► In this work, we produce transplastomic tobacco plants expressing the BRV C486 VP8* protein. ► VP8* protein produced in tobacco chloroplasts accumulated as a very stable protein. ► VP8* plant ...extracts were able to induce a strong immune response in female mice. ► Female mice immunized with VP8* were able to passively protect their offspring from challenge.
Group A rotavirus is a major leading cause of diarrhea in mammalian species worldwide. In Argentina, bovine rotavirus (BRV) is the main cause of neonatal diarrhea in calves. VP4, one of the outermost capsid proteins, is involved in various virus functions. Rotavirus infectivity requires proteolytic cleavage of VP4, giving an N-terminal non-glycosilated sialic acid-recognizing domain (VP8*), and a C-terminal fragment (VP5*) that remains associated with the virion. VP8* subunit is the major determinant of the viral infectivity and one of the neutralizing antigens.
In this work, the C486 BRV VP8* protein was produced in tobacco chloroplasts. Transplastomic plants were obtained and characterized by Southern blot, northern blot and western blot. VP8* was highly stable in the transplastomic leaves, and formed insoluble aggregates that were partially solubilized by sonication. The recombinant protein yield was 600
μg/g of fresh tissue (FT). Both the soluble and insoluble fractions of the VP8* plant extracts were able to induce a strong immune response in female mice as measured by ELISA and virus neutralization test. Most important, suckling mice born to immunized dams were protected against oral challenge with virulent rotavirus. Results presented here contribute to demonstrate the feasibility of using antigens expressed in transplastomic plants for the development of subunit vaccines.
The prevalence of obesity (BMI ≥30) in US women approximates 40%. Severely obese women (BMI ≥40) have increased rates of perioperative morbidity and mortality. Minimally invasive surgical (MIS) ...options have improved perioperative outcomes but become limited for patients with severely elevated BMI, particularly ≥60. Contrary to previously published conclusions, utilizing panniculectomy at the time of surgical staging can make laparoscopic surgery feasible in this patient population.
Retrospective review of patients undergoing concurrent panniculectomy and total laparoscopic hysterectomy (TLH). Twenty-one patients between 2009–2022 were identified through surgical logs. Data was collected regarding successful completion of laparoscopy as well as intraoperative and postoperative complications within 30 days of surgery.
Average preoperative BMI was 53.3 (range 41–79). A laparoscopic procedure was scheduled in all 21 patients. Laparoscopy was successfully completed in 20/21 cases (95%). One case required conversion from laparoscopic hysterectomy to laparotomy. Mean blood loss was 238ml (range 100–500 ml). The median weight of pannus resection was 6.6 kg (range 4.2–38.5 kg). One patient required intraoperative blood transfusion due to operative losses as the pannus removed was >38 kg. Median operative time was minutes 214 (range 169–322 mins). 90% of patients were discharged by post operative day 2 (range day 1–5). Two-thirds of patients were discharged without need for home health services. No patients required readmission within 30 days following surgery and no patients required ICU admission. There were no events of venous thromboembolism, bowel obstruction or surgical site complications occurred.
Our pilot data demonstrates utilizing panniculectomy at the time of hysterectomy is successful in facilitating laparoscopic surgery for severely obese patients. No major complications were seen during admission or in the 30-day postoperative period, and the additional inpatient stay is minimal. The current data is the basis of ongoing research regarding long-term effects of combined panniculectomy and laparoscopic hysterectomy, with specific attention to hypertension, diabetes, weight management and patient quality of life.
To estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation.
We conducted a population-based cohort study. ...All uterine sarcomas from 2006-2013 in an integrated health care system were identified. Age- and race-specific incidences of occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed. Crude and adjusted risk ratios of recurrence and death associated with morcellation at 1, 2, and 3 years were estimated using Poisson regression with inverse probability weighting.
