In modern cancer treatment, there is significant interest in studying the use of drug molecules either directly injected into the bloodstream or delivered by nanoparticle carriers of various shapes and sizes. During treatment, these carriers may extravasate through pores in the tumor vasculature that form during angiogenesis. We provide an analytical, computational, and experimental examination of the extravasation of point particles (e.g. drug molecules) and finite sized spheroidal particles. We study the advection-diffusion process in a model microvasculature, consisting of a shear flow over and a pressure driven suction flow into a circular pore in a flat surface.
https://ift.tt/2vKvMYD
Πέμπτη 16 Αυγούστου 2018
Extravasation of Brownian spheroidal nanoparticles through vascular pores
Human dystrophin structural changes upon binding to anionic membrane lipids
Scaffolding proteins play important roles in supporting the plasma membrane (sarcolemma) of muscle cells. Among them, dystrophin strengthens the sarcolemma through protein-lipid interactions, while its absence due to gene mutations leads to the severe Duchenne muscular dystrophy. Most of the dystrophin protein consists of a central domain made of 24 spectrin-like coiled-coil repeats (R). Using small-angle neutron scattering (SANS) and the contrast variation technique, we specifically probed the structure of the three first consecutive repeats 1 to 3 (R1-3), a part of dystrophin known to physiologically interact with membrane lipids.
https://ift.tt/2KZLp32
Mother’s Infant and Young Child Feeding (IYCF) knowledge improved timely initiation of complementary feeding of children aged 6–24 months in the rural population of northwest Ethiopia
Appropriate complementary feeding is vital to reduce young child morbidity and mortality. However, it continues as sub-optimal in Ethiopia, and literatures are also scarce. Therefore, this study aimed to deter...
https://ift.tt/2BjwYrb
Correction to: Antihypertensive medication adherence and associated factors among adult hypertensive patients at Jimma University Specialized Hospital, southwest Ethiopia
After publication of our article [1] we became aware that we had not obtained permission to reproduce the questions from the eight-item Morisky's Medication Adherence Scale. The table in this Correction replac...
https://ift.tt/2Mvt4j3
Plitidepsin: a potential new treatment for relapsed/refractory multiple myeloma
Future Oncology, Ahead of Print.
https://ift.tt/2OLTaw3
Hereditary cancer testing challenges: assembling the analytical pieces to solve the patient clinical puzzle
Future Oncology, Ahead of Print.
https://ift.tt/2MlAqXq
High Concentration of Fluoride Can Be Increased Risk of Abortion
Abstract
The presence of fluoride in drinking water can be either beneficial or harmful for human health, depending on its concentration. Most adverse effects of fluoride are observed at high concentrations (above 1.5 mg/L). This study was aimed to evaluate the effect of fluoride concentrations in drinking water on spontaneous abortion in two regions: one with low fluoride concentration and another with high fluoride concentration. The results showed that there is a relationship between the concentration of fluoride in drinking water and abortion, so that the risk of abortion increased at high concentrations of fluoride. However, further studies are needed to clarify this relationship due to the small area and population in this study.
https://ift.tt/2MtVXMK
Fluoride Alters Serum Elemental (Calcium, Magnesium, Copper, and Zinc) Homeostasis Along with Erythrocyte Carbonic Anhydrase Activity in Fluorosis Endemic Villages and Restores on Supply of Safe Drinking Water in School-Going Children of Nalgonda District, India
Abstract
The present study aimed to determine the serum trace elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg)) along with erythrocyte carbonic anhydrase (CA) activity and effect of intervention with safe drinking water for 5 years in the school children of fluorosis endemic area. For this purpose, three categories of villages were selected based on drinking water fluoride (F): Category I (control, F = 1.68 mg/L), category II (affected F = 3.77 mg/L), and category III (intervention village) where initial drinking water F was 4.51 mg/L, and since the last 5 years, they were drinking water containing < 1.0 mg/L F. The results revealed that urinary F was significantly (P < 0.05) higher in category II compared to categories I and III. A significant (P < 0.05) increase in serum Cu and Mg was observed in category II compared to category I. Serum Zn and Ca was significantly (P < 0.05) decreased in categories II and III compared to category I. The erythrocyte CA activity was decreased in the category II compared to category I. However, in the category III, erythrocyte CA activity was comparable to the control group. In conclusion, F exposure altered elemental homeostasis which has restored to some extent on intervention by safe drinking water for 5 years in school-going children.
https://ift.tt/2MCdRx3
Influences of Copper/Zinc-Loaded Montmorillonite on Growth Performance, Mineral Retention, Intestinal Morphology, Mucosa Antioxidant Capacity, and Cytokine Contents in Weaned Piglets
Abstract
The effects of copper/zinc-loaded montmorillonite (Cu/Zn-Mt) on growth performance, mineral retention, intestinal morphology, mucosa antioxidant capacity, and cytokine contents in weaned piglets were investigated in the present study. One hundred eight piglets weaned at 21 ± 1 days of age (Duroc × Landrace× Yorkshire; average initial weight of 6.36 kg) were allotted to three treatments for 2 weeks. The three treatments were as follows: (1) control group: basal diet; (2) Cu/Zn-Mt group: basal diet + 39 mg/kg Cu and 75 mg/kg Zn as Cu/Zn-Mt; (3) Cu + Zn + Mt group: basal diet + mixture of CuSO4, ZnSO4, and Mt (equal amount of Cu, Zn, and Mt to the Cu/Zn-Mt group). Each treatment had six pens of six piglets. The results showed that as compared with the control group and the Cu + Zn + Mt group, Cu/Zn-Mt supplementation increased (P < 0.05) the average daily gain and the gain/feed ratio; Cu/Zn-Mt supplementation increased (P < 0.05) the Cu and Zn concentrations in serum, jejunum, and ileum mucosa, villus height, the ratio of villus height to crypt depth, and the activities of SOD, GSH-Px, and IL-10 levels, and decreased the malondialdehyde concentrations in the jejunum and ileum, and intestinal IL-1β, IL-6, and TNF-α levels. Moreover, supplementation with the mixture of CuSO4, ZnSO4, and Mt had no effect on the growth performance, but increased the mucosa Cu and Zn concentrations, intestinal morphology, antioxidant capacity, and immune function in the duodenum, while it had no effect on the above indexes in the jejunum and ileum. The results indicated that Mt could be used as a controlled carrier for Cu and Zn, which made Cu/Zn-Mt have better biological activities in the intestine than the mixture of Cu, Zn, and Mt.
https://ift.tt/2BfuHxe
Zinc Supplementation Does Not Affect Glucagon Response to Intravenous Glucose and Insulin Infusion in Patients with Well-Controlled Type 2 Diabetes
Abstract
Glucagon dysregulation is an essential component in the pathophysiology of type 2 diabetes. Studies in vitro and in animal models have shown that zinc co-secreted with insulin suppresses glucagon secretion. Zinc supplementation improves blood glucose control in patients with type 2 diabetes, although there is little information about how zinc supplementation may affect glucagon secretion. The objective of this study was to evaluate the effect of 1-year zinc supplementation on fasting plasma glucagon concentration and in response to intravenous glucose and insulin infusion in patients with type 2 diabetes. A cross-sectional study was performed after 1-year of intervention with 30 mg/day zinc supplementation or a placebo on 28 patients with type 2 diabetes. Demographic, anthropometric, and biochemical parameters were determined. Fasting plasma glucagon and in response to intravenous glucose and insulin infusion were evaluated. Patients of both placebo and supplemented groups presented a well control of diabetes, with mean values of fasting blood glucose and glycated hemoglobin within the therapeutic goals established by ADA. No significant differences were observed in plasma glucagon concentration, glucagon/glucose ratio or glucagon/insulin ratio fasting, after glucose or after insulin infusions between placebo and supplemented groups. No significant effects of glucose or insulin infusions were observed on plasma glucagon concentration. One-year zinc supplementation did not affect fasting plasma glucagon nor response to intravenous glucose or insulin infusion in well-controlled type 2 diabetes patients with an adequate zinc status.
https://ift.tt/2MibxeZ
Selenium-Enriched Saccharomyces cerevisiae Reduces the Progression of Colorectal Cancer
Abstract
Colorectal cancer is one of the most common causes of mortality in the world while malnutrition is responsible for one third of the problem. Selenium has been recommended for prevention of colorectal cancer. The present study was conducted to investigate the effect of selenium-enriched Saccharomyces cerevisiae in reducing colorectal cancer progression in rats. Five groups of 170–200-g weight rats (n = 40) including healthy and cancer controls, Saccharomyces cerevisiae, selenium, and selenium-enriched Saccharomyces cerevisiae-treated groups were examined. All animals except healthy control group received 40 mg 1,2-dimethylhydrazine (DMH) per kilogram weight of rat twice a week. The healthy group received normal saline, and synchronously, selenium group received soluble selenium (4 mg/mL), Saccharomyces cerevisiae and selenium-enriched groups received yeast with the density of 5 × 108 CFU/mL by daily gavage. All treatments were carried out for 5 weeks after the last injection. Animals were autopsied, and aberrant crypt foci (ACF) of ejected colon were studied in the 40th week. Microscopic sections were prepared for hematoxylin and eosin. Furthermore, immunohistochemical staining of CD31, BCL2, and P53 antibodies was performed. Macroscopic and microscopic evaluations showed that DMH had the least destructive effect in selenium-enriched Saccharomyces cerevisiae group compared to other groups. Selenium-enriched Saccharomyces cerevisiae reduces colorectal cancer progression by various mechanisms such as reduction in the number and size of ACF and alteration in the function of the proteins such as P53, BCL2, and CD31.
https://ift.tt/2BjUELS
A Neuro-Comparative Study between Single/Successive Thorium Dose Intoxication and Alginate Treatment
Abstract
The adult male albino rats were grouped into five groups (control group and four variably treated groups with thorium (Th) in single or successive with or without alginate treatment). The IP administration of thorium nitrate (13.6 mg/kg b.wt.) induced a regional distribution and accumulation ordered as cerebellum > cerebral cortex > brain stem > hippocampus > hypothalamus > striatum. Also, it induces a significant increase in Na+, Ca2+, and Fe3+ ion content and malondialdehyde (MDA) level while K+ ions and glutathione (GSH) level were significantly decreased. On the other hand, the daily oral administration of 5% alginate showed a significant decreasing in the accumulation of thorium in the different brain areas and mitigated its hazardous effects. By the alginate treatment, Na+, Ca2+, Fe3+, and level of MDA were declined while K+ ions and GSH level showed a significant increase. The improvement of the investigated parameters was attributed to the specific chelating, regeneration, and antioxidant properties of the alginate. So, alginate administration could ameliorate the hazardous effects of thorium nitrate.
