Histone H3 E50K mutation confers oncogenic activity and supports an EMT phenotype.

Sequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that mutations that convert histone H3 amino acid 50 from a glutamate to a lysine (H3E50K) support an oncogenic phenotype in human cells. Expression of H3E50K is sufficient to transform human cells as evidenced by a dramatic increase in cell migration and invasion, and a statistically significant increase in proliferation and clonogenicity. H3E50K also increases the invasive phenotype in the context of co-occurring BRAF mutations, which are present in patient tumors characterized by H3E50K. H3E50 lies on the globular domain surface in a region that contacts H4 within the nucleosome. We find that H3E50K perturbs proximal H3 post-translational modifications globally and dysregulates gene expression, activating the epithelial to mesenchymal transition. Functional studies using S. cerevisiae reveal that, while yeast cells that express H3E50K as the sole copy of histone H3 show sensitivity to cellular stressors, including caffeine, H3E50K cells display some genetic interactions that are distinct from the characterized H3K36M oncohistone yeast model. Taken together, these data suggest that additional histone H3 mutations have the potential to be oncogenic drivers and function through distinct mechanisms that dysregulate gene expression.

The influence of time of birth and seasonal variations on weight loss in breastfeeding neonates.

BACKGROUND: Breastfeeding (BF) neonates generally lose weight after birth. Neonatal factors like gestational age, birth weight and mode of delivery can affect the neonatal weight loss after birth. Similarly, maternal age, parity and illness may contribute to newborn weight loss. However, influence of the time of birth and season on changes in weight is not well elucidated. OBJECTIVE: The aim of this study is to determine the effect of birth time and the seasonal variations on weight loss in BF newborns. METHODS: In this retrospective study of a prospectively maintained database of two sets of groups, from January 2013 to October 2016, were evaluated- Birth time group and Seasonal group; Birth time of the groups was: night time 7pm to 7am and day time 7am to 7pm; and the seasonal variations groups studies were summer, fall, winter and spring. Weight loss of >5%, 7%, and 10% at <24 hours (h), 48 h and 72 h of birth, respectively, were considered as a significant weight loss. Preterm, exclusively formula fed and neonates admitted to NICU were excluded. RESULTS: A total of 2044 newborns were analyzed. In the birth time group, babies born during the night time had significantly lost >5% of birth weight at <24 h (p < 0.01) and >7% birth weight at <48 h of life (p < 0.02). Weight loss >10% at <72 h was similar in both birth time cohorts. C-section, prolonged rupture of membrane, and maternal pre-delivery hospital stay for >12 h were significant contributing factors. Whereas, seasonal variations were not associated with weight loss in neonates. CONCLUSION: BF babies born at night time lose significantly more weight during the first two days of life and seasonal association was not found to affect weight loss in the neonates.

Intraocular pressure and glaucoma in the Zuni indians.

A glaucoma-screening examination was performed on 119 full-blooded Zuni Indians and 286 control subjects who were aged 40 years or older. The mean intraocular pressure (IOP) of the Zuni Indians was significantly lower than that of the control group, adjusted for age and sex differences, in both diabetic and nondiabetic subjects. The control group demonstrated an increasing IOP with age, while the Zunis did not. The prevalence of ocular hypertension was significantly greater in the control group than in the Zunis. The majority of the Zuni subjects with ocular hypertension had diabetes mellitus. None of the Zuni Indians who were screened had primary open-angle glaucoma and none had a family history of glaucoma.

Trabeculectomy, phacoemulsification, and posterior chamber lens implantation with and without 5-fluorouracil.

Subconjunctival 5-fluorouracil has been an effective adjunct in glaucoma filtering surgery. We investigated the effectiveness of 5-fluorouracil in primary trabeculectomy combined with phacoemulsification and posterior chamber intraocular lens implantation (glaucoma triple procedure). Seventy-four patients were enrolled and randomly assigned into two groups to receive either no 5-fluorouracil (control patients) or low-dose 5-fluorouracil (mean total dose, 24.8 mg; mean number of injections, 5.0 +/- 1.3). The mean preoperative intraocular pressure was 20.1 +/- 5.4 mm Hg for the 5-fluorouracil group and 21.0 +/- 5.2 mm Hg for the control group (P = .48, Student's unpaired t-test). The mean number of medications was 2.2 +/- 1.0 and 2.0 +/- 1.0 (P = .49, Mann Whitney U test), respectively. At all postoperative visits, there were no statistically significant differences in mean intraocular pressures between the two groups. Mean follow-up was 13.2 months for 5-fluorouracil-treated patients and 15.0 months for control patients. At the last postoperative visit, mean intraocular pressures were 15.4 +/- 3.7 mm Hg and 15.0 +/- 5.0 mm Hg, respectively (P = .45, Student's unpaired t-test). Both groups showed comparable visual outcome (20/40 or better in 31 of 38 5-fluorouracil-treated patients [82%] vs 32 of 36 control patients [89%]) and a decrease in number of medications needed, 0.7 +/- 1.0 and 0.7 +/- 0.9, respectively (P = .96, Mann Whitney U test). Thus, 5-fluorouracil administered as in our study did not seem to have any effect in primary trabeculectomy combined with phacoemulsification and posterior chamber intraocular lens implantation.

