Emergency department revisits for nontraumatic dental conditions in Massachusetts

BackgroundInadequate access to oral health care and palliative care provided in the emergency department (ED) creates a pattern of repeat nontraumatic dental condition (NTDC) ED visits. The authors examined NTDC ED revisits and assessed the determinants associated with these visits in Massachusetts.MethodsThe authors examined NTDC ED revisits in Massachusetts during 2013 using the Massachusetts All-Payer Claims Database. The authors report patient characteristics of those who made a single NTDC ED visit and of those who made NTDC ED revisits within 30 days of the index NTDC ED visit. The authors used a multilevel logistic regression model to examine the determinants associated with NTDC ED repeat visits.ResultsIn 2013, 21.5% of NTDC ED visits were revisits. Men from 26 through 35 years of age who were enrolled in Medicaid and who did not make an outpatient dental office visit within 30 days of the index NTDC ED visit had increased odds of repeat visits.ConclusionsThe sizable proportion of NTDC ED repeat visits indicates that certain patients in Massachusetts experience consistent and systematic barriers in accessing appropriate and timely oral health care.Practical ImplicationsPrioritizing young adults and Medicaid enrollees for ED diversion programs and setting up a formal referral process via connecting patients to dental offices and community health centers after an NTDC ED visit may reduce NTDC ED revisits and provide appropriate oral health care to these patients.     

2-Phenylindole and Arylsulphonamide: Novel Scaffolds Bactericidal against Mycobacterium tuberculosis

相似文献   

In vivo hepatocyte MR imaging using lactose functionalized magnetoliposomes

The aim of this study was to assess a novel lactose functionalized magnetoliposomes (MLs) as an MR contrast agent to target hepatocytes as well as to evaluate the targeting ability of MLs for in vivo applications. In the present work, 17 nm sized iron oxide cores functionalized with anionic MLs bearing lactose moieties were used for targeting the asialoglycoprotein receptor (ASGP-r), which is highly expressed in hepatocytes. Non-functionalized anionic MLs were tested as negative controls. The size distribution of lactose and anionic MLs was determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). After intravenous administration of both MLs, contrast enhancement in the liver was observed by magnetic resonance imaging (MRI). Label retention was monitored non-invasively by MRI and validated with Prussian blue staining and TEM for up to eight days post MLs administration. Although the MRI signal intensity did not show significant differences between functionalized and non-functionalized particles, iron-specific Prussian blue staining and TEM analysis confirmed the uptake of lactose MLs mainly in hepatocytes. In contrast, non-functionalized anionic MLs were mainly taken up by Kupffer and sinusoidal cells. Target specificity was further confirmed by high-resolution MR imaging of phantoms containing isolated hepatocytes, Kupffer cell (KCs) and hepatic stellate cells (HSCs) fractions. Hypointense signal was observed for hepatocytes isolated from animals which received lactose MLs but not from animals which received anionic MLs. These data demonstrate that galactose-functionalized MLs can be used as a hepatocyte targeting MR contrast agent to potentially aid in the diagnosis of hepatic diseases if the non-specific uptake by KCs is taken into account.     

Transdermal vitamin D supplementation—A potential vitamin D deficiency treatment

Vitamin D deficiency has high prevalence worldwide. Vitamin D3, the active form of vitamin D, exhibits array of roles in body, from calcium homeostasis and bone mineralization to cancer, neurological disorders, immunomodulatory action, and cardiac health. Current approaches for supplementing vitamin D3 are restricted to oral and parenteral routes. This review highlights recent research in the field of transdermal delivery of vitamin D, its active form and analogues with the aid of penetration enhancers and novel carrier system as nutritional supplement in case of vitamin D deficiency. The penetration of vitamin D3 is challenging; however, by means of reducing hydrophobicity of the active and encapsulating vitamin D3 in a suitable carrier system, penetration is achieved. The results show that penetration of vitamin D3 through skin is feasible. Further clinical trials could strengthen these results. However, the present research till date shows transdermal vitamin D3 a promising way of supplementation.     

