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1.
Revista Digital de Postgrado ; 13(2): e395, ago.2024. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1567364

RESUMO

Introducción: Durante el desarrollo embriológico, el espacio retrorrectal o presacro está ocupado por células pluripotenciales y, por tanto, puede contener un grupo heterogéneo de tumores. El quiste dermoide es una entidad muy rara dentro de este grupo de tumores. Descripción de caso: femenina de 36 años de edad, con sensación de pesadez en hipogastrio, dolor en sedestación, y cambios en patrón evacuatorio; se realizó palpación abdominal, tacto rectal positivo para masa blanda dolorosa; eco endoanal y resonancia evidenciaron lesión ocupante de espacio presacro. Se realizó exéresis completa vía abdominal, con diagnóstico histopatológico definitivo de quiste dermoide. Discusión: un tumor presacro involucra un reto diagnóstico y terapéutico debido a la gran variedad de diagnósticos diferenciales. En el presente caso se diagnosticó un quiste dermoide, tumor benigno, fuera de su localización habitual. Conclusión: los tumores retrorrectales son lesiones poco habituales, es necesaria la exéresis completa y su posterior estudio histopatológico, para establecer su naturaleza. (AU)


Introduction: During embryological development, the retrorectal or presacral space is occupiedby pluripotent cells and, therefore, may contain a heterogeneous group of tumors. The dermoid cyst is a very rare entity within this group of tumors. Materials and methods: We present a case of a 36-year-old female patient with a sensation of heaviness inthe hypogastrium. Magnetic resonance imaging was performed in which presacral tumor was evident. Results: complete abdominal excision was performed, with a definitive histopathological diagnosis of dermoid cyst. Discussion: a presacral tumor involves a diagnostic and therapeutic challenge due to the great variety of differential diagnoses. The present case was diagnosed with a dermoid cyst, a benign tumor, outside its usual location. Conclusion: Retrorectal tumors are rare tumors, in which complete excision and histopathological report are necessary. (AU)


Assuntos
Humanos , Feminino , Adulto , Cisto Dermoide/diagnóstico , Canal Anal , Reto/patologia , Sacro/patologia , Biópsia , Tomografia Computadorizada de Emissão
2.
Inflamm Bowel Dis ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39190809

RESUMO

BACKGROUND: Patient concerns and preferences are important in the management of inflammatory bowel disease (IBD: Crohn's disease [CD], ulcerative colitis). In the absence of contemporary data, we aimed to determine patient concerns and preferences and establish if there are demographic or disease-related differences. METHODS: We surveyed patients with IBD at Massachusetts General Hospital between July and September 2023. The Rating Form of Inflammatory Bowel Disease Patient Concerns (RFIPC) and a set of supplemental questions rated on a visual analog scale (0-100 mm) were administered to patients and compared by age, disease type, sex, and surgery status. Additionally, a survey administered to treating providers gathered insight into the difference between patient and provider perceptions of concerns. RESULTS: A total of 350 patients and 30 providers completed the survey. The mean age was 47 years; 50% were female, 49% had CD, and 80% were on advanced IBD therapy. Effects of medication (median = 54), energy level (median = 53), and having an ostomy bag (median = 52) were rated highest by patients. Older patients rated most disease complication and treatment-related concerns similar to younger adults; those aged 35-59 years had the greatest level of concern for most questions. Sex, disease activity, and prior surgical history also impacted patients' concerns. Providers perceived patients' worries as higher than those rated by patients themselves. CONCLUSIONS: A shared decision-making model targeting the achievement of disease remission and addressing concerns rated highly by patients is important to meet the goal of care for patients with IBD.


The highest rated concerns among patients with inflammatory bowel disease were needing an ostomy, energy level, and concern with medications. Older patients had a similar level of disease-related concerns as younger patients. There has been no secular decrease in patient concerns.

3.
ChemMedChem ; : e202400241, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136604

RESUMO

A series of novel 4-acetyl-1,3,4-oxadiazole derivatives was designed and synthesized for their biological evaluation in vitro against Trypanosoma cruzi and Leishmania mexicana. Additionally, compounds were evaluated by molecular docking on the cruzain of T. cruzi (TcCz) and the cysteine protease B (CPB) of L. mexicana (LmCPB) to know their potential mechanism of binding. Compound OX-12 had better trypanocidal activity against NINOA (IC50= 10.5 µM) and A1 (IC50= 21.7 µM) T. cruzi strains that reference drug benznidazole (IC50= 30.3 µM and 39.8 µM, respectively). Compound OX-2 had the best biological activity against L. mexicana in M379 (IC50= 11.9 µM) and FCQEPS (IC50= 34.0 µM) strains that the reference drug glucantime (IC50 ˃120 µM). All the compounds showed important interactions with residues on the active site of TcCz (Gly66, Trp26, Leu67, and Ala138) and LmCPB (Gly67, Asn62, Leu68, and Ala140). Finally, the molecular dynamics simulations of the compound OX-12 shown moderate stability from 40 to 115 ns with an RMSD value of 6.5 Å. Meanwhile, compound OX-2 showed a minor stability in complex with CPB from 25 to 200 ns of simulation (RMSD <9 Å). These results encourage to develop more potent and efficient trypanocidal and leishmanicidal agents using the 1,3,4-oxadiazole scaffold.

