Laparoscopic Resection of a Small Bowel Lipoma with Incidental Intussusception

Small bowel lipomas, which can cause intussusception and gastrointestinal bleeding, can be managed with laparoscopic resection when diagnosed preoperatively

Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates

RNAi is a powerful method for suppressing gene expression that has tremendous potential for therapeutic applications. However, because endogenous RNAi plays a role in normal cellular functions, delivery and expression of siRNAs must be balanced with safety. Here we report successful stable expression in primates of siRNAs directed to chemokine (c-c motif) receptor 5 (CCR5) introduced through CD34+ hematopoietic stem/progenitor cell transplant. After hematopoietic reconstitution, to date 14 months after transplant, we observe stably marked lymphocytes expressing siRNAs and consistent down-regulation of chemokine (c-c motif) receptor 5 expression. The marked cells are less susceptible to simian immunodeficiency virus infection ex vivo. These studies provide a successful demonstration that siRNAs can be used together with hematopoietic stem cell transplant to stably modulate gene expression in primates and potentially treat blood diseases such as HIV-1

Positive correlation of employment and psychological well-being for veterans with major abdominal surgery

Background Intestinal stomas (ostomies) have been associated negatively with multiple aspects of health-related quality of life. This article examines the relationship between employment status and psychological well-being (PWB) in veterans who underwent major bowel procedures with or without ostomy. Methods Veterans from 3 Veterans Affairs (VA) medical centers were surveyed using the City of Hope ostomy-specific questionnaire and the Short Form 36 item Veteran’s version (SF-36V). Response rate was 48% (511 of 1,063). Employment and PWB relationship was assessed using multiple regression with age, income, SF-36V physical component summary (PCS), and employment status as independent variables. Results Employed veterans reported higher PWB compared with unemployed veterans (P = .003). Full-time workers also reported higher PWB than part-time or unemployed workers (P = .001). Ostomy was not an independent predictor of PWB. Conclusions Employment among veterans after major abdominal surgery may have intrinsic value for PWB. Patients should be encouraged to return to work, or do volunteer work after recovery

Consortium of Otolaryngology Journal Editors: Collegiality and Contributions

There is a new tradition in the otolaryngology publishing community that is unique to our specialty, so far as we know. Editors-in-Chief of otolaryngology journals in the United States, and intermittently some of our international colleagues such as the Editor of the Journal of Laryngology and Otology (England), sit down together twice a year to discuss topics of mutual interest, maintain lines of communication and friendships, and share perspectives on the evolution of otolaryngology—head and neck surgery and needs that our journals might help address. To establish these collegial, uninhibited, informative, and productive meetings, Dr Robert Ruben proposed the idea of a Consortium of Otolaryngology Journal Editors. During the consortium’s formative years, the organization was solidified and supported by Jonas Johnson who was Editor-in-Chief of Laryngoscope from 2003 to 2008 and whose journal funded our meetings. The editors have discussed many topics including standardization of terminology, duplicate publication and plagiarism, increasing physician interest and involvement in peer-review, peer-review education, new publication models and their implications for our colleagues, support for resident presentations at scientific meetings, innovations at individual journals that might prove useful for other journals, increasing international involvement in our journals, predatory journals, and other topics

Robert Dahl and the Right to Workplace Democracy

Do employees possess a moral right to democratic voice at work? In A Preface To Economic Democracy and other writings over the past two decades, Robert Dahl has developed a neo-Kantian proof for the existence of such a right. Even if we accept the norm of distributive justice upon which Dahl founds his proof, voluntary subjection to authoritarian power in firms does not violate the legitimate entitlements of employees. While adult residents of territorial associations do possess a moral right to political equality, polities and firms are qualitatively different types of associations in which the entitlements of subjects are distinct. Subjection to power is acquired in different ways in the two kinds of associations, and this difference deprives employees—but not residents—of a right to democratic voice as a matter of moral desert

Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer

BACKGROUND:Cancers often arise within an area of cells (e.g. an epithelial patch) that is predisposed to the development of cancer, i.e. a "field of cancerization" or "field defect." Sporadic colon cancer is characterized by an elevated mutation rate and genomic instability. If a field defect were deficient in DNA repair, DNA damages would tend to escape repair and give rise to carcinogenic mutations.PURPOSE:To determine whether reduced expression of DNA repair proteins Pms2, Ercc1 and Xpf (pairing partner of Ercc1) are early steps in progression to colon cancer.RESULTS:Tissue biopsies were taken during colonoscopies of 77 patients at 4 different risk levels for colon cancer, including 19 patients who had never had colonic neoplasia (who served as controls). In addition, 158 tissue samples were taken from tissues near or within colon cancers removed by resection and 16 tissue samples were taken near tubulovillous adenomas (TVAs) removed by resection. 568 triplicate tissue sections (a total of 1,704 tissue sections) from these tissue samples were evaluated by immunohistochemistry for 4 DNA repair proteins. Substantially reduced protein expression of Pms2, Ercc1 and Xpf occurred in field defects of up to 10 cm longitudinally distant from colon cancers or TVAs and within colon cancers. Expression of another DNA repair protein, Ku86, was infrequently reduced in these areas. When Pms2, Ercc1 or Xpf were reduced in protein expression, then either one or both of the other two proteins most often had reduced protein expression as well. The mean inner colon circumferences, from 32 resections, of the ascending, transverse and descending/sigmoid areas were measured as 6.6 cm, 5.8 cm and 6.3 cm, respectively. When combined with other measurements in the literature, this indicates the approximate mean number of colonic crypts in humans is 10 million.CONCLUSIONS:The substantial deficiencies in protein expression of DNA repair proteins Pms2, Ercc1 and Xpf in about 1 million crypts near cancers and TVAs suggests that the tumors arose in field defects that were deficient in DNA repair and that deficiencies in Pms2, Ercc1 and Xpf are early steps, often occurring together, in progression to colon cancer.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Complications among colorectal cancer survivors: SF-6D preference-weighted quality of life scores

