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1.
Biomed Environ Sci ; 37(5): 479-493, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38843921

RESUMO

Objective: To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons (PAHs) during critical brain development and explore their potential link with the intestinal microbiota. Methods: Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs (OH-PAHs) in 36-month-old children. Subsequently, 37 children were categorized into low- and high-exposure groups based on the sum of the ten OH-PAHs. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples. Furthermore, fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results: The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group (variable importance for projection > 1, P < 0.05). Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene, fluorine, and phenanthrene ( r = 0.336-0.531). The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states, including amino acid, lipid, and nucleotide metabolism. Additionally, these distinct metabolites were significantly associated with specific intestinal flora abundances ( r = 0.34-0.55), which were mainly involved in neurodevelopment. Conclusion: Higher PAH exposure in young children affected metabolic homeostasis, particularly that of certain gut microbiota-derived metabolites. Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.


Assuntos
Microbioma Gastrointestinal , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/urina , Masculino , Pré-Escolar , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/metabolismo , Metabolômica , Metaboloma/efeitos dos fármacos
2.
Biomed Environ Sci ; 37(5): 494-502, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38843922

RESUMO

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Citocinas , Humanos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Citocinas/sangue , Citocinas/metabolismo , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Alanina Transaminase/sangue
3.
Ann Oncol ; 35(6): 537-548, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38844309

RESUMO

BACKGROUND: Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort. PATIENTS AND METHODS: Patients were randomized 1 : 1 : 1 to arm A [nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W (four doses)] or arm B [nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W (four doses)], each followed by nivolumab 240 mg Q2W, or arm C (nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W). The primary objectives were safety, tolerability, investigator-assessed objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1. RESULTS: A total of 148 patients were randomized across treatment arms. At 60-month minimum follow-up (62.6-month median follow-up), the ORR was 34% (n = 17), 27% (n = 13), and 29% (n = 14) in arms A, B, and C, respectively. The median DOR was 51.2 months [95% confidence interval (CI) 12.6 months-not estimable (NE)], 15.2 months (95% CI 7.1 months-NE), and 21.7 months (95% CI 4.2 months-NE), respectively. The median overall survival (OS) was 22.2 months (34/50; 95% CI 9.4-54.8 months) in arm A, 12.5 months (38/49; 95% CI 7.6-16.4 months) in arm B, and 12.7 months (40/49; 95% CI 7.4-30.5 months) in arm C; 60-month OS rates were 29%, 19%, and 21%, respectively. In an exploratory analysis of OS by response (6-month landmark), the median OS was meaningfully longer for responders versus nonresponders for all arms. No new safety signals were identified with longer follow-up. There were no new discontinuations due to immune-mediated adverse events since the primary analysis. CONCLUSIONS: Consistent with the primary analysis, the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit, with no new safety signals in patients with advanced HCC following sorafenib treatment, further supporting its use as a second-line treatment in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Ipilimumab , Neoplasias Hepáticas , Nivolumabe , Sorafenibe , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Seguimentos , Idoso de 80 Anos ou mais
4.
J Environ Sci (China) ; 145: 75-87, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38844325

RESUMO

Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication. Now, it is also recognized as an emerging environmental contaminant. Pregnant women may be exposed to prednisone actively or passively through multiple pathways and cause developmental toxicity to the fetus. However, the impact of prenatal prednisone exposure (PPE) on fetal kidney development remains unclear. In this study, pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses (0.25, 0.5, or 1 mg/(kg·day)), or at the dose of 1 mg/(kg·day) in different gestational days (GD) (GD0-9, GD10-18, or GD0-18). The pregnant mice were euthanized on GD18. HE staining revealed fetal kidney dysplasia, with an enlarged glomerular Bowman's capsule space and a reduced capillary network in the PPE groups. The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups. However, overall gene expression in renal tubules and collecting ducts were markedly increased. All of the above effects were more pronounced in high-dose, full-term pregnancy, and female fetuses. Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2, increased the expression of Hnf1ß, Hnf4α, and Wnt9b, and inhibited the expression of glial cell line-derived neurotrophic factor (GDNF) and Notch signaling pathways. In conclusion, this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney, and the time effect is manifested as full-term pregnancy > early pregnancy > mid-late pregnancy.