4.
Acta Biochim Pol ; 71: 13004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39041003

RESUMO

CD36 is a type 2 cell surface scavenger receptor expressed in various tissues. In macrophages, CD36 recognizes oxidized low-density lipoprotein (ox-LDL), which promotes the formation of foam cells, the first step toward an atherosclerotic arterial lesion. CD36 possesses a variety of posttranslational modifications, among them N-glycosylation and O-GlcNAc modification. Some of the roles of these modifications on CD36 are known, such as N-linked glycosylation, which provides proper folding and trafficking to the plasma membrane in the human embryonic kidney. This study aimed to determine whether variations in the availability of UDP-GlcNAc could impact Rab-5-mediated endocytic trafficking and, therefore, the cellular localization of CD36. These preliminary results suggest that the availability of the substrate UDP-GlcNAc, modulated in response to treatment with Thiamet G (TMG), OSMI-1 (O-GlcNAcylation enzymes modulators) or Azaserine (HBP modulator), influences the localization of CD36 in J774 macrophages, and the endocytic trafficking as evidenced by the regulatory protein Rab-5, between the plasma membrane and the cytoplasm.


Assuntos
Antígenos CD36 , Macrófagos , Antígenos CD36/metabolismo , Macrófagos/metabolismo , Animais , Camundongos , Linhagem Celular , Glicosilação , Membrana Celular/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Hexosaminas/metabolismo , Hexosaminas/biossíntese , Proteínas rab5 de Ligação ao GTP/metabolismo , Transporte Proteico , Vias Biossintéticas , Processamento de Proteína Pós-Traducional
5.
Ann Vasc Surg ; 109: 273-283, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069123

RESUMO

BACKGROUND: Graft/stent thrombosis is the leading cause of amputation in patients over 60, and while dual antiplatelet therapy is the standard of care, there is a significant variability in platelet response and limited guidance on measuring effectiveness. Thromboelastography with platelet mapping (TEG-PM) can objectively detail an individual's coagulation profile, namely the strength of the clot and its response to antiplatelet medication. Although TEG-PM has been used for predicting postoperative bleeding and assessing platelet dysfunction in traumatic brain injury, its application in thrombosis diseases such as peripheral artery disease remains unexplored. The aim of this observational study was to determine if objective measures of clot strength could predict a high clinical risk of thrombosis. METHODS: Patients >60 years with peripheral artery disease undergoing revascularization were prospectively evaluated from 2021 to 2023. They were clinically followed for 1 year to detect any thrombotic events. TEG-PM was used to objectively evaluate coagulation profiles in patients at 1, 3, 6, and 9 months. These follow-up periods were chosen based on studies showing that 1-3 month intervals in the first year after lower extremity revascularization optimize therapy and risk control. The TEG-PM data preceding a thrombotic/stenotic event in patients with thrombosis was compared to the last known well TEG-PM event in those without a thrombotic/stenotic event. We stratified the groups based on the occurrence of thrombosis/stenotic events. Descriptive statistics were applied to characterize each group and a chi-square test was conducted to assess the variance between both groups. An unpaired t-test was run to identify differences in platelet function. Receiver operating characteristic analysis was performed to determine the optimal TEG-PM cutoff for predicting a higher risk of thrombosis. RESULTS: One hundred and fifty-eight patients were analyzed, from whom 28 (17.7%) experienced a thrombotic event. The thrombosis cohort exhibited significantly greater MAADP, MAFibrin, and MAThrombin [50.2 vs. 40.0, P < 0.05], [18.19 vs. 14.64, P < 0.05], and [63.8 vs. 58.5, P < 0.05], respectively, indicative of greater clot strength. By receiver operating characteristic analysis, the optimal predictor cut-off for MAADP, indicating a higher risk of thrombosis, was >42 mm [P < 0.05] with 82% sensitivity and 50% specificity. CONCLUSIONS: An increase in clot strength was found to be predictive of thrombosis/stenosis within 30 days. Using a MAADP cut-off greater than 42 mm might serve as an alternative approach to tailor the use of antiplatelet medication, potentially reducing the risk of thrombosis.

6.
Ann Vasc Surg ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39067844

RESUMO

BACKGROUND: Elevated glycated hemoglobin (HbA1c) is associated with vascular complications, including arterial thrombosis post-revascularization. However, the objective relationship between levels of HbA1c and coagulation profiles has not been established. This study aims to determine the association between specific coagulation parameters and variations in HbA1c in patients undergoing lower extremity revascularization. METHODS: Patients with Peripheral Artery Disease (PAD) undergoing revascularization were prospectively evaluated between December 2020 and July 2023. Patients were categorized based on their HbA1c levels, and their thromboelastography with platelet mapping (TEG-PM) results were compared at baseline, post-operatively day 1, 1 month, 3 months and 6 months. The parameters included Maximum Amplitude (MA) with both adenosine diphosphate (ADP) and arachidonic acid (AA), as well as ADP and AA percent aggregation indicating clot strength. The study further assessed the differences in these parameters between groups with varying HbA1c levels through the use of unpaired Student t test for pairwise analysis and Mann-Whitney U tests. RESULTS: Among 830 samples, those with HbA1c above 6.5 demonstrated a significant increase in ADP MA (52.6 vs. 43.5, p<0.01), AA MA (36.6 vs. 29.65, p<0.05), clot strength without platelets ActF MA (activator F: 13.10 vs. 10.80, p<0.01), and heparin neutralized uninhibited clot strength from thrombin activation HKH MA (heparinized kaolin with heparinase: 61.10 vs. 57.70, p<0.01) values at baseline. Post-operatively, patients with HbA1c levels greater than 6.5 had higher median functional fibrinogen CFF FLEV levels (citrated functional fibrinogen: 40.95 vs. 371.35, p<0.05) and higher formation of fibrin in response to stimulation of thrombin by tissue factor CFF MA values (22.90 vs. 20.40, p<0.05) when measured within 36 hours of intervention, with these trends staying consistent during the 1-month follow-up visit. The trend analysis revealed a progressive increase in ADP MA values with rising HbA1c values, indicating a unit increase in the thrombotic risk relationship. Regression analysis showed a positive relationship between HbA1c and both ADP MA (a 2.261 unit increase for each unit increase in HbA1c) and AA MA. The R-square values indicate that HbA1c only explains a small percentage of the variance in these parameters, suggesting the confounding influence of other factors contributing to thrombosis. CONCLUSION: Elevated HbA1c levels appear to be associated with pro-thrombotic tendencies in clot dynamics as measured by TEG-PM, particularly in parameters related to platelet function. HbA1c explains a limited proportion of the variability in these measures, emphasizing the need for a comprehensive approach to evaluating clotting profiles in patients. This study lays the groundwork for further investigation into personalized antithrombotic strategies for patients with varying HbA1c levels.

