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Daily living activities present a diverse array of task and environmental constraints, highlighting the critical role of adapting gait initiation (GI) for an individual's quality of life. This study investigated the effects of GI directions, obstacle negotiation, and leg dominance on anticipatory postural adjustments and stepping kinematics. Fourteen active, young, healthy individuals participated in GI across 4 directions-forward, medial 45°, lateral 45°, and lateral 90°-with variations in obstacle presence and leg dominance. Results revealed a consistent decreasing trend in maximum center of pressure displacement, anticipatory postural adjustment duration, step distance, and swing leg velocity with lateral shifts in GI directions, yet the step duration and swing leg heel trajectory were not affected by GI directions except in lateral 90° GI. Center of pressure displacements were intricately scaled to directional propulsive forces generation, and the stepping kinematics were influenced by the directional modifications in movements. With obstacles, modifications in anticipatory postural adjustment metrics and stepping kinematics reflected the obstacle clearance movements. The dominant leg GI exhibited longer step durations and greater movement variability in medial 45° GI. The current investigation of GI factors expands our existing understanding of GI dynamics and offers valuable insights applicable to fall prevention and gait rehabilitation strategies.
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We report on the detailed structural analysis of a series of 11 new quaternary rare earths containing thiosilicates, AkRE2Si2S8 (Ak = Ca and Sr; RE = La, Ce, Pr, Nd, Sm, Gd, and Tb), synthesized using the flux-assisted boron chalcogen mixture method. High quality crystals were grown and used to determine their crystal structures by single crystal X-ray diffraction. All members of the AkRE2Si2S8 series crystallize in the trigonal crystal system with space group R3Ì c (space group no. 167). Polycrystalline powders were used for physical property measurements, including magnetic susceptibility, diffuse reflectance in the UV-visible range, and scintillation. Magnetic measurements indicated that CaRE2Si2S8 (RE = Nd and Tb) exhibits paramagnetic behavior with a slightly negative Weiss constant. The band gaps of the materials were determined from diffuse reflectance data, and optical band gaps were estimated to be 2.5(1) and 2.9(1) eV for CaCe2Si2S8 and CaGd2Si2S8, respectively. CaCe2Si2S8, CaTb2Si2S8, and SrCe2Si2S8 exhibited intense green luminescence upon irradiation with 375 nm ultraviolet light and, furthermore, scintillated when exposed to X-rays. Radioluminescence measurements of CaCe2Si2S8 powder revealed green emission with an intensity approximately 14% of that emitted by bismuth germanium oxide powder.
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Health effects of space radiation are a serious concern for astronauts on long-duration missions. The lens of the eye is one of the most radiosensitive tissues in the body and, therefore, ocular health risks for astronauts is a significant concern. Studies in humans and animals indicate that ionizing radiation exposure to the eye produces characteristic lens changes, termed "radiation cataract," that can affect visual function. Animal models of radiation cataractogenesis have previously utilized inbred mouse or rat strains. These studies were essential for determining morphological changes and dose-response relationships between radiation exposure and cataract. However, the relevance of these studies to human radiosensitivity is limited by the narrow phenotypic range of genetically homogeneous animal models. To model radiation cataract in genetically diverse populations, longitudinal cataract phenotyping was nested within a lifetime carcinogenesis study in male and female heterogeneous stock (HS/Npt) mice exposed to 0.4 Gy HZE ions (n = 609) or 3.0 Gy γ-rays (n = 602) and in unirradiated controls (n = 603). Cataractous change was quantified in each eye for up to 2 years using Merriam-Focht grading criteria by dilated slit lamp examination. Virtual Optomotry™ measurement of visual acuity and contrast sensitivity was utilized to assess visual function in a subgroup of mice. Prevalence and severity of posterior lens opacifications were 2.6-fold higher in HZE ion and 2.3-fold higher in γ-ray irradiated mice compared to unirradiated controls. Male mice were at greater risk for spontaneous and radiation associated cataracts. Risk for cataractogenesis was associated with family structure, demonstrating that HS/Npt mice are well-suited to evaluate genetic determinants of ocular radiosensitivity. Last, mice were extensively evaluated for cataract and tumor formation, which revealed an overlap between individual susceptibility to both cancer and cataract.
