Summary Here we describe an in vitro primary culture system for C. elegans germline stem cells. This culture system was used to identify a bacterial folate as a positive regulator of germ cell proliferation. Folates are a family of B-complex vitamins that function in one-carbon metabolism to allow the de novo synthesis of amino acids and nucleosides. We show that germ cell proliferation is stimulated by the folate 10-formyl-tetrahydrofolate-Glun both in vitro and in animals. Other folates that can act as vitamins to rescue folate deficiency lack this germ cell stimulatory activity. The bacterial folate precursor dihydropteroate also promotes germ cell proliferation in vitro and in vivo, despite its inability to promote one-carbon metabolism. The folate receptor homolog FOLR-1 is required for the stimulation of germ cells by 10-formyl-tetrahydrofolate-Glun and dihydropteroate. This work defines a folate and folate-related compound as exogenous signals to modulate germ cell proliferation.
Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions.
Primary renal lymphoma (PRL) is a rare disease process which represents less than 1% of all renal masses and is an uncommon type of Non-Hodgkin's Lymphoma. PRL is of clinical significance due to the fact that unlike the more commonly seen renal cell carcinoma, PRL is treated with neoadjuvant chemotherapy followed by nephrectomy. This challenges the long held notion that preoperative biopsies are not necessary prior to nephrectomy for renal masses. In this paper, we present a case of a primary renal lymphoma and discuss its clinical significance.
The Caenorhabditis elegans germ line is an important model system for the study of germ stem cells. Wild-type C. elegans germ cells are syncytial and therefore cannot be isolated in in vitro cultures. In contrast, the germ cells from tumorous mutants can be fully cellularized and isolated intact from the mutant animals. Here we describe a detailed protocol for the isolation of germ cells from tumorous mutants that allows the germ cells to be maintained for extended periods in an in vitro primary culture. This protocol has been adapted from Chaudhari et al., 2016.
INTRODUCTION: With rising life expectancy and low birth rates, elderly people make up an increasing proportion of the population of the United States. Studies estimate that by 2050, the nonagenarian population will reach 8.7 million. Elderly people have significant medical care needs and their need for surgical care will require nuanced evaluation of their surgical candidacy and operative risks.METHODS: A retrospective analysis was performed through chart review to identify nonagenarians and centenarians who underwent acute care surgery over 6 years at our community hospital. Demographic and surgical data were found and compared to outcomes to assess factors that impact outcome.RESULTS: 120 patients over the age of 90 underwent 124 surgical procedures at our institution between 2015 and 2020. Ages ranged from 90-101, with 61% women and 39% men. The most common procedures performed were cholecystectomy ( 18), open groin hernia repair (13), and laparotomy with large bowel resection (12). Congestive heart failure, dementia, American Society of Anesthesia score and Johns Hopkins Class of Surgery were associated with increased mortality, while hyperlipidemia was protective. 33% of patients developed postoperative complications and 42% required an ICU stay while 84% survived to discharge.CONCLUSION: Although surgery is often avoided in elderly patients, especially those over ninety, many patients in this population tolerate acute care surgery well with a vast majority surviving to discharge. With appropriate discussion with the patient on risks, benefits, and alternatives to surgery, it is appropriate to proceed to the operating room.
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