7.
Ann Surg ; 280(3): 463-472, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38860382

RESUMO

OBJECTIVE: The aim of this prospective study was to (1) objectively quantify the impact of sex on platelet function in patients with peripheral artery disease (PAD) taking antiplatelet and anticoagulant medications and (2) to develop and test a personalized, iterative algorithm that personalizes thromboprophylaxis that incorporates platelet function testing. BACKGROUND: Women with PAD have worse outcomes as compared with their male counterparts despite having lower risk factors. This health disparity may be mitigated by personalizing thromboprophylaxis regimens. METHODS: Patients undergoing revascularization were enrolled. Serial thromboelastography (TEG) and TEG with platelet mapping (TEG-PM) were performed up to 6 months postoperatively to determine objective coagulation profiles. In a subset of patients, the Antiplatelet Coagulation Exactness (ACE) algorithm was implemented, where patients were iteratively evaluated with TEG and given antiplatelet medications to maintain platelet inhibition at >29%. Statistical analysis was performed using unpaired t test, analysis of variance, and Fisher exact test. RESULTS: One hundred eighty-one patients met the study criteria. Fifty-eight (32%) patients were females and 123 (68%) were males. In the Aspirin cohort, females showed significantly greater clot strength as maximum amplitude - arachidonic acid (MA AA ) and significantly lower platelet inhibition than males: (37.26 vs 32.38, P <0.01) and (52.95% vs 61.65%, P <0.05), respectively. In the Clopidogrel cohort, females showed higher Maximum Amplitude - Adenosine Diphosphate (MA ADP ) (42.58 vs 40.35, P = not significant [NS]) compared with males. Females on dual antiplatelet therapy had higher MA ADP (39.74 vs 35.07, P =NS) and lower platelet inhibition (45.25% vs 54.99%, P= NS) than males. The incidence of thrombosis of the revascularized segment, defined as thrombotic event, was objectively identified on an arterial duplex. Women showed significantly higher thrombotic events than men (22.95% vs 10.57%, P< 0.05) on the same medication. In our pilot study, implementation of the ACE algorithm led to a significant decrease in the thrombosis rate (3%), including nonthrombotic events for females, versus the historic thrombotic rate (22%) from our institution. CONCLUSIONS: Women with PAD exhibited higher platelet reactivity, clot strength, and reduced platelet inhibition in response to antiplatelet therapy. The use of the ACE algorithm to tailor antiplatelet medication in patients with PAD post-revascularization, resulted in a significant decrease in thrombotic event rates. This may serve as an opportune way to mitigate outcome sex-specific disparities caused by inadequate thromboprophylaxis in women.


Assuntos
Anticoagulantes , Doença Arterial Periférica , Inibidores da Agregação Plaquetária , Tromboelastografia , Humanos , Feminino , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/complicações , Idoso , Estudos Prospectivos , Anticoagulantes/uso terapêutico , Fatores Sexuais , Pessoa de Meia-Idade , Algoritmos , Testes de Função Plaquetária , Trombose/prevenção & controle , Trombose/etiologia
8.
Hepatol Commun ; 8(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38704651

RESUMO

BACKGROUND: Alcohol-associated liver disease is a complex disease regulated by genetic and environmental factors such as diet and sex. The combination of high-fat diet and alcohol consumption has synergistic effects on liver disease progression. Female sex hormones are known to protect females from liver disease induced by high-fat diet. In contrast, they promote alcohol-mediated liver injury. We aimed to define the role of female sex hormones on liver disease induced by a combination of high-fat diet and alcohol. METHODS: Wild-type and protein arginine methyltransferase (Prmt)6 knockout female mice were subjected to gonadectomy (ovariectomy, OVX) or sham surgeries and then fed western diet and alcohol in the drinking water. RESULTS: We found that female sex hormones protected mice from western diet/alcohol-induced weight gain, liver steatosis, injury, and fibrosis. Our data suggest that these changes are, in part, mediated by estrogen-mediated induction of arginine methyltransferase PRMT6. Liver proteome changes induced by OVX strongly correlated with changes induced by Prmt6 knockout. Using Prmt6 knockout mice, we confirmed that OVX-mediated weight gain, steatosis, and injury are PRMT6 dependent, while OVX-induced liver fibrosis is PRMT6 independent. Proteomic and gene expression analyses revealed that estrogen signaling suppressed the expression of several components of the integrin pathway, thus reducing integrin-mediated proinflammatory (Tnf, Il6) and profibrotic (Tgfb1, Col1a1) gene expression independent of PRMT6 levels. Integrin signaling inhibition using Arg-Gly-Asp peptides reduced proinflammatory and profibrotic gene expression in mice, suggesting that integrin suppression by estrogen is protective against fibrosis development. CONCLUSIONS: Taken together, estrogen signaling protects mice from liver disease induced by a combination of alcohol and high-fat diet through upregulation of Prmt6 and suppression of integrin signaling.


