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INTRODUCTION: Older patients are more susceptible to medication use, and physiological changes resulting from aging and organic dysfunctions presented by critically ill patients may alter the pharmacokinetic or pharmacodynamic behavior. Thus, critically ill older people present greater vulnerability to the occurrence of pharmacotherapeutic problems. OBJECTIVE: To evaluate pharmacotherapy and the development of potential adverse drug reactions (ADRs) in older patients admitted to an intensive care unit (ICU). METHOD: A cohort study was conducted in an ICU for adults of a Brazilian University Hospital during a 12-month period. The patients' pharmacotherapy was evaluated daily, considering the occurrence of ADRs and drug-drug interactions (DDIs), the use of potentially inappropriate medications (PIMs) for older people, and the pharmacotherapy anticholinergic burden (ACB). A trigger tool was used for active search of ADRs, with subsequent causality evaluation. PIM use was evaluated by means of the Beers criteria and the STOPP/START criteria. The ABC scale was employed to estimate ACB. The Micromedex® and Drugs.com® medication databases were employed to evaluate the DDIs. RESULTS: The sample of this study consisted of 41 patients, with a mean age of 66.8â¯years old (±5.2). The 22 triggers used assisted in identifying 15 potential ADRs, and 26.8% of the patients developed them. The mean estimated ACB score was 3.0 (±1.8), and the patients used 3.1 (±1.4) and 3.3 (±1.6) PIMs according to the Beers and the STOPP criteria, respectively. A total of 672 DDIs were identified, with a mean of 16.8 (±9.5) DDIs/patient during ICU hospitalization. Our findings show an association between occurrence of ADRs in the ICU and polypharmacy (p=.03) and DDIs (p=.007), corroborating efforts for rational medication use as a preventive strategy. CONCLUSIONS: Using tools to evaluate the pharmacotherapy for older people in intensive care can assist in the recognition and prevention of pharmacotherapeutic problems, with emphasis on the identification of ADRs through the observation of triggers and subsequent causality analysis.
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PURPOSE: To evaluate glycemic variability (GV) using continuous glucose monitoring (CGM) in individuals with and without type 2 diabetes mellitus (T2DM) undergoing Roux-en-Y gastric bypass (RYGB). METHODS: This prospective cohort study compared the CGM data of fourteen patients with T2DM (n = 7) and without T2DM (n = 7) undergoing RYGB. After 6 months, these patients were compared to a non-operative control group (n = 7) matched by BMI, sex, and age to the T2DM group. RESULTS: Fourteen patients underwent RYGB, with a mean BMI of 46.9 ± 5.3 kg/m2 and an average age of 47.9 ± 8.9 years; 85% were female. After 6 months post-surgery, the total weight loss (TWL) was 27.1 ± 6.3%, with no significant differences between the groups. Patients without diabetes had lower mean interstitial glucose levels (81 vs. 94 and 98 mg/dl, p < 0.01) and lower glucose management indicator (GMI) (5.2 vs. 5.6 and 5.65%, p = 0.01) compared to the control and T2DM groups, respectively. The coefficient of variation (CV) significantly increased only in patients with diabetes (17% vs. 26.7%, p < 0.01). Both groups with (0% vs. 2%, p = 0.03) and without (3% vs. 22%, p = 0.03) T2DM experienced an increased time below range with low glucose (54-69 mg/dL). However, patients without T2DM had significantly less time in rage (70-180 mg/dL) (97% vs. 78%, p = 0.04). CONCLUSION: Significant differences in CGM metrics among RYGB patients suggest an increase in glycemic variability after surgery, with a longer duration of hypoglycemia, especially in patients without T2DM.
