Identification of the molecular signatures integral to regenerating photoreceptors in the retina of the zebra fish

Investigating neuronal and photoreceptor regeneration in the retina of zebra fish has begun to yield insights into both the cellular and molecular means by which this lower vertebrate is able to repair its central nervous system. However, knowledge about the signaling molecules in the local microenvironment of a retinal injury and the transcriptional events they activate during neuronal death and regeneration is still lacking. To identify genes involved in photoreceptor regeneration, we combined light-induced photoreceptor lesions, laser-capture microdissection of the outer nuclear layer (ONL) and analysis of gene expression to characterize transcriptional changes for cells in the ONL as photoreceptors die and are regenerated. Using this approach, we were able to characterize aspects of the molecular signature of injured and dying photoreceptors, cone photoreceptor progenitors, and microglia within the ONL. We validated changes in gene expression and characterized the cellular expression for three novel, extracellular signaling molecules that we hypothesize are involved in regulating regenerative events in the retina

Barbed suture vs conventional tenorrhaphy: biomechanical analysis in an animal model.

BACKGROUND: The advantages of barbed suture for tendon repair could be to eliminate the need for a knot and to better distribute the load throughout the tendon so as to reduce the deformation at the repair site. The purpose of this study was to evaluate the breaking force and the repair site deformation of a new barbed tenorrhaphy technique in an animal model. MATERIALS AND METHODS: Sixty porcine flexor tendons were divided randomly into three groups and repaired with one of the following techniques: a new 4-strand barbed technique using 2/0 polypropylene Quill™ SRS or 2/0 polydioxanone Quill™ SRS and a modified Kessler technique using 3/0 prolene. All tendons underwent mechanical testing to assess the 2-mm gap formation force, the breaking force and the mode of failure. The percentage change in tendon cross-sectional area before and after repair was calculated. RESULTS: The two-sample Student t-test demonstrated a significant increase in 2-mm gap formation force and in breaking force with barbed sutures, independently from suture material, when compared to traditional Kessler suture. Concerning the tendon profile, we registered less bunching at the repair site in the two barbed groups compared with the Kessler group. CONCLUSIONS: This study confirms the promising results achieved in previous ex vivo studies about the use of barbed suture in flexor tendon repair. In our animal model, tenorrhaphy with Quill™ SRS suture guarantees a breaking force of repair that exceeds the 40-50 N suggested as sufficient to initiate early active motion, and a smoother profile at the repair site. LEVEL OF EVIDENCE: Not applicable

Neuroendocrine (Merkel cell) carcinoma of the retroperitoneum with no identifiable primary site

<p>Abstract</p> <p>Background</p> <p>Neuroendocrine carcinoma is an aggressive neoplasm that mainly affects elderly Caucasians and typically arises in sun-exposed areas of the skin. The disease is rather rare and only a relatively few cases present with no apparent primary lesion.</p> <p>Case presentation</p> <p>We report a case of an 81-year-old Caucasian male with neuroendocrine carcinoma, which initially presented as a large retroperitoneal mass. Pathological and immunohistochemical analysis of the transabdominal CT-guided biopsy specimen revealed tissue consistent with neuroendocrine carcinoma. The patient underwent exploratory laparotomy and the mass was successfully excised along with an associated mesenteric lymph node.</p> <p>Discussion</p> <p>There are currently two possible explanations for what occurred in our patient. First, the retroperitoneal mass could be a massively enlarged lymph node where precursor cells became neoplastic. This would be consistent with a presumptive diagnosis of primary nodal disease. Alternatively, an initial skin lesion could have spontaneously regressed and the retroperitoneal mass represents a single site of metastasis. Since Merkel cell precursors have never been identified within lymph nodes, the latter theory seems more befitting. Moreover, metastasis to the retroperitoneal lymph nodes has been reported as relatively common when compared to other sites such as liver, bone, brain and skin.</p> <p>Conclusion</p> <p>Wide local excision of the primary tumor is the surgical treatment of choice for localized disease. We propose that further studies are needed to elucidate the true efficacy of chemotherapy in conventional as well as unconventional patients with neuroendocrine carcinoma.</p

Atmospheric Evolution

Earth's atmosphere has evolved as volatile species cycle between the atmosphere, ocean, biomass and the solid Earth. The geochemical, biological and astrophysical processes that control atmospheric evolution are reviewed from an "Earth Systems" perspective, with a view not only to understanding the history of Earth, but also to generalizing to other solar system planets and exoplanets.Comment: 34 pages, 3 figures, 2 tables. Accepted as a chapter in "Encyclopaedia of Geochemistry", Editor Bill White, Springer-Nature, 201

Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients

<p>Abstract</p> <p>Background</p> <p>Sensorineural hearing loss (SNHL) is one of the major long term side effects from radiation therapy (RT) in nasopharyngeal cancer (NPC) patients. This study aims to review the incidences of SNHL when treating with different radiation techniques. The additional objective is to determine the relationship of the SNHL with the radiation doses delivered to the inner ear.</p> <p>Methods</p> <p>A retrospective cohort study of 134 individual ears from 68 NPC patients, treated with conventional RT and IMRT in combination with chemotherapy from 2004-2008 was performed. Dosimetric data of the cochlea were analyzed. Significant SNHL was defined as > 15 dB increase in bone conduction threshold at 4 kHz and PTA (pure tone average of 0.5, 1, 2 kHz). Relative risk (RR) was used to determine the associated factors with the hearing threshold changes at 4 kHz and PTA.</p> <p>Results</p> <p>Median audiological follow up time was 14 months. The incidence of high frequency (4 kHz) SNHL was 44% for the whole group (48.75% in the conventional RT, 37% with IMRT). Internal auditory canal mean dose of > 50 Gy had shown a trend to increase the risk of high frequency SNHL (RR 2.02 with 95% CI 1.01-4.03, p = 0.047).</p> <p>Conclusion</p> <p>IMRT and radiation dose limitation to the inner ear appeared to decrease SNHL.</p

Resolving the Evolutionary History of Campanula (Campanulaceae) in Western North America

Recent phylogenetic works have begun to address long-standing questions regarding the systematics of Campanula (Campanulaceae). Yet, aspects of the evolutionary history, particularly in northwestern North America, remain unresolved. Thus, our primary goal in this study was to infer the phylogenetic positions of northwestern Campanula species within the greater Campanuloideae tree. We combined new sequence data from 5 markers (atpB, rbcL, matK, and trnL-F regions of the chloroplast and the nuclear ITS) representing 12 species of Campanula with previously published datasets for worldwide campanuloids, allowing us to include approximately 75% of North American Campanuleae in a phylogenetic analysis of the Campanuloideae. Because all but one of North American Campanula species are nested within a single campanuloid subclade (the Rapunculus clade), we conducted a separate set of analyses focused specifically on this group. Our findings show that i) the campanuloids have colonized North America at least 6 times, 4 of which led to radiations, ii) all but one North American campanuloid are nested within the Rapunculus clade, iii) in northwestern North America, a C. piperi – C. lasiocarpa ancestor gave rise to a monophyletic Cordilleran clade that is sister to a clade containing C. rotundifolia, iv) within the Cordilleran clade, C. parryi var. parryi and C. parryi var. idahoensis exhibit a deep, species-level genetic divergence, and v) C. rotundifolia is genetically diverse across its range and polyphyletic. Potential causes of diversification and endemism in northwestern North America are discussed

Merkel cell carcinoma of skin-current controversies and recommendations

The review covers the current recommendations for Merkel cell carcinoma (MCC), with detailed discussion of many controversies. The 2010 AJCC staging system is more in-line with other skin malignancies although more complicated to use. The changes in staging system over time make comparison of studies difficult. A wide excision with margins of 2.5–3 cm is generally recommended. Even for primary </= 1 cm, there is a significant risk of nodal and distant metastases and hence sentinel node biopsy should be done if possible; otherwise adjuvant radiotherapy to the primary and nodal region should be given. Difficulties of setting up trials owing to the rarity of the disease and the mean age of the patient population result in infrequent reports of adjuvant or concurrent chemotherapy in the literature. The benefit, if any, is not great from published studies so far. However, there may be a subgroup of patients with high-risk features, e.g. node-positive and excellent performance status, for whom adjuvant or concurrent chemotherapy may be considered. Since local recurrence and metastases generally occur within 2 years of the initial diagnosis, patients should be followed more frequently in the first 2 years. However delayed recurrence can still occur in a small proportion of patients and long-term follow-up by a specialist is recommended provided that the general condition of the patient allows it. In summary, physician judgment in individual cases of MCC is advisable, to balance the risk of recurrence versus the complications of treatment

Clinical emergence of neurometastatic merkel cell carcinoma: a surgical case series and literature review

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm of possible viral origin and is known for its aggressive behavior. The incidence of MCC has increased in the last 15 years. Merkel cell carcinoma has the potential to metastasize, but rarely involves the central nervous system. Herein, we report three consecutive surgical cases of MCC presenting at a single institution within 1 year. We used intracavitary BCNU wafers (Gliadel®) in two cases. Pathological features, including CK20 positivity, consistent with MCC, were present in all cases. We found 33 published cases of MCC with CNS involvement. We suggest that the incidence of neurometastatic MCC may be increasing, parallel to the increasing incidence of primary MCC. We propose a role for intracavitary BCNU wafers in the treatment of intra-axial neurometastatic MCC