Assuntos
Estradiol , Integrinas , Camundongos Knockout , Proteína-Arginina N-Metiltransferases , Transdução de Sinais , Animais , Camundongos , Feminino , Transdução de Sinais/efeitos dos fármacos , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Integrinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ovariectomia , Etanol/efeitos adversos , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/prevenção & controle , Cirrose Hepática Alcoólica/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
9.
Pediátr. Panamá ; 53(1): 20-24, 30 de abril de 2024.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1553027

RESUMO

El Staphylococcus aureus causa una variedad de infecciones localizadas e invasivas supurativas y 3 síndromes mediados por toxinas: Síndrome de choque tóxico estafilocócico (STSS, por sus siglas en ingles), síndrome de piel escaldada estafilocócica (SSSS) e intoxicación alimentaria1. La escarlatina estafilocócica está relacionada con las toxinas del STSS y SSSS. De hecho, se pudieron describir dos síndromes diferentes cada uno relacionado a un tipo de toxina que eran formas atenuadas de estas entidades. El curso de esta patología generalmente es autolimitado, pero puede evolucionar rápidamente a enfermedad severa que ponga en peligro la vida. Un entendimiento de este conjunto de patologías nos permite abordar al paciente de una manera oportuna, manteniendo la vigilancia y en caso de ser necesario intervenir para evitar el advenimiento del STSS que puede desembocar en falla orgánica múltiple e incluso la muerte. Esta revisión se trata de un caso atendido en la unidad de quemados del Hospital del Niño Dr. José Renán Esquivel (HDNJRE) en el mes de mayo del 2023 con quemadura por contacto complicada con escarlatina estafilocócica. (provisto por Infomedic International)


Staphylococcus aureus causes a variety of localized and invasive suppurative infections and 3 toxin-mediated syndromes: staphylococcal toxic shock syndrome (STSS), staphylococcal scalded skin syndrome (SSSS) and food poisoning1 . Staphylococcal scarlet fever is related to STSS and SSSS toxins. In fact, two different syndromes each related to a type of toxin could be described which were attenuated forms of these entities. The course of this pathology is usually self-limiting, but can rapidly progress to severe life-threatening disease. An understanding of this set of pathologies allows us to approach the patient in a timely manner, maintaining vigilance and if necessary intervening to prevent the advent of STSS that can lead to multiple organ failure and even death. This review is about a case treated at the burn unit of the Hospital del Niño Dr. José Renán Esquivel (HDNJRE) in May 2023 with contact burn complicated by staphylococcal scarlet fever. (provided by Infomedic International)

10.
Dent Med Probl ; 61(1): 121-128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37098828

RESUMO

One potential application of neural networks (NNs) is the early-stage detection of oral cancer. This systematic review aimed to determine the level of evidence on the sensitivity and specificity of NNs for the detection of oral cancer, following the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) and Cochrane guidelines. Literature sources included PubMed, ClinicalTrials, Scopus, Google Scholar, and Web of Science. In addition, the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the risk of bias and the quality of the studies. Only 9 studies fully met the eligibility criteria. In most studies, NNs showed accuracy greater than 85%, though 100% of the studies presented a high risk of bias, and 33% showed high applicability concerns. Nonetheless, the included studies demonstrated that NNs were useful in the detection of oral cancer. However, studies of higher quality, with an adequate methodology, a low risk of bias and no applicability concerns are required so that more robust conclusions could be reached.


Assuntos
Neoplasias Bucais , Redes Neurais de Computação , Humanos , Sensibilidade e Especificidade , Neoplasias Bucais/diagnóstico
11.
Biomed Res Int ; 2023: 6152905, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027043

RESUMO

According to the World Health Organization, cardiovascular diseases (CVDs) are the leading cause of death worldwide across nearly all ethnic groups. Inherited cardiac conditions comprise a wide spectrum of diseases that affect the heart, including abnormal structural features and functional impairments. In Latin America, CVDs are the leading cause of death within the region. Factors such as population aging, unhealthy diet, obesity, smoking, and a sedentary lifestyle have increased the risk of CVD. The Latin American population is characterized by its diverse ethnic composition with varying percentages of each ancestral component (African, European, and Native American ancestry). Short tandem repeats (STRs) are DNA sequences with 2-6 base pair repetitions and constitute ~3% of the human genome. Importantly, significant allele frequency variations exist between different populations. While studies have described that STRs are in noncoding regions of the DNA, increasing evidence suggests that simple sequence repeat variations may be critical for proper gene activity and regulation. Furthermore, several STRs have been identified as potential disease predisposition markers. The present review is aimed at comparing and describing the frequencies of autosomal STR polymorphisms potentially associated with cardiovascular disease predisposition in Latin America compared with other populations.