Assuntos
Rim , Prednisona , Feminino , Animais , Gravidez , Camundongos , Rim/efeitos dos fármacos , Rim/embriologia , Prednisona/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Masculino , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Exposição Materna/efeitos adversos
5.
BMJ Case Rep ; 17(6)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844354

RESUMO

Enteric gram-negative bacteria-associated peritoneal dialysis (PD) peritonitis is common. These organisms are such as Escherichia coli, Klebsiella and Enterobacter species. Pantoea dispersa belongs to the order Enterobacterales, it has known benefits and a role in agricultural and environmental biotechnology. Pantoea dispersa, although still relatively rare, is being increasingly recognised to cause human infections. We are reporting a case of PD peritonitis caused by Pantoea dispersa in a kidney failure patient on continuous ambulatory peritoneal dialysis (CAPD). His peritonitis was treated well with intraperitoneal antibiotics and the patient can resume his CAPD therapy. The increasing reports of Pantoea dispersa-related human infections warrant concerns, both in immunocompromised and immunocompetent patients.


Assuntos
Antibacterianos , Infecções Relacionadas a Cateter , Infecções por Enterobacteriaceae , Pantoea , Diálise Peritoneal Ambulatorial Contínua , Peritonite , Humanos , Pantoea/isolamento & purificação , Masculino , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritonite/microbiologia , Peritonite/tratamento farmacológico , Peritonite/etiologia , Peritonite/diagnóstico , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/diagnóstico , Antibacterianos/uso terapêutico , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Pessoa de Meia-Idade
6.
Neurosurg Rev ; 47(1): 260, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844595

RESUMO

INTRODUCTION: The prone transpsoas technique (PTP) is a modification of the traditional lateral lumbar interbody fusion approach, which was first published in the literature in 2020. The technique provides several advantages, such as lordosis correction and redistribution, single-position surgery framework, and ease of performing posterior techniques when needed. However, the prone position also leads to the movement of some retroperitoneal, vascular, and neurological structures, which could impact the complication profile. Therefore, this study aimed to investigate the occurrence of major complications in the practice of early adopters of the PTP approach. METHODS: A questionnaire containing 8 questions was sent to 50 participants and events involving early adopters of the prone transpsoas technique. Of the 50 surgeons, 32 completed the questionnaire, which totaled 1963 cases of PTP surgeries. RESULTS: Nine of the 32 surgeons experienced a major complication (28%), with persistent neurological deficit being the most frequent (7/9). Of the total number of cases, the occurrence of permanent neurological deficits was approximately 0,6%, and the rate of vascular and visceral injuries were both 0,05% (1/1963 for each case). CONCLUSION: Based on the analysis of the questionnaire responses, it can be concluded that PTP is a safe technique with a very low rate of serious complications. However, future studies with a more heterogeneous group of surgeons and a more rigorous linkage between answers and patient data are needed to support the findings of this study.


Assuntos
Complicações Pós-Operatórias , Músculos Psoas , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Decúbito Ventral , Inquéritos e Questionários , Vértebras Lombares/cirurgia , Masculino , Feminino
7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(5): 514-519, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38845499

