the amount of subcutaneous fat while enhancing insulin sensitivity and reducing visceral fat. Partial or virtually complete lack of adipose tissue (lipodystrophy) is associated with insulin resistance and its clinical manifestations, including essential hypertension, hypertriglyceridemia, reduced HDL-c, type 2 diabetes, cardiovascular disease, and kidney disease. Patients with Prader Willi syndrome manifest severe subcutaneous obesity without insulin resistance. The impaired ability to accumulate fat in the subcutaneous adipose tissue may be due to deficient triglyceride synthesis, inadequate formation of lipid droplets, or defective adipocyte differentiation. Lean and obese humans develop insulin resistance when the capacity to store fat in the subcutaneous adipose tissue is exhausted and deposition of triglycerides is no longer attainable at that location. Existing adipocytes become large and reflect the presence of insulin resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Squamous odontogenic tumor (SOT) is a rare benign but locally infiltrative tumor often misdiagnosed as other entities, such as ameloblastoma and squamous cell carcinoma, due to overlapping morphological findings. We document here the clinicopathological and imaging findings of an aggressive intraosseous SOT in the posterior left region of the maxilla in a 25-year-old male patient. On intraoral examination, the tumor extended from the region of the left lateral incisor to the upper left premolar and was covered by reddish mucosa, with discrete areas of ulceration. Imaging exams revealed an osteolytic lesion causing thinning, erosion, and buccal and lingual cortical plate perforation associated with an impacted canine. Microscopically, the tumor showed a proliferation of islands of well-differentiated squamous epithelium in a variably collagenized background. The peripheral cells of the islands were flat or slightly cuboidal and did not exhibit nuclei with peripheral palisade and reverse polarization. The diagnosis of SOT was rendered. The patient underwent surgical resection and has been under clinical follow-up for approximately 12 months with no signs of recurrence. A careful morphological evaluation is essential to avoid misdiagnosis and ensure a satisfactory treatment approach., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The emergence and reemergence of mosquito-borne diseases in Brazil such as yellow fever, zika, chikungunya, and dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus across the country since its first detection in 2014 in Northeast Brazil. In this work, we carried out on-site training activities in genomic surveillance in partnership with the National Network of Public Health Laboratories that have led to the generation of 422 chikungunya virus genomes from 12 Brazilian states over the past two years (2021-2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersal dynamics of the chikungunya virus East-Central-South-African lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C > T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving the genetic diversity of the chikungunya virus in Brazil., (© 2023. The Author(s).)

The development of green synthesized polymeric nanoparticles with anticancer studies has been an emerging field in academia and the pharmaceutical and chemical industries. Vegetable oils are potential substitutes for petroleum derivatives, as they present a clean and environmentally friendly alternative and are available in abundance at relatively low prices. Biomass-derived chemicals can be converted into monomers with a unique structure, generating materials with new properties for the synthesis of sustainable monomers and polymers. The production of bio-based polymeric nanoparticles is a promising application of green chemistry for biomedical uses. There is an increasing demand for biocompatible and biodegradable materials for specific applications in the biomedical area, such as cancer therapy. This is encouraging scientists to work on research toward designing polymers with enhanced properties and clean processes, containing oncology active pharmaceutical ingredients (APIs). The nanoencapsulation of these APIs in bio-based polymeric nanoparticles can control the release of the substances, increase bioavailability, reduce problems of volatility and degradation, reduce side effects, and increase treatment efficiency. This review discusses the use of green chemistry for bio-based nanoparticle production and its application in anticancer medicine. The use of castor oil for the production of renewable monomers and polymers is proposed as an ideal candidate for such applications, as well as more suitable methods for the production of bio-based nanoparticles and some oncology APIs available for anticancer application.