Assuntos
Doenças Cardiovasculares , Genética Populacional , Humanos , América Latina/epidemiologia , Doenças Cardiovasculares/genética , Frequência do Gene , Repetições de Microssatélites , Suscetibilidade a Doenças
12.
J Thorac Dis ; 15(9): 4757-4764, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37868906

RESUMO

Background: Smoking relapse after surgical resection for lung cancer (LC) remains a health concern. This study aims to determine various factors associated with postoperative smoking relapse in patients undergoing surgical resection for stage I non-small cell lung cancer (NSCLC) at an urban safety net hospital. Methods: We analyzed the demographic and clinical variables of all patients who underwent surgical resection for stage I NSCLC from 2002 to 2016 at our institution. Based on the post-operative smoking history, we segregated the cohort into two groups: relapse and abstinent. Chi-squared and analysis of variance tests were used to identify the variables that registered a significant difference between the two groups. Further, we used univariable and multivariable logistic regression to determine association between variables and smoking relapse. Results: We analyzed data from 168 patients, excluding those with inadequate smoking history and never smokers. In total, 64 (38.1%) patients experienced smoking relapse, and 104 (61.9%) remained abstinent. The age, annual income, and race showed significant differences between the two groups. Multivariable logistic regression reflected that black patients had higher odds of relapse than white patients [odds ratio (OR) =3.26, confidence interval (CI): 1.54-6.89, P=0.002] and the chances of relapse decreased as the age increased (5-year age gap, OR =0.70, CI: 0.58-0.85, P<0.001). Conclusions: Black race and younger age at the time of surgery are associated with smoking relapse after surgery for stage I NSCLC. Targeted smoking cessation programs catered towards these patient groups may help reduce the prevalence of post-operative smoking.

13.
Mol Cancer Res ; 21(10): 1023-1036, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37363949

RESUMO

Activating estrogen receptor alpha (ER; also known as ESR1) mutations are present in primary endometrial and metastatic breast cancers, promoting estrogen-independent activation of the receptor. Functional characterizations in breast cancer have established unique molecular and phenotypic consequences of the receptor, yet the impact of ER mutations in endometrial cancer has not been fully explored. In this study, we used CRISPR-Cas9 to model the clinically prevalent ER-Y537S mutation and compared results with ER-D538G to discover allele-specific differences between ER mutations in endometrial cancer. We found that constitutive activity of mutant ER resulted in changes in the expression of thousands of genes, stemming from combined alterations to ER binding and chromatin accessibility. The unique gene expression programs resulted in ER-mutant cells developing increased cancer-associated phenotypes, including migration, invasion, anchorage-independent growth, and growth in vivo. To uncover potential treatment strategies, we identified ER-associated proteins via Rapid Immunoprecipitation and Mass Spectrometry of Endogenous Proteins and interrogated two candidates, CDK9 and NCOA3. Inhibition of these regulatory proteins resulted in decreased growth and migration, representing potential novel treatment strategies for ER-mutant endometrial cancer. IMPLICATIONS: This study provides insight into mutant ER activity in endometrial cancer and identifies potential therapies for women with ER-mutant endometrial cancer.


Assuntos
Neoplasias da Mama , Neoplasias do Endométrio , Feminino , Humanos , Alelos , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Neoplasias da Mama/patologia , Mutação , Neoplasias do Endométrio/genética , Fenótipo
14.
Pharmaceuticals (Basel) ; 16(4)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37111300

RESUMO

Protozoan parasite diseases cause significant mortality and morbidity worldwide. Factors such as climate change, extreme poverty, migration, and a lack of life opportunities lead to the propagation of diseases classified as tropical or non-endemic. Although there are several drugs to combat parasitic diseases, strains resistant to routinely used drugs have been reported. In addition, many first-line drugs have adverse effects ranging from mild to severe, including potential carcinogenic effects. Therefore, new lead compounds are needed to combat these parasites. Although little has been studied regarding the epigenetic mechanisms in lower eukaryotes, it is believed that epigenetics plays an essential role in vital aspects of the organism, from controlling the life cycle to the expression of genes involved in pathogenicity. Therefore, using epigenetic targets to combat these parasites is foreseen as an area with great potential for development. This review summarizes the main known epigenetic mechanisms and their potential as therapeutics for a group of medically important protozoal parasites. Different epigenetic mechanisms are discussed, highlighting those that can be used for drug repositioning, such as histone post-translational modifications (HPTMs). Exclusive parasite targets are also emphasized, including the base J and DNA 6 mA. These two categories have the greatest potential for developing drugs to treat or eradicate these diseases.

15.
Revista Digital de Postgrado ; 12(1): 357, abr. 2023. ilus, graf
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1509835

RESUMO

El Síndrome de Chediak-Higashi (SCH) es una patología de herencia autosómica recesiva debido principalmente a mutaciones del gen regulador del tráfico lisosómico (LYST), causando grados dermatológicamente diferentes de albinismo óculocutáneo, infecciones recurrentes, disfunción fagocítica primaria, en el desarrollo y proliferación de todas las líneas celulares. Se presenta caso de preescolar masculino de 2 años de edad, ingresado por aumento de volumen bilateral en región cervical y fiebre, en malas condiciones generales, con áreas de hiperpigmentación en piel, cabello y cejas de coloración grisácea, adenopatías generalizadas y visceromegalias; leucocitosis con linfocitosis y neutropenia, anemia, trombocitopenia, hipoalbuminemia, hipertrigliceridemia e hiperferritinemia; en vista de la infrecuente coexistencia de dichas características con albinismo óculocutáneo; es evaluado por hematología y dermatología evidenciándose inclusiones citoplasmáticas y melanosomas gigantes, respectivamente, compatibles con SCH, confirmándose diagnóstico. El conocimiento del SCH es importante para la oportuna sospecha clínica-diagnóstica e inicio de protocolos terapéuticos en consenso, que garanticen un manejo eficaz para su sobrevida(AU)


