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Graded transcription factors are pivotal regulators of embryonic patterning, but whether their role changes over time is unclear. A light-regulated protein degradation system was used to assay temporal dependence of the transcription factor Dorsal in dorsal-ventral axis patterning of Drosophila embryos. Surprisingly, the high-threshold target gene snail only requires Dorsal input early but not late when Dorsal levels peak. Instead, late snail expression can be supported by action of the Twist transcription factor, specifically, through one enhancer, sna.distal This study demonstrates that continuous input is not required for some Dorsal targets and downstream responses, such as twist , function as molecular ratchets., (© 2020 Irizarry et al.; Published by Cold Spring Harbor Laboratory Press.)

Objective: To compare aromatase inhibitors (AIs) with progestins as adjuvant hormonal therapy(AHT) for low-grade endometrial stromal sarcomas (LGESSs)., Methods: We reviewed cases with LGESS at our institution from 1984 to 2017. Disease recurrence and recurrence-free survival (RFS) were assessed among patients who received AI, progestins, or no AHT., Results: Among 39 patients with LGESS, 18 received progestins, 13 received AI, and 8 received no AHT. Thirty patients had stage I disease, and 9 had stage II to IV disease. All underwent hysterectomies. Disease recurred in 70% (7/10) of stage I patients who received no AHT, compared to 14.3% (1/7) receiving AI, and 7.7% (1/13) receiving progestins ( P = .003). Among stage I patients taking AI, mean RFS was 153.1 months (95% confidence interval [CI]: 110-195.6) versus 306.2 months (95% CI: 259.7-352.6) for progestin patients and 90.8 months (95% CI: 56.8-124.9) for those who received no AHT. In stage II to IV patients, mean RFS was 148.5 months (95% CI: 148.5-148.5) and 120.8 months (95% CI: 55.8-185.9) for the AI and progestin groups, respectively. All stage II to IV patients received AHT. Among stage I patients, median follow-up time for RFS was 159.1 months for progestin patients, 52.6 months for AI, and 53.1 months for those who received no AHT. Of this, 69% of stage I patients taking progestins reduced/stopped treatment prematurely due to side effects. None of the patients taking AI discontinued treatment early., Conclusion: Aromatase inhibitor is associated with longer RFS in patients with advanced LGESS, is better tolerated than progestins, and can be primary AHT for LGESS.

Rapid mitotic divisions and a fixed transcription rate limit the maximal length of transcripts in early Drosophila embryos. Previous studies suggested that transcription of long genes is initiated but aborted, as early nuclear divisions have short interphases. Here, we identify long genes that are expressed during short nuclear cycles as truncated transcripts. The RNA binding protein Sex-lethal physically associates with transcripts for these genes and is required to support early termination to specify shorter transcript isoforms in early embryos of both sexes. In addition, one truncated transcript for the gene short-gastrulation encodes a product in embryos that functionally relates to a previously characterized dominant-negative form, which maintains TGF-β signaling in the off-state. In summary, our results reveal a developmental program of short transcripts functioning to help temporally regulate Drosophila embryonic development, keeping cell signaling at early stages to a minimum in order to support its proper initiation at cellularization., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although smart infusion pumps are intended to prevent medication errors by alerting users about doses that exceed set thresholds, a large number of clinically insignificant alarms and alerts create the potential for alert and alarm fatigue. We searched the PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for peer-reviewed literature (January 1, 2004-August 31, 2017) on managing smart pump alerts, alarms, and related fatigue. Twenty-nine articles that met the inclusion criteria were reviewed and organized into themes. Smart pumps give users two types of signals: alarms that indicate mechanical issues such as occlusion, air in the line, or low battery; and clinical alerts that indicate that a programmed dose exceeds a predefined safety limit. Mechanical alarms occur with greater frequency than clinical alerts, but alarms and alerts vary widely by pump model, patient population, time of day, month, and type of drug. Several causes of clinically insignificant alerts and alarms may be actionable, and strategies proposed in the literature include development of a multidisciplinary team to oversee the quality improvement effort with involvement of end users, standardization of medication administration practices, widening of drug limit library thresholds when clinically appropriate, maintaining up-to-date drug limit libraries, and interoperability. Whereas many strategies have been proposed, and case studies have been reported, none have been rigorously evaluated. In addition, more research is needed related to managing occlusion and air-in-line alarms, especially for complicated infusions. Future work should focus on the evaluation of specific and replicable alert and alarm reduction strategies with a greater emphasis on quantitative metrics., (© 2018 Pharmacotherapy Publications, Inc.)

