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1.
J Environ Sci (China) ; 147: 332-341, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003051

RESUMO

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.


Assuntos
Arsênio , Exposição Ambiental , Síndrome Metabólica , Ácido Úrico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arsênio/sangue , Arsênio/toxicidade , China/epidemiologia , População do Leste Asiático , Exposição Ambiental/efeitos adversos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/sangue , Ácido Úrico/sangue
2.
J Environ Sci (China) ; 147: 382-391, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003056

RESUMO

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.


Assuntos
Arsênio , Exposição Ambiental , Estresse Oxidativo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , 8-Hidroxi-2'-Desoxiguanosina , Arsênio/toxicidade , Biomarcadores/urina , China , Estudos Transversais , Dano ao DNA , População do Leste Asiático , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Estudos Longitudinais , Estresse Oxidativo/efeitos dos fármacos
3.
S D Med ; 77(1): 31-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38986146

RESUMO

This case report presents an occurrence of three generalized seizures within 30 minutes of ingestion of lysergic acid diethylamide (LSD) in a 15-year-old female patient with treatment-resistant depressive disorder recently started on low-dose lithium therapy. She had no personal or family history of seizure, brain injury or other neurological disorder. The patient had a history of monthly LSD use on several occasions in the setting of ongoing fluoxetine and longacting bupropion (Wellbutrin XL) treatment, with seizures occurring only after initiation of lithium. Although the definitive causal link cannot be established, this case report suggests an increased seizure risk with combination of LSD and lithium, even at subtherapeutic serum lithium levels. This case emphasizes the need for further research, careful clinical practice, and patient education regarding the potential dangers of using psychedelic substances with psychopharmacological treatment.


Assuntos
Dietilamida do Ácido Lisérgico , Convulsões , Humanos , Feminino , Adolescente , Dietilamida do Ácido Lisérgico/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Alucinógenos/efeitos adversos , Alucinógenos/administração & dosagem , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico
4.
BMJ Open ; 14(7): e085637, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38986559

RESUMO

INTRODUCTION: Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock. METHODS AND ANALYSIS: This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers. ETHICS AND DISSEMINATION: Ethics approval has been provided by Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000499785.


Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateteres Venosos Centrais , Neoplasias , Humanos , Criança , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres Venosos Centrais/efeitos adversos , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Ácido Edético/uso terapêutico , Austrália , Trombose/prevenção & controle , Trombose/etiologia , Nova Zelândia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Qualidade de Vida , Heparina/efeitos adversos , Heparina/administração & dosagem , Heparina/uso terapêutico
5.
Antimicrob Resist Infect Control ; 13(1): 75, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992708

RESUMO

BACKGROUND: Nasal carriage of Staphylococcus aureus is a risk factor for surgical site infections (SSI) in orthopaedic surgery. The efficacy of decolonisation for S. aureus on reducing the risk of SSI is uncertain in this speciality. The objective was to evaluate the impact of a nasal screening strategy of S. aureus and targeted decolonisation on the risk of S. aureus SSI. METHODS: A retrospective pre-post and here-elsewhere study was conducted between January 2014 and June 2020 in 2 adult orthopaedic surgical sites (North and South) of a French university hospital. Decolonisation with Mupirocin and Chlorhexidine was conducted in S. aureus carriers starting February 2017 in the South site (intervention group). Scheduled surgical procedures for hip, knee arthroplasties, and osteosyntheses were included and monitored for one year. The rates of S. aureus SSI in the intervention group were compared to a historical control group (South site) and a North control group. The risk factors for S. aureus SSI were analysed by logistic regression. RESULTS: A total of 5,348 surgical procedures was included, 100 SSI of which 30 monomicrobial S. aureus SSI were identified. The preoperative screening result was available for 60% (1,382/2,305) of the intervention group patients. Among these screenings, 25.3% (349/1,382) were positive for S. aureus and the efficacy of the decolonisation was 91.6% (98/107). The rate of S. aureus SSI in the intervention group (0.3%, 7/2,305) was not significantly different from the historical control group (0.5%, 9/1926) but differed significantly from the North control group (1.3%, 14/1,117). After adjustment, the risk factors of S. aureus SSI occurrence were the body mass index (ORaper unit, 1.05; 95%CI, 1.0-1.1), the Charlson comorbidity index (ORaper point, 1.34; 95%CI, 1.0-1.8) and operative time (ORaper minute, 1.01; 95%CI, 1.00-1.02). Having benefited from S. aureus screening/decolonisation was a protective factor (ORa, 0.24; 95%CI, 0.08-0.73). CONCLUSIONS: Despite the low number of SSI, nasal screening and targeted decolonisation of S. aureus were associated with a reduction in S. aureus SSI.


