In vitro growth of follicles is a promising technology to generate large quantities of competent oocytes from immature follicles and could expand the potential of assisted reproductive technologies ...(ART). Isolated follicle culture is currently the primary method used to develop and mature follicles in vitro. However, this procedure typically requires complicated, time-consuming procedures, as well as destruction of the normal ovarian microenvironment. Here we describe a simplified 3-D ovarian culture system that can be used to mature multilayered secondary follicles into antral follicles, generating developmentally competent oocytes in vitro. Ovaries recovered from mice at 14 days of age were cut into 8 pieces and placed onto a thick Matrigel drop (3-D culture) for 10 days of culture. As a control, ovarian pieces were cultured on a membrane filter without any Matrigel drop (Membrane culture). We also evaluated the effect of activin A treatment on follicle growth within the ovarian pieces with or without Matrigel support. Thus we tested four different culture conditions: C (Membrane/activin-), A (Membrane/activin+), M (Matrigel/activin-), and M+A (Matrigel/activin+). We found that the cultured follicles and oocytes steadily increased in size regardless of the culture condition used. However, antral cavity formation occurred only in the follicles grown in the 3-D culture system (M, M+A). Following ovarian tissue culture, full-grown GV oocytes were isolated from the larger follicles to evaluate their developmental competence by subjecting them to in vitro maturation (IVM) and in vitro fertilization (IVF). Maturation and fertilization rates were higher using oocytes grown in 3-D culture (M, M+A) than with those grown in membrane culture (C, A). In particular, activin A treatment further improved 3-D culture (M+A) success. Following IVF, two-cell embryos were transferred to recipients to generate full-term offspring. In summary, this simple and easy 3-D ovarian culture system using a Matrigel drop and activin A supplementation (M+A) provides optimal and convenient conditions to support growth of developmentally competent oocytes in vitro.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims Increased intake of dietary fiber has been proposed to reduce the risk of inflammatory bowel disease (Crohn's disease CD and ulcerative colitis UC). However, few prospective studies ...have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed up over 26 years, who participated in the Nurses' Health Study, followed up for 3,317,425 person-years. Dietary information was prospectively ascertained via administration of a validated semiquantitative food frequency questionnaire every 4 years. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence, 8/100,000 person-years) and 338 cases of UC (incidence, 10/100,000 person-years). Compared with the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval, 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% confidence interval, 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusions Based on data from the Nurses' Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.
Dietary fats influence intestinal inflammation and regulate mucosal immunity. Data on the association between dietary fat and risk of Crohn's disease (CD) and ulcerative colitis (UC) are limited and ...conflicting.
We conducted a prospective study of women enrolled in the Nurses' Health Study cohorts. Diet was prospectively ascertained every 4 years using a validated semi-quantitative food frequency questionnaire. Self-reported CD and UC were confirmed through medical record review. We examined the effect of energy-adjusted cumulative average total fat intake and specific types of fat and fatty acids on the risk of CD and UC using Cox proportional hazards models adjusting for potential confounders.
Among 170,805 women, we confirmed 269 incident cases of CD (incidence 8/100,000 person-years) and 338 incident cases of UC (incidence 10/100,000 person-years) over 26 years and 3,317,338 person-years of follow-up. Cumulative energy-adjusted intake of total fat, saturated fats, unsaturated fats, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were not associated with risk of CD or UC. However, greater intake of long-chain n-3 PUFAs was associated with a trend towards lower risk of UC (HR 0.72, 95% CI 0.51 to 1.01). In contrast, high long-term intake of trans-unsaturated fatty acids was associated with a trend towards an increased incidence of UC (HR 1.34, 95% CI 0.94 to 1.92).
A high intake of dietary long-chain n-3 PUFAs may be associated with a reduced risk of UC. In contrast, high intake of trans-unsaturated fats may be associated with an increased risk of UC.
Self‐assembly of various metallo‐supramolecular coordination polyelectrolytes (MEPEs) based on pyridine ring functionalized ditopic bis‐terpyridines, as well as the electrochromic property is ...presented. MEPEs derived from electron‐donating OMe functionalized ligands exhibit rapid switching rates, good reversibility, high stability, and an optical memory. The first structure‐property relationships are proposed, which are needed for the de novo design and fabrication of new materials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Learning points for clinicians. The absence of tactile feedback is a technical challenge in robot-assisted surgery (RAS). As a result, mechanical compression of vascular tissue by the robotic arm can ...cause vascular injury, including arterial dissection. Therefore, intraoperative monitoring of the vascular status of the lower limb may be important during intrapelvic RAS surgery.
Objectives
To describe the results of orthogonal plating (OP) as a treatment for fractures of the radius and ulna in toy‐breed dogs.
Materials and Methods
The medical records (June 2011 to April ...2019) of toy‐breeds in which the OP technique using non‐locking cuttable plates was employed to treat radial and ulnar fractures were reviewed. The inclusion criteria included a bodyweight of 3.5 kg or less, fracture of the diaphysis of the radius and ulna of one or both forelimbs, and the availability of follow‐up radiographs. Revision surgeries were also included.
Results
Fifteen limbs that underwent initial fracture repair and five that underwent revision surgery met the inclusion criteria. The radial and ulnar fractures healed in 19 limbs at the final follow‐up. Synostosis of the radius and ulna at the fracture sites was observed in one limb. Re‐fracture after cranial plate removal was observed in one case. All dogs exhibited successful return of normal limb function at the final clinical and radiographic follow‐up (mean, 104.7 ± 67.1 days; median, 79.5 days; range: 35 to 248 days). Long‐term follow‐up data obtained via telephone interviews to owners or referring veterinarians were available for 15 cases and confirmed maintenance of normal limb function in all dogs (mean, 32.5 ± 17.6 months; median, 26 months; range: 11 to 69 months).
