Novel molecular targets in gastric adenocarcinoma.

Gastric adenocarcinoma (GAC) is the third leading cause of cancer-related death worldwide. A high mortality rate and resistance to treatment protocols due to a heterogeneous molecular pathogenesis has made discovering the key etiologic molecular alterations of the utmost importance. The remarkable role played by epigenetic modifications in repressing or activating many cancer-related genes and forming new epigenetic signatures can affect cancer initiation and progression. Hence, targeting the key epigenetic drivers could potentially attenuate cancer progression. MLLs, ARID1A and EZH2 are among the major epigenetic players that are frequently mutated in GACs. In this paper, we have proposed the existence of a network between these proteins that, together with PCAF and KDM6A, control the 3D chromatin structure and regulate the expression of tumor suppressor genes (TSGs) and oncogenes in GAC. Therefore, we suggest that manipulating the expression of EZH2, PCAF, and KDM6A or their downstream targets may reduce the cancerous phenotype in GAC

Subtenon carboplatin in the management of intraocular retinoblastoma

Purpose: To evaluate the efficacy of adjuvant subtenon carboplatin in the management of intraocular retinoblastoma. Methods: This study was conducted as a randomized, double-masked clinical trial. A diagnosis of intraocular retinoblastoma was made based on clinical examination, ultrasonography and orbital CT-scanning. The greatest basal dimension of the tumors was estimated in disc diameter (DD) by indirect ophthalmoscopy. Tumor thickness was determined by ultrasonography. Each eye was assigned to one of 10 blocks based on tumor stage (Reese-Ellsworth classification) and randomly received systemic chemotherapy alone (control group) or systemic chemotherapy plus 20mg subtenon carboplatin (case group). Indirect laser photocoagulation or cryotherapy was performed as additional treatment. Results: The study included 35 tumors in 17 eyes of 14 patients (19 tumors in 8 eyes in the control group and 16 tumors in 9 eyes in the case group). There was 57.22 and 61.73 decrease in tumor thickness in the control and case groups, respectively. This difference was not statistically significant (P=0.12). The decrease in greatest basal tumor dimension in the control group (47.32) was not significantly different from that in the case group (38.80). One eye (12.5) in the control group and 3 eyes (33.3) in the case group were enucleated. Conclusion: Adjuvant subtenon carboplatin does not seem to increase the efficacy of systemic chemotherapy in the treatment of intraocular retinoblastoma

EVALUATING EXTENSIVE SHEEP FARMING SYSTEMS

Data from each of 5 commercial, extensive sheep farms in Cumbria, UK were used as parameters in a linear program (LP) representing labour and grazing management in such farming systems. The LP maximised ewe enterprise gross margin subject to constraints dictated by the labour availability and land types on each farm. Under the assumptions used, labour availability and price restricted ewe numbers well below those observed in practice on 2 farms i.e. land resources were adequate for the farming system practiced. On two other farms stocking levels and hence returns were limited by the availability of forage and hence feed input prices relative to output. On one farm, greater grassland productivity was the key determinant of system performance. It was concluded that a holistic systems approach was needed to properly evaluate these farming systems in terms of their potential contribution to animal welfare, land use, profit and hence their sustainabilityLivestock Production/Industries, Extensive, Sheep, Economics, LP,

Bilateral maxillary, sphenoid sinuses and lumbosacral spinal cord extramedullary relapse of CML following allogeneic stem cell transplant

Isolated extramedullary relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant is rare. There is a case report of a child who developed a granulocytic sarcoma of the maxillary and sphenoid sinuses and lumbosacral spinal cord mass 18 months after allogeneic bone marrow transplant for CML. He was presented with per orbital edema and neurological deficit of lower extremities and a mass lesion was found on spinal cord imaging. No evidence of hematologic relapse was identified at that time by bone marrow histology or cytogenetic. The patient died 1 month later with a picture of pneumonia, left ventricular dysfunction and a cardiopulmonary arrest on a presumed underlying sepsis with infectious etiology. Granulocytic sarcoma should be considered in the differential diagnosis of mass lesions presenting after allogeneic bone marrow transplantation for CML, even if there is no evidence of bone marrow involvement. © 2016, Tehran University of Medical Sciences (TUMS). All Rights Reserved

