The Effects of Pregabalin and the Glial Attenuator Minocycline on the Response to Intradermal Capsaicin in Patients with Unilateral Sciatica

BACKGROUND: Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. AIM: This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. METHODS/RESULTS: Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 mg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce precapsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin. CONCLUSIONS: It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glialmediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain.Nicole M. Sumracki, Mark R. Hutchinson, Melanie Gentgall, Nancy Briggs, Desmond B. Williams and Paul Rola

Ischemic Stroke and Depression

Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH–D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 ± 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 ± 6.7 years). We required a SIGH–D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH–D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke

Frequency and Clinical Determinants of Dementia after Ischemic Stroke

Objective: To investigate the frequency and clinical determinants of dementia after ischemic stroke. Methods: The authors administered neurologic, neuropsychological, and functional assessments to 453 patients (age 72.0 ± 8.3 years) 3 months after ischemic stroke. They diagnosed dementia using modified Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. Results: The authors diagnosed dementia in 119 of the 453 patients (26.3%). Regarding dementia subtypes, 68 of the 119 patients (57.1%) were diagnosed with vascular dementia, 46 patients (38.7%) were diagnosed with AD with concomitant stroke, and 5 patients (4.2%) had dementia for other reasons. Logistic regression suggested that dementia was associated with a major hemispheral stroke syndrome (OR 3.0), left hemisphere (OR 2.1) and right hemisphere (OR 1.8) infarct locations versus brainstem/cerebellar locations, infarcts in the pooled anterior and posterior cerebral artery territories versus infarcts in other vascular territories (OR 1.7), diabetes mellitus (OR 1.8), prior stroke (OR 1.7), age 80 years or older (OR 12.7) and 70 to 79 years (OR 3.9) versus 60 to 69 years, 8 or fewer years of education (OR 4.1) and 9 to 12 years of education (OR 3.0) versus 13 or more years of education, black race (OR 2.6) and Hispanic ethnicity (OR 3.1) versus white race, and northern Manhattan residence (OR 1.6). Conclusions: Dementia is frequent after ischemic stroke, occurring in one-fourth of the elderly patients in the authors’ cohort. The clinical determinants of dementia include the location and severity of the presenting stroke, vascular risk factors such as diabetes mellitus and prior stroke, and host characteristics such as older age, fewer years of education, and nonwhite race/ethnicity. The results also suggest that concomitant AD plays an etiologic role in approximately one-third of cases of dementia after stroke

Relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort.

OBJECTIVES: To describe the characteristics of children and adults with incident type 1 diabetes in contemporary, multiethnic UK, focusing on differences between the islet autoantibody negative and positive. DESIGN: Observational cohort study. SETTING: 146 mainly secondary care centres across England and Wales. PARTICIPANTS: 3312 people aged ≥5 years were recruited within 6 months of a clinical diagnosis of type 1 diabetes via the National Institute for Health Research Clinical Research Network. 3021 were of white European ethnicity and 291 (9%) were non-white. There was a small male predominance (57%). Young people <17 years comprised 59%. MAIN OUTCOME MEASURES: Autoantibody status and characteristics at presentation. RESULTS: The majority presented with classical osmotic symptoms, weight loss and fatigue. Ketoacidosis was common (42%), especially in adults, and irrespective of ethnicity. 35% were overweight or obese. Of the 1778 participants who donated a blood sample, 85% were positive for one or more autoantibodies against glutamate decarboxylase, islet antigen-2 and zinc transporter 8. Presenting symptoms were similar in the autoantibody-positive and autoantibody-negative participants, as was the frequency of ketoacidosis (43%vs40%, P=0.3). Autoantibody positivity was less common with increasing age (P=0.0001), in males compared with females (82%vs90%, P<0.0001) and in people of non-white compared with white ethnicity (73%vs86%, P<0.0001). Body mass index was higher in autoantibody-negative adults than autoantibody-positive adults (median, IQR 25.5, 23.1-29.2vs23.9, 21.4-26.7 kg/m2; P=0.0001). Autoantibody-negative participants were more likely to have a parent with diabetes (28%vs16%, P<0.0001) and less likely to have another autoimmune disease (4%vs8%, P=0.01). CONCLUSIONS: Most people assigned a diagnosis of type 1 diabetes presented with classical clinical features and islet autoantibodies. Although indistinguishable at an individual level, autoantibody-negative participants as a group demonstrated features more typically associated with other diabetes subtypes. TRIAL REGISTRATION NUMBER: ISRCTN66496918; Pre-results

Association of DASH Diet With Cardiovascular Risk Factors in Youth With Diabetes Mellitus: The SEARCH for Diabetes in Youth Study

We have shown that adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is related to blood pressure in youth with type 1 and type 2 diabetes mellitus. We explored the impact of the DASH diet on other cardiovascular disease risk factors

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Social Gerontology- Integrative and Territorial Aspects: A Citation Analysis of Subject Scatter and Database Coverage

To determine the mix of resources used in social gerontology research, a citation analysis was conducted. A representative sample of citations was selected from three prominent gerontology journals and information was added to determine subject scatter and database coverage for the cited materials. Results indicate that a significant portion of gerontology research, even from a social science perspective, relies roughly equally on medical resources as it does social science resources. Furthermore, there is a small but defined core of literature constituting scholarly “territory” unique to gerontology. Analysis of database indexing indicated that broad, interdisciplinary databases provide more comprehensive coverage of the cited materials than do subject-specific databases

Sugar-sweetened and diet beverage consumption is associated with cardiovascular risk factor profile in youth with type 1 diabetes

The prevalence of cardiovascular disease (CVD) risk factors among youth with type 1 diabetes is high and associated with age, gender, and race/ethnicity. It has also been shown that youth with type 1 diabetes often do not follow dietary recommendations. The objective of this cross-sectional observational study was to explore the association of sugar-sweetened and diet beverage intake with A1c, plasma lipids, adiponectin, leptin, systolic, and diastolic blood pressure in youth with type 1 diabetes. We examined data from 1,806 youth age 10–22 years with type 1 diabetes, of which 22% were minority (10% Hispanic, 8% African Americans, 4% other races) and 48% were female. Sugar-sweetened beverage, diet beverage, and mineral water intake was assessed with a food frequency questionnaire. After adjustment for socio-demographic and clinical covariates, physical activity and total energy intake, high sugar-sweetened beverage intake (at least one serving per day vs. none), was associated with higher levels of total cholesterol, LDL cholesterol, and plasma triglycerides, but not with A1c. High diet beverage intake was associated with higher A1c, total cholesterol, LDL cholesterol, and triglycerides. These associations were partially confounded by body mass index, saturated fat and total fiber intake. High sugar-sweetened beverage intake may have an adverse effect on CVD risk in youth with type 1 diabetes. Diet beverage intake may be a marker of unhealthy lifestyle which, in turn, is associated with worse metabolic control and CVD risk profile in these youth. Youth with diabetes should be encouraged to minimize sugar-sweetened beverage intake