Background: Adjuvant therapy for gastric adenocarcinoma has shown a survival advantage, though it may be underutilized. The purpose of this study is to examine how infrequently adjuvant therapy is administered with curative intent gastrectomy for node positive gastric cancer and the long-term effects to patients., Methods: The National Cancer Database was queried from 2006-2013 for patients with node positive gastric adenocarcinoma undergoing a potentially curative gastrectomy. Overall survival was compared between patients who received adjuvant chemotherapy or chemoradiation and those who did not., Results: Of 2,565 patients, 793 (30.9%) patients did not receive any adjuvant chemotherapy or radiation therapy, while 147 (5.7%) received peri-operative chemotherapy and 723 (28.2%) received post-operative chemoradiation. From 2006-2013, the percentage of patients receiving peri-operative chemotherapy rose from 1.1% to 9.9%, while those receiving post-operative chemoradiation decreased from 39.7% to 21.6%. The adjusted restricted mean survival time over 5 years for no adjuvant therapy was 27.7 months, peri-operative chemotherapy was 39.6 months, and post-operative chemoradiation was 37.7 months (P<0.0001)., Conclusions: Approximately one third of patients treated for node positive gastric cancer undergo surgical resection without adjuvant therapy. This is associated with poorer survival, highlighting the need for improvement in multimodality care and cancer outcomes., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

Background: Colon and rectal gastrointestinal stromal tumors (GISTs) are rare and poorly characterized. Because the majority of treatment guidelines for GISTs are extrapolated from tumors of gastric and small bowel origin, our aim was to better characterize the unique clinicopathologic features and prognostic factors of colon and rectal GISTs to guide clinical care., Methods: The National Cancer Data Base (NCDB) was queried from 2006 to 2013 for cases of GISTs in the stomach, colon, and rectum. Patient demographics, clinical characteristics, and survival were compared., Results: A total of 11,302 gastric GISTs were compared to 398 colon and 393 rectal GISTs. After propensity matching, compared to gastric GISTs, rectal GISTs had improved overall survival (HR =0.695, P=0.0264), while colon GISTs had worse overall survival (HR =1.6, P=0.0005). Surgical treatment for rectal GISTs was more likely to be local excision compared to colonic GISTs (51.1% vs. 8.4%, P<0.0001). Colon and gastric GISTs were less likely to receive systemic therapy compared to rectal GISTs (34.2% vs. 34.0% vs. 55.2%, P<0.0001). Adjuvant systemic therapy conveyed a survival advantage to rectal GISTs (HR =0.47, P=0.042) but not colon GISTs. There was a negative impact of adjuvant therapy on survival for colon GISTs <5 cm (HR =3.41, P=0.032)., Conclusions: Patients with rectal GISTs live longer than those with colon and gastric GISTs, and adjuvant therapy prolongs their survival. Many patients with colon GISTs are treated with adjuvant therapy despite a detrimental effect on survival. Tumor biology of colon and rectal GISTs needs to be better studied to tailor treatment., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: End-of-life care for patients with advanced cancer is aggressive and costly. Oncologists inconsistently estimate life expectancy and address goals of care. Currently available prognostication tools are based on subjective clinical assessment. An objective prognostic tool could help oncologists and patients decide on a realistic plan for end-of-life care. We developed a predictive model (Imminent Mortality Predictor in Advanced Cancer [IMPAC]) for short-term mortality in hospitalized patients with advanced cancer., Methods: Electronic health record data from 669 patients with advanced cancer who were discharged from Yale Cancer Center/Smilow Cancer Hospital were extracted. Statistical learning techniques were used to develop a tool to estimate survival probabilities. Patients were randomly split into training (70%) and validation (30%) sets 20 times. We tested the predictive properties of IMPAC for mortality at 30, 60, 90, and 180 days past the day of admission., Results: For mortality within 90 days at a 40% sensitivity level, IMPAC has close to 60% positive predictive value. Patients estimated to have a greater than 50% chance of death within 90 days had a median survival time of 47 days. Patients estimated to have a less than 50% chance of death had a median survival of 290 days. Area under the receiver operating characteristic curve for IMPAC averaged greater than .70 for all time horizons tested. Estimated potential cost savings per patient was $15,413 (95% CI, $9,162 to $21,665) in 2014 constant dollars., Conclusion: IMPAC, a novel prognostic tool, can generate life expectancy probabilities in real time and support oncologists in counseling patients about end-of-life care. Potentially avoidable costs are significant.