A framework for estimating society’s economic welfare following the introduction of an animal disease: the case of Johne’s disease

Animal diseases are global issues affecting the productivity and financial profitability of affected farms. Johne’s disease is distributed on farms worldwide and is an endemic contagious bacterial infection in ruminants caused by Mycobacterium avium subspecies paratuberculosis. In cattle, the clinical disease manifests itself as chronic enteritis resulting in reduced production, weight loss, and eventually death. Johne’s disease is prevalent in the UK, including Scotland. Direct costs and losses associated with Johne’s disease have been estimated in previous research, confirming an important economic impact of the disease in UK herds. Despite this, the distributional impact of Johne’s disease among milk consumers and producers in Scotland has not been estimated. In this paper, we evaluate the change in society’s economic welfare, namely to dairy producers (i.e. infected and uninfected herds) and milk consumers in Scotland induced by the introduction of Johne’s disease in the national Scottish dairy herd. At the national-level, we conclude that the economic burden falls mainly on producers of infected herds and, to a lesser extent, milk consumers, while producers of uninfected herds benefit from the presence of Johne’s. An infected producer’s loss per cow is approximately two times larger in magnitude than that of an uninfected producer’s gain. Such economic welfare estimates are an important comparison of the relative costs of national herd prevalence and the wider economic welfare implications for both producers and consumers. This is particularly important from a policy, public good, cost sharing, and human health perspective. The economic welfare framework presented in this paper can be applied to other diseases to examine the relative burden of society’s economic welfare of alternative livestock disease scenarios. In addition, the sensitivity analysis evaluates uncertainty in economic welfare given limited data and uncertainty in the national herd prevalence, and other input parameters, associated with Johne’s disease in Scotland. Therefore, until the prevalence of Johne’s is better understood, the full economic cost to Scottish dairy herds remains uncertain but in the meantime the sensitivity analysis evaluates the robustness of economic welfare to such uncertainties

Impacts of labour on interactions between economics and animal welfare in extensive sheep farms

This study quantified interactions between animal welfare and farm profitability in British extensive sheep farming systems. Qualitative welfare assessment methodology was used to assess welfare from the animal's perspective in 20 commercial extensive sheep farms and to estimate labour demand for welfare, based on the assessed welfare scores using data collected from farm inventories. The estimated labour demand was then used as a coefficient in a linear program based model to establish the gross margin maximising farm management strategy for given farm situations, subject to constraints that reflected current resource limitations including labour supply. Regression analysis showed a significant relationship between the qualitative welfare assessment scores and labour supply on the inventoried farms but there was no significant relationship between current gross margin and assessed welfare scores. However, to meet the labour demand of the best welfare score, a reduction in flock size and in the average maximum farm gross margin was often required. These findings supported the hypothesis that trade-offs between animal welfare and farm profitability are necessary in providing maximum animal welfare via on-farm labour and sustainable British extensive sheep farming systems.Sheep, Labour, Animal Welfare, Linear Programme, Livestock Production/Industries, C6, Q10, Q19, Q57,

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced

The effects of hydro-ethanolic extract of Capparis spinosa (C. spinosa) on lipopolysaccharide (LPS)-induced inflammation and cognitive impairment: Evidence from in vivo and in vitro studies

