Quantification of the effects of an alpha-2 adrenergic agonist on reflex properties in spinal cord injury using a system identification technique

<p>Abstract</p> <p>Background</p> <p>Despite numerous investigations, the impact of tizanidine, an anti-spastic medication, on changes in reflex and muscle mechanical properties in spasticity remains unclear. This study was designed to help us understand the mechanisms of action of tizanidine on spasticity in spinal cord injured subjects with incomplete injury, by quantifying the effects of a single dose of tizanidine on ankle muscle intrinsic and reflex components.</p> <p>Methods</p> <p>A series of perturbations was applied to the spastic ankle joint of twenty-one spinal cord injured subjects, and the resulting torques were recorded. A parallel-cascade system identification method was used to separate intrinsic and reflex torques, and to identify the contribution of these components to dynamic ankle stiffness at different ankle positions, while subjects remained relaxed.</p> <p>Results</p> <p>Following administration of a single oral dose of Tizanidine, stretch evoked joint torque at the ankle decreased significantly (p < 0.001) The peak-torque was reduced between 15% and 60% among the spinal cord injured subjects, and the average reduction was 25%. Using systems identification techniques, we found that this reduced torque could be attributed largely to a reduced reflex response, without measurable change in the muscle contribution. Reflex stiffness decreased significantly across a range of joint angles (p < 0.001) after using tizanidine. In contrast, there were no significant changes in intrinsic muscle stiffness after the administration of tizanidine.</p> <p>Conclusions</p> <p>Our findings demonstrate that tizanidine acts to reduce reflex mechanical responses substantially, without inducing comparable changes in intrinsic muscle properties in individuals with spinal cord injury. Thus, the pre-post difference in joint mechanical properties can be attributed to reflex changes alone. From a practical standpoint, use of a single "test" dose of Tizanidine may help clinicians decide whether the drug can helpful in controlling symptoms in particular subjects.</p

Sexual dysfunction and fertility-related distress in young adults with cancer over 5 years following diagnosis: study protocol of the Fex-Can Cohort study

BACKGROUND: There is a lack of firm knowledge regarding sexual problems and fertility-related distress in young adults following a diagnosis with cancer. Establishing such understanding is essential to identify patients in need of specific support and to develop cancer care accordingly. This study protocol describes the Fex-Can Cohort study, a population-based prospective cohort study investigating sexual dysfunction and fertility-related distress in young adults diagnosed with cancer in Sweden. The primary objective of the study is to determine the prevalence and predictors of sexual dysfunction and fertility-related distress following a cancer diagnosis in young adulthood compared to prevalence rates for the general population. Further aims are to investigate the trajectories of these issues over time, the co-existence between sexual dysfunction and fertility-related distress, and the relation between these issues and body image, anxiety and depression, health-related quality of life, self-efficacy related to sexuality and fertility, and fertility-related knowledge. METHODS: Participants in the Fex-Can Cohort will be identified via the Swedish National Quality Registries for Brain Tumors, Breast Cancer, Gynecological Oncology, Lymphoma, and Testicular Cancer. All patients diagnosed at the ages of 18-39, during a period of 18 months, will be invited to participate. Established instruments will be used to measure sexual function (PROMIS SexFS), fertility-related distress (RCAC), body image (BIS), anxiety and depression (HADS), and health-related quality of life (QLQ-C30); Self-efficacy and fertility-related knowledge will be assessed by study-specific measures. The survey will be administered to participants at baseline (approximately 1.5 year after diagnosis) and at 3 and 5 years post-diagnosis. Registry data will be used to collect clinical variables. A comparison group of 2000 young adults will be drawn from the Swedish population register (SPAR) and subsequently approached with the same measures as the cancer group. DISCUSSION: The study will determine the prevalence and predictors of sexual dysfunction and fertility-related distress in young men and women with cancer. The findings will form a basis for developing interventions to alleviate sexual problems and fertility-related distress in young adults with cancer in the short and long term. TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was therefore not obtained

Effects of an Early Handling-Like Procedure and Individual Housing on Anxiety-Like Behavior in Adult C57BL/6J and DBA/2J Mice

Manipulations of rearing conditions have been used to examine the effects of early experience on adult behavior with varying results. Evidence suggests that postnatal days (PND) 15–21 are a time of particular susceptibility to environmental influences on anxiety-like behavior in mice. To examine this, we subjected C57BL/6J and DBA/2J mice to an early handling-like procedure. Pups were separated from dams from PND 12–20 for 30 minutes daily or received standard care. On PND 21, pups were weaned and either individually- or group- housed. On PND 60, anxiety-like behavior was examined on the elevated zero-maze. Although individually- housed animals took longer to enter an open quadrant of the maze, they spent more time in the open than group-housed animals. Additionally, we observed a trend of reduced anxiety-like behavior in C57BL/6J, but not DBA/2J mice that underwent the handling-like procedure