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Catarata , Cristalino , Lesões por Radiação , Camundongos , Ratos , Masculino , Feminino , Humanos , Animais , Catarata/etiologia , Catarata/epidemiologia , Catarata/patologia , Lesões por Radiação/epidemiologia , Cristalino/patologia , Cristalino/efeitos da radiação , Raios gama/efeitos adversos , Íons , Relação Dose-Resposta à RadiaçãoRESUMO
Ion mobility (IM) separations, especially when combined with mass spectrometry, offer the opportunity for the rapid analysis and characterization of mixtures. However, the limited resolution afforded by many IM systems means that in practice applications may be limited. Here we have employed an IM separation on a high-resolution cyclic IM device with MS/MS to separate and characterize mixtures of sulfated isomers of tyrosine and associated metabolites containing multiple sulfated isoforms present in reaction mixtures. The cIMS device allowed ions, not resolved using a single pass, to be subjected to multiple passes, enabling the resolution of those with similar collision cross sections (CCS). Predicted single pass CCS values calculated for the isomers likely to be present in these mixtures showed only small differences between them, ranging between of between 0.1 - 0.7 % depending on structure. These small differences highlight the high degree of mobility resolution required for separating the isomers. Experimentally different isoforms of tyrosine sulfate and sulfated tyrosine metabolites could be sufficiently resolved via multipass separations (3-35 passes). This degree of separation provided resolving powers of up to 384 CCS/ΔCCS for sulfated dopamine which enabled good MS/MS spectra to be generated. In human urine the presence of a single sulfated form of tyrosine was detected and identified as the O-sulfate after 3 passes based on the synthetic standard. Of the other tyrosine-related sulfates for which synthetic standards had been prepared only dopamine sulfate was detected in this sample.
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Sulfatos , Espectrometria de Massas em Tandem , Humanos , Dopamina , Isomerismo , Isoformas de ProteínasRESUMO
In this investigation, we examined the influence of two approaches of motor skill learning (differential learning and repetition-based) for an explosive motor skill. Twenty-seven individuals completed four training sessions of a standing broad jump task, presented with either differential training or a repetition-based approach. We collected pre-and post-training assessments that included maximal jump distances used to index performance and the recording of ground reaction forces to determine potential biomechanical changes (normalized vertical ground reaction force - GRFvert, rate of force development - RFD, and horizontal take-off velocity - Vhor). Results showed that differential training exhibited greater jump distances than repetition-based training (p < .001) but no training effect was found for jump distances between pre- and post-assessments for either training approach (p = .15). However, a significant increase occurred for Vhor with greater velocities achieved following training (p = .03). Overall, differential training failed to show the expected performance enhancements for a discrete, explosive motor task; this may be related to limited exposure and task specific demands of the movement. Further research is needed to better understand the task factors influencing skill acquisition from differential training.
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Exercício Pliométrico , Humanos , Movimento , Posição OrtostáticaRESUMO
This work examines the temporal structure of force fluctuations during maximal handgrip with detrended fluctuation analysis (DFA α). Here, we assess the influence of fatigue and sex on force complexity during unimanual handgrip for the fatigued and the contralateral, non-fatigued hand. Participants randomly completed experimental sessions requiring fatiguing handgrip contractions or control measurements only. Maximal unimanual forces of both hands were measured before and after the fatigue trial or a time-matched control visit. DFA revealed substantially lower alpha values for females (PRE = 1.15, POST = 1.25) compared to males (PRE = 1.30, POST = 1.33) regardless of fatigue (p < 0.01, d = 0.738) for the dominant hand with a similar pattern observed for the contralateral, non-fatigued hand (p = 0.045, d = 0.561). Females also showed greater alpha changes (Δ = 0.09) versus males (Δ = 0.01) following fatigue (p = 0.028, ηp2 = 0.151). The data provide evidence of reduced force complexity during successive maximal handgrip contractions for females, but not males. Our findings highlight task-specific factors involving force control and demonstrate the utility of complexity analyses to provide insights regarding the influence of sex on motor control strategies.