https://ift.tt/2MibwHX
Effects of Copper and Zinc Supplementation on Weight Gain and Hematological Parameters in Pre-weaning Calves
Abstract
Cow-calf operations may be affected by trace mineral deficiencies, particularly copper (Cu) and zinc (Zn) deficiency, which may decrease the calf daily weight gain and alter hematological parameters. We evaluated the effect of Cu and Zn supplementation on pre-weaning calves (n = 40; 92 ± 6 kg initial body weight) from the Salado River basin, Buenos Aires, Argentina. Calves were divided into four groups (n = 10 each) and subcutaneously administered 0.3 mg/kg Cu (Cu group), 1 mg/kg Zn (Zn group), Cu and Zn together (Cu + Zn group), and sterile saline solution (control group) every 40 days for 120 days. Plasma Cu and Zn concentrations, hematological parameters, and weight were recorded every 40 days. A completely randomized 2 × 2 factorial treatment design was used and data were analyzed with a mixed model for repeated measures over time. Cu and Zn were detected in plasma after the second sampling. Cu × Zn interaction was significant (p = 0.09), being Cu concentration higher in the Cu + Zn than in the Cu group. Differences in weight gain (Zn × time interaction; p < 0.01) were observed in the Zn but not in the Cu group (p > 0.1). On the other hand, none of the treatments altered any of the hematological parameters assessed (p > 0.1). Our results show the risk of lower weight gain due to Zn deficiency in pre-weaning calves raised in the Salado River basin.
https://ift.tt/2Ejo3WS
Preliminary Study of Mechanisms of Fluoride-Induced Suppression of Nitric Oxide Synthesis in Human Umbilical Vein Endothelial Cells
Abstract
This study was aimed to determine if excessive exposure to fluoride could suppress the synthesis of nitric oxide (NO) and to detail the mechanisms involved. With the exception of the control group, human umbilical vein endothelial cells (HUVECs) were treated with sodium fluoride (NaF) (1.2 μg/mL) for 24 h, with or without a 2-h pretreatment with 100 nM insulin-like growth factor 1 (IGF-1, a PI3K/AKT agonist), or 10 μM histamine (HIS, a eNOS agonist). The levels of NO in culture fluids, as well as the expressions of eNOS, p-eNOS, PI3K, AKT, and p-AKT, were compared. The levels of NO significantly decreased in all experimental groups; however, the levels of NO were obviously higher in the NaF + HIS and NaF + IGF-1 groups, compared to the NaF group. The p-eNOS/eNOS ratios dropped clearly in NaF and NaF + HIS groups, while that in the NaF + HIS group was distinctly higher than that in the NaF group. The p-AKT/AKT ratios went down apparently in NaF and NaF + IGF-1 groups, while that in the NaF + IGF-1 group was overtly higher than that of the NaF group. Excessive exposure to fluoride inhibited the synthesis of NO. The PI3K/AKT/eNOS pathway played a crucial role in the reduced expression of NO caused by excessive fluoride exposure.
https://ift.tt/2vPcr8r
pH-Dependent Effects of L-Cysteine on Mercury Dissolution of α-HgS and β-HgS
Abstract
Mercury sulfide is an insoluble inorganic mercury compound, and it is the main chemical form in traditional oral mercury-containing medicines. Hg2+ has a high affinity for thiols, and small molecule thiols in the gastrointestinal tract may promote mercury dissolution of mercury sulfide by binding to Hg2+. L-cysteine is the only amino acid that possesses a reducing sulfhydryl group (-SH), out of the 20 amino acids. This study investigates the effect of L-cysteine on mercury dissolution of mercury sulfide at pHs ranging from 1.2 to 7.2. The results showed that L-cysteine had different pH-dependent effects on the mercury dissolution of α-HgS and β-HgS. For α-HgS, the dissolved mercury concentration increased from 5.47 ± 0.97 ng/mL to 12.49 ± 0.54 ng/mL when the pH rose from 1.2 to 4.2, and decreased to 3.37 ± 0.70 ng/mL at pH 6.0 and then increased to 9.36 ± 0.79 ng/mL at pH 7.2. For β-HgS, the dissolved mercury concentration increased from 151.09 ± 2.25 ng/mL to 2346.71 ± 62.62 ng/mL when the pH increased from 1.2 to 7.2. In conclusion, L-Cys was distinctly enhanced upon mercury dissolution of α-HgS and β-HgS with increasing pH. These results may contribute to our understanding of the mercury absorption mechanism of traditional oral mercury-containing medicines.
https://ift.tt/2BfM2pN
Heavy Metal Components in Blood and Urinary Stones of Urolithiasis Patients
Abstract
Lifestyle, food intake, and exposure to chemicals are potential risk factors for the development of calcium urolithiasis. Pb, Cd, and Hg have been proved to cause renal illness, and urinary tract stones might be caused by exposure to metals. Therefore, this study aimed to measure the concentration of metals in urinary tract stones and blood simultaneously in urolithiasis patients. Moreover, we intended to determine whether urinary tract stones can be regarded as a biomarker of exposure or an effect marker in a population with environmental exposure to metals. Thirty-five urolithiasis patients (case) and 34 healthy inhabitants (control) were recruited in this study. The contents of Pb, Cd, Cr, Cu, Ni, As, Zn, and Hg were determined in urinary stones and blood in the case and control groups. The most abundant metals were Zn and Cu in blood and Zn and Ni in urinary stones. Significantly higher levels of Zn, Ni, and As were found in calcium phosphate stones than in calcium oxalate or uric acid stones. The majority of metals were not present at consistent levels in both blood and urinary stones, except for Zn. Urinary stones might be explained as providing another metabolic pathway for metal contamination. Moreover, as the metals with the highest content in urinary stones were Ni and Zn, and Ni content was very much higher than in other countries, contamination by Ni should be further taken into consideration if there is any serious contamination in Taiwan.
https://ift.tt/2Bd4yit
Dietary Supplementation with Chromium Picolinate Influences Serum Glucose and Immune Response of Brown-Egg Laying Hens
Abstract
To investigate the effect of chromium picolinate (CrPic) on egg production performance, egg quality, blood indices, and immune function of laying hens, 270 23-week-old Beijing Red brown-egg laying hens were randomly assigned to one of three treatments with six replicates of 15 birds per replicate for each treatment in a completely randomized design. Laying hens were fed a Cr-unsupplemented corn-soybean meal basal diet (control, containing 0.45 mg Cr/kg by analysis) or the basal diet supplemented with 0.4 or 0.6 mg Cr/kg from CrPic for 10 weeks. Laying hens fed diets supplemented with CrPic had a lower (P < 0.05) serum glucose (GLU) concentration and higher (P < 0.03) serum antibody titer against Newcastle disease than those fed the control diet at 33 weeks of age. However, supplemental CrPic had no effect (P > 0.05) on egg production and egg quality of brown-egg laying hens from 24 to 33 weeks of age. The results from this study indicated that supplemental CrPic decreased serum GLU and enhanced the immune function of brown-egg laying hens.
https://ift.tt/2MBuc4K
The Protective Role of Selenium in AFB 1 -Induced Tissue Damage and Cell Cycle Arrest in Chicken’s Bursa of Fabricius
Abstract
Aflatoxin B1 (AFB1) is a naturally occurring secondary metabolites of Aspergillus flavus and Aspergillus parasiticus, and is the most toxic form of aflatoxins. Selenium (Se) with antioxidant and detoxification functions is one of the essential trace elements for human beings and animals. This study aims to evaluate the protective effects of Se on AFB1-induced tissue damage and cell cycle arrest in bursa of Fabricius (BF) of chickens. The results showed that a dietary supplement of 0.4 mg·kg−1 Se alleviated the histological lesions induced by AFB1, as demonstrated by decreasing vacuoles and nuclear debris, and relieving oxidative stress. Furthermore, flow cytometry studies showed that a Se supplement protected AFB1-induced G2M phase arrest at 7 days and G0G1 phase arrest at 14 and 21 days. Moreover, the mRNA expression results of ATM, Chk2, p53, p21, cdc25, PCNA, cyclin D1, cyclin E1, cyclin B3, CDK6, CDK2, and cdc2 indicated that Se supplement could restore these parameters to be close to those in the control group. It is concluded that a dietary supplement of 0.4 mg kg−1 Se could diminish AFB1-induced immune toxicity in chicken's BF by alleviating oxidative damage and cell cycle arrest through an ATM-Chk2-cdc25 route and the ATM-Chk2-p21 pathway.
https://ift.tt/2BixFRr
Probiotics as a Complementary Therapy in the Model of Cadmium Chloride Toxicity: Crosstalk of β-Catenin, BDNF, and StAR Signaling Pathways
Abstract
Cadmium chloride (CdCl2) is a ubiquitous environmental toxicant that causes a variety of disturbances in biological systems, including brain dysfunction and testicular tissue degeneration. On the other hand, it is supposed that beneficial properties of probiotic bacteria (Lactobacillus and Acidobacillus) are related to their capacity to adhere or bind different targets, thus leading to improved intestinal microbial balance and other benefits to the host. Bearing aforementioned in mind, the present study was undertaken to investigate the protective effect of probiotic supplementation against cadmium chloride-induced brain and testis toxicity in mice model. Animals received Lactobacillus and Acidobacillus either alone or added to folic acid for 1 week before CdCl2 intoxication in a dose of 20 mg/kg BW followed by probiotics (5 × 109) and/or folic acid (12 mg/kg) treatment for 3 weeks. The levels of malondialdehyde (MDA), butyrl choline esterase (BCHE), reduced glutathione (GSH), and total superoxide dismutase (SOD) activities were investigated. Finally, cadmium neurotoxicity was determined by estimating the gene expression of β-catenin and brain-derived neurotrophic factor (BDNF), as well as estimating the alterations in testicular function by determining acid phosphatase level in addition to steroidogenic acute regulatory protein (StAR) and 17-hydroxy steroid dehydrogenase (17-β HSD) gene expression. Based on our results, we can conclude that exposure of mice to cadmium chloride resulted in a significant elevation in MDA, BCHE levels accompanied with a significant reduction in GSH and SOD activities compared to the control value. CdCl2 also downregulated the gene expression of β-catenin and BDNF, as well as acid phosphatase level, in addition to StAR and 17-β HSD gene expression. These deviated parameters were significantly modulated in the co-treated animals with probiotics compared with the cadmium-treated group. In conclusion, Lactobacillus and folic acid in a mixture with cadmium acted beneficially to an organism, increasing the cadmium excretion in feces, and consequently increasing β-catenin and BDNF in brain tissue and StAR and 17-β HSD in testis and improving their functions. Histoarchitecture analysis confirmed these results.
https://ift.tt/2C8PtcU
Association of Hypertension, Body Mass Index, and Waist Circumference with Fluoride Intake; Water Drinking in Residents of Fluoride Endemic Areas, Iran
Abstract
Hypertension is becoming a global epidemic for both rural and urban populations; it is a major public health challenge in Iran. Fluoride can be a risk factor for hypertension. Cross-sectional analysis was conducted in two study areas to assess the relation of fluoride with blood pressure prevalence, BMI, waist circumference, and waist-to-hip ratio (WHR) among different age groups in both sexes. The mean value of fluoride concentration in the drinking water from the four study villages varied from 0.68 to 10.30 mg/L. The overall prevalence of HTN and prehypertension in all subjects was 40.7%. The prevalence of isolated systolic hypertension, isolated diastolic hypertension, systolic-diastolic hypertension, and prehypertension in the total sample population was 1.15, 0.28, 9.53, and 29.76%, respectively. The odd ratio of hypertension in residents who drank water with high fluoride levels was higher than that in residents who drank water with lower level of fluoride (OR 2.3, 1.03–5.14). Logistic regression results showed that age (P < 0.001), sex (P = 0.018), BMI (P = 0.015), and the fluoride level in drinking water (P = 0.041) had a significant relationship with increased blood pressure. There were no statistically significant correlations between fluoride and BMI, hip circumference, and waist to hip ratio (WHR). The findings of this study are important for health care personnel and policymakers.
