Characterization and predictive value of volume changes of extremity and pelvis soft tissue sarcomas during radiation therapy prior to definitive wide excision

PURPOSE: The purpose of this study was to characterize and evaluate the clinical significance of volume changes of soft tissue sarcomas during radiation therapy (RT), prior to definitive surgical resection. MATERIALS AND METHODS: Patients with extremity or pelvis soft tissue sarcomas treated at our institution from 2013 to 2016 with RT prior to resection were identified retrospectively. Tumor volumes were measured using cone-beam computed tomography obtained daily during RT. Linear regression evaluated the linearity of volume changes. Kruskal-Wallis tests, Mann-Whitney U tests, and linear regression evaluated predictors of volume change. Logistic and Cox regression evaluated volume change as a predictor of resection margin status, histologic treatment response, and tumor recurrence. RESULTS: Thirty-three patients were evaluated. Twenty-nine tumors were high grade. Prior to RT, median tumor volume was 189 mL (range, 7.2 to 4,885 mL). Sixteen tumors demonstrated significant linear volume changes during RT. Of these, 5 tumors increased and 11 decreased in volume. Myxoid liposarcoma (n = 5, 15%) predicted decreasing tumor volume (p = 0.0002). Sequential chemoradiation (n = 4, 12%) predicted increasing tumor volume (p = 0.008) and corresponded to longer times from diagnosis to RT (p = 0.01). Resection margins were positive in three cases. Five patients experienced local recurrence, and 7 experienced distant recurrence, at median 8.9 and 6.9 months post-resection, respectively. Volume changes did not predict resection margin status, local recurrence, or distant recurrence. CONCLUSION: Volume changes of pelvis and extremity soft tissue sarcomas followed linear trends during RT. Volume changes reflected histologic subtype and treatment characteristics but did not predict margin status or recurrence after resection.

Variáveis morfogênicas e estruturais de sorgo forrageiro implantado com diferentes arranjos populacionais sob pastoreio contínuo / Morphogenetic and structural variables of sorghum implanted with different population arrangements under continuous grazing

O objetivo do estudo foi avaliar os efeitos da utilização de diferentes arranjos populacionais na implantação de sorgo forrageiro nas características morfogênicas e estruturais do pasto. Os tratamentos foram 22 ou 44cm entrelinhas e 12 ou 24kg de sementes ha-1. O método de pastoreio foi contínuo. Foram utilizadas 36 novilhas, com idade e peso corporal médios de 15 meses de 262kg. As variáveis morfogênicas não foram influenciadas significativamente (P>0,05) pelos arranjos populacionais e pelos períodos de avaliação, sendo obtidos taxa de alongamento e senescência foliar de 1,43 e 1,11cm dia-1afilho-1, respectivamente, taxa de aparecimento foliar e intervalo de surgimento de folhas de 0,28 folhas dia-1afilho-1 e 3,81 dias, filocrono e duração de vida foliar de 72,99 e 351,68 graus dia, nessa ordem. As características estruturais do pasto foram influenciadas pelos períodos de avaliação. Do primeiro para o terceiro período de avaliação, foi verificada uma redução de 65,53% no número de folhas em alongamento e de 47,79% no número de folhas vivas.(AU)

The objective of the study was to evaluate the effects of using different population arrangements in the implementation of sorghum in the morphogenetic and structural characteristics of the pasture. The treatments were 22 or 44cm between rows and 12 or 24kg ha-1 of seed. The grazing method was continuous. The sample consisted of 36 heifers with an average age of 15 months and average body weight of 262kg. Morphogenic variables were not significantly influenced (P>0.05) by population arrangements and evaluation periods, elongation rate and leaf senescence of 1.43 and 1.11cm afilho-1 day-1 being obtained, respectively, and leaf appearance rate of leaf appearance leaves the range of 0.28 day-1 and 1afilho 3.81 days, phyllochron and leaf duration of life of 72.99 and 351.68 degree day, in that order. The structural characteristics of the pasture were influenced by evaluation periods. From the first to the third evaluation period, a reduction of 65.53% in the number of leaves in stretching and 47.79% in the number of living leaves was verified.(AU)

Fate of Outstanding COIDA Occupational Disease Claims Following Closure of the Western Cape Provincial Medical Advisory Panel in 2008 : An audit

Background and objectives: The Western Cape Provincial Medical Advisory Panel (PMAP) was established in 2004 in terms of Section 70(1) of COIDA. A primary function was to improve the efficiency of medical assessment of occupational disease claims. The PMAP was closed by the Compensation Commissioner in 2008. This audit aimed to determine the fate of claims outstanding at the time of closure. Methods: A total of 68 claims outstanding in April 2008 were followed up by telephone; email and/or internet to determine what proportion had progressed or; if accepted; had resulted in a permanent disablement compensation payment. Results: Of the 68 claims; 31 (44) were confirmed as having progressed. Of these; payment of permanent disablement awards could be confirmed in only 15 claims (22). The remaining 56 either showed no progress or no longer had a record in the COIDA system. Those stages of the claims process that had previously been aided by PMAP functioning had deteriorated in efficiency. Conclusions: Overall; the low proportion of outstanding claims finalised and awarded is consistent with inefficiency in claims handling of occupational disease; a finding echoed by recent complaints about general Compensation Fund performance from both healthcare providers and parliamentary investigation

Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification

The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.

