Miracle-dz/UniFAR-FTUs huggingface dataset:
The integrated curriculum in medical education: AMEE Guide No. 96

Abstract The popularity of the term “integrated curriculum” has grown immensely in medical education over the last two decades, but what does this term mean and how do we go about its design, implementation, and evaluation? Definitions and application of the term vary greatly in the literature, spanning from the integration of content within a single lecture to the integration of a medical school's comprehensive curriculum. Taking into account the integrated curriculum's historic and evolving base of knowledge and theory, its support from many national medical education organizations, and the ever-increasing body of published examples, we deem it necessary to present a guide to review and promote further development of the integrated curriculum movement in medical education with an international perspective. We introduce the history and theory behind integration and provide theoretical models alongside published examples of common variations of an integrated curriculum. In addition, we identify three areas of particular need when developing an ideal integrated curriculum, leading us to propose the use of a new, clarified definition of “integrated curriculum”, and offer a review of strategies to evaluate the impact of an integrated curriculum on the learner. This Guide is presented to assist educators in the design, implementation, and evaluation of a thoroughly integrated medical school curriculum.
Phase II trial of ixabepilone, an epothilone B analog, in patients with metastatic breast cancer previously untreated with taxanes.

PURPOSE Ixabepilone is an epothilone B analog that binds to microtubules and results in microtubule stabilization and mitotic arrest. Ixabepilone was evaluated for efficacy and safety in a phase II clinical trial for women with metastatic breast cancer. PATIENTS AND METHODS Patients were eligible if they had not previously received treatment with a taxane and had measurable metastatic breast cancer. Ixabepilone was administered at 6 mg/m(2)/d intravenously days 1 through 5 every 3 weeks until unacceptable toxicity or disease progression. Patients underwent pretreatment and post-treatment tumor biopsies, and tissues were analyzed for acetylated alpha-tubulin, tau-1, and p53 expression when possible. RESULTS Twenty-three patients received 210 cycles with a median of eight cycles (range, two to 22 cycles) per patient. Thirteen patients (57%; exact 95% CI, 34.5% to 76.8%) had partial responses, six patients (26%) had stable disease, and four patients (17%) had progressive disease. Median time to progression and duration of response were 5.5 and 5.6 months, respectively. Four patients required dose reductions for neutropenia, neuropathy, or fatigue. Grade 3 or 4 toxicities included neutropenia (22%), fatigue (13%), anorexia (9%), and motor neuropathy (4%). Thirty-nine percent of patients experienced grade 1, 13% experienced grade 2, and none experienced grade 3/4 sensory neuropathy. The six patients with paired biopsies all had increases in tumor alpha-tubulin acetylation after treatment. Baseline or cycle 2 acetylated alpha-tubulin, tau-1, or p53 expression did not correlate with clinical response. CONCLUSION Women with metastatic breast cancer previously untreated with taxanes have a meaningful durable response to single-agent ixabepilone therapy. Minimal hematologic toxicity and no grade 3 sensory neuropathy were noted.
The Development and Maintenance of Paclitaxel-induced Neuropathic Pain Require Activation of the Sphingosine 1-Phosphate Receptor Subtype 1*

