Self-reported difficulties with everyday function, cognitive symptoms, and cognitive function in people with HIV

BACKGROUND: We determined factors associated with self-reported decline in activities of daily living (ADLs) and symptoms of cognitive impairment in HIV positive (HIV+) adults in five European clinics. METHODS: HIV+ adults underwent computerized and pen-and-paper neuropsychological tests and questionnaires of cognitive symptoms and ADLs. We considered cognitive function in five domains, psychosocial factors and clinical parameters as potentially associated with symptoms. Separate regression analyses were used to determine factors associated with decline in ADL (defined as self-reported decline affecting ≥2 ADLs and attributed to cognitive difficulties) and self-reported frequency of symptoms of cognitive impairment. We also estimated the diagnostic accuracy of both questionnaires as tests for cognitive impairment. RESULTS: 448 patients completed the assessments (mean age 45.8 years, 84% male, 87% white, median CD4 count 550 cells/mm, median time since HIV diagnosis 9.9 years, 81% virologically suppressed [HIV-1 plasma RNA <50 copies/mL]). Ninety-six (21.4%) reported decline in ADLs and attributed this to cognitive difficulties. Self-reported decline in ADLs and increased symptoms of cognitive impairment were both associated with worse performance on some cognitive tests. There were also strong associations with financial difficulties, depressive and anxiety symptoms, unemployment, and longer time since HIV diagnosis. Both questionnaires performed poorly as diagnostic tests for cognitive impairment. CONCLUSION: Patients' own assessments of everyday function and symptoms were associated with objectively-measured cognitive function. However, there were strong associations with other psychosocial issues including mood and anxiety disorders and socioeconomic hardship. This