https://ift.tt/2MxaaZf
Mitochondria-Mediated Pathway Regulates C2C12 Cell Apoptosis Induced by Fluoride
Abstract
This study was designed to investigate the mechanisms of excessive fluoride-induced apoptosis via mitochondria-mediated pathway in skeletal muscle cells (C2C12 cells). C2C12 cells were cultured with the fluoride concentrations (0, 1, and 2.5 mmol/L) for 48 h. The morphology and ultrastructural changes of C2C12 cells were observed using a light microscope and transmission electron microscope (TEM). The protein expression levels of apoptosis factors, including Bax, Bcl-2, cytochrome c (Cyt c), caspase-3, and caspase-9, were measured using real-time polymerase chain reaction (real-time PCR) and immunocytofluorescence. The morphology and ultrastructure of C2C12 cells were seriously damaged by fluoride at 1 and 2.5 mmol/L doses, including swollen mitochondria, vacuolization, ridge breakage, and disappearance of the nuclear membrane. Simultaneously, compared with the control group, the expression levels of Bax, Bcl-2, Cyt c, caspase-3, and caspase-9 were up-regulated after fluoride treatment. Excessive fluoride damages the ultrastructure in mitochondria, leading to the release of Cyt c from the mitochondria to cytoplasm in C2C12 cells; thereby, activated caspases cascade apoptosis process through a mitochondria-mediated pathway.
https://ift.tt/2BjUgwU
A Comparison of Iodine Status in Children and Pregnant Women After a Policy Change in the Iodized Salt Standard in Shanghai, China
Abstract
In Shanghai, a new iodized salt standard was implemented in 2012. To provide evidence to the government, we compared iodine status before (35 mg/kg) and after (30 mg/kg) adjustment in vulnerable populations living in Shanghai. The probability-proportional-to-size sampling technique was used to select at least 360 pregnant women for urine iodine test and at least 1200 students for thyroid measurement and the household salt test. Of these students, at least 360 performed urine iodine test. The median thyroid volume and the median household salt iodine concentration of children aged 8–10 years were 1.80 ml and 24.8 mg/kg in 2015, and 0.97 ml and 28.3 mg/kg in 2011. The median urine iodine concentration (UIC) of pregnant women was 126.52 and 139.77 μg/L in 2015 and 2011. All differences were statistically significant (P < 0.05). The median UIC of students was 171.40 and 181.63 μg/L in 2015 and 2011, the difference was not statistically significant. Multivariate linear regression analysis showed that thyroid volume in children was associated with sex, age, region, and household salt iodized concentration. The current iodized salt concentration meets the basic needs of the population's iodine requirements except for pregnant women. Periodic monitoring is necessary particularly in vulnerable groups.
https://ift.tt/2Mnvf9v
Cross-sectional Study: Relationship Between Serum Selenium and Hypertension in the Shandong Province of China
Abstract
Although selenium, which is a necessary trace element for the human body, has been considered to be beneficial to the cardiovascular system and helpful to lower blood pressure, more and more evidence shows that high amounts of selenium are a risk factor for hypertension. A random multistage sampling which included the cluster method was performed; a total of 9076 urban and rural residents between 18 and 80 years old in the Shandong province of China were investigated by questionnaire, physical examination, and laboratory tests. The prevalence of hypertension was 42.1% in males and 35.3% in females. The mean (standard deviation) selenium concentration was 124.68 (36.32) μg/l in males and 119.54 (31.88) μg/l in females. After adjusting for potential confounders, logistic regression analysis showed that the highest selenium levels were associated with a risk of hypertension (OR = 1.192; 95% CI 1.009–1.407) in females, while there was no significant difference in males (OR = 1.043; 95% CI 0.864–1.259). Our findings suggest that high selenium levels in females are more likely to increase the risk of hypertension compared to similar levels in males. More attention should be paid to the metabolic mechanisms and physiological effects of selenium in females.
https://ift.tt/2BqRUwy
Autophagy Protects MC3T3-E1 Cells upon Aluminum-Induced Apoptosis
Abstract
Aluminum (Al) exposure has adverse effects on osteoblasts, and the effect might be through autophagy-associated apoptosis. In this study, we showed that aluminum trichloride (AlCl3) could induce autophagy in MC3T3-E1 cells, as demonstrated by monodansylcadaverine (MDC) staining and the expressions of the ATG3, ATG5, and ATG9 genes. We found AlCl3 inhibited MC3T3-E1 cell survival rate and caused apoptosis, as evidenced by CCK-8 assay, Annexin V/PI double staining, and increased expressions of Bcl-2, Bax, and Caspase-3 genes. In addition, increased autophagy induced by rapamycin further attenuated the MC3T3-E1 cell apoptosis rate after AlCl3 exposure. These results support the hypothesis that autophagy plays a protective role in impeding apoptosis caused by AlCl3. Activating autophagy may be a strategy for treatment of Al-induced bone disease.
https://ift.tt/2Mx9VgN
Comparing the Effects of Chitosan Scaffolds Containing Various Divalent Metal Phosphates on Osteogenic Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth
Abstract
Inducing the differentiation of stem cells from human exfoliated deciduous teeth (SHEDs) proceeds with low efficiency, which greatly limits clinical applications. Divalent metal elements play an important role in osteoinductivity for bone remodeling because they can simulate bone formation and decrease bone resorption. The purpose of this study was to investigate the effect of some divalent metal phosphates on osteogenic differentiation from human exfoliated deciduous teeth. These divalent metal ions can be gradually released from the scaffold into the culture medium and continually induce osteoblastic differentiation. Experimental results revealed that SHEDs cultured in chitosan scaffolds containing divalent metal phosphates had notably increased osteoblastic differentiation compared with cells cultured without divalent metal phosphates. This effect was due to the high activity of alkaline phosphatase, as well as the bone-related gene expression of collagen type I, Runx2, osteopontin, osteocalcin, VEGF, and Ang-1, shown through RT-PCR and bone-related protein immunocytochemistry stains. A calcium-content assay further revealed significant enhancement of deposited minerals on the scaffolds after 21 days of culture, particularly for magnesium phosphate and zinc phosphate. Thus, divalent metals, except for barium phosphate, effectively promoted SHED cell differentiation and osteoblastic cell maturation. This study demonstrated that the divalent metal elements magnesium, strontium, and zinc could effectively induce SHED osteoblastic differentiation for use in tissue engineering and bone repair.
https://ift.tt/2EGwidu
Addressing Unintended Consequences of Gender Diversity Interventions on Women’s Sense of Belonging in STEM
Abstract
Validated interventions that increase bias literacy (i.e., knowledge of gender bias) and decrease sexism are critical to addressing pervasive gender biases in science, technology, engineering, and mathematics (STEM). However, interventions that highlight existing gender inequities may inadvertently act as a social identity threat cue for women. Including identity-safe cues in diversity interventions (i.e., suggesting that women are valued in STEM) may lessen these problematic outcomes. To explore this possibility, we conducted three experiments utilizing Video Interventions for Diversity in STEM (VIDS), a validated diversity intervention relying on high quality videos to convey the existence of gender bias in STEM. Consistent with prior research, relative to control conditions, VIDS led to greater bias literacy and lower gender bias among both men and women (Experiments 1 and 2) and encouraged women's intentions to take collective action (Experiment 2). At the same time, compared to control conditions, VIDS resulted in lower sense of belonging in the sciences, greater negative affect, and greater self-reported social identity threat, both among women from the general U.S. population (Experiments 1 and 2) and female scientists (Experiment 3). Including identity-safe cues, which present a positive female scientist role model (Experiment 2) or suggest that gender bias can be overcome (Experiments 2 and 3), helped alleviate VIDS' harmful effects on women's belonging and trust in the sciences, but had limited impact on stereotype threat. These findings highlight the need for researchers and practitioners to examine potential unintended negative consequences of diversity interventions and investigate techniques to buffer such outcomes.
https://ift.tt/2PhshRp
Tailoring chemotherapy for the African-centric S47 variant of TP53
The tumor suppressor TP53 is the most frequently mutated gene in human cancer and serves to restrict tumor initiation and progression. Single nucleotide polymorphisms (SNPs) in TP53 and p53 pathway genes can have a marked impact on p53 tumor suppressor function, and some have been associated with increased cancer risk and impaired response to therapy. Approximately 6% of Africans and 1% of African-Americans express a p53 allele with a serine instead of proline at position 47 (Pro47Ser). This SNP impairs p53-mediated apoptosis in response to radiation and genotoxic agents and is associated with increased cancer risk in humans and in a mouse model. In this study, we compared the ability of wild type (WT) and S47 p53 to suppress tumor development and respond to therapy. Our goal was to find therapeutic compounds that are more, not less, efficacious in S47 tumors. We identified the superior efficacy of two agents, cisplatin and BET inhibitors, on S47 tumors compared to WT. Cisplatin caused dramatic decreases in the progression of S47 tumors by activating the p53/PIN1 axis to drive the mitochondrial cell death program. These findings serve as important proof of principle that chemotherapy can be tailored to p53 genotype.
https://ift.tt/2L1SErv
CD44-targeted PLGA nanoparticles incorporating paclitaxel and FAK siRNA overcome chemoresistance in epithelial ovarian cancer
Chemotherapy is commonly used in the treatment of ovarian cancer, yet most ovarian cancers harbor inherent resistance or develop acquired resistance. Therefore, novel therapeutic approaches to overcome chemoresistance are required. In this study, we developed a hyaluronic acid-labeled poly(d,l-lactide-co-glycolide) nanoparticle (HA-PLGA-NP) encapsulating both paclitaxel (PTX) and focal adhesion kinase (FAK) siRNA as a selective delivery system against chemoresistant ovarian cancer. The mean size and zeta potential of the HA-PLGA-NP were 220 nm and -7.3 mV, respectively. Incorporation efficiencies for PTX and FAK siRNA in the HA-PLGA-NPs were 77% and 85%, respectively. HA-PLGA-NP showed higher binding efficiency for CD44-positive tumor cells as compared to CD44-negative cells. HA-PLGA (PTX+FAK siRNA)-NP caused increased cytotoxicity and apoptosis in drug-resistant tumor cells. Treatment of human epithelial ovarian cancer (EOC) tumor models HeyA8-MDR (p < 0.001) and SKOV3-TR (p < 0.001) with HA-PLGA (PTX+FAK siRNA)-NP resulted in significant inhibition of tumor growth. Moreover, in a drug-resistant, patient-derived xenograft (PDX) model, HA-PLGA (PTX+FAK siRNA)-NP significantly inhibited tumor growth compared with PTX alone (p < 0.002). Taken together, HA-PLGA-NP acts as an effective and selective delivery system for both the chemotherapeutic and the siRNA in order to overcome chemoresistance in ovarian carcinoma.
https://ift.tt/2nHLejN
Oxygen-enhanced and dynamic contrast-enhanced optoacoustic tomography provide surrogate biomarkers of tumour vascular function, hypoxia and necrosis.