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a critical dose-limiting side effect of many chemotherapeutic agents, including paclitaxel. Results: Spinal activation of the S1P-to-S1PR1 axis contributes to the development and maintenance of paclitaxel-induced neuropathic pain through enhanced neuroinflammatory processes. Conclusion: Inhibition of S1PR1 blocks and reverses paclitaxel-induced neuropathic pain without interfering with anticancer effects. Significance: Targeting the S1PR1 signaling pathway could be an effective approach for the treatment of CIPN. The ceramide-sphingosine 1-phosphate (S1P) rheostat is important in regulating cell fate. Several chemotherapeutic agents, including paclitaxel (Taxol), involve pro-apoptotic ceramide in their anticancer effects. The ceramide-to-S1P pathway is also implicated in the development of pain, raising the intriguing possibility that these sphingolipids may contribute to chemotherapy-induced painful peripheral neuropathy, which can be a critical dose-limiting side effect of many widely used chemotherapeutic agents. We demonstrate that the development of paclitaxel-induced neuropathic pain was associated with ceramide and S1P formation in the spinal dorsal horn that corresponded with the engagement of S1P receptor subtype 1 (S1PR1)-dependent neuroinflammatory processes as follows: activation of redox-sensitive transcription factors (NFκB) and MAPKs (ERK and p38) as well as enhanced formation of pro-inflammatory and neuroexcitatory cytokines (TNF-α and IL-1β). Intrathecal delivery of the S1PR1 antagonist W146 reduced these neuroinflammatory processes but increased IL-10 and IL-4, potent anti-inflammatory/neuroprotective cytokines. Additionally, spinal W146 reversed established neuropathic pain. Noteworthy, systemic administration of the S1PR1 modulator FTY720 (Food and Drug Administration-approved for multiple sclerosis) attenuated the activation of these neuroinflammatory processes and abrogated neuropathic pain without altering anticancer properties of paclitaxel and with beneficial effects extended to oxaliplatin. Similar effects were observed with other structurally and chemically unrelated S1PR1 modulators (ponesimod and CYM-5442) and S1PR1 antagonists (NIBR-14/15) but not S1PR1 agonists (SEW2871). Our findings identify for the first time the S1P/S1PR1 axis as a promising molecular and therapeutic target in chemotherapy-induced painful peripheral neuropathy, establish a mechanistic insight into the biomolecular signaling pathways, and provide the rationale for the clinical evaluation of FTY720 in chronic pain patients.
Etiology of childhood pneumonia: serologic results of a prospective, population-based study.

BACKGROUND To investigate the etiology of pediatric community-acquired pneumonia, we conducted a prospective, population-based study covering the total population <15 years of age (n = 8851) in 4 municipalities in eastern Finland. MATERIALS AND METHODS The number of patients was 201; chest radiographs were available for all cases and paired sera for serologic assays were available for >90% of cases. The methods included assays for antibody response to 3 pneumococcal antigens, specific pneumococcal immune complex assays and conventional antibody tests for mycoplasmal, chlamydial and viral infections. RESULTS Serologic evidence of specific microbial etiology was obtained in 133 (66%) of the pneumonia patients. Bacterial infection was diagnosed in 102 cases (51%) and viral infection in 51 cases (25%). Streptococcus pneumoniae was the most common agent (57 cases; 28%), followed by Mycoplasma pneumoniae (44; 22%), respiratory syncytial virus (43; 21%) and Chlamydia spp. (29; 14%). Haemophilus influenzae was identified in only 6% and Moraxella catarrhalis in only 3% of the children. More than one specific infection was found in 51 patients (25%). The proportion of pneumococcal cases varied from 24 to 36% by age. Mycoplasma infections were seen mostly in patients > or =5 years and Chlamydia infections in patients > or =10 years of age. CONCLUSIONS The results of our prospective, strictly population-based study confirm the importance of S. pneumoniae in the etiology of community-acquired pneumonia in children of all ages. M. pneumoniae and Chlamydia pneumoniae are important from the age of 5 years onwards.
Joint orientation and position estimation from differential RSS measurements at on-body nodes

In the specific context of wearable wireless networks, this work aims at improving the accuracy and the robustness of radiolocation solutions based on standard narrow-band radio technologies for user-centric mobile applications. The proposed solution takes benefits from off-body or body-to-body radio links, with respect to fixed elements of infrastructure or to other mobile equipped subjects, respectively. The main idea is to infer relative angular information between the carrying body's heading and the median direction of arrival of received signals. For this sake, we rely on differential received power measurements issued at judiciously placed on-body nodes. Light calibration procedures (e.g., based on the full-scale dynamics of observed measurements) and joint absolute position/orientation estimation algorithms then enable to cover both individual/non-cooperative and collective/cooperative navigation needs. The performance is assessed by means of field experiments with IEEE 802.15. 4-compliant integrated devices operating at 2.4 GHz and an optical motion capture system delivering the ground truth reference. On this occasion, our proposal is shown to be resilient against mobile Non-line of Sight (NLoS) situations (e.g., in crowded environments).
Neuraxial blockade for external cephalic version: Cost analysis

