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1.
J Neurosci Res ; 102(8): e25370, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39158105

RESUMO

Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.


Assuntos
Lipopolissacarídeos , Transtornos da Memória , Doenças Neuroinflamatórias , Condicionamento Físico Animal , Ratos Wistar , Animais , Masculino , Lipopolissacarídeos/toxicidade , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Ratos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/induzido quimicamente , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Treinamento Resistido/métodos , Córtex Cerebral/metabolismo , Córtex Cerebral/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Receptor Muscarínico M1/metabolismo
2.
Dig Dis ; 42(3): 257-264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38452742

RESUMO

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.


Assuntos
Doenças Inflamatórias Intestinais , Pancreatite , Sistema de Registros , Humanos , Feminino , Pancreatite/induzido quimicamente , Pancreatite/genética , Masculino , Adulto , Estudos de Casos e Controles , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pessoa de Meia-Idade , Predisposição Genética para Doença , Fatores de Risco , Variação Genética , Mercaptopurina/efeitos adversos , Mercaptopurina/uso terapêutico
3.
Am J Emerg Med ; 81: 92-98, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38713933

RESUMO

BACKGROUND: Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status and the presence of electrocardiographic and electrolytic disturbances. OBJECTIVE: To identify factors associated with seven-day and thirty-day mortality in digoxin poisoning. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective, observational, multicenter study was conducted across 15 Hospital Emergency Departments (HED) in Spain. All patients over 18 years of age who presented to participating HEDs from 2015 to 2021 were included. The inclusion criteria encompassed individuals meeting the criteria for digoxin poisoning, whether acute or chronic. OUTCOMES MEASURE AND ANALYSIS: To identify independent factors associated with 7-day and 30-day mortality, a multivariate analysis was conducted. This analysis included variables of clinical significance, as well as those exhibiting a trend (p < 0.1) or significance in the bivariate analysis. MAIN FINDINGS: A total of 658 cases of digoxin poisoning were identified. Mortality rates were 4.5% (30 patients) at seven days and 11.1% (73 patients) at thirty days. Regarding 7-day mortality, the mean age of deceased patients was comparable to survivors (84.7 (8.9) vs 83.9 (7.9) years; p = ns). The multivariate analysis revealed that factors independently associated with 7-day mortality encompassed the extent of dependence assessed by the Barthel Index (BI 60-89 OR 0.28; 95% CI 0.10-0.77; p = 0.014 and BI>90 OR 0.22; 95% CI 0.08-0.63; p = 0.005), the identification of ventricular arrhythmias (OR 1.34; 95% CI 1.34-25.21; p = 0.019), and the presence of circulatory (OR 2.84; 95% CI 1.19-6.27; p = 0.019) and neurological manifestations (OR 2.67; 95% CI 1.13-6.27; p = 0.025). Factors independently associated with 30-day mortality encompassed extent of dependence (BI 60-89 OR 0.37; 95% CI 0.20-0.71; p = 0.003 and BI>90 OR 0.18; 95% CI 0.09-0.39; p < 0.001) and the identification of circulatory (OR 2.13; 95% CI 1.10-4.15; p = 0.025) and neurological manifestations (OR 2.39; 95% CI 1.25-3.89; p = 0.006). CONCLUSIONS: The study identifies the degree of dependency assessed by the Barthel Index and the presence of cardiovascular and neurological symptoms as independent predictors of both 7-day and 30-day mortality. Additionally, the detection of ventricular arrhythmia is also an independent factor for 7-day mortality.


Assuntos
Digoxina , Humanos , Feminino , Digoxina/intoxicação , Digoxina/sangue , Masculino , Estudos Retrospectivos , Idoso , Idoso de 80 Anos ou mais , Espanha/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Fatores de Risco , Pessoa de Meia-Idade
4.
Dev Psychobiol ; 66(6): e22532, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39106347

RESUMO

Given the scarcity of studies addressing substance consumption and its relationship with attachment styles and early maladaptive schemas in adolescents, the present study is proposed. Aims of this study are to analyze the relationship among attachment styles, early maladaptive schemas, and substance use; test the predictive role of attachment styles on substance use; and observe the mediating role of early maladaptive schemas in the relationship between attachment and substance use. The sample consisted of 1533 adolescents from Ecuador (53.9% males) aged between 14 and 18 years (M = 15.76; SD = 1.25). The attachment styles of security, value to parental authority, parental permissiveness, parental interference, self-sufficiency and resentment against parents, childhood trauma, and family concern predict substance use (tobacco, alcohol, tranquilizers/sedatives or sleeping pills, hashish or marijuana, cocaine, GHB or liquid ecstasy, ecstasy, amphetamines/speed, hallucinogens, heroin, inhalants/volatiles), and the mediating role of early maladaptive schemas is confirmed (explained variance up to 33.33%). Identifying risk or vulnerability factors, such as attachment and early maladaptive schemas related to substance consumption, is especially relevant for designing and implementing preventive interventions in the adolescent population.