Subject(s)
Blood Glucose , Continuous Glucose Monitoring , Diabetes Mellitus, Type 2 , Gastric Bypass , Obesity, Morbid , Weight Loss , Adult , Female , Humans , Male , Middle Aged , Blood Glucose/metabolism , Blood Glucose/analysis , Blood Glucose Self-Monitoring , Continuous Glucose Monitoring/statistics & numerical data , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/surgery , Glycemic Control , Obesity, Morbid/surgery , Obesity, Morbid/blood , Prospective Studies , Weight Loss/physiologyABSTRACT
The objective was to evaluate the change in color, hardness, and roughness produced by carbamide peroxide (CP) at two different concentrations on two resins. The 16% or 45% CP was applied to 66 resin discs with and without Bis-GMA. The color was measured with a spectrophotometer, and ΔEab and ΔE00 were calculated. Microhardness tester and SEM were used. In both composites, the a* and b* coordinates tended to be red and yellow, respectively, and were significant in the Bis-GMA group (p < 0.05). The ΔEab and ΔE00 were higher in the composite with Bis-GMA, regardless of the treatment received (p < 0.05). The microhardness was reduced in both composites regardless of the PC concentration compared to the control (p < 0.05). The 45% CP reduced the microhardness in the resin group with Bis-GMA compared to 16% CP (p < 0.001) but was not significant in the resin without Bis-GMA (p = 1). An increase in roughness was directly proportional to the concentration of CP, and it was more notable in the composite without Bis-GMA. The composite with Bis-GMA showed a greater tendency to darken than the one without Bis-GMA. The surface hardness of the composite was reduced in both composites and was not influenced by CP concentration in the composite without Bis-GMA. Bleaching is a common procedure nowadays. It is important to know how CP affects composites to establish a prognosis of the treatments in terms of color change, roughness, and hardness.
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The aim of the present study is to report a clinical case of a patient diagnosed with a late adverse reaction to the injection of filler material - persistent and intermittent delayed swelling (PIDS) - in which photobiomodulation therapy (PBMT) with low-power laser was used for edema reduction. This is an observational, descriptive, and retrospective work of a case report. The female patient, aged 73 years old, had undergone dermal filler six years before and complained of increased volume in the face region (glabellar region, labiomental sulcus, and nasolabial folds) and was submitted to ultrasound and anatomopathological analysis. PBMT using a low-power laser (660 nm and 808 nm, simultaneous irradiation, in contact, 2 J/point, 100 mW) proved to be effective for the non-invasive approach of late adverse reaction to dermal filler, such as PIDS, a common complication related to the use of dermal fillers.
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The transplacental transmission of parasites and hemoparasites is crucial for understanding the epidemiology of diseases. This study aimed to assess the prevalence of hemopathogens in bovine fetuses at various gestational periods. Samples were obtained from a slaughterhouse in the state of Minas Gerais, Brazil, and a total of 236 fetuses were collected. DNA extracted from blood samples (145) and organ samples (a pool of brain and spleen) (236) underwent a nested PCR (nPCR) assay to detect Babesia spp., Theileria spp., Trypanosoma vivax, Anaplasma marginale, Anaplasma bovis, Anaplasma phagocytophilum, Ehrlichia minasensis, and hemotropic Mycoplasma spp. Additionally, serological analysis of 145 plasma samples was conducted using the indirect fluorescent antibody test-IFAT to detect IgG against Babesia bovis, Babesia bigemina, A. marginale, and Trypanosoma vivax. The observed prevalence of transplacental transmission was 19.3 %, 6.2 %, 42.7 % and 2.7 %, for A. marginale, B. bigemina, 'Candidatus M. haemobos', and Mycoplasma wenyonii, respectively. The prevalence of A. marginale by gestational trimester was 16 % (13/81) in the second trimester and 23 % (14/60) in the third trimester, with no positive samples in the first trimester. Regarding the species B. bovis and B. bigemina, all evaluated animals tested negative by nPCR, and no serological evidence for B. bovis was found by the IFAT. Babesia bigemina demonstrated an overall seroprevalence of 6.2 % (9/145), with 4.8 % (7/145) in the last trimester and 1.3 % (2/145) in the second trimester of pregnancy. In total, 42.7 % (62/145) of blood samples were positive for 'Candidatus M. haemobos', with 42 % (34/81) in the middle trimester, and 43 % (26/60) in the final trimester of pregnancy. Mycoplasma wenyonni was detected in 2.7 % (4/145) blood samples, all in coinfection with 'C. M. haemobos'. The prevalence by pregnancy trimester was 25 % (1/4) in the first trimester; 1.2 % (1/81) in the second trimester and 3.3 % (2/60) in the third trimester of pregnancy. Hemopathogen DNA was detected in fetus blood samples but not the brain or spleen samples. All the samples were negative for T. vivax, Theileria spp., Anaplasma spp. and Ehrlichia spp. Overall, in this study, approximately 70 % of fetuses were positive for one or more of the studied parasites. No significant associations were observed between pairs of pathogens, except 'C. M. haemobos' and A. marginale.