Neuraxial blockade (epidural or spinal anesthesia/analgesia) with external cephalic version increases the external cephalic version success rate. Hospitals and insurers may affect access to neuraxial blockade for external cephalic version, but the costs to these institutions remain largely unstudied. The objective of this study was to perform a cost analysis of neuraxial blockade use during external cephalic version from hospital and insurance payer perspectives. Secondarily, we estimated the effect of neuraxial blockade on cesarean delivery rates.
Efficacy and tolerability of lercanidipine in patients with hypertension: results of a Phase IV study in general practice

Introduction: Calcium antagonists are very effective drugs, recommended as first-line therapy in hypertension. However, their large use in clinical practice is often limited by a high incidence of peripheral oedema. Calcium antagonists of the third generation, such as lercanidipine, have been shown to be as effective as first- and second-generation calcium antagonists, while showing a better side-effect profile. Objective and methods: The purpose of the present Phase IV study was to investigate the efficacy and tolerability of lercanidipine in a large unselected population of hypertensive patients managed in private practice in Switzerland. A total of 504 physicians participated in this survey and 2199 patients were included. Treatment with lercanidipine was introduced at a dose of 10 mg and titration to 20 mg was optional according to the physician's decision. Evaluations of blood pressure control and tolerability were made after 4 and 8 weeks. Results: The results of the present study show that lercanidipine is an effective and well tolerated antihypertensive agent in newly treated hypertensive patients. In this group of patients, 63% reached the target blood pressure (≤ 140/90 mmHg) with lercanidipine alone. Lercanidipine is also an effective alternative in patients who are insufficiently controlled with another therapy, or in patients not tolerating other calcium channel blockers. Finally, lercanidipine is well-tolerated, with a very low rate of drop-out (1 – 2%) because of adverse events, and a low occurrence of peripheral oedema. Conclusion: Lercanidipine is an effective and well tolerated calcium channel blocker of the third generation. This new calcium antagonist represents a very useful tool to improve blood pressure control in the community.
Acute lethal crush-injured rats can be successfully rescued by a single injection of high-dose dexamethasone through a pathway involving PI3K-Akt-eNOS signaling

BACKGROUND Crush syndrome (CS) is characterized by ischemia/reperfusion–induced rhabdomyolysis and the subsequent onset of systemic inflammation. CS is associated with a high mortality, even when patients are treated with conventional therapy. We hypothesized that treatment of lethal CS rat model with dexamethasone (DEX) have therapeutic effects on the laboratory findings and clinical course and outcome. METHODS To create a CS model, anesthetized rats were subjected to bilateral hind limb compression with rubber tourniquets for 5 hours and randomly divided into three groups as follows: saline-treated CS group, CS groups treated with low (0.1 mg/kg) and high doses (5.0 mg/kg) of DEX. Saline for the CS group or DEX for the DEX-treated CS groups was intravenously administered immediately before reperfusion. Under continuous monitoring and recording of arterial blood pressures, blood and tissue samples were collected for histologic and biochemical analysis at designated period before and after reperfusion. RESULTS Ischemic compression of rat hind limbs reduced the nitrite content in the crushed muscle, and the subsequent reperfusion induced reactive oxygen species–mediated circulatory collapse and systemic inflammation, finally resulting in a mortality rate of 76% by 48 hours after reperfusion. A single injection of high-dose DEX immediately before reperfusion activated endothelial nitric oxide synthase (eNOS) by sequential phosphorylation through the nongenomic phosphoinositide 3-kinase (PI3K)–Akt–eNOS signaling pathway. DEX also exhibited anti-inflammatory effects by modulating proinflammatory and anti-inflammatory mediators, consequently suppressing myeloperoxidase activities and subsequent systemic inflammation, showing a complete recovery of the rats from lethal CS. CONCLUSION These results indicate that high-dose DEX reduces systemic inflammation and contributes to the improved survival rate in a rat CS model.
Why Does Interest in Government Careers Decline among Public Affairs Graduate Students?