Therapeutic cooperation between auranofin,a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer

Triple-negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25–30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non-TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA-approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA-MB-231 xenograft and patient-derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8^+Ve T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner. Moreover, combination of AF with anti-PD-L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti-PD-L1 antibody that warrants further clinical investigation for TNBC patients.     

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras‐driven lung tumours

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision‐cut slices from Kras‐driven non‐small‐cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen‐activated protein kinase (MAPK) activity in adenocarcinoma. In addition, high intertumour and intratumour variability was detected, particularly of MAPK and mammalian target of rapamycin (mTOR) complex 1 activity. Using short‐term treatment of slice explants, we showed that cytotoxic responses to combination MAPK and phosphoinositide 3‐kinase–mTOR inhibition correlate with the spatially defined activities of both pathways. Thus, whereas genetic drivers determine histopathology spectra, histopathology‐associated and spatially variable signalling activities determine drug sensitivity. Our study is in support of spatial aspects of signalling heterogeneity being considered in clinical diagnostic settings, particularly to guide the selection of drug combinations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Impact of the age of transfused red blood cells in the trauma population: A feasibility study

Following injury, transfusion of red blood cells (RBCs) of increased storage duration has been associated with an increased morbidity and mortality. Prospective trials focusing on the impact of the storage age of RBCs in severely bleeding trauma patients have failed to accrue patients. This has been attributed to an inability to maintain a large inventory of fresh RBCs, and the difficulties in obtaining consent in severely bleeding trauma patients. To address these issues, we performed a prospective, observational pilot study to evaluate the feasibility of conducting a trial focusing on RBC age in patients following injury.     

Apoptogenic activity of ethyl acetate extract of leaves of Memecylon edule on human gastric carcinoma cells via mitochondrial dependent pathway

ObjectiveTo evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule (EtAc-LME) in MKN-74, NUGC gastric cancer cells and non cancerous gastric mucous cells (GES-1), and to explore the mechanism of EtAc-LME induced apoptosis.MethodsThe mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases, PARP cleavage, expression of cytochrome-c (Cyt-c) was determined by western blotting, mRNA expression of Bcl-2, Bax by RT-PCR, loss of mitochondrial potential using DiOC6 dye, annexin binding assay and its influence on cell cycle arrest by flow cytometry.ResultsThe results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells (NUGC and MKN-74) compared to normal gastric cells (GES-1), suggesting more specific cytotoxicity to the malignant cells. Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway.ConclusionsThe present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.     

Coordination of fingertip forces during precision grip in premanifest Huntington's disease

Precision grip control is important for accurate object manipulation and requires coordination between horizontal (grip) and vertical (load) fingertip forces. Manifest Huntington's disease (HD) subjects demonstrate excessive and highly variable grip force and delayed coordination between grip and load forces. Because the onset of these impairments is unknown, we examined precision grip control in premanifest HD (pre‐HD) subjects. Fifteen pre‐HD and 15 age‐ and sex‐matched controls performed the precision grip task in a seated position. Subjects grasped and lifted an object instrumented with a force transducer that measured horizontal grip and vertical load forces. Outcomes were preload time, loading time, maximum grip force, mean static grip force, and variability for all measures. We compared outcomes across groups and correlated grip measures with the Unified Huntington's Disease Rating Scale and predicted age of onset. Variability of maximum grip force (P < .0001) and variability of static grip force (P < .00001) were higher for pre‐HD subjects. Preload time (P < .007) and variability of preload time (P < .006) were higher in pre‐HD subjects. No differences were seen in loading time across groups. Variability of static grip force (r² = 0.23) and variability of preload time (r² = 0.59) increased with predicted onset and were correlated with tests of cognitive function. Our results indicate that pre‐HD patients have poor regulation of the transition between reach and grasp and higher variability in force application and temporal coordination during the precision grip task. Force and temporal variability may be good markers of disease severity because they were correlated with predicted onset of disease. © 2011 Movement Disorder Society