Definitive chemoradiation in non metastatic squamous cell carcinoma anal canal: a single institution experience

Background: To analyze the oncological outcomes in anal canal squamous cell carcinoma treated with concurrent chemoradiotherapy. Materials and Methods: A single centre retrospective hospital based study with sample size of 51 patients of anal canal Squamous cell carcinoma treated with concurrent chemoradiotherapy with mitomycin @10mg/m2 and 5FU based. Disease free survival (DFS), Colostomy free survival (CFS) and Overall survival (OS) rates were calculated by Kaplan-Meier method. Results: Among 51 eligible patients, after a median follow up of 46 months (range 10-68 months). The 3year Disease free survival (DFS) was 73.9%. 3patients developed locoregional recurrence while 1patient developed distant metastasis. At 3 years Overall survival (OS) rate was 77%. Out of 44 patients 6 patients lost to follow up while 2 patients died due to progressive disease and 2 due to non cancer causes. 3year Colostomy free survival (CFS) rate was 59%. Total 18 out of 44 patients underwent colostomy. No grade 3 or 4 late toxicities occurred after completion of treatment. Conclusion: This study concluded that definitive chemoradiotherapy achieves good local control, overall survival and colostomy free survival with acceptable toxicity and can be recommended as standard treatment in patients with carcinoma anal canal

Dosimetric study for mastectomy carcinoma left breast cases with volumetric modulated arc therapy (VMAT)

Background: Radiation therapy for breast cancer has evolved from conventional to 3-dimentional radiation therapy (3-DCRT) and through more precise IMRT and VMAT. 3-DCRT is preferred for ca breast treatment as it reduces low dose area in contra lateral lung but with the advances in radiotherapy image guided techniques can deliver precise and lower doses to OARs with better coverage. This study is aimed to evaluate the doses of PTV, heart and ipsi-lateral lung with contra lateral lung doses delivered by VMAT technique. Method and material: Total 10 patients of carcinoma left breast with mastectomy were selected for VMAT planning with prescription of 45 Gy/20#. Eclipse 16.1 treatment planning system was used and treatment was delivered by True Beam with 6 MV photon energy with image guidance. The VMAT technique includes the non-continuous partial arc and continuous partial arc to deliver the dose. Dose volume histogram (DVH) was used to analyze for doses of planning target volume (PTV) and organs at risk (OARs). Results: PTV was covered with average 94.96% of prescribed dose. The average homogeneity index was found 0.02 and average conformity index was found 0.97 for VMAT plans. Mean doses for heart were measured 14.49±2.11Gy and for V25Gy 11.16±1.97Gy. Ipsilateral lung mean doses were observed 16.23±1.01 Gy, V20Gy doses were 28.73±1.52Gy, V30Gy doses were 14.78±2.5Gy and V40Gy doses were 5.59±1.98Gy. The contralateral lung mean doses were reported 7.69±1.79Gy and V10Gy 19.05±2.05Gy. Average planning target volume was 1710.98cc. The average homogeneity index was 0.02 and conformity index was 0.96. Conclusion: OARs doses with the use of VMAT with continuous and partial arcs are within limit and PTV coverage was also satisfactory. The contralateral lung doses were also within limit. For more precise treatment and low doses of heart and contra lateral lung VMAT technique can be preferred for carcinoma left breast treatment

Dosimetric and volumetric analysis in endobronchial brachytherapy treatment of carcinoma lung patients: A pilot study