Measuring the functional status of tumour vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatio-temporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that overcomes these challenges. By acquiring data at multiple wavelengths, OT can interrogate haemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumour vascular function, hypoxia and necrosis. We found that vascular maturity led to changes in vascular function that affected tumour perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumour and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumour hypoxia quantified ex vivo. Our findings indicate that OT may offer a significant advantage for localised imaging of tumour response to vascular targeted therapies when compared to existing clinical DCE methods.
https://ift.tt/2KZdM1u
Interferon-gamma PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy
Interferon-gamma (IFN-gamma) is an attractive target for imaging active anti-tumor immunity due to its function in the T cell signaling axis. Here we test an IFN-gamma immuno-positron emission tomography (immunoPET) probe for its capacity to identify adaptive immunotherapy (ITx) response after HER2/neu vaccination in both spontaneous salivary and orthotopic neu+ mouse mammary tumors. IFN-gamma immunoPET detected elevated cytokine levels in situ post-vaccination, which inversely correlated with tumor growth rate, an indicator of response to therapy. In a model of induced T cell anergy where CD8 T cells infiltrate the tumor, but upregulate PD-1, IFN-gamma tracer uptake was equivalent to isotype control, illustrating a lack of anti-tumor T cell activity. The IFN-gamma immunoPET tracer detected IFN-gamma protein sequestered on the surface of tumor cells, likely in complex with the IFN-gamma receptor, which may explain imaging localization of this soluble factor in vivo. Collectively, we find that the activation status of cytotoxic T cells is annotated by IFN-gamma immunoPET, with reduced off-target binding to secondary lymphoid tissues compared to imaging total CD3+ tumor infiltrating lymphocytes. Targeting of soluble cytokines such as IFN-gamma by PET imaging may provide valuable non-invasive insight into the function of immune cells in situ.
https://ift.tt/2nJE5zm
Transcriptomics and transposon mutagenesis identify multiple mechanisms of resistance to the FGFR inhibitor AZD4547
In human cancers, fibroblast growth factor receptor (FGFR) signaling is frequently hyperactivated by deregulation of FGF ligands or by activating mutations in the FGFR receptors such as gene amplifications, point mutations and gene fusions. As such, FGFR inhibitors are considered an attractive therapeutic strategy for patients with mutations in FGFR family members. We previously identified Fgfr2 as a key driver of invasive lobular carcinoma (ILC) in an in vivo insertional mutagenesis screen using the Sleeping Beauty (SB) transposon system. Here we explore whether these FGFR-driven ILCs are sensitive to the FGFR inhibitor AZD4547 and use transposon mutagenesis in these tumors to identify potential mechanisms of resistance to therapy. Combined with RNA sequencing-based analyses of AZD4547-resistant tumors, our in vivo approach identified several known and novel potential resistance mechanisms to FGFR inhibition, most of which converged on reactivation of the canonical MAPK-ERK signaling cascade. Observed resistance mechanisms included mutations in the tyrosine kinase domain of FGFR2, overexpression of MET, inactivation of RASA1, and activation of the drug-efflux transporter ABCG2. ABCG2 and RASA1 were identified only from de novo transposon insertions acquired during AZD4547 treatment, demonstrating that insertional mutagenesis in mice is an effective tool for identifying potential mechanisms of resistance to targeted cancer therapies.
https://ift.tt/2nHL8Zt
In vivo estimation of oncolytic virus populations within tumors
The use of replication-competent viruses as oncolytic agents is rapidly expanding, with several oncolytic viruses approved for cancer therapy. As responses to therapy are highly variable, understanding the dynamics of therapy is critical for optimal application of virotherapy in practice. Although mathematical models have been developed to understand the dynamics of tumor virotherapy, a scarcity of in vivo data has made difficult parametrization of these models. To tackle this problem, we studied the in vitro and in vivo spread of two oncolytic measles viruses that induce expression of the sodium iodide symporter (NIS) in cells. NIS expression enabled infected cells to concentrate radioactive isotopes that could be reproducibly and quantitatively imaged using SPECT/CT. We observed a strong linear relationship in vitro between infectious virus particles, viral N and NIS gene expression, and radioactive isotope uptake. In vivo radioisotope uptake was highly correlated with viral N and NIS gene expression. Similar expression patterns between viral N and NIS gene expression in vitro and in vivo implied that the oncolytic virus behaved similarly in both scenarios. Significant titers of viable virus were consistently isolated from tumors explanted from mice that had been injected with oncolytic MV. We observed a weaker but positive in vivo relationship between radioisotope uptake and the viable virus titer recovered from tumors; this was likely due to anisotropies in the viral distribution in vivo. These data suggest that methods that enable quantitation of in vivo anisotropies are required for continuing development of oncolytic virotherapy.
https://ift.tt/2L0fUpB
ErbB3 targeting enhances the effects of MEK inhibitor in wild-type BRAF/NRAS melanoma
MEK-ERK1/2 signaling is elevated in melanomas that are wild-type for both BRAF and NRAS (WT/WT), but patients are insensitive to MEK inhibitors. Stromal-derived growth factors may mediate resistance to targeted inhibitors, and optimizing the use of targeted inhibitors for WT/WT melanoma patients is a clinical unmet need. Here, we studied adaptive responses to MEK inhibition in WT/WT cutaneous melanoma. TCGA dataset and tumor microarray studies of WT/WT melanomas showed that high levels of neuregulin-1 (NRG1) were associated with stromal content and ErbB3 signaling. Of growth factors implicated in resistance to targeted inhibitors, NRG1 was effective at mediating resistance to MEK inhibitors in patient-derived WT/WT melanoma cells. Furthermore, ErbB3-ErbB2 signaling was adaptively upregulated following MEK inhibition. Patient-derived cancer-associated fibroblast studies demonstrated that stromal-derived NRG1 activated ErbB3/ErbB2 signaling and enhanced resistance to MEK inhibitor. ErbB3- and ErbB2-neutralizing antibodies blocked the protective effects of NRG1 in vitro and cooperated with MEK inhibitor to delay tumor growth in both cell line and patient-derived xenograft models. These results highlight tumor microenvironment regulation of targeted inhibitor resistance in WT/WT melanoma and provide a rationale for combining MEK inhibitors with anti-ErbB3/ErbB2 antibodies in WT/WT cutaneous melanoma patients for whom there are no effective targeted therapies options.
https://ift.tt/2vP5DIf
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy [Review]
Immune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentially curative therapeutic approaches. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Indeed, an extraordinary amount of preclinical and clinical investigation is exploring the therapeutic potential of negative and positive costimulatory molecules. Insights into the underlying biological mechanisms and functions of these molecules have, however, lagged significantly behind. Such understanding will be essential for the rational design of next-generation immunotherapies. Here, we review the current state of our understanding of T-cell costimulatory mechanisms and checkpoint blockade, primarily of CTLA4 and PD-1, and highlight conceptual gaps in knowledge.
Significance: This review provides an overview of immune checkpoint blockade therapy from a basic biology and immunologic perspective for the cancer research community. Cancer Discov; 8(9); 1–18. ©2018 AACR.
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DeepLesion Dataset Aids Tumor Detection [News in Brief]
Collection contains more than 30,000 annotated CT scans from patients with various cancers.
https://ift.tt/2nGWqgm
Targeting the MTF2-MDM2 axis sensitizes refractory acute myeloid leukemia to chemotherapy [Research Briefs]
Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that Metal Response Element Binding Transcription Factor 2/Polycomblike 2 (MTF2/PCL2) plays a fundamental role in the Polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2-deficient CD34+CD38- cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft (PDX) mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML.
https://ift.tt/2BiH37B
CDK4/6 inhibitors: what is the best cocktail?
CDK4/6 inhibitors have shown a great potential in the new armamentarium against cancer. However, their effect as single agents is limited and the hopes are on new combinatory strategies. Recent data suggest that inhibiting mTOR may significantly cooperate with cell cycle arrest in a variety of cancers.
https://ift.tt/2nJoL5K
Methylphenidate Good First-Choice Pediatric ADHD Drug
THURSDAY, Aug. 16, 2018 -- Methylphenidate should be considered as a first choice for the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents, while amphetamines should be considered as a first choice in adults,...
https://ift.tt/2w887AP
CDC: Brucellosis in Dogs Remains a Public Health Risk
THURSDAY, Aug. 16, 2018 -- Brucella canis is an under-recognized infection in dogs that poses a threat to human health, according to a report published in the August issue of the U.S. Centers for Disease Control and Prevention's Emerging Infectious...
https://ift.tt/2nKjACT
Practice Names, Logos Should Be Carefully Designed
THURSDAY, Aug. 16, 2018 -- Practice names and logos should be carefully designed to emphasize what is unique about a practice, according to a blog post published in Physicians Practice. Rebecca Fox, M.D., from FoxCare Integrative health in...
https://ift.tt/2w8873N
Doctors Remove Contact Lens Embedded in Eyelid for Years
THURSDAY, Aug. 16, 2018 -- Doctors recently removed a contact lens that was embedded in a woman's eyelid for nearly three decades after she was hit in the eye while playing badminton. The case was highlighted in the Aug. 10 online edition of BMJ...
https://ift.tt/2PggJxJ
NIH Panel Will No Longer Review Gene Therapy Experiments
THURSDAY, Aug. 16, 2018 -- A U.S. National Institutes of Health oversight panel will no longer review all applications for gene therapy experiments, according to a perspective piece published online Aug. 15 in the New England Journal of...
https://ift.tt/2w58coA
Planning for an uncertain future in progressive neurological disease: a qualitative study of patient and family decision-making with a focus on eating and drinking
Dysphagia and other eating and drinking difficulties are common in progressive neurological diseases. Mealtimes can become a major source of difficulty and anxiety for patients and their families. Decisions ab...
https://ift.tt/2BfB2sv
Do fragments and glycosylated isoforms of alpha-1-antitrypsin in CSF mirror spinal pathophysiological mechanisms in chronic peripheral neuropathic pain? An exploratory, discovery phase study
Post-translational modifications (PTMs) generate a tremendous protein diversity from the ~ 20,000 protein-coding genes of the human genome. In chronic pain conditions, exposure to pathological processes in the...
https://ift.tt/2Midfx0
Wearables for gait and balance assessment in the neurological ward - study design and first results of a prospective cross-sectional feasibility study with 384 inpatients
Deficits in gait and balance are common among neurological inpatients. Currently, assessment of these patients is mainly subjective. New assessment options using wearables may provide complementary and more ob...
https://ift.tt/2BfASBp
Exceptional association of two species of bacteria causing mediastinitis: Haemophilus influenzae (H. influenzae) and Aggregatibacter aphrophilus (A. aphrophilus)
Post cardiac surgery mediastinitis is the major infectious complication, despite the development of surgical techniques and the application of strict preventive measures.
https://ift.tt/2PdCPkx
Microlesion effects, suboptimal lead placement and disease progression are critical determinants for DBS tolerance in essential tremor
Merchant et al. propose a computerized spiral analysis test for differentiation of essential tremor (ET) patients who develop "early tolerance" to deep brain stimulation (DBS) benefits (within two years) from those who exhibit sustained improvements (Merchant et al., 2018). In their study, ET patients were identified to develop "early tolerance" if they had a higher degree of severity score and a greater loop-to-loop width variability index on spiral drawings. The latter characteristic is usually observed in patients with underlying cerebellar dysfunction.
https://ift.tt/2OHOdnJ
Management of ulcerative colitis in a real-life setting: an Italian multicenter, prospective, observational AIGO study
No data are available on the variability in the clinical management of ulcerative colitis (UC) patients by Italian gastroenterologists. Therefore, improving the standards of UC care as provided by the National Welfare Clinical Path (PDTA), in accordance with the European Crohn's and Colitis Organization (ECCO) guidelines for UC, is not easy.
https://ift.tt/2L3GSwu
The Arcuate Fracture: A Descriptive Radiographic Study
Publication date: Available online 16 August 2018
Source: Injury
Author(s): Brian H. Cohen, Steven F. DeFroda, Jonathan D. Hodax, David Johnson, J. Kristopher Ware, Paul D. Fadale
Abstract
Purpose
To assess plain radiographic morphology of arcuate fractures in order to identify patterns and help shape treatment algorithm for proximal fibula fracture.