Assuntos
Comportamento do Adolescente , Apego ao Objeto , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Equador , Masculino , Feminino , Relações Pais-Filho
5.
Cell Stress Chaperones ; 29(3): 359-380, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38570009

RESUMO

Protein misfolding and mislocalization are common themes in neurodegenerative disorders, including motor neuron disease, and amyotrophic lateral sclerosis (ALS). Maintaining proteostasis is a crosscutting therapeutic target, including the upregulation of heat shock proteins (HSP) to increase chaperoning capacity. Motor neurons have a high threshold for upregulating stress-inducible HSPA1A, but constitutively express high levels of HSPA8. This study compared the expression of these HSPs in cultured motor neurons expressing three variants linked to familial ALS: TAR DNA binding protein 43 kDa (TDP-43)G348C, fused in sarcoma (FUS)R521G, or superoxide dismutase I (SOD1)G93A. All variants were poor inducers of Hspa1a, and reduced levels of Hspa8 mRNA and protein, indicating multiple compromises in chaperoning capacity. To promote HSP expression, cultures were treated with the putative HSP coinducer, arimoclomol, and class I histone deacetylase inhibitors, to promote active chromatin for transcription, and with the combination. Treatments had variable, often different effects on the expression of Hspa1a and Hspa8, depending on the ALS variant expressed, mRNA distribution (somata and dendrites), and biomarker of toxicity measured (histone acetylation, maintaining nuclear TDP-43 and the neuronal Brm/Brg-associated factor chromatin remodeling complex component Brg1, mitochondrial transport, FUS aggregation). Overall, histone deacetylase inhibition alone was effective on more measures than arimoclomol. As in the FUS model, arimoclomol failed to induce HSPA1A or preserve Hspa8 mRNA in the TDP-43 model, despite preserving nuclear TDP-43 and Brg1, indicating neuroprotective properties other than HSP induction. The data speak to the complexity of drug mechanisms against multiple biomarkers of ALS pathogenesis, as well as to the importance of HSPA8 for neuronal proteostasis in both somata and dendrites.


Assuntos
Esclerose Lateral Amiotrófica , Biomarcadores , Proteínas de Ligação a DNA , Inibidores de Histona Desacetilases , Neurônios Motores , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Biomarcadores/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Humanos , Neurônios Motores/metabolismo , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Animais , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSC70/metabolismo , Proteínas de Choque Térmico HSC70/genética , Hidroxilaminas/farmacologia , Células Cultivadas , Proteína FUS de Ligação a RNA/metabolismo , Proteína FUS de Ligação a RNA/genética , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética
6.
Antioxidants (Basel) ; 13(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39061870

RESUMO

While cytostatic chemotherapy targeting DNA is known to induce genotoxicity, leading to cell cycle arrest and cytokine secretion, the impact of these drugs on fibroblast-epithelial cancer cell communication and metabolism remains understudied. Our research focused on human breast fibroblast RMF-621 exposed to nonlethal concentrations of cisplatin and doxorubicin, revealing reduced proliferation, diminished basal and maximal mitochondrial respirations, heightened mitochondrial ROS and lactate production, and elevated MCT4 protein levels. Interestingly, RMF-621 cells enhanced glucose uptake, promoting lactate export. Breast cancer cells MCF-7 exposed to conditioned media (CM) from drug-treated stromal RMF-621 cells increased MCT1 protein levels, lactate-driven mitochondrial respiration, and a significantly high mitochondrial spare capacity for lactate. These changes occurred alongside altered mitochondrial respiration, mitochondrial membrane potential, and superoxide levels. Furthermore, CM with doxorubicin and cisplatin increased migratory capacity in MCF-7 cells, which was inhibited by MCT1 (BAY-8002), glutamate dehydrogenase (EGCG), mitochondrial pyruvate carrier (UK5099), and complex I (rotenone) inhibitors. A similar behavior was observed in T47-D and ZR-75-1 breast cancer cells. This suggests that CM induces metabolic rewiring involving elevated lactate uptake to sustain mitochondrial bioenergetics during migration. Treatment with the mitochondrial-targeting antioxidant mitoTEMPO in RMF-621 and the addition of an anti-CCL2 antibody in the CM prevented the promigratory MCF-7 phenotype. Similar effects were observed in THP1 monocyte cells, where CM increased monocyte recruitment. We propose that nonlethal concentrations of DNA-damaging drugs induce changes in the cellular environment favoring a promalignant state dependent on mitochondrial bioenergetics.

