This volume explores multiple examples of how to connect classrooms to communities through service learning and participatory research to teach issues of social justice. The various chapters provide ...examples of how collaborations between students, faculty, and community partners are creating models of democratic spaces (on campus and off campus) where the students are teachers and the teachers are students. The purpose of this volume is to provide examples of how service learning can be integrated into courses addressing social justice issues. At the same time, it is about demonstrating the power of service learning in advancing a course content that is community-based and socially engaged. To stimulate the adaptation of the approaches described in these books, each volume includes an Activity / Methodology table that summarizes key elements of each example, such as class size, pedagogy, and other disciplinary applications. Click here for the table to this title.
To address whether preoperative chemotherapy plus surgery or surgery plus adjuvant chemotherapy prolongs disease-free survival compared with surgery alone among patients with resectable ...non-small-cell lung cancer.
In this phase III trial, 624 patients with stage IA (tumor size > 2 cm), IB, II, or T3N1 were randomly assigned to surgery alone (212 patients), three cycles of preoperative paclitaxel-carboplatin followed by surgery (201 patients), or surgery followed by three cycles of adjuvant paclitaxel-carboplatin (211 patients). The primary end point was disease-free survival.
In the preoperative arm, 97% of patients started the planned chemotherapy, and radiologic response rate was 53.3%. In the adjuvant arm, 66.2% started the planned chemotherapy. Ninety-four percent of patients underwent surgery; surgical procedures and postoperative mortality were similar across the three arms. Patients in the preoperative arm had a nonsignificant trend toward longer disease-free survival than those assigned to surgery alone (5-year disease-free survival 38.3% v 34.1%; hazard ratio HR for progression or death, 0.92; P = .176). Five-year disease-free survival rates were 36.6% in the adjuvant arm versus 34.1% in the surgery arm (HR 0.96; P = .74).
In early-stage patients, no statistically significant differences in disease-free survival were found with the addition of preoperative or adjuvant chemotherapy to surgery. In this trial, in which the treatment decision was made before surgery, more patients were able to receive preoperative than adjuvant treatment.
Primary amines are one of the most predominant functional groups found in organic molecules. These entities help form the chemical architecture of natural products, bioactive molecules, synthetic ...building blocks and catalysts. Due to their ubiquitous presence, the development of strategies for the construction of C-C or C-X bonds through deaminative processes is of high importance. Deaminative methods offer new possibilities on the retrosynthetic rationale, and enable late-stage-functionalization of complex structures. As a result of the recent development of photoinduced processes, a variety of photo-mediated deaminative protocols employing 2,4,6-triphenyl-pyridinium salts - Katritzky Salts - as activating agents have been recently realized. This review covers the most recent developments of deaminative strategies by using Katritzky Salts as alkyl radical reservoirs, with particular concern on photoinduced processes applied to organic synthesis.
Primary amines are one of the most predominant functional groups found in organic molecules. This review covers the most recent developments on photocatalytic deaminative strategies by using Katritzky Salts as alkyl radical reservoirs.
Enzymatic biocatalysis is a sustainable technology. Enzymes are versatile and highly efficient biocatalysts, and have been widely employed due to their biodegradable nature. However, because the ...three-dimensional structure of these enzymes is predominantly maintained by weaker non-covalent interactions, external conditions, such as temperature and pH variations, as well as the presence of chemical compounds, can modify or even neutralize their biological activity. The enablement of this category of processes is the result of the several advances in the areas of molecular biology and biotechnology achieved over the past two decades. In this scenario, metal–organic frameworks (MOFs) are highlighted as efficient supports for enzyme immobilization. They can be used to ‘house’ a specific enzyme, providing it with protection from environmental influences. This review discusses MOFs as structures; emphasizes their synthesis strategies, properties, and applications; explores the existing methods of using immobilization processes of various enzymes; and lists their possible chemical modifications and combinations with other compounds to formulate the ideal supports for a given application.