Limbus-based vs fornix-based conjunctival flap in combined glaucoma and cataract surgery with adjunctive mitomycin C.

PURPOSE: To determine the efficacy and safety of limbus-based vs fornix-based conjunctival flaps in patients with primary open-angle glaucoma undergoing trabeculectomy combined with phacoemulsification and intraocular lens implantation with adjunctive subconjunctival mitomycin C. METHODS: In a prospective study, 69 eyes of 69 patients with primary open-angle glaucoma, visually symptomatic cataracts, and no previous incisional ocular surgery were randomly assigned to limbus-based and fornix-based conjunctival flap groups. All patients received trabeculectomy combined with phacoemulsification and posterior chamber lens implantation with 1-minute (0.5 mg/ ml) application of subconjunctival mitomycin C. RESULTS: The mean intraocular pressures were significantly (P < .05) lower on significantly (P < .05) fewer medications postoperatively at 1 week, 1 month, 3, 6, 9, 12, and 15 to 18 months, and at last follow-up in both groups than they had been preoperatively. However, there were no significant (P > .05) differences in postoperative mean intraocular pressure, mean number of medications, and visual acuity between the two groups at any time interval. Hypotony with wound leak was significantly (P = .019) higher in the limbus-based group. Other postoperative complications were not significantly (P > .05) different between the two groups. CONCLUSIONS: There was no notable difference in glaucoma control or visual outcome between limbus-based and fornix-based conjunctival flaps in primary trabeculectomy combined with phacoemulsification and lens implantation with adjunctive subconjunctival mitomycin C. The fornix-based flap was as safe as, if not safer than, the limbus-based flap in the glaucoma triple procedure with adjunctive subconjunctival mitomycin C.

Acting-out behavior: scenarios for successful intervention.

The decision to physically restrain a patient or other individual on your property may have to made quickly, and with varying degrees of available support and assistance. A training program for clinical staff members and security personnel in successfully dealing with acting-out situations is essential.

Posterior capsular opacification in phacotrabeculectomy : a long-term comparative study of silicone versus acrylic intraocular lens.

PURPOSE: To investigate the long-term outcomes of silicone versus acrylic intraocular lens (IOL) implantation in phacotrabeculectomy (PT) with special emphasis on posterior capsular opacification. DESIGN: Long-term follow-up on prior 1-year prospective, randomized study. PARTICIPANTS: A total of 200 eyes of 200 consecutive primary open-angle glaucoma patients who had undergone primary PT with capsular bag implantation of either a silicone IOL (102 eyes) or an acrylic IOL (98 eyes) according to the initial short-term prospective, randomized study protocol. INTERVENTION: The study eyes underwent primary trabeculectomy, phacoemulsification, and posterior chamber IOL implantation. Adjunctive mitomycin C was used selectively, primarily in patients with one or more risk factors for filtration failure. MAIN OUTCOME MEASURES: Incidence of posterior capsular opacification (PCO), best-corrected visual acuity (BCVA), intraocular pressure (IOP), number of pressure-lowering medications, and filtration success rates, defined as maintenance of target IOP while on one (criteria 1) or zero (criteria 2) pressure-lowering medications without further surgical intervention. RESULTS: At 3-year follow-up, the PCO rate and BCVA did not differ significantly between the two groups (P: > 0.05 for both). In addition, there were no significant differences in IOP, number of medications, and filtration success rate between the two groups (P: > 0.05 for each). CONCLUSIONS: There were no significant long-term differences between the silicone and acrylic IOL groups in PCO, BCVA, IOP, number of medications, and success of filtration surgery after PT. Both groups attained significant improvement in BCVA and IOP control after surgery.

Comparative study of silicone versus acrylic foldable lens implantation in primary glaucoma triple procedure.