Subject(s)
Cattle Diseases , Mycoplasma , Animals , Brazil/epidemiology , Cattle , Female , Cattle Diseases/epidemiology , Cattle Diseases/microbiology , Cattle Diseases/parasitology , Mycoplasma/isolation & purification , Pregnancy , Prevalence , Babesia/isolation & purification , Fetus/microbiology , Fetus/parasitology , Mycoplasma Infections/epidemiology , Mycoplasma Infections/veterinary , Mycoplasma Infections/microbiology , Theileria/isolation & purification , Trypanosoma vivax/isolation & purification , Infectious Disease Transmission, Vertical/veterinary , Anaplasma/isolation & purification , Babesiosis/epidemiology , Babesiosis/parasitology , Anaplasmosis/epidemiology , Anaplasmosis/microbiology , Ehrlichia/isolation & purificationABSTRACT
INTRODUCTION: Recently, calcium silicate-based sealers (CSSs) have gained popularity in endodontic practice due to their biocompatibility and antimicrobial properties. They are considered viable alternatives to epoxy resin-based sealers. With the increased use of CSSs and warm vertical compaction techniques in root canal treatment, evaluating the impact of heat on CSSs properties is essential, therefore this review aimed to present a qualitative synthesis of available in vitro studies assessing the impact of heat on the physical-chemical properties of CSSs. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines, a systematic advanced electronic search was performed in Scopus, Embase, Medline (via PubMed), Web of Science, and Cochrane databases in November 2023 and updated in April 2024. In vitro studies that evaluated the physical-chemical properties of CSSs were eligible. PRILE 2021 guidelines were used for the assessment of the risk of bias-included studies. RESULTS: The search identified a total of 6421 preliminary results and 10 studies were included for qualitative assessment. Eleven different physiochemical properties were assessed by the included studies. Setting time and flow were the most evaluated property among the studies. A qualitative synthesis of the evidence on each property is presented. CONCLUSIONS: Based on the in vitro studies assessed in the present systematic review, results reveal that exposing CSSs to heat can accelerate their setting time, reduce their flow, and increase their film thickness. Concerns persist regarding solubility, viscosity, radiopacity, dimensional change, microhardness, porosity, and compressive strength, requiring further research. Certain CSSs, such as MTA Fillapex and Endosequence BC sealer HiFlow, show minimal changes under heat, making them potential candidates for warm filling techniques.
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Calcium Compounds , Hot Temperature , Root Canal Filling Materials , Silicates , Calcium Compounds/chemistry , Silicates/chemistry , Root Canal Filling Materials/chemistry , Humans , Materials TestingABSTRACT
Latin American and the Caribbean regions (LAC) harbor one of the most biodiverse areas of the world, the Neotropics. True bugs (Hemiptera: Heteroptera) are a diverse lineage of insects, with more than 45,000 species, particularly speciose in the Neotropical region. True bugs are fundamental in the dynamics of natural and modified ecosystems, with several species critical to agriculture and public health. We compiled Heteroptera research in LAC from 1998-2022 using bibliographic databases. Productivity, collaborative networks, and the main topics studied were analyzed. A total of 1,651 Heteroptera studies from LAC were found, with continuous growth being 2021 the most prolific. Four categories (Taxonomy of extant species, Faunistic inventories and new records, Pest species biology, and Community ecology) represent most of the published research. About 60 percent of the records evaluated correspond to five families (Pentatomidae, Reduviidae, Coreidae, Miridae, and Rhyparochromidae). We emphasize the need to keep working on Heteroptera taxonomy because it will allow further advances in other areas such as phylogenetic analyses, biogeography, ecology, and natural history, among others. The results of our analyses characterize the current state of heteropterology in the region, establishing a baseline for future studies and efforts to broaden the knowledge of the group.