Histological manifestations of diabetic kidney disease (DKD) include mesangiolysis, mesangial matrix expansion, mesangial cell proliferation, thickening of the glomerular basement membrane, podocyte loss, foot process effacement, and hyalinosis of the glomerular arterioles, interstitial fibrosis, and tubular atrophy. Glomerulomegaly is a typical finding. Histological features of DKD may occur in the absence of clinical manifestations, having been documented in patients with normal urinary albumin excretion and normal glomerular filtration rate. Furthermore, the histological picture progresses over time, while clinical data may remain normal. Conversely, histological lesions of DKD improve with metabolic normalization following effective pancreas transplantation. Insulin resistance has been associated with the clinical manifestations of DKD (nephromegaly, glomerular hyperfiltration, albuminuria, and kidney failure). Likewise, insulin resistance may underlie the histological manifestations of DKD. Morphological changes of DKD are absent in newly diagnosed type 1 diabetes patients (with no insulin resistance) but appear afterward when insulin resistance develops. In contrast, structural lesions of DKD are typically present before the clinical diagnosis of type 2 diabetes. Several heterogeneous conditions that share the occurrence of insulin resistance, such as aging, obesity, acromegaly, lipodystrophy, cystic fibrosis, insulin receptor dysfunction, and Alström syndrome, also share both clinical and structural manifestations of kidney disease, including glomerulomegaly and other features of DKD, focal segmental glomerulosclerosis, and C3 glomerulopathy, which might be ascribed to the reduction in the synthesis of factor H binding sites (such as heparan sulfate) that leads to uncontrolled complement activation. Alström syndrome patients show systemic interstitial fibrosis markedly similar to that present in diabetes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the glomeruli, mesangial cells produce mesangial matrix while podocytes wrap glomerular capillaries with cellular extensions named foot processes and tether the glomerular basement membrane (GBM). The turnover of the mature GBM and the ability of adult podocytes to repair injured GBM are unclear. The actin cytoskeleton is a major cytoplasmic component of podocyte foot processes and links the cell to the GBM. Predominant components of the normal glomerular extracellular matrix (ECM) include glycosaminoglycans, proteoglycans, laminins, fibronectin-1, and several types of collagen. In patients with diabetes, multiorgan composition of extracellular tissues is anomalous, including the kidney, so that the constitution and arrangement of glomerular ECM is profoundly altered. In patients with diabetic kidney disease (DKD), the global quantity of glomerular ECM is increased. The level of sulfated proteoglycans is reduced while hyaluronic acid is augmented, compared to control subjects. The concentration of mesangial fibronectin-1 varies depending on the stage of DKD. Mesangial type III collagen is abundant in patients with DKD, unlike normal kidneys. The amount of type V and type VI collagens is higher in DKD and increases with the progression of the disease. The GBM contains lower amount of type IV collagen in DKD compared to normal tissue. Further, genetic variants in the α3 chain of type IV collagen may modulate susceptibility to DKD and end-stage kidney disease. Human cellular models of glomerular cells, analyses of human glomerular proteome, and improved microscopy procedures have been developed to investigate the molecular composition and organization of the human glomerular ECM., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Abstract: An alteration in extracellular matrix (ECM) production by vascular smooth muscle cells is a crucial event in the pathogenesis of vascular diseases such as aging-related, atherosclerosis and allograft vasculopathy. The human target of rapamycin (TOR) is involved in the synthesis of ECM by vascular smooth muscle cells. TOR inhibitors reduce arterial stiffness, blood pressure, and left ventricle hypertrophy and decrease cardiovascular risk in kidney graft recipients and patients with coronary artery disease and heart allograft vasculopathy. Other drugs that modulate ECM production such as cilostazol and colchicine have also demonstrated a beneficial cardiovascular effect. Clinical studies have consistently shown that cilostazol confers cardiovascular protection in peripheral vascular disease, coronary artery disease, and cerebrovascular disease. In patients with type 2 diabetes, cilostazol prevents the progression of subclinical coronary atherosclerosis. Colchicine reduces arterial stiffness in patients with familial Mediterranean fever and patients with coronary artery disease. Pathophysiological mechanisms underlying the