Methods
A search of radiographic reports at a level 1 trauma center from 2014 to 2016 using MONTAGE search software for the phrases "arcuate fracture", "fibular head avulsion", or "fibular head fracture" was conducted. Descriptive measurements were obtained including dimensions of the fragment, the displacement of the fragment from its anatomic position, and the orientation of the primary fracture line relative to the axis of the fibular diaphysis in both the sagittal and coronal plane. After review of the measurements and radiographs, fracture patterns were assessed based off previous knowledge previous knowledge of posterior lateral corner (PLC) anatomy.
Results
Radiographic reports of 48 knees (48 patients) met inclusion criteria. The distance of fractures from the proximal aspect of the fibula averaged 9.25 ± 5.53 mm on AP radiographs, and 9.42 ± 4.89 mm on lateral radiographs. The medial-to-lateral width of the proximal fragment averaged 20.09 ± 7.94 mm on AP radiographs, while the anterior-to-posterior width measured on lateral radiographs averaged 17.53 ± 8.48 mm. Orientation of the primary fracture line was calculated at an average of 23.04 ± 14.95° from the perpendicular on the AP view, and 21.55 ± 17.44° from the perpendicular on the lateral. Maximal displacement at the primary fracture line on the AP view was 4.95 ± 8.49 mm). Maximal displacement on the lateral measured 3.98 ± 7.01 mm. Recurring fracture patterns were identified and described. Assessment revealed 11 (22.9%) pattern 1 fractures, six (12.5%) pattern 2 fractures, 31 (64.58%) pattern 3 fractures, possibly correlating with anatomical features and fracture mechanism.
Conclusions
These measurements and recurring patterns in our study shows the heterogeneity of the size and displacement of these fracture fragments and demonstrates the need for further studies in order to create an anatomic descriptive classification for arcuate fractures, which could be used for clinically for treatment.
https://ift.tt/2nJegzq
Fixation of unstable ankle fractures using a long hindfoot nail Abstract
Publication date: Available online 16 August 2018
Source: Injury
Author(s): G. Baker, A.I.W. Mayne, C. Andrews
Abstract
Background
Management of fragility fractures of the ankle is challenging. Non-operative treatment often requires significant periods of reduced weight bearing. Operative fixation is difficult due to osteoporotic bone and poor soft tissues.
The aim of this study was to review the initial experience of treating unstable ankle fractures with a retrograde femoral nail used as a long tibiotalocalcaneal nail.
Patients and Methods
Sixteen patients were treated from January 2014 until November 2017. Mean age was 73 (50–96) and twelve of the sixteen patients were female. All patients had three or more co-morbidities and an American Society of Anaesthesiologists score of 3. All patients had unstable ankle fracture configurations and were classified using the AO classification.
Results
All patients regained baseline mobility by final follow-up (mean 21 months follow-up). Four of the twelve patients died within 12 months of surgery. There were no wound complications or deep infections. There were no cases of metalwork failure or peri-prosthetic fracture.
Discussion
Use of a retrograde femoral nail has been shown to be a safe and effective option in the management of unstable ankle fractures in elderly and frail patients. This technique may lead to lower wound complications compared to traditional fixation techniques and allows earlier mobilisation.
https://ift.tt/2MSF8Il
FDA Approves First Generic Version of EpiPen
August 16, 2018 -- The U.S. Food and Drug Administration today approved the first generic version of EpiPen and EpiPen Jr (epinephrine) auto-injector for the emergency treatment of allergic reactions, including those that are life-threatening...
https://ift.tt/2MsCT1f
Acute toxicity profiles of hypofractionated adjuvant and salvage radiotherapy after radical prostatectomy: results of a prospective study
Moderate hypofractionated adjuvant and salvage RT, as administered with Helical Tomotherapy, was acutely safe after RP as it was associated with acceptable rates of slight-to-moderate acute GU and GI toxicity in 112 patients. Uroflowmetry emerged as a reliable test for RT-related GU toxicity. A longer follow-up is needed to confirm these promising clinical outcomes.
https://ift.tt/2PgO5gg
The prognostic significance of p16 status in patients with vulvar cancer treated with vulvectomy and adjuvant radiation
This is a retrospective analysis from a single institution examining 39 women with vulvar squamous cell carcinoma treated with adjuvant radiation therapy noting how outcomes differed according to p16 status—measured through immunohistochemistry. We observed fewer in-field relapses and improved progression-free survival in women whose tumors were p16 positive. There was no difference in overall survival between groups. This is the largest cohort of patients treated with adjuvant radiation therapy with known p16 status.
https://ift.tt/2ODbuav
Scholarly Activity Training during Residency: Ensuring a Meaningful Experience for All Graduates
Learning the basic principles of scientific research and participating in scholarly activity are critical parts of the residency experience and are mandated by the Accreditation Council for Graduate Medical Education (ACGME).1 Participating in scholarly activity may benefit residents by helping cultivate their skills in appraising scientific literature critically and fostering self-directed learning.2-4 A robust experience may also help residents to develop meaningful relationships with faculty mentors and nurture an interest in pursuing a fellowship and academic career.
https://ift.tt/2vPZk7j
Target Organ Abnormalities in Pediatric Hypertension
In 2013, the US Preventive Services Task Force, in an update of their 2003 report, concluded that there was insufficient evidence to assess the balance of benefits and harms of screening for primary hypertension in children and adolescents to prevent subsequent cardiovascular disease in childhood or adulthood.1 The US Preventive Service Task Force used a review of published evidence to come to their conclusion. Their review produced an "I" Statement. This means that, based on their key questions, there is insufficient evidence for or against blood pressure screening in children and adolescents.
https://ift.tt/2L4equI
Regulations of Night Shifts of Pediatric Residents: Review of Responses to a European Survey
The regulation of residents' night shifts and weekly working hours increasingly is being questioned and investigated to better understand the benefits and harms. Studies on the effects of fatigue on function appeared in the media in the early 1970s in the US (Table I; available at www.jpeds.com); one of the first studies demonstrated that interns "deprived of sleep were significantly less able to recognize arrhythmias on the electrocardiographic task" and "judged themselves to have abnormalities in cognitive, perceptual, and physiologic areas of function."5 A review of the current literature questions the effect of subsequent American changes in the night shift hours and weekly work hours of the residents.
https://ift.tt/2vMd0Ae
Preliminary clinical experience with robotic retroperitoneoscopic pancreatic surgery
Abstract
Backgrounds
Retroperitoneoscopic surgery has shown advantages in urological surgery. However, its application in pancreatic surgery for neoplasm is rare. Robotic surgical system with its magnified view and flexible instruments may provide a superior alternative to conventional laparoscopic system in retroperitoneoscopic surgery. We aimed to evaluate the safety, feasibility, and short-term outcomes in a series of patients treated by robotic retroperitoneoscopic pancreatic surgery.
Case presentation
Between March 2016 and May 2016, four patients with solitary pancreatic neuroendocrine neoplasms were treated with robotic retroperitoneoscopic surgery. Prospective collected clinical data were retrospectively analyzed. Three patients underwent distal pancreatectomy (one combined with resection of left adrenal adenoma), and one patient enucleation. The mean operative time was 80 min (range 30–110 min). The estimated blood loss was insignificant. There was no conversion to open procedure. The mean postoperative hospital stay was 5.25 days (range 4–6 days). The mean tumor size was 1.375 cm (range 1.0–1.8 cm) in diameter. All patients' blood glucose level returned to normal range within 1 week postoperatively. Two patients had pancreatic biochemical leak. No patients underwent subsequent treatment, and no recurrence occurred during the 12-month follow-up period.
Conclusions
This study preliminarily indicates that robotic retroperitoneoscopic pancreatic surgery is safe and feasible for neoplasms in the dorsal portion of distal pancreas in selected patients, with some potential advantages of straightforward access, simple and fine manipulation, short operative time, and fast recovery.
https://ift.tt/2MVF2zt
Monitoring Urine Flow to Prevent Overcorrection of Hyponatremia: Derivation of a Safe Upper Limit Based on the Edelman Equation
Overly fast correction of hyponatremia is the most important risk factor for osmotic demyelination, which can result in severe neurologic deficits and mortality.1 Despite widespread awareness of the problem, overcorrection of hyponatremia still occurs. Because the most common reason is the development of sudden substantial water diuresis,2 integrating some form of urine volume monitoring is a logical measure to improve safety in hyponatremic patients.3
https://ift.tt/2Pcs2ax
Outcomes of the First and Second Hemodialysis Fistula: A Cohort Study
Fistulas are the preferred form of hemodialysis access; however, many fistulas fail to mature into usable accesses after creation. Data for outcomes after placement of a second fistula are limited.
https://ift.tt/2BjfVW0
Renal Disorders in Pregnancy: Core Curriculum 2019
As the incidence of chronic kidney disease increases and women pursue pregnancy at more advanced ages, the management of kidney disease in pregnancy has become increasingly relevant to the practicing nephrologist. Women with kidney disorders face several challenges in pregnancy due to increased physiologic demands on the kidney and risk for disease progression, the potential teratogenicity of medications, and the increased risk for complications such as preeclampsia and preterm delivery. Challenges posed by an underlying disease process in pregnancy, such as autoimmune disease or diabetes mellitus, necessitate an interdisciplinary team to ensure good maternal and fetal outcomes.
https://ift.tt/2PgbhLt
Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe: Results From the ERA-EDTA Registry
Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT.
https://ift.tt/2KZgQum
Electrophoretic Crystallization of Ultrathin High-performance Metal-organic Framework Membranes
A simple, reproducible, and versatile approach for the synthesis of intergrown, polycrystalline metal-organic framework membranes on a wide range of unmodified porous and non-porous supports is presented.
https://ift.tt/2KYsTrS
Comparison of the association of predicted fat mass, body mass index, and other obesity indicators with type 2 diabetes risk: two large prospective studies in US men and women
Abstract
Obesity, defined by body mass index (BMI), is a well-established risk factor of type 2 diabetes, but BMI has been criticized for its inability to discriminate fat mass and lean body mass. We examined the association between predicted fat mass and type 2 diabetes risk in two large US prospective cohorts, and compared the magnitude of the association with BMI and other obesity indicators. Validated anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey were used to estimate predicted fat mass and percent fat for 97,111 participants from the Health Professionals Follow-up Study (1987–2012) and the Nurses' Health Study (1986–2012) who were followed up for type 2 diabetes. Multivariable-adjusted hazard ratios for type 2 diabetes across quintiles of predicted fat mass were 1.00, 1.96, 2.96, 3.90, and 8.38 for men and 1.00, 2.20, 3.50, 5.73, and 12.1 for women; of BMI were 1.00, 1.69, 2.45, 3.54, and 6.94 for men and 1.00, 1.76, 2.86, 4.88, and 9.88 for women. Predicted FM showed the strongest association with type 2 diabetes in men followed by waist circumference (WC), waist-to-height ratio (WHtR), predicted percent fat, BMI, Waist-to-hip ratio (WHR), and a body shape index (ABSI). For women, the strongest association was shown for WHtR, followed by WC, predicted percent fat, predicted fat mass, BMI, ABSI, and WHR. Compared to BMI, predicted fat mass demonstrated consistently stronger association with type 2 diabetes risk. However, there was inconclusive evidence to suggest that predicted fat mass is substantially superior to other obesity indicators.