Assuntos
Antibacterianos , Clorexidina , Mupirocina , Procedimentos Ortopédicos , Infecções Estafilocócicas , Staphylococcus aureus , Infecção da Ferida Cirúrgica , Mupirocina/administração & dosagem , Mupirocina/uso terapêutico , Clorexidina/uso terapêutico , Clorexidina/administração & dosagem , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Estudos Retrospectivos , Infecções Estafilocócicas/prevenção & controle , Feminino , Masculino , Staphylococcus aureus/efeitos dos fármacos , Pessoa de Meia-Idade , Idoso , Procedimentos Ortopédicos/efeitos adversos , Fatores de Risco , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Cuidados Pré-Operatórios , Portador Sadio/tratamento farmacológico , Programas de Rastreamento , França
6.
Trials ; 25(1): 471, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992720

RESUMO

BACKGROUND: Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, The standard treatment recommendation for women with early cervical cancer is radical hysterectomy with pelvic lymph node dissection, however, articles published in recent years have concluded that the treatment outcome of laparoscopic surgery for cervical cancer is inferior to that of open surgery. Thus, we choose a surgically new approach; the laparoscopic cervical cancer surgery in the open state is compared with the traditional open cervical cancer surgery, and we hope that patients can still have a good tumor outcome and survival outcome. This trial will investigate the effectiveness of laparoscopic cervical cancer surgery in the open-state treatment of early-stage cervical cancer. METHOD AND DESIGN: This will be an open-label, 2-armed, randomized, phase-III single-center trial of comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer. A total of 740 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound, and radiology data will be collected at baseline, and then at the study assessments and procedures performed at baseline and 1 week, 6 weeks, and 3 months, and follow-up visits begin at 3 months following surgery and continue every 3 months thereafter for the first 2 years and every 6 months until year 4.5. The primary aim is the rate of disease-free survival at 4.5 years. The secondary aims include treatment-related morbidity, costs and cost-effectiveness, patterns of recurrence, quality of life, pelvic floor function, and overall survival. CONCLUSIONS: This prospective trial aims to show the equivalence of the laparoscopic cervical cancer surgery in the open state versus the transabdominal radical hysterectomy approach for patients with early-stage cervical cancer following a 2-phase protocol. TRIAL REGISTRATION: ChiCTR2300075118. Registered on August 25, 2023.


Assuntos
Histerectomia , Laparoscopia , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Feminino , Histerectomia/métodos , Histerectomia/efeitos adversos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Resultado do Tratamento , Ensaios Clínicos Fase III como Assunto , Adulto , Pessoa de Meia-Idade , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Qualidade de Vida
7.
Med Sci Monit ; 30: e943529, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992933