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Fadiga Muscular , Músculo Esquelético , Humanos , Masculino , Feminino , Força da Mão , Fractais , Caracteres Sexuais , Fadiga , Eletromiografia , Contração IsométricaRESUMO
The use of HILIC-based separations for the analysis of polar metabolites in metabolic phenotyping studies is well established. Here, we demonstrate the increased coverage of the polar metabolome obtained by travelling wave (TW) ion mobility (IM) instruments combined with HILIC and mass spectrometry (MS) for metabotyping rat and mouse urine samples. Profiling was performed using either a linear TW IM-MS based instrument with a path length of 40 cm or an instrument with a cyclic travelling wave analyser (cIM) with a path length of 95 cm. Due to the added resolution afforded by using both the linear and cyclic IM geometries with MS detection (IM-MS) significant increases in feature count (m/z-tR pairs) were generally obtained compared to HILIC-MS alone. In addition, the use of both linear and cyclic IM-MS improved the quality of the mass spectra obtained as a result of the separation of co-eluting analytes. As would be expected from the increased path length of the cyclic IM-MS instrument compared to the linear device, the largest gains in feature detection were obtained for the HILIC-cIM-MS combination. By increasing the resolution of coeluting components, the cyclic IM-MS instrumentation also provided the largest improvement in the quality of the mass spectral data obtained. When applied to mouse urines obtained from both control and gefitinib-dosed mice, time-related changes were detected in those obtained from the treated animals that were not seen in the controls. Polar metabolites affected by drug administration included, but were not limited to, hypoxanthine, 1,3-dimethyluracil and acetylcarnitine. The changes seen in the relative concentrations of these endogenous metabolites appeared to be related to drug concentrations in the plasma and urine suggesting a pharmacometabodynamic link.
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Líquidos Corporais , Metaboloma , Ratos , Camundongos , Animais , Espectrometria de Massas/métodos , Cromatografia Líquida de Alta Pressão/métodos , Interações Hidrofóbicas e Hidrofílicas , Metabolômica/métodosRESUMO
BACKGROUND: Improved COVID-19 prevention is needed for immunocompromised individuals. METHODS: Prospective study of healthcare workers (HCW) and immunocompromised participants with baseline serology following 2 mRNA vaccines and who were retested after dose 3 (D3); multivariable regression was used to identify predictors of serological responses. IFNγ/TNFα T-cell responses were assessed in a subset. RESULTS: 536 participants were included: 492 immunocompromised [(206 solid organ transplant (SOT), 128 autoimmune, 80 hematologic malignancy (HM), 48 solid tumor, 25 HIV], 44 HCW. D3 significantly increased Spike IgG levels among all, but SOT and HM participants had the lowest median antibody levels post-D3 (increase from 0.09 to 0.83 and 0.27 to 1.92, respectively), versus HCW and persons with HIV, autoimmune conditions, and solid tumors (increases from 4.44 to 19.79, 2.9 to 15.75, 3.82 to 16.32, and 4.1 to 25.54, respectively). Seropositivity post-D3 was lowest for SOT (49.0%) and HM (57.8%), versus others (>90% seropositive). Neutralization post-D3 was lowest among SOT and HM. Predictors of lower antibody levels included low baseline levels and shorter intervals between vaccines. T-cell responses against Spike increased significantly among HCW and non-significantly among immunocompromised individuals. CONCLUSIONS: D3 significantly improves serological but not T-cell responses among immunocompromised individuals. SOT and HM patients have suboptimal responses to D3.
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A series of transition-metal-containing rare earth thiosilicates, RE3TM0.5SiS7 (RE = Gd-Yb; TM = Fe, Co, Ni), was obtained via flux crystal growth utilizing the boron chalcogen mixture (BCM) method. The series includes the first reported ytterbium-containing thiosilicates crystallizing in this structure type. The thiosilicates crystallize in the hexagonal crystal system in space group P63. The use of the BCM method to synthesize phase-pure samples of the title compounds for magnetic measurements is discussed, highlighting how the approach avoids some of the difficulties that plague typical chalcogenide syntheses. Magnetic measurements demonstrate that some of the compounds order antiferromagnetically and exhibit transition temperatures below 15 K.