7.
Med Intensiva (Engl Ed) ; 48(6): 317-325, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38388219

RESUMO

OBJECTIVE: To describe the incidence of hypophosphatemia in patients admitted to the ICU who have required mechanical ventilation. To analyze the presence of risk factors and its relationship with nutritional practice. DESIGN: Prospective observational study. SETTING: Polyvalent ICUs of 2 University Hospitals. PATIENTS OR PARTICIPANTS: Patients on invasive mechanical ventilation ≥72 h with normal level of phosphorus at admission. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Electrolyte levels (phosphorus, magnesium, potassium) were determined on admission to the ICU and at 96 h. Risk categories on admission, caloric intake, insulin doses and acid-base status during the first 4 days of admission were recorded. Incidence was calculated as the number of patients who developed hypophosphataemia after admission. Univariate analysis was performed for between-group comparison and multivariate analysis of potential risk factors. RESULTS: 89 patients were included. The incidence of hypophosphataemia was 32.6%. In these patients phosphorus decreased from 3.57 ±â€¯1.02 mmol/l to 1.87 ±â€¯0.65 mmol/l (52.3%). The mean kcal/kg/24 h provided in the first 4 days was 17.4 ±â€¯4.1, with no difference between the group that developed hypophosphataemia and the group that did not. Significant risk factors were insulin doses administered and pH and PaCO2 values. CONCLUSIONS: The incidence of hypophosphataemia at 96 h from admission in mechanically ventilated patients is high and unrelated to the risk category and hypocaloric nutritional practice used. Insulin dosis and acid-base status are the main determinants of its occurrence.


Assuntos
Hipofosfatemia , Unidades de Terapia Intensiva , Síndrome da Realimentação , Respiração Artificial , Humanos , Hipofosfatemia/epidemiologia , Hipofosfatemia/etiologia , Respiração Artificial/estatística & dados numéricos , Fatores de Risco , Feminino , Masculino , Síndrome da Realimentação/epidemiologia , Síndrome da Realimentação/etiologia , Incidência , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Fósforo/sangue , Ingestão de Energia , Admissão do Paciente/estatística & dados numéricos , Insulina/uso terapêutico , Insulina/administração & dosagem
8.
Psicothema ; 36(1): 64-71, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38227301

RESUMO

BACKGROUND: The Self-Absorption Scale (SAS) is one of the few instruments that measure dysfunctional self-focused attention or self-absorption, a transdiagnostic factor of vulnerability to various emotional disorders. The internal structure of the Spanish version of the SAS and its relationship with other variables have not been examined, nor has whether its subscales provide relevant information. These were the two goals of the present study. METHOD: The factor structure of the SAS, its internal consistency, and its relationship with depression and post-traumatic stress were analyzed in a Spanish community sample of 519 adults. RESULTS: The SAS presented a symmetrical bifactor structure with a general factor of self-absorption that explained most of the variance in the items and two specific factors of private and public self-absorption. The total scale and the two subscales of the SAS exhibited excellent, good or adequate reliability coefficients (alphas/omegas = .70 ­ .88) and correlated with depression and post-traumatic stress ( r = .34 ­ .46). CONCLUSIONS: The SAS provides reliable, valid measures of dysfunctional self-focused attention in Spanish adults, but its Private and Public Self-absorption subscales are not much more useful than the information provided by its total scale.


Assuntos
Transtornos do Humor , Adulto , Humanos , Reprodutibilidade dos Testes
9.
Rev Bras Epidemiol ; 27Suppl 1(Suppl 1): e240014.supl.1, 2024.
Artigo em Inglês, Português | MEDLINE | ID: mdl-39166586

RESUMO

OBJECTIVE: The objective of the present study is to describe the sociodemographic and behavioral characteristics of a group of transgender women and travestis (TGW) with a history of incarceration and the institutional and social context of this experience in Brazil. METHODS: The analyzed data were derived from the TransOdara Study, a cross-sectional study conducted in five Brazilian capitals from December 2019 to July 2021. Participants were recruited using the Respondent-Driven Sampling (RDS) technique, in which, after an initial formative and exploratory stage, the first participants were identified; in turn, these participants recruited up to six other transgender women and travestis for the research. The study's outcome was the experience of incarceration throughout life, captured through the question: "Have you ever been arrested in your life?" RESULTS: A total of 1,245 TGW were interviewed, of which 20.3% (n=253) experienced incarceration. Incarceration was more frequent among those aged 33 to 42 years (35.6%), with lower level of education (45.5%, p<0.001), engaged in informal work (30.3%), without a partner (67.2%), and among those who reported illicit drug use (66.4%). The majority (60.9%) of TGW were incarcerated with cisgender men, and the most common reasons for imprisonment were drug trafficking (30.4%) followed by robbery (29.2%). Over a quarter of the interviewees (26.3%) experienced assault, and 13.8% reported experiencing sexual violence during incarceration. CONCLUSION: The results emphasize the high prevalence of incarceration among TGW. This incarceration takes place in male wards and in a context of high rates of physical and sexual violence.