https://ift.tt/2Mvjq05
Transient Expression in Nicotiana Benthamiana Leaves for Triterpene Production at a Preparative Scale
Transient heterologous expression of biosynthetic enzymes in Nicotiana benthamiana leaves can divert endogenous supplies of 2,3-oxidosqualene towards the production of new high-value triterpene products. Herein is described a detailed protocol for rapid (5 days) preparative-scale production of triterpenes and analogs utilizing this powerful plant-based platform.
https://ift.tt/2MjGnUE
The Generation of Closed Femoral Fractures in Mice: A Model to Study Bone Healing
The murine closed femoral fracture model is a powerful platform to study fracture healing and novel therapeutic strategies to accelerate bone regeneration. The goal of this surgical protocol is to generate unilateral closed femoral fractures in mice using an intramedullary steel rod to stabilize the femur.
https://ift.tt/2Bj5MZE
Synaptic Microcircuit Modeling with 3D Cocultures of Astrocytes and Neurons from Human Pluripotent Stem Cells
https://ift.tt/2nKctdo
Alcohol consumption during pregnancy and risk of small-for-gestational-age newborn
Publication date: Available online 16 August 2018
Source: Women and Birth
Author(s): J.M. Martínez-Galiano, C. Amezcua-Prieto, I. Salcedo-Bellido, R. Olmedo-Requena, A. Bueno-Cavanillas, M. Delgado-Rodriguez
Abstract
Background
Contradictory results have been published on the association of alcohol consumption during pregnancy with perinatal outcomes, including the risk of small for gestational age newborn.
Aim
To determine whether alcohol consumption during pregnancy is associated with the risk of small for gestational age newborn.
Method
A case-control study with 518 pairs of pregnant Spanish women in five hospitals was conducted; cases were women with small for gestational age newborn and age-matched (±2 years) controls were women with non-small for gestational age newborn. Data were gathered on demographic characteristics, socioeconomic status, toxic habits, and diet. Alcohol intake was recorded with a self-administered 137 food frequency questionnaire and with a personal interview, Alcohol intake was categorized –. Agreement in alcohol intake results between direct interview and frequency food questionnaire was evaluated with the Kappa index. Crude and adjusted odds ratios and their 95% confidence intervals were estimated by conditional logistic regression.
Findings
Poor agreement was observed between food frequency questionnaire and personal interview results for both cases (κ = 0.23) and controls (κ = 0.14). A food frequency questionnaire-recorded intake of less than 4 g/day was associated with a significantly lower odds ratios for small for gestational age newborn (odds ratios = 0.62, 95% confidence intervals, 0.43–0.88), whereas an interview-recorded intake of <4 g/day was not related to small for gestational age newborn (odds ratios = 0.86, 95% confidence intervals, 0.49–1.54).
Conclusions
A very moderate alcohol intake during pregnancy may have a negative association with the risk of having a small for gestational age newborn.
https://ift.tt/2nKuCrG
Patient-centered EMS leadership
Patient-centered care partnerships with patients and family need to start at the top
https://ift.tt/2vOKXjl
How to keep PTSD out of your EMS agency
Recognize the risk factors and symptoms of PTSD, and how to manage self-talk and meditate to reduce its physical and emotional effects
https://ift.tt/2L00pxM
A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
https://ift.tt/2PfLH9f
Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
https://ift.tt/2OGXjB3
Counseling Needed for Pediatric Patients With Impaired Fertility
THURSDAY, Aug. 16, 2018 -- Counseling about impaired fertility and sexual function for at-risk pediatric populations in developmentally appropriate ways is essential, according to a clinical report published in the August issue of Pediatrics. Leena...
https://ift.tt/2Pa4pPE
Weight Gain After Quitting Smoking May Up T2DM Risk
THURSDAY, Aug. 16, 2018 -- Smoking cessation accompanied by weight gain is linked to increased risk of type 2 diabetes, according to a study published in the Aug. 16 issue of the New England Journal of Medicine. Yang Hu, from the Harvard T.H. Chan...
https://ift.tt/2nHj6NF
Two Strategies for Preventing Diabetes in Minority Patients
THURSDAY, Aug. 16, 2018 -- Recognizing the barriers to care for minority patients with type 2 diabetes could reduce the incidence of type 2 diabetes nationwide, according to an article published by the American Medical Association's AMA Wire. Noting...
https://ift.tt/2MOUu0j
Patient Portals Don't Appear to Have Much Traction
THURSDAY, Aug. 16, 2018 -- Patient portals have not taken off as expected, according to an article published in Medical Economics. Portals enable patients to view their health records and lab results online, share the information with other...
https://ift.tt/2MPnp4A
Vit D Independently, Inversely Tied to Cholesterol in Children
THURSDAY, Aug. 16, 2018 -- Serum 25-hydroxyvitamin D [25(OH)D] is independently and inversely associated with total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol in children, according to a...
https://ift.tt/2nHH9fq
Steps Provided for Discharging Patient From Practice
THURSDAY, Aug. 16, 2018 -- Certain steps should be taken when discharging a patient for failure or inability to meet financial obligations, according to an article published in Physicians Practice. Failure or inability to meet financial obligations...
https://ift.tt/2MOUm0P
ACA Coverage Gains Include Workers Without Insurance
THURSDAY, Aug. 16, 2018 -- After the expanded coverage provisions of the Affordable Care Act (ACA) were implemented in 2014, self-employed individuals and wage earners without employer-sponsored health coverage offers had coverage gains equal to or...
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Ibalizumab Active in Multidrug Resistant HIV-1 Infection
THURSDAY, Aug. 16, 2018 -- Ibalizumab has antiviral activity among patients with multidrug resistant (MDR) HIV-1 infection, according to a study published in the Aug. 16 issue of the New England Journal of Medicine. Brinda Emu, M.D., from the Yale...
https://ift.tt/2MOUjSH
Healthy Brain-pituitary Slices for Electrophysiological Investigations of Pituitary Cells in Teleost Fish
The article describes an optimized protocol for making viable brain-pituitary tissue slices, using the teleost fish medaka (Oryzias latipes), followed by electrophysiological recordings of pituitary cells using the patch-clamp technique with the perforated patch configuration.
https://ift.tt/2PfDt0R
Diagnostic value of FDG-PET versus magnetic resonance imaging for detecting spondylitis: a systematic review and meta-analysis
Publication date: Available online 16 August 2018
Source: The Spine Journal
Author(s): Yanlin Yin, Xinwei Liu, Xinming Yang, Jie Guo, Qiang Wang, Lixing Chen
Abstract
Background
Spondylitis is a rare infection in bone requiring multiple diagnostic strategies for verification.
Purpose
This study aimed to compare the diagnostic values of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) in detecting spondylitis.
Methods
Online PubMed, Embase, and Cochrane Library databases were systematically searched through September 2017 for studies comparing the diagnostic values of 18F-FDG-PET and MRI. The summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve were calculated using Stata software. The ratio of these indexes between 18F-FDG-PET and MRI was also determined.
Results
The summary results for 18F-FDG-PET were as follows: sensitivity=0.96 [95% confidence intervals (CI), 0.84–0.99]; specificity=0.90 (95% CI, 0.79–0.96); PLR=9.83 (95% CI, 4.39–22.03); NLR=0.05 (95% CI, 0.01–0.19); DOR=124.08 (95% CI, 39.04–394.34); and area under the SROC=0.97 (95% CI, 0.95–0.98). The summary sensitivity, specificity, PLR, NLR, DOR, and area under the SROC for MRI were 0.76 (95% CI, 0.65–0.84), 0.62 (95% CI, 0.45–0.77), 2.01 (95% CI, 1.36–2.98), 0.39 (95% CI, 0.27–0.56), 5.08 (95% CI, 2.66–9.69), and 0.77 (95% CI, 0.73–0.80). The summary results of sensitivity (P = 0.034), specificity (P = 0.006), PLR (P < 0.001), DOR (P < 0.001), and area under the SROC (P < 0.001) were higher in 18F-FDG-PET than in MRI. However, NLR (P = 0.003) was lower in 18F-FDG-PET than in MRI.
Conclusion
18F-FDG-PET had higher diagnostic value compared with MRI in detecting spondylitis.
https://ift.tt/2KYbX4A
Observed Patterns of Cervical Radiculopathy: How Often do They Differ from a Standard, “Netter-diagram” Distribution?
Publication date: Available online 16 August 2018
Source: The Spine Journal
Author(s): Steven J. McAnany, John M. Rhee, Evan O. Baird, Weilong Shi, Jeffrey Konopka, Thomas M. Neustein, Rafael Arceo
Abstract
Background
Traditionally, cervical radiculopathy is thought to present with symptoms and signs in a standard, textbook, reproducible pattern as seen in a "Netter diagram." To date, no study has directly examined cervical radicular patterns attributable to single level pathology in patients undergoing ACDF.
Purpose
The purpose of this study is to examine cervical radiculopathy patterns in a surgical population and determine how often patients present with the standard textbook (i.e. "Netter diagram") versus non-standard patterns.
Study Design/Setting
Retrospective study
Patient Sample
Patients who had single-level radiculopathy with at least 75% improvement of pre-operative symptoms following ACDF were included.
Outcome Measures
Epidemiological variables were collected including age, sex, weight, body mass index, laterality of symptoms, duration of symptoms prior to operative intervention, and the presence of diabetes mellitus. The observed pattern of radiculopathy at presentation, including associated neck, shoulder, upper arm, forearm, and hand pain/numbness, was determined from chart review and patient-derived pain diagrams.
Methods
We identified all patients with single level cervical radiculopathy operated on between March 2011 and March 2016 by six surgeons. The observed pattern of radiculopathy was compared to a standard textbook pattern of radiculopathy that strictly adheres to a dermatomal map Fisher's exact test was used to analyze categorical data and Student's t-test was used for continuous variables. A one-way ANOVA was used to determine differences in the observed versus expected radicular pattern. A logistic regression model assessed the effect of demographic variables on presentation with a non-standard radicular pattern.
Results
Overall, 239 cervical levels were identified. The observed pattern of pain and numbness followed the standard pattern in only 54% (129/239; p=0.35). When a non-standard radicular pattern was present, it differed by 1.68 dermatomal levels from the standard (p<0.0001). Neck pain on the radiculopathy side was the most prevalent symptom; it was found in 81% (193/239) of patients and did not differ by cervical level (p=0.72). In a logistic regression model, none of the demographic variables of interest were found to significantly impact the likelihood of presenting with a non-standard radicular pattern.