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Overweight and obesity are consistently associated with lower physical activity (PA) levels and greater sedentary behavior (SB) in population studies. To date, no review has evaluated the factors associated with these behaviors in the specific population who have developed obesity/overweight. The aim of this systematic review was to identify the correlates/determinants of SB and PA in adults with overweight and obesity. Five databases were searched for studies, which reported factors or outcomes relating to PA or SB in adults living with overweight/obesity, published from 1980 to 2021. The factors were categorized using a socioecological model, strength, and direction of association. Of 34,058 articles retrieved, 45 studies were included, and 155 factors were identified. Self-efficacy, intrinsic motivation, exercise enjoyment, self-perceived good health, and social support were consistently associated with higher levels of PA. Consistent negative correlations were married females, increased BMI, obesity severity, pain, number of comorbidities, lack of time, energy, and willpower, and hilly terrain. Few studies (n = 12) examined SB, and no evidence for consistent associations were found. This review identified several correlates specific to PA in this population. Further studies are required to identify directionality and distal correlates for PA and all correlate levels of SB.
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Sobrepeso , Comportamento Sedentário , Feminino , Humanos , Adulto , Exercício Físico , Obesidade/epidemiologia , Índice de Massa CorporalRESUMO
This study investigated the effects of a non-contact boxing exercise program on maximum expiratory pressure and aerodynamic voice measurements. METHODS: Eight adult males diagnosed with Parkinson's disease participated in the study. Individuals participated in twice-weekly exercise classes lasting one hour across 12-months. Dependent variables were measured on three baseline days and then at six additional time points. A pressure meter acquired maximum expiratory pressure, and a pneumotachograph system acquired transglottal airflow and subglottal air pressure. RESULTS: Measures of average maximum expiratory pressure significantly increased after 9- and 12- months of exercise when compared to baseline. There was an increasing trend for these measures in all participants, with a corresponding large effect size. Measures of transglottal airflow and subglottal pressure did not change over the course of 9- or 12-months, although their stability may indicate that the exercise program influenced maintenance of respiratory-phonatory coordination during voicing. CONCLUSIONS: A non-contact boxing exercise program had a significant effect on maximum expiratory pressure in people with Parkinson's disease. The aerobic nature of the program and challenges to the respiratory muscles potentially explain the "ingredient" causing this effect. The small sample size of this pilot study necessitates future research incorporating larger and more diverse participants.
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Nine new rare earth magnesium-containing thiosilicates of the formula RE3Mg0.5SiS7 (Ln = Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er) were synthesized in an alkali halide flux using the boron chalcogen mixture (BCM) method. Crystals of high quality were produced, and their structures were determined by single-crystal X-ray diffraction. The compounds crystallize in the hexagonal crystal system in the P63 space group. Phase pure powders of the compounds were used for magnetic susceptibility measurements and for second-harmonic generation (SHG) measurements. Magnetic measurements indicate that Ce3Mg0.5SiS7, Sm3Mg0.5SiS7, and Dy3Mg0.5SiS7 exhibit paramagnetic behavior with a negative Weiss temperature over the 2-300 K temperature range. SHG measurements of La3Mg0.5SiS7 demonstrated SHG activity with an efficiency of 0.16 times the standard potassium dihydrogen phosphate (KDP).
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The metabolism and pharmacokinetics of fasiglifam (TAK-875, 2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid), a selective free fatty acid receptor 1 (FFAR1)/GPR40 agonist, were studied following intravenous (5 mg/kg) and oral administration (10 and 50 mg/kg) to male and female Sprague Dawley rats.Following intravenous dosing at 5 mg/kg, peak observed plasma concentrations of 8.8/9.2 µg/ml were seen in male and female rats respectively.Following oral dosing, peak plasma concentrations at 1 h of ca. 12.4/12.9 µg/ml for 10 mg/kg and 76.2/83.7 µg/ml for 50 mg/kg doses were obtained for male and female rats respectively. Drug concentrations then declined in the plasma of both sexes with t1/2's of 12.4 (male) and 11.2 h (female). Oral bioavailability was estimated to be 85-120% in males and females at both dose levels.Urinary excretion was low, but in a significant sex-related difference, female rats eliminated ca. 10-fold more drug-related material by this route.Fasiglifam was the principal drug-related compound in plasma, with 15 metabolites, including the acyl glucuronide, also detected. In addition to previously identified metabolites, a novel biotransformation, that produced a side-chain shortened metabolite via elimination of CH2 from the acetyl side chain was noted with implications for drug toxicity.