Incentive structure in team-based learning: graded versus ungraded Group Application exercises / 보건의료교육평가

PURPOSE: Previous studies on team-based learning (TBL) in medical education demonstrated improved learner engagement, learner satisfaction, and academic performance; however, a paucity of information exists on modifications of the incentive structure of "traditional" TBL practices. The current study investigates the impact of modification to conventional Group Application exercises by examining student preference and student perceptions of TBL outcomes when Group Application exercises are excluded from TBL grades. METHODS: During the 2009-2010 and 2010-2011 academic years, 175 students (95.6% response rate) completed a 22-item multiple choice survey followed by 3 open response questions at the end of their second year of medical school. These students had participated in a TBL supplemented preclinical curriculum with graded Group Application exercises during year one and ungraded Group Application exercises during year two of medical school. RESULTS: Chi-square analyses showed significant differences between grading categories for general assessment of TBL, participation and communication, intra-team discussion, inter-team discussion, student perceptions of their own effort and development of teamwork skills. Furthermore, 83.8% of students polled prefer ungraded Group Application exercises with only 7.2% preferring graded and 9.0% indicating no preference. CONCLUSION: The use of ungraded Group Application exercises appears to be a successful modification of TBL, making it more "student-friendly" while maintaining the goals of active learning and development of teamwork skills.

Pharmacognostic and phytochemical studies on Ayurvedic drugs Ativisha and Musta

The study include the establishment of pharmacognostic and phytochemical characters of Ativisha (Aconitum heterophyllum Wall. ex Royle, Ranunculaceae) and to compare them with its substitutes, Cyperus rotundus L. (Musta), C. scariosus R. Br., Cyperaceae, and Cryptocoryne spiralis (Retz.) Fisch. ex Wydler, Araceae (Country Ativisha). Morphology of the four species was compared in authentic samples collected from the field. We performed histological, histochemical, phytochemical tests, using standard protocols. HPLC studies were done on aqueous extracts of samples in a Shimadzu HPLC system and the peaks were observed at 254 nm. Pharmacognostic characterization of Ativisha and others was done as completely as possible. On basis of histochemical analyses revealed the presence of alkaloid, terpenoid-alkaloid complex, lipids and calcium oxalate majorly. There was less than 50% similarity between Ativisha and the other three species in microscopic characters. There was greater similarity (87%) between the two Cyperus species. The phytochemical studies, on the other hand, showed less similarity (79.2%) between the two Cyperus species. There was greater phytochemical similarity (84.6%) between Aconitum and Cryptocoryne, which justifies the name "Country Ativisha" for the latter. Based on anatomical and histochemical analysis, structural as well as chemical parameters helpful in distinguishing Ativisha from the other three species were established. The phytochemical profiles showed that A. heterophyllum and Cyperus species have five common HPLC peaks which may explain some of their common therapeutic activities. Ativisha and Cryptocoryne show greater phytochemical similarities to one another and this explains why the latter is used in Siddha system of medicine as country Ativisha.

Perspectives on the role of mTORC2 in B lymphocyte development, immunity and tumorigenesis

Mammalian target of rapamycin complex 2 (mTORC2) is a key downstream mediator of phosphoinositol-3-kinase (PI3K) dependent growth factor signaling. In lymphocytes, mTORC2 has emerged as an important regulator of cell development, homeostasis and immune responses. However, our current understanding of mTORC2 functions and the molecular mechanisms regulating mTORC2 signaling in B and T cells are still largely incomplete. Recent studies have begun to shed light on this important pathway. We have previously reported that mTORC2 mediates growth factor dependent phosphorylation of Akt and facilitates Akt dependent phosphorylation and inactivation of transcription factors FoxO1 and FoxO3a. We have recently explored the functions of mTORC2 in B cells and show that mTORC2 plays a key role in regulating survival and immunoglobulin (Ig) gene recombination of bone marrow B cells through an Akt2-FoxO1 dependent mechanism. Ig recombination is suppressed in proliferating B cells to ensure that DNA double strand breaks are not generated in actively dividing cells. Our results raise the possibility that genetic or pharmacologic inhibition of mTORC2 may promote B cell tumor development as a result of inefficient suppression of Ig recombination in dividing B cells. We also propose a novel strategy to treat cancers based on our recent discovery that mTORC2 regulates Akt protein stability.