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1.
Cancer ; 130(3): 467-475, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37788149

RESUMO

BACKGROUND: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study. METHODS: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age. RESULTS: In the total birth cohort (n = 6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70). CONCLUSIONS: This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.


Assuntos
Síndrome de Beckwith-Wiedemann , Neoplasias Renais , Neoplasias Hepáticas , Tumor de Wilms , Lactente , Criança , Humanos , Incidência , Síndrome de Beckwith-Wiedemann/complicações , Síndrome de Beckwith-Wiedemann/epidemiologia , Síndrome de Beckwith-Wiedemann/genética , Tumor de Wilms/epidemiologia , Neoplasias Renais/complicações , Neoplasias Hepáticas/complicações
2.
Pediatr Blood Cancer ; 71(9): e31169, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38961583

RESUMO

Methotrexate is a critical component of curative chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but is associated with neurotoxicity. Information on long-term outcomes following an acute neurotoxic event is limited. Therefore, this report compares neurocognitive performance more than 12 months post diagnosis (mean = 4 years) between ALL patients with (n = 25) and without (n = 146) a history of acute neurotoxicity. Compared to children with no documented on-treatment neurotoxic event, children who experienced a neurotoxic event during treatment exhibited poorer performance on measures of fine motor function (p = .02) and attention (p = .02). Children with ALL who experience acute neurotoxicity may be candidates for early neuropsychological screening and intervention.


Assuntos
Antimetabólitos Antineoplásicos , Metotrexato , Síndromes Neurotóxicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Feminino , Masculino , Síndromes Neurotóxicas/etiologia , Criança , Pré-Escolar , Antimetabólitos Antineoplásicos/efeitos adversos , Adolescente , Seguimentos , Testes Neuropsicológicos , Prognóstico
3.
Pediatr Nephrol ; 39(2): 569-577, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37552466

RESUMO

BACKGROUND: In patients requiring mechanical circulatory support (MCS), the incidence of acute kidney injury (AKI) is between 37 and 63%. In this study, we performed an exploratory analysis evaluating the relationship of multiple urine biomarkers with AKI development in pediatric MCS patients. METHODS: This is a single center retrospective study in a pediatric cohort receiving MCS from August 2014 to November 2020. We measured 14 urine biomarkers of kidney injury on day 1 following MCS initiation and analyzed their association with development of AKI in the first 7 days of MCS initiation. RESULTS: Sixty patients met inclusion criteria. Patients with AKI were more likely to be supported by venoarterial extracorporeal membrane oxygenation (65% vs. 8.3%, p < 0.001), compared to the no AKI group and less likely to have ventricular assist devices (10% vs. 50%, p < 0.001). There was a significant increase in the median urine albumin and urine osteoactivin in the AKI group, compared to the no AKI group (p = 0.020 and p = 0.018, respectively). When normalized to urine creatinine (UCr), an increased log osteoactivin/UCr was associated with higher odds of AKI development (OR: 2.05; 95% CI: 1.07, 4.44; p = 0.028), and higher log epidermal growth factor (EGF)/UCr (OR: 0.41; 95% CI: 0.15, 0.96) was associated with decreased odds of AKI. CONCLUSIONS: Early increase in urine osteoactivin is associated with AKI development within 7 days of MCS initiation in pediatric patients. Contrary, an increased urine EGF is associated with kidney protection. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Injúria Renal Aguda , Fator de Crescimento Epidérmico , Humanos , Criança , Estudos Retrospectivos , Biomarcadores/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Creatinina/urina , Fatores de Transcrição
4.
Eur J Pediatr ; 183(8): 3253-3262, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38700692

RESUMO

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.  Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.


Assuntos
Doença de Crohn , Ustekinumab , Humanos , Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Adolescente , Criança , Resultado do Tratamento , Indução de Remissão , Índice de Gravidade de Doença
5.
Int J Sport Nutr Exerc Metab ; 34(4): 207-217, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38653456

RESUMO

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.


