Uncontrolled Thyroid during Pregnancy Alters the Circulative and Exerted Metabolome.

Normal levels of thyroid hormones (THs) are essential for a normal pregnancy outcome, fetal growth and the normal function of the central nervous system. Hypothyroidism, a common endocrine disorder during pregnancy, is a significant metabolic factor leading to cognitive impairments. It is essential to investigate whether patients with thyroid dysfunction may present an altered circulative and excreted metabolic profile, even after receiving treatment with thyroxine supplements. NMR metabolomics was employed to analyze 90 serum and corresponding colostrum samples. Parallel analyses of the two biological specimens provided a snapshot of the maternal metabolism through the excretive and circulating characteristics of mothers. The metabolomics data were analyzed by performing multivariate statistical, biomarker and pathway analyses. Our results highlight the impact of hypothyroidism on metabolites' composition during pregnancy and lactation. Thyroid disorder causing metabolite fluctuations may lead to impaired lipid and glucose metabolic pathways as well as aberrant prenatal neurodevelopment, thus posing a background for the occurrence of metabolic syndrome or neurogenerative diseases later in life. This risk applies to not only untreated but also hypothyroid women under replacement therapy since our findings in both biofluids framed a different metabolic phenotype for the latter group, thus emphasizing the need to monitor women adequately after treatment initiation.

Isokinetic Muscle Strength and Knee Function in Anatomical Anterior Cruciate Ligament Reconstruction With Hamstring Autografts: A Prospective Randomized Comparative Study Between Suspensory and Expandable Femoral Fixation in Male Patients.

Background Clinical performance, anterior knee stability, and isokinetic strength after anterior cruciate ligament (ACL) reconstruction with hamstring autografts are mainly influenced by graft selection, femoral tunnel preparation, and type of femoral fixation. Expandable femoral fixation devices are expected to provide a stronger initial fixation with circular graft compression, a blind-ended tunnel in the femur with less enlargement, and a theoretical double-band ACL equivalent through graft rotation. This study aimed to evaluate isokinetic strength and functional capacity after ACL reconstruction with hamstring tendons using two different anatomical femoral fixation techniques (expandable vs fixed-looped button). Methodology A total of 48 male patients with ACL deficient knees were randomized to two different femoral fixation groups, namely, the expandable (AperFix) and the standard cortical (Button) group. The primary outcome measures were isokinetic hamstrings and quadriceps strength capabilities and the hamstrings/quadriceps ratio at 60 degrees/second (°/s) and 180°/s using a Cybex before and at three, six, nine, 12, and 24 months after surgery. Secondary measurements were anteroposterior knee stability at two years (using KT-1000 arthrometer) and the functional outcome using the International Knee Documentation Committee (IKDC 2000) form, the Tegner activity scale, and the Lysholm knee score. Data were compared using a paired t-test and analysis of variance, with a p < 0.05 level of significance. Results Most patients regained the 60°/s quadriceps strength between three and 12 months (62.5% for the Button group vs. 50% for the AperFix group), as well as the 180°/s strength (79.17% vs 70.83%); however, at the 24-month evaluation, seven (29.17%) patients in the Button group and five (20.83%) in the AperFix group had significant deficits. The 60°/s flexor strength was regained in the first six months in 19 (79.17%) patients in the Button group and in 16 (66.7%) patients in the AperFix group, whereas the percentages for the 180°/s strength were 79.17% and 75%, respectively. Beyond the 24-month evaluation, only three (12.5%) patients in the Button group and four (16.67%) in the AperFix group had significant flexor deficits. Regarding the H/Q ratio, at 60°/s, the mean recovery time was six and 7.5 months for the Button and AperFix groups, respectively, whereas 15 and 12 patients, respectively, did not recover during the two-year duration. At 180°/s, a mean recovery time of six months was needed for the button group, and nine patients did not recover two years later. For the AperFix group, nine months were needed, and 12 patients did not recover in two years. Clinical performance and anterior knee stability showed no statistically significant differences between groups. Conclusions Although there were no significant differences in clinical performance, knee stability, and isokinetic strength testing between expandable and cortical button femoral fixation groups, return to play was doubtful at two years postoperatively.

Three-Dimensional Cell Metabolomics Deciphers the Anti-Angiogenic Properties of the Radioprotectant Amifostine.

Aberrant angiogenesis is a hallmark for cancer and inflammation, a key notion in drug repurposing efforts. To delineate the anti-angiogenic properties of amifostine in a human adult angiogenesis model via 3D cell metabolomics and upon a stimulant-specific manner, a 3D cellular angiogenesis assay that recapitulates cell physiology and drug action was coupled to untargeted metabolomics by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The early events of angiogenesis upon its most prominent stimulants (vascular endothelial growth factor-A or deferoxamine) were addressed by cell sprouting measurements. Data analyses consisted of a series of supervised and unsupervised methods as well as univariate and multivariate approaches to shed light on mechanism-specific inhibitory profiles. The 3D untargeted cell metabolomes were found to grasp the early events of angiogenesis. Evident of an initial and sharp response, the metabolites identified primarily span amino acids, sphingolipids, and nucleotides. Profiles were pathway or stimulant specific. The amifostine inhibition profile was rather similar to that of sunitinib, yet distinct, considering that the latter is a kinase inhibitor. Amifostine inhibited both. The 3D cell metabolomics shed light on the anti-angiogenic effects of amifostine against VEGF-A- and deferoxamine-induced angiogenesis. Amifostine may serve as a dual radioprotective and anti-angiogenic agent in radiotherapy patients.