Abstract This study explores the predictors of government career preferences using a higher education socialization framework. Existing research suggests that students’ interest in government careers declines over the course of training in public administration graduate programs. This study investigates the extent to which characteristics of degree program, individual background, professional community, and personal community could explain this downward trend. One hundred public affairs master’s degree programs were randomly selected for involvement in this study. From the programs invited, 26 programs agreed to participate, and 552 master’s degree– seeking students responded to a survey. While the findings confirmed that career interest in government is related to a number of factors, such as gender, work experience, interaction with professionals, and involvement in a professional association, these findings did not fully explain the declining interest among students in graduate programs in public administration. Implications of the findings are discussed.
Beliefs about willpower determine the impact of glucose on self-control

Significance The present research provides critical new findings about the role of glucose ingestion in self-control and cognitive performance. It argues against the popular view that self-control depends on a limited physiological resource (blood glucose) that is depleted by even brief acts of self-control and is restored by glucose consumption. Instead, the results highlight the critical role of beliefs about willpower in self-control performance. Past research found that the ingestion of glucose can enhance self-control. It has been widely assumed that basic physiological processes underlie this effect. We hypothesized that the effect of glucose also depends on people’s theories about willpower. Three experiments, both measuring (experiment 1) and manipulating (experiments 2 and 3) theories about willpower, showed that, following a demanding task, only people who view willpower as limited and easily depleted (a limited resource theory) exhibited improved self-control after sugar consumption. In contrast, people who view willpower as plentiful (a nonlimited resource theory) showed no benefits from glucose—they exhibited high levels of self-control performance with or without sugar boosts. Additionally, creating beliefs about glucose ingestion (experiment 3) did not have the same effect as ingesting glucose for those with a limited resource theory. We suggest that the belief that willpower is limited sensitizes people to cues about their available resources including physiological cues, making them dependent on glucose boosts for high self-control performance.
Detection of astrovirus in pediatric stool samples by immunoassay and RNA probe

Two new astrovirus assays, a rapid biotin-avidin enzyme immunoassay (EIA) and RNA probe hybridization, were developed and compared with an established astrovirus assay, an indirect EIA, and immune electron microscopy. Sensitivity and specificity were evaluated by using a screening panel of 22 astrovirus-positive and 305 astrovirus-negative fecal specimens. The biotin-avidin assay was equivalent in performance to the reference indirect assay, and both could detect about 10 ng of viral protein. Although the probe was more sensitive than either EIA and could detect higher dilutions of virus in tissue culture and stool specimens, it did not detect more astrovirus-positive fecal specimens. Of the 22 astrovirus-positive specimens detected by the EIAs, 20 were confirmed by immune electron microscopy with hyperimmune rabbit antiserum. To determine the usefulness of EIAs for large epidemiologic studies, EIAs were used to screen 1,289 stool specimens from three studies of children with and without diarrhea. Astrovirus was detected in 3.5% of specimens from children with diarrhea and 1.9% of specimens from those without diarrhea. Our results indicate that the biotin-avidin EIA is an efficient, sensitive, and specific method for routinely screening large numbers of fecal samples and that its application in epidemiologic studies may yield higher rates of astrovirus infection than have been found previously by other methods.
Primary gastric Ki‐1 positive anaplastic large cell lymphoma: A report of two cases

Two cases with primary gastric Ki‐1 positive anaplastic large cell lymphoma are presented. Morphologic features of both cases involved pleomorphism of the neoplastic cells, fibrosis and lymphatic infiltration. The neoplastic cells in both cases were positive for BerH2 (CD30), LCA(CD45), lysozyme and alpha‐1‐antitrypsin (α1‐AT). In additional case, the neoplastic cells were additionally positive for MAC387 and (α1,‐antichymotrypsin (α,‐ACT). The neoplastic cells in these cases were negative for L26(CD20), UCHL‐1 (CD45RO), DAKO CD3 and epithelial membrane antigen (EMA). According to the results of the phenotypic studies, the authors consider that the neoplastic cells have some of the features of histiocytes.
Past Trends and Future Estimation of Annual Breast Cancer Incidence in Osaka, Japan.