Assuntos
Absorciometria de Fóton , Metabolismo Basal , Composição Corporal , Estradiol , Ciclo Menstrual , Progesterona , Humanos , Feminino , Composição Corporal/efeitos dos fármacos , Metabolismo Basal/efeitos dos fármacos , Ciclo Menstrual/efeitos dos fármacos , Adulto Jovem , Estradiol/sangue , Progesterona/sangue , Adulto , Estudos Retrospectivos , Contraceptivos Hormonais/administração & dosagem , Contraceptivos Hormonais/farmacologia , Atletas , Adolescente
6.
J Am Chem Soc ; 145(16): 9059-9071, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37040588

RESUMO

Single-strand breaks (SSBs) induced via electron attachment were previously observed in dry DNA under ultrahigh vacuum (UHV), while hydrated electrons were found not able to induce this DNA damage in an aqueous solution. To explain these findings, crossed electron-molecular beam (CEMB) and anion photoelectron spectroscopy (aPES) experiments coupled to density functional theory (DFT) modeling were used to demonstrate the fundamental importance of proton transfer (PT) in radical anions formed via electron attachment. Three molecular systems were investigated: 5'-monophosphate of 2'-deoxycytidine (dCMPH), where PT in the electron adduct is feasible, and two ethylated derivatives, 5'-diethylphosphate and 3',5'-tetraethyldiphosphate of 2'-deoxycytidine, where PT is blocked due to substitution of labile protons with the ethyl residues. CEMB and aPES experiments confirmed the cleavage of the C3'/C5'-O bond as the main dissociation channel related to electron attachment in the ethylated derivatives. In the case of dCMPH, however, electron attachment (in the aPES experiments) yielded its parent (intact) radical anion, dCMPH-, suggesting that its dissociation was inhibited. The aPES-measured vertical detachment energy of the dCMPH- was found to be 3.27 eV, which agreed with its B3LYP/6-31++G(d,p)-calculated value and implied that electron-induced proton transfer (EIPT) had occurred during electron attachment to the dCMPH model nucleotide. In other words, EIPT, subduing dissociation, appeared to be somewhat protective against SSB. While EIPT is facilitated in solution compared to the dry environment, the above findings are consistent with the stability of DNA against hydrated electron-induced SSB in solution versus free electron-induced SSB formation in dry DNA.


Assuntos
Hominidae , Prótons , Animais , Modelos Moleculares , Elétrons , DNA/química , Ânions/química , Dano ao DNA
7.
Cancer ; 129(8): 1287-1294, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36692972

RESUMO

BACKGROUND: High-dose methotrexate (HD-MTX; 5000 mg/m2 ) is an important component of curative therapy in many treatment regimens for high-risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose-limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD-MTX in an ethnically diverse population of patients with ALL. METHODS: The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD-MTX at Texas Children's Cancer Center (2010-2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke-like symptoms) occurring within 21 days of HD-MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity. RESULTS: Overall, 351 patients (58.1% Latino) who received 1183 HD-MTX infusions were evaluated. Thirty-five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three-fold increased odds (OR, 3.32; 95% CI, 0.98-11.21; p = .05) for neurotoxicity compared with creatinine elevation <25%. Notably, predictors of neurotoxicity differed by ethnicity. Specifically, Latino children experienced a nearly six-fold increase in neurotoxicity odds (OR, 5.80; 95% CI, 1.39-24.17; p = .02) with serum creatinine elevation ≥50% compared with creatinine elevation <25%. CONCLUSIONS: The current findings indicate that serum creatinine elevations ≥50% may be associated with an increased risk for neurotoxicity among Latino children with ALL and may identify potential candidates for therapeutic or supportive care interventions.


Assuntos
Síndromes Neurotóxicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Metotrexato , Antimetabólitos Antineoplásicos/uso terapêutico , Creatinina , Estudos Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Síndromes Neurotóxicas/epidemiologia , Síndromes Neurotóxicas/etiologia
8.
J Phys Chem A ; 127(34): 7186-7197, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37590893