RESUMO

BACKGROUND Heart failure and end-stage renal disease often coexist, and management of heart failure can be challenging in patients during hemodialysis. Sacubitril-valsartan (SV) is the first drug to receive regulatory approval for use in patients with chronic heart failure with reduced ejection fraction (HFrEF) and New York Heart Association (NYHA) classification II, III, or IV. This study aimed to evaluate the efficacy and safety of SV for use in chronic heart failure patients on maintenance hemodialysis (MHD). MATERIAL AND METHODS From September 2021 to October 2022, 28 patients on MHD with chronic heart failure at the hemodialysis center of Shaanxi Second Provincial People's Hospital were regularly followed. During the 12-week follow-up period, all patients were administered SV at doses of 100-400 mg per day. Biochemical indicators, echocardiographic parameters, life quality scores, and adverse events were evaluated. RESULTS We enrolled 28 patients. Compared with the baseline levels, NYHA class III in these patients treated with SV was significantly decreased from 60.71% to 32.14% (P<0.05), left ventricular ejection fraction (LVEF) was significantly improved from 44.29±8.92% to 53.32±7.88% (P<0.001), the Physical Component Summary (PCS) score was significantly improved from 40.0±6.41 to 56.20±9.86 (P<0.001), and the Mental Component Summary (MCS) score was significantly improved from 39.99±6.14 to 52.59±11.0 (P<0.001). CONCLUSIONS We demonstrated that SV improved NYHA classification and LVEF values of patients on MHD with chronic heart failure and also improved their quality of life.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca , Diálise Renal , Valsartana , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Valsartana/uso terapêutico , Masculino , Feminino , Aminobutiratos/uso terapêutico , Aminobutiratos/farmacologia , Aminobutiratos/efeitos adversos , Compostos de Bifenilo/uso terapêutico , Pessoa de Meia-Idade , Diálise Renal/métodos , Estudos Retrospectivos , Idoso , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Resultado do Tratamento , Qualidade de Vida , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Tetrazóis/uso terapêutico , Tetrazóis/efeitos adversos , Tetrazóis/farmacologia , Doença Crônica
8.
Pharmacol Res Perspect ; 12(4): e1222, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38992963

RESUMO

Gentamicin is an aminoglycoside antibiotic with a rapid bactericidal effect on the treatment of many infections. However, its use at high concentrations for more than 7 days causes nephrotoxic side effects. This study investigated the potential of Resatorvid and alpha lipoic acid (ALA) in mitigating gentamicin-induced nephrotoxicity in rats, considering biochemical, histopathological, and molecular parameters. This study randomly distributed 34 Wistar albino rats into four groups: healthy control (n = 6), Gentamicin (80 mg/kg, n = 7), Gentamicin + Sham (%10 hydroalcoholic solution, n = 7), Gentamicin + Resatorvid (5 mg/kg, n = 7), and Gentamicin + ALA (100 mg/kg, n = 7). Resatorvid treatment led to a statistically significant decrease in urinary IL-18, KIM-1, and NGAL levels, whereas ALA treatment significantly reduced KIM-1 levels compared to the gentamicin-only group. Both Resatorvid and ALA showed partial reductions in urine creatinine levels. Moreover, treatments with Resatorvid and ALA resulted in statistically significant decreases in NRF-2, CAS-3, and NR4A2 expressions. However, only Resatorvid demonstrated a statistically significant decrease in NF-B expression. These findings highlight the potential of Resatorvid in ameliorating gentamicin-induced nephrotoxicity, thereby expanding the therapeutic utility of gentamicin and enhancing its efficacy against infections.


Assuntos
Antibacterianos , Gentamicinas , Ratos Wistar , Ácido Tióctico , Gentamicinas/toxicidade , Gentamicinas/efeitos adversos , Animais , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico , Ratos , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Masculino , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Creatinina/sangue , Creatinina/urina , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Moléculas de Adesão Celular
9.
BMC Pharmacol Toxicol ; 25(1): 41, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997770

RESUMO

BACKGROUND AND AIM: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770). CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.