Subject(s)
Heteroptera , Latin America , Animals , Caribbean Region , Heteroptera/classification , Research/trends , Research/classification , BibliometricsABSTRACT
Trypanosoma cruzi is a parasite with a high capacity to adapt to the host. Animal models have already demonstrated that the tropism of this parasite occurs not only in cardiac/digestive tissues but also in adipose tissue (AT). That said, the consequences ofT. cruziinfection for AT and the implications of treatment with Benzonidazole in this tissue are under discussion. Here, we tested the hypothesis that T. cruzi infection in adipose tissue upon treatment with Benzonidazole (Bz) and the interaction of mononuclear immune cells (PBMC) influences the relative expression of ACAT1, FASN, and PNPLA2 genes. Thus, stem cells derived from adipose tissue (ADSC) after adipogenic differentiation were indirectly cultivated with PBMC after infection with the T. cruzi Y strain and treatment with Bz. We use the TcSAT-IAM system and RT-qPCR to evaluate the parasite load and the relative quantification (ΔCt) of the ACAT1, FASN, and PNPLA2 genes. Our results demonstrate that treatment with Bz did not reduce adipocyte infection in the presence (p-value: 0.5796) or absence (p-value: 0.1854) of cultivation with PBMC. In addition, even though there is no statistical difference when compared to the control group (AT), T. cruzi induces the FASN expression (Rq: 14.00). However, treatment with Bz in AT suggests the increases of PNPLA2 expression levels (Rq: 12.58), even in the absence of T. cruzi infection. During indirect cultivation with PBMC, T. cruzi smooths the expression of PNPLA2 (Rq: 0.824) and instigates the expression of ACAT1 (Rq: 1.632) and FASN (Rq: 1.394). Furthermore, the treatment with Bz during infection induces PNPLA2 expression (Rq: 1.871), maintaining FASN expression levels (Rq: 1.334). Given this, our results indicate that treatment with Benzonidazole did not decrease T. cruzi infection in adipose tissue. However, treating the adipocyte cells with Bz during the interaction with PBMC cells influences the lipid pathways scenario, inducing lipolytic metabolism through the expression of PNPLA2.
Subject(s)
Acyltransferases , Adipose Tissue , Fatty Acid Synthase, Type I , Leukocytes, Mononuclear , Lipase , Trypanosoma cruzi , Humans , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/parasitology , Adipose Tissue/parasitology , Adipose Tissue/metabolism , Trypanosoma cruzi/drug effects , Trypanosoma cruzi/genetics , Lipase/genetics , Lipase/metabolism , Fatty Acid Synthase, Type I/genetics , Fatty Acid Synthase, Type I/metabolism , Acetyl-CoA C-Acetyltransferase/genetics , Acetyl-CoA C-Acetyltransferase/metabolism , Chagas Disease/drug therapy , Chagas Disease/parasitology , Chagas Disease/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Parasite Load , Gene Expression , Cells, CulturedABSTRACT
Oral Mucosal Lesions (OMLs) are conditions of the oral mucosa that cause alterations in their presentation and pain in the affected patient, highlighting their importance for study. The aim of this research is to determine the prevalence of oral lesions in the Ecuadorian Austro. Descriptive statistics were used to associate variables, yielding statistically significant findings based on oral lesions, sex, and geographical environment. This study was conducted under the appropriate bioethical permissions. The results obtained correspond to the prevalence of lesions by province. Morona Santiago displays a rate of 17% for abscesses, surpassing the provinces of Azuay (13.50%) and Cañar (10.67%). However, gingivitis for pathology, Azuay stands out with 13.17%, while Cañar and Morona Santiago present 10.50% and 8.33%, respectively. There is also a predominant occurrence of abscesses in rural areas (41.17%) compared to urban ones (26.33%). Regarding sex, girls show a higher percentage of abscesses (41.17%) compared to boys who have a clear tendency to present GUM lesions (22.33%). The data indicates that in the studied provinces, geographical environment and sex are key variables to understand the distribution of oral lesions. These findings encourage us to continue pursuing this type of research, which contributes to improving the quality of life for children.
