Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

Cardiometabolic and immune factors associated with increased common carotid artery intima-media thickness and cardiovascular disease in patients with systemic lupus erythematosus.

BACKGROUND AND AIM: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. METHODS AND RESULTS: Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets. CONCLUSION: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.

ADHD Endophenotypes in Caribbean Families.

Objective: The aim of this study is to contrast the genetics of neuropsychological tasks in individuals from nuclear families clustering ADHD in a Caribbean community. Method: We recruited and clinically characterized 408 individuals using an extensive battery of neuropsychological tasks. The genetic variance underpinning these tasks was estimated by heritability. A predictive framework for ADHD diagnosis was derived using these tasks. Results: We found that individuals with ADHD differed from controls in tasks of mental control, visuospatial ability, visuoverbal memory, phonological and verbal fluency, verbal and semantic fluency, cognitive flexibility, and cognitive ability. Among them, tasks of mental control, visuoverbal memory, phonological fluency, semantic verbal fluency, and intelligence had a significant heritability. A predictive model of ADHD diagnosis using these endophenotypes yields remarkable classification rate, sensitivity, specificity, and precision values (above 80%). Conclusion: We have dissected new cognitive endophenotypes in ADHD that can be suitable to assess the neurobiological and genetic basis of ADHD.

Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group.

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

How to measure health status in rheumatoid arthritis in non-English speaking patients: validation of a Spanish version of the Health Assessment Questionnaire Disability Index (Spanish HAQ-DI).

The HAQ-Disability Index (HAQ-DI) is a useful instrument to measure health status in rheumatoid arthritis (RA) patients. Translation into another language requires a validation process, however. We have translated the HAQ-DI to be used on Spanish-speaking populations. We administered the questionnaire to 97 RA patients during the course of routine medical care. Reliability, measured by a test-retest with a one-month interval, was high (Spearman's rho = 0.89). Convergent and construct validity was obtained for all comparisons (Pearson's r > 0.4). The instrument was sensitive in detecting clinical improvement. We conclude that the Spanish HAQ-DI retains the characteristics of the original index and can be used to assess outcome in Spanish-speaking patients with RA. The procedure described may be used to translate the instrument into other languages either directly from English or from the Spanish version presented here.

A retrospective study of treatment of cerebral toxoplasmosis in AIDS patients with trimethoprim-sulphamethoxazole.

AIMS OF THE STUDY: a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE). PATIENTS AND METHODS: we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks. RESULTS: 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity. CONCLUSIONS: TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

[Effectiveness of interventions for the control and prevention of tuberculosis in health care facilities: a review of ATS,CDC, OSHA recommendations]. / Appropriatezza degli interventi di prevenzione e controllo dell'infezione tubercolare nelle strutture sanitarie: revisione delle raccomandazioni ATS, CDC, OSHA.

BACKGROUND: Health care workers (HCWs) are occupationally exposed to a multitude of biological hazards, and among these to the risk of tuberculosis (TB) infection, especially involving individuals working in specific workplace (TB and Chest divisions, Infectious Diseases wards, Microbiology laboratories) and performing thoracic endoscopy and "cough-inducing" procedures. According to national legislation (title VIII D.lgs. 626/94, 1998 Health Minister guide lines document) concerning the control and prevention of TB transmission among HCWs, health care facilities are required to (i) perform an accurate risk assessment and (ii) implement an exposure control plan and worker health surveillance program, thus involving the occupational health professionals. OBJECTIVES: The aim of this paper is to provide a general view of the epidemiological and scientific evidence related to the effectiveness of health interventions in the prevention of occupational TB infection. METHODS: Comparative evaluation and critical review of U.S. CDC (1994) guidelines, OSHA (1997) rules, and the most recent ATS and CDC (2000) "statement" documents. RESULTS: In low risk groups TCT shows decreased positive predictive value, high variability, and can be confounded by other factors (age, BCG, MNT), thus reducing its diagnostic value for latent TB infection. CONCLUSIONS: Recent recommendations on the control of TB infection in health care settings underline the need of implementing accurate risk evaluation in all hospital units, compared to the epidemiological profile in the community, and "targeted tuberculin testing" programs among high risk HCWs.

Incidence and severity of oral mucositis in patients undergoing haematopoietic SCT--results of a multicentre study.