Chediak-Higashi syndrome (SCH) is an auto somal recessive in herited pathology mainly due to mutations ofthe LYST gene, causing dermatologically different degrees of oculocutaneous albinism, recurrent infections, primary phagocytic dysfunction, in the development and proliferation of all cell lines. We present a case of a 2-year-old male preschool, admitted due to bilateral volume increase in thecervical region and fever, in poor general conditions, with areas of hyperpigmentation in skin, hair and eyebrows of grayish coloration, generalized lymphadenopathy and visceromegaly; leukocytosis with lymphocytosis and neutropenia, anemia, thrombocytopenia, hypoalbuminemia, hypertriglyceridemia,and hyperferritinemia; in view of the infrequent coexistence of these characteristics with oculocutaneous albinism; it isevaluated by hematology and dermatology, showing cytoplasmicinclusions and giant melanosomes, respectively, compatiblewith SCH, confirming the diagnosis. Knowledge of SCH is important for timely clinical-diagnostic suspicion and initiation of consensus therapeutic protocols that guarantee effective management for survival(AU)


Assuntos
Humanos , Masculino , Pré-Escolar , Síndrome de Chediak-Higashi/patologia , Albinismo Oculocutâneo/genética , Antibacterianos
16.
Odontoestomatol ; 25(42)2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1529061

RESUMO

Las lesiones periapicales son procesos inflamatorios que generan la reabsorción de los tejidos mineralizados. En pacientes diabéticos este proceso puede verse afectado. Este trabajo tiene como objetivo identificar la asociación entre la diabetes mellitus y las lesiones periapicales y conocer si los pacientes diabéticos presentan mayor prevalencia y severidad. Se realizó una revisión amplia de la literatura disponible, de tipo narrativa. Se consultaron las bases de datos PubMed (Medline) y SciELO y los recursos Timbó y Google Scholar. Los criterios de exclusión fueron: trabajos anteriores al año 2010 y reportes de caso Se incluyeron artículos anteriores a la fecha de exclusión por considerarse relevantes para el trabajo. A pesar que la evidencia científica continúa siendo insuficiente y el diseño de los estudios debe mejorarse, se demuestra asociación entre lesiones periapicales y diabetes mellitus. Esto implica que los pacientes diabéticos podrían presentar mayor prevalencia y severidad de lesiones.


As lesões periapicais são processos inflamatórios que geram a reabsorção de tecidos mineralizados. Em pacientes diabéticos este processo pode ser afetado. Este trabalho tem como objetivo identificar a associação entre diabetes mellitus e lesões periapicais e saber se os pacientes diabéticos apresentam maior prevalência e gravidade. Foi realizada uma revisão abrangente da literatura disponível, do tipo narrativa. Foram consultadas as bases de dados PubMed (Medline) e SciELO e os recursos Timbó e Google Acadêmico. Os critérios de exclusão foram: trabalhos anteriores ao ano de 2010 e relatos de casos.Os artigos anteriores à data de exclusão foram incluídos por serem considerados pertinentes ao trabalho. Apesar de as evidências científicas ainda serem insuficientes e o delineamento dos estudos precisar ser aprimorado, foi demonstrada uma associação entre lesões periapicais e diabetes mellitus. Isso implica que os pacientes diabéticos podem ter maior prevalência e gravidade das lesões.


Summary Periapical lesions are inflammatory processes that generate the resorption of mineralized tissues. In diabetic patients this process may be affected. This work aims to identify the association between diabetes mellitus and periapical lesions and to know if diabetic patients have a higher prevalence and severity. A comprehensive review of the available literature, of a narrative type, was carried out. The PubMed (Medline) and SciELO databases and the Timbó and Google Scholar resources were consulted. The exclusion criteria were: works prior to the year 2010 and case reports. Articles prior to the exclusion date were included, as they were considered relevant to the work. Despite the fact that the scientific evidence is still insufficient and the design of the studies should be improved, an association between periapical lesions and diabetes mellitus has been demonstrated. This implies that diabetic patients could have a higher prevalence and severity of lesions.

17.
Rev. Soc. Argent. Diabetes ; 56(suple. 2): 53-59, may. - ago. 2022. ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1396867

RESUMO

En la hipoglucemia secundaria, el tratamiento de la diabetes mellitus (DM) se define ante un valor de glucemia por debajo de 70 mg/dl, pudiendo manifestarse por síntomas autonómicos y neuroglucopénicos, con consecuencias a corto y largo plazo, como el deterioro de las funciones cognitivas y el aumento del riesgo cardiovascular, entre otras. La hipoglucemia en personas con DM1 es más frecuente que en aquellas con DM2. Los factores que incrementan su riesgo son: el retraso en la ingesta de comida, el alcohol, el ejercicio intenso, el ayuno y la neuropatía autonómica. Por otro lado, las hipoglucemias inadvertidas se asocian con un mayor riesgo de hipoglucemia grave. Los niños y adultos mayores son un grupo vulnerable a estos eventos que, en muchos casos, presentan síntomas difíciles de distinguir. A su vez, la hipoglucemia durante el embarazo se asocia con mayor riesgo de complicaciones. Otro grupo importante para detectar estos episodios son los pacientes hospitalizados a fin de disminuir la morbimortalidad asociada a los mismos. La calidad de vida está claramente afectada en los pacientes que sufren episodios de hipoglucemia, por lo cual resulta esencial instaurar estrategias de prevención como la educación, el monitoreo glucémico, realizar modificaciones en la dieta y el ejercicio, y ajustar la medicación. El tratamiento, en caso de no presentar pérdida de conciencia, será por vía oral, de lo contrario, se recurrirá a glucosa endovenosa o glucagón intramuscular.


