Post-translational modifications are necessary for collagen precursor molecules (procollagens) to acquire final shape and function. However, the mechanism and contribution of collagen modifications that occur outside the endoplasmic reticulum and Golgi are not understood. We discovered that VIPAR, with its partner proteins, regulate sorting of lysyl hydroxylase 3 (LH3, also known as PLOD3) into newly identified post-Golgi collagen IV carriers and that VIPAR-dependent sorting is essential for modification of lysines in multiple collagen types. Identification of structural and functional collagen abnormalities in cells and tissues from patients and murine models of the autosomal recessive multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis syndrome caused by VIPAR and VPS33B deficiencies confirmed our findings. Thus, regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis and for the development and function of multiple organs and tissues.
ObjectiveThe optimal vitamin D intake for nursing women is controversial. Deterioration, at least in bone mass, is reported during lactation. This study evaluated whether vitamin D supplementation during lactation enhances the maternal and infant’s vitamin D status, bone mass and body composition.Design and MethodsAfter term delivery, 174 healthy mothers were randomized to receive 1200 IU/d (800 IU/d+400 IU/d from multivitamins) or 400 IU/d (placebo+400 IU/d from multivitamins) of cholecalciferol for 6 months while breastfeeding. All infants received 400 IU/d of cholecalciferol. Serum 25-hydroxyvitamin D [25(OH)D], iPTH, calcium, urinary calcium, and densitometry were performed in mother-offspring pairs after delivery, and at 3 and 6 months later.ResultsA total of 137 (79%) (n = 70; 1200 IU/d, n = 67; 400 IU/d) completed the study. 25(OH)D was similar in both groups at baseline (13.7 ng/ml vs. 16.1 ng/ml; P = 0.09) and at 3 months (25.7 ng/ml vs. 24.5 ng/ml; P = 0.09), but appeared higher in the 1200 IU/d group at 6 months of supplementation (25.6 ng/ml vs. 23.1 ng/ml; P = 0.009). The prevalence of 25(OH)D <20 ng/ml was comparable between groups at baseline (71% vs. 64%, P = 0.36) but lower in the 1200 IU/d group after 3 months (9% vs. 25%, P = 0.009) and 6 months (14% vs. 30%, P = 0.03). Maternal and infants’ iPTH, calciuria, bone mass and body composition as well as infants’ 25(OH)D levels were not significantly different between groups during the study. Significant negative correlations were noted between maternal 25(OH)D and fat mass (R = −0.49, P = 0.00001), android fat mass (R = −0.53, P = 0.00001), and gynoid fat mass (R = −0.43, P = 0.00001) after 6 months of supplementation.ConclusionsVitamin D supplementation at a dose of 400 IU/d was not sufficient to maintain 25(OH)D >20 ng/ml in nursing women, while 1200 IU/d appeared more effective, but had no effect on breastfed offspring vitamin D status, or changes in the bone mass and the body composition observed in both during breastfeeding.Trial RegistrationClinicalTrials.gov NCT01506557
Objective: New technologies to measure pain responses, such as heart rate variability and skin conductance hold promise in the development of tools that can be reliable and quantifiable of detecting pain. The main objective of this study was to assess the capability of two monitors i.e., Newborn Infant Parasympathetic Evaluation (NIPE) and Skin Conductance Algesimeter for detecting procedural pain in non-anesthetized infants.Materials and Methods: Thirty-three non-anesthetized infants were enrolled to the study. To detect pain caused by heel stick, NIPE, and Skin Conductance monitors and behavioral pain scales were used. Three minutes before and just after heel stick, pain was evaluated by behavioral scales, and simultaneously over the whole period by NIPE and SCA.Results: A statistically significant decrease of NIPE Index and an increase of SCA values were found after the HS procedure. There were no statistically significant differences between the decrease in NIPEi values and the increase in PPS values between subgroups based on pain assessment by behavioral-scale scores.Conclusion: Both NIPE and SCA can be useful for detection of procedural pain and may constitue an additional valuable tool for better handling of pain among patients treated in NICUs. More studies on larger groups of patients are needed.
Objective The aim of this study is to evaluate the ability of the Newborn Infant Parasympathetic Evaluation (NIPE) index to detect the response to nociceptive stimuli in nonanesthetized infants and to compare these results to simultaneous scoring by behavioral scales. Study Design Thirty-six nonanesthetized infants admitted to neonatal/pediatric intensive care unit (N/PICUs) were enrolled to the study. Due to faulty records of the data, three patients had to be excluded. To detect pain caused by noxious stimuli, the heart-rate-variability-derived NIPE index and behavioral pain scales designed for measuring procedural pain in nonverbal children were used. Results Forty-one painful events were available for analysis. We observed in the whole group a statistically significant decrease in NIPE values at 1, 2, and 3 minutes after a painful stimulus, in comparison to the NIPE value at rest and the statistically significant differences between the minimum NIPE value within 3 minutes after the stimulus in comparison to NIPE value at rest in the whole group, as well as in the subgroups of moderate and severe pain. Receiver operating characteristic (ROC) analysis has shown the strong sensitivity and specificity of the NIPE in detecting the noxious stimuli (ROC AUC: 0.767). We also found that the stronger the sensation of pain was, the more rapidly NIPE reached its lowest value. Discussion Our study indicates that the painful procedures are associated with a significant decrease in the NIPE value within 3 minutes after a noxious stimulus. Based on our observation, the minimum value within 3 minutes from the painful procedure seems to be the most distinctive value.
Background: High prevalence of vitamin D deficiency in pregnancy is recorded. Aim: To establish determinants of postpartum 25-hydroxyvitamin D (25(OH)D) levels on mothers and offspring. Methods: 25(OH)D level was measured in cord blood and maternal blood collected ≤3 weeks postpartum. Maternal socioeconomic status, vitamin D intake, sun exposure during pregnancy and maternal and neonatal fat mass (FM; dual X-ray absorptiometry) were assessed within 3 weeks postpartum. Results: A total of 174 mother-offspring pairs were enrolled. Maternal 25(OH)D <20 ng/ml was seen in 32 (51%) of summer and 82 (74%) of winter deliveries. Women with 25(OH)D <20 ng/ml had a 2-fold lower percentage of vitamin D intake of ≥800 IU/day than women with 25(OH)D ≥20 ng/ml (p = 0.02). FM (%) was comparable between groups (p > 0.05). Multiple regression analysis revealed the delivery season, prenatal vitamin D intake ≥800 IU/day and duration of supplementation to be the determinants of maternal 25(OH)D level (R2 = 0.26, p < 0.001). Maternal 25(OH)D level, season of birth and duration of maternal supplementation explained 83% of the variance in cord blood 25(OH)D level (R2 = 0.83, p < 0.001). Conclusions: The key determinants of higher maternal vitamin D status were the summer-autumn season of delivery and prenatal use of ≥800 IU/day of vitamin D. The cord blood 25(OH)D level was mainly determined by maternal 25(OH)D level and season of birth.
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