Development and validation of the Migraine Screen Questionnaire (MS-Q)

AIM: To develop and evaluate the clinimetric properties of a new migraine screening questionnaire: the Migraine Screen Questionnaire (MS-Q). BACKGROUND: Migraine is a public health problem requiring screening programs and tools to ensure early detection. METHODS: A questionnaire was developed based on the criteria of the International Headache Society (IHS) and a review of the literature by a committee of experts. Stage I: The original version of the MS-Q was distributed by mail and completed by Pfizer employees and self-administered to neurological patients; all subjects were afterward evaluated by a neurologist who was blinded to the MS-Q results, to establish an independent IHS diagnosis. Stage II: A final version of the MS-Q was administered to neurological patients to confirm clinimetric properties. Logistic regression and receiver-operator characteristic curve statistical methods were used and the 95% confidence interval, sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values, were estimated. RESULTS: Of the 605 subjects recruited, 465 were evaluable (325 in stage I and 140 in stage II). Of the original 15 items, 5 conformed the final version of the MS-Q: frequency and intensity of headache; a duration of between 4 hours and 3 days; nausea; sensitivity to light/noise; and disability. A cutoff point of > or = 4 points showed a sensitivity of 0.93 (95% CI = 0.87 to 0.99), specificity of 0.81 (95% CI = 0.72 to 0.91), PPV of 0.83 (95% CI = 0.75 to 0.91), and NPV of 0.92 (95% CI = 0.85 to 0.99). Cronbach's alpha coefficient = 0.82. CONCLUSIONS: The MS-Q showed adequate validity and reliability, and it could be a good screening tool for application to clinical practice and research.     

Collagen synthesis and heart failure

Little is known about collagen metabolism in heart failure, with or without left ventricular systolic dysfunction. We studied serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type-I synthesis, and of the carboxy-terminal telopeptide of collagen type I (ICTP), a marker of collagen type-I degradation, in 70 patients admitted for heart failure (35 with depressed left ventricular systolic function and 35 with preserved left ventricular systolic function) and in 30 control subjects. Patients with kidney failure, liver disease, metabolic bone disease, rheumatic disease, recent (within 3 months) major trauma or surgery, or serious wounds were excluded. The concentration of the collagen synthesis marker, PIP, was higher in heart failure patients than control subjects, at 140+/-56.38 mg/L vs 113.66+/-36.6 microg/L, respectively (P=.01). However, there was no difference in the concentration of the collagen degradation marker, ICTP, between heart failure patients and control subjects, at 2.89+/-2.37 mg/L vs 2.26+/-1.7 microg/l, respectively. In heart failure patients, left ventricular systolic function had nonsignificant effect on the PIP or ICTP concentration.     

Picornavirus IRES: structure function relationship

Picornavirus infections have been a challenging problem in human health. Genome organisation of picornavirus is unique in having a long, heavily-structured, multifunctional 5'untranslated region, preceding a single open reading frame from which all viral proteins are produced. Within the 5'leader, an internal region termed ribosome entry site (IRES) regulates viral protein synthesis in a 5'-independent manner. The IRES element itself is a distinctive feature of the picornavirus mRNAs, allowing efficient viral protein synthesis in infected cells in spite of a severe modification of translation initiation factors induced by viral proteases that lead to a fast inhibition of cellular protein synthesis. Picornavirus IRES elements are strongly structured, bearing several motifs, phylogenetically conserved, which are essential for IRES activity. Together with RNA structure, RNA-binding proteins play an essential role in the activity of the IRES element, having a profound effect on viral pathogenesis. Recent data on the involvement of these conserved motifs in RNA structure and protein recognition is discussed in detail. Understanding the interplay between these two components of IRES function is crucial to develop viral strategies aimed to use the viral RNA as the target of antiviral approaches.     

Task-specific sensory and motor preparatory activation revealed by contingent magnetic variation

The present report studied the magnetic counterpart (CMV) of the auditory contingent negative variation (CNV). The ear where the target auditory stimulus would be presented was cued with a visual central arrow at a validity of 84%. The subject's behavioral response and the magnetoencephalographic (MEG) and electroencephalographic (EEG) signals were recorded. The central cue diminished reaction times (RTs) to the auditory target in the valid conditions with respect to the invalid conditions, indicating that the attentional manipulation was effective. The averaged magnetic field power during the preparatory period was significantly higher than baseline, suggesting the simultaneous presence of a magnetic counterpart of the electric CNV--the CMV. The field maps of the CMV grand averages showed two different and well-established periods: an early one with a magnetic field distribution that suggests a central source, and a late one with a field topography comparable to a low-intensity auditory-evoked field (M1). Single-dipole analysis of the preparatory phase in the subject's magnetic resonance images (MRI) demonstrated the presence of dipolar activity in the posterior cingulate (PCC) and posterior parietal cortices (PPC), superior temporal gyrus (STG) and motor cortices (MC). The lateralization of this activity depended on the orientation of the central cue. These results suggest that the action and perceptual-related areas needed to process the expected subsequent imperative task are recruited during the preparatory periods, influencing the behavioral RTs.     