Assuntos
Antibacterianos , Transtornos da Coagulação Sanguínea , Cefoperazona , Sulbactam , Humanos , Cefoperazona/uso terapêutico , Cefoperazona/efeitos adversos , Sulbactam/uso terapêutico , Sulbactam/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , China , Transtornos da Coagulação Sanguínea/induzido quimicamente , Adulto , Pacientes Internados , População do Leste Asiático
10.
Malar J ; 23(1): 208, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997771

RESUMO

BACKGROUND: To interrupt residual malaria transmission and achieve successful elimination of Plasmodium falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT), without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of haemolysis in patients with G6PD deficiency (G6PDd), PQ use is uncommon. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. METHODS: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and haemoglobin (Hb) concentrations. G6PD levels were measured by a quantiative CareSTART™ POCT S1 biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. RESULTS: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 28-15) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to - 0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PDd ACT + SLD-PQ group (- 0.60 g/dL) than in the G6PDd ACT alone group (- 0.48 g/dL); however, there was no statistically significant difference (P = 0.465). Overall, D14 losses were 0.10 g/dl (95% CI = - 0.00 to 0.20) and 0.05 g/dl (95% CI = - 0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). CONCLUSIONS: This study's findings indicate that using SLD-PQ in combination with ACT is safe for uncomplicated P. falciparum malaria regardless of the patient's G6PD status in Ethiopian settings. Caution should be taken in extrapolating this finding in other settings with diverse G6DP phenotypes.


Assuntos
Antimaláricos , Artemisininas , Deficiência de Glucosefosfato Desidrogenase , Hemoglobinas , Malária Falciparum , Primaquina , Malária Falciparum/tratamento farmacológico , Humanos , Etiópia , Masculino , Primaquina/administração & dosagem , Primaquina/uso terapêutico , Primaquina/efeitos adversos , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Feminino , Estudos Longitudinais , Hemoglobinas/análise , Adolescente , Adulto Jovem , Deficiência de Glucosefosfato Desidrogenase/complicações , Pessoa de Meia-Idade , Criança , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Estudos de Coortes , Pré-Escolar , Plasmodium falciparum/efeitos dos fármacos
11.
Arthritis Res Ther ; 26(1): 129, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997785

RESUMO

BACKGROUND: Despite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised (MNX) rats. METHODS: We evaluated KBP-336's effect on pain-like symptoms in Sprague Dawley (SD) rats on high-fat diet (HFD) that underwent meniscectomy using the von Frey test to measure the 50% paw withdrawal threshold (PWT) and analyzed using one-way ANOVA. Short in vivo studies and in vitro cell receptor expression systems were used to illustrate receptor pharmacology. RESULTS: After 30 weeks on HFD, including an 8-week treatment, female MNX animals receiving KBP-336 4.5 nmol/Kg/72 h had lower body weight and smaller adipose tissues than their vehicle-treated counterparts. After 20 weeks on HFD, including an 8-week treatment, male rats receiving KBP-336 had lower body weight than the vehicle group. In both the female and male rats, the MNX groups on KBP-336 treatment had a higher PWT than the vehicle-treated MNX group. Aiming to identify the receptor influencing pain alleviation, KBP-336 was compared to the long-acting human calcitonin (hCTA). Single-dose studies on 12-week-old male rats showed that hCTA lowers CTX-I without affecting food intake, confirming its calcitonin receptor selectivity. On the metabolic OA model with 18 weeks of HFD, including 6-week treatment, hCTA at 100 nmol/Kg/24 h and KBP-336 at 0.5, 1.5, and 4.5 nmol/Kg/72 h produced significantly higher PWT in MNX animals compared to MNX animals on vehicle treatment. hCTA and KBP-336 at 0.5 nmol/Kg did not affect body weight and fat tissues. CONCLUSION: Overall, KBP-336 improved the pain observed in the metabolic OA model. Calcitonin receptor activation proved to be essential in this antinociceptive effect.