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Receptores Acoplados a Proteínas G , Sulfonas , Ratos , Masculino , Feminino , Animais , Ratos Sprague-Dawley , Administração Intravenosa , Receptores Acoplados a Proteínas G/agonistas , Administração Oral , Injeções IntravenosasRESUMO
Background: Performance asymmetries between the lower limbs have been reported across a variety of variables and for numerous motor tasks including double leg squats. Additionally, the degree of symmetry is often used as a recovery metric during rehabilitation programs. Hypothesis/Purpose: The purpose of this investigation was to examine leg asymmetry during a bodyweight double leg squat task and assess the effects of squat speed in a physically active population. Study Design: Cross-over Study Design. Methods: Eighteen healthy individuals completed two sets of 20 squats at two tempos (preferred tempo and 60 bpm) while ground reaction force and center of pressure data were recorded using dual force plates. Peak vertical ground reaction force, force impulse, and center of pressure (COP) standard deviation in the anterior-posterior (AP) and mediolateral (ML) direction were calculated and analyzed to identify any differences between legs, tempo, and as a function of repetitions. Significance was set at ρ ≤ .05. Results: The subjects exhibited greater ground reaction forces during the self-paced tempo compared to the metronome-paced tempo (F 1,79 = 14.48, p < .001) with the preferred leg generating larger values than the non-preferred leg during the self-paced condition. There was also a significant tempo x leg interaction for force impulse (F 1,79 = 5.927, p = 0.015). A greater amount of COP variability was found in the preferred leg compared to the non-preferred leg in both the AP (F 1,79 = 30.147, p < 0.001) and ML (F 1,79 = 41.204, p < 0.001) directions. Conclusions: These findings highlight the importance of considering multiple levels of analysis when assessing lower limb symmetry as separate variables may provide differential evidence for asymmetry. Practically, these results emphasize the need for coaches and practitioners to consider different degrees of lower limb asymmetries that may impact the development and design of strength and rehabilitation programs. Level of Evidence: 3.
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During upright standing, individuals often use co-contraction muscle activity at the ankle joint when encountering increased postural difficulty; however, this strategy has been shown to be maladaptive. The purpose of the current investigation was to examine the effect of sloped standing on postural sway and muscle co-contraction at the ankle joint as a function of postural difficulty. Twelve young (21.67 ± 1.11 years) adults performed upright standing on flat, declined, and inclined support surfaces. Center of pressure displacements indexed postural sway while electromyography data were collected for the tibialis anterior and gastrocnemius medialis muscles. A co-contraction index and a nonlinear coupling metric (cross-approximate entropy) were computed between ankle dorsiflexor and plantar flexor muscles (tibialis anterior/gastrocnemius medialis) activity. The results showed that higher degrees of postural difficulty led to increased amounts of sway as well as increased sway regularity. Lower co-contraction index was observed for higher degrees of postural difficulty; however, increased dynamic coupling occurred with deviations from the flat standing condition. Overall, increased postural difficulty as manipulated by sloped standing (in either inclined or declined conditions) resulted in individuals adopting a more regular sway trajectory that may be due, in part, to a stronger dynamic coupling strategy occurring at the neuromuscular level.
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Contração Muscular , Equilíbrio Postural , Eletromiografia/métodos , Humanos , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Equilíbrio Postural/fisiologia , Posição OrtostáticaAssuntos
Icterícia , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Readmissão do PacienteRESUMO
With the increased use of technology, relaxation interventions are finding their way into technology devices like virtual reality head-mounted displays (VR HMDs). However, there is a lack of evidence on the efficacy of VR relaxation interventions to reduce anxiety in athletes and how that is portrayed in their movement patterns. The purpose of the current study was to examine how a VR relaxation intervention affected perceived anxiety levels and penalty kick performance of female soccer players. Thirteen female soccer players took five penalty kicks in baseline, stress-induced, and VR relaxation conditions. Perceived levels of anxiety, self-confidence, mental effort, heart rate (HR), accelerometry of the lumbar spine and thigh, and performance in each condition was obtained. Results indicated that the VR intervention significantly reduced cognitive anxiety and somatic anxiety from baseline (p = 0.002; p = 0.001) and stress (p < 0.001; p < 0.001) with large effect sizes (Kendall's W = 0.72; 0.83). VR significantly increased self-confidence from baseline (p = 0.002) and stress (p = 0.001) with a large effect size (Kendall's W = 0.71). Additionally, all participants felt that VR helped them relax. Mental effort was significantly higher in the stress condition compared to that in baseline (p = 0.007) with moderate effect size (Kendall's W = 0.39). Peak acceleration and performance were not significantly influenced by stress or VR. This study serves as an initial step to evaluate VR relaxation interventions on performance in female soccer players.