Whereas transcriptional silencing of genes due to epigenetic mechanisms is one of the most important alterations in acute lymphoblastic leukemia (ALL), some recent studies indicate that DNA ...methylation contributes to down-regulation of miRNAs during tumorigenesis. To explore the epigenetic alterations of miRNAs in ALL, we analyzed the methylation and chromatin status of the miR-124a loci in ALL. Expression of miR-124a was down-regulated in ALL by hypermethylation of the promoter and histone modifications including decreased levels of 3mk4H3 and AcH3 and increased levels of 2mK9H3, 3mK9H3, and 3mK27H3. Epigenetic down-regulation of miR-124a induced an up-regulation of its target, CDK6, and phosphorylation of retinoblastoma (Rb) and contributed to the abnormal proliferation of ALL cells both in vitro and in vivo. Cyclin-dependent kinase 6 (CDK6) inhibition by sodium butyrate or PD-0332991 decreased ALL cell growth in vitro, whereas overexpression of pre-miR124a led to decreased tumorigenicity in a xenogeneic in vivo Rag2(-/-)gammac(-/-) mouse model. The clinical implications of these findings were analyzed in a group of 353 patients diagnosed with ALL. Methylation of hsa-miR-124a was observed in 59% of the patients, which correlated with down-regulation of miR-124a (P < 0.001). Furthermore, hypermethylation of hsa-miR-124a was associated with higher relapse rate (P = 0.001) and mortality rate (P < 0.001), being an independent prognostic factor for disease-free survival (P < 0.001) and overall survival (P = 0.005) in the multivariate analysis. These results provide the grounds for new therapeutic strategies in ALL either targeting the epigenetic regulation of microRNAs and/or directly targeting the CDK6-Rb pathway.
Background
During COVID‐19 pandemic in Spain, elective procedures were canceled or postponed, mainly due to health care systems overwhelming.
Objective
The objective of this study was to evaluate the ...consequences of interrupting invasive procedures in patients with chronic cardiac diseases due to the COVID‐19 outbreak in Spain.
Methods
The study population is comprised of 2,158 patients that were pending on elective cardiac invasive procedures in 37 hospitals in Spain on the 14th of March 2020, when a state of alarm and subsequent lockdown was declared in Spain due to the COVID‐19 pandemic. These patients were followed‐up until April 31th.
Results
Out of the 2,158 patients, 36 (1.7%) died. Mortality was significantly higher in patients pending on structural procedures (4.5% vs. 0.8%, respectively; p < .001), in those >80 year‐old (5.1% vs. 0.7%, p < .001), and in presence of diabetes (2.7% vs. 0.9%, p = .001), hypertension (2.0% vs. 0.6%, p = .014), hypercholesterolemia (2.0% vs. 0.9%, p = .026) Correction added on December 23, 2020, after first online publication: as per Dr. Moreno's request changes in p‐values were made after original publication in ., chronic renal failure (6.0% vs. 1.2%, p < .001), NYHA > II (3.8% vs. 1.2%, p = .001), and CCS > II (4.2% vs. 1.4%, p = .013), whereas was it was significantly lower in smokers (0.5% vs. 1.9%, p = .013). Multivariable analysis identified age > 80, diabetes, renal failure and CCS > II as independent predictors for mortality.
Conclusion
Mortality at 45 days during COVID‐19 outbreak in patients with chronic cardiovascular diseases included in a waiting list due to cancellation of invasive elective procedures was 1.7%. Some clinical characteristics may be of help in patient selection for being promptly treated when similar situations happen in the future.
Importance
To provide a normative vessel density (VD) database for the macula through swept‐source optical coherence tomography angiography (OCTA) and to assess the main determinants of this ...measurement.
Background
In contrast with dye angiography, the recently introduced OCTA technique allows for the non‐invasive measurement of retinal and choroidal VD metrics.
Design
Cross‐sectional study.
Participants
The right eyes of 346 healthy subjects were studied. In 105 subjects both eyes were imaged.