OBJECTIVE: To compare silicone versus acrylic foldable intraocular lens (IOL) implantation in primary glaucoma triple procedure (PGTP). DESIGN: Prospective, randomized. PARTICIPANTS: A total of 79 eyes of 79 primary open-angle glaucoma (POAG) patients in need of combined surgery were randomized to a silicone IOL group (36 eyes) and acrylic IOL group (43 eyes). INTERVENTION: The study eyes underwent PGTP, which consisted of primary trabeculectomy, phacoemulsification, and posterior chamber IOL implantation. Adjunctive mitomycin C (MMC) (0.5 mg/ml for 1 minute) was used selectively only in patients with one or more risk factors for filtration failure of PGTP. MAIN OUTCOME MEASURES: Snellen visual acuity, intraocular pressure (IOP), slit-lamp biomicroscopy, and number of glaucoma medications were measured, performed, or determined preoperatively and at regular intervals postoperatively. RESULTS: There were no significant differences in the mean number of postoperative glaucoma medications at 1, 2, 3, 4-6, and 9-12 months and at last follow-up (P > 0.05); mean change in corrected visual acuity best attained (P = 0.315) or at last follow-up (P = 0.223) between the silicone and acrylic groups. Both groups had significant decreases in mean IOP and mean number of medications postoperatively at all times (P < 0.05). However, the postoperative IOP > 25 mmHg and IOP spike > 5 mmHg above preoperative IOP during the first month were significantly higher in the acrylic group (P = 0.026). The mean postoperative IOP at 1 month in the acrylic group was also significantly higher than the silicone group (14.1 +/- 5.0, 11.2 +/- 3.9, P = 0.005). Conversely, there were no significant differences in mean postoperative IOP at 2, 3, 4-6, and 9-12 months and at last follow-up between the silicone and acrylic groups (P > 0.05). Suture removal or release occurred significantly more frequently in the acrylic IOL group during the first month and the first 2 months (48.8% and 60.5%) than the silicone group (25.0% and 36.1%, P = 0.030 and 0.031, respectively). There were no significant differences in postoperative complications or surgical interventions between the two groups (P > 0.05). CONCLUSIONS: During the first year following the PGTP with selective use of MMC, there were no significant differences in the medical dependency or visual outcomes or complications between the silicone and acrylic groups. Both groups attained significant decreases in IOP postoperatively. However, the mean IOP was significantly higher in the acrylic than the silicone group at 1 month postoperatively, and postoperative IOP > 25 mmHg and IOP spike > 5 mmHg above preoperative IOP were significantly greater in the acrylic group. There were significantly more suture releases in the acrylic IOL group than the silicone IOL group in the first 2 months postoperatively.

Transscleral suture fixation of posterior chamber lenses combined with trabeculectomy.

OBJECTIVE: To evaluate the outcome of transscleral suture-fixated posterior chamber intraocular lens (PCIOL) implantation in glaucoma patients when combined with a trabeculectomy. DESIGN: A retrospective study of 56 consecutive glaucoma patients with a minimum follow-up of 6 months after transscleral suture-fixated PCIOL implantation combined with trabeculectomy. SETTING: Patients were drawn from the clinical glaucoma practice of the Kresge Eye Institute, Detroit, MICHIGAN: PATIENTS: Fifty-six eyes of 56 consecutive chronic glaucoma patients who had undergone transscleral suture-fixated PCIOL implantation in combination with a trabeculectomy were included in the analysis. RESULTS: The mean follow-up time was 38.5 +/- 19.1 months. Mean intraocular pressure (IOP) was significantly reduced, from 22.9 +/- 10.9 mmHg before surgery to 16.7 +/- 6.7 mmHg at the last follow-up visit (P = 0.0005), with the mean number of medications used also significantly decreased, from 2.3 +/- 0.9 to 1.9 +/- 0.9 (P = 0.0002). Postoperative IOP control to 21 mmHg or less was achieved or maintained in 84% of patients. Visual acuity improved or remained stable within two Snellen lines of the preoperative level in 39 eyes (70%) and within three Snellen lines in 45 eyes (80%) at the last follow-up visit. Overall, 46% to 68% of the patients had both stable visual acuity and satisfactory pressure control at the last postoperative visit, depending on criteria of varying stringency. However, 19 eyes (34%) required one or more additional surgical interventions for pressure control. Patients with anterior chamber intraocular lens (ACIOL) complications, diabetes mellitus, or a preoperative IOP level of more than 21 mmHg on maximum tolerated medications were especially prone to requiring additional surgical interventions. CONCLUSIONS: We conclude that transscleral suture-fixated PCIOL implantation can be combined successfully with a trabeculectomy and can be useful in glaucoma patients in need of both visual rehabilitation and IOP control. However, patients with ACIOL complications, diabetes, or preoperative IOP of more than 21 mmHg on maximum tolerated medications were prone to requiring additional surgical interventions.