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PURPOSE: To assess the performance of a proton-specific knowledge based planning (KBPP) model in creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of patients with prostate cancer. MATERIALS AND METHODS: Forty-five patients with localized prostate cancer, who had previously been treated with volumetric modulated arc therapy, were selected and replanned with robustly optimized IMPT. A KBPP model was generated from the results of 30 of the patients, and the remaining 15 patient results were used for validation. The KBPP model quality and accuracy were evaluated with the model-provided organ-at-risk regression plots and metrics. The KBPP quality was also assessed through comparison of expert and KBPP-generated IMPT plans for target coverage and organ-at-risk sparing. RESULTS: The resulting R 2 (mean ± SD, 0.87 ± 0.07) between dosimetric and geometric features, as well as the χ2 test (1.17 ± 0.07) between the original and estimated data, showed the model had good quality. All the KBPP plans were clinically acceptable. Compared with the expert plans, the KBPP plans had marginally higher dose-volume indices for the rectum V65Gy (0.8% ± 2.94%), but delivered a lower dose to the bladder (-1.06% ± 2.9% for bladder V65Gy). In addition, KBPP plans achieved lower hotspot (-0.67Gy ± 2.17Gy) and lower integral dose (-0.09Gy ± 0.3Gy) than the expert plans did. Moreover, the KBPP generated better plans that demonstrated slightly greater clinical target volume V95 (0.1% ± 0.68%) and lower homogeneity index (-1.13 ± 2.34). CONCLUSIONS: The results demonstrated that robustly optimized IMPT plans created by the KBPP model are of high quality and are comparable to expert plans. Furthermore, the KBPP model can generate more-robust and more-homogenous plans compared with those of expert plans. More studies need to be done for the validation of the proton KBPP model at more-complicated treatment sites.
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Thousands of babies are given toys for their zeroth birthday But what happens if that baby is admitted to neonatal intensive care? In a global first, we describe the population of toys found in incubators on neonatal intensive care unit.
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Unidades de Terapia Intensiva Neonatal , Terapia Intensiva Neonatal , Estudos Transversais , Hospitalização , Humanos , Recém-Nascido , Jogos e BrinquedosRESUMO
The effects of intravenous gefitinib (10 mg/kg), an anilinoquinazoline thymidylate kinase inhibitor (TKI), selective for the epidermal growth factor receptor (EGFR), on the urinary metabotypes of mice were studied. We hypothesized that, in response to the administration of gefitinib, there might be significant changes in the excretion of many endogenous metabolites in the urine, which could be correlated with the plasma pharmacokinetics (PK) of the drug. In order to investigate this conjecture, urine from male C57 BL6 mice was collected before IV dosing (10 mg/kg) and at 0-3, 3-8, and 8-24 h post-dose. The samples were profiled by UPLC/IM/MS and compared with the profiles obtained from undosed control mice with the data analyzed using multivariate statistical analysis (MVA). This process identified changes in endogenous metabolites over time and these were compared with drug and drug metabolite PK and excretion. While the MVA of these UPLC/IM/MS data did indeed reveal time-related changes for endogenous metabolites that appeared to be linked to drug administration, this analysis did not highlight the presence of either the drug or its metabolites in urine. Endogenous metabolites affected by gefitinib administration were identified by comparison of mass spectral, retention time and ion mobility-derived collision cross section data (compared to authentic standards wherever possible). The changes in endogenous metabolites resulting from gefitinib administration showed both increases (e.g., tryptophan, taurocholic acid, and the dipeptide lysyl-arginine) and decreases (e.g., deoxyguanosine, 8-hydroxydeoxyguanosine, and asparaginyl-histidine) relative to the control animals. By 8-24 h, the post-dose concentrations of most metabolites had returned to near control values. From these studies, we conclude that changes in the amounts of endogenous metabolites excreted in the urine mirrored, to some extent, the plasma pharmacokinetics of the drug. This phenomenon is similar to pharmacodynamics, where the pharmacological effects are related to the drug concentrations, and by analogy, we have termed this effect "pharmacometabodynamics".