Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin

BACKGROUND: Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. METHODS: Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. RESULTS: (111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). CONCLUSION: This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors

Fresh-blood-free diet for rearing malaria mosquito vectors

Mosquito breeding depends on the supply of fresh vertebrate blood, a major bottleneck for large-scale production of Anopheles spp. Feeding alternatives to fresh blood are thus a priority for research, outdoor large-cage trials and control interventions. Several artificial meal compositions were tested and Anopheles oogenesis, egg laying and development into the next generation of adult mosquitoes were followed. We identified blood-substitute-diets that supported ovarian development, egg maturation and fertility as well as, low progeny larval mortality, and normal development of offspring into adult mosquitoes. The formulated diet is an effective artificial meal, free of fresh blood that mimics a vertebrate blood meal and represents an important advance for the sustainability of Anopheles mosquito rearing in captivity.Agência financiadora / Número do subsídio Bill and Melinda Gates Foundation OPP1138841 Fundacao para a Ciencia e Tecnologia GHTM - UID/Multi/04413/201 CCMAR - UID/Multi/04326/2013 UID/Multi/04326/2013 RF SFRH/BPD/89811/2012 FAPEAM, Brazil 19716.UNI472.2459.20022014info:eu-repo/semantics/publishedVersio

An exploration of social determinants of health amongst internally displaced persons in northern Uganda

Social determinants of health describe the conditions in which people are born, grow, live, work and age and their influence on health. These circumstances are shaped by the distribution of money, power and resources at global, national and local levels, which are themselves influenced by policy choices. Armed conflict and forced displacement are important influences on the social determinants of health. There is limited evidence on the social determinants of health of internally displaced persons (IDPs) who have been forced from their homes due to armed conflict but remain within the borders of their country. The aim of this study was to explore the social determinants of overall physical and mental health of IDPs, including the response strategies used by IDPs to support their health needs. Northern Uganda was chosen as a case-study, and 21 face-to-face semi-structured interviews with IDPs were conducted in fifteen IDP camps between November and December 2006

Water table depth modulates productivity and biomass across Amazonian forests

Aim: Water availability is the major driver of tropical forest structure and dynamics. Most research has focused on the impacts of climatic water availability, whereas remarkably little is known about the influence of water table depth and excess soil water on forest processes. Nevertheless, given that plants take up water from the soil, the impacts of climatic water supply on plants are likely to be modulated by soil water conditions. Location: Lowland Amazonian forests. Time period: 1971–2019. Methods: We used 344 long-term inventory plots distributed across Amazonia to analyse the effects of long-term climatic and edaphic water supply on forest functioning. We modelled forest structure and dynamics as a function of climatic, soil-water and edaphic properties. Results: Water supplied by both precipitation and groundwater affects forest structure and dynamics, but in different ways. Forests with a shallow water table (depth <5 m) had 18% less above-ground woody productivity and 23% less biomass stock than forests with a deep water table. Forests in drier climates (maximum cumulative water deficit < −160 mm) had 21% less productivity and 24% less biomass than those in wetter climates. Productivity was affected by the interaction between climatic water deficit and water table depth. On average, in drier climates the forests with a shallow water table had lower productivity than those with a deep water table, with this difference decreasing within wet climates, where lower productivity was confined to a very shallow water table. Main conclusions: We show that the two extremes of water availability (excess and deficit) both reduce productivity in Amazon upland (terra-firme) forests. Biomass and productivity across Amazonia respond not simply to regional climate, but rather to its interaction with water table conditions, exhibiting high local differentiation. Our study disentangles the relative contribution of those factors, helping to improve understanding of the functioning of tropical ecosystems and how they are likely to respond to climate change

Association between exposure to traumatic events and anxiety disorders in a post-conflict setting: a cross-sectional community study in South Sudan

Background The negative effect of exposure to traumatic events on mental health is well known. Most studies of the effects of trauma on mental health in war-affected populations have focused on post-traumatic stress disorder (PTSD) and depression. Although some studies confirm the existence of anxiety symptoms in war-affected populations, the extent to which exposure to traumatic events is independently associated with anxiety diagnoses (other than PTSD) has received less attention. The study aimed to determine whether having an anxiety diagnosis, other than PTSD, was associated with experiencing traumatic events in a post-conflict setting, across genders and after controlling for demographic and socio-economic variables. Methods In this cross-sectional community study (n = 1200), we applied the Harvard Trauma Questionnaire (HTQ) to investigate the extent of trauma exposure and PTSD. The Mini-International Neuropsychiatric Interview (MINI) was used to investigate the prevalence of anxiety disorders: generalized anxiety disorder (GAD), panic disorder (PD), social phobia, obsessive-compulsive disorder (OCD), and agoraphobia. Multinomial logistic regression analyses were conducted to examine the association between these disorders, previous trauma exposure, and socio-economic factors. Results The participants were 56.4% male and 43.6% female. The age ranged between 18 and 73 years old (Mean 34.63, SD = 12.03). The estimated rates of GAD-only and PD-only (without comorbidity with PTSD) were 5.5% and 3.1%, respectively. Exposure to traumatic events and socio-economic disadvantage were significantly associated with having one or more anxiety diagnoses. After controlling for age, sex, rural/urban setting, and socio-economic disadvantage, exposure to trauma was independently associated with anxiety diagnosis. There were gender differences in the pattern of risk factors for having PTSD, GAD or PD. Conclusion In individuals with a history of war-related trauma exposure, attention should be given to symptoms of GAD and PD, in addition to PTSD symptoms

A comparison between radioimmunotherapy and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis of colonic origin in rats.

Contains fulltext : 52894.pdf (publisher's version ) (Closed access)BACKGROUND: Cytoreductive surgery (CS) followed by heated intraperitoneal chemotherapy (HIPEC) is considered the standard of care for the treatment of patients with peritoneal carcinomatosis (PC) of colorectal cancer (CRC). These surgical procedures result in a median survival of 2 years at the cost of considerable morbidity and mortality. In preclinical studies, radioimmunotherapy (RIT) improved survival after CS in a model of induced PC of colonic origin. In the present studies we aimed to compare the efficacy and toxicity of CS followed by adjuvant RIT in experimental PC to the standard of care, HIPEC. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in three groups of Wag/Rij rats. Treatment comprised CS only, CS + RIT or CS + HIPEC, immediately after surgery. RIT consisted of intraperitoneal administration of 74 MBq Lutetium-177 labeled MG1. HIPEC was performed by a closed abdomen perfusion technique using mitomycin C (16 mg/L during 60 minutes). The primary endpoint was survival. RESULTS: CS only or combined with RIT was well tolerated. Rats receiving CS + HIPEC were lethargic, suffered from diarrhea, and lost significantly more weight in the first postoperative week. Median survival of rats treated with CS + RIT was significantly longer than after CS alone (97 and 57 days, respectively, P < .004), whereas survival after CS + HIPEC or CS alone were not significantly different (76 and 57 days, respectively, P = .17). CONCLUSION: Survival after CS was significantly improved by RIT with Lutetium-177-MG1 in rats with PC of colorectal origin. Adjuvant HIPEC did not improve survival and was more toxic than adjuvant RIT