Body composition assessed by anthropometry and bioelectric impedance analysis in older persons recovering from cerebrovascular accident

We investigated body composition in older patients who had experienced a cerebrovascular accident (CVA) and were participating in a recovery program that included physical exercise. We studied 61 persons in two groups. One group consisted of 13 men and 12 women (mean age, 68 years) who were receiving day center care to recover from a CVA that had occurred from six months to one year previously. The second group (control) consisted of 20 men and 16 women (mean age, 68 years) in good health, residing in a retirement home. Most subjects in both groups were able to perform normal activities of daily living without help and showed a high degree of independence (> 60 on the Barthel scale). Bioelectric impedance and anthropometric methods were used to measure the magnitude of changes in fat-free mass and fat mass. Percentage total body fat measured with bioelectric impedance was higher in both groups than when measured anthropometrically. The anthropometric values and bioelectric impedance results in patients who participated in a physical exercise program were similar to the findings in control subjects. The anticipated loss in muscle mass and gain in body fat as a result of inactivity associated with illness was not seen, possibly because of the personalized program of continuous physical exercise. Our comparison of older people recovering from CVA and apparently healthy older people illustrates the benefits of physical exercise in compensating for changes in body composition as a result of immobility during convalescence.     

Functional sequelae of tuberculous pleurisy in patients correctly treated

STUDY OBJECTIVES: To assess the functional sequelae (FS) of patients with tuberculous pleurisy (TP), to analyze the influence of different factors in the occurrence of these FS, and, finally, to evaluate the relationship between the FS and roentgenographic sequelae. DESIGN: An observational, retrospective study. SETTING: A community teaching hospital in Alicante, Spain. PATIENTS AND METHODS: From April 1986 to July 2000, all patients with a firmly established diagnosis of TP, who had been functionally studied at the end of follow-up, were included in the study. A diagnosis of TP was considered to be definitive when the presence of granuloma on a pleural biopsy specimen was demonstrated or when a culture was positive for Mycobacterium tuberculosis in pleural fluid (PF) or tissue. The general characteristics of the study population and PF were compared in patients with or without restrictive FS (ie, FVC or TLC < 80%), looking for risk factors for developing this complication. RESULTS: Eighty-one of 150 patients who had been treated for TP were eligible for the study. At the end of follow-up, eight patients (10%) had a restrictive FS. These patients had a lower PF lactate dehydrogenase concentration (p < 0.001), a higher PF concentration of cholesterol (p < 0.03) and triglycerides (p < 0.03), and a higher percentage of lymphocytes (p < 0.04). A weak correlation was found between the FVC and the intensity of radiographic pleural thickening (r = - 0.298; p < 0.01). CONCLUSIONS: The FS in patients with TP is restrictive in type, infrequent, and usually mild. A higher PF lipid content or a more chronic inflammatory pleural reaction at diagnosis appear to be risk factors for developing a FS. The correlation between FS and roentgenographic sequelae is poor.     

Progranulin deficiency induces overactivation of WNT5A expression via TNF-α/NF-κB pathway in peripheral cells from frontotemporal dementia-linked granulin mutation carriers

BackgroundLoss-of-function progranulin gene (GRN) mutations have been identified as the major cause of frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein 43 (TDP-43) pathology (frontotemporal lobar degeneration [FTLD]-TDP); however, little is known about the association between progranulin (PGRN) deficiency and neuronal loss in individuals with FTLD-TDP. Previously we reported enhanced proliferative activity associated with the activation of WNT5A/CDK6/pRb signalling in PGRN-deficient cells. The objective of this work was to elucidate the association between PGRN deficiency, WNT5A signalling and cell proliferation in immortalized lymphoblasts from carriers of the c.709–1G > A GRN mutation (asymptomatic and FTLD-TDP).MethodsWe assessed cell proliferation in carriers of the c.709–1G > A GRN gene mutation and controls without GRN mutation and without sign of neurologic degeneration by cell counting or using an MTT assay. We used a luciferase assay to measure the nuclear factor-κ (NF-κ) activity. We evaluated messenger RNA levels using quantitative real-time polymerase chain reaction and protein levels by immunoblotting. Co-immunoprecipitation was used to analyze the interaction between PGRN and its receptors.ResultsWe enrolled 19 carriers of the GRN gene mutation and 10 controls in this study. The PGRN-deficient cells showed increased expression of WNT5A due to NF-κB signalling overactivation. We observed a competition between PGRN and tumour necrosis factor-α (TNF-α) for binding both TNF receptors (TNFR) I and II. Blocking NF-κB signalling using wedelolactone or specific antibodies against TNFRs inhibited WNT5A overexpression and proliferation of PGRN-deficient cells. Conversely, the activation of NF-κB signalling by TNF-α increased WNT5A-dependent proliferation of control cells.LimitationsAll cell lines were derived from individuals harboring the same splicing GRN mutation. Nevertheless, most of the known GRN mutations lead to haploinsufficiency of the protein.ConclusionOur results revealed an important role of NF-κB signalling in PGRN-associated FTLD-TDP and confirm that PGRN can bind to TNF-α receptors regulating the expression of WNT5A, suggesting novel targets for treatment of FTLD-TDP linked to GRN mutations.