RESUMO

A collaborative effort between experiment and theory toward elucidating the electronic and molecular structures of uranium-gold clusters is presented. Anion photoelectron spectra of UAun-(n = 3-7) were taken at the third (355 nm) and fourth (266 nm) harmonics of a Nd:YAG laser, as well as excimer (ArF 193 nm) photon energies, where the experimental adiabatic electron affinities and vertical detachment energies values were measured. Complementary first-principles calculations were subsequently carried out to corroborate experimentally determined electron detachment energies and to determine the geometry and electronic structure for each cluster. Except for the ring-like neutral isomer of UAu6 where one unpaired electron is spread over the Au atoms, all other neutral and anionic UAun clusters (n = 3-7) were calculated to possess open-shell electrons with the unpaired electrons localized on the central U atom. The smaller clusters closely resemble the analogous UFn species, but significant deviations are seen starting with UAu5 where a competition between U-Au and Au-Au bonding begins to become apparent. The UAu6 system appears to mark a transition where Au-Au interactions begin to dominate, where both a ring-like and two heavily distorted octahedral structures around the central U atom are calculated to be nearly isoenergetic. With UAu7, only ring-like structures are calculated. Overall, the calculated electron detachment energies are in good agreement with the experimental values.

9.
Dev Med Child Neurol ; 65(8): 1118-1122, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36631915

RESUMO

In this case series of four paediatric patients, we present the first described cases of immunotherapy-responsive autoimmune nodopathy with IgG2 antineurofascin antibodies. In three cases, the antineurofascin antibodies were predominantly of the IgG2 subclass, a novel finding in comparison to previously described adult cases where IgG4 and/or IgG1/3 have typically been described. One patient had low signal for IgG2 with predominant IgG1 and IgG4 antibodies, a pattern commonly seen in adult patients. Two patients had antibodies targeting all three neurofascin isoforms (155, 186, and 140), whereas antibodies in the sera from the third targeted only the nodal isoforms 186 and 140, and the fourth patient only neurofascin 155. The three patients with IgG2 predominant antibodies appear to be responsive to intravenous immunoglobulin (IVIG) to varying degrees thus far, whereas the patient with IgG1/4 antibodies had poor response to IVIG but good response to steroids. Although the full clinical significance of IgG2 predominant antineurofascin antibodies in the context of childhood polyneuropathy remains unclear, emerging evidence of serological-phenotypic correlation may inform prognostication and therapeutic decision-making, warranting further study into this area. WHAT THIS PAPER ADDS: Paediatric immunotherapy-responsive nodopathies were associated with antineurofascin antibodies predominantly of the IgG2 subclass in 3 out of 4 patients. Identification of antibodies and understanding their phenotypic relevance could predict response to treatment and guide therapeutic decision-making in children.


Assuntos
Imunoglobulina G , Imunoglobulinas Intravenosas , Adulto , Humanos , Criança
10.
Pediatr Hematol Oncol ; 40(4): 407-411, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35862575

RESUMO

Survivors of childhood central nervous system (CNS) tumors experience early-onset aging-related phenotypes. DNA methylation (DNAm) age is an emerging epigenetic biomarker of physiologic age and may be predictive of chronic health conditions in long-term survivors. This report describes the course of epigenetic age acceleration using post-diagnosis blood samples (median: 3.9 years post-diagnosis; range: 0.04-15.96) from 83 survivors of pediatric CNS tumors. Epigenetic age acceleration was detected in 72% of patients, with an average difference between chronologic and DNAm age of 2.58 years (95% CI: 1.75-3.41, p < 0.001). Time from diagnosis to sample collection correlated with the magnitude of epigenetic age acceleration.


Assuntos
Neoplasias do Sistema Nervoso Central , Neoplasias Cerebelares , Meduloblastoma , Tumores Neuroectodérmicos Primitivos , Humanos , Meduloblastoma/genética , Meduloblastoma/terapia , Meduloblastoma/patologia , Tumores Neuroectodérmicos Primitivos/genética , Tumores Neuroectodérmicos Primitivos/terapia , Tumores Neuroectodérmicos Primitivos/patologia , Sobreviventes , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/terapia , Epigênese Genética
11.
Int J Sport Nutr Exerc Metab ; 33(4): 198-208, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37160293

