IL-10 and IL-1ß Serum Levels, Genetic Variants, and Metabolic Syndrome: Insights into Older Adults' Clinical Characteristics.

Populational aging is marked by chronic noncommunicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1ß are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1ß serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarly, IL-1ß levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

The 3'UTR VNTR SLC6A3 Genetic Variant and Major Depressive Disorder: A Systematic Review.

Major Depressive Disorder (MDD) is a disabling and particularly persistent mental disorder that is considered to be a priority public health problem. The active human dopamine transporter (DAT), which is encoded by the SLC6A3 gene, regulates the dopamine concentration in the synaptic cleft. In this sense, this neurotransmitter is primordial in modulating human emotions. This systematic review aims to verify the SLC6A3 (DAT1) 3'UTR VNTR (rs28363170) gene variant's SS (9R/9R) genotype and S (9R) allele frequency fluctuation and its influence on the modulation of pharmacotherapy in MDD. For this purpose, we searched different databases, and after applying the eligibility criteria, six articles were selected. Studies have shown an association between the SS (9R/9R) genotypic and S (9R) allelic presence with the risk of developing MDD, in addition to influencing the decrease in response to antidepressant therapy. However, despite the findings, disagreements were observed between other studies. For this reason, further studies with the SLC6A3 3'UTR VNTR (rs28363170) variant in different populations are necessary to understand this polymorphism's role in the onset of this disease.

MAOA uVNTR Polymorphism Influence on Older Adults Diagnosed with Diabetes Mellitus/Systemic Arterial Hypertension.

Background: Monoamine oxidase (MAO) is involved in several biological processes associated with well-being and mental health, and alterations in its function might directly impact various mental disorders. Some mental disorders concomitantly occur in individuals with clinical characteristics, such as substance abuse and diabetes. Objective: To analyze the functional MAOA uVNTR polymorphism genotype frequency in an older adult population with diabetes mellitus/arterial hypertension and associate this frequency with clinical characteristics impacting daily life. Methodology. Older adults diagnosed with diabetes mellitus, systemic arterial hypertension, or both (DM/SAH) were selected and had their MAOA gene genotyped for uVNTR polymorphism. The revised Beck Depression Inventory (BDI) and a questionnaire were also applied to determine their mental health and clinical characteristics. Results: The allelic variants detected among the participants were the 2R, 3R, 4R, and 3R/4R heterozygous genotypes. Genotypes solely containing the 3R allele had patients who marked yes for smoking and alcoholism, and only those with the 3R genotypes (female 3R/3R homozygote or male 3R∗ hemizygote) were significant. Although not statistically significant, only 3R and 3R/4R genotypes presented cases of severe depression per the revised BDI interpretations. Conclusion: The MAOA uVNTR polymorphism's low-activity 3R allele presence in an older adult population diagnosed with DM/SAH may represent a risk for developing substance use (alcohol and smoking) dependence.

Prevalence and Antimicrobial Resistance of Salmonella spp. Isolated From Chilled Chicken Meat Commercialized at Retail in Federal District, Brazil.

Salmonella represents one of the most common foodborne pathogens, frequently associated with the contamination of poultry products, constituting a prominent worldwide public health concern. This study determined the prevalence and antimicrobial resistance of Salmonella spp. in chilled chicken meat (115 samples) commercialized at retail in the Federal District, Brazil. Microbiological tests were performed to screen for Salmonella spp. in the chicken meat samples, and the isolated strains were confirmed by the invA gene presence (PCR technique). The strains were evaluated for antimicrobial susceptibility by the disk diffusion technique (Kirby-Bauer method) and tested for the presence of the sul2, blaCTX, and tetB antimicrobial resistance genes. The Salmonella spp. prevalence in chilled chicken meat sold at retail in the Federal District, Brazil, was 46.1% (53 of 115 chicken meat samples analyzed had invA gene-positive strains). Seventy-eight strains of Salmonella spp. isolated from the 53 contaminated samples showed higher resistance to amoxicillin/clavulanic acid (83.3%), followed by sulfonamide (64.1%) and tetracycline (46.2%); 53.8% of the isolates were multidrug-resistant (MDR). The sul2 gene that confers resistance to sulfonamide was found in 53 strains (68.0%), the blaCTX gene that confers resistance to beta-lactams was identified in 39 strains (50.0%), and the tetB gene that confers resistance to tetracycline was identified in 29 strains (37.2%). The high percentage of Salmonella contamination in chicken meat can pose a risk to consumers' health due to the possibility of causing salmonellosis. In addition, many isolates were MDR and carried antimicrobial resistance genes. Public agencies can use these results to develop effective public health policies and strategies to ensure the safety of these food products.

MAOA uVNTR Genetic Variant and Major Depressive Disorder: A Systematic Review.