cardioprotective effect of these drugs may be related to interactions between the cytoskeleton, TOR signaling, and cyclic adenosine monophosphate (cAMP) synthesis that remain to be fully elucidated. Adult vascular smooth muscle cells exhibit a contractile phenotype and produce little ECM. Conditions that upregulate ECM synthesis induce a phenotypic switch toward a synthetic phenotype. TOR inhibition with rapamycin reduces ECM production by promoting the change to the contractile phenotype. Cilostazol increases the cytosolic level of cAMP, which in turn leads to a reduction in ECM synthesis. Colchicine is a microtubule-destabilizing agent that may enhance the synthesis of cAMP., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with diabetes are at a high risk for kidney disease and cardiovascular disease (CVD). Inadequate glycemic control or conventional cardiovascular risk factors do not fully explain these vascular complications. Insulin resistance has been established as a powerful and independent risk factor for both CVD and diabetic kidney disease (DKD). The source of dietary protein (animal versus vegetable) largely defines the degree of insulin sensitivity. Animal protein intake activates glucagon secretion and magnifies insulin resistance while vegetable food enhances insulin sensitivity. Reducing animal meat while augmenting vegetable protein has demonstrated definite advantages regarding insulin sensitivity., Aims and Methods: A comprehensive literature search was conducted on the PubMed database up to December 2021 on the differential effect of animal versus vegetable protein on DKD. Articles written in English concerning human subjects were included., Results: Animal protein is strongly associated with clinical features of DKD (glomerular hyperfiltration, albuminuria and kidney function decline) and CVD. Conversely, plant-sourced protein has a strong beneficial effect on both DKD and CVD. Plant-based diets have demonstrated to be nutritionally safe in subjects from the general population, patients with diabetes, and patients with kidney disease. Available evidence suggests that the dietary potassium load due to plant-sourced food does not usually induce hyperkalemia, although future research is required to establish the effect of meat (and subsequent insulin resistance) and vegetable food on kalemia., Conclusions: Nutritional advice to patients with diabetes should consider the strikingly different effect of animal versus vegetable protein on insulin resistance and its clinical consequences., Competing Interests: Declaration of competing interest The authors declare that there are not conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Aims: Human target of rapamycin (TOR) is a kinase that stimulates protein synthesis in the skeletal muscle in response to amino acids and physical activity., Methods: A comprehensive literature search was conducted on the PubMed database from its inception up to May 2021 to retrieve information on the effects of TOR and glucagon on muscle function. Articles written in English regarding human subjects were included., Results: l-leucine activates TOR to initiate protein synthesis in the skeletal muscle. Glucagon has a crucial role suppressing skeletal muscle protein synthesis by increasing l-leucine oxidation and the irreversible loss of this amino acid. Glucagon-induced l-leucine oxidation suppresses TOR and attenuates the ability of skeletal muscle to synthesize proteins. Conditions associated with increased glucagon secretion typically feature reduced ability to synthesize proteins in the skeletal muscle that may evolve into sarcopenia. Animal protein ingestion, unlike vegetable protein, stimulates glucagon secretion. High intake of animal protein increases l-leucine oxidation and promotes the use of amino acids as fuel. Sarcopenia and arterial stiffness characteristically occur together in conditions featuring insulin resistance, such as aging. Insulin resistance mediates the relationship between aging and sarcopenia and arterial stiffness. The loss of skeletal muscle fibers that characterizes sarcopenia is followed by collagen and lipid accumulation. Likewise, insulin resistance is associated with arterial stiffness and intima-media thickening due to adaptive accretion of collagen and lipids in the arterial wall., Conclusions: Human TOR participates in the pathogenesis of sarcopenia and arterial stiffness, although its effects remain to be fully elucidated., Competing Interests: Declaration of competing interest The authors declare that there are not conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Melanoma is an aggressive malignant tumor, rarely observed in the oral cavity. The aim of this study was to describe the clinicopathologic features of a series of oral melanomas., Material and Methods: A retrospective descriptive study was performed. A total of 15,482 biopsy