There were 125 hysterectomies with occult uterine sarcomas identified among 34,728 hysterectomies performed for leiomyomas. The incidence of occult uterine sarcoma and leiomyosarcoma was 1 of 278 or 3.60 (95% confidence interval CI 2.97-4.23) and 1 of 429 or 2.33 (95% CI 1.83-2.84) per 1,000 hysterectomies. For stage I leiomyosarcoma (n=111), eight (7.2%) were power and 27 (24.3%) nonpower-morcellated. The unadjusted 3-year probability of disease-free survival for no morcellation, power and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P=.15); overall survival was 0.64, 0.75, and 0.68, respectively (P=.97). None of the adjusted risk ratios for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76) (5.12, 95% CI 1.33-19.76, P=.02). We had inadequate power to infer differences for all other comparisons including 3-year survival and power morcellation.
Morcellation is associated with decreased early survival of women with occult leiomyosarcomas. We could not accurately assess associations between power morcellation and 3-year survival as a result of small numbers.
Despite histologically negative lymph nodes, approximately 15% of patients with early-stage cervical cancer will develop recurrence. Micrometastases have been shown to be important in staging and ...treatment of breast cancers and melanoma and have been identified by polymerase chain reaction analysis in cervical cancers. This study sought to estimate the frequency of micrometastases identified by immunohistochemistry in histologically negative lymph nodes and compare this to other known risk factors for recurrence of cervical cancer.
Early-stage (stages IA2, IB1, and IB2) cervical cancer patients of all histologic subtypes were identified from the surgical logs of the Los Angeles County-University of Southern California Medical Center for the period 1994-2000. One hundred thirty-two patients had histologically negative lymph nodes. Immunohistochemical assay was performed on 3,106 lymph nodes by using antibodies against cytokeratins AE-1 and CAM 5.2 in combination according to standard protocols. The stained nodes were then evaluated for the presence of micrometastases and compared against the respective clinicopathologic information in each case.
Micrometastases were detected in 19 of 132 (15%, 95% confidence interval CI 9%, 22%) patients, found in 29 of the 3,106 (0.9%) lymph nodes evaluated. Vascular space invasion was seen in 50 of 132 cases (38%, 95% CI 30%, 47%) and in 8 of 19 (42%, 95% CI 21%, 66%) cases with micrometastases. Surgical margins of the resected specimen were negative in 120 of 132 cases (91%, 95% CI 84%, 95%) and in 16 of 19 (84%, 95%CI 60%, 96%) of those cases with micrometastases. Micrometastases were seen most frequently in pelvic lymph nodes (25 of 29, 86%). Patients with more than 20 lymph nodes removed were more likely to demonstrate metastasis (P <.001). There was no statistically significant association between micrometastasis and vascular space invasion or tumor volume.
Micrometastases are identifiable in histologically negative lymph nodes in 15% (95% CI 9%, 22%) of early-stage cancer patients, a frequency which approximates the recurrence rate for patients with negative nodes. In this series, patients with greater numbers of lymph nodes analyzed were more likely to have lymph node micrometastasis identified. There appears to be no relationship between tumor volume and the identification of micrometastases. Although micrometastases can be identified in histologically negative lymph nodes, their presence is not strongly associated with other known factors of cervical cancer recurrence. Further research is needed to determine whether the presence of lymph node micrometastases is associated with an unfavorable prognosis.
II-3
Guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) for women with pathogenic variants of non-BRCA and Lynch syndrome-associated ovarian cancer susceptibility genes. Optimal ...timing and findings at the time of RRSO for these women remains unclear. We sought to characterize practice patterns and frequency of occult gynecologic cancers for these women at our two institutions.
Women with germline ovarian cancer susceptibility gene pathogenic variants who underwent RRSO between 1/2000–9/2019 were reviewed in an IRB-approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records.
26 Non-BRCA (9 BRIP1, 9 RAD51C, and 8 RAD51D) and 75 Lynch (36 MLH1, 18 MSH2, 21 MSH6) pathogenic variants carriers were identified. Median age at time of RRSO was 47. There were no occurrences of occult ovarian or fallopian tube cancer in either group. Two patients (3%) in the Lynch group had occult endometrial cancer. Median follow up was 18 and 35 months for non-BRCA and Lynch patients, respectively. No patient developed primary peritoneal cancer upon follow up. Post-surgical complications occurred in 9/101 (9%) of patients. Hormone replacement therapy (HRT) was rarely used despite reported post-menopausal symptoms in 6/25 (23%) and 7/75 (37%) patients, respectively.
