The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice

BACKGROUND: Apo2L/TRAIL has considerable promise for cancer therapy based on the fact that this member of the tumor necrosis factor family induces apoptosis in the majority of malignant cells, while normal cells are more resistant. Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the effect is synergistic. The majority of this work has been carried out using cell lines. Therefore, investigation of how patient tumors respond to Apo2L/TRAIL can validate and/or complement information obtained from cell lines and prove valuable in the design of future clinical trials. METHODS: We have investigated the Apo2L/TRAIL sensitivity of patient derived pancreatic tumors using a patient tumor xenograft/ SCID mouse model. Mice bearing engrafted tumors were treated with Apo2L/TRAIL, gemcitabine or a combination of both therapies. RESULTS: Patient tumors grown as xenografts exhibited a spectrum of sensitivity to Apo2L/TRAIL. Both Apo2L/TRAIL sensitive and resistant pancreatic tumors were found, as well as tumors that showed heterogeneity of response. Changes in apoptotic signaling molecules in a sensitive tumor were analyzed by Western blot following Apo2L/TRAIL treatment; loss of procaspase 8, Bid and procaspase 3 was observed and correlated with inhibition of tumor growth. However, in a tumor that was highly resistant to killing by Apo2L/TRAIL, although there was a partial loss of procaspase 8 and Bid in response to Apo2L/TRAIL treatment, loss of procaspase 3 was negligible. This resistant tumor also expressed a high level of the anti-apoptotic molecule Bcl-X(L )that, in comparison, was not detected in a sensitive tumor. Importantly, in the majority of these tumors, addition of gemcitabine to Apo2L/TRAIL resulted in a greater anti-tumor effect than either therapy used alone. CONCLUSION: These data suggest that in a clinical setting we will see heterogeneity in the response of patients' tumors to Apo2L/TRAIL, including tumors that are highly sensitive as well as those that are resistant. While much more work is needed to understand the molecular basis for this heterogeneity, it is very encouraging, that Apo2L/TRAIL in combination with gemcitabine increased therapeutic efficacy in almost every case and therefore may be a highly effective strategy for controlling human pancreatic cancer validating and expanding upon what has been reported for cell lines

Human mandibular shape is associated with masticatory muscle force

Understanding how and to what extent forces applied to the mandible by the masticatory muscles influence its form, is of considerable importance from clinical, anthropological and evolutionary perspectives. This study investigates these questions. Head CT scans of 382 adults were utilized to measure masseter and temporalis muscle cross-sectional areas (CSA) as a surrogate for muscle force, and 17 mandibular anthropometric measurements. Sixty-two mandibles of young individuals (20-40 years) whose scans were without artefacts (e.g., due to tooth filling) were segmented and landmarked for geometric morphometric analysis. The association between shape and muscle CSA (controlled for size) was assessed using two-block partial least squares analysis. Correlations were computed between mandibular variables and muscle CSAs (all controlled for size). A significant association was found between mandibular shape and muscle CSAs, i.e. larger CSAs are associated with a wider more trapezoidal ramus, more massive coronoid, more rectangular body and a more curved basal arch. Linear measurements yielded low correlations with muscle CSAs. In conclusion, this study demonstrates an association between mandibular muscle force and mandibular shape, which is not as readily identified from linear measurements. Retrodiction of masticatory muscle force and so of mandibular loading is therefore best based on overall mandibular shape

Family physicians' effort to stay in charge of the medical treatment when patients have home care by district nurses. A grounded theory study

<p>Abstract</p> <p>Background</p> <p>District nurses (DNs) provide home care for old persons with a mixture of chronic diseases, symptoms and reduced functional ability. Family physicians (FPs) have been criticised for their lack of involvement in this care. The aim of this study was to obtain increased knowledge concerning the FP's experience of providing medical treatment for patients with home care provided by DNs by developing a theoretical model that elucidates how FPs handle the problems they encounter regarding the individual patients and their conditions.</p> <p>Methods</p> <p>Semi-structured interviews were conducted with 13 Swedish FPs concerning one of their registered patients with home care by a DN, and the treatment of this patient. Grounded theory methodology (GTM) was used in the analyses.</p> <p>Results</p> <p>The core category was the effort to stay in charge of the medical treatment. This involved three types of problems: gaining sufficient insight, making adequate decisions, and maintaining appropriate medical treatment. For three categories of patients, the FPs had problems staying in charge. Patients with reduced functional ability had problems providing information and maintaining treatment. Patients who were "fixed in their ways" did not provide information and did not comply with recommendations, and for patients with complex conditions, making adequate decisions could be problematic. To overcome the problems, four different strategies were used: relying on information from others, supporting close observation and follow-up by others, being constantly ready to change the goal of the treatment, and relying on others to provide treatment.</p> <p>Conclusion</p> <p>The patients in this study differed from most other patients seen at the healthcare centre as the consultation with the patient could not provide the usual foundation for decisions concerning medical treatment. Information from and collaboration with the DN and other home care providers was essential for the FP's effort to stay in charge of the medical treatment. The complexity of the situation made it problematic for the FP to make adequate decisions about the goal of the medical treatment. The goal of the treatment had to be constantly evaluated based on information from the DN and other care providers, and thus this information was absolutely crucial.</p