RESUMO

OBJECTIVE: To investigate the effect of mild hypothermia on macrophage polarization in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and to clarify its role in lung injury. METHODS: According to a random number table method, 18 male C57BL/6 mice were divided into sham operation group (Sham group), ALI normothermic model group (NT group) and ALI mild hypothermia treatment group (HT group), with 6 mice in each group. The ALI model in mice was established by the method of tracheal instillation of LPS, and temperature control was administered at 1 hour after surgery. The anus temperature in NT group was kept at 36-38?centigrade, while the anus temperature in HT group was kept at 32-34?centigrade. The target anus temperature in both groups were maintained for 6 hours and then slowly rewarmed to 36-38 centigrade. The Sham group was infused with an equal amount of physiological saline through the trachea without temperature control. After 24 hours of modeling, serum was collected and mice were sacrificed to obtain lung tissue. Pathological changes in lung tissue were observed under light microscopy and semi-quantitative lung injury score was performed. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum levels of interleukins (IL-1ß, IL-10). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to test the indicators of macrophage polarization, such as the mRNA expressions of CD86, IL-6, CD206 and arginase 1 (Arg1) in the lung tissue. The protein expression of M1 macrophage marker inducible nitric oxide synthase (iNOS) and M2 macrophage marker Arg1 were detected by Western blotting. RESULTS: Compared with the Sham group, the NT group appeared significant pulmonary hemorrhage and edema, thickened lung septum, inflammatory cell infiltration, and lung injury score was significantly increased; serum IL-1ß level was significantly elevated; IL-10 level was increased without statistical significance; the expressions of CD86 mRNA, IL-6 mRNA and iNOS protein were significantly elevated, and CD206 mRNA was significantly decreased; the mRNA and protein expressions of Arg1 decreased, but there were no significant differences. Compared with the NT group, the pathological injury of lung tissue in HT group was significantly reduced, and the lung injury score was significantly decreased (4.78±0.96 vs. 8.56±1.98, P < 0.01); serum IL-1ß level was decreased (ng/L: 13.52±1.95 vs. 27.18±3.87, P < 0.01), and IL-10 level was significantly increased (ng/L: 42.59±15.79 vs. 14.62±4.47, P < 0.01); IL-6 mRNA expression was decreased in lung tissue (2-ΔΔCt: 3.37±0.92 vs. 10.04±0.91, P < 0.05), the expression of M1 macrophage markers CD86 mRNA and iNOS protein were significantly decreased [CD86 mRNA (2-ΔΔCt): 0.52±0.16 vs. 1.95±0.33, iNOS protein (iNOS/ß-actin): 0.57±0.19 vs. 1.11±0.27, both P < 0.05], the expression of M2 macrophage markers CD206 mRNA, Arg1 mRNA and Arg1 protein were significantly increased [CD206 mRNA (2-ΔΔCt): 3.99±0.17 vs. 0.34±0.17, Arg1 mRNA (2-ΔΔCt): 2.33±0.73 vs. 0.94±0.23, Arg1 protein (Arg1/ß-actin): 0.96±0.09 vs. 0.31±0.11, all P < 0.05]. CONCLUSIONS: Mild hypothermia can alleviate the inflammatory response and protect lung tissue in ALI mice, which may be related to the inhibition of M1 macrophage polarization and promotion of M2 macrophage polarization.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Macrófagos , Camundongos Endogâmicos C57BL , Animais , Lesão Pulmonar Aguda/terapia , Masculino , Camundongos , Macrófagos/metabolismo , Lipopolissacarídeos/efeitos adversos , Óxido Nítrico Sintase Tipo II/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Hipotermia Induzida , Interleucina-1beta/metabolismo , Modelos Animais de Doenças
8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(5): 527-531, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38845501