Hypoglycemia due to treatment of diabetes mellitus (DM) is defined by a blood glucose value below 70 mg/dl, which can manifest itself by autonomic and neuroglycopenic symptoms, with short- and long-term consequences, such as impaired cognitive functions and increased cardiovascular risk, among others. Hypoglycemia in people with DM1 is more frequent than in those with DM2. Factors that increase its risk are: delayed food intake, alcohol, intense exercise, fasting and autonomic neuropathy. On the other hand, inadvertent hypoglycemia is associated with an increased risk of severe hypoglycemia. Children and older adults are a vulnerable group to these events that, in many cases, present symptoms that are difficult to distinguish. Hypoglycemia during pregnancy is associated with an increased risk of complications. Another important group to detect these episodes are hospitalized patients in order to reduce the morbimortality associated with them. Quality of life is clearly affected in patients who suffer episodes of hypoglycemia, so it is essential to implement prevention strategies such as education, glycemic monitoring, dietary and exercise modifications, and medication adjustment. Treatment, if there is no loss of consciousness, will be oral, otherwise, intravenous glucose or intramuscular glucagon will be used.


Assuntos
Diabetes Mellitus , Terapêutica , Glicemia , Hipoglicemia
18.
Rev. Soc. Argent. Diabetes ; 56(supl.2): 53-59, mayo 2022. tab, graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1431398

RESUMO

En la hipoglucemia secundaria, el tratamiento de la diabetes mellitus (DM) se define ante un valor de glucemia por debajo de 70 mg/dl, pudiendo manifestarse por síntomas autonómicos y neuroglucopénicos, con consecuencias a corto y largo plazo, como el deterioro de las funciones cognitivas y el aumento del riesgo cardiovascular, entre otras. La hipoglucemia en personas con DM1 es más frecuente que en aquellas con DM2. Los factores que incrementan su riesgo son: el retraso en la ingesta de comida, el alcohol, el ejercicio intenso, el ayuno y la neuropatía autonómica. Por otro lado, las hipoglucemias inadvertidas se asocian con un mayor riesgo de hipoglucemia grave. Los niños y adultos mayores son un grupo vulnerable a estos eventos que, en muchos casos, presentan síntomas difíciles de distinguir. A su vez, la hipoglucemia durante el embarazo se asocia con mayor riesgo de complicaciones. Otro grupo importante para detectar estos episodios son los pacientes hospitalizados a fin de disminuir la morbimortalidad asociada a los mismos. La calidad de vida está claramente afectada en los pacientes que sufren episodios de hipoglucemia, por lo cual resulta esencial instaurar estrategias de prevención como la educación, el monitoreo glucémico, realizar modificaciones en la dieta y el ejercicio, y ajustar la medicación. El tratamiento, en caso de no presentar pérdida de conciencia, será por vía oral, de lo contrario, se recurrirá a glucosa endovenosa o glucagón intramuscular.


Hypoglycemia due to treatment of diabetes mellitus (DM) is defined by a blood glucose value below 70 mg/dl, which can manifest itself by autonomic and neuroglycopenic symptoms, with short- and long-term consequences, such as impaired cognitive functions and increased cardiovascular risk, among others. Hypoglycemia in people with DM1 is more frequent than in those with DM2. Factors that increase its risk are: delayed food intake, alcohol, intense exercise, fasting and autonomic neuropathy. On the other hand, inadvertent hypoglycemia is associated with an increased risk of severe hypoglycemia. Children and older adults are a vulnerable group to these events that, in many cases, present symptoms that are difficult to distinguish. Hypoglycemia during pregnancy is associated with an increased risk of complications. Another important group to detect these episodes are hospitalized patients in order to reduce the morbimortality associated with them. Quality of life is clearly affected in patients who suffer episodes of hypoglycemia, so it is essential to implement prevention strategies such as education, glycemic monitoring, dietary and exercise modifications, and medication adjustment.