Conclusions
Observed patterns of cervical radiculopathy only followed the standard pattern in 54% of patients and did not differ by the cervical level involved. Cervical radiculopathy often presents with a non-standard pattern. Surgeons should think broadly when identifying causative levels because they frequently may not adhere to textbook descriptions in actual clinical practice.
Level of Evidence: III
https://ift.tt/2PciqMG
Fungal spinal epidural abscess: a case series of nine patients
Publication date: Available online 16 August 2018
Source: The Spine Journal
Author(s): Huiliang Yang, Akash A. Shah, Sandra B. Nelson, Joseph H. Schwab
Abstract
Background context
Fungal spinal epidural abscess (FSEA) is a rare entity with high morbidity and mortality. Reports describing the clinical features, diagnosis, treatment, and outcomes of FSEA are scarce in the literature.
Purpose
This study aimed to describe the clinical features, diagnosis, treatment and outcomes of FSEA.
Study design
This study is designed as a retrospective clinical case series.
Patient sample
A continuous series of patients with the diagnosis of FSEA who presented at our institution from 1993 to 2016.
Methods
We reviewed the electronic medical records of patients with SEA who were treated within our hospital system from 1993 to 2016. We only included SEA cases were caused by fungi. We also reviewed FSEA cases in the English-language literature from 1952 to 2017 to analyse the features of FSEA.
Results
From a database of 1,053 SEA patients, we identified 9 patients with FSEA. Aspergillus fumigatus was isolated from 2 (22%) patients, and Candida species were isolated from 7 (78%). Focal spine pain, neurologic deficit, and fever were demonstrated in 89%, 50%, and 44% of FSEA cases, respectively. Five of 9 cases involved the thoracic spine, and 8 were located anterior to the thecal sac. Three cases had fungemia, 6 had long symptom duration (>2 weeks) prior to presentation, 7 had concurrent immunosuppression, and 8 had vertebral osteomyelitis. Additionally, 1 case had residual motor deficit at last follow-up, 1 had S1 sensory radicular symptoms, 2 suffered recurrent FSEA, 2 died within hospitalization, and 2 died within 90 days after discharge.
Conclusions
In summary, the classic diagnostic triad (focal spine pain, neurologic deficit, and fever) is not of great clinical utility for FSEA. Biopsy, intraoperative tissue culture, and blood culture can be used to diagnose FSEA. The most common pathogens of FSEA are Aspergillus and Candida species. Therefore, empiric treatment for FSEA should cover these species while definitive identification is pending. FSEA is found in patients with poor baseline health status, which is the essential reason for its high mortality.
https://ift.tt/2OG99eN
KPNA2 promotes metabolic reprogramming in glioblastomas by regulation of c-myc
Abstract
Background
Cancer cells maintain energy metabolism mainly by glycolysis, even under sufficient oxygen conditions. It gives cancer cells better growth advantages under complicated internal environment. KPNA2 is a novel oncogene that has received much attention in recent years, but the exact mechanisms of KPNA2 in tumorigenesis and progression are largely unknown. Especially its potential roles in the metabolic transformation of tumors still remain to be explored.
Methods
The expressions of KPNA2 in glioblastoma and normal human brain samples were analyzed by immunohistochemical analysis. The activities of key enzymes in glycolysis, the production of lactate acid and glucose uptake were investigated by colorimetry. GLUT-1 expression was measured by flow cytometry. CCK8 was used to examine the cell viability in vitro, and the xenograft models in nude mice were established to explore the roles of KPNA2 in vivo. In addition, Co-IP, subcellular fractionation, western blot, immunofluorescence and luciferase assay were used to investigate the internal connection between KPNA2, c-myc and E2F1.
Results
In the present study, we found that KPNA2 was highly expressed in the glioma compared to the normal brain tissues. Level of KPNA2 was an independent predictor of prognosis in the glioma patients. Knockdown of KPNA2 in the glioblastoma cell lines U87 and U251 decreased deoxyglucose uptake, activities of the key glycolytic enzymes and lactate production. The level of oxidative phosphorylation (OXPHOS) was moderately decreased. Additioanlly, tumor proliferation and invasiveness were concomitantly downregulated. We have identified c-myc as a potential mediator of KPNA2. Aberrant expression of KPNA2 significantly changed the subcellular distribution of c-myc as well as its expression level. E2F1, another key cargo protein of KPNA2, was further identified to play a potential role in regulating the transcription of c-myc by KPNA2.
Conclusions
Our findings suggested that KPNA2, a potential tumor oncogene, performs its function in part via regulating cellular metabolism through c-myc signaling axis. It would provide a possible explanation for Warburg effect and thus offer a new perspective to the roles of KPNA2 in gliomagenesis.
https://ift.tt/2nKcGNS
Percutaneous Screw Fixation for Painful Non-Union of Lateral Malleolus Ankle Fractures
Publication date: Available online 16 August 2018
Source: Injury
Author(s): Timothy J. Batten, Charlotte Scott-Davies, Michael Butler, Stephen W. Parsons, Richard P. Walter
Abstract
Introduction
Lateral malleolus non-union can cause pain and loss of function. Standard treatment involves open approach with debridement, bone-grafting and plate stabilisation, with published surgical site infection rates to 17%. To minimise the risk of soft tissue complications and allow early mobilisation, we describe a technique for percutaneous cannulated screw stabilisation.
Materials and Methods
Retrospective case review for all percutaneous lateral malleolus non-union stabilisation procedures undertaken in our hospital between 2011 and 2017 was performed. Fracture union was diagnosed by resolution of pain and swelling, with a return to full weight-bearing mobilisation and two-view radiographs consistent with union.
Results
Twelve cases were reviewed. All fractures united. There was one superficial wound infection treated with oral antibiotics, and one early case with drill-piece fracture requiring conversion to open procedure with plate stabilisation.
Conclusion
We believe this to be the first report of percutaneous stabilisation for non-union of lateral malleolus fractures. We demonstrate this to be a safe and effective technique.
https://ift.tt/2KYhhVV
Genetic variation within endolysosomal system is associated with late-onset Alzheimer’s disease
Abstract
Late-onset Alzheimer's disease is the most common dementia type, yet no treatment exists to stop the neurodegeneration. Evidence from monogenic lysosomal diseases, neuronal pathology and experimental models suggest that autophagic and endolysosomal dysfunction may contribute to neurodegeneration by disrupting the degradation of potentially neurotoxic molecules such as amyloid-β and tau. However, it is uncertain how well the evidence from rare disorders and experimental models capture causal processes in common forms of dementia, including late-onset Alzheimer's disease. For this reason, we set out to investigate if autophagic and endolysosomal genes were enriched for genetic variants that convey increased risk of Alzheimer's disease; such a finding would provide population-based support for the endolysosomal hypothesis of neurodegeneration. We quantified the collective genetic associations between the endolysosomal system and Alzheimer's disease in three genome-wide associations studies (combined n = 62 415). We used the Mergeomics pathway enrichment algorithm that incorporates permutations of the full hierarchical cascade of SNP-gene-pathway to estimate enrichment. We used a previously published collection of 891 autophagic and endolysosomal genes (denoted as AphagEndoLyso, and derived from the Lysoplex sequencing platform) as a proxy for cellular processes related to autophagy, endocytosis and lysosomal function. We also investigated a subset of 142 genes of the 891 that have been implicated in Mendelian diseases (MenDisLyso). We found that both gene sets were enriched for genetic Alzheimer's associations: an enrichment score 3.67 standard deviations from the null model (P = 0.00012) was detected for AphagEndoLyso, and a score 3.36 standard deviations from the null model (P = 0.00039) was detected for MenDisLyso. The high enrichment score was specific to the AphagEndoLyso gene set (stronger than 99.7% of other tested pathways) and to Alzheimer's disease (stronger than all other tested diseases). The APOE locus explained most of the MenDisLyso signal (1.16 standard deviations after APOE removal, P = 0.12), but the AphagEndoLyso signal was less affected (3.35 standard deviations after APOE removal, P = 0.00040). Additional sensitivity analyses further indicated that the AphagEndoLyso Gene Set contained an aggregate genetic association that comprised a combination of subtle genetic signals in multiple genes. We also observed an enrichment of Parkinson's disease signals for MenDisLyso (3.25 standard deviations) and for AphagEndoLyso (3.95 standard deviations from the null model), and a brain-specific pattern of gene expression for AphagEndoLyso in the Gene Tissue Expression Project dataset. These results provide evidence that a diffuse aggregation of genetic perturbations to the autophagy and endolysosomal system may mediate late-onset Alzheimer's risk in human populations.https://ift.tt/2MS0t4J
Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency
Optimized partial depletion of Mbd3 had been implicated in deterministic reprogramming. Hanna and colleagues now dissect the subcomplex within Mbd3/NuRD that underlies this outcome. Gatad2a is identified as a flexible component that can be entirely ablated without compromising somatic cell proliferation and yet still similarly yields deterministic mouse iPSC formation.
https://ift.tt/2Mo4gd5
Low serum gastrin associated with ER + breast cancer development via inactivation of CCKBR/ERK/P65 signaling
Abstract
Background
Gastrin is an important gastrointestinal hormone produced primarily by G-cells in the antrum of the stomach. It normally regulates gastric acid secretion and is implicated in a number of human disease states, but how its function affects breast cancer (BC) development is not documented. The current study investigated the suppressive effects of gastrin on BC and its underlying mechanisms.
Methods
Serum levels of gastrin were measured by enzyme-linked immunosorbent assay (ELISA) and correlation between gastrin level and development of BC was analyzed by chi-square test. Inhibitory effects of gastrin on BC were investigated by CCK-8 assay and nude mice models. Expressions of CCKBR/ERK/P65 in BC patients were determined through immunohistochemistry (IHC) and Western blot. Survival analysis was performed using the log-rank test.
Results
The results indicated that the serum level of gastrin in BC patients was lower compared with normal control. Cellular and molecular experiments indicated that reduction of gastrin is associated with inactivation of cholecystokinin B receptor (CCKBR)/ERK/P65 signaling in BC cells which is corresponding to molecular type of estrogen receptor (ER) positive BC. Furthermore, we found that low expression of gastrin/CCKBR/ERK /P65 was correlated to worse prognosis in BC patients. Gastrin or ERK/P65 activators inhibited ER+ BC through CCKBR-mediated activation of ERK/P65. Moreover, combination treatment with gastrin and tamoxifen more efficiently inhibited ER+ BC than tamoxifen alone.
Conclusions
We concluded that low serum gastrin is related to increased risk of ER+ BC development. The results also established that CCKBR/ERK/P65 signaling function is generally tumor suppressive in ER+ BC, indicating therapies should focus on restoring, not inhibiting, CCKBR/ERK/P65 pathway activity.
https://ift.tt/2OFNW4F
Lesions of “uncertain malignant potential” in the breast (B3) identified with mammography screening
Abstract
Background
Core needle biopsy (CNB) is a standard diagnostic procedure in the setting of breast cancer screening. However, CNB may result in the borderline diagnoses of lesion of uncertain malignant potential (B3). The aim of this study was to access the outcome of lesions diagnosed as B3 category in a large series of screen-detected cases to evaluate the rates of malignancy for the different histological subtypes.
Methods
We identified all CNBs over a six-year period (2009-2015) in a breast cancer screening unit in Germany. A total of 8.388 CNB's were performed for screen detected breast lesions. B3 diagnosis comprised 4.5% (376/8.388). Of the 376 patients who were diagnosed as B3, 299 underwent subsequent excision biopsy with final excision histology.