records from two oral and maxillofacial pathology services in Brazil were analyzed. All cases of oral melanomas were reviewed, and clinical, demographic, histopathological data, treatment, and follow-up status were collected. In addition, immunohistochemistry stains (pan-cytokeratin AE1/AE3, vimentin, α-SMA, CD45, S-100 protein, HMB-45, Melan A, and Ki-67) were performed., Results: The series comprised of 5 males (71.4%) and 2 females (28.6%), with a mean age of 58.0 ± 9.2 years (range: 45-69 years) and a 2.5:1 male-to-female ratio. The gingiva (n = 3, 42.8%) and hard palate (n = 2, 28.6%) were the most common affected sites, presenting clinically as ulcerated swellings with a brown to black color. Cervical lymph node metastasis was detected in three patients during the first examination. Microscopically, 6 cases (85.7%) were melanotic, and one (14.3%) was amelanotic. Most cases (n = 4, 57.1%) presented a predominance of epithelioid cells. S-100 and HMB-45 were positive in all cases (n = 7, 100.0%). In contrast, only 4 cases (57.1%) were positive for Melan-A. The proliferative index with Ki-67 was high, with labeling index ranging from 70.0% to more than 90% of positive cells. Five patients died from complications of the tumors after a mean follow-up period of 7.8 months., Conclusions: Melanoma is an aggressive malignant tumor that rarely occurs in the oral cavity. It occurs mainly in adult and elderly patients and often is diagnosed in advanced stages. The current findings were similar to previous studies and reflected the characteristics of the services from where lesions were retrieved.

Patients with kidney disease have a strikingly high cardiovascular risk in the absence of conventional cardiovascular risk factors, including smoking or elevation of cholesterol associated with low-density lipoprotein. Kidney failure remains independently associated with increased cardiovascular risk in patients with diabetes, underlining the specific adverse influence of kidney disease on cardiovascular risk. Vascular injury develops in asymptomatic patients with kidney failure early in the course of the disease. Defective arterial vasodilation, increased arterial stiffness, increased intima-media thickness, and vascular calcification develop in patients with kidney disease long before clinical evidence of cardiovascular events. Even mildly reduced kidney function is associated with a subclinical vascular disease, which is a predictor of worse cardiovascular outcome in patients with kidney failure, similar to the general population and patients with diabetes. Insulin resistance is a typical feature of kidney disease that occurs during the entire span of the disorder, from mild dysfunction to the dialysis phase. Insulin resistance (or its clinical manifestations, the metabolic syndrome or its components) is independently associated with a subclinical vascular injury in patients with kidney disease. Additionally, the risk of developing incident kidney disease and the rapid decline in kidney function is higher in patients with insulin resistance. Animal protein consumption increases dietary acid load and intensifies insulin resistance. Consistently, meat intake promotes diabetes, cardiovascular disease, and kidney failure, while the consumption of plant-based food is protective against the development of the vascular disease. Insulin resistance is a robust cardiovascular risk factor in the general population, patients with diabetes, and patients with kidney disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Single nucleotide polymorphisms (SNPs) in immune-related genes have been shown to play a role in driving the development of the severe phenotypes of dengue virus (DENV) infection. We assessed the association between IFNL3 gene SNP (rs12979860) and dengue clinical outcomes in children. Patients with dengue-related symptoms (aged 1-15 years) admitted at a public hospital in Northeast Brazil were invited to participate. The association between rs12979860 polymorphism and dengue classification and clinical signs and symptoms were analysed. A total of 206 DENV-infected children were included: 53.4% of the infections were classified as severe dengue. The T allele carriers had higher risk of developing severe dengue when compared to CC genotype carriers (OR: 1.81; 95% CI: 0.98-3.32 p = .054). The T allele carriers also showed longer fever episodes when compared to patients with the CC genotype (OR: 1.90; 95%CI: 1.07-3.38; p = .027). On the other hand, the ones carrying the CT/TT genotype had 70% lower chance of developing thrombocytopenia when compared to those with the CC genotype (OR: 0.30; 95%CI: 0.08-0.88; p = .042). Our findings demonstrated that the T allele carriers of the IFNL3 gene had higher risk of developing severe dengue, suggesting a link between IFN-λ expression and DENV immunopathogenesis., (© 2020 John Wiley & Sons Ltd.)

