Corneal Neurotization for Neurotrophic Keratopathy: Clinical Outcomes and In Vivo Confocal Microscopic and Histopathological Findings

Purpose: To describe the long-term outcomes and in vivo confocal microscopic (IVCM) and histopathological findings after corneal neurotization surgery. / Methods: We included 2 patients who underwent corneal neurotization surgery for severe unilateral neurotrophic keratopathy secondary to cerebellopontine angle meningioma. Corneal sensation was measured using the Cochet–Bonnet esthesiometer (CBE) (0–60 mm). IVCM was performed using the Heidelberg HRT3 Rostock Corneal Module. Histopathological examination was performed on the excised corneoscleral disc of patient 2. / Results: In patient 1, corneal sensation improved from 0 mm preoperatively to 60 mm in all 4 quadrants by 2 years postoperatively and was maintained at 5 years postoperatively with identifiable subbasal and stromal corneal nerves on IVCM. In patient 2, corneal sensation improved from 0 mm preoperatively to 10 mm in 3 quadrants (9 months postoperatively) but returned to 0 mm in all quadrants by 2 years postoperatively. IVCM failed to identify any subbasal and stromal corneal nerves. At 5 years postoperatively, evisceration was performed to ameliorate uncontrolled and persistent ocular pain and poor cosmesis. Histopathological examination of the excised corneoscleral disc confirmed the presence of normal-sized, central corneal stromal nerve fascicles but without direct continuity with the transplanted perilimbal nerve bundles. / Conclusions: Our study elucidates the mechanism of corneal neurotization surgery at a cellular level. Although only 1 patient achieved long-term improvement in corneal sensation postoperatively, the findings on IVCM and histopathological examination suggest that partial regeneration/maintenance of corneal nerves after corneal neurotization surgery is likely attributed to the paracrine neurotrophic support, instead of direct sprouting, from the perilimbal transplanted nerve fascicles

Yeast axial-element protein, Red1, binds SUMO chains to promote meiotic interhomologue recombination and chromosome synapsis

The synaptonemal complex (SC) is a tripartite protein structure consisting of two parallel axial elements (AEs) and a central region. During meiosis, the SC connects paired homologous chromosomes, promoting interhomologue (IH) recombination. Here, we report that, like the CE component Zip1, Saccharomyces cerevisiae axial-element structural protein, Red1, can bind small ubiquitin-like modifier (SUMO) polymeric chains. The Red1–SUMO chain interaction is dispensable for the initiation of meiotic DNA recombination, but it is essential for Tel1- and Mec1-dependent Hop1 phosphorylation, which ensures IH recombination by preventing the inter-sister chromatid DNA repair pathway. Our results also indicate that Red1 and Zip1 may directly sandwich the SUMO chains to mediate SC assembly. We suggest that Red1 and SUMO chains function together to couple homologous recombination and Mec1–Tel1 kinase activation with chromosome synapsis during yeast meiosis

Pediatric resident and faculty attitudes toward self-assessment and self-directed learning: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The development of self-assessment and self-directed learning skills is essential to lifelong learning and becoming an effective physician. Pediatric residents in the United States are now required to use Individualized Learning Plans (ILPs) to document self-assessment and self-directed learning. A better understanding of resident and faculty attitudes and skills about self-assessment and self-directed learning will allow more successful integration of lifelong learning into residency education. The objective of this study was to compare faculty and resident attitudes, knowledge and skills about self-assessment, self-directed learning and ILPs.</p> <p>Methods</p> <p>Survey of pediatric residents and faculty at a single institution. Respondents rated their attitudes, knowledge, and self-perceived skills surrounding self-assessment, self-directed learning and ILPs.</p> <p>Results</p> <p>Overall survey response rate was 81% (79/97); 100% (36/36) residents and 70% (43/61) faculty. Residents and faculty agreed that lifelong learning is a necessary part of being a physician. Both groups were comfortable with assessing their own strengths and weaknesses and developing specific goals to improve their own performance. However, residents were less likely than faculty to continuously assess their own performance (44% vs. 81%; p < 0.001) or continuously direct their own learning (53% vs. 86%; p < 0.001). Residents were more likely than faculty to believe that residents should be primarily responsible for directing their own learning (64% vs. 19%; p < 0.0001), but at the same time, more residents believed that assigned clinical (31% vs. 0%; p < 0.0001) or curricular (31% vs. 0%; p < 0.0001) experiences were sufficient to make them competent physicians. Interns were less likely than senior residents to have a good understanding of how to assess their own skills (8% vs. 58%; p = 0.004) or what it means to be a self-directed learner (50% vs. 83%; p = 0.04).</p> <p>Qualitative comments indicated that while ILPs have the potential to help learners develop individualized, goal-directed learning plans based on strengths and weaknesses, successful implementation will require dedicated time and resident and faculty development.</p> <p>Conclusion</p> <p>These findings suggest that training and experience are necessary for physicians to understand the role of self-directed learning in education. Deliberate practice, for example by requiring residents to use ILPs, may facilitate self-directed, lifelong learning.</p

