BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer

1. Download high-res image (188KB)
2. Download full-size image

     

Patient and surgeon experience with the endotine forehead device for brow and forehead lift

PURPOSE:: To report our experience with the Endotine forehead fixation device (Coapt Systems, Palo Alto, CA, U.S.A.), a bioabsorbable fixation method for forehead and brow lift. METHODS:: Retrospective noncomparative case series of 31 patients who underwent forehead and brow lift surgery using the Endotine device in a single center during a 12-month period from 2004 to 2005. RESULTS: A mean brow lift of 2.8 mm (SD, 0.2-7.1 mm) was achieved. There were no cases of recurrence during the follow-up period of 4 months to 22 months. Problems encountered included palpability, tenderness, and numbness. In the majority of cases, these symptoms resolved within a few months and were not troublesome to the patient. Other problems included visible lumps, device mobility, and exacerbation of a high hairline. Patient satisfaction was high, with 95.3% of patients saying they were either happy or very happy with the results; 81% of patients said they would recommend the Endotine as a method of fixation. All surgeons were pleased by the lift achieved and felt the device was easy to use. Problems reported by the surgeons included 1 dislocated device, discomfort, palpability beyond 15 months, a lack of lateral compared with central lift, and cost. Two of the 3 surgeons are still using the Endotine device as the preferred method of fixation. CONCLUSIONS:: The Endotine device is effective, safe, and easy to use, and has high patient satisfaction. Problems included numbness, tenderness, and palpability. A preference for other fixation methods was indicated by some because of cost, length of surgery, and the amount of lift achieved.     

Statin-induced necrotizing autoimmune myopathy: a systematic review

Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.     

Structural,Magnetic, and Electrical Properties of CoFe2O4 Nanostructures Synthesized Using Microwave-Assisted Hydrothermal Method

Magnetic nanostructures of CoFe₂O₄ were synthesized via a microwave-assisted hydrothermal route. The prepared nanostructures were investigated using X-ray diffraction (XRD), field emission electron microscopy (FE-SEM), energy dispersive X-ray (EDX) spectroscopy, high-resolution transmission electron microscopy (HR-TEM), selective area electron diffraction (SAED) pattern, DC magnetization, and dielectric spectroscopy measurements. The crystal structure studied using HR-TEM, SAED, and XRD patterns revealed that the synthesized nanostructures had a single-phase nature and ruled out the possibility of any secondary phase. The lattice parameters and unit cell volume determined from the XRD data were found to be 8.4821 Å and 583.88 ų. The average crystallite size (~7.0 nm) was determined using Scherrer’s equation. The FE-SEM and TEM micrographs revealed that the prepared nanostructures had a spherical shape morphology. The EDX results showed that the major elements present in the samples were Co, Fe, and O. The magnetization (M) versus temperature (T) measurements specified that the CoFe₂O₄ nanostructures showed ferromagnetic ordering at room temperature. The blocking temperature (T_B) determined using the M-T curve was found to be 315 K. The magnetic hysteresis (M-H) loop of the CoFe₂O₄ nanostructures recorded at different temperatures showed the ferromagnetic behavior of the CoFe₂O₄ nanostructures at temperatures of 200 K and 300 K, and a superparamagnetic behavior at 350 K. The dielectric spectroscopy studies revealed a dielectric constant (ε′) and loss tangent (tanδ) decrease with the increase in the frequency, as well as demonstrating a normal dispersion behavior, which is due to the Maxwell–Wagner type of interfacial polarization. The values of ε′ and tanδ were observed to increase with the increase in the temperature.     

Evaluation of antifungal susceptibility and clinical characteristics in fungal keratitis in a tertiary care center in North India