Human Milk Banking-Facts and Issues to Resolve

The number of human milk banks is increasing worldwide. Although the beneficial effects of feeding premature infants with their mother’s milk are well documented, less is known about the effects of feeding these infants with pasteurized donor milk. We propose a randomized trial comparing the effects of a 100% human milk-based diet (human milk supplemented with a human milk-derived fortifier) and a diet (partially) based on bovine milk. In theory, human milk has a beneficial effect on various aspects of human physiology, most of which become apparent after infancy. We therefore propose an extensive follow-up program that takes this aspect into consideration. Other issues concerning the practice of human milk banks need to be addressed as well as optimization of the feeding strategies for preterm infants

Rapid Enzymatic Response to Compensate UV Radiation in Copepods

Ultraviolet radiation (UVR) causes physical damage to DNA, carboxylation of proteins and peroxidation of lipids in copepod crustaceans, ubiquitous and abundant secondary producers in most aquatic ecosystems. Copepod adaptations for long duration exposures include changes in behaviour, changes in pigmentation and ultimately changes in morphology. Adaptations to short-term exposures are little studied. Here we show that short-duration exposure to UVR causes the freshwater calanoid copepod, Eudiaptomus gracilis, to rapidly activate production of enzymes that prevent widespread collateral peroxidation (glutathione S-transferase, GST), that regulate apoptosis cell death (Caspase-3, Casp-3), and that facilitate neurotransmissions (cholinesterase-ChE). None of these enzyme systems is alone sufficient, but they act in concert to reduce the stress level of the organism. The interplay among enzymatic responses provides useful information on how organisms respond to environmental stressors acting on short time scales

Conservation status of a recently described endemic land snail, Candidula coudensis, from the Iberian Peninsula

Research ArticleWe assessed the distribution, population size and conservation status of Candidula coudensis, a recently described endemic land snail from Portugal. From March 2013 to April 2014, surveys were carried out in the region where the species was described. We found an extent of occurrence larger than originally described, but still quite small (13.5 km2). The species was found mainly in olive groves, although it occurred in a variety of other habitats with limestone soils, including grasslands, scrublands and stone walls. Minimum population estimate ranged from 110,000–311,000 individuals. The main identified potential threats to the species include wildfires, pesticides and quarrying. Following the application of IUCN criteria, we advise a conservation status of either “Least Concern” or “Near-threatened” under criterion D (restricted population)info:eu-repo/semantics/publishedVersio

Watchfully checking rapport with the Primary Child Health Care nurses - a theoretical model from the perspective of parents of foreign origin

<p>Abstract</p> <p>Background</p> <p>Worldwide, multicultural interaction within health care seems to be challenging and problematic. This is also true among Primary Child Health Care nurses (PCHC nurses) in the Swedish Primary Child Health Care services (PCHC services). Therefore, there was a need to investigate the parents' perspective in-depth.</p> <p>Aim</p> <p>The aim of the study was to construct a theoretical model that could promote further understanding of the variety of experiences of parents of foreign origin regarding their interaction with the PCHC nurses at PCHC services.</p> <p>Method</p> <p>The study used Grounded Theory Methodology. Twenty-one parents of foreign origin in contact with PCHC servicies were interviewed.</p> <p>Results</p> <p>In our study parents were watchfully checking rapport, i.e. if they could perceive sympathy and understanding from the PCHC nurses. This was done by checking the nurse's demeanour and signs of judgement. From these interviews we created a theoretical model illustrating the interactive process between parents and PCHC nurses.</p> <p>Conclusion</p> <p>We found it to be of utmost importance for parents to be certain that it was possible to establish rapport with the PCHC nurse. If not, disruptions in the child's attendance at PCHC services could result. PCHC nurses can use the theoretical model resulting from this study as a basis for understanding parents, avoiding a demeanour and judgements that may cause misunderstandings thus promoting high-quality interaction in PCHC services.</p