19.
Rev. estomatol. Hered ; 32(2): 119-128, abr.-jun. 2022. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1409338

RESUMO

RESUMEN Los estreptococos del grupo viridans (EGV) son un grupo heterogéneo de bacterias saprófitas anaerobias facultativas que forman parte de la flora normal de cavidad oral. El incremento de la resistencia antibiótica de este grupo de bacterias cobra importancia en pacientes hospitalizados con terapia antibiótica prolongada, en los cuales estos microorganismos pueden ser sustituidos por bacterias multirresistentes. Objetivos: Determinar el porcentaje de cepas de EGV aisladas de cavidad oral resistentes a los antibióticos utilizados en el tratamiento de diversas patologías infecciosas hospitalarias. Material y Métodos: Estudio observacional descriptivo en el que se incluyeron 60 pacientes hospitalizados con historia de terapia antibiótica por más de 3 semanas. Las muestras se procesaron siguiendo protocolos estandarizados de recolección, aislamiento e identificación para EGV de cavidad oral y un protocolo de pruebas de sensibilidad antibiótica. Los resultados se muestran en tablas y gráficas de frecuencia. Resultados: La principal indicación para terapia antibiótica intrahospitalaria fue infección orofacial: 28,33%. La penicilina fue el antibiótico más utilizado ya sea en terapia única, combinada o múltiple en todos los pacientes. Se aislaron en total 108 cepas de EGV, con un promedio de 1,8 cepas por paciente. La especie predominantemente identificada fue S. mutans. El 96,3% de las cepas de EGV fue sensible a todos los antibióticos incluidos en el panel. Conclusiones: El uso de distintas combinaciones y modalidades de terapia antibiótica no tiene efecto en la susceptibilidad de EGV aislados de cavidad oral en pacientes hospitalizados, independiente de la duración del tratamiento.


ABSTRACT Viridans group streptococci (VGS) are a heterogeneous group of saprophytic facultative anaerobic bacteria that are part of the normal flora of the oral cavity. The increased resistance to multiple antibiotics in this group of bacteria becomes important in prolonged antibiotic therapies inpatient where these common microorganisms are replaced by multi-resistant bacteria. Objectives: To determine the percentage of VGS strains isolated from oral cavity resistant to antibiotics used in hospital infectious diseases. Material and methods: This is a descriptive cross-sectional study that included 60 hospitalized patients with a history of antibiotic therapy for more than 3 weeks. The samples were processed following standardized protocols for collection, isolation and identification of oral cavity VGS and a protocol of antibiotic susceptibility testing. The results are shown in tables and graphics of absolute and relative frequencies. Results: The main indication for antibiotic therapy was orofacial infection with a 28.33%. Penicillin was the antibiotic further used either in single, combined or multiple therapies in all patients. A total of 108 samples (1.8 per patient swabs) were collected. The predominantly identified specie was Streptococcus mutans. The 96.3% of all VGS strains were sensitive to all antibiotics included in the panel. Conclusion: Using different combinations and types of antibiotic therapy inpatient has no effect on the susceptibility of VGS isolated from oral cavity separate from treatment.

20.
Rev. Nutr. (Online) ; 35: e220173, 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1422819

RESUMO

ABSTRACT Objective: To evaluate the consumption of processed and ultra-processed foods in Paraguayan adults and its relationship with quality of life and sleep quality. Methods: A cross-sectional descriptive observational study was carried out on Paraguayan adults in May 2022. An online survey was applied in which sociodemographic data, frequency of food consumption using the NOVA classification and Pan American Health Organization criteria, quality of life evaluated by the European Quality of Life-5 Dimensions and report of hours of sleep were collected. Results: A total of 273 Paraguayan adults were included in the study, of which 71.1% were female, 51.6% lived in the capital, 53.1% were single, 66% had a university educational level and the average age was 36.48±13.2. Regarding the consumption of processed and ultra-processed foods, the critical nutrients most consumed daily were free sugars by 34.0%, and fats by 23.4% of the population. The global quality of life index was low (0,58±0,05) and 69.0% reported insufficient hours of sleep. Statistically significant relationships were found between the consumption of processed and ultra-processed foods with quality of life and quality of sleep (p<0.05 for both). Conclusion: The most consumed critical nutrients in the Paraguayan adult population are free sugars and fats, finding a significant relationship between the consumption of processed and ultra-processed foods with quality of life and quality of sleep.


RESUMO Objetivo: Avaliar o consumo de alimentos processados e ultraprocessados em adultos paraguaios e sua relação com a qualidade de vida e qualidade do sono. Métodos: Foi realizado um estudo observacional descritivo transversal em adultos paraguaios em maio de 2022. Foi aplicado um questionário online onde foram questionados datos sociodemográficos, frequência de consumo alimentar pela classificação NOVA e critérios da Organização Pan-Americana da Saúde, qualidade de vida avaliada pelo Qualidade de Vida Europeia-5 Dimensões - foram coletados e relato de horas de sono. Resultados: Foram incluídas no estudo 273 paraguaios, das quais 71,1% eram do sexo feminino, 51,6% residiam na capital, 53,1% eram solteiras, 66,0% tinham nível universitário e a média de idade foi de 36,48±13,2 anos. Em relação ao consumo de alimentos processados e ultraprocessados, os nutrientes críticos mais consumidos diariamente foram os açúcares livres por 34.0% e as gorduras por 23,4% da população. O índice global de qualidade de vida foi baixo (0,58±0,05) e 69.0% relataram horas insuficientes de sono. Foram encontradas relações estatisticamente significativas entre o consumo de alimentos processados e ultraprocessados com qualidade de vida e qualidade do sono (p<0,05 para ambos). Conclusão: Os nutrientes críticos mais consumidos na população adulta paraguaia são os açúcares e gorduras livres, encontrando uma relação significativa entre o consumo de alimentos processados e ultraprocessados com a qualidade de vida e qualidade do sono.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Qualidade de Vida , Qualidade do Sono , Alimento Processado , Paraguai/etnologia , Estudos Transversais , Inquéritos e Questionários , Ingestão de Alimentos/etnologia , Fatores Sociodemográficos , Duração do Sono
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