ALDH Activity Correlates with Metastatic Potential in Primary Sarcomas of Bone.

Osteosarcoma (OS), chondrosarcoma (CSA), and Ewings sarcoma (ES) are the most common primary malignancies of bone, and are rare diseases. As with all sarcomas, the prognosis of these diseases ultimately depends on the presence of metastatic disease. Survival is therefore closely linked with the biology and metastatic potential of a particular bone tumor's cells. Here we describe a significant correlation of aldehyde dehydrogenase (ALDH) activity and the presence/absence of distant metastases in ten consecutive cases of human bone sarcomas. Additionally, cultured human CSA cells, which are historically chemo- and radio-resistant, may be sensitive to the ALDH inhibitor, disulfiram. While it is premature to draw broad conclusions from such a small series, the importance of ALDH activity and inhibition in the metastatic potential of primary bone sarcomas should be investigated further

Numerical modelling of the transport of trace gases including methane in the subsurface of Mars

We model the transport of gas through the martian subsurface in order to quantify the timescales of release of a trace gas with a source at depth using a Fickian model of diffusion through a putative martian regolith column. The model is then applied to the case of methane previously observed in the martian atmosphere. We investigate which parameters in the model have the greatest effect on transport timescales and find that transport is very sensitive to the pressure profile of the subsurface, but relatively insensitive to the temperature profile. Uncertainties in the composition, structure and physical conditions of the martian subsurface also introduce uncertainties in the timescales calculated. It was found that methane may take several hundred thousand Mars-years to diffuse from a source at depth. Purely diffusive transport cannot explain transient release that varies on timescales of less than one martian year from sources such as serpentinization or methanogenic organisms at depths of more than 2 km. However, diffusion of gas released by the destabilisation of methane clathrate hydrates close to the surface, for example caused by transient mass wasting events or erosion, could produce a rapidly varying flux of methane into the atmosphere of more than 10-3 kg m-2 s-1 over a duration of less than half a martian year, consistent with observations of martian methane variability. Seismic events, magmatic intrusions or impacts could also potentially produce similar patterns of release, but are far more complex to simulate

Analysis of weight changes after left gastric artery embolization in a cancer-naive population

PURPOSE:We aimed to evaluate weight changes after left gastric artery (LGA) embolization in a retrospective cancer-naive cohort.METHODS:A retrospective study was conducted to identify patients who underwent LGA embolization for gastrointestinal bleeding (GI). Patients with known cancer diagnoses at the time of LGA embolization were excluded. Pre- and postprocedure weights were assessed. Statistical analysis was performed using paired t-test and Wilcoxon signed-rank test.RESULTS:A total of 39 patients were identified. In 21 patients who had documented pre- and postprocedural weights, a median of 16.3 kg weight loss (P = 0.045) was observed over a median time of 12 months (range, 2–72). In patients who had pre- and postprocedure endoscopies (n=6), 2 had worsening ulcers following LGA embolization and 4 had stable or no abnormal findings.CONCLUSION:Our preliminary observation suggests that LGA embolization is well tolerated and results in unintended weight loss. Larger studies are needed to confirm these preliminary findings

EMBIO trial study protocol: left gastric artery embolisation for weight loss in patients living with obesity with a BMI 35–50 kg/m²

Introduction: Left gastric artery embolisation (LGAE) is a well-established treatment for major upper gastrointestinal (GI) bleeding when control is not established via upper GI endoscopy and recently has shown promising results for weight loss in small single arm studies. LGAE could be a treatment option in between our current tier-3 and tier-4 services for obesity. EMBIO is a National Institute for Health Research funded trial, a multicentre double-blinded randomised controlled trial between Imperial College National Health Service Trust and University College London Hospital, comparing LGAE versus Placebo procedure. The key aims of the trial is to evaluate LGAE efficacy on weight loss, its mechanism of action, safety profile and obesity-related comorbidities. / Methods and analysis: 76 participants will be recruited from the existing tier-3 database after providing informed consent. Key inclusion criteria include adults aged 18–70 with a body mass index 35–50 kg/m2 and appropriate anatomy of the left gastric artery and coeliac plexus on CT Angiogram. Key exclusion criteria included previous major abdominal and bariatric surgery, weight >150 kg, type 2 diabetes on any medications other than metformin and the use of weight modifying medications. Participants will undergo mechanistic visits 1 week prior to the intervention and 3, 6 and 12 months postintervention. Informed consent will be received from each participant and they will be randomised in a 1:1 ratio to left gastric artery embolisation and placebo treatment. Blinding strategies include the use of moderate doses of sedation, visual and auditory isolation. All participants will enter a tier-3 weight management programme postintervention. The primary analysis will estimate the difference between the groups in the mean per cent weight loss at 12 months. / Ethics and dissemination: This trial shall be conducted in full conformity with the 1964 Declaration of Helsinki and all subsequent revisions. Local research ethics approval was granted by London-Central Research Ethics Committee, (Reference 19/LO/0509) on 11 October 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) issued the Letter of No Objection on 8 April 2022 (Reference CI/2022/0008/GB). The trial’s development and progress are monitored by an independent trial steering committee and data monitoring and ethics committee. The researchers plan to disseminate results at conferences, in peer- reviewed journals as well as lay media and to patient organisations. / Trial registration number: ISRCTN16158402

Enhanced Hsp70 Expression Protects against Acute Lung Injury by Modulating Apoptotic Pathways