RESUMO

The aim of this audit was to assess the representation of female athletes, dietary control methods, and gold standard female methodology that underpins the current guidelines for chronic carbohydrate (CHO) intake strategies for athlete daily training diets. Using a standardized audit, 281 studies were identified that examined high versus moderate CHO, periodized CHO availability, and/or low CHO, high fat diets. There were 3,735 total participants across these studies with only ∼16% of participants being women. Few studies utilized a design that specifically considered females, with only 16 studies (∼6%) including a female-only cohort and six studies (∼2%) with a sex-based comparison in their statistical procedure, in comparison to the 217 studies (∼77%) including a male-only cohort. Most studies (∼72%) did not provide sufficient information to define the menstrual status of participants, and of the 18 studies that did, optimal methodology for control of ovarian hormones was only noted in one study. While ∼40% of male-only studies provided all food and beverages to participants, only ∼20% of studies with a female-specific design used this approach for dietary control. Most studies did not implement strategies to ensure compliance to dietary interventions and/or control energy intake during dietary interventions. The literature that has contributed to the current guidelines for daily CHO intake is lacking in research that is specific to, or adequately addresses, the female athlete. Redressing this imbalance is of high priority to ensure that the female athlete receives evidence-based recommendations that consider her specific needs.


Assuntos
Atletas , Dieta , Carboidratos da Dieta , Humanos , Masculino , Feminino , Dieta/normas , Guias como Assunto , Caracteres Sexuais , Carboidratos da Dieta/administração & dosagem
12.
J Am Chem Soc ; 144(43): 19685-19688, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36279217

RESUMO

Here, anion photoelectron spectroscopy and first-principles quantum chemistry are used to demonstrate to what degree Au can act as a surrogate for F in UF6 and its anion. Unlike UF6, UAu6 exhibits strong ligand-ligand, i.e., Au-Au, interactions, resulting in three low-lying isomers, two of which are three-dimensional while the third isomer has a ring-like quasi two-dimensional structure. Additionally, all the UAu6 isomers have open-shell electrons, which in nearly all cases are localized on the central U atom. The adiabatic electron affinity and vertical detachment energy are measured to be 3.05 ± 0.05 and 3.28 ± 0.05 eV, respectively, and are in very good agreement with calculations.


Assuntos
Elétrons , Ligantes , Espectroscopia Fotoeletrônica , Ânions/química , Isomerismo
13.
Microb Ecol ; 84(1): 182-197, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34406445

RESUMO

Keystone species or ecological engineers are vital to the health of an ecosystem; however, often, their low abundance or biomass present challenges for their discovery, identification, visualization and selection. We report the development of fluorescent in situ hybridization of transcript-annealing molecular beacons (FISH-TAMB), a fixation-free protocol that is applicable to archaea and bacteria. The FISH-TAMB method differs from existing FISH methods by the absence of fixatives or surfactants in buffers, the fast hybridization time of as short as 15 min at target cells' growth temperature, and the omission of washing steps. Polyarginine cell-penetrating peptides are employed to deliver molecular beacons (MBs) across prokaryotic cell walls and membranes, fluorescently labeling cells when MBs hybridize to target mRNA sequences. Here, the detailed protocol of the preparation and application of FISH-TAMB is presented. To demonstrate FISH-TAMB's ability to label intracellular mRNA targets, differentiate transcriptional states, detect active and rare taxa, and keep cell viability, labeling experiments were performed that targeted the messenger RNA (mRNA) of methyl-coenzyme M reductase A (mcrA) expressed in (1) Escherichia coli containing a plasmid with a partial mcrA gene of the methanogen Methanosarcina barkeri (E. coli mcrA+); (2) M. barkeri; and (3) an anaerobic methanotrophic (ANME) enrichment from a deep continental borehole. Although FISH-TAMB was initially envisioned for mRNA of any functional gene of interest without a requirement of prior knowledge of 16S ribosomal RNA (rRNA)-based taxonomy, FISH-TAMB has the potential for multiplexing and going beyond mRNA and thus is a versatile addition to the molecular ecologist's toolkit, with potentially widespread application in the field of environmental microbiology.