Assuntos
Prisioneiros , Pessoas Transgênero , Humanos , Estudos Transversais , Pessoas Transgênero/estatística & dados numéricos , Pessoas Transgênero/psicologia , Brasil/epidemiologia , Adulto , Feminino , Masculino , Prisioneiros/estatística & dados numéricos , Prisioneiros/psicologia , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Fatores Socioeconômicos , Encarceramento
10.
Nat Commun ; 15(1): 3584, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678026

RESUMO

HROB promotes the MCM8-9 helicase in DNA damage response. To understand how HROB activates MCM8-9, we defined their interaction interface. We showed that HROB makes important yet transient contacts with both MCM8 and MCM9, and binds the MCM8-9 heterodimer with the highest affinity. MCM8-9-HROB prefer branched DNA structures, and display low DNA unwinding processivity. MCM8-9 unwinds DNA as a hexamer that assembles from dimers on DNA in the presence of ATP. The hexamer involves two repeating protein-protein interfaces between the alternating MCM8 and MCM9 subunits. One of these interfaces is quite stable and forms an obligate heterodimer across which HROB binds. The other interface is labile and mediates hexamer assembly, independently of HROB. The ATPase site formed at the labile interface contributes disproportionally more to DNA unwinding than that at the stable interface. Here, we show that HROB promotes DNA unwinding downstream of MCM8-9 loading and ring formation on ssDNA.


Assuntos
Reparo do DNA , Proteínas de Ligação a DNA , Proteínas de Manutenção de Minicromossomo , Humanos , Trifosfato de Adenosina/metabolismo , DNA/metabolismo , DNA/química , DNA de Cadeia Simples/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Manutenção de Minicromossomo/metabolismo , Proteínas de Manutenção de Minicromossomo/genética , Ligação Proteica , Multimerização Proteica , Reparo do DNA/genética
11.
Int J Neonatal Screen ; 10(3)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39051408

RESUMO

A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n = 162,729; incidence = 1:1323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical signs (p = 0.02), lower serum TSH (p < 0.01), and higher free T4 (p < 0.01) compared to those in Group 2 at diagnosis. Reducing the b-TSH cut-off from 10 to 6 mIU/L increased screening sensitivity, allowing a third of diagnoses, mainly mild cases, not being missed. However, when evaluating the performances of b-TSH cut-offs (6, 7, 8, 9, and 10 mIU/L), the lower values were associated with low positive predictive values (PPVs) and unacceptable increased recall rates (0.57%) for a public health care program. A proposed strategy is to adopt a higher b-TSH cut-off in the first sample and a lower one in the subsequent samples from the same child, which yields a greater number of diagnoses with an acceptable PPV.

12.
Viruses ; 16(7)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39066180

RESUMO

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. METHODS: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. RESULTS: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133-595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. CONCLUSION: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children.


Assuntos
Vírus BK , Síndrome Nefrótica , Humanos , Síndrome Nefrótica/virologia , Síndrome Nefrótica/complicações , Adolescente , Criança , Masculino , Feminino , Pré-Escolar , Vírus BK/genética , Vírus BK/isolamento & purificação , Lactente , Estudos Prospectivos , DNA Viral/genética , Herpesviridae/genética , Herpesviridae/classificação , Herpesviridae/isolamento & purificação , Coinfecção/virologia , Infecções por Herpesviridae/virologia , Adenoviridae/genética , Adenoviridae/isolamento & purificação , Adenoviridae/classificação
13.
Steroids ; 203: 109352, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38128896