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Introduction: Engaging with nature has been widely acknowledged for its positive impact on well-being. Traditionally, assessments of nature exposure focus on estimating green space exposure and outdoor time. However, the Nature Exposure Scale (NES) offers a unique approach by evaluating the quality of nature experiences, encompassing both deliberate and spontaneous encounters. Methods: This study aimed to assess the validity and reliability of the NES in the context of Portugal. Exploratory Factor Analysis (PCA) and Confirmatory Factor Analysis (CFA) were employed to examine the underlying structure of the scale. Additionally, reliability assessments, along with tests of convergent and divergent validity, were conducted. Data were collected from a sample of 558 adults and 241 adolescents between 2016 and 2018. Results: The findings revealed strong internal consistency of the NES, supported by acceptable correlation values and robust factor loadings within a unidimensional model. The scale effectively predicted variations in nature exposure across diverse professional activities. Discussion: In summary, the 4-item NES emerged as a reliable tool for assessing nature exposure in various settings, effectively bridging a gap in the Portuguese context. The scale demonstrated potential for cross-cultural research and was particularly adept at predicting nature exposure in different professional contexts. The results suggest that the NES can enhance our understanding of the impact of nature on well-being in diverse cultural settings. Conclusion: The study underscores the reliability of the NES in assessing nature exposure in Portugal, paving the way for further exploration in Portuguese-speaking regions. The scale holds promise for advancing research on the relationship between nature and well-being, contributing valuable insights across different cultural contexts.
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Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.
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Chikungunya Fever , Chikungunya virus , Animals , Humans , Chikungunya Fever/complications , Proteomics , Chikungunya virus/genetics , Cytokines/metabolismABSTRACT
INTRODUCTION: American Tegumentary Leishmaniasis (ATL) treatment is based on pentavalent antimonials (Sb5+), but these drugs have been associated to several adverse effects. Hearing loss and tinnitus during treatment with meglumine antimoniate (MA) have already been reported. This study aimed to describe the usefulness of self-reporting of hearing loss and tinnitus in diagnosing MA-induced ototoxicity. METHODS: A prospective longitudinal study was conducted with 102 patients with parasitological diagnosis of ATL, treated with different MA schemes. The presence of clinical auditory toxicity was defined as the emergence or worsening of self-reporting hearing loss and/or tinnitus during monitoring. Measures of sensitivity, specificity, and the positive and negative predictive value of the patient's self-reporting of hearing loss and tinnitus in relation to the result of the audiometric test (considered the gold standard) were calculated. RESULTS: The age of the evaluated patients ranged from 15 to 81 years, with a median of 41 years, and most were male (73.5%). Seventy-five patients (73.5%) had cutaneous leishmaniasis and 27 (26.5%) mucosal leishmaniasis. Eighty-six patients (84.3%) received intramuscular (IM) treatment and 16 (15.7%) were treated with intralesional MA. During treatment, 18 (17,6%) had tinnitus and 7 (6,9%) had complaint of hearing loss. 53 (52%) patients had cochlear toxicity confirmed by tone threshold audiometry and high frequency audiometry, from which 60% received a dose of 20 mg Sb5+/kg/day (p = 0.015) and 96.2% were treated with IM MA (p = 0.001). Tinnitus has greater specificity and positive predictive value than hearing loss, with a low number of false positives, but with a high false negative value. CONCLUSION: Although the large number of false negatives suggests that self-report of hearing loss or tinnitus cannot be considered a good screening test for referring the patient to an audiometry, the low number of false positives suggests the need to value the patient's complaint for referral. Otherwise, this study reinforces the importance of audiological monitoring during treatment with MA, especially in those patients with self-reporting of hearing loss or tinnitus when treated with 20 mg Sb5+/kg/day via IM.