Assuntos
Metano , Microbiota , Archaea , DNA Arqueal/genética , Escherichia coli/genética , Hibridização in Situ Fluorescente/métodos , Metano/metabolismo , Oxirredutases/genética , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo
14.
J Pediatr Gastroenterol Nutr ; 75(5): 601-607, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048178

RESUMO

OBJECTIVES: To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome. METHODS: Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented. RESULTS: In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0-16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P < 0.001]. Combined CS-free clinical and biomarker remission (CRP < 5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P < 0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8-4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89-8.68, P < 0.001). CONCLUSIONS: Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Masculino , Criança , Adolescente , Feminino , Infliximab/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Monitoramento de Medicamentos , Resultado do Tratamento , Doenças Inflamatórias Intestinais/tratamento farmacológico , Indução de Remissão , Biomarcadores
15.
J Phys Chem A ; 126(27): 4432-4443, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35767645

RESUMO

The results of ab initio correlated molecular orbital theory electronic structure calculations for low-lying electronic states are presented for UH and UH- and compared to photoelectron spectroscopy measurements. The calculations were performed at the CCSD(T)/CBS and multireference CASPT2 including spin-orbit effects by the state interacting approach levels. The ground states of UH and UH- are predicted to be 4Ι9/2 and 5Λ6, respectively. The spectroscopic parameters Te, re, ωe, ωexe, and Be were obtained, and potential energy curves were calculated for the low energy Ω states of UH. The calculated adiabatic electron affinity is 0.468 eV in excellent agreement with an experimental value of 0.462 ± 0.013 eV. The lowest vertical detachment energy was predicted to be 0.506 eV for the ground state, and the adiabatic ionization energy (IE) is predicted to be 6.116 eV. The bond dissociation energy (BDE) and heat of formation values of UH were obtained using the IE calculated at the Feller-Peterson-Dixon level. For UH, UH-, and UH+, the BDEs were predicted to be 225.5, 197.9, and 235.5 kJ/mol, respectively. The BDE for UH is predicted to be ∼20% lower in energy than that for ThH. The analysis of the natural bond orbitals shows a significant U+H- ionic component in the bond of UH.

16.
J Phys Chem A ; 126(50): 9392-9407, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36508745

RESUMO

A combination of high-level ab initio calculations and anion photoelectron detachment (PD) measurements is reported for the UC, UC-, and UC+ molecules. To better compare the theoretical values with the experimental photoelectron spectrum (PES), a value of 1.493 eV for the adiabatic electron affinity (AEA) of UC was calculated at the Feller-Peterson-Dixon (FPD) level. The lowest vertical detachment energy (VDE) is predicted to be 1.500 eV compared to the experimental value of 1.487 ± 0.035 eV. A shoulder to lower energy in the experimental PD spectrum with the 355 nm laser can be assigned to a combination of low-lying excited states of UC- and excited vibrational states. The VDEs calculated for the low-lying excited electronic states of UC at the SO-CASPT2 level are consistent with the observed additional electron binding energies at 1.990, 2.112, 2.316, and 3.760 eV. Potential energy curves for the Ω states and the associated spectroscopic properties are also reported. Compared to UN and UN+, the bond dissociation energy (BDE) of UC (411.3 kJ/mol) is predicted to be considerably lower. The natural bond orbitals (NBO) calculations show that the UC0/+/- molecules have a bond order of 2.5 with their ground-state configuration arising from changes in the oxidation state of the U atom in terms of the 7s orbital occupation: UC (5f27s1), UC- (5f27s2), and UC+ (5f27s0). The behavior of the UN and UC sequence of molecules and anions differs from the corresponding sequences for UO and UF.

17.
J Phys Chem A ; 126(43): 7944-7953, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36269194

RESUMO

The results of calculations of the properties of the anion UN- including electron detachment are described, which further expand our knowledge of this diatomic molecule. High-level electronic structure calculations were conducted for the UN and UN- diatomic molecules and compared to photoelectron spectroscopy measurements. The low-lying Ω states were obtained using multireference CASPT2 including spin-orbit effects up to ∼20,000 cm-1. At the Feller-Peterson-Dixon (FPD) level, the adiabatic electron affinity (AEA) of UN is estimated to be 1.402 eV and the vertical detachment energy (VDE) is 1.423 eV. The assignment of the UN excited states shows good agreement with the experimental results with a VDE of 1.424 eV. An Ω = 4 ground state was obtained for UN- which is mainly associated with the 3H ΛS state. Thermochemical calculations estimate a bond dissociation energy (BDE) for UN- (U- + N) of 665.9 kJ/mol, ∼15% larger than that of UN and UN+. The NBO analysis reveals U-N triple bonds for the UN, UN-, and UN+ species.