RESUMO

Physical exercise is recognized as a non-pharmacological approach to treat and protect against several neuroinflammatory conditions and thus to prevent brain disorders. However, the interest in ergogenic resources by athletes and bodybuilding practitioners is widespread and on the rise. These substances shorten the process of performance gain and improve aesthetics, having led to the prominent use and abuse of hormones in the past years. Recent evidence has shown that the purinergic system, composed of adenine nucleotides, nucleosides, enzymes, and receptors, participates in a wide range of processes within the brain, such as neuroinflammation, neuromodulation, and cellular communication. Here, we investigated the effects of the anabolic androgenic steroid (AAS) testosterone (TES) at a dose of 70 mg/kg/week in female rats and the neuroprotective effect of resistance exercise related to the purinergic system and oxidative stress parameters. Our findings showed a decrease in ATP and ADO hydrolysis in treated and trained animals. Furthermore, there was an increase in the density of purinoceptors (P2X7 and A2A) and inflammatory markers (IBA-1, NRLP3, CASP-1, IL-1ß, and IL-6) in the cerebral cortex of animals that received AAS. On the other hand, exercise reversed neuroinflammatory parameters such as IBA-1, NLRP3, CASP-1, and IL-1ß and improved antioxidant response and anti-inflammatory IL-10 cytokine levels. Overall, this study shows that the use of TES without indication or prescription disrupts brain homeostasis, as demonstrated by the increase in neuroinflammation, and that the practice of exercise can protect brain health.


Assuntos
Anabolizantes , Treinamento Resistido , Humanos , Ratos , Feminino , Animais , Testosterona , Anabolizantes/farmacologia , Doenças Neuroinflamatórias , Congêneres da Testosterona/farmacologia , Encéfalo
14.
Sleep Med ; 122: 20-26, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39111059

RESUMO

The aims were (i) to determine the effects of Cognitive behavioral therapy for insomnia (CBT-I) on sleep disturbances, pain intensity and disability in patients with chronic musculoskeletal pain (CMP), and (ii) to determine the dose-response association between CBT-I dose (total minutes) and improvements in sleep disorders, pain intensity and disability in patients with CMP. A comprehensive search was conducted in PubMed/MEDLINE, Web of Science, CINAHL, and SCOPUS until December 17, 2023. Randomized clinical trials (RCTs) using CBT-I without co-interventions in people with CMP and sleep disorders were eligible. Two reviewers independently extracted data and assessed risk of bias and certainty of the evidence. A random effects meta-analysis was applied to determine the effects on the variables of interest. The dose-response association was assessed using a restricted cubic spline model. Eleven RCTs (n = 1801 participants) were included. We found a significant effect in favor of CBT-I for insomnia (SMD: -1.34; 95%CI: -2.12 to -0.56), with a peak effect size at 450 min of CBT-I (-1.65, 95%CI: -1.89 to -1.40). A non-significant effect was found for pain intensity. A meta-analysis of disability was not possible due to the lack of data. This review found benefits of CBT-I for insomnia compared to control interventions, with a large effect size. In addition, it was estimated that a 250-min dose of CBT-I had a large effect on reducing insomnia and that the peak effect was reached at 450 min. These novel findings may guide clinicians in optimizing the use of CBT-I in people with CMP and insomnia.

15.
J Nutr Biochem ; 127: 109602, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38373509

RESUMO

This study evaluated the effect of vitamin D3 (VIT D3) supplementation on the enzymatic activities and density of ectonucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5-nucleotidase (E-5'-NT), adenosine deaminase (ADA), as well as the density of P2 × 7R, P2Y12R, A1R, A2AR receptors, IL-1ß, and oxidative parameters in type 2 diabetic rats. Forty male Wistar rats were fed a high carbohydrate-high fat diet (HCHFD) and received an intraperitoneal injection containing a single dose of streptozotocin (STZ, 35 mg/kg). Animals were divided into four groups: 1) control; 2) control/VIT D3 12 µg/kg; 3) diabetic; and 4) diabetic/VIT D3 12 µg/kg. Results show that VIT D3 reduced blood glucose, ATP hydrolysis, ADA activity, P2Y12R density (platelets), as well as ATP, ADP, and AMP hydrolysis and ADA activity (synaptosomes). Moreover, VIT D3 increased insulin levels and AMP hydrolysis (platelets) and improved antioxidant defense. Therefore, we suggest that VIT D3 treatment modulates hyperglycemia-induced changes via purinergic enzymes and receptor expression, consequently attenuating insulin homeostasis dysregulation in the diabetic state.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Insulinas , Ratos , Masculino , Animais , Ratos Wistar , Colecalciferol/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Vitaminas , Monofosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo
16.
Emergencias ; 35(6): 423-431, 2023 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38116966

