Sex differences and risk factors for bleeding in Alagille syndrome.

Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1Ndr/Ndr mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1Ndr/Ndr mice, using retina as a model. Jag1Ndr/Ndr mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1Ndr/Ndr mice represent a new model for vascular compromise in ALGS.

Studying Different Operating Conditions on Reverse Osmosis Performance in the Treatment of Wastewater Containing Nickel (II) Ions.

The reverse osmosis performance in removing nickel ions from artificial wastewater was experimentally and mathematically assessed. The impact of temperature, pressure, feed concentration, and feed flow rate on the permeate flux and Ni (II) rejection % were studied. Experiments were conducted using a SEPA CF042 Membrane Test Skid-TFC BW30XFR with applied pressures of 10, 20, 30, and 40 bar and feed concentrations of 25, 50, 100, and 150 ppm with varying operating temperatures of 25, 35, and 45 °C, while the feed flow rate was changed between 2, 3.2, and 4.4 L/min. The permeate flux and the Ni (II) removal % were directly proportional to the feed temperature and operating pressure, but inversely proportional to the feed concentration, where the permeate flux increased by 49% when the temperature was raised from 25 to 45 °C, while the Ni (II) removal % slightly increased by 4%. In addition, the permeate flux increased by 188% and the Ni (II) removal % increased to 95.19% when the pressure was raised from 10 to 40 bar. The feed flow rate, on the other hand, had a negligible influence on the permeate flux and Ni (II) removal %. The temperature correction factor (TCF) was determined to be directly proportional to the feed temperature, but inversely proportional to the operating pressure; nevertheless, the TCF was unaffected either by the feed flow rate or the feed concentration. Based on the experimental data, mathematical models were generated for both the permeate flux and nickel removal %. The results showed that both models matched the experimental data well.

Altering calcium and phosphorus supplementation in pregnancy and lactation affects offspring craniofacial morphology in a sex-specific pattern.

INTRODUCTION: The effects on offspring craniofacial bone morphology and accretion because of altered maternal exposure to dietary components such as calcium (Ca) and phosphorus (P) are unclear. The objective of this study was to investigate the changes in offspring skull morphology and tissue mineral density (TMD), including sex-specific changes, with exposure to a maternal diet high in Ca-to-P levels during gestation and lactation in mice. METHODS: Time-mated FVB wild-type mice were fed a normal or experimental diet during gestation until weaning. The experimental diet contained a 3-fold increase in Ca and a 3-fold decrease in P (Ca:P molar ratio, 10.5) compared with normal mouse chow (Ca:P molar ratio, 1.5). The heads of 6-week-old control and experimental offspring mice were collected and scanned using microcomputed tomography. Three-dimensional geometric morphometric analysis was performed to analyze changes in craniofacial morphology. TMD measurements were also analyzed. RESULTS: We observed subtle changes and no significant differences between offspring control and experimental skulls when we compared all samples. However, when we separated skulls by sex, we discovered significant differences in craniofacial morphology and TMD. Experimental female offspring possessed skulls that were smaller, narrower transversely, taller vertically, and decreased in TMD. Experimental male offspring possessed skulls that were larger, wider transversely, shorter vertically, and increased in TMD. CONCLUSIONS: Maternal exposure to diet and increased Ca:P molar ratio during gestation and lactation led to significant, sex-specific morphologic and TMD changes in 6-week-old mouse skulls.

Neural regulation of bone marrow adipose tissue.

Bone marrow adipose tissue (BMAT) is an important cellular component of the skeleton. Understanding how it is regulated by the nervous system is crucial to the study of bone and bone marrow related diseases. BMAT is innervated by sympathetic and sensory axons in bone and fluctuations in local nerve density and function may contribute to its distinct physiologic adaptations at various skeletal sites. BMAT is directly responsive to adrenergic signals. In addition, neural regulation of surrounding cells may modify BMAT-specific responses, providing many potential avenues for both direct and indirect neural regulation of BMAT metabolism. Lastly, BMAT and peripheral adipose tissues share the same autonomic pathways across the central neuraxis and regulation of BMAT may occur in diverse clinical settings of neurologic and metabolic disease. This review will highlight what is known and unknown about the neural regulation of BMAT and discuss opportunities for future research in the field.