Subject(s)
Antiprotozoal Agents , Deafness , Hearing Loss , Leishmaniasis, Cutaneous , Organometallic Compounds , Ototoxicity , Tinnitus , Humans , Male , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Female , Meglumine Antimoniate/adverse effects , Tinnitus/chemically induced , Tinnitus/diagnosis , Tinnitus/drug therapy , Meglumine/adverse effects , Antiprotozoal Agents/therapeutic use , Longitudinal Studies , Prospective Studies , Organometallic Compounds/adverse effects , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/drug therapy , Hearing Loss/chemically induced , Hearing Loss/diagnosisABSTRACT
BACKGROUND: Obesity is believed to be a risk factor for COVID-19 and unfavorable outcomes, although data on this remains to be better elucidated. OBJECTIVE: To evaluate the impact of obesity on the endpoints of patients hospitalized due to SARS-CoV-2. METHODS: This retrospective cohort study evaluated patients hospitalized at a tertiary hospital (Hospital das Clínicas da Faculdade de Medicina da USP) from March to December 2020. Only patients positive for COVID-19 (real-time PCR or serology) were included. Data were collected from medical records and included clinical and demographic information, weight and height, SAPS-3 score, comorbidities, and patient-centered outcomes (mortality, and need for mechanical ventilation, renal replacement therapy, or vasoactive drugs). Patients were divided into categories according to their BMI (underweight, eutrophic, overweight and obesity) for comparison porpoise. RESULTS: A total of 2547 patients were included. The mean age was 60.3 years, 56.2% were men, 65.2% were white and the mean BMI was 28.1 kg/m2. SAPS-3 score was a risk factor for all patient-centered outcomes (HR 1.032 for mortality, OR 1.03 for dialysis, OR 1.07 for vasoactive drug use, and OR 1.08 for intubation, p < 0.05). Male sex increased the risk of death (HR 1.175, p = 0.027) and dialysis (OR 1.64, p < 0.001), and underweight was protective for vasoactive drug use (OR 0.45, p = 0.027) and intubation (OR 0.31, p < 0.003). CONCLUSION: Obesity itself was not an independent factor for worse patient-centered outcomes. Critical clinical state (indirectly evaluated by SAPS-3) appears to be the most important variable related to hard outcomes in patients infected with COVID-19.
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BACKGROUND/AIMS: Longitudinal studies assessing the impact of genetic polymorphisms on outcomes in patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) are scarce. This study aimed to evaluate the effect of PNPLA3 and TM6SF2 risk alleles on hepatic and extrahepatic outcomes in T2DM-MASLD individuals. METHODS: Patients' polymorphisms were analysed as follows: PNPLA3 CC, CG and GG; TM6SF2 CC and CT + TT; combined comparing no mutant allele, one allele G or T or ≥2 alleles G or T. Hierarchical models were built to assess associations between polymorphisms and outcomes, independently of confounding factors. Multivariate logistic regression was used for cirrhosis and its complications and extrahepatic cancer, and Cox regression for cardiovascular events (CVEs) and all-cause mortality. RESULTS: In total, 407 T2DM-MASLD patients (62.1 ± 10.5 years, 67.6% women) were followed for 11 (6-13) years. Having at least one G or T allele independently increased the risk of cirrhosis in the separate analysis of PNPLA3 and TM6SF2. Combined polymorphism analysis demonstrated an even higher risk of cirrhosis if two or more risk alleles were present (OR 18.48; 95% CI 6.15-55.58; p < .001). Regarding cirrhosis complications, the risk was higher in PNPLA3 GG and TM6SF2 CT + TT, also with an even higher risk when two or more risk alleles were present in the combined evaluation (OR 27.20; 95% CI 5.26-140.62; p < .001). There were no associations with CVEs or mortality outcomes. CONCLUSION: In T2DM, PNPLA3 and TM6SF2 polymorphisms, individually and additively, impact MASLD severity, with an increased risk of cirrhosis and its complications.
Subject(s)
Diabetes Mellitus, Type 2 , Fatty Liver , Non-alcoholic Fatty Liver Disease , Humans , Female , Male , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Liver Cirrhosis/genetics , Fibrosis , Prognosis , Non-alcoholic Fatty Liver Disease/genetics , Genotype , Membrane Proteins/geneticsABSTRACT
The therapeutic regimen for the treatment of American Tegumentary Leishmaniasis (ATL) is targeted at the death of the parasite; therefore, it is essential to develop a treatment that can act on the parasite, combined with the modulation of the inflammatory profile. Thus, the aim of this study was to make an in vitro evaluation of the therapeutic potential of Chlorella vulgaris extract (CV) and Imiquimod for ATL. Selectivity indices (SI) were determined by inhibitory concentration assays (IC50) in L. braziliensis cells and cytotoxic concentrations (CC50) were measured in human cells using the MTT method, based on the CV microalgae extract (IC50 concentrations of 15.63 to 500 µg/mL; CC50 concentrations of 62.5-1000 µg/mL) in comparison with the reference drugs and Imiquimod. The immune response was evaluated in healthy human cells by gene expression (RT-qPCR) and cytokine production (Flow Cytometry). The CV extract (SI = 6.89) indicated promising results by showing higher SI than meglumine antimoniate (SI = 3.44) (reference drug). In all analyses, CV presented a protective profile by stimulating the production of Th1 profile cytokines to a larger extent than the reference drugs. Imiquimod showed a high expression for Tbx21, GATA3, RORc and Foxp3 genes, with increased production only of the TNF cytokine. Therefore, the data highlight the natural extract and Imiquimod as strong therapeutic or adjuvant candidates against ATL, owing to modulation of immune response profiles, low toxicity in human cells and toxic action on the parasite.