RESUMO

OBJECTIVES: To determine whether income was associated with unexpected in-hospital mortality in older patients treated in Spanish public health system hospital emergency departments. MATERIAL AND METHODS: Fifty-one public health system hospital emergency departments in Spain voluntarily participated in the study. Together the hospitals covered 25% of the population aged 65 years or older included in all patient registers during a week in the pre-pandemic period (April 1-7, 2019) and a week during the COVID-19 pandemic (March 30 to April 5, 2020). We estimated a patient's gross income as the amount published for the postal code of the patient's address. We then calculated the standardized gross income (SGI) by dividing the patient's estimated income by the mean for the corresponding territory (Spanish autonomous community). The existence and strength of an association between the SGI and in-hospital mortality was evaluated by means of restricted cubic spline (RCS) curves adjusted for 10 patient characteristics at baseline. Odds ratios (ORs) for each income level were expressed in relation to a reference SGI of 1 (the mean income for the corresponding autonomous community). We compared the COVID-19 and pre-pandemic periods by means of first-order interactions. RESULTS: Of the 35 280 patients attended in the 2 periods, gross income could be ascertained for 21 180 (60%), 15437 in the pre-pandemic period and 5746 during the COVID-19 period. SGIs were slightly higher for patients included before the pandemic (1.006 vs 0.994; P = .012). In-hospital mortality was 5.6% overall and higher during the pandemic (2.8% pre-pandemic vs 13.1% during COVID-19; P .001). The adjusted RCS curves showed that associations between income and mortality differed between the 2 periods (interaction P = .004). Whereas there were no significant income-influenced differences in mortality before the pandemic, mortality increased during the pandemic in the lowest-income population (SGI 0.5 OR, 1.82; 95% CI, 1.32-3.37) and in higher-income populations (SGI 1.5 OR, 1.32; 95% CI, 1.04-1.68, and SGI 2 OR, 1.92; 95% CI, 1.14-3.23). We found no significant differences between patients with COVID-19 and those with other diagnoses (interaction P = .667). CONCLUSION: The gross income of patients attended in Spanish public health system hospital emergency departments, estimated according to a patient's address and postal code, was associated with in-hospital mortality, which was higher for patients with the lowest and 2 higher income levels. The reasons for these associations might be different for each income level and should be investigated in the future.


OBJETIVO: Determinar si el nivel económico durante la primera ola pandémica tuvo una influencia diferente a la esperable en la mortalidad intrahospitalaria de los pacientes mayores atendidos en los servicios de urgencias (SU) de los hospitales públicos españoles. METODO: Cincuenta y un SU públicos españoles que participaron voluntariamente y que dan cobertura al 25% de la población incluyeron todos los registros de pacientes de edad 65 años atendidos durante una semana del periodo preCOVID (1-4-2019 a 7-4-2019) y una semana del periodo COVID (30-3-2020 a 5-4-2020). Se identificó la renta bruta (RB) asignada al código postal de residencia de cada paciente y se calculó la RB normalizada (RBN) dividiendo aquella por la RB media de su comunidad autónoma. La existencia y fuerza de la relación entre RBN y mortalidad intrahospitalaria se determinó mediante curvas spline cúbicas restringidas (SCR) ajustadas por 10 características basales del paciente. Las OR para cada situación económica se expresó en relación con una RBN de 1 (referencia, renta correspondiente a la media de la comunidad autónoma). La comparación entre periodo COVID y no COVID se realizó mediante el estudio de interacción de primer grado. RESULTADOS: De los 35.280 registros de pacientes atendidos en ambos periodos, se disponía de la RB en 21.180 (60%): 15.437 del periodo preCOVID y 5.746 del periodo COVID. La RBN de los pacientes incluidos fue discretamente superior en el periodo preCOVID (1,006 versus 0,994; p = 0,012). La mortalidad intrahospitalaria fue del 5,6%, y fue superior durante el periodo COVID (2,8% versus 13,1%; p 0,001). Las curvas SCR ajustadas mostraron una asociación entre nivel económico y mortalidad diferente entre ambos periodos (p interacción = 0,004): en el periodo preCOVID no hubo diferencias significativas de mortalidad en función de la RBN, mientras que en el periodo COVID la mortalidad se incrementó en rentas bajas (OR = 1,82, IC 95% = 1,32-3,37 para RBN de 0,5) y en rentas altas (OR = 1,32, IC 95% = 1,04-1,68 y OR = 1,92, IC 95% = 1,14-3,23 para RBN de 1,5 y 2, respectivamente), sin diferencias significativas entre pacientes con COVID y con otros diagnósticos (p interacción = 0,667). CONCLUSIONES: Durante la primera ola de la pandemia COVID, la RB asignada al código postal de residencia de los pacientes atendidos en los SU públicos españoles se asoció con la mortalidad intrahospitalaria, que aumentó en pacientes de rentas bajas y altas. Las razones de estas asociaciones pueden ser distintas para cada segmento económico y deben ser investigadas en el fututo.