Results
Out of 376 patients diagnosed with B3 lesions, the prevalence of different histopathology showed 161 (42.8%) patients with atypical ductal hyperplasia (ADH), 98 (26.1%) with flat epithelial atypia (FEA), 50 women (13.3%) showed lobular neoplasia (LN), in 40 (10.6%) patients papillary findings and in 27 patients (7.2%) a radial scar complex. Final excision histology was benign in 74% (221/299) and malignant in 26% (78/299) of the patients. Lesion specific positive predictive values (PPV) for a subsequent diagnosis of in situ or invasive carcinoma were as follows: ADH 40%, FEA 20.5%, papillary lesion 13.5%, radial scar 16.6%, LN 0%.
Conclusion
Our results show that approximately one-third of core needle biopsies of screen detected breast lesions classified as B3 are premalignant or malignant on excision.
Lesions of uncertain malignant potential of the breast (B3) are heterogeneous in respect to risk of malignancy.
https://ift.tt/2PeEEh6
PIK3CA mutation is a favorable prognostic factor in esophageal cancer: molecular profile by next-generation sequencing using surgically resected formalin-fixed, paraffin-embedded tissue
Abstract
Background
Practical and reliable genotyping procedures with a considerable number of samples are required not only for risk-adapted therapeutic strategies, but also for stratifying patients into future clinical trials for molecular-targeting drugs. Recent advances in mutation testing, including next-generation sequencing, have led to the increased use of formalin-fixed paraffin-embedded tissue. We evaluated gene alteration profiles of cancer-related genes in esophageal cancer patients and correlated them with clinicopathological features, such as smoking status and survival outcomes.
Methods
Surgically resected formalin-fixed, paraffin-embedded tissue was collected from 135 consecutive patients with esophageal cancer who underwent esophagectomy. Based on the assessment of DNA quality with a quantitative PCR-based assay, uracil DNA glycosylase pretreatment was performed to ensure quality and accuracy of amplicon-based massively parallel sequencing. Amplicon-based massively parallel sequencing was performed using the Illumina TruSeq® Amplicon Cancer Panel. Gene amplification was detected by quantitative PCR-based assay. Protein expression was determined by automated quantitative fluorescent immunohistochemistry.
Results
Data on genetic alterations were available for 126 patients. The median follow-up time was 1570 days. Amplicon-based massively parallel sequencing identified frequent gene alterations in TP53 (66.7%), PIK3CA (13.5%), APC (10.3%), ERBB4 (7.9%), and FBXW7 (7.9%). There was no association between clinicopathological features or prognosis with smoking status. Multivariate analyses revealed that the PIK3CA mutation and clinical T stage were independent favorable prognostic factors (hazard ratio 0.34, 95% confidence interval: 0.12–0.96, p = 0.042). PIK3CA mutations were significantly associated with APC alterations (p = 0.0007) and BRAF mutations (p = 0.0090).
Conclusions
Our study provided profiles of cancer-related genes in Japanese patients with esophageal cancer by next-generation sequencing using surgically resected formalin-fixed, paraffin-embedded tissue, and identified the PIK3CA mutation as a favorable prognosis biomarker.
https://ift.tt/2OG4WHZ
Simultaneous detection of lung fusions using a multiplex RT-PCR next generation sequencing-based approach: a multi-institutional research study
Abstract
Background
Gene fusion events resulting from chromosomal rearrangements play an important role in initiation of lung adenocarcinoma. The recent association of four oncogenic driver genes, ALK, ROS1, RET, and NTRK1, as lung tumor predictive biomarkers has increased the need for development of up-to-date technologies for detection of these biomarkers in limited amounts of material.
Methods
We describe here a multi-institutional study using the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel to interrogate previously characterized lung tumor samples.
Results
Reproducibility between laboratories using diluted fusion-positive cell lines was 100%. A cohort of lung clinical research samples from different origins (tissue biopsies, tissue resections, lymph nodes and pleural fluid samples) were used to evaluate the panel. We observed 97% concordance for ALK (28/30 positive; 71/70 negative samples), 95% for ROS1 (3/4 positive; 19/18 negative samples), and 93% for RET (2/1 positive; 13/14 negative samples) between the AmpliSeq assay and other methodologies.
Conclusion
This methodology enables simultaneous detection of multiple ALK, ROS1, RET, and NTRK1 gene fusion transcripts in a single panel, enhanced by an integrated analysis solution. The assay performs well on limited amounts of input RNA (10 ng) and offers an integrated single assay solution for detection of actionable fusions in lung adenocarcinoma, with potential savings in both cost and turn-around-time compared to the combination of all four assays by other methods.
https://ift.tt/2vQ68S5
Differential expression of Cosmc, T-synthase and mucins in Tn-positive colorectal cancers
Abstract
Background
The Tn neoantigen (GalNAcα1-O-Ser/Thr) is an O-glycan expressed in various types of human cancers. Studies in several Tn-expressing cancer cell lines and pancreatic tumors have identified loss of Cosmc expression caused by either mutations or promoter hypermethylation. In this study, we explored the mechanism(s) for Tn expression in human colorectal cancers (CRC).
Methods
Tn-expressing cell populations were isolated from CRC cell lines by Fluorescence-associated cell sorting (FACS). The expression of the Tn and sialylated Tn (STn) antigens, Cosmc, T-synthase, and mucins was characterized in paired specimens with CRC and in CRC cell lines by immunostaining, western blot, and qPCR.
Results
Using well-defined monoclonal antibodies, we confirmed prevalent Tn/STn expression in CRC samples. However, a majority of these tumors had elevated T-synthase activity and expression of both Cosmc and T-synthase proteins. Meanwhile, Tn antigen expression was not caused by mucin overproduction. In addition, we found that Tn-expressing CRC cell lines had either loss-of-function mutations in Cosmc or reversible Tn antigen expression, which was not caused by the deficiency of T-synthase activity.
Conclusions
Our results demonstrate multiple mechanisms for Tn expression in CRCs.
https://ift.tt/2OG4U2P
Galectin 3 expression in regional lymph nodes and lymph node metastases of oral squamous cell carcinomas
Abstract
Background
Neck dissection is standard in surgical management of oral squamous cell carcinomas (oscc). However, the immunologic link between primary tumor and lymph nodes is insufficiently understood. Galectin 3 (Gal3) promotes M2 polarization of macrophages and contributes to immunosuppression. The current study analyzes the association between Gal3 expression in regional lymph nodes of oscc with histomorphologic parameters (T-, N-, L- Pn-stage, grading) of the primary tumor. Additionally, Gal3 expression is correlated with markers of macrophage polarization (M1 vs. M2).
Methods
Preoperative diagnostic biopsies (n = 26), tumor resection specimens (n = 34), tumor-free lymph nodes (n = 28) and lymph node metastases (n = 10) of T1/T2 oscc patients were immunohistochemically analyzed for Gal3 and macrophage marker (CD68, CD11c, CD163 and MRC1) expression. The number of positive cells and the expression ratios were quantitatively assessed.
Results
High Gal3 expression in tumor-free regional lymph nodes was significantly (p < 0.05) associated with increased tumor size. The epithelial compartment of lymph node metastases showed a significantly (p < 0.05) increased Gal3 expression compared to biopsies and tumor resection specimens. Cell density of M2 macrophages was significantly (p < 0.05) and positively correlated with the number of Gal3 expressing cells in lymph nodes and tumor specimens.
Conclusion
Gal3 expression in regional lymph nodes might be associated with oscc progression. The increased Gal3 expression in regional lymph nodes of larger tumors underlines the need of immunomodulatory treatment concepts in early-stage oscc. Blocking of Gal3 might be a therapeutic option in oral cancer.
https://ift.tt/2vMG5LK
Wandering spleen caused by subcapsular haemorrhage
Description
A 51-year-old woman 8 years post- human leukocyte antigen (HLA)-matched allogeneic haematopoietic cell transplant presented to her gynaecologist with abdominal pain and a new, large abdominopelvic mass that had gradually grown over a few weeks. She reported severe vomiting followed by days of debilitating abdominal pain during a self-limited gastroenteritis 4 weeks earlier. Her medical history was notable for follicular lymphoma with associated splenomegaly. While she achieved complete remission after haematopoietic cell transplant, she continued to have thrombocytopaenia. She had no history of abdominal surgery and had one vaginal birth. At presentation, she complained of mild abdominal pain and fullness in her lower abdomen and denied other systemic or gastrointestinal symptoms. Her physical examination was notable only for a firm, non-tender abdominopelvic mass spanning most of her lower abdomen. Her labs were significant for thrombocytopaenia (132 k/uL) and mildly low white blood cell count (WBC 2.79 K/uL) and a normal...
https://ift.tt/2OJ9KN1
What are the odds? Prostate metastases to ureter and peritoneum
In patients with prostate cancer, metastases mostly develop in bone, lung, liver, pleura and adrenal glands. Prostate carcinoma metastases to the ureter are very rare, and the peritoneum is an even rarer site of prostate metastases. We present two cases of ureteral metastases of prostate cancer, of which one patient also developed malignant ascites and peritoneal metastases. An overview of the literature on these metastatic sites is also provided. Both patients presented with hydronephrosis and a ureteral mass. Biopsies of the masses were taken, which showed the presence of prostate carcinoma metastases. The first patient was treated with chemotherapy but was diagnosed with progressive disease and died 3 years later. The second patient was diagnosed with pathology-confirmed peritoneal metastases 8 months later. He died 2 years after presentation with hydronephrosis.
https://ift.tt/2Pe3FZS
Acute biliary pancreatitis masking haemobilia due to a false aneurysm of the right hepatic artery after laparoscopic cholecystectomy
Laparoscopic cholecystectomy is a commonly performed surgical procedure. The postoperative course is often uncomplicated; however, complications like infection, biliary leakage, and bleeding and bile duct injury can occur. Here we report on a patient with common bile duct obstruction and haemobilia due to a false aneurysm of the right hepatic artery after laparoscopic cholecystectomy, masked by biliary pancreatitis, complicated by an infarction of the liver after embolisation. The aetiology of upper gastrointestinal bleeding greatly varies. This case is an uncommon case of gastrointestinal bleeding due to a false aneurysm of the right hepatic artery, which was successfully treated.
https://ift.tt/2OFtpgu
Rapid and life-threatening heart failure induced by pazopanib
A 70-year-old man with history of stage IV renal cell carcinoma, chronic atrial fibrillation on warfarin, coronary artery disease status post-percutaneous coronary intervention resulting in an ischaemic cardiomyopathy with left ventricular ejection fraction of 40%–45%, presented with shortness of breath 10 days after starting pazopanib. Within the first week of starting pazopanib, the patient developed fatigue and progressive dyspnoea on exertion. His symptoms quickly worsened and he had compromised mental status. He was transferred to the intensive care unit (ICU) and intubated due to continued respiratory distress. He was found to be in cardiogenic shock and was started on inotropic support with dobutamine and norepinephrine. With maximum support, the patient was slowly weaned off vasopressors and was successfully extubated on ICU day 9. His hospital stay lasted 29 days with management of multiple medical complications, and he was eventually discharged to a rehabilitation facility.
https://ift.tt/2vNp6Zy
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