Purpose:To study the antifungal susceptibility of common corneal pathogenic fungi to antifungal agents in the North Indian population.Methods:Prospective study of the antifungal sensitivity testing (natamycin, amphotericin B, voriconazole, itraconazole, fluconazole, posaconazole, caspofungin, micafungin) of fungal isolates from 50 cases of culture positive fungal keratitis by using E test method. Details noted included demographic data, visual acuity, clinical details, grade of keratitis, healing time, and success in medical management.Results:Of 50 patients with fungal keratitis (mean age: 40.28 ± 16.77 years), 12 eyes healed within 3 weeks, 14 had a delayed healing response, and 24 had chronic keratitis. Among the 15 cases of Fusarium isolates, 93.3% were sensitive to natamycin, while 40% to amphotericin B; 66.6% to voriconazole, 13.4% to itraconazole and fluconazole each. 80% of Fusarium cases (n = 12) showed susceptibility to posaconazole. Among Aspergillus flavus isolates, 53.4% (n = 8) were sensitive to natamycin, with only 40% (n = 7) showing sensitivity to amphotericin B and good susceptibility to azoles. MIC against susceptible Fusarium spp. for natamycin was 3–16 µg/mL, amphotericin B: 1–8 µg/mL, voriconazole: 0.5–1.5 µg/mL, itraconazole: 0.5–12 µg/mL, posaconazole: 0.094–1.5 µg/mL. MIC against Aspergillus flavus was natamycin: 8–32 µg/mL, amphotericin B: 0.5–16 µg/mL, voriconazole: 0.025–4 µg/mL, itraconazole: 0.125–8 µg/mL, posaconazole: 0.047–0.25 µg/mL; against Aspergillus niger isolates, to natamycin was 6 µg/mL (n=1), amphotericin B 8–12 µg/mL (n = 3), voriconazole: 0.125–0.19 µg/mL (n = 3), itraconazole: 0.38–0.75 µg/mL, posaconazole: 0.064–0.19 µg/mL and against Aspergillus fumigatus (n = 1), was natamycin4 µg/mL, amphotericin B - 8 µg/mL, voriconazole 0.25 µg/mL, itraconazole 1 µg/mL, and posaconazole 0.19 µg/mL. MIC against susceptible Acremonium spp. for natamycin was 1.5–16 µg/mL, amphotericin B: 0.5–8 µg/mL, voriconazole: 0.19–3 µg/mL, itraconazole: 0.125 µg/mL, posaconazole: 0.125–0.5 µg/mL and against susceptible Curvularia was natamycin 0.75–4 µg/mL, amphotericin B 0.5–1 µg/mL, voriconazole 0.125–0.19 µg/mL, itraconazole 0.047–0.094 µg/mL, posaconazole 0.047–0.094 µg/mL. MIC against Mucor spp.+ Rhizopus spp. (n = 1) was natamycin: 8 µg/mL, amphotericin B: 0.75 µg/mL, posaconazole: 1.5 µg/mL. MIC against of Alternaria (n = 1) was voriconazole: 0.19 µg/mL, posaconazole: 0.094 µg/mL. MIC against Penicillium (n=1) was natamycin: 8 µg/mL, voriconazole: 0.25 µg/mL, itraconazole: 0.5 µg/mL, and Posaconazole: 0.125 µg/mL.Conclusion:Our observations highlight the variations in susceptibility to antifungal agents. Posaconazole seems to be effective with low MIC against common corneal pathogenic fungal isolates.     

Pharmacological conversion of gut epithelial cells into insulin-producing cells lowers glycemia in diabetic animals

As a highly regenerative organ, the intestine is a promising source for cellular reprogramming for replacing lost pancreatic β cells in diabetes. Gut enterochromaffin cells can be converted to insulin-producing cells by forkhead box O1 (FoxO1) ablation, but their numbers are limited. In this study, we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine. Accordingly, lineage-tracing experiments show that, upon genetic or pharmacologic FoxO1 ablation, the Paneth/goblet lineage can also undergo conversion to the insulin lineage. We designed a screening platform in gut organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process in mice and human adult intestinal organoids. We identified a triple blockade of FOXO1, Notch, and TGF-β that, when tested in insulin-deficient streptozotocin (STZ) or NOD diabetic animals, resulted in near normalization of glucose levels, associated with the generation of intestinal insulin-producing cells. The findings illustrate a therapeutic approach for replacing insulin treatment in diabetes.     

Orthostatic Hypotension and Falls in Older Adults: A Systematic Review and Meta-analysis

ObjectivesOrthostatic hypotension is a potential risk factor for falls in older adults, but existing evidence on this relationship is inconclusive. This study addresses the association between orthostatic hypotension and falls.DesignSystematic review and meta-analysis of the cross-sectional and longitudinal studies assessing the association between orthostatic hypotension and falls, as preregistered in the PROSPERO database (CRD42017060134).Setting and participantsA literature search was performed on February 20, 2017, in MEDLINE (from 1946), PubMed (from 1966), and EMBASE (from 1947) using the terms orthostatic hypotension, postural hypotension, and falls. References of included studies were screened for other eligible studies. Study selection was performed independently by 2 reviewers using the following inclusion criteria: published in English; mean/median age of the population ≥65 years; blood pressure measurement before and after postural change; and assessment of the association of orthostatic hypotension with falls. The following studies were excluded: conference abstracts, case reports, reviews, and editorials. Data extraction was performed independently by 2 reviewers.MeasuresUnadjusted odds ratios of the association between orthostatic hypotension and falls were used for pooling using a random effects model. Studies were rated as high, moderate, or low quality using the Newcastle-Ottawa Scale.ResultsOut of 5646 studies, 63 studies (51,800 individuals) were included in the systematic review and 50 studies (49,164 individuals) in the meta-analysis. Out of 63 studies, 39 were cross-sectional and 24 were longitudinal. Orthostatic hypotension was positively associated with falls (odds ratio 1.73, 95% confidence interval 1.50-1.99). The result was independent of study population, study design, study quality, orthostatic hypotension definition, and blood pressure measurement method.Conclusions and implicationsOrthostatic hypotension is significantly positively associated with falls in older adults, underpinning the clinical relevance to test for an orthostatic blood pressure drop and highlighting the need to investigate orthostatic hypotension treatment to potentially reduce falls.