18.
J Chem Phys ; 157(23): 234304, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36550022

RESUMO

Mass spectrometric analysis of anionic products that result from interacting Ir- with H2O shows the efficient generation of [Ir(H2O)]- complexes and IrO- molecular anions. Anion photoelectron spectra of [Ir(H2O)]-, formed under various source conditions, exhibit spectral features that are due to three different forms of the complex: the solvated anion-molecule complex, Ir-(H2O), as well as the intermediates, [H-Ir-OH]- and [H2-Ir-O]-, where one and two O-H bonds have been broken, respectively. The measured and calculated vertical detachment energy values are in good agreement and, thus, support identification of all three types of isomers. The calculated reaction pathway shows that the overall reaction Ir- + H2O → IrO- + H2 is exothermic. Two minimum energy crossing points were found, which shuttle intermediates and products between singlet and triplet potential surfaces. This study presents the first example of water activation and splitting by single Ir- anions.

19.
Int J Sport Nutr Exerc Metab ; 32(2): 114-127, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35168200

RESUMO

Female-specific research on sports science and sports medicine (SSSM) fails to mirror the increase in participation and popularity of women's sport. Females have historically been excluded from SSSM research, particularly because their physiological intricacy necessitates more complex study designs, longer research times, and additional costs. Consequently, most SSSM practices are based on research with men, despite potential problems in translation to females due to sexual dimorphism in biological and phenotypical parameters as well as differences in event characteristics (e.g., race distances/durations). Recognition that erroneous extrapolations may hamper the efforts of females to maximize their athletic potential has created an impetus to acknowledge and readdress the sex disparity in SSSM research. To direct the priorities for future research, it is prudent to first develop a comprehensive understanding of the gaps in current knowledge by systematically "auditing" the literature. By conducting audits of the literature to highlight underdeveloped topics or identify potential problems with the quality of research, this information can then be used to expediently direct new research activities. This paper therefore presents a standardized audit methodology to establish the representation of female athletes in subdisciplines of existing SSSM research, including a template for reporting the results of key metrics. This standardized audit process will enable comparisons over time and between research subdisciplines. This working guide provides an important step toward achieving sex equity across SSSM research, with the eventual goal of providing evidence-based recommendations specific to the female athlete.


Assuntos
Medicina Esportiva , Esportes , Atletas , Feminino , Humanos , Esportes/fisiologia
20.
J Community Health Nurs ; 39(1): 25-39, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35191788

RESUMO

To explore prostate and depression screening practices as well as predictors for prostate screening among a diverse group of men seen at a nurse-led community health center. This was a retrospective, exploratory study. Social factors, depression, and prostate screening data on 267 male patients were retrieved from medical records from 2014 to 2018. Patients that were not screened for depression were associated with a lower probability of having received a PSA screening (OR = .40, p = 02). Of those screened for depression, higher scores were associated with lower PSA screening (OR = .89, p = .02). Patients who self-identified as Hispanic (OR = .19, p <. 001), African American (AA) (OR = .06, P = .01) or White (OR = .12, P = .02) had lower odds of PSA screening compared to Black-Caribbean. The above clinical evidence is a practice implication for nurses and health care professionals. Depression screening predicted higher rates of prostate screening, while higher depression scores predicted lower prostate screening. AA and Hispanic subgroups were less likely to be screened for prostate cancer than the non-U.S. born Black-Caribbean men. Findings underscore the importance of developing community-based culturally sensitive approaches to prostate preventative care. Nurses and health providers must understand that diversity within the "Black" population exists, and these differences drive health behaviors. Person-centered care that is culturally sensitive will be essential in developing trust with communities of color to increase prostate cancer screening and health equity.


Assuntos
Depressão , Detecção Precoce de Câncer , Disparidades nos Níveis de Saúde , Neoplasias da Próstata , População Negra , Centros Comunitários de Saúde , Depressão/diagnóstico , Depressão/etnologia , Humanos , Masculino , Próstata , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/prevenção & controle , Saúde Pública , Estudos Retrospectivos
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