Reliable assessment of glycemia is central to the management of diabetes. The kidneys play a vital role in maintaining glucose homeostasis through glucose filtration, reabsorption, consumption, and ...generation. This review article highlights the role of the kidneys in glucose metabolism and discusses the benefits, pitfalls, and evidence behind the glycemic markers in patients with chronic kidney disease. We specifically highlight the role of continuous glucose monitoring as an emerging minimally invasive technique for glycemic assessment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact ...result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that established different populations around the world. We selected 19 common variants found to be reproducibly associated to T2D risk in European populations and studied them in a large multiethnic case-control study (6,142 cases and 7,403 controls) among men and women from 5 racial/ethnic groups (European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians). In analysis pooled across ethnic groups, the allelic associations were in the same direction as the original report for all 19 variants, and 14 of the 19 were significantly associated with risk. In summing the number of risk alleles for each individual, the per-allele associations were highly statistically significant (P<10(-4)) and similar in all populations (odds ratios 1.09-1.12) except in Japanese Americans the estimated effect per allele was larger than in the other populations (1.20; P(het) = 3.8×10(-4)). We did not observe ethnic differences in the distribution of risk that would explain the increased prevalence of type 2 diabetes in these groups as compared to European Americans. The consistency of allelic associations in diverse racial/ethnic groups is not predicted under the hypothesis of Goldstein regarding "synthetic associations" of rare mutations in T2D.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Anterior distal femoral hemiepiphysiodesis using intra-articular plates for correction of pediatric fixed knee flexion deformities (FKFD) has two documented complications: postoperative ...knee pain and implant loosening. The aim of this study is to investigate the mechanical properties of a novel extra-articular technique for anterior distal femoral hemiepiphysiodesis in patients with FKFD and to compare them to the conventional technique.
Materials and methods
Sixteen femoral sawbones were osteotomized at the level of the distal femoral physis and fixed by rail frames to allow linear distraction simulating longitudinal growth. Each sawbone was tested twice: first using the conventional technique with eight plates placed anteriorly just medial and lateral to the femoral sulcus (group A) and then with plates inserted in the proposed novel location at the most anterior part of the medial and lateral surfaces of the femoral condyles with screws in the coronal plane (group B). Gradual linear distraction was performed, and the resulting angular correction was measured. Strain gauges were attached to the plates, and the amount of strain (and equivalent stress) over the plates in response to linear distraction was recorded. The two groups were compared using the Wilcoxon signed-rank test.
Results
The amount of angular correction was statistically higher in group B (extra-articular plates) at 5, 10-, and 15-mm of distraction (
p
< 0.001). As regards stress over the plates, the maximum stress and the area under the curve (sum of all stresses measured throughout the distraction process) were significantly higher when the plates were inserted at the conventional position (group A) (
p
< 0.001).
Conclusions
During anterior distal femoral hemiepiphysiodesis, the fixation of the eight plates in the coronal plane at the anterior part of the femoral condyles may produce a greater amount of correction and a lower degree of stress over the implants as compared to the conventional technique.
The XPA1 human pancreatic cancer cell line is dimorphic, with spindle stem-like cells and round non-stem cells. We report here the in vitro IC
50
values of stem-like and non-stem XPA1 human ...pancreatic cells cells for: (1) 5-fluorouracil (5-FU), (2) cisplatinum (CDDP), (3) gemcitabine (GEM), and (4) tumor-targeting Salmonella typhimurium A1-R (A1-R). IC
50
values of stem-like XPA1 cells were significantly higher than those of non-stem XPA1 cells for 5-FU (P = 0.007) and CDDP (P = 0.012). In contrast, there was no difference between the efficacy of A1-R on stem-like and non-stem XPA1 cells. In vivo, 5-FU and A1-R significantly reduced the tumor weight of non-stem XPA1 cells (5-FU; P = 0.028; A1-R; P = 0.011). In contrast, only A1-R significantly reduced tumor weight of stem-like XPA1 cells (P = 0.012). The combination A1-R with 5-FU improved the antitumor efficacy compared with 5-FU monotherapy on the stem-like cells (P = 0.004). The results of the present report indicate A1-R is a promising therapy for chemo-resistant pancreatic cancer stem-like cells.
We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared ...with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival.
To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N = 98) and in cell lines (N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines.
Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na(+)-dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling.
These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival.
Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only ...are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.
Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic ...steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep) in male but not female mice. Gene profiling identifies sulfotransferase family 1E (Sult1e1), which encodes a sulfotransferase E1 responsible for inactivation of estrogen, as a gene upregulated in NASH in both genders and most conspicuously in male IkbkbΔhep mice having worst NASH and lowest plasma estradiol levels. LXRα is enriched to LXRE on Sult1e1 promoter in male WT and IkbkbΔhep mice with NASH, and a Sult1e1 promoter activity is increased by LXRα and its ligand and augmented by expression of a S32A mutant of IκBα. These results demonstrate striking gender differences in regulation by IKKβ of high cholesterol saturated fat diet-induced metabolic changes including NASH and suggest hepatocyte IKKβ is protective in male due at least in part to its ability to repress LXR-induced Sult1e1. Our findings also raise a caution for systemic IKK inhibition for the treatment of NASH as it may exacerbate the disease in male patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lateral column lengthening is a common method for treatment of patients with symptomatic flat feet. Although variations of the technique have been described by many authors, there is a lack of ...agreement about the exact location of the osteotomy. Most authors tried to find the interval between the anterior and middle talocalcaneal facets but did not offer a reproducible method to achieve this purpose. The use of a plantarflexion anteroposterior view of the foot provides better visualization of the anatomic landmarks and helps to precisely perform the osteotomy anterior to the sustentaculum tali, with protection of the anterior and middle talocalcaneal facets.
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