Background Societal preference-weighted health-related quality of life (HRQOL) scores enable comparing multi-dimensional health states across diseases and treatments for research and policy. Objective To assess the effects of living with a permanent intestinal stoma, compared to a major bowel resection, among colorectal cancer (CRC) survivors. Research Design Cross-sectional multivariate linear regression analysis to explain preference-weighted HRQOL scores. Subjects Six-hundred-forty CRC survivors (≥5 years) from three group-model HMOs; ostomates and non-ostomates with colorectal resections for CRC were matched on gender, age (±5 years), time since diagnosis, and tumor site (rectum vs. colon). Measures SF-6D scoring system applied to Medical Outcomes Study Short Form-36 version 2 (SF-36v2); City of Hope Quality of Life-Ostomy (mCOH-QOL-O); Charlson-Deyo comorbidity index. Methods Survey of CRC survivors linked to respondents’ clinical data extracted from HMO files. Results Response rate was 52%. Ostomates and non-ostomates had similar sociodemographic characteristics. Mean SF-6D score was 0.69 for ostomates, compared to 0.73 for non-ostomates (p <.001), but other factors explained this difference. Complications of initial cancer surgery, and prior-year comorbidity burden and hospital use were negatively associated with SF-6D scores, while household income was positively associated. Conclusions CRC survivors’ SF-6D scores were not associated with living with a permanent ostomy after other factors were taken into account. Surgical complications, comorbidities, and metastatic disease lowered the preference-weighted HRQOL of CRC survivors with and without ostomies. Further research to understand and reduce late complications from CRC surgeries as well as associated depression is warranted

Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer

In carcinogenesis, the "field defect" is recognized clinically because of the high propensity of survivors of certain cancers to develop other malignancies of the same tissue type, often in a nearby location. Such field defects have been indicated in colon cancer. The molecular abnormalities that are responsible for a field defect in the colon should be detectable at high frequency in the histologically normal tissue surrounding a colonic adenocarcinoma or surrounding an adenoma with advanced neoplasia (well on the way to a colon cancer), but at low frequency in the colonic mucosa from patients without colonic neoplasia

Clonal Tracking of Rhesus Macaque Hematopoiesis Highlights a Distinct Lineage Origin for Natural Killer Cells

SummaryAnalysis of hematopoietic stem cell function in nonhuman primates provides insights that are relevant for human biology and therapeutic strategies. In this study, we applied quantitative genetic barcoding to track the clonal output of transplanted autologous rhesus macaque hematopoietic stem and progenitor cells over a time period of up to 9.5 months. We found that unilineage short-term progenitors reconstituted myeloid and lymphoid lineages at 1 month but were supplanted over time by multilineage clones, initially myeloid restricted, then myeloid-B clones, and then stable myeloid-B-T multilineage, long-term repopulating clones. Surprisingly, reconstitution of the natural killer (NK) cell lineage, and particularly the major CD16+/CD56− peripheral blood NK compartment, showed limited clonal overlap with T, B, or myeloid lineages, and therefore appears to be ontologically distinct. Thus, in addition to providing insights into clonal behavior over time, our analysis suggests an unexpected paradigm for the relationship between NK cells and other hematopoietic lineages in primates

BCL11A enhancer edited hematopoietic stem cells persist in rhesus monkeys without toxicity

Gene editing of the erythroid-specific BCL11A enhancer in hematopoietic stem and progenitor cells (HSPCs) from sickle cell disease (SCD) patients induces fetal hemoglobin (HbF) without detectable toxicity as assessed by mouse xenotransplant. Here, we evaluated autologous engraftment and HbF induction potential of erythroid-specific BCL11A enhancer edited HSPCs in four non-human primates. We utilized a single guide RNA (sgRNA) with identical human and rhesus target sequences to disrupt a GATA1 binding site at the BCL11A +58 erythroid enhancer. Cas9 protein and sgRNA ribonucleoprotein complex (RNP) was electroporated into rhesus HSPCs, followed by autologous infusion after myeloablation. We found that gene edits persisted in peripheral blood (PB) and bone marrow (BM) for up to 101 weeks similarly for BCL11A enhancer or control locus (AAVS1) targeted cells. Biallelic BCL11A enhancer editing resulted in robust gamma-globin induction, with the highest levels observed during stress erythropoiesis. Indels were evenly distributed across PB and BM lineages. Off-target edits were not observed. Non-homologous end-joining repair alleles were enriched in engrafting HSCs. In summary, we find that edited HSCs can persist for at least 101 weeks post-transplant, and biallelic edited HSCs provide substantial HbF levels in PB red blood cells, together supporting further clinical translation of this approach