Reframing NCDs? An analysis of current debates

There have been many debates in recent years as to whether the communicable disease versus non-communicable disease (NCD) division is a meaningful one in disease classification. Several critiques have been raised about the framing of NCDs, regarding not only the prominent role that infections play in the aetiology of NCDs, but also the communicability of many social determinants of NCDs and the individualistic, ‘lifestyle’ framing of NCDs that tends to focus on health behaviours to the neglect of socio-political, environmental, and structural determinants of health. In this paper, we give a historical overview of the usage of the NCD terminology and analyse some of the recent debates regarding the naming and framing of NCDs. We argue that a lack of reflection on the assumptions underlying the naming and framing of NCDs may lead to the collection of insufficient epidemiological data, the development of inappropriate interventions and the provision of inadequate care. Work in social epidemiology, health promotion, medical anthropology, demography, and other fields may provide insights into the ways in which efforts targeting NCDs may be reframed to improve impact and efficacy. In addition, concepts such as multimorbidity and syndemics, frameworks such as ecosocial theory and approaches based in the social sciences may provide a way forward in the conceptualization of disease

Development and preliminary evaluation of EMPOWER for surrogate decision-makers of critically ill patients

OBJECTIVE: The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates' mental health and patient outcomes. METHOD: Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15-20 min modules, totaling 1.5-2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments. RESULTS: Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = -0.41), peritraumatic distress (d = -0.24), and experiential avoidance (d = -0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = -0.94), depression (d = -0.23), anxiety (d = -0.29), and experiential avoidance (d = -0.30). SIGNIFICANCE OF RESULTS: Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial

Mycobacterium tuberculosis osteomyelitis in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): a case report

The incidence of tuberculosis is increasing in the United States. Extra-pulmonary involvement is more common in patients with HIV/AIDS. The diagnosis of Tuberculosis osteomyelitis requires a high degree of suspicion for accurate and timely diagnosis

Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience (EMPOWER) among Surrogate Decision-Makers of ICU Patients: study protocol for a randomized controlled trial

Background Critical illness increases the risk for poor mental health outcomes among both patients and their informal caregivers, especially their surrogate decision-makers. Surrogates who must make life-and-death medical decisions on behalf of incapacitated patients may experience additional distress. EMPOWER (Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience) is a novel cognitive-behavioral, acceptance-based intervention delivered in the intensive care unit (ICU) setting to surrogate decision-makers designed to improve both patients’ quality of life and death and dying as well as surrogates’ mental health. Methods Clinician stakeholder and surrogate participant feedback (n = 15), as well as results from an open trial (n = 10), will be used to refine the intervention, which will then be evaluated through a multisite randomized controlled trial (RCT) (n = 60) to examine clinical superiority to usual care. Feasibility, tolerability, and acceptability of the intervention will be evaluated through self-report assessments. Hierarchical linear modeling will be used to adjust for clustering within interventionists to determine the effect of EMPOWER on surrogate differences in the primary outcome, peritraumatic stress. Secondary outcomes will include symptoms of post-traumatic stress disorder, prolonged grief disorder, and experiential avoidance. Exploratory outcomes will include symptoms of anxiety, depression, and decision regret, all measured at 1 and 3 months from post-intervention assessment. Linear regression models will examine the effects of assignment to EMPOWER versus the enhanced usual care group on patient quality of life or quality of death and intensity of care the patient received during the indexed ICU stay assessed at the time of the post-intervention assessment. Participant exit interviews will be conducted at the 3-month assessment time point and will be analyzed using qualitative thematic data analysis methods. Discussion The EMPOWER study is unique in its application of evidence-based psychotherapy targeting peritraumatic stress to improve patient and caregiver outcomes in the setting of critical illness. The experimental intervention will be strengthened through the input of a variety of ICU stakeholders, including behavioral health clinicians, physicians, bereaved informal caregivers, and open trial participants. Results of the RCT will be submitted for publication in a peer-reviewed journal and serve as preliminary data for a larger, multisite RCT grant application