The curve that describes the relationship between glomerular filtration rate (GFR) and cardiovascular risk is U-shaped, indicating that both reduced GFR (kidney failure) and elevated GFR (glomerular hyperfiltration) are equivalent cardiovascular risk factors. The elevated cardiovascular risk associated with abnormal GFR is not explained by standard cardiovascular risk factors. The relationship between GFR and all-cause mortality follows a similar pattern, so that altered GFR (either low or high) increases the risk for overall mortality. Glomerular hyperfiltration is an adaptive process that arises under conditions that demand improved kidney excretory capacity, such as animal protein ingestion and kidney failure. Unlike vegetable protein, animal protein consumption increases dietary acid load and requires an elevation of the GFR to restore acid-base balance. The loss of functioning nephrons in diseased kidneys requires a compensatory increase of the GFR in the nephrons that remain working to enhance whole-kidney GFR. A major factor that raises GFR is the pancreatic hormone glucagon. Glucagon infusion and endogenous glucagon release increase GFR in healthy subjects and patients with kidney failure. In addition to its kidney hemodynamic effect, glucagon causes insulin resistance. Like hyperglucagonemia, insulin resistance develops across the entire spectrum of abnormal GFR, from glomerular hyperfiltration to advanced kidney disease. Insulin resistance is associated with subclinical vascular injury in the general population and patients with diabetes and kidney failure, being a strong cardiovascular risk factor in these population groups. Animal protein consumption activates glucagon secretion and promotes insulin resistance, having a detrimental effect on cardiovascular disease and renal outcomes., Competing Interests: The authors declare that they have no conflict of interest., (© 2020 Adeva-Andany et al. Published by IMR press.)

Diet composition has a marked impact on the risk of developing type 2 diabetes and cardiovascular disease. Prospective studies show that dietary patterns with elevated amount of animal products and low quantity of vegetable food items raise the risk of these diseases. In healthy subjects, animal protein intake intensifies insulin resistance whereas plant-based foods enhance insulin sensitivity. Similar effects have been documented in patients with diabetes. Accordingly, pre-pregnancy intake of meat (processed and unprocessed) has been strongly associated with a higher risk of gestational diabetes whereas greater pre-pregnancy vegetable protein consumption is associated with a lower risk of gestational diabetes. Population groups that modify their traditional dietary habit increasing the amount of animal products while reducing plant-based foods experience a remarkable rise in the frequency of type 2 diabetes. The association of animal protein intake with insulin resistance is independent of body mass index. In obese individuals that consume high animal protein diets, insulin sensitivity does not improve following weight loss. Diets aimed to lose weight that encourage restriction of carbohydrates and elevated consumption of animal protein intensify insulin resistance increasing the risk of developing type 2 diabetes and cardiovascular disease. The effect of dietary components on insulin sensitivity may contribute to explain the striking impact of eating habits on the risk of type 2 diabetes and cardiovascular disease. Insulin resistance predisposes to type 2 diabetes in healthy subjects and deteriorates metabolic control in patients with diabetes. In nondiabetic and diabetic individuals, insulin resistance is a major cardiovascular risk factor., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Indolent systemic mastocytosis (ISM) patients have a normal life expectancy, except in the 5% to 10% of cases that progress to more advanced SM (advSM), which has a significantly poorer outcome. Mutations in genes other than KIT frequently found in myeloid neoplasms have been associated with a poorer outcome among advSM, whereas limited information exists about their frequency and prognostic impact in ISM. We investigated the frequency and prognostic impact of variants in 18 genes, found to be altered in advSM, in 322 ISM patients (median follow-up, 5.7 years) divided into discovery (n = 200) and validation (n = 122) cohorts. Overall, 71 genetic variants were detected in 55 of 322 (17%) patients. Mutated ISM cases, particularly those carrying ASXL1 , RUNX1 , and/or DNMT3A ( A / R / D ) pathogenic variant allele frequencies (VAFs) ≥ 30%, exhibited significantly shortened ( P < .001) progression-free survival (PFS) and overall survival (OS). Multivariate analysis showed that serum β2-microglobulin (sβ2M) levels > 2.5 µg/mL (hazard ratio [HR], 9.8; P = .001), together with a KIT D816V VAF ≥ 1% in bone marrow (BM) (HR, 10.1; P = .02) and pathogenic variants of A / R / D VAFs ≥ 30% (HR, 4.2; P = .02), were the best combination of independent predictors for PFS. In turn, A / R / D gene pathogenic VAF ≥ 30% was the only independent predictor for OS (HR, 51.8; P < .001). Based on these variables, 2 scoring systems were constructed for risk stratification of ISM at diagnosis with significantly different 10-year PFS (100%, 91%, 0% for scores of 0, 1, ≥2, respectively) and OS (100% and 50% for scores of 0 and 1) rates., (© 2019 by The American Society of Hematology.)