RESUMO

OBJECTIVE: To investigate the predictive value of albumin-to-fibrinogen ratio (AFR) for postoperative acute kidney injury (AKI) in infants with ventricular septal defect repair under cardiopulmonary bypass (CPB). METHODS: A retrospective analysis was conducted on infants diagnosed with ventricular septal defect in Anhui Children's Hospital from January 2019 to July 2023. The infants were divided into AKI group and non-AKI group according to whether AKI occurred in hospital after operation. Demographic data, preoperative data, intraoperative data, postoperative data and laboratory results during CPB were collected. Multivariate Logistic regression analysis was used to find the factors of AKI after ventricular septal defect repair with CPB. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of AFR for postoperative AKI after ventricular septal defect repair with CPB. RESULTS: A total of 215 children were collected, including 28 in AKI group and 187 in non-AKI group. There were no significant differences in age, gender, body weight, height, history of pneumonia and history of chronic heart failure between the two groups, but the left ventricular ejection fraction (LVEF) in the AKI group was significantly lower than that in the non-AKI group (0.526±0.028 vs. 0.538±0.030, P = 0.048). The duration of CPB (minutes: 74.1±12.1 vs. 65.8±11.3, P < 0.001), aortic cross-clamping (minutes: 41.7±9.7 vs. 37.2±9.4, P = 0.021) and hypothermic circulation arrest (21.4% vs. 8.6%, P = 0.047) in AKI group were significantly higher than those in non-AKI group, but there were no significant differences in the proportion of ultrafiltration and urine volume between the two groups. The length of intensive care unit (ICU) stay in AKI group was significantly longer than that in non-AKI group (days: 5.3±2.0 vs. 4.0±1.7, P < 0.001), but there were no significant differences in duration of mechanical ventilation and the proportion of postoperative hypotension between the two groups. During CPB, the levels of blood glucose (mmol/L: 9.4±1.3 vs. 8.8±0.8, P < 0.001), blood lactic acid (mmol/L: 2.2±0.3 vs. 2.0±0.3, P = 0.015) and serum creatinine (µmol/L: 79.7±11.5 vs. 74.4±10.9, P = 0.018) in AKI group were significantly higher than those in non-AKI group, while the AFR was significantly lower than that in non-AKI group (8.5±1.3 vs. 10.2±1.6, P < 0.001), but there were no significant differences in the levels of hemoglobin, blood urea nitrogen, alanine aminotransferase and aspartate aminotransferase between the two groups during CPB. Multivariate Logistic regression showed that AFR was a protective factor for AKI after ventricular septal defect repair with CPB [odds ratio (OR) = 0.439, 95% confidence interval (95%CI) was 0.288-0.669, P < 0.001]. Blood glucose (OR = 2.133, 95%CI was 1.239-3.672, P = 0.006) and blood lactic acid (OR = 5.568, 95%CI was 1.102-28.149, P = 0.038) were risk factors for AKI after ventricular septal defect repair with CPB. ROC curve analysis showed that the area under the curve (AUC) of AFR in predicting AKI after ventricular septal defect repair with CPB was 0.804 (95%CI was 0.712-0.897, P < 0.001). When the optimal cut-off value was less than 9.05, the corresponding sensitivity was 75.0% and the specificity was 72.7%. CONCLUSIONS: Low AFR (≤9.05) during CPB is an independent risk factor for AKI after ventricular septal defect repair with CPB. AFR during CPB has a high predictive value for postoperative AKI after ventricular septal defect repair with CPB.


Assuntos
Injúria Renal Aguda , Ponte Cardiopulmonar , Fibrinogênio , Comunicação Interventricular , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Lactente , Ponte Cardiopulmonar/efeitos adversos , Comunicação Interventricular/cirurgia , Masculino , Feminino , Complicações Pós-Operatórias/diagnóstico , Valor Preditivo dos Testes , Curva ROC , Modelos Logísticos , Fatores de Risco
11.
Recent Adv Food Nutr Agric ; 15(1): 59-73, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38847153

RESUMO

BACKGROUND: Cognitive impairment is amongst the most substantial mental health problems in elderly people, and inflammation is an underlying mechanism for cognitive impairment. The dietary inflammatory index (DII®) reflects the overall inflammatory potential of individuals' diets. The current study aimed to assess the relationship between the DII and cognitive function among the Iranian old population. METHODS: This cross-sectional study was conducted on 221 subjects≥65 years old in healthcare centers in five socioeconomically distinct districts of Tehran, Iran. Dietary intake data were obtained using a validated food frequency questionnaire (FFQ). Energy-adjusted-DII (E-DIITM) scores were calculated for each participant according to a total of 35 food parameters, which were available from the FFQ. Mini mental state examination (MMSE), a brief screening questionnaire was used to assess cognitive function. RESULTS: E-DII scores were not significantly associated with cognitive function, both in the crude model (ß=-0.04, p-value=0.82) and after adjusting for potential confounders (ß=0.22, pvalue= 0.14). Additionally, in the unadjusted model, individuals in the highest tertile of E-DII score had increased odds of mild cognitive impairment (OR=1.13, p-trend=0.01) compared to those older adults in the lowest tertile of E-DII score. However, after controlling for potential confounders, these relationships faded (AOR=1.46, p-trend=0.12). CONCLUSION: The findings of the present study showed no significant relationship between E- DII and cognitive function among the Iranian elderly. Future prospective studies should be undertaken to explore the association between diet-associated inflammation and cognitive decline in the elderly.


Assuntos
Cognição , Disfunção Cognitiva , Dieta , Inflamação , Humanos , Irã (Geográfico)/epidemiologia , Idoso , Masculino , Feminino , Estudos Transversais , Inflamação/epidemiologia , Cognição/fisiologia , Dieta/efeitos adversos , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Idoso de 80 Anos ou mais , Inquéritos e Questionários
12.
J Neurosci Res ; 102(6): e25360, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847288

RESUMO

Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.