BACKGROUND Although the breast cancer incidence rate in Japan is lower than in western countries, the age-specific rates have markedly increased in recent years, along with the problems of declining birth rate and an aging population. MATERIALS AND METHODS We examined past trends of age-specific breast cancer incidence using data from the Osaka Cancer Registry from 1976 to 2010, and estimated future trends until 2025 based on the changes observed and population dynamics using a log linear regression model. RESULTS The age-specific breast cancer incidence rate has increased consistently from the 1970s, and the rates have caught up with those of Japanese-Americans in the US. Assuming the increasing tendency of age-specific breast cancer incidence to be constant, the average annual incidence of breast cancer will increase 1.7-fold from 2006-2010 to 2021-2025. Furthermore, the number of patients aged 80 years should increase 3.4-fold. CONCLUSIONS The medical demand for breast cancer care in Japan may increase explosively in the future, particularly among the elderly. We need to prepare for such a future increase in demand for care, although careful monitoring is needed to confirm these results.
Photodynamic activity of a glucoconjugated silicon(IV) phthalocyanine on human colon adenocarcinoma

Photodynamic therapy (PDT) involves the use of a non-toxic photosensitizer which exhibits killing effect upon activation by light. In the past few years, we have synthesized a number of novel second generation photosensitizers of superior properties, most of them are phthalocyanines. Among them, the glucoconjugated silicon(IV) phthalocyanine, SiPcGlu, shows potent phototoxicity against the human colorectal adenocarcinoma HT29 cells. In the present study, its action mechanism was investigated. The initiation of apoptosis by SiPcGlu-PDT, subsequent to reactive oxygen species production, was shown by the results of TUNEL assay, annexin V & propidium iodide staining and DNA ladder pattern analysis. Confocal microscopy revealed the presence of SiPcGlu in lysosome, mitochondria and endoplasmic reticulum. SiPcGlu-PDT did not cause any damage to the lysosomal membrane; whereas in the mitochondria, it caused membrane depolarization and the release of cytochrome c into the cytosol, which subsequently brought about caspase-3 activation. In the endoplasmic reticulum, the treatment led to Ca2+ release and an increase in the expression level of the chaperone protein GRP78. These observations suggest that SiPcGlu-PDT triggered the apoptotic pathways in both mitochondria and endoplasmic reticulum, but not the lysosome. A preliminary study of the photodynamic activity of SiPcGlu in the in vivo animal model was also carried out. It retarded tumor growth in HT29 tumor-bearing nude mice while causing no apparent toxicity to the animal.
Risk factors for nonelective hospitalization in frail and older adult, inner-city outpatients.

PURPOSE In our study, we sought to improve the accuracy of predicting the risk of hospitalization and to identify older, inner-city patients who could be targeted for preventive interventions. DESIGN AND METHODS Participants (56% were African American) in a randomized trial were from a primary care practice and included 1,041 patients living in the inner city who were either > or = 75 years of age or were > or = 50 years of age with severe disease. As a secondary analysis, we assessed patient characteristics at baseline involving five domains of health, including utilization and satisfaction. We followed participants for 12 months and recorded the occurrence of nonelective hospitalization within the study period. We developed a multivariate model using logistic regression to predict this outcome. RESULTS The following patient characteristics independently predicted an increased risk for nonelective hospitalization: having the diagnosis of congestive heart failure, diabetes mellitus, or anemia; and having more medications prescribed, having a lower body mass index, and having more emergency department visits during the previous year. Better physical functioning reduced the risk of hospitalization. IMPLICATIONS Moderate accuracy of a prediction model (0.73) was observed. In addition to focusing on patients with chronic disease, helping them maintain physical functioning may help reduce nonelective hospitalization.