Mitochondrial β-oxidation of fatty acids generates acetyl-coA, NADH and FADH 2 . Acyl-coA synthetases catalyze the binding of fatty acids to coenzyme A to form fatty acyl-coA thioesters, the first step in the intracellular metabolism of fatty acids. l-carnitine system facilitates the transport of fatty acyl-coA esters across the mitochondrial membrane. Carnitine palmitoyltransferase-1 transfers acyl groups from coenzyme A to l-carnitine, forming acyl-carnitine esters at the outer mitochondrial membrane. Carnitine acyl-carnitine translocase exchanges acyl-carnitine esters that enter the mitochondria, by free l-carnitine. Carnitine palmitoyltransferase-2 converts acyl-carnitine esters back to acyl-coA esters at the inner mitochondrial membrane. The β-oxidation pathway of fatty acyl-coA esters includes four reactions. Fatty acyl-coA dehydrogenases catalyze the introduction of a double bond at the C2 position, producing 2-enoyl-coA esters and reducing equivalents that are transferred to the respiratory chain via electron transferring flavoprotein. Enoyl-coA hydratase catalyzes the hydration of the double bond to generate a 3-l-hydroxyacyl-coA derivative. 3-l-hydroxyacyl-coA dehydrogenase catalyzes the formation of a 3-ketoacyl-coA intermediate. Finally, 3-ketoacyl-coA thiolase catalyzes the cleavage of the chain, generating acetyl-coA and a fatty acyl-coA ester two carbons shorter. Mitochondrial trifunctional protein catalyzes the three last steps in the β-oxidation of long-chain and medium-chain fatty acyl-coA esters while individual enzymes catalyze the β-oxidation of short-chain fatty acyl-coA esters. Clinical phenotype of fatty acid oxidation disorders usually includes hypoketotic hypoglycemia triggered by fasting or infections, skeletal muscle weakness, cardiomyopathy, hepatopathy, and neurological manifestations. Accumulation of non-oxidized fatty acids promotes their conjugation with glycine and l-carnitine and alternate ways of oxidation, such as ω-oxidation., (Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Despite recent therapeutic advances, systemic mastocytosis (SM) remains an incurable disease due to limited complete remission (CR) rates even after novel therapies. To date, no study has evaluated the expression on SM bone marrow mast cells (BMMC) of large panel of cell surface suitable for antibody-targeted therapy. In this study, we analyzed the expression profile of six cell-surface proteins for which antibody-based therapies are available, on BMMC from 166 SM patients vs. 40 controls. Overall, variable patterns of expression for the markers evaluated were observed among SM BMMC. Thus, CD22, CD30, and CD123, while expressed on BMMC from patients within every subtype of SM, showed highly variable patterns with a significant fraction of negative cases among advanced SM (aggressive SM (ASM), ASM with an associated clonal non-MC lineage disease (ASM-AHN) and MC leukemia (MCL)), 36%, 46%, and 39%, respectively. In turn, CD25 and FcεRI were found to be expressed in most cases (89% and 92%) in virtually all BMMC (median: 92% and 95%) from both indolent and advanced SM, but with lower/absent levels in a significant fraction of MC leukemia (MCL) and both in MCL and well-differentiated SM (WDSM) patients, respectively. In contrast, CD33 was the only marker expressed on all BMMC from every SM patient. Thus, CD33 emerges as the best potentially targetable cell-surface membrane marker in SM, particularly in advanced SM.