Assuntos
Agonistas dos Receptores da Amilina , Osteoartrite , Ratos Sprague-Dawley , Receptores da Calcitonina , Redução de Peso , Animais , Receptores da Calcitonina/agonistas , Receptores da Calcitonina/metabolismo , Ratos , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Agonistas dos Receptores da Amilina/farmacologia , Feminino , Redução de Peso/efeitos dos fármacos , Analgésicos/farmacologia , Masculino , Dieta Hiperlipídica/efeitos adversos , Humanos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico
12.
Ecotoxicol Environ Saf ; 281: 116664, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38954909

RESUMO

BACKGROUND: Observational studies have reported associations between air pollutants and brain imaging-derived phenotypes (IDPs); however, whether this relationship is causal remains uncertain. METHODS: We conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the causal relationships between 5 types of air pollutants (N=423,796 to 456,380 individuals) and 587 reliable IDPs (N=33,224 individuals). Two-step MR was also conducted to assess whether the identified effects are mediated through the modulation of circulating cytokines (N=8293). RESULTS: We found genetic evidence supporting the association of nitrogen oxides (NOx) with mean intra-cellular volume fraction (ICVF) in the left uncinate fasciculus (IVW ß=-0.42, 95 % CI -0.62 to -0.23, P=1.51×10-5) and mean fractional anisotropy (FA) in the left uncinate fasciculus (IVW ß=-0.42, 95 % CI -0.62 to -0.21, P=4.89×10-5). In further two-step MR analyses, we did not find evidence that genetic predictions of any circulating cytokines mediated the association between NOx and IDPs. CONCLUSION: This study provides evidence for the association between air pollutants and brain IDPs, emphasizing the importance of controlling air pollution to improve brain health.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Encéfalo , Fenótipo , Humanos , Poluição do Ar/efeitos adversos , Poluentes Atmosféricos/toxicidade , Encéfalo/diagnóstico por imagem , Análise da Randomização Mendeliana , Óxidos de Nitrogênio , Citocinas/genética , Citocinas/sangue , Neuroimagem
13.
Ecotoxicol Environ Saf ; 281: 116649, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38954910

RESUMO

Limited evidence has suggested a relationship between phthalate exposure and biological aging. This study investigated the association between phthalate exposure and biological aging, focusing on the mediating role of inflammation and the interaction with dietary nutrient intake. Data were analyzed from a nationwide cross-sectional survey comprising 12,994 participants aged 18 and above. Eight phthalate metabolites were detected in spot urine samples. Biological aging was assessed using the Klemera-Doubal method-biological age (KDM-BA) acceleration, phenotypic age (PA) acceleration, and homeostatic dysregulation (HD). The systemic immune-inflammation index (SII) evaluated systemic inflammation. The individual and combined associations between phthalate exposure and biological aging were assessed using linear regression, weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp). The participants had a mean age of 47 years, with 50.7 % male and 44.8 % non-Hispanic white. Most phthalate metabolites were positively correlated with KDM-BA acceleration (ß = 0.306-0.584), PA acceleration (ß = 0.081-0.281), and HD (ß = 0.016-0.026). Subgroup analysis indicated that men, older individuals, and non-Hispanic whites are particularly sensitive populations. WQS regression and qgcomp analyses consistently indicated a positive association between mixed phthalate exposure and HD, highlighting MEHHP as the most significant contributing metabolite. Mediation analyses showed inflammation partially mediated the association between phthalate metabolites and biological aging. Significant interactions regarding biological aging were found between specific phthalate metabolites and dietary nutrients (carotenoids, vitamins A, B1, B2, B6, B12, niacin, and selenium) intake. These findings indicated that the association between phthalate exposure and biological aging was mediated by inflammation, with nutrient intake mitigating this effect.