Assuntos
COVID-19 , Humanos , Idoso , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Mortalidade Hospitalar , Espanha/epidemiologia
17.
Arq Bras Cardiol ; 120(12): e20230646, 2023 Dec.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38232246

RESUMO

Central Illustration : Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023 Proposal for including strain in the integrated diastolic function assessment algorithm, adapted from Nagueh et al.67 Am: mitral A-wave duration; Ap: reverse pulmonary A-wave duration; DD: diastolic dysfunction; LA: left atrium; LASr: LA strain reserve; LVGLS: left ventricular global longitudinal strain; TI: tricuspid insufficiency. Confirm concentric remodeling with LVGLS. In LVEF, mitral E wave deceleration time < 160 ms and pulmonary S-wave < D-wave are also parameters of increased filling pressure. This algorithm does not apply to patients with atrial fibrillation (AF), mitral annulus calcification, > mild mitral valve disease, left bundle branch block, paced rhythm, prosthetic valves, or severe primary pulmonary hypertension.


Figura Central : Posicionamento do Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia sobre o Uso do Strain Miocárdico na Rotina do Cardiologista ­ 2023 Proposta de inclusão do strain no algoritmo integrado de avaliação da função diastólica, adaptado e traduzido de Nagueh et al. 67 AE: átrio esquerdo; Ap: duração da onda A reversa pulmonar; Am: duração da onda A mitral; DD: disfunção diastólica; FEVEr: fração de ejeção do ventrículo esquerdo reduzida; IT: insuficiência tricúspide; SAEr: strain do AE de reservatório; SLGVE: strain longitudinal global do ventrículo esquerdo. Se remodelamento concêntrico, confirmar com SLGVE. Na presença de FEVEr, tempo de desaceleração da onda E mitral (TDE) < 160 ms e onda S < D pulmonar também são parâmetros de pressão de enchimento aumentada. Esse algoritmo não se aplica a pacientes com fibrilação atrial (FA), calcificação do anel mitral ou valvopatia mitral maior que discreta, bloqueio de ramo esquerdo (BRE), ritmo de marca-passo, próteses valvares ou hipertensão pulmonar (HP) primária grave.


Assuntos
Fibrilação Atrial , Cardiologia , Disfunção Ventricular Esquerda , Humanos , Ecocardiografia Doppler , Brasil , Fibrilação Atrial/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Função Ventricular Esquerda
19.
J. bras. nefrol ; 46(1): 70-78, Mar. 2024. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1534765

RESUMO

ABSTRACT Introduction: Acute Kidney Injury (AKI) in the Intensive Care Unit (ICU) have concepts of diagnosis and management have water balance as their main point of evaluation. In our ICU, from 2004 to 2012, the nephrologist's participation was on demand only; and as of 2013 their participation became continuous in meetings to case discussion. The aim of this study was to establish how an intense nephrologist/intensivist interaction influenced the frequency of dialysis indication, fluid balance and pRIFLE classification during these two observation periods. Methods: Retrospective study, longitudinal evaluation of all children with AKI undergoing dialysis (2004 to 2016). Parameters studied: frequency of indication, duration and volume of infusion in the 24 hours preceding dialysis; diuresis and water balance every 8 hours. Non-parametric statistics, p ≤ 0.05. Results: 53 patients (47 before and 6 after 2013). There were no significant differences in the number of hospitalizations or cardiac surgeries between the periods. After 2013, there was a significant decrease in the number of indications for dialysis/year (5.85 vs. 1.5; p = 0.000); infusion volume (p = 0.02), increase in the duration of dialysis (p = 0.002) and improvement in the discrimination of the pRIFLE diuresis component in the AKI development. Conclusion: Integration between the ICU and pediatric nephrology teams in the routine discussion of cases, critically approaching water balance, was decisive to improve the management of AKI in the ICU.