Antibodies are the most widely used reagent for isolation and detection of specific proteins. However, using antibodies that are not highly specific in these studies can generate inaccurate and misleading data. Protein microarrays offer a platform by which antibody cross-reactivity against a broad range of cellular antigens can be simultaneously and quantitatively profiled. This protocol describes in detail the process of array pretreatment, antibody binding, washing, scanning and quantitative analysis of antibody specificity.

Background: The transition to practice for new graduate nurses poses distinct challenges at the point of care. The complicated work environment necessitates a preceptorship model that maintains safety at all times., Method: This study used survey, focus groups, and interviews to assess the effects of the married state preceptorship model (MSPM) on the experiences and perceptions of the new nurses and preceptors in a hospital setting., Results: The result validated the original findings from the new nurses' survey, indicating all (N = 28, 100%) of the new nurses found the MSPM to be beneficial, promote safety, and lessen anxiety, and 27 (96%) thought it helped them to assume a full patient load. The preceptors' survey revealed that 29 (97%) of the preceptors thought the MSPM promoted safety, 30 (100%) thought it boosted confidence, and 30 (100%) believed it meet the needs of the new nurses., Conclusion: The study showed same thematic saturation on partnership, critical thinking, learning, and transition. The change in culture has been strengthened in the replicate study referring to their acclimatization in the unit through the MSPM. J Contin Educ Nurs. 2016;47(11):511-517., (Copyright 2016, SLACK Incorporated.)

Alzheimer's disease (AD) is the fourth leading cause of death in Puerto Rico. Using multi-media resources and in-person education may be an effective approach to improve knowledge and awareness of AD. The Un Café por el Alzheimer program in Puerto Rico incorporates an education component at coffee shops and a social media campaign using Facebook. The current study evaluates this initiative through an analysis of pre/post education survey results and social media content and use. Surveys contained close-ended and open-ended questions to understand participants' perceptions and knowledge about AD. Post-education surveys also included questions related to program satisfaction. Social media analysis of the Facebook community page examined posts from March 1 to September 30, 2015. Descriptive statistics were used to analyze survey and Facebook data. Four education sessions were conducted with a total of 212 participants. Fifty-one of the participants completed both pre- and post-surveys. Following the education program participants reported improved knowledge of risk and protective factors. All participants reported learning new information from the program. There were a total of 250 posts on the Un Café por el Alzheimer community Facebook page; 168 posts related to AD. The Facebook page reached 294,109 people, with 9963 page likes, 610 comments, 17,780 post clicks, and 3632 shares. There was an average increase of 64.8 % in number of people reached by the Facebook page following the education sessions. The approach of combining social media resources and in-person education is beneficial to increase public awareness of AD and disseminate health information.