Assuntos
Envelhecimento , Biomarcadores , Exposição Ambiental , Inflamação , Ácidos Ftálicos , Humanos , Ácidos Ftálicos/urina , Masculino , Pessoa de Meia-Idade , Inflamação/induzido quimicamente , Estudos Transversais , Feminino , Adulto , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Dieta , Poluentes Ambientais/urina , Idoso , Adulto Jovem , Adolescente
14.
Support Care Cancer ; 32(7): 482, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955817

RESUMO

PURPOSE: The study investigates cryotherapy's efficacy in mitigating Chemotherapy-induced peripheral neuropathy (CIPN), an adverse effect of chemotherapy that often leads to dosage reduction or treatment discontinuation. METHOD: The study was registered with PROSPERO (CRD42023428936). A literature search was conducted using the PubMed, Embase, and Cochrane Library databases. Randomized and nonrandomized controlled trials that investigated the effects of cryotherapy on CIPN were included for systematic review and meta-analysis. The primary outcome for prevention was the incidence of CIPN. RESULTS: We identified 17 trials involving 2,851 patients. In total, 11 trials compared the incidence of CIPN between cryotherapy and control groups. Significant differences in the incidence of CIPN at the midpoint and end of chemotherapy were observed, with risk ratios (RRs) of 0.23 (95% confidence interval [CI] = 0.13 to 0.43) and 0.54 (95% CI = 0.33 to 0.88), respectively. Cryotherapy also significantly reduced the incidence of sensory CIPN, with an RR of 0.67 (95% CI = 0.49 to 0.92). Additionally, cryotherapy demonstrated a significant reduction in the incidence of CIPN in patients with gynecological cancers (RR = 0.24, 95% CI = 0.14 to 0.41). Significantly favorable global quality of life scores following chemotherapy (standardized mean difference = 1.43; 95% CI = 0.50 to 2.36) and relieved neuropathic symptoms were found with cryotherapy. CONCLUSIONS: Cryotherapy demonstrates a pronounced preventive effect against the development of CIPN, providing substantial symptomatic relief and quality of life improvements for patients undergoing chemotherapy. The administration of cryotherapy through the use of frozen gloves and socks, or continuous-flow cooling systems, optimally initiated 15 min prior to and concluded 15 min following chemotherapy, is recommended for achieving maximum therapeutic efficacy.


Assuntos
Antineoplásicos , Crioterapia , Doenças do Sistema Nervoso Periférico , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Doenças do Sistema Nervoso Periférico/terapia , Crioterapia/métodos , Antineoplásicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Incidência , Neoplasias/tratamento farmacológico
15.
Breast Cancer Res ; 26(1): 109, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956693

RESUMO

BACKGROUND: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). METHODS: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. RESULTS: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(ß) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(ß) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). CONCLUSIONS: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.


Assuntos
Densidade da Mama , Mama , Mamografia , Testosterona , Pessoas Transgênero , Humanos , Densidade da Mama/efeitos dos fármacos , Feminino , Adulto , Testosterona/uso terapêutico , Mamografia/métodos , Mama/diagnóstico por imagem , Mama/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Índice de Massa Corporal , Procedimentos de Readequação Sexual/efeitos adversos , Procedimentos de Readequação Sexual/métodos
16.
Per Med ; 21(4): 205-209, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38958204

RESUMO

We report the case of an 87-year-old female patient who was diagnosed with metastatic non-small-cell lung cancer harboring MET exon 14 skipping mutation (MET ex14) and PD-L1 expression of 60%. A first-line treatment with atezolizumab was started with primary resistance. Then, a second-line treatment with capmatinib, a selective type Ib MET tyrosine kinase inhibitor, was started, achieving a partial response. The patient is still alive and on treatment with capmatinib 300 mg twice daily after 20 months, with a good tolerability and no evidence of disease progression.In summary, our patient experienced a long-lasting response (>18 months) with capmatinib as second-line treatment. Further analyses evaluating the efficacy and tolerability of MET tyrosine kinase inhibitors are warranted, especially in the elderly, a non-small-cell lung cancer population whose tumors could more frequently harbor MET ex14 mutation.


[Box: see text].