Febrile illness diagnostics and the malaria-industrial complex: a socio-environmental perspective

Abstract Background Global prioritization of single-disease eradication programs over improvements to basic diagnostic capacity in the Global South have left the world unprepared for epidemics of chikungunya, Ebola, Zika, and whatever lies on the horizon. The medical establishment is slowly realizing that in many parts of sub-Saharan Africa (SSA), particularly urban areas, up to a third of patients suffering from acute fever do not receive a correct diagnosis of their infection. Main body Malaria is the most common diagnosis for febrile patients in low-resource health care settings, and malaria misdiagnosis has soared due to the institutionalization of malaria as the primary febrile illness of SSA by international development organizations and national malaria control programs. This has inadvertently created a “malaria-industrial complex” and historically obstructed our complete understanding of the continent’s complex communicable disease epidemiology, which is currently dominated by a mélange of undiagnosed febrile illnesses. We synthesize interdisciplinary literature from Ghana to highlight the complexity of communicable disease care in SSA from biomedical, social, and environmental perspectives, and suggest a way forward. Conclusion A socio-environmental approach to acute febrile illness etiology, diagnostics, and management would lead to substantial health gains in Africa, including more efficient malaria control. Such an approach would also improve global preparedness for future epidemics of emerging pathogens such as chikungunya, Ebola, and Zika, all of which originated in SSA with limited baseline understanding of their epidemiology despite clinical recognition of these viruses for many decades. Impending ACT resistance, new vaccine delays, and climate change all beckon our attention to proper diagnosis of fevers in order to maximize limited health care resources

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1

Myeloproliferative neoplasms (MPNs) originate from genetically transformed hematopoietic stem cells that retain the capacity for multilineage differentiation and effective myelopoiesis. Beginning in early 2005, a number of novel mutations involving Janus kinase 2 (JAK2), Myeloproliferative Leukemia Virus (MPL), TET oncogene family member 2 (TET2), Additional Sex Combs-Like 1 (ASXL1), Casitas B-lineage lymphoma proto-oncogene (CBL), Isocitrate dehydrogenase (IDH) and IKAROS family zinc finger 1 (IKZF1) have been described in BCR-ABL1-negative MPNs. However, none of these mutations were MPN specific, displayed mutual exclusivity or could be traced back to a common ancestral clone. JAK2 and MPL mutations appear to exert a phenotype-modifying effect and are distinctly associated with polycythemia vera, essential thrombocythemia and primary myelofibrosis; the corresponding mutational frequencies are ∼99, 55 and 65% for JAK2 and 0, 3 and 10% for MPL mutations. The incidence of TET2, ASXL1, CBL, IDH or IKZF1 mutations in these disorders ranges from 0 to 17% these latter mutations are more common in chronic (TET2, ASXL1, CBL) or juvenile (CBL) myelomonocytic leukemias, mastocytosis (TET2), myelodysplastic syndromes (TET2, ASXL1) and secondary acute myeloid leukemia, including blast-phase MPN (IDH, ASXL1, IKZF1). The functional consequences of MPN-associated mutations include unregulated JAK-STAT (Janus kinase/signal transducer and activator of transcription) signaling, epigenetic modulation of transcription and abnormal accumulation of oncoproteins. However, it is not clear as to whether and how these abnormalities contribute to disease initiation, clonal evolution or blastic transformation

Vulnerability and its discontents: the past, present, and future of climate change vulnerability research

The concept of vulnerability is well established in the climate change literature, underpinning significant research effort. The ability of vulnerability research to capture the complexities of climate-society dynamics has been increasingly questioned, however. In this paper, we identify, characterize, and evaluate concerns over the use of vulnerability approaches in the climate change field based on a review of peer-reviewed articles published since 1990 (n = 587). Seven concerns are identified: neglect of social drivers, promotion of a static understanding of human-environment interactions, vagueness about the concept of vulnerability, neglect of cross-scale interactions, passive and negative framing, limited influence on decision-making, and limited collaboration across disciplines. Examining each concern against trends in the literature, we find some of these concerns weakly justified, but others pose valid challenges to vulnerability research. Efforts to revitalize vulnerability research are needed, with priority areas including developing the next generation of empirical studies, catalyzing collaboration across disciplines to leverage and build on the strengths of divergent intellectual traditions involved in vulnerability research, and linking research to the practical realities of decision-making