Ethnopharmacological relevance: Capparis spinose (C. spinosa) belonging to Capparaeae, originates from dry areas in the west or central Asia and Mediterranean basin. For thousands of years, C. spinosa has been reported to be used as a therapeutic traditional medicine to relieve various ailments including rheumatism, pain and inflammatory diseases. Aim of the study: There are several studies mentioning that systemic inflammation results in learning and memory impairments through the activation of microglia. The objective of this study was to investigate the effect of C. spinosa on both in vivo and in vitro models of neuroinflammation and cognitive impairment using lipopolysaccharide (LPS). Materials and methods: In vivo: 40 male rats were used in the present study. Cognitive impairment was induced using LPS (1 mg/kg/d; i.p.) for 4 weeks. Treatment with C. spinosa (100 and 300 mg/kg/d; p.o.) was performed 1 h before LPS administration. At the end of the experiment, rats were undergone for behavioral and biochemical analysis. In vitro: Primary microglia isolated from mouse was used in the present study. The cells were pretreated with C. spinosa extract (10�300 μg/ml) and then stimulated with LPS (1 μg/ml). The expression levels of inflammatory and anti-inflammatory cytokines were elucidated using Real-Time PCR and ELISA methods. Results: The escape latency in the Morris water maze test in the LPS group was significantly greater than the control group (p < 0.001), while, in extract-treated groups, it was less than the LPS group (p < 0.001). Additionally, we found that the levels of IL-1β, TNF-α, and iNOS/Arg-1 ratio was also significantly lower in extract-treated groups than the LPS group (p < 0.001). The results revealed that C. spinosa extract significantly reduced the levels of TNF-α, iNOS, COX-2, IL-1β, IL-6, NO and PGE2, and the ratios of iNOS/Arg-1 and NO/urea, following the LPS-induced inflammation in microglia (p < 0.001). Conclusions: Our finding provides evidence that C. spinosa has a neuroprotective effect, and might be considered as an effective therapeutic agent for the treatment of neurodegenerative diseases that are accompanied by microglial activation, such as AD. © 202

Trade-offs<i> </i>between indicators of performance and sustainability in breeding suckler beef herds

SUMMARYManagement of beef suckler cattle herds requires a difficult but vitally important balance between farm profits, animal health and welfare and sustainable food production. A dynamic programming (DP) model was implemented to investigate the consequences of replacement and management decisions on the interactions and possible trade-offs between animal welfare, fertility and profitability in breeding beef suckler cattle herds. The model maximized profit from the current cow and all successors by identifying the best keep/replace decision. The 150 states incorporated in the DP model were all combinations of: ten cow-parity, five calving periods including one barren state (five in total) as fertility indicators and three body condition scores at weaning as an animal welfare indicator reflecting feeding and nutritional conditions of animals. Statistical models were fitted to data from a breeding suckler cattle herd, consisting of performance records of 200 cattle over 5 years, to parameterize the DP model. Estimated parameters used in the DP model were: (i) probabilities of transitions between states and (ii) probability of involuntary culling. These estimates were used in the form of conditional probabilities of successful or failed (as a result of involuntary culling) transitions to the next state. In addition, statistical models were used to estimate probability of calving difficulty. There was strong evidence (P&lt;0·001) that parity affected calving difficulty and weak evidence (P= 0·067) that parity affected the incidence of involuntary culling. The DP model outcomes indicated that cows calving very early, i.e. those who conceived in the first 21 days after artificial insemination, showed reduced frequencies of calving difficulty as well as voluntary culling, and so gave better financial returns than late-calving cows and barren cows. As a result, fewer replacements were needed that reduced the frequency of calving difficulty, further implying a win–win scenario for both profit and welfare. In contrast, in late-calving animals, the frequency of calving difficulty increased and they were less profitable and more prone to be culled. Results of sensitivity analysis showed that the optimum voluntary culling rate was sensitive to commodity market prices. These findings suggest well-informed nutrition and reproduction management could deliver a win–win outcome for profit and animal welfare.</jats:p

Bouveret's syndrome as an unusual cause of gastric outlet obstruction: a case report

An 83 year old caucasian gentleman presented with vomiting and left sided abdominal pain. A subsequent upper GI endoscopy demonstrated a large smooth mass impacted within the duodenum. A cholecysto-duodenal fistula was discovered at laparotomy, with a large gallstone impacted in the duodenum. A diagnosis of Bouveret's syndrome was made. The management of this rare cause of gastric outlet obstruction is discussed