Oral mucositis (OM) is a common side effect experienced during haematopoietic SCT (HSCT), and it can have a significant impact on the quality of life of patients. A descriptive nurse-led study was undertaken in 19-member centres of the Italian national transplant group (GITMO) evaluating incidence, severity and duration of OM in patients undergoing HSCT. Data from 1841 patients between 2002 and 2006 was analyzed. Initial medical history and oral cavity assessment was performed. Assessment was repeated on the day of transplant, then daily, using the WHO (World Health Organisation) oral toxicity scale. A total of 71% of the patients evaluated developed mucositis and 21.6% developed severe mucositis. Duration of OM in most cases lasted for 10-14 days and resolved along with marrow reconstitution. Oral mucostitis is a frequent side effect in patients undergoing HSCT. The onset of severe mucositis seems to be related to the conditioning regimen used. This database provides a descriptive overview of the incidence and severity of mucositis and has encouraged participating centres to adopt routine evaluation and measurement of the oral cavity. The assessment tools are still used in some centres, providing a basis for further collaborative research projects.

Regulation of inflammatory responses to Bordetella pertussis by N(G)-monomethyl-L-arginine in mice intranasally infected.

To investigate effect of MMLA, an inhibitor of nitric oxide (NO) production, on regulation of inflammatory responses to Bordetella pertussis infection, mice were infected intranasally, and treated with various concentrations of MMLA. Ten days after infection, mice treated with MMLA at dosage of 100 mg/kg, given intraperitoneally in a single dose or for 5 consecutive days, showed at histopathologic examination, a significant decrease of intensity of inflammation (scores, 0.6 +/- 0.2 and 0.9 +/- 0.5 respectively). A decrease of cellular accumulation of neutrophils and lymphocytes in the bronchoalveolar lavage (BAL) fluid was observed in infected mice treated with MMLA, especially at dosage of 10 mg/kg, given in a single dose intraperitoneally. In addition, BP-infected mice treated with MMLA (100 mg/kg, intraperitoneally) for 5 consecutive days showed higher mortality rate than untreated mice infected with B. pertussis, and the number of B. pertussis in lungs of mice treated with MMLA was significantly increased. However, MMLA treatment of infected mice had some effect on levels of IFN-gamma and nitrite/nitrate (end-stable products of NO) in the BAL fluid. This study indicates that NO may play a role either as microbiocidal agent or as a modulator of immune regulation, inasmuch as it may upregulate tissue inflammatory response to B. pertussis.

Intravenous drug use, relationship with providers, and stage of HIV disease influence the prescription rates of protease inhibitors.

OBJECTIVE: To assess rates of prescriptions of protease inhibitors (PI) and determinants of not being prescribed PIs in a cohort of HIV-infected people eligible (according to published guidelines) for highly active antiretroviral therapy (HAART). DESIGN: Cross-sectional survey. METHODS: A total of 684 patients with CD4+ counts <500 cells/microl were enrolled from seven Italian HIV treatment centers from October 1997 to April 1998. A questionnaire on health-related quality of life (MOS-HIV) and patient ratings of the quality of care was administered. Sociodemographic variables, HIV disease-related factors, and prescribed antiretroviral therapy were also recorded. RESULTS: 61% of those enrolled were prescribed PI (median, 7.5 months). In addition, 75% of patients had previously received antiretroviral therapy. Fewer than 1% were prescribed nonnucleoside reverse transcriptase inhibitors (NNRTIs). Using multivariable logistic regression considering those with CD4+ counts <500 cells/microl, patients reporting the least information received (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.58), injecting drug users (IDUs; OR, 1.73; 95% CI, 1.18-2.54), people with CD4+ counts >200 cells/microl (OR, 1.76; 95% CI, 1.19-2.61), and patients with early stage disease (OR, 2.24; 95% CI, 1.73-2.90) were less likely to have be prescribed PIs. CONCLUSIONS: Of patients eligible for HAART, only 61% were prescribed PIs. People who wanted more information, IDUs, and patients in earlier disease stages are significantly less likely to be prescribed PIs. Access to HAART remains a critical issue in the management of HIV disease.

Quality of life in rheumatoid arthritis: validation of a Spanish version of the Arthritis Impact Measurement Scales (Spanish-AIMS)

OBJECTIVE: To translate and validate The Arthritis Impact Measurement Scales (AIMS) to be used by Spanish speaking populations. METHODS: We administered the questionnaire to 97 outpatients with rheumatoid arthritis (RA) during routine patient care, in most cases with a trained interviewer. Reliability was assessed in stable patients using test-retest at a one-month interval. Internal consistency was evaluated with the coefficient of reliability. Convergent and construct validation was tested using ARA functional class, disease severity, disease activity, patient global assessment, and pain scores. Responsiveness was evaluated with one-tailed Student's t test and percentage of change. RESULTS: Test-retest reliability was statistically significant for all scales except Activities of Daily Living and Anxiety. The coefficient of reliability was > 0.7 for all scales. Convergent and construct validity was detected with the constructs employed (Pearson's r > 0.4). Four/nine scales detected improvement (p < 0.05) in those patients in whom clinical change was recorded. CONCLUSION: The Spanish-AIMS retained the methodological properties of the original version and can be used as an outcome measure in Spanish speaking patients with RA.