Assuntos
Tonsila do Cerebelo , Dieta Hiperlipídica , Ácido Glutâmico , Hipocampo , Transmissão Sináptica , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Hipocampo/metabolismo , Tonsila do Cerebelo/metabolismo , Transmissão Sináptica/fisiologia , Ratos , Ácido Glutâmico/metabolismo , Norepinefrina/metabolismo , Ratos Wistar , Cognição/fisiologia , Aprendizagem da Esquiva/fisiologia
13.
Ugeskr Laeger ; 186(22)2024 May 27.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38847300

RESUMO

Acute pancreatitis (AP) is a sudden inflammation of the pancreas which often manifests as a mild disease but can be associated with high morbidity and mortality. Drug-induced AP is rare and most likely underdiagnosed. Vedolizumab is a human monoclonal antibody with gut-selective integrin antagonist effect, and it is used for treatment of inflammatory bowel disease (IBD). Budesonid is a glucocorticoid which is released in the colon and it is also used in IBD treatment. This is a case report where vedolizumab or budesonide caused acute pancreatitis in a young man with ulcerative colitis.


Assuntos
Anticorpos Monoclonais Humanizados , Budesonida , Colite Ulcerativa , Fármacos Gastrointestinais , Pancreatite , Humanos , Colite Ulcerativa/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Pancreatite/induzido quimicamente , Budesonida/efeitos adversos , Budesonida/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Adulto , Doença Aguda , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos
14.
Ugeskr Laeger ; 186(22)2024 May 27.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38847299

RESUMO

This is a case report of a 44-year-old premenopausal woman who was admitted to hospital due to uncontrollable and life-threatening vaginal bleeding after starting rivaroxaban treatment for atrial fibrillation. She had a medical history with menorrhagia due to an intrauterine fibroma. She did not respond sufficiently to factor X supplement or other non-surgical medical interventions. The bleeding subsided after bilateral embolization of aa. uterinae.


Assuntos
Fibrilação Atrial , Inibidores do Fator Xa , Rivaroxabana , Hemorragia Uterina , Humanos , Rivaroxabana/efeitos adversos , Feminino , Adulto , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Hemorragia Uterina/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Leiomioma/tratamento farmacológico , Menorragia/induzido quimicamente , Menorragia/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico
15.
Ugeskr Laeger ; 186(21)2024 May 20.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38847310

RESUMO

Amoxicillin/clavulanate is a commonly used antibiotic. Though relatively rare, amoxicillin/clavulanate carries the highest incidence of idiosyncratic drug-induced liver disease. This case report presents an 80-year-old woman treated for simple respiratory tract infection with amoxicillin/clavulanate who was subsequently hospitalized with malaise and icterus and a biochemical cholestatic pattern with high alkaline phosphatase and bilirubin. Diagnostically challenging, ultimately, liver biopsy revealed drug-induced liver injury with a fatal course after attempt of supportive, symptomatic treatment.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Antibacterianos , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Feminino , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Evolução Fatal , Colestase Intra-Hepática/induzido quimicamente
16.
Cereb Cortex ; 34(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38847535

RESUMO

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Encéfalo , Fissura , Sinais (Psicologia) , Comportamento Impulsivo , Imageamento por Ressonância Magnética , Metanfetamina , Humanos , Masculino , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico por imagem , Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Adulto , Fissura/fisiologia , Comportamento Impulsivo/fisiologia , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Metanfetamina/efeitos adversos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-38847554

RESUMO

The aim of the present study was to determine the associations between the MICB genetic variability and the expression and the risk of development of post-transplant complications after allogeneic hematopoietic stem cell transplantation (HSCT). HSCT recipients and their donors were genotyped for two MICB polymorphisms (rs1065075, rs3828903). Moreover, the expression of a soluble form of MICB was determined in the recipients' serum samples after transplantation using the Luminex assay. Our results revealed a favorable role of the MICB rs1065075 G allele. Recipients with donors carrying this genetic variant were less prone to developing chronic graft-versus-host disease (cGvHD) when compared to recipients without any symptoms of this disease (41.41% vs. 65.38%, p = 0.046). Moreover, the MICB rs1065075 G allele was associated with a lower incidence of cytomegalovirus (CMV) reactivation, both as a donor (p = 0.015) and as a recipient allele (p = 0.039). The MICB rs1065075 G variant was also found to be associated with decreased serum soluble MICB (sMICB) levels, whereas serum sMICB levels were significantly higher in recipients diagnosed with CMV infection (p = 0.0386) and cGvHD (p = 0.0008) compared to recipients without those complications. A protective role of the G allele was also observed for the rs3828903 polymorphism, as it was more frequently detected among donors of recipients without cGvHD (89.90% vs. 69.23%; p = 0.013). MICB genetic variants, as well as serum levels of sMICB, may serve as prognostic factors for the risk of developing cGvHD and CMV infection after allogeneic HSCT.