Microarrays can provide large amounts of data for genetic relative expression in illnesses of interest such as cancer in short time. These data, however, are stored and often times abandoned when new experimental technologies arrive. This work reexamines lung cancer microarray data with a novel multiple criteria optimization-based strategy aiming to detect highly differentially expressed genes. This strategy does not require any adjustment of parameters by the user and is capable to handle multiple and incommensurate units across microarrays. In the analysis, groups of samples from patients with distinct smoking habits (never smoker, current smoker) and different gender are contrasted to elicit sets of highly differentially expressed genes, several of which are already associated to lung cancer and other types of cancer. The list of genes is provided with a discussion of their role in cancer, as well as the possible research directions for each of them., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The thisbe (ths) gene encodes a Drosophila fibroblast growth factor (FGF), and mutant females are viable but sterile suggesting a link between FGF signaling and fertility. Ovaries exhibit abnormal morphology including lack of epithelial sheaths and muscle tissues that surround ovarioles. Here we investigated how FGF influences Drosophila ovary morphogenesis and identified several roles. Heartless (Htl) FGF receptor was found to be expressed within somatic cells at the larval and pupal stages, and phenotypes were uncovered using RNAi. Differentiation of terminal filament cells was affected, but this effect did not alter the ovariole number. In addition, proliferation of epithelial sheath progenitors, the apical cells, was decreased in both htl and ths mutants, while ectopic expression of the Ths ligand led to these cells' over-proliferation suggesting that FGF signaling supports ovarian muscle sheath formation by controlling apical cell number in the developing gonad. Additionally, live imaging of adult ovaries was used to show that htl RNAi mutants, hypomorphic mutants in which epithelial sheaths are present, exhibit abnormal muscle contractions. Collectively, our results demonstrate that proper formation of ovarian muscle tissues is regulated by FGF signaling in the larval and pupal stages through control of apical cell proliferation and is required to support fertility., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Establishing how a series of potentially important genes might relate to each other is relevant to understand the origin and evolution of illnesses, such as cancer. High-throughput biological experiments have played a critical role in providing information in this regard. A special challenge, however, is that of trying to conciliate information from separate microarray experiments to build a potential genetic signaling path. This work proposes a two-step analysis pipeline, based on optimization, to approach meta-analysis aiming to build a proxy for a genetic signaling path.

The objective of this study was to estimate the incidence of cancer and human papillomavirus (HPV)-related cancers and the risk of death (by cancer status) among people living with AIDS (PLWA) in Puerto Rico. We used data from the Puerto Rico AIDS Surveillance Program and Central Cancer Registry (1985-2005). Cancers with highest incidence were cervix (299.6/100,000) for women and oral cavity/oropharynx for men (150.0/100,000); the greatest excess of cancer incidence for men (standardized incidence ratio, 86.8) and women (standardized incidence ratio, 52.8) was for anal cancer. PLWA who developed a cancer had decreased survival and increased risk of death compared with those who did not have cancer. Cancer control strategies for PLWA will be essential for improving their disease survival.

Introduction: Evaluation of the extent of socioeconomic inequalities in cancer incidence and mortality is essential to generate hypotheses in population health research and provides evidence for population-based strategies for comprehensive cancer control. The objective of this study was to create an area-based socioeconomic position (SEP) index to assess possible socioeconomic disparities in incidence and mortality of selected cancers in Puerto Rico., Methods: Data for cancer incidence and mortality from 1995 to 2004 were obtained from the Puerto Rico Central Cancer Registry and the Puerto Rico Department of Health, and Puerto Rico socioeconomic data were obtained from the US Census 2000. We used principal component and factor analysis methods to construct the SEP index at the municipality level. We calculated age-adjusted incidence and mortality for each SEP area and used rate ratios to evaluate the differences by SEP., Results: Incidence and mortality of cancer in Puerto Rico varied by SEP area. In general, the incidence and mortality for cancers of the esophagus and stomach were higher for municipalities with the lowest SEP; in contrast, rates for breast, colorectal, kidney, pancreas, prostate, and thyroid were higher for areas with the highest SEP., Conclusion: These results highlight cancer disparities in Puerto Rico by SEP level that warrant further research.