Background: To analyze the radiation doses received by Organ at Risk (OAR) nearby the target volume and volumetric changes in the target volume in carcinoma lung patients irradiated in three treatment session of endobronchial brachytherapy (EBBT). Methods: Dosimetric analysis was conducted on patients of carcinoma Lung received three session of Endobronchial brachytherapy treatment in High Dose Rate brachytherapy unit with Ir-192 source. A flexible Lumencare catheter was inserted into the bronchus and positioned catheter tip at the tumor. Length of the implanted catheter was measured with the source position simulator device. Acquired three dimensional CT image data set with x-ray marker was sent to TPS to generate an optimized treatment plan. The OAR’s and target volume were delineated for the accurate assessment of doses in each brachytherapy treatment session. The prescribed dose was normalization at 1.0cm from the center of the catheter. Doses to OAR’s and target volume were noted down from the DVH and detailed dose volume table from TPS. The prescribed dose was 7Gy per fraction in three fractions. Doses to OAR’s and Target volumes were also evaluated for each treatment session of the patient. The change in the volume of the target irradiated was noted down from the dose volume table in TPS. Results: Thirty sessions were evaluated in this study as these were infrequent procedures to perform. Average mean dose to Esophagus was varied from 1.18Grey to 0.85Grey, average maximum dose to Heart was varied from 4.77Grey to 3.69Grey and average maximum dose to left coronary artery was varied from 0.44Grey to 0.91Grey. Average changes in the volume of a Target volume was found in varied from 20.45cc to 13.70cc in each treatment session and found there is signification volume reduction in the target volume irradiated. Conclusion: This study showed that the doses to OARs are significantly increased in second and third session of EBBT and the doses to OAR’s were in their tolerance limit. There is a significant volume reduction in volume of the target in second and third treatment EBBT session. It implies that the EBBT is much effective in the treatment of lung carcinoma patients having disease lesion in primary and secondary bronchus

Comparison of Rates of Fast and Catastrophic Visual Field Loss in Three Glaucoma Subtypes.

Purpose:To compare the distribution of visual field progression rates in three subgroups of glaucoma, being primary angle-closure glaucoma (PACG), POAG, and juvenile open-angle glaucoma (JOAG). Methods:We assessed glaucoma patients treated in an Indian tertiary care setting with at least four visual field assessments. We determined rates from a single eye of each of 525 patients using linear regression of the summary index mean deviation (MD) over time. The main outcome measures were the proportions of fast (<-1.0 to -2.0 dB/y) and catastrophic (<-2 dB/y) visual field progression. Bootstrapped 95% CIs allowed comparison with published data from a large clinical cohort in Canada. Results:The combined proportion of fast and catastrophic progressors in our cohort was less than half that in the Canada dataset (2.3% vs. 5.8%), despite median progression rates differing by only 0.03 dB/y. PACG, POAG, and JOAG represented 45%, 32%, and 12% of our cohort, respectively. Baseline MD values were similarly distributed between these subtypes. All subtypes showed a similar shaped distribution for progression rates, with median progression rates of -0.03, -0.05, and 0.02 dB/y for PACG, POAG, and JOAG, respectively. Combined proportions of fast and catastrophic progression rates did not significantly differ between subtypes. Conclusions:Differences in fast and catastrophic visual field progression can exist despite only small changes in median progression rates, highlighting the importance of considering the full shape of the progression rate distribution when comparing the risk of devastating visual field loss

MAdCAM-1-Mediated Intestinal Lymphocyte Homing Is Critical for the Development of Active Experimental Autoimmune Encephalomyelitis

Lymphocyte homing into the intestine is mediated by binding of leukocytes to mucosal addressin cell adhesion molecule 1 (MAdCAM-1), expressed on endothelial cells. Currently, the immune system of the gut is considered a major modulator not only of inflammatory bowel disease, but also of extra-intestinal autoimmune disorders, including multiple sclerosis (MS). Despite intense research in this field, the exact role of the intestine in the pathogenesis of (neuro-)inflammatory disease conditions remains to be clarified. This prompted us to investigate the role of MAdCAM-1 in immunological processes in the intestine during T cell-mediated autoimmunity of the central nervous system (CNS). Using the experimental autoimmune encephalomyelitis model of MS, we show that MAdCAM-1-deficient (MAdCAM-1-KO) mice are less susceptible to actively MOG35−55-induced disease. Protection from disease was accompanied by decreased numbers of immune cells in the lamina propria and Peyer's patches as well as reduced immune cell infiltration into the spinal cord. MOG35−55-recall responses were intact in other secondary lymphoid organs of MAdCAM-1-KO mice. The composition of specific bacterial groups within the microbiome did not differ between MAdCAM-1-KO mice and controls, while MAdCAM-1-deficiency severely impaired migration of MOG35−55-activated lymphocytes to the gut. Our data indicate a critical role of MAdCAM-1 in the development of CNS inflammation by regulating lymphocyte homing to the intestine, and may suggest a role for the intestinal tract in educating lymphocytes to become encephalitogenic