Oral and maxillofacial metastatic tumors are uncommon, with the breast, prostate, lung, and kidney representing the most common primary sites. Less than 1% of all breast cancers occur in male patients, and to date, only 8 cases of metastatic breast adenocarcinoma to the oral and maxillofacial region in a male patient have been reported in the literature. An 88-year-old male with previous history of a successfully treated primary breast adenocarcinoma 12 years earlier was referred for evaluation of an oral swelling lasting 6 months. Intraoral examination revealed a 2-cm reddish, pedunculated nodule with a smooth surface located in the left retromolar region. Imaging revealed maxillary sinus involvement. The patient underwent incisional biopsy, and microscopic evaluation revealed invasive tumor islands compounded by malignant epithelial cells, sometimes exhibiting ductal arrangement, which were positive for the estrogen receptor and gross cystic disease fluid protein 15. The final diagnosis was metastatic breast adenocarcinoma. Breast metastases are exceedingly rare in the oral and maxillofacial region of male patients; however, clinicians should consider breast metastasis when evaluating reddish oral nodules in older patients, including men, especially those with a history of malignancy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Diabetes is a common metabolic disorder that involves glucose, amino acids, and fatty acids. Either insulin deficiency or insulin resistance may cause diabetes. Insulin deficiency causes type 1 diabetes and diabetes associated with total pancreatectomy. Glucagon produces insulin resistance. Glucagon-induced insulin resistance promotes type 2 diabetes and diabetes associated with glucagonoma. Further, glucagon-induced insulin resistance aggravates the metabolic consequences of the insulin-deficient state. A major metabolic effect of insulin is the accumulation of glucose as glycogen in the liver. Glucagon opposes hepatic insulin action and enhances the rate of gluconeogenesis, increasing hepatic glucose output. In order to support gluconeogenesis, glucagon promotes skeletal muscle wasting to supply amino acids as gluconeogenic precursors. Glucagon promotes hepatic fatty acid oxidation to supply energy required to sustain gluconeogenesis. Hepatic fatty acid oxidation generates β-hydroxybutyrate and acetoacetate (ketogenesis). Prospective studies reveal that elevated glucagon secretion at baseline occurs in healthy subjects who develop impaired glucose tolerance at follow-up compared with subjects who maintain normal glucose tolerance, suggesting a relationship between elevated glucagon secretion and development of impaired glucose tolerance. Prospective studies have identified animal protein consumption as an independent risk factor for type 2 diabetes and cardiovascular disease. Animal protein intake activates glucagon secretion inducing sustained elevations in plasma glucagon. Glucagon is a major hormone that causes insulin resistance. Insulin resistance is an established cardiovascular risk factor additionally to its pathogenic role in diabetes. Glucagon may be a potential link between animal protein intake and the risk of developing type 2 diabetes and cardiovascular disease.