Background: Cancer remains one of the leading causes of morbidity and mortality worldwide and is the second cause of death in Puerto Rico (PR). This article describes the incidence and the mortality from cancer in PR for the period of 1987 to 2004., Methods: We analyzed data from the PR Central Cancer Registry and the PR Demographic Registry from 1987-2004, for the leading cancer types in men and women in PR. Age-adjusted incidence and mortality rates were estimated by sex, municipality, health region and primary site and were age-standardized to the 2000 PR population., Results: Incidence rates for overall cancer remained constant in men and increased in women (APC = 0.6%, p < 0.05), while mortality rates decreased (APC = -1.0%) for both sexes. A significant increase was observed in the cancer incidence rates for colorectal cancer in men, while in women, an increase in breast, colorectal, and corpus and uterus cancer was observed. Mortality rates decreased for most of the major cancers types in both sexes, except for colorectal cancer in men which showed a significant increase (p < 0.05)., Conclusion: The most important cancer types in PR (prostate, breast, colorectal, and lung) for both incidence and mortality are susceptible to primary prevention (eliminating or reducing risk factors) or to secondary prevention (early diagnosis) strategies. Our results are essential for the development of cancer prevention and control strategies in the Island.

A 68-year-old athletic woman presented to our institution in January 2002 with a several-month history of progressing complaints of pain, swelling, and loss of motion in the right knee. These manifestations had begun the previous July during a game of tennis. She experienced persisting pain and recurring effusions. Because the patient had been residing in another state between July and January, rheumatologic and orthopaedic evaluations of the knee, including a magnetic resonance imaging (MRI), had been performed at a geographically distant (but affiliated) institution. The resulting presumptive diagnosis was a "wear and tear" degenerative articular disorder of the knee. A program of anti-inflammatory medication and physical therapy was begun for several months but produced no therapeutic benefit by the time the patient presented at our institution. After examination confirmed marked losses of both flexion and extension of the knee, effusion, and exquisite medial joint tenderness, an MRI was repeated, using intra-articular gadolinium as a contrast agent. It revealed an intra-articular mass encircling the medial and posterior extents of the medial femoral condyle. An arthroscopic multiportal excisional biopsy was performed. It revealed the existence of a juxta-articular myxoma. The patient recovered most of the range of motion during the next several months, and the effusion and severe pain gradually dissipated. The patient was subsequently followed by sequential physical examinations and MRIs, performed at increasing intervals of time, without recurrence of a mass or of her flagrant symptoms in the first year post surgery. Though the patient's diagnosis was established and treatment outcome was satisfactory, many issues were brought up in this case regarding most appropriate selection of diagnostic tests and treatment approaches.

Anterior cruciate ligament (ACL) injuries are especially common in the younger athletic population. In 1998, more than 100,000 ACL reconstructions were performed. MR imaging examination has proved to be valuable in imaging and evaluating ACL reconstructions. This article reviews different surgical reconstruction procedures, indications for postoperative MR imaging, and the MR imaging appearance seen in routine ACL reconstructions and in complications associated with ACL reconstructions.

MR imaging is an accurate, noninvasive, and cost-effective method for the evaluation of acute knee ligament injuries and in the examination of the postoperative knee. Understanding the normal anatomy and the pertinent clinical aspects of knee injuries is a prerequisite for accurate interpretation of MR imaging studies. The increasing popularity of ACL reconstruction following disruption of this ligament requires knowledge of the various surgical techniques and their MR imaging appearance as well as the appearance of possible complications.