The Acute respiratory distress syndrome (ARDS) is a highly lethal inflammatory lung disorder. Apoptosis plays a key role in its pathogenesis. We showed that an adenovirus expressing the 70 kDa heat shock protein Hsp70 (AdHSP) protected against sepsis-induced lung injury. In this study we tested the hypothesis that AdHSP attenuates apoptosis in sepsis-induced lung injury

Validation of the questionnaire on beliefs about medication with type 2 diabetic patients

O presente trabalho teve como objectivo validar o Questionário Crenças sobre a Medicação, que avalia Crenças Gerais e Crenças Específicas, estudando suas propriedades psicométricas em uma amostra de 387 pacientes diabéticos tipo 2. O estudo de validade para as Crenças Gerais revelou uma solução de um factor, com um alfa de 0,76, e para as Crenças Específicas, dois factores – Necessidades e Preocupações –, com um alfa de 0,77 e 0,69 respectivamente. Quanto à validade de constructo, verificou-se uma relação entre as Crenças Gerais e a subescala Necessidades das Crenças Específicas com Adesão à Medicação, avaliada pela Escala de Avaliação de Aderência Médica. O instrumento apresenta boas qualidades psicométricas para ser utilizado em pacientes diabéticos tipo 2.The present paper focused on the validation of the Questionnaire on Beliefs about Medication, which assesses both General Beliefs and Specific Beliefs. The psychometric properties of the instrument were analyzed on a sample of 387 type 2 diabetic patients. The validity study for General Beliefs found a unifactorial solution, with an alpha of .76, and for Specific Beliefs, a two-factor solution – Necessities and Concern –, with an alpha of .77 and .69, respectively. In terms of construct validity, a relationship between General Beliefs, subscale Necessities from Specific Beliefs, and adherence to medication, as evaluated by Medical Adherence Rating Scale, was found. The instrument presents good psychometric qualities to be used in type 2 diabetic patients.Fundação para a Ciência e Tecnologia (FCT

Reflection and the art of coaching: fostering high-performance in olympic ski cross

In preparation for the 2010 Vancouver Winter Olympic Games, the lead author engaged in systematic reflection in an attempt to implement coaching behaviours and create practice environments that promoted athlete development (psycho-social and physical performance). The research was carried out in relation to his work as head Ski Cross coach working with (primarily) three athletes in their quest for Olympic qualification and subsequent performance success in the Olympic Games. This project sought to examine coach-athlete interactions. Of particular interest were coach and athlete responses regarding the implementation of autonomy supportive coaching behaviours in a high context. Autonomy supportive coaching behaviours have previously been strongly associated with positive athlete psycho-social and performance outcomes, however, a paucity of research has examined its implementation in high-performance contexts. Through the use of participant ethnography, it was possible to gain considerable insights regarding athletes' perceptions of choice, implications of perceived athletic hierarchies, as well as cultural and experience-related influences on training and performance expectations

Facilitating factors and barriers to malaria research utilization for policy development in Malawi

BACKGROUND : Research on various determinants of health is key in providing evidence for policy development, thereby leading to successful interventions. Utilization of research is an intricate process requiring an understanding of contextual factors. The study was conducted to assess enhancing factors and barriers of research utilization for malaria policy development in Malawi. METHODS : Qualitative research approach was used through in-depth interviews with 39 key informants that included malaria researchers, policy makers, programme managers, and key stakeholders. Purposive sampling and snowballing techniques were used in identifying key informants. Interview transcripts were entered in QSR Nvivo 11 software for coding and analysis. RESULTS : Respondents identified global efforts as key in advancing knowledge translation, while local political will has been conducive for research utilization. Other factors were availability of research, availability of diverse local researchers and stakeholders supporting knowledge translation. While barriers included: lack of platforms for researcher-public engagement, politics, researchers’ lack of communication skills, lack of research collaborations, funder driven research, unknown World Health Organization policy position, and the lack of a malaria research repository. CONCLUSION : Overall, the study identified facilitating factors to malaria research utilization for policy development in Malawi. These factors need to be systematically coordinated to address the identified barriers and improve on malaria research utilization in policy development. Malaria research can be key in the implementation of evidence-based interventions to reduce the malaria burden and assist in the paradigm shift from malaria control to elimination in Malawi.University of Pretoria Institute for Sustainable Malaria Control (UP ISMC)http://www.malariajournal.comam2016School of Health Systems and Public Health (SHSPH

A functional AT/G polymorphism in the 5'-untranslated region (UTR) of SETDB2 in the IgE locus on human chromosome 13q14

The immunoglobulin E (IgE)-associated locus on human chromosome 13q14 influencing asthma-related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously ungenotyped mutation (AT/G, rs386770867) in the 5′-untranslated region of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P=0.0012). Electrophoretic mobility shift assays revealed that the transcription factor Ying Yang 1 binds to the AT allele, whereas SRY (Sex determining Region Y) binds to the G allele. Allele-specific transcription analysis (allelotyping) was performed in 35 individuals heterozygous for rs386770867 from a panel of 200 British families ascertained through probands with severe stage 3 asthma. The AT allele was found to be significantly overexpressed in these individuals (P=1.26 × 10(−21)). A dual-luciferase assay with the pGL3 luciferase reporter gene showed that the AT allele significantly affects transcriptional activities. Our results indicate that the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2