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Éxons , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas c-met , Humanos , Feminino , Proteínas Proto-Oncogênicas c-met/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Idoso de 80 Anos ou mais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação/genética , Éxons/genética , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Benzamidas/uso terapêutico , Benzamidas/efeitos adversos , Resultado do Tratamento , Acrilamidas/uso terapêutico , Acrilamidas/administração & dosagem , Acrilamidas/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Imidazóis , Triazinas
17.
Ecotoxicol Environ Saf ; 281: 116671, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38959788

RESUMO

BACKGROUND: With the advancement of medical technology, tools such as electrosurgical equipment, laser knives, and ultrasonic scalpels have made modern medical procedures more convenient and effective. However, the generation of surgical smoke during these procedures poses significant health risks to medical personnel. Despite this, only a few studies have examined the literature systematically in this area. By analyzing bibliometric data on surgical smoke, we can gain insights into current research hotspots and forecast future trends. METHODS: This study included literature related to surgical smoke from the Web of Science and China National Knowledge Infrastructure (CNKI) databases, covering the period from 2000 to 2024. We used VOSviewer, CiteSpace, and BioBERT to visualize research trends and hotspots. RESULTS: In the early stages of research, the focus was mainly on the composition, generation mechanisms, and susceptible populations related to surgical smoke. In recent years, with the development of laparoscopic surgery and the global COVID-19 pandemic, research interests have shifted towards occupational protection of healthcare workers and public health. Currently, the research in this field primarily explores the promoting effects of surgical smoke on conditions such as inflammation and tumors, as well as occupational protection and health education for healthcare workers. Disease research focuses heavily on Smoke Inhalation Injury, Infections, Neoplasms, Postoperative Complications, and Inflammation. CONCLUSION: We explored future research directions in the field of surgical smoke using VOSviewer, CiteSpace, and BioBERT. Our findings indicate that current research focuses on investigating the promoting effects of surgical smoke on conditions such as inflammation and tumors, as well as on occupational protection and health education for healthcare workers. We summarized existing preventive measures, aiming to facilitate further research advancements and the translation of research outcomes into clinical results. These efforts provide new insights for advancing research in occupational protection of healthcare workers.


Assuntos
Exposição Ocupacional , Fumaça , Fumaça/efeitos adversos , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Bibliometria , SARS-CoV-2 , China , Pessoal de Saúde/estatística & dados numéricos
18.
Int J Mol Sci ; 25(13)2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38999973

RESUMO

Several hepatic disorders are influenced by gut microbiota, but its role in idiosyncratic drug-induced liver injury (iDILI), whose main causative agent is amoxicillin-clavulanate, remains unknown. This pioneering study aims to unravel particular patterns of gut microbiota composition and associated metabolites in iDILI and iDILI patients by amoxicillin-clavulanate (iDILI-AC). Thus, serum and fecal samples from 46 patients were divided into three study groups: healthy controls (n = 10), non-iDILI acute hepatitis (n = 12) and iDILI patients (n = 24). To evaluate the amoxicillin-clavulanate effect, iDILI patients were separated into two subgroups: iDILI non-caused by amoxicillin-clavulanate (iDILI-nonAC) (n = 18) and iDILI-AC patients (n = 6). Gut microbiota composition and fecal metabolome plus serum and fecal bile acid (BA) analyses were performed, along with correlation analyses. iDILI patients presented a particular microbiome profile associated with reduced fecal secondary BAs and fecal metabolites linked to lower inflammation, such as dodecanedioic acid and pyridoxamine. Moreover, certain taxa like Barnesiella, Clostridia UCG-014 and Eubacterium spp. correlated with significant metabolites and BAs. Additionally, comparisons between iDILI-nonAC and iDILI-AC groups unraveled unique features associated with iDILI when caused by amoxicillin-clavulanate. In conclusion, specific gut microbiota profiles in iDILI and iDILI-AC patients were associated with particular metabolic and BA status, which could affect disease onset and progression.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Ácidos e Sais Biliares , Doença Hepática Induzida por Substâncias e Drogas , Fezes , Microbioma Gastrointestinal , Metaboloma , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Fezes/microbiologia , Ácidos e Sais Biliares/metabolismo , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Masculino , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Metaboloma/efeitos dos fármacos , Pessoa de Meia-Idade , Adulto , Idoso
19.
Int J Mol Sci ; 25(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39000013

