Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value

Persistence with statin therapy in Hungary

Introduction: Persistence with lipid-lowering drug therapy by cardiovascular patients in Hungary has not been studied previously. This study was designed to determine the rate with which Hungarian patients with hyperlipidemia persist in taking lipid-lowering agents, and to compare this with rates reported from other countries. Material and methods: This was a retrospective study that utilized data from the Institutional Database of the National Health Insurance Fund to analyze persistence rates with statins and ezetimibe. The study included data for patients who started lipid-lowering therapy between January 1, 2007, and March 31, 2009. Variables included type of lipid-lowering therapy, year of therapy start, and patient age. Main outcome measures were medians of persistence in months, percentages of patients persisting in therapy for 6 and 12 months, and Kaplan-Meier persistence plots. Results: The percentage of patients who persisted with overall statin therapy was 46% after 1 month, 40.3% after 2 months, 27% after 6 months, and 20.1% after 12 months. Persistence was slightly greater for statin therapy started during 2008 than during 2007. Older patients were more persistent with therapy than younger patients. Persistence with the combination of ezetimibe-statin therapy was greater than with statin or ezetimibe monotherapy. Conclusions: Persistence with statin therapy by patients in Hungary was low compared with other countries. Low persistence may have negated potential clinical benefits of long-term statin therapy

Endogenous fantasy and learning in digital games.

Many people believe that educational games are effective because they motivate children to actively engage in a learning activity as part of playing the game. However, seminal work by Malone (1981), exploring the motivational aspects of digital games, concluded that the educational effectiveness of a digital game depends on the way in which learning content is integrated into the fantasy context of the game. In particular, he claimed that content which is intrinsically related to the fantasy will produce better learning than that which is merely extrinsically related. However, this distinction between intrinsic and extrinsic (or endogenous and exogenous) fantasy is a concept that has developed a confused standing over the following years. This paper will address this confusion by providing a review and critique of the empirical and theoretical foundations of endogenous fantasy, and its relevance to creating educational digital games. Substantial concerns are raised about the empirical basis of this work and a theoretical critique of endogenous fantasy is offered, concluding that endogenous fantasy is a misnomer, in so far as the "integral and continuing relationship" of fantasy cannot be justified as a critical means of improving the effectiveness of educational digital games. An alternative perspective on the intrinsic integration of learning content is described, incorporating game mechanics, flow and representations

Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases

In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is predominantly performed to exclude inflammatory diseases and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However, large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define a normal reference spectrum of routine CSF parameters in neurodegenerative diseases. Routine CSF parameters (white cell count, lactate and albumin concentrations, CSF/serum quotients of albumin (Qalb), IgG, IgA, IgM, and oligoclonal IgG bands (OCB)) were retrospectively analyzed in an academic research setting. A total of 765 patients (Alzheimer’s disease (AD), Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), vascular dementia (VD), frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), motor neuron diseases (MND), spinocerebellar ataxia (SCA), Huntington’s disease (HD)) and non-demented control groups including a group of patients with muscular disorders (MD). The main outcome measures included statistical analyses of routine CSF parameters. Mildly elevated Qalb were found in a small percentage of nearly all subgroups and in a higher proportion of patients with PSP, MSA, VD, PDD, and MND. With the exception of 1 MND patient, no intrathecal Ig synthesis was observed. Isolated OCBs in CSF were sometimes found in patients with neurodegenerative diseases without elevated cell counts; lactate levels were always normal. A slightly elevated Qalb was observed in a subgroup of patients with neurodegenerative diseases and does not exclude the diagnosis. Extensive elevation of routine parameters is not characteristic and should encourage a re-evaluation of the clinical diagnosis