Electrospun ZnO Nanowires as Gas Sensors for Ethanol Detection

ZnO nanowires were produced using an electrospinning method and used in gas sensors for the detection of ethanol at 220 °C. This electrospinning technique allows the direct placement of ZnO nanowires during their synthesis to bridge the sensor electrodes. An excellent sensitivity of nearly 90% was obtained at a low ethanol concentration of 10 ppm, and the rest obtained at higher ethanol concentrations, up to 600 ppm, all equal to or greater than 90%

Constitutively Nuclear FOXO3a Localization Predicts Poor Survival and Promotes Akt Phosphorylation in Breast Cancer

Background: The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis. Methodology/Principal Findings: Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway. Conclusions/Significance: Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell death or cell cycle arrest. As such, sustained nuclear FOXO3a expression in breast cancer may culminate in cancer progression and the development of an aggressive phenotype similar to that observed in cytotoxic chemotherapy resistant breast cancer cell models. © 2010 Chen et al.published_or_final_versio

Reining in uncontrolled inflammasome with PKA

During the course of infection, the detection of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) by pattern-recognition receptors (PRRs) can lead to inflammasome formation, with subsequent activation of ccaspase-1, secretion of interleukin 1β (IL-1β) and IL-18, and cell death via pyroptosis. However, this process must be tightly controlled, as uncontrolled inflammasome activation can lead to a plethora of disease outcomes. In this issue, Mortimer et al. describe how phosphorylation of the PRR NLRP3 by the kinase PKA, after inflammasome activation, attenuates the inflammasome to halt the inflammatory response3. Gain-of-function mutations in the gene encoding NLRP3 cause a family of related autoimmune disorders called ‘CAPS’ (‘cryopyrin-associated periodic syndrome’) that result in aberrant activation of the NLRP3 inflammasome with uncontrolled secretion of IL-1β and IL-18. The authors also provide insight into why some of the NLRP3 mutations that induce CAPS drive unregulated activation of the inflammasome

Fostering Critical Thinking, Reasoning, and Argumentation Skills through Bioethics Education

Developing a position on a socio-scientific issue and defending it using a well-reasoned justification involves complex cognitive skills that are challenging to both teach and assess. Our work centers on instructional strategies for fostering critical thinking skills in high school students using bioethical case studies, decision-making frameworks, and structured analysis tools to scaffold student argumentation. In this study, we examined the effects of our teacher professional development and curricular materials on the ability of high school students to analyze a bioethical case study and develop a strong position. We focused on student ability to identify an ethical question, consider stakeholders and their values, incorporate relevant scientific facts and content, address ethical principles, and consider the strengths and weaknesses of alternate solutions. 431 students and 12 teachers participated in a research study using teacher cohorts for comparison purposes. The first cohort received professional development and used the curriculum with their students; the second did not receive professional development until after their participation in the study and did not use the curriculum. In order to assess the acquisition of higher-order justification skills, students were asked to analyze a case study and develop a well-reasoned written position. We evaluated statements using a scoring rubric and found highly significant differences (p<0.001) between students exposed to the curriculum strategies and those who were not. Students also showed highly significant gains (p<0.001) in self-reported interest in science content, ability to analyze socio-scientific issues, awareness of ethical issues, ability to listen to and discuss viewpoints different from their own, and understanding of the relationship between science and society. Our results demonstrate that incorporating ethical dilemmas into the classroom is one strategy for increasing student motivation and engagement with science content, while promoting reasoning and justification skills that help prepare an informed citizenry

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)