Assuntos
Infecções por Citomegalovirus , Predisposição Genética para Doença , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade Menor , Transplante Homólogo , Humanos , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/etiologia , Infecções por Citomegalovirus/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Transplante Homólogo/efeitos adversos , Adulto , Pessoa de Meia-Idade , Doença Crônica , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo de Nucleotídeo Único , Alelos , Genótipo , Adulto Jovem , Citomegalovirus/fisiologia , Adolescente , Risco , Fatores de Risco
18.
Minerva Surg ; 79(3): 303-308, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847767

RESUMO

BACKGROUND: Our aim was to describe the clinical outcomes of surgical interventions performed for the management of colonoscopy-related perforations and to compare these outcomes with those of matched colorectal surgeries performed in elective and emergency settings. METHODS: We included patients with endoscopic colonic perforation who underwent surgical intervention from the 2014-2017 National Surgery Quality Improvement Program participant use data colorectal targeted procedure file. The primary outcome in this study was short term surgical morbidity and mortality. Patients (group 1) were matched with 1:2 ratio to control patients undergoing same surgical interventions for other indications on an elective (group 2) or emergency basis (group 3). Bivariate analysis was conducted to compare categorical variables between the three groups, and multivariate logistic regression was used to evaluate the association between the surgical indication and 30-day postoperative outcomes. RESULTS: A total of 590 patients were included. The average age of the patients was 66.5±13.6 with female gender predominance (381, 64.6%) The majority of patients underwent open colectomy (365, 61.9%) while the rest had suturing (140, 23.7%) and laparoscopic colectomy (85, 14.4%). Overall mortality occurred in 4.1% and no statistically significant difference in mortality was found between the three techniques (P=0.468). Composite morbidity occurred in 163 patients (27.6%). It was significantly lower in laparoscopic colectomy (14.1%) compared to 30.2% and 29.4% in open colectomy and suturing approaches (P=0.014). Patients undergoing colectomy for iatrogenic colonic perforation had less mortality, infection rates and sepsis, as well as bleeding episodes compared to those who had colectomy on an emergent basis. Outcomes were comparable between the former group and patients undergoing elective colectomy for other indications. CONCLUSIONS: Surgical management of colonoscopy related perforations is safe and effective with outcomes that are similar to that of patients undergoing elective colectomy.


Assuntos
Colectomia , Colonoscopia , Perfuração Intestinal , Humanos , Perfuração Intestinal/cirurgia , Perfuração Intestinal/mortalidade , Perfuração Intestinal/epidemiologia , Feminino , Masculino , Idoso , Colonoscopia/efeitos adversos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Laparoscopia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Procedimentos Cirúrgicos Eletivos , Doenças do Colo/cirurgia , Doenças do Colo/mortalidade , Colo/cirurgia , Colo/lesões , Técnicas de Sutura , Resultado do Tratamento , Idoso de 80 Anos ou mais
19.
Minerva Surg ; 79(3): 309-314, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847768