No occult ovarian or tubal cancers were observed in either group. No recurrent or primary gynecologic-related cancers occurred upon follow-up. Despite frequent menopausal symptoms, HRT use was rare. Both groups experienced surgical complications when hysterectomy and/or concurrent colon surgery was performed suggesting concurrent surgeries should only be performed when indicated.
•Median age of RRSO was 47 yo with no occult ovarian/fallopian tube cancer supporting current RRSO guidelines.•Surgical complications in this population were largely seen with concomitant hysterectomy and colectomy.•There was very low uptake in post-surgery hormone replacement therapy in these patients undergoing RRSO.
Context
Coastal landscapes evolve in response to sea-level rise (SLR) through a variety of geologic processes and ecological feedbacks. When the SLR rate surpasses the rate at which these processes ...build elevation and drive lateral migration, inundation is likely.
Objectives
To examine the role of land cover diversity and composition in landscape response to SLR across the northeastern United States.
Methods
Using an existing probabilistic framework, we quantify the probability of inundation, a measure of vulnerability, under different SLR scenarios on the coastal landscape. Resistant areas—wherein a dynamic response is anticipated—are defined as
unlikely
(p < 0.33) to inundate. Results are assessed regionally for different land cover types and at 26 sites representing varying levels of land cover diversity.
Results
Modeling results suggest that by the 2050s, 44% of low-lying, habitable land in the region is
unlikely
to inundate, further declining to 36% by the 2080s. In addition to a decrease in SLR resistance with time, these results show an increasing uncertainty that the coastal landscape will continue to evolve in response to SLR as it has in the past. We also find that resistance to SLR is correlated with land cover composition, wherein sites containing land cover types adaptable to SLR impacts show greater potential to undergo biogeomorphic state shifts rather than inundating with time.
Conclusions
Our findings support other studies that have highlighted the importance of ecological composition and diversity in stabilizing the physical landscape and suggest that flexible planning strategies, such as adaptive management, are particularly well suited for SLR preparation in diverse coastal settings.
•Adjuvant gemcitabine-docetaxel chemotherapy increased significantly from 2006 to 2013•White women were more likely to receive adjuvant chemotherapy than other ethnicities.•Adjuvant ...gemcitabine-docetaxel was not associated with improved survival.
To assess recent trends of administering adjuvant gemcitabine-docetaxel (GD) chemotherapy for Stage I uterine leiomyosarcoma, and to compare disease-free and overall survival between women who received and did not receive adjuvant GD chemotherapy.
All patients diagnosed with Stage I uterine leiomyosarcoma in a California-Colorado population-based health plan inclusive of 2006–2013 were included in a retrospective cohort. Adjuvant GD chemotherapy rates, clinico-pathologic characteristics and survival estimates were assessed.
Of 111 women with Stage I uterine leiomyosarcoma, 33 received adjuvant GD (median 4cycles), 77 received no chemotherapy, and 1 patient excluded for non-GD chemotherapy. GD-chemotherapy and no-chemotherapy groups were similar with respect to age, stage (IA/IB), uterine weight, mitotic index, body mass index, and Charlson comorbidity score. Non-Hispanic white women were twice as likely to receive adjuvant chemotherapy as non-white or Hispanic women (37.7 vs. 17.1%, P=0.02). The proportion of women receiving adjuvant GD chemotherapy increased from 6.5% in 2006–2008 to 46.9% in 2009–2013 (P<0.001). There was no significance difference in unadjusted Kaplan-Meyer estimated disease-free (P=0.95) or overall survival (P=0.43) between GD-chemotherapy and no-chemotherapy cohorts. Corresponding adjusted Cox proportional hazard ratios for adjuvant GD chemotherapy compared to no chemotherapy were 1.01 (95% confidence interval CI 0.57–1.80, P=0.97) for recurrence and 1.28 (95% CI 0.69–2.36, P-0.48) for mortality.
Use of adjuvant GD chemotherapy for Stage I uterine leiomyosarcoma has increased significantly in the last decade, despite unclear benefit. Compared to no chemotherapy, 4–6cycles of adjuvant GD chemotherapy does not appear to alter survival outcomes.
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