Subject(s)
Antiprotozoal Agents , Chlorella vulgaris , Leishmania braziliensis , Leishmaniasis, Cutaneous , Humans , Imiquimod/therapeutic use , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitology , CytokinesABSTRACT
OBJECTIVES: The current in vitro study aims to evaluate silk fibroin with and without the addition of graphene as a potential scaffold material for regenerative endodontics. MATERIAL AND METHODS: Silk fibroin (SF), Silk fibroin/graphene oxide (SF/GO) and silk fibroin coated with reduced graphene oxide (SF/rGO) scaffolds were prepared (n = 30). The microarchitectures and mechanical properties of scaffolds were evaluated using field emission scanning electron microscopy (FESEM), pore size and water uptake, attenuated total reflectance fourier transformed infrared spectroscopy (ATR-FTIR), Raman spectroscopy and mechanical compression tests. Next, the study analyzed the influence of these scaffolds on human dental pulp stem cell (hDPSC) viability, apoptosis or necrosis, cell adhesion, odontogenic differentiation marker expression and mineralized matrix deposition. The data were analyzed with ANOVA complemented with the Tukey post-hoc test (p < 0.005). RESULTS: SEM analysis revealed abundant pores with a size greater than 50 nm on the surface of tested scaffolds, primarily between 50 nm and 600 µm. The average value of water uptake obtained in pure fibroin scaffolds was statistically higher than that of those containing GO or rGO (p < 0.05). ATR-FTIR evidenced that the secondary structures did not present differences between pure fibroin and fibroin coated with graphene oxide, with a similar infrared spectrum in all tested scaffolds. Raman spectroscopy showed a greater number of defects in the links in SF/rGO scaffolds due to the reduction of graphene. In addition, adequate mechanical properties were exhibited by the tested scaffolds. Regarding biological properties, hDPSCs attached to scaffolds were capable of proliferating at a rate similar to the control, without affecting their viability over time. A significant upregulation of ALP, ON and DSPP markers was observed with SF/rGO and SF/GO groups. Finally, SF/GO and SF/rGO promoted a significantly higher mineralization than the control at 21 days. SIGNIFICANCE: Data obtained suggested that SF/GO and SF/rGO scaffolds promote hDPSC differentiation at a genetic level, increasing the expression of key osteo/odontogenic markers, and supports the mineralization of the extracellular matrix. However, results from this study are to be interpreted with caution, requiring further in vivo studies to confirm the potential of these scaffolds.
Subject(s)
Fibroins , Graphite , Humans , Fibroins/chemistry , Tissue Scaffolds/chemistry , Tissue Engineering/methods , Graphite/chemistry , Dental Pulp , Cell Differentiation , Water , Cell Proliferation , Stem CellsABSTRACT
PURPOSE: Sublingual varicose veins are a common vascular lesion with different names, such as caviar tongue or vascular malformations. This study aimed to investigate whether there is an association between sublingual varicose veins and cardiovascular diseases by observing arterial hypertension, diabetes, thrombosis, and infarction. In addition, to evaluate a series of thrombi that affected the oral cavity and to analyze their clinical aspects and relate them to possible systemic alterations. METHODS: This is a cross-sectional study consisting of a sample of 134 varicosities, 23 vascular malformations, and 4 thrombosis. RESULTS: Lingual varicosities are more frequently observed in women aged 57.4 ± 16.4 years. Hypertension was present in lingual varicosities (n = 73), as well as diabetes (n = 107), reports of thrombosis (n = 41), and infarction (n = 45). Arterial hypertension was decompensated (n = 12). The most frequent underlying diseases were diabetes (p < 0.001), infarction (p = 0.012), and thrombosis (p = 0.004), and the most commonly used drug was losartan. CONCLUSION: It can be inferred from the present study that lingual varicosities are related to cardiovascular diseases and can serve as a parameter to measure their decompensation.