We assessed components of lenticular short-circuit current in adult hypertensive Dahl salt-sensitive rats (DS) during chronic control (0.4% sodium) versus high (3% sodium) dietary NaCl intake begun at the age of 4 weeks until rats were studied. We also evaluated the influence of barium, a potassium channel blocker, and ouabain, a specific inhibitor of Na+, K(+)-ATPase activity, by adding them to the anterior lens surface, thus measuring barium-sensitive, ouabain-sensitive, and barium- and ouabain-in-sensitive short-circuit currents. During control NaCl intake, short-circuit current in DS and their control group, Dahl salt-resistant rats (DR), did not differ significantly. DS were subclassified into cataract-prone rats and rats unlikely to develop cataracts on the basis of their initial pressor response to the change from a normal to high NaCl diet during the first weeks of age. Although only transparent lenses were studied, total lens short-circuit current was already markedly decreased in the cataract-prone subgroup compared with DS unlikely to develop cataracts and control DR. This was in sharp contrast to the increase in short-circuit current previously reported in Sprague-Dawley rats and now observed in control DR in response to high dietary NaCl. The decrease in lens short-circuit current in cataract-prone rats was associated with lower absolute values of barium- and ouabain-sensitive short-circuit currents as well as with low barium- and ouabain-insensitive short-circuit current. Although the barium- and ouabain-sensitive components of the short-circuit current were similar in DS unlikely to develop cataracts and DR, the barium- and ouabain-insensitive component of the short-circuit current was lower in DS unlikely to develop cataracts than values in DR. Interestingly, this component of lens short-circuit current also increased in DR during chronic high NaCl, whereas the opposite change occurred in cataract-prone DS and DS unlikely to develop cataracts. Thus, the barium- and ouabain-insensitive short-circuit current may be a mechanism that protects the normal lens from developing cataracts. Possible candidates for this short-circuit current component are voltage-dependent potassium channels, calcium-activated potassium channels, or both. Our studies show altered lens short-circuit current in response to high NaCl intake in cataract-prone DS and suggest the possibility of altered lens potassium transport during sustained hypertension but before loss of lens transparency.

A 22-year-old athlete developed chronic pain in the forearm aggravated by weight lifting. Physical examination revealed localized tenderness at the junction of the middle and distal third of the ulnar diaphysis. X-ray films revealed an osteolytic lesion at the same level. The patient developed an overt fracture at the same site when he failed to stop sports activities against advice. The fracture healed uneventfully with immobilization in a sleeve cast.

We have previously reported a high incidence of cataract formation in adult hypertensive salt-sensitive rats, suggesting that hypertension may be an important cataractogenic risk factor. Weanling salt-sensitive rats that eventually developed cataracts showed a marked increase in the pressor response to a high-sodium diet compared to salt-sensitive rats that did not develop cataracts. A lens and aqueous fluid electrolyte imbalance occurred in all adult salt-sensitive rats examined, but was greater in the salt-sensitive rats that developed cataracts, suggesting an alteration in lens and/or ciliary ion transport in cataracts associated with hypertension. In the present study, lens 86Rb uptake was measured in adult hypertensive salt-sensitive rats prior to cataract formation. 'Cataract-prone' salt-sensitive hypertensive rats (increased pressor response to a high sodium diet given at weanling age), salt-sensitive hypertensive rats unlikely to develop cataracts and control salt-resistant rats were studied at the age of 16 weeks. Total and ouabain-insensitive lens 86Rb uptake were measured for the determination of ouabain-sensitive uptake, an index of Na+,K+-ATPase activity. Lens ouabain-sensitive 86Rb uptake was low in adult hypertensive cataract-prone salt-sensitive rats before cataract formation compared with values in control resistant rats. Intermediate values were observed in hypertensive salt-sensitive rats unlikely to develop cataracts. These data suggest that altered ion transport may play a pivotal role in cataractogenesis associated with this model of hypertension. The data are also consistent with the concept of a generalized defect in epithelial ion transport, at least in salt-sensitive hypertension.