Clinical Significance
OP allowed the successful open reduction of radial and ulnar fractures, facilitating bone union in both the radius and ulna and a return to normal limb function in a series of toy‐breed dogs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Long-term data on the influence of cigarette smoking, especially cessation, on the risk of Crohn's disease (CD) and ulcerative colitis (UC) are limited.
We conducted a prospective study of 229,111 ...women in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). Biennially, we collected updated data on cigarette smoking, other risk factors, and diagnoses of CD or UC confirmed by medical record review.
Over 32 years in NHS and 18 years in NHS II, we documented 336 incident cases of CD and 400 incident cases of UC. Compared with never smokers, the multivariate hazard ratio (HR) of CD was 1.90 (95% confidence interval (CI), 1.42-2.53) among current smokers and 1.35 (95% CI, 1.05-1.73) among former smokers. Increasing pack-years was associated with increasing risk of CD (Ptrend < 0.0001), whereas smoking cessation was associated with an attenuation of risk. By contrast, the multivariate HR of UC was 0.86 (95% CI, 0.61-1.20) among current smokers and 1.56 (95% CI, 1.26-1.93) among former smokers. The risk of UC was significantly increased within 2-5 years of smoking cessation (HR, 3.06; 95% CI, 2.00-4.67) and remained persistently elevated over 20 years.
Current smoking is associated with an increased risk of CD, but not UC. By contrast, former smoking is associated with an increased risk of UC, with risk persisting over two decades after cessation.
Diet plays a role in the pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC). Dietary zinc may influence risk of disease through effects on autophagy, innate and adaptive immune response ...and maintenance of the intestinal barrier.
We analysed data from 170 776 women from the Nurses Health Study I and Nurses Health Study II, who were followed for 26 years. Zinc intake was assessed using semi-quantitative food frequency questionnaires administered every 4 years. Incident CD and UC were ascertained by medical record review. Cox proportional hazards models adjusting for potential confounders determined the independent association between zinc intake and incident disease.
Over 3 317 550 person-years (p-y) of follow-up, we identified 269 incident cases of CD and 338 incident cases of UC. Zinc intake ranged from 9 mg/day in the lowest quintile to 27 mg/day in the highest quintile. Compared with women with the lowest quintile of intake, the multivariate hazard ratios (HR) for CD were 0.92 95% confidence interval (CI), 0.65 – 1.29) for women in the second quintile of intake, 0.60 (95% CI, 0.40 – 0.89) for the third quintile, 0.57 (95% CI, 0.38 – 0.86) for fourth quintile and 0.74 (95% CI, 0.50 – 1.10) for the highest quintile (Ptrend = 0.003). The association was stronger for dietary zinc (HR 0.63, 95% CI, 0.43 – 0.93, comparing extreme quintiles) than for zinc intake from supplements. Neither dietary nor supplemental zinc modified risk of UC.
In two large prospective cohorts of women, intake of zinc was inversely associated with risk of CD but not UC.
The transcription factor E2F1 has pivotal roles in both cell proliferation and cell death, and is an important molecular target in cancer. Under proliferative conditions E2F1 induces the expression ...of genes that promote cell cycle progression, such as E2F2, whereas under proapoptotic conditions E2F1 induces expression of genes such as p73 that lead to apoptosis. The mechanism by which the apoptotic function of E2F1 is activated remains unclear, however. We now show that members of the E2F family are covalently conjugated with the ubiquitin-like modifier NEDD8. Overexpression of SENP8, a NEDD8-specific cysteine protease, resulted in deNEDDylation of E2F1 and promoted its transactivation activity at the p73 gene but not at the E2F2 gene. Knockdown of SENP8, on the other hand, attenuated p73 expression and apoptosis induced by E2F1 or by DNA damage. SENP8 also promoted the interaction between E2F1 and its cofactor Microcephalin 1, which is required for p73 induction. These results suggest that NEDDylation is a molecular trigger that modifies the target specificity of E2F1, and could have important implications for E2F1 regulation of apoptosis.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Although Asian thyroid practices have implemented the American Thyroid Association guidelines, significant deviations in actual risk of malignancy (ROM) have been reported. With review of the ...literature from Asia, the authors examine the underlining reasons for actual ROMs reported in Asia being so different from western practice based on the author's perspective. Although the most popular diagnostic system for thyroid cytology used in Asian countries is the Bethesda system, the Japan Thyroid Association published clinical guidelines, including a national reporting system for thyroid cytology, to adapt conservative clinical management (active surveillance and strict triage patients for surgery) for low‐risk thyroid carcinomas. As less aggressive clinical management is favoured in Asian societies, strict triage of patients with indeterminate thyroid nodules for surgery is usually applied, which ultimately reduces overtreatment of indolent thyroid tumours. As a result, low resection rates and high ROMs for indeterminate nodules were achieved in Asian practices using the same Bethesda system. Recently, borderline thyroid tumours were introduced in the thyroid tumour classification and significant decreases in ROMs have been reported in the indeterminate categories in western practice. However, ROM of indeterminate nodules remained high in Asian practice even after borderline tumours were deemed benign. These results suggested that the diagnostic threshold of papillary thyroid carcinoma‐type nuclear features varied among practices (stricter in Asia than in western practice), and diagnostic surgery was not performed for a significant number of indeterminate nodules with benign clinical features in Asian practice, resulting in low rates of borderline tumours in surgically‐treated patients.
Although Asian thyroid practices have implemented the American Thyroid Association guidelines and the Bethesda system for reporting thyroid cytopathology, significant deviations in actual risk of malignancy have been reported. With review of the literature and analyses of thyroid practices in Asia, the author examines the underlining reasons why actual ROMs reported in Asia are so different from those in Western practice based on the author's perspective.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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