Major Depressive Disorder (MDD) is a highly prevalent multifactorial psychopathology affected by neurotransmitter levels. Monoamine Oxidase A (MAOA) influences several neural pathways by modulating these levels. This systematic review (per PRISMA protocol and PECOS strategy) endeavors to understand the MAOA uVNTR polymorphism influence on MDD and evaluate its 3R/3R and 3R* genotypic frequencies fluctuation in MDD patients from different populations. We searched the Web of Science, PubMed, Virtual Health Library, and EMBASE databases for eligible original articles that brought data on genotypic frequencies related to the MAOA uVNTR variant in patients with MDD. We excluded studies with incomplete data (including statistical data), reviews, meta-analyses, and abstracts. Initially, we found 43 articles. After removing duplicates and applying the inclusion/exclusion criteria, seven articles remained. The population samples studied were predominantly Asians, with high 3R and 4R allele frequencies. Notably, we observed higher 3R/3R (female) and 3R* (male) genotype frequencies in the healthy control groups and higher 4R/4R (female) and 4R* (male) genotype frequencies in the MDD groups in the majority of different populations. Despite some similarities in the articles analyzed, there is still no consensus on the MAOA uVNTR variant's role in MDD pathogenesis.

Altered Visceral Adipose Tissue Predictors and Women's Health: A Unicenter Study.

(1) Background: The excess visceral adipose tissue (VAT) accumulation in women may reflect an early or advanced state of a metabolic disorder and a higher risk of cardiovascular disease than other types of obesity. This study aimed to determine the predictor variables (demographic information, anthropometric data, and blood biomarkers) for changes in VAT in adult women. (2) Methods: This cross-sectional study was conducted with women aged 18-59 years attending nutritional consultation at the Centro Universitário de Brasília (CEUB)'s nutrition school clinic, Brazil. All participants' medical records were reviewed throughout the study and data of interest were collected. Various anthropometric measurements and biochemical exams were performed and analyzed in a univariate logistic regression model to identify the possible risk factors predictors for the presence of altered VAT. (3) Results: Our logistic regression model considered body mass index (BMI) greater than 25 kg/m2, lipid accumulation product (LAP), and waist-hip ratio (WHR) as predictors of altered VAT. (4) Conclusion: LAP has a robust predictive capacity for changes in visceral fat in adult women, followed by WHR and BMI, making these variables effective in assessing the risk for changes in visceral fat and their inclusion essential in the individual and collective clinical practice.

Dispensing of psychotropic drugs in the Brazilian capital city before and during the COVID-19 pandemic (2018-2020).

Objective: Evaluate the data on the psychotropic drugs dispensed by private community pharmacies before and during the SARS-CoV-2 pandemic. Methods: This cross-sectional study compared the quarterly and annual consumption of psychotropic drugs per Defined Daily Dose per 1000 inhabitants-day (DHD). Interrupted time series were also constructed to expose changes in the consumption pattern in the periods before and after March 2020. Results: Among the 20 most consumed psychoactive drugs, 12 were antidepressants, for example, escitalopram (DHD 7.996 and 10.626; p < 0.001), and sertraline (DHD 6.321 and 8.484; p < 0.001), in addition to the hypnotic zolpidem (DHD 6.202 and 8.526; p < 0.001). The time series reveals (R 2 value) a variation in drug dispensing, in DHD values, during the pandemic. Conclusion: Despite the higher variance, a significant increase is clearly seen in the consumption trends of psychoactive drugs, particularly antidepressants, consistent with the pandemic's influence on the general population's mental health.

BDNF Genetic Variant and Its Genotypic Fluctuation in Major Depressive Disorder.

Major depressive disorder (MDD) still has an unknown etiology and mechanisms. Many studies have been conducted seeking to associate and understand the connection of different genetic variants to this disease. Researchers have extensively studied the brain-derived neurotrophic factor (BDNF) Val66Met genetic variant in MDD; yet, their findings remain inconsistent. This systematic review sought to verify the GG (Val/Val) genotype frequency fluctuation in different populations with MDD. For this, we searched in different databases and, after applying the eligibility criteria, selected 17 articles. Most studies demonstrate the higher frequency of the ancestral (wild) GG (Val/Val) genotype, although associations of the polymorphic A (Met) allele, changes in BDNF protein serum levels, or both were also found in MDD, whether related to the disease's development or other factors. Nevertheless, despite these findings, disagreements between several studies are seen. For this reason, further BDNF Val66Met genetic variant studies should not only bridge the gap in the knowledge of this polymorphism's role in MDD's different facets but also analyze the genotypic and phenotypic heterogeneity in different populations to help provide a better quality of life for patients.

Presence of Tetracycline and Sulfonamide Resistance Genes in Salmonella spp.: Literature Review.

Tetracyclines and sulfonamides are broad-spectrum antibacterial agents which have been used to treat bacterial infections for over half a century. The widespread use of tetracyclines and sulfonamides led to the emergence of resistance in a diverse group of bacteria. This resistance can be studied by searching for resistance genes present in the bacteria responsible for different resistance mechanisms. Salmonella is one of the leading bacteria causing foodborne diseases worldwide, and its resistance to tetracyclines and sulfonamides has been widely reported. The literature review searched the Virtual Health Library for articles with specific data in the studied samples: the resistance genes found, the primers used in PCR, and the thermocycler conditions. The results revealed that Salmonella presented high rates of resistance to tetracycline and sulfonamide, and the most frequent samples used to isolate Salmonella were poultry and pork. The tetracycline resistance genes most frequently detected from Salmonella spp. were tetA followed by tetB. The gene sul1 followed by sul2 were the most frequently sulfonamide resistance genes present in Salmonella. These genes are associated with plasmids, transposons, or both, and are often conjugative, highlighting the transference potential of these genes to other bacteria, environments, animals, and humans.

Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better.

Most people infected with the fungus Paracoccidioides spp. do not get sick, but approximately 5% develop paracoccidioidomycosis. Understanding how host immunity determinants influence disease development could lead to novel preventative or therapeutic strategies; hence, we used two mouse strains that are resistant (A/J) or susceptible (B10.A) to P. brasiliensis to study how dendritic cells (DCs) respond to the infection. RNA sequencing analysis showed that the susceptible strain DCs remodeled their transcriptomes much more intensely than those from the resistant strain, agreeing with a previous model of more intense innate immunity response in the susceptible strain. Contrastingly, these cells also repress genes/processes involved in antigen processing and presentation, such as lysosomal activity and autophagy. After the interaction with P. brasiliensis, both DCs and macrophages from the susceptible mouse reduced the autophagy marker LC3-II recruitment to the fungal phagosome compared to the resistant strain cells, confirming this pathway's repression. These results suggest that impairment in antigen processing and presentation processes might be partially responsible for the inefficient activation of the adaptive immune response in this model.

Association of Vitamin D with the TaqI Polymorphism of the VDR Gene in Older Women Attending the Basic Health Unit of the Federal District, DF (Brazil).

Aging is accompanied by various functional modifications determined by their environment, lifestyle, nutrition, and genetics. Based on these factors, it is essential to verify the vitamin deficiency in the elderly population. Hypovitaminosis D is commonly present in human aging, increasing the chances of developing noncommunicable chronic diseases. The VDR gene TaqI polymorphism may modify the vitamin D metabolic pathway by altering the interaction between the vitamin D receptor and the active circulating vitamin D. Therefore, this study aimed to investigate the association between serum vitamin D and biochemical and genetic factors, considering the TaqI polymorphism of the VDR gene, in an elderly population of the Federal District. The study was a descriptive, case-control, quantitative, and cross-sectional type and was conducted in two basic health units in the administrative region of Ceilândia, Federal District, DF, Brazil, with women aged 60 years or older. Anthropometric, biochemical, and genetic parameters (VDR TaqI polymorphism) were evaluated. The adopted significance level was 5%, and statistical analyses were performed using the SPSS version 20.0 program. The study consisted of 128 participants. The most prevalent age was from 60 to 65 years (N = 53; 41.4%). 66 elderly (51.6%) were part of the case group (hypovitaminosis D), while 62 were in the control group. In the case group, 30.2% had grade I obesity, 77.3% were hypertensive, and 51.5% were diabetic. The TT genotype was present in 47% of the case group and 54.8% in the control group (p=0.667). There was no association between serum vitamin D levels and the VDR gene variant TaqI polymorphism in an elderly Brazilian population.

Mechanisms of action of antimicrobial peptides ToAP2 and NDBP-5.7 against Candida albicans planktonic and biofilm cells.

Candida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis. Fungal infections treatment faces three major challenges: the limited number of therapeutic options, the toxicity of the available drugs, and the rise of antifungal resistance. In this study, we demonstrate the antifungal activity and mechanism of action of peptides ToAP2 and NDBP-5.7 against planktonic cells and biofilms of C. albicans. Both peptides were active against C. albicans cells; however, ToAP2 was more active and produced more pronounced effects on fungal cells. Both peptides affected C. albicans membrane permeability and produced changes in fungal cell morphology, such as deformations in the cell wall and disruption of ultracellular organization. Both peptides showed synergism with amphotericin B, while ToAP2 also presents a synergic effect with fluconazole. Besides, ToAP2 (6.25 µM.) was able to inhibit filamentation after 24 h of treatment and was active against both the early phase and mature biofilms of C. albicans. Finally, ToAP2 was protective in a Galleria mellonella model of infection. Altogether these results point to the therapeutic potential of ToAP2 and other antimicrobial peptides in the development of new therapies for C. albicans infections.

Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds.

Fungal infections have become an important medical condition in the last decades, but the number of available antifungal drugs is limited. In this scenario, the search for new antifungal drugs is necessary. The protocol reported here details a method to screen peptides for their antifungal properties. It is based on the broth microdilution susceptibility test from the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines with modifications to suit the research of antimicrobial peptides as potential new antifungals. This protocol describes a functional assay to evaluate the activity of antifungal compounds and may be easily modified to suit any particular class of molecules under investigation. Since the assays are performed in 96-well plates using small volumes, a large-scale screening can be completed in a short amount of time, especially if carried out in an automation setting. This procedure illustrates how a standardized and adjustable clinical protocol can help the bench-work pursuit of new molecules to improve the therapy of fungal diseases.

The Role of the NIS (SLC5A5) Gene in Papillary Thyroid Cancer: A Systematic Review.

Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Genetic and epigenetic alterations play a decisive role in the onset of several human neoplasms. Mutations and polymorphisms are two frequent genetic alterations. Located on chromosome 19 (19p13.11), the NIS SLC5A5 (solute carrier family 5 member 5) gene encodes a highly specialized and efficient 80-90 kDa transmembrane glycoprotein that mediates active transport of iodide from the bloodstream into the follicular cells. Given the highly significant role of NIS in the physiology and the cancer pathogenesis process, this paper's objective is to provide a comprehensive assessment of the associations between NIS gene and protein with papillary thyroid cancer.

The Effects of Paracoccidioides brasiliensis Infection on GM-CSF- and M-CSF-Induced Mouse Bone Marrow-Derived Macrophage from Resistant and Susceptible Mice Strains.

Considering the importance of macrophages as the first line of defense against fungal infection and the different roles played by the two M1- and M2-like polarized macrophages, we decided to evaluate the effects of Paracoccidioides brasiliensis infection on GM-CSF- and M-CSF-induced bone marrow-derived macrophages (BMM) from the A/J and B10.A mouse strains, an established model of resistance/susceptibility to PCM, respectively. Upon differentiation, the generated GM- or M-BMMs were characterized by morphological analyses, gene expression profiles, and cytokines production. Our main results demonstrate that GM-BMMs derived from A/J and B.10 produced high levels of pro- and anti-inflammatory cytokines that may contribute to generate an unbalanced early immune response. In accordance with the literature, the B10.A susceptible mice lineage has an innate tendency to polarize into M1-like phenotype, whereas the opposite phenotype occurs in A/J resistance mice. In this context, our data support that susceptibility and resistance are strongly correlated with M1 and M2 polarization, respectively.

Antimicrobial effect of farnesol, a Candida albicans quorum sensing molecule, on Paracoccidioides brasiliensis growth and morphogenesis.

BACKGROUND: Farnesol is a sesquiterpene alcohol produced by many organisms, and also found in several essential oils. Its role as a quorum sensing molecule and as a virulence factor of Candida albicans has been well described. Studies revealed that farnesol affect the growth of a number of bacteria and fungi, pointing to a potential role as an antimicrobial agent. METHODS: Growth assays of Paracoccidioides brasiliensis cells incubated in the presence of different concentrations of farnesol were performed by measuring the optical density of the cultures. The viability of fungal cells was determined by MTT assay and by counting the colony forming units, after each farnesol treatment. The effects of farnesol on P. brasiliensis dimorphism were also evaluated by optical microscopy. The ultrastructural morphology of farnesol-treated P. brasiliensis yeast cells was evaluated by transmission and scanning electron microscopy. RESULTS: In this study, the effects of farnesol on Paracoccidioides brasiliensis growth and dimorphism were described. Concentrations of this isoprenoid ranging from 25 to 300 microM strongly inhibited P. brasiliensis growth. We have estimated that the MIC of farnesol for P. brasiliensis is 25 microM, while the MLC is around 30 microM. When employing levels which don't compromise cell viability (5 to 15 microM), it was shown that farnesol also affected the morphogenesis of this fungus. We observed about 60% of inhibition in hyphal development following P. brasiliensis yeast cells treatment with 15 microM of farnesol for 48 h. At these farnesol concentrations we also observed a significant hyphal shortening. Electron microscopy experiments showed that, despite of a remaining intact cell wall, P. brasiliensis cells treated with farnesol concentrations above 25 microM exhibited a fully cytoplasmic degeneration. CONCLUSION: Our data indicate that farnesol acts as a potent antimicrobial agent against P. brasiliensis. The fungicide activity of farnesol against this pathogen is probably associated to cytoplasmic degeneration. In concentrations that do not affect fungal viability, farnesol retards the germ-tube formation of P. brasiliensis, suggesting that the morphogenesis of this fungal is controlled by environmental conditions.