Non-monotonic changes in clonogenic cell survival induced by disulphonated aluminum phthalocyanine photodynamic treatment in a human glioma cell line

<p>Abstract</p> <p>Background</p> <p>Photodynamic therapy (PDT) involves excitation of sensitizer molecules by visible light in the presence of molecular oxygen, thereby generating reactive oxygen species (ROS) through electron/energy transfer processes. The ROS, thus produced can cause damage to both the structure and the function of the cellular constituents resulting in cell death. Our preliminary investigations of dose-response relationships in a human glioma cell line (BMG-1) showed that disulphonated aluminum phthalocyanine (AlPcS₂) photodynamically induced loss of cell survival in a concentration dependent manner up to 1 μM, further increases in AlPcS₂concentration (>1 μM) were, however, observed to decrease the photodynamic toxicity. Considering the fact that for most photosensitizers only monotonic dose-response (survival) relationships have been reported, this result was unexpected. The present studies were, therefore, undertaken to further investigate the concentration dependent photodynamic effects of AlPcS₂.</p> <p>Methods</p> <p>Concentration-dependent cellular uptake, sub-cellular localization, proliferation and photodynamic effects of AlPcS₂were investigated in BMG-1 cells by absorbance and fluorescence measurements, image analysis, cell counting and colony forming assays, flow cytometry and micronuclei formation respectively.</p> <p>Results</p> <p>The cellular uptake as a function of extra-cellular AlPcS₂concentrations was observed to be biphasic. AlPcS₂was distributed throughout the cytoplasm with intense fluorescence in the perinuclear regions at a concentration of 1 μM, while a weak diffuse fluorescence was observed at higher concentrations. A concentration-dependent decrease in cell proliferation with accumulation of cells in G₂+M phase was observed after PDT. The response of clonogenic survival after AlPcS₂-PDT was non-monotonic with respect to AlPcS₂concentration.</p> <p>Conclusions</p> <p>Based on the results we conclude that concentration-dependent changes in physico-chemical properties of sensitizer such as aggregation may influence intracellular transport and localization of photosensitizer. Consequent modifications in the photodynamic induction of lesions and their repair leading to different modes of cell death may contribute to the observed non-linear effects.</p

Pseudorabies Virus Infection Alters Neuronal Activity and Connectivity In Vitro

Alpha-herpesviruses, including human herpes simplex virus 1 & 2, varicella zoster virus and the swine pseudorabies virus (PRV), infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP) firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural function seen in PRV-infected animals

Scholarly Impact: A Pluralistic Conceptualisation.

We critically assess a common approach to scholarly impact that relies almost exclusively on a single stakeholder (i.e., other academics). We argue that this approach is narrow and insufficient, and thereby threatens the credibility and long-term sustainability of the management research community. We offer a solution in the form of a broader and novel conceptual and measurement framework of scholarly impact: a pluralist perspective. It proposes actions that depart from the current win–lose and zero-sum views that lead to false trade-offs such as research versus practice, rigor versus relevance, and research versus service. Our proposed pluralist conceptualization can be instrumental in enabling business schools and other academic units to clarify their strategic direction in terms of which stakeholders they are trying to affect and why, the way future scholars are trained, and the design and implementation of faculty performance management systems. We argue that the adoption of a pluralist conceptualization of scholarly impact can increase motivation for engaged scholarship and design-science research that is more conducive to actionable knowledge as opposed to exclusive career-focused advances, enhance the relevance and value of our scholarship, and thereby help to narrow the much-lamented chasm between research and practice

Open angle glaucoma as a manifestation of Waardenburg&#x2032;s syndrome.

Waardenburg&#x2032;s syndrome is a rare, autosomal dominant disorder, with several clinical signs, each with variable penetrance. We report this case of Waardenburg&#x2032;s syndrome with bilateral open-angle glaucoma with unique gonioscopic findings