RESUMO

Obesity is a global health concern implicated in numerous chronic degenerative diseases, including type 2 diabetes, dyslipidemia, and neurodegenerative disorders. It is characterized by chronic low-grade inflammation, gut microbiota dysbiosis, insulin resistance, glucose intolerance, and lipid metabolism disturbances. Here, we investigated the therapeutic potential of environmental enrichment (EE) to prevent the progression of gut dysbiosis in mice with high-fat diet (HFD)-induced metabolic syndrome. C57BL/6 male mice with obesity and metabolic syndrome, continuously fed with an HFD, were exposed to EE. We analyzed the gut microbiota of the mice by sequencing the 16s rRNA gene at different intervals, including on day 0 and 12 and 24 weeks after EE exposure. Fasting glucose levels, glucose tolerance, insulin resistance, food intake, weight gain, lipid profile, hepatic steatosis, and inflammatory mediators were evaluated in serum, adipose tissue, and the colon. We demonstrate that EE intervention prevents the progression of HFD-induced dysbiosis, reducing taxa associated with metabolic syndrome (Tepidimicrobium, Acidaminobacteraceae, and Fusibacter) while promoting those linked to healthy physiology (Syntrophococcus sucrumutans, Dehalobacterium, Prevotella, and Butyricimonas). Furthermore, EE enhances intestinal barrier integrity, increases mucin-producing goblet cell population, and upregulates Muc2 expression in the colon. These alterations correlate with reduced systemic lipopolysaccharide levels and attenuated colon inflammation, resulting in normalized glucose metabolism, diminished adipose tissue inflammation, reduced liver steatosis, improved lipid profiles, and a significant reduction in body weight gain despite mice's continued HFD consumption. Our findings highlight EE as a promising anti-inflammatory strategy for managing obesity-related metabolic dysregulation and suggest its potential in developing probiotics targeting EE-modulated microbial taxa.


Assuntos
Dieta Hiperlipídica , Disbiose , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Obesidade , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Camundongos , Obesidade/metabolismo , Obesidade/microbiologia , Masculino , Glucose/metabolismo , Camundongos Obesos , Resistência à Insulina , Síndrome Metabólica/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/microbiologia
20.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000036

RESUMO

Air pollution, a growing concern for public health, has been linked to various respiratory and cardiovascular diseases. Emerging evidence also suggests a link between exposure to air pollutants and neurodegenerative diseases, particularly Alzheimer's disease (AD). This review explores the composition and sources of air pollutants, including particulate matter, gases, persistent organic pollutants, and heavy metals. The pathophysiology of AD is briefly discussed, highlighting the role of beta-amyloid plaques, neurofibrillary tangles, and genetic factors. This article also examines how air pollutants reach the brain and exert their detrimental effects, delving into the neurotoxicity of air pollutants. The molecular mechanisms linking air pollution to neurodegeneration are explored in detail, focusing on oxidative stress, neuroinflammation, and protein aggregation. Preclinical studies, including in vitro experiments and animal models, provide evidence for the direct effects of pollutants on neuronal cells, glial cells, and the blood-brain barrier. Epidemiological studies have reported associations between exposure to air pollution and an increased risk of AD and cognitive decline. The growing body of evidence supporting air pollution as a modifiable risk factor for AD underscores the importance of considering environmental factors in the etiology and progression of neurodegenerative diseases, in the face of worsening global air quality.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença de Alzheimer , Humanos , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Poluição do Ar/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/toxicidade , Fatores de Risco , Animais , Material Particulado/efeitos adversos , Estresse Oxidativo , Doenças Neurodegenerativas/etiologia , Exposição Ambiental/efeitos adversos , Encéfalo/patologia , Encéfalo/metabolismo
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