Conservative treatment of a comminuted cervical fracture in a racehorse

The 'classical' or 'Hangman' neck fracture involves the odontoid peg (process) of the second cervical vertebra (C2), and is described as an axial, dens or odontoid peg fracture in both the veterinary and human literature. Possible surgical treatment in both foals and adult horses requires a technique that allows decompression, anatomical alignment and stabilisation of the odontoid fracture. A limited number of surgical cases in foals have been reported in literature, but never in an adult horse. A mature Irish Thoroughbred racehorse was diagnosed with a type 2a odontoid peg fracture. Clinical signs included reluctance to move the head and neck, a left hind limb lameness and a neurological status of grade 2. The horse was treated conservatively and raced successfully five months after the diagnosed injury

Oleic Acid Biosynthesis in Plasmodium falciparum: Characterization of the Stearoyl-CoA Desaturase and Investigation as a Potential Therapeutic Target

BACKGROUND:Plasmodium falciparum parasitization of erythrocytes causes a substantial increase in the levels of intracellular fatty acids, notably oleic acid. How parasites acquire this monounsaturated fatty acid has remained enigmatic. Here, we report on the biochemical and enzymatic characterization of stearoyl-CoA desaturase (SCD) in P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS:Metabolic labeling experiments allowed us to demonstrate the production of oleic acid from stearic acid both in lysates of parasites incubated with [(14)C]-stearoyl-CoA and in parasite-infected erythrocytes labeled with [(14)C]-stearic acid. Optimal SCD activity was detected in schizonts, the stage of maximal membrane synthesis. This activity correlated with a late trophozoite stage-specific induction of PFE0555w transcripts. PFE0555w harbors a typical SCD signature. Similar to mammalian SCDs, this protein was found to be associated with the endoplasmic reticulum, as determined with PFE0555w-GFP tagged transgenic P. falciparum. Importantly, these parasites exhibited increased rates of stearic to oleic acid conversion, providing additional evidence that PFE0555w encodes the plasmodial SCD (PfSCD). These findings prompted us to assess the activity of sterculic acid analogues, known to be specific Delta9-desaturase inhibitors. Methyl sterculate inhibited the synthesis of oleic acid both with parasite lysates and infected erythrocytes, most likely by targeting PfSCD. This compound exhibited significant, rapid and irreversible antimalarial activity against asexual blood stages. This parasiticidal effect was antagonized by oleic acid. CONCLUSION/SIGNIFICANCE:Our study provides evidence that parasite-mediated fatty acid modification is important for blood-stage survival and provides a new strategy to develop a novel antimalarial therapeutic based on the inhibition of PfSCD

Curation of complex, context-dependent immunological data

BACKGROUND: The Immune Epitope Database and Analysis Resource (IEDB) is dedicated to capturing, housing and analyzing complex immune epitope related data . DESCRIPTION: To identify and extract relevant data from the scientific literature in an efficient and accurate manner, novel processes were developed for manual and semi-automated annotation. CONCLUSION: Formalized curation strategies enable the processing of a large volume of context-dependent data, which are now available to the scientific community in an accessible and transparent format. The experiences described herein are applicable to other databases housing complex biological data and requiring a high level of curation expertise

VEGFR2 Translocates to the Nucleus to Regulate Its Own Transcription

Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is the major mediator of the angiogenic effects of VEGF. In addition to its well known role as a membrane receptor that activates multiple signaling pathways, VEGFR2 also has a nuclear localization. However, what VEGFR2 does in the nucleus is still unknown. In the present report we show that, in endothelial cells, nuclear VEGFR2 interacts with several nuclear proteins, including the Sp1, a transcription factor that has been implicated in the regulation of genes needed for angiogenesis. By in vivo chromatin immunoprecipitation (ChIP) assays, we found that VEGFR2 binds to the Sp1-responsive region of the VEGFR2 proximal promoter. These results were confirmed by EMSA assays, using the same region of the VEGFR2 promoter. Importantly, we show that the VEGFR2 DNA binding is directly linked to the transcriptional activation of the VEGFR2 promoter. By reporter assays, we found that the region between -300/-116 relative to the transcription start site is essential to confer VEGFR2-dependent transcriptional activity. It was previously described that nuclear translocation of the VEGFR2 is dependent on its activation by VEGF. In agreement, we observed that the binding of VEGFR2 to DNA requires VEGF activation, being blocked by Bevacizumab and Sunitinib, two anti-angiogenic agents that inhibit VEGFR2 activation. Our findings demonstrate a new mechanism by which VEGFR2 activates its own promoter that could be involved in amplifying the angiogenic response