RESUMO

BACKGROUND: Hemorrhoids are a common problem associated with symptoms, like swelling, local thrombosis and generally with a decreased quality of life, often in otherwise healthy subjects. Hemorrhoids can be classified by grades (I to IV) according to their severity. In this registry study subjects treated with excisional hemorrhoidectomy (EH) for the first time, were included. After surgery, edema tends to complicate surgical areas causing relevant symptoms. Most hemorrhoids symptoms are related to alterations in bowel habits. Increase in diet fibers to avoid constipation, exercise, and limiting straining reduce recurrence after surgery. METHODS: The aim of the registry study was to evaluate the effects of Pycnogenol® (Horphag Research, Geneva, Switzerland) on relieving postoperative symptoms following hemorrhoidectomy. Pycnogenol® 150 mg/day was used between one month before surgery up to one month after surgery. The main postoperative symptoms were scored. RESULTS: Thirty-eight subjects completed the 60-day supplement registry study. Eighteen subjects were supplemented with Pycnogenol® in addition to the standard management (SM) and 20 subjects only received SM and were considered as controls. The two groups were comparable for age, sex and main symptoms distribution and for their clinical characteristics at inclusion. No other disease was present. The scores for pain, discomfort, and constipation were significantly lower with the supplement compared to controls (P<0.05) 10 and 30 days after surgery. In addition, the quality-of-life score was higher with Pycnogenol® (P<0.05) while bleeding (minimal, not clinically evaluable) and a possible residual anal stenosis (requiring a longer period of observation) were barely observed. A satisfactory return to activity was observed 30 days after surgery in the 18 subjects using Pycnogenol®, and in only 15 out of 20 patients (75%) in the control group (P<0.05). All Pycnogenol® subjects were able to drive and perform daily tasks in comparison with 14 out of 20 subjects in the control group. The proportion of patients that took pain medication from day 10 to 30 post-surgery was significantly lower in the Pycnogenol® group than in controls (P<0.05). CONCLUSIONS: In this post-surgical pilot, registry study, Pycnogenol® was effective in preventing and controlling postoperative symptoms after hemorrhoidectomy. To confirm the results, more cases are needed, including different surgical methods and clinical conditions. Mucosal and cutaneous edema and perianal swelling - generally seen after surgery - seem to be clearly reduced with Pycnogenol® and the supplement intake was associated with a more regular and pain-controlled convalescence and healing.


Assuntos
Flavonoides , Hemorroidectomia , Hemorroidas , Extratos Vegetais , Sistema de Registros , Humanos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/administração & dosagem , Flavonoides/uso terapêutico , Flavonoides/administração & dosagem , Masculino , Feminino , Hemorroidas/cirurgia , Hemorroidectomia/efeitos adversos , Pessoa de Meia-Idade , Adulto , Suplementos Nutricionais , Qualidade de Vida , Idoso , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento
20.
Langenbecks Arch Surg ; 409(1): 176, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847886

RESUMO

BACKGROUND: No single technique of remnant pancreas reconstruction after pancreaticoduodenectomy (PD) has been demonstrated to be superior to the others in the prevention of post-operative pancreatic fistula (POPF), and the accumulation of surgical experience is closely related to the quality of this anastomosis. The aim of the current study was to evaluate the feasibility and patient outcomes of a simplified technique involving a single-layer continuous pancreaticojejunostomy (PJA) with Falciform ligament reinforcement that can be used with all types of pancreases. METHODS: A single-centre and single-surgeon study was performed. One hundred consecutive patients undergoing pancreatic resection with subsequent PJA using a novel technique performed by a single surgeon were included in the study. Patient demographics, pre-operative treatments, risk factors for POPF, and post-operative morbidity and mortality and long-term patient outcome were prospectively recorded and reported. RESULTS: From March 2018 to March 2022, 59 male and 41 female patients were included. 91 patients underwent PD for malignancy with 32 receiving neoadjuvant treatment. 59 patients were classified as intermediate/high risk for POPF according to validated fistula prediction models. There were 12 POPF Type B and 2 POPF Type C. The overall morbidity rate was 16% with no 90-day mortality. 3 patients underwent reoperation. The median length of hospitalisation was 12.6 days and 82% of eligible patients commenced and completed adjuvant chemotherapy. CONCLUSION: Single-layer continuous dunking PJA with Falciform ligament reinforcement is a simplified and feasible method for PJA with a low associated complication rate.


Assuntos
Fístula Pancreática , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Pancreaticojejunostomia , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Pancreaticojejunostomia/métodos , Pancreaticojejunostomia/efeitos adversos , Idoso , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fístula Pancreática/prevenção & controle , Fístula Pancreática/etiologia , Adulto , Pancreatectomia/métodos , Pancreatectomia/efeitos adversos , Estudos de Viabilidade , Resultado do Tratamento
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