RESUMO Introdução: Os conceitos sobre diagnóstico e conduta da Lesão Renal Aguda (LRA) na Unidade de Terapia Intensiva (UTI) tem como ponto primordial a avaliação do balanço hídrico. Em nossa UTI, de 2004 a 2012, a participação do nefrologista era sob demanda. A partir de 2013, a participação passou a ser contínua em reunião de discussão de casos. O objetivo deste estudo foi determinar como a maior interação nefrologista/intensivista influenciou a frequência de indicação de diálise, no balanço hídrico e na classificação pRIFLE durante esses dois períodos de observação. Método: Estudo retrospectivo, avaliação longitudinal de todas as crianças com LRA em diálise (2004 a 2016). Parâmetros estudados: frequência de indicação, tempo de duração e volume de infusão nas 24 horas precedendo a diálise; diurese e balanço hídrico a cada 8 horas. Estatística não paramétrica, p ≤ 0,05. Resultado: 53 pacientes (47 antes e 6 após 2013). Sem diferença significativa no número de internações e nem de cirurgias cardíacas entre os períodos. Após 2013, houve diminuição significativa no número de indicação de diálise/ano (5,85 vs. 1,5; p = 0,000); no volume de infusão (p = 0,02), aumento do tempo de duração da diálise (p = 0,002) e melhora da discriminação do componente diurese do pRIFLE na indicação de LRA. Conclusão: Integração entre equipes de UTI e nefrologia pediátrica na discussão rotineira de casos, abordando criticamente o balanço hídrico, foi determinante para a melhora na conduta da LRA na UTI.

20.
Horiz. med. (Impresa) ; 23(3)jul. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1514217

RESUMO

Objetivo: Determinar la eficacia de la implementación del Consultorio de Atención Inmediata como estrategia de gestión de calidad en el Servicio de Emergencia de un hospital público de Lima, Perú. Materiales y métodos: Estudio analítico, cuasi experimental de antes y después, con grupos diferentes, que se realizó en 338 usuarios externos atendidos en el Servicio de Emergencia del Hospital María Auxiliadora. Se evaluó el tiempo de espera antes y después de la implementación del Consultorio de Atención Inmediata, así como la satisfacción a través del cuestionario SERVQUAL modificado -validado y recomendado por el Ministerio de Salud (Minsa) y aplicado en el grupo de posimplementación-, además de su relación con el tiempo de espera obtenido. El análisis se realizó a través del software de IBM SPSS S25.0 mediante medidas de frecuencias y porcentajes, diferencia de medias en grupos distintos con el test de Levene y la medida no paramétrica del coeficiente de correlación de Spearman con un nivel de significancia p < 0,05. Resultados: Los resultados mostraron predominio del sexo femenino (60,95 %), en el rango de edad de 14 a 29 años (24,56 %), en la prioridad IV (67,16 %); el tiempo de espera para la atención tuvo una media de 17,70 previo a la implementación y una media de 4,27 posterior a esta, por lo tanto, hubo una diferencia significativa después de la estrategia de gestión (p < 0,00). La satisfacción del Consultorio de Atención Inmediata se obtuvo en el 56,21 % de los usuarios externos, con énfasis en la dimensión empatía (76,33 %) y capacidad de respuesta (69,23 %), mientras que la dimensión con menor satisfacción fue la fiabilidad (48,52 %), además de obtener una correlación significativa inversa entre el tiempo de espera y la satisfacción (p < 0,01 y rho: -0,39). Conclusiones: La implementación del Consultorio de Atención Inmediata en el Servicio de Emergencia fue eficaz; en consecuencia, el tiempo de espera disminuyó, lo cual, a su vez, generó satisfacción en el usuario externo.


Objective: To determine the effectiveness of the implementation of the Immediate Care Office as a quality management strategy at the Emergency Service of a public hospital in Lima, Peru. Materials and methods: An analytical, quasi-experimental, before-and-after study conducted with 338 outpatients from different groups treated at the Emergency Service of Hospital María Auxiliadora. Before and after the implementation of the Immediate Care Office, waiting time, satisfaction-assessed through the modified SERVQUAL questionnaire, which was validated and recommended by the Ministry of Health and administered to the postimplementation group-as well as the relationship between satisfaction and waiting time were evaluated. The analysis was performed using IBM SPSS statistics V25.0, frequencies and percentages, the mean difference of both groups obtained through the Levene's test, and the nonparametric measurement of the Spearman's correlation coefficient with a significance level of p < 0.05. Results: The results showed a predominance of the female sex (60.95 %), the 14-to-29-year age range (24.56 %) and the Emergency Severity Index level IV (67.16 %). The average waiting time accounted for 17.70 and 4.27 before and after the office implementation, respectively. Therefore, there was a significant difference after the management strategy (p < 0.00). Out of all outpatients, 56.21 % were satisfied with the implementation of the Immediate Care Office, mainly with the empathy (76.33 %) and responsiveness (69.23 %) dimensions, while reliability was the dimension with the lowest satisfaction score (48.52 %). Additionally, there was a significant inverse correlation between waiting time and satisfaction (p < 0.01 and rho: -0.39). Conclusions: The implementation of the Immediate Care Office at the Emergency Service was effective since it reduced the waiting time, which in turn brought satisfaction to the outpatients.

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