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD

The association between foot-care self efficacy beliefs and actual foot-care behaviour in people with peripheral neuropathy: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>People with diabetes and peripheral neuropathy often do not implement the foot-care behavioural strategies that are suggested by many health professionals. The concept of self-efficacy has been shown to be an effective predictor of behaviour in many areas of health. This study investigated the relationships between foot-care self-efficacy beliefs, self-reported foot-care behaviour and history of diabetes-related foot pathology in people with diabetes and loss of protective sensation in their feet.</p> <p>Methods</p> <p>Ninety-six participants were included in this cross-sectional study undertaken in a regional city of Australia. All participants had diabetes and clinically diagnosed loss of protective sensation in their feet. The participants completed a self-report pen-paper questionnaire regarding foot-care self efficacy beliefs (the "Foot Care Confidence Scale") and two aspects of actual foot-care behaviour-preventative behaviour and potentially damaging behaviour. Pearson correlation coefficients were then calculated to determine the association between foot-care self-efficacy beliefs and actual reported foot-care behaviour. Multiple analysis of variance was undertaken to compare mean self-efficacy and behaviour subscale scores for those with a history of foot pathology, and those that did not.</p> <p>Results</p> <p>A small positive correlation (r = 0.2, p = 0.05) was found between self-efficacy beliefs and preventative behaviour. There was no association between self-efficacy beliefs and potentially damaging behaviour. There was no difference in self-efficacy beliefs in people that had a history of foot pathology compared to those that did not.</p> <p>Conclusion</p> <p>There is little association between foot-care self-efficacy beliefs and actual foot-care behaviour. The usefulness of measuring foot-care self-efficacy beliefs to assess actual self foot-care behaviour using currently available instruments is limited in people with diabetes and loss of protective sensation.</p

Predictive value of the QFR in detecting vulnerable plaques in non-flow limiting lesions: a combined analysis of the PROSPECT and IBIS-4 study

“This is a post-peer-review, pre-copyedit version of an article published in Int J Cardiovasc Imaging. The final authenticated version is available online at: https://doi.org/10.1007/s10554-020-01805-9”

Head injury from falls in children younger than 6 years of age

The risk of serious head injury (HI) from a fall in a young child is ill defined. The relationship between the object fallen from and prevalence of intracranial injury (ICI) or skull fracture is described. Method Cross-sectional study of HIs from falls in children (<6 years) admitted to UK hospitals, analysed according to the object fallen from and associated Glasgow Coma Score (GCS) or alert, voice, pain, unresponsive (AVPU) and CT scan results. Results Of 1775 cases ascertained (median age 18 months, 54.7% boys), 87% (1552) had a GCS=15/AVPU=alert. 19.3% (342) had a CT scan: 32% (110/342) were abnormal; equivalent to 5.9% of the overall population, 16.9% (58) had isolated skull fractures and 13.7% (47) had ICI (49% (23/47) had an associated skull fracture). The prevalence of ICI increased with neurological compromise; however, 12% of children with a GCS=15/AVPU=alert had ICI. When compared to falls from standing, falls from a person's arms (233 children (mean age 1 year)) had a significant relative OR for a skull fracture/ICI of 6.94 (95% CI 3.54 to 13.6), falls from a building (eg, window or attic) (mean age 3 years) OR 6.84 (95% CI 2.65 to 17.6) and from an infant or child product (mean age 21 months) OR 2.75 (95% CI 1.36 to 5.65). Conclusions Most HIs from a fall in these children admitted to hospital were minor. Infants, dropped from a carer's arms, those who fell from infant products, a window, wall or from an attic had the greatest chance of ICI or skull fracture. These data inform prevention and the assessment of the likelihood of serious injury when the object fallen from is known

Articulated Whole-Body Atlases for Small Animal Image Analysis: Construction and Applications

Bone and mineral researc

Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease

<p>Abstract</p> <p>Background</p> <p>The emergence and continuing spread of Chronic Wasting Disease (CWD) in cervids has now reached 14 U.S. states, two Canadian provinces, and South Korea, producing a potential for transmission of CWD prions to humans and other animals globally. In 2005, CWD spread for the first time from the Midwest to more densely populated regions of the East Coast. As a result, a large cohort of individuals attending a wild game feast in upstate New York were exposed to a deer that was subsequently confirmed positive for CWD.</p> <p>Methods</p> <p>Eighty-one participants who ingested or otherwise were exposed to a deer with chronic wasting disease at a local New York State sportsman's feast were recruited for this study. Participants were administered an exposure questionnaire and agreed to follow-up health evaluations longitudinally over the next six years.</p> <p>Results</p> <p>Our results indicate two types of risks for those who attended the feast, a <it>Feast Risk </it>and a G<it>eneral Risk</it>. The larger the number of risk factors, the greater the risk to human health if CWD is transmissible to humans. Long-term surveillance of feast participants exposed to CWD is ongoing.</p> <p>Conclusion</p> <p>The risk data from this study provide a relative scale for cumulative exposure to CWD-infected tissues and surfaces, and those in the upper tiers of cumulative risk may be most at risk if CWD is transmissible to humans.</p