Methods
Foveal and parafoveal macular VD measurements were obtained in the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and in the choriocapillaris (CC) layer. Also recorded were age, sex, axial length (AL), foveal and choroidal thickness (CT).
Main Outcome Measures
Normative database and determinants of macular VD measured by OCTA.
Results
Mean participant age was 38.3 ± 20.1 years (mean ± SD) (range 5‐83). Foveal VDs in the different plexuses were: SCP 22.1% ± 5.0% (7.3‐35.1), DCP 19.9% ± 6.3% (6.9‐51.2) and CC: 52.8% ± 4.3% (40.2‐62.1). Parafoveal VDs ranged from 45.4% ± 3.7% to 51.8% ± 4.6%. Positive correlation was observed between foveal VD and foveal thickness (R = .327), as well as between parafoveal DCP VD and CT (R = .250;P ≤ .006), while correlation with age was negative in the SCP and CC (R = −.283;P < .001). No associations were detected between macular VD and sex or AL (P ≥ .05).
Conclusion and Relevance
Macular VD showed wide individual variation, was positively correlated with foveal thickness and with CT, negatively correlated with age, and showed no correlation with AL or sex.
Abstract
Mobile medical imaging devices are invaluable for clinical diagnostic purposes both in and outside healthcare institutions. Among the various imaging modalities, only a few are readily ...portable. Magnetic resonance imaging (MRI), the gold standard for numerous healthcare conditions, does not traditionally belong to this group. Recently, low-field MRI technology companies have demonstrated the first decisive steps towards portability within medical facilities and vehicles. However, these scanners’ weight and dimensions are incompatible with more demanding use cases such as in remote and developing regions, sports facilities and events, medical and military camps, or home healthcare. Here we present in vivo images taken with a light, small footprint, low-field extremity MRI scanner outside the controlled environment provided by medical facilities. To demonstrate the true portability of the system and benchmark its performance in various relevant scenarios, we have acquired images of a volunteer’s knee in: (i) an MRI physics laboratory; (ii) an office room; (iii) outside a campus building, connected to a nearby power outlet; (iv) in open air, powered from a small fuel-based generator; and (v) at the volunteer’s home. All images have been acquired within clinically viable times, and signal-to-noise ratios and tissue contrast suffice for 2D and 3D reconstructions with diagnostic value. Furthermore, the volunteer carries a fixation metallic implant screwed to the femur, which leads to strong artifacts in standard clinical systems but appears sharp in our low-field acquisitions. Altogether, this work opens a path towards highly accessible MRI under circumstances previously unrealistic.
Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of ...endoplasmic reticulum (ER) stress, c‐Jun‐N‐terminal kinase (JNK), Akt, and 5′AMP‐activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3–12 hr) ER stress characterized by an increase of Ser51P‐eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185P‐JNK1/2/JNK1/2, Thr172P‐AMPKα, Ser413P‐Foxo3a, Thr308P‐AKt/AKt and Thr32P‐Foxo3a/Foxo3a ratios, and reduction of Ser2481P‐mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim
EL, Beclin‐1, Bcl‐xL, Bcl‐2, autophagy markers, and reduction of myeloid cell leukemia‐1 (Mcl‐1) expression. The progressive increase of CHOP expression, and reduction of Thr308P‐AKt/AKt and Ser473P‐AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim
EL expression and caspase‐3 activity (24 hr). Small interfering‐RNA (si‐RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase‐3 in sorafenib‐treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor‐derived xenograft model. In conclusion, the early sorafenib‐induced ER stress and regulation of JNK and AMPK‐dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK‐CHOP‐dependent rise of Bim
EL, which was associated with the shift from autophagy to apoptosis. The kinetic of Bim
EL expression profile might also be related to the tight balance between AKt‐ and AMPK‐related signaling leading to Foxo3a‐dependent BIM
EL upregulation.
The early sorafenib‐induced endoplasmic reticulum (ER) stress and regulation of JNK and AMPK‐dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK‐CHOP‐dependent rise of BimEL, which was associated with the shift from autophagy to apoptosis.
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