Systemic mastocytosis (SM) is a highly heterogeneous disease with indolent and aggressive forms, with the mechanisms leading to malignant transformation still remaining to be elucidated. Here, we investigated the presence and frequency of genetic variants in 34 SM patients with multilineal KIT D816V mutations. Initial screening was performed by targeted sequencing of 410 genes in DNA extracted from purified bone marrow cells and hair from 12 patients with nonadvanced SM and 8 patients with advanced SM, followed by whole-genome sequencing (WGS) in 4 cases. Somatic mutations were further investigated in another 14 patients with advanced SM. Despite the fact that no common mutation other than KIT D816V was found in WGS analyses, targeted next-generation sequencing identified 67 nonsynonymous genetic variants involving 39 genes. Half of the mutations were somatic (mostly multilineal), whereas the other half were germline variants. The presence of ≥1 multilineal somatic mutation involving genes other than KIT D816V, ≥3 germline variants, and ≥1 multilineal mutation in the SRSF2 , ASXL1 , RUNX1 , and/or EZH2 genes ( S/A/R/E genes), in addition to skin lesions, splenomegaly, thrombocytopenia, low hemoglobin levels, and increased alkaline phosphatase and β2-microglobulin serum levels, were associated with a poorer patient outcome. However, the presence of ≥1 multilineal mutation, particularly involving S/A/R/E genes, was the only independent predictor for progression-free survival and overall survival in our cohort., (© 2018 by The American Society of Hematology.)

Background: Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation-associated compartments of bone marrow (BM) and peripheral blood (PB) CD34 + hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation., Methods: The distribution of different maturation-associated subsets of BM and PB CD34 + HPC from 64 newly diagnosed (KIT-mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS-purified PB cell compartments were also investigated for the KIT mutation., Results: ISM patients showed higher percentages of both BM and PB MC-committed CD34 + HPC vs controls, particularly among ISM cases with MC-restricted KIT mutation (ISM MC ); this was associated with progressive blockade of maturation of CD34 + HPC to the neutrophil lineage from ISM MC to multilineage KIT-mutated cases (ISM ML ). Regarding the frequency of KIT-mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT-mutated PB CD34 + HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs- MC and ISMs+ MC to ISM ML patients., Conclusion: The presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34 + HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34 + HPC potentially contributing to early dissemination of the disease., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

A 2(3) full factorial design was used to identify the main effects and interactions of pH, collagen concentration and temperature on the degree of collagen hydrolysis (DH) by collagenase from Penicillium aurantiogriseum URM 4622. Increases in both pH and collagen concentration improved DH, and a positive interaction effect was observed for these variables. On the other hand, temperature had a negative main effect on DH. The maximum value of DH (4.65 μg/mL) was achieved at 7.5 mg/mL collagen concentration, pH 8.0 and 25 °C. The peptide profile showed several peptides with molecular weights lower than 2 kDa and exhibited antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. An antioxidant activity of 84.7 ± 0.24 % towards the radical ABTS• + was obtained with 50 mg/mL hydrolysates. This study demonstrated that collagen hydrolysed by P. aurantiogriseum URM 4622 collagenase possesses interesting antibacterial and antioxidant activities.

Spinturnicid mites are ectoparasites that infest the wings of bats, and species of the genus Periglischrus Kolenati, 1857 are associated exclusively with bats of the family Phyllostomidae. We tested the hypothesis that a long-term evolutionary association led P. iheringi to choose very specific wing locations to infest the great fruit-eating bats, Artibeus lituratus. Seven anatomical wing regions and the uropatagium from 140 bats were analyzed and a total of 78 parasites were collected. Periglischrus iheringi had a significant preference for the plagiopatagium and dactylopatgium major wing regions (i.e., large, proximal regions) and infestation was directly correlated to area (r=0.9744). However, other factors may also influence mite choice, such as higher and more stable temperature and humidity, vascularization and lower risk of displacement.

We describe the isolation of a novel flavivirus, isolated from a pool of mosquitoes identified as Culex (Culex) chidesteri collected in 2010 in the Pantanal region of west-central Brazil. The virus is herein designated Nhumirim virus (NHUV) after the name of the ranch from which the mosquito pool was collected. Flavivirus RNA was detected by real-time RT-PCR of homogenized mosquitoes and from the corresponding C6/36 culture supernatant. Based on full-genome sequencing, the virus isolate was genetically distinct from but most closely related to Barkedji virus (BJV), a newly described flavivirus from Senegal. Phylogenetic analysis demonstrated that NHUV grouped with mosquito-borne flaviviruses forming a clade with BJV. This clade may be genetically intermediate between the Culex-borne flaviviruses amplified by birds and the insect-only flaviviruses.