Local properties of a functionally graded interphase between cementum and dentin

The study of natural interfaces may provide information necessary to engineer functionally graded biomaterials for bioengineering applications. In this study, the mechanical, structural, and chemical composition variations associated with a region between cementum and dentin were studied with the use of nanoindentation, microindentation, optical microscopy, and Raman microspectroscopy techniques. Three-millimeter-thick transverse sections (N = 5) were obtained from the apical one-third of the roots of sterilized human molars. The samples were ultrasectioned at room temperature with the use of a diamond knife and an ultramicrotome. Longitudinal ground sections of 100 microm thickness were prepared and stained with von Kossa stain to determine the mineralized regions within the molar roots. Raman microspectroscopy was used to determine the relative inorganic content, mainly apatite (PO4(3-)nu1 mode at 960 cm(-1)) and organic content, mainly collagen (C--H stretch at 2940 cm(-1)) between cementum and dentin bulk tissues. The microindentation and nanoindentation results indicated a gradual transition in hardness from cementum to dentin over a width ranging from 100 to 200 microm. However, the variation in hardness data for cementum and dentin by nanoindentation was larger (0.62 +/- 0.21, 0.77 +/- 0.14 GPa) than from microindentation (0.49 +/- 0.03, 0.69 +/- 0.07 GPa). Within the 100 to 200 microm region there was a 10 to 50 microm fibrillar hydrophilic cementum-dentin junction (CDJ) with mechanical properties significantly lower than either the cementum or the dentin side of CDJ. Light microscopy revealed a 100 to 200 microm translucent region between cementum and dentin. Raman microspectroscopy results showed a variation in organic and inorganic composition 80 to 140 microm wide. It was concluded that a morphologically and biomechanically different CDJ lies within a wider cementum-dentin interphase. Hence, cementum, dentin, and the interphase can be classified as a functionally graded dental tissue within the root of a tooth.     

Aging does not alter cytosolic calcium levels of cortical synaptosomes in Fischer 344 rats

Several lines of experimental evidence support an association between altered Ca²⁺ regulation and aging. It has been supposed that free cytosolic Ca²⁺ concentrations ([Ca²⁺]_i) may decrease or increase in aged animals. In this study, both resting and KCl-stimulated [Ca²⁺]_i were measured in purified cortical synaptosomes from young (3 mo.), middle-aged (12 mo.), and old (24 mo.) Fischer 344 rats. Two additional groups of rats were included, one middle-aged and one old which were trained on a treadmill for 6 months prior to experimentation. The [Ca²⁺]_i was determined using the fluorescent Ca²⁺ chelator fura-2. Net KCl-dependent changes (ΔK) in [Ca²⁺]_i were determined by the difference between stimulatory (100 μM Ca²⁺/60 mM KCl) and resting (100 μM Ca²⁺/5 mM KCl buffer) conditions among the 3 age groups. Significant increases in [Ca²⁺]_i were observed in each age group upon depolarization with 60 mM KCl. However, there were no significant age-dependent differences in either resting [Ca²⁺]_i or KCl-stimulated [Ca²⁺]_i.     

Macular deposits in galactokinase deficiency

Deficiency of the enzyme, galactokinase, is a recognized cause of "juvenile" lens opacities; these opacities are felt to be its only clinical expression. The deficiency itself is inherited as an autosomal recessive and as such is expected to be clinically manifest in the homozygote. We have recently demonstrated cataracts and associated bilateral macular deposits in a white male who is heterozygous for the deficiency of the enzyme and whose dietary intake of milk and its products is extremely high. To our knowledge, intraretinal deposits have not previously been described in patients with galactokinase deficiency, and their clinical significance and biochemical makeup can only be speculative. Dietary restriction of galactose is recommended for all individuals proven to be deficient in this enzyme, whether homozygous or heterozygous.     

Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness

Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4⁺ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4⁺ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4⁺ T cell immune responsiveness.     

Risk factors for delayed graft function and their impact on graft outcomes in live donor kidney transplantation

International Urology and Nephrology - Delayed graft function (DGF) is a manifestation of acute kidney injury uniquely framed within the transplant process and a predictor of poor long-term graft...     

The role of sperm in inducing genomic changes in the implantation: An experimental study

Endometrial receptivity and implantation are important topics in reproductive sciences. No evidence was found to support sperm involvement in endometrial receptivity and its associated factors. This study aimed to explore the effect of the normal human spermatozoa–endometrium cell interaction in regulating genes in the endometrial receptivity pathway. Semen samples were collected from a healthy and fertile man; then, they were incubated with endometrial cells for 24 hr and considered as the sperm group. A group was cultured without spermatozoa and considered as a control group. About 24 hr later, cells were collected from the bottom of the culture dish. The expressions of the VEGF, FGF2, HBEGF, LIFR, EGF, LIF, MUC1, HOXA10, CSF and PGR genes were evaluated in the two groups. Statistical analysis was performed using an independent sample test. Compared with the control group, in the sperm group, the mRNA levels of PGR (p = .0451), VEGF (p = .0101), HBEGF (p = .0163), EFG (p = .0339), FGF2 (p = .012), LIF (p = .0324), LIFR (p = .0321) and HOXA10 (p = .0098) were significantly upregulated. The results showed that there is a need for the interaction between spermatozoa and endometrium for implantation and can be used for preparing uterine in in vitro fertilisation cycles.     

The impact of COVID-19 on liver injury in various age

The coronavirus disease 2019 (COVID-19) disease was first detected in December 2019 in Wuhan, China. This disease is currently one of the most important global health problems. The novel coronavirus COVID-19 is a respiratory illness, that has caused a deadly pandemic that is spreading rapidly around the world. It is not only a respiratory system virus that causes severe lung disease, but also a systemic disease agent that can affect all systems. People with COVID-19 disease usually have respiratory signs, however, the liver disorder is not an uncommon presentation. In addition, many studies around the world have revealed that the liver is injured to various degrees in patients with severe acute respiratory syndrome coronavirus 2 disease. This review mainly focuses on the impact of COVID-19 on Liver Injury at various ages.     

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons’ knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.     

Sleeve gastrectomy prior to liver transplantation is superior to medical weight loss in reducing posttransplant metabolic complications

Strategies to optimize the management of obesity-related metabolic complications after liver transplantation (LT) are needed. We examined the effect of pre-LT sleeve gastrectomy (SG), as compared to medical weight loss (MWL), on post-LT outcomes. This is a cohort study of adults (≥18 years) with medically complicated obesity who were eligible for pre-LT SG and underwent LT from January 1, 2006 to June 1, 2016. Logistic regression models evaluated the association of SG on post-LT diabetes and hypertension, defined as new-onset or progressive disease post-LT. Cox regression models evaluated the association of SG on recurrent and de novo nonalcoholic fatty liver disease (NAFLD). Among 70 LT recipients who were eligible for pre-LT SG, 14 (20%) underwent SG and 56 (80%) underwent MWL only. Mean follow-up was 5.2 years post-LT. The SG cohort sustained higher % total body weight loss at 3 years post-LT (28.9% vs. 5.4%, p < .001). In multivariable analyses, SG was associated with significantly lower risk of post-LT diabetes (OR 0.04, 95% CI 0.00–0.41, p = .01), hypertension (OR 0.15, 95% CI 0.04–0.67, p = .01), and recurrent and de novo NAFLD (HR 0.19, 95% CI 0.04–0.91, p = .04). When compared to MWL, SG resulted in sustained weight loss and significantly lower risk of diabetes, hypertension, and recurrent and de novo NAFLD post-LT.