Subject(s)
Hypertension , Varicose Veins , Humans , Cross-Sectional Studies , Female , Middle Aged , Male , Hypertension/complications , Aged , Adult , Thrombosis , Mouth Floor/blood supply , Tongue/blood supply , Aged, 80 and overABSTRACT
Introdução: a hanseníase apresenta potencial incapacitante secundário às reações hansênicas. Existe considerável número de indivíduos com episódios recorrentes de reação durante o tratamento. Objetivo: identificar características clínicas e histopatológicas que diferenciem pacientes com reação hansênica ou não. Método: estudo prospectivo de julho/2015 a dezembro/2016, com avaliação de indivíduos com diagnóstico novo de hanseníase atendidos no serviço de dermatologia do Complexo Hospitalar Clementino Fraga, na cidade de João Pessoa, Paraíba, Brasil. Os sujeitos foram classificados segundo os critérios de Ridley-Jopling/Madrid e por classificação operacional. Realizaram exame histopatológico no momento do diagnóstico e após 12 meses, e reavaliados após 6 e 12 meses do diagnóstico. Resultados: o grupo sem reação apresentou maior número de lesões com nítida delimitação. Observou-se predomínio das formas multibacilares entre indivíduos com reação. Quanto ao grau de incapacidade, o grupo com reação apresentou maior número de indivíduos com grau de incapacidade maior que zero. No grupo sem reação, encontrou-se menor frequência de fatores predisponentes. Notou-se correlação positiva do índice baciloscópico de biópsia cutânea com a ocorrência de reações. Discussão: a ausência de delimitação periférica das lesões pode se correlacionar com o surgimento de reação hansênica. O predomínio de reação entre os indivíduos que apresentavam grau de incapacidade maior que zero sugere associação de deficiência física e doença multibacilar. A ausência de fatores predisponentes aponta menor risco de reação hansênica. Observou-se correlação positiva do índice baciloscópico da biópsia com a ocorrência das reações. Conclusão: a significativa prevalência de reações graves enfatizam a importância do estudo contínuo da hanseníase e a necessidade de identificar precocemente as características clínicas sugestivas de reações hansênicas.(AU)
Introduction: leprosy reactions have the potential to cause disabilities. Many individuals experience recurrent episodes of reaction during treatment. Objective:to identify clinical and histopathological characteristics that differentiate patients with leprosy reactions from those without leprosy reactions. Method: this is a prospective study conducted from July 2015 to December 2016, evaluating individuals newly diagnosed with leprosy and treated at the dermatology service of the Clementino Fraga Hospital Complex in João Pessoa, Paraíba, Brazil. The subjects were classified according to the Ridley-Jopling/Madrid criteria and operational classification. They underwent a histopathological examination at the time of diagnosis and 12 months later, and were reassessed 6 and 12 months after the diagnosis. Results: the group without a reaction had a greater number of lesions with clear delimitation. Individuals with a reaction showed a predominance of multibacillary forms. The group with a reaction had a greater number of individuals with a degree of disability greater than zero. A positive correlation was observed between the bacilloscopic index and the occurrence of reactions. Discussion: the lack of clear boundaries around the lesions may be linked to the onset of a leprosy reaction. The higher incidence of reactions in individuals with some degree of physical disability indicates a correlation between disability and multibacillary disease. Additionally, a positive correlation was found between the bacilloscopic index of the biopsy and the occurrence of reactions. Conclusion: the high incidence of severe reactions underscores the need for ongoing studies on leprosy and the identification of early clinical characteristics that suggest leprosy reactions.(AU)
Subject(s)
Humans , Male , Female , Leprosy/pathology , Leprosy/therapy , Brazil/epidemiology , Retrospective StudiesABSTRACT
Importance: The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear. Objective: To evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU). Design, Setting, and Participants: The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020. Interventions: Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care. Main Outcomes and Measures: The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group. Results: Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006). Conclusions and Relevance: This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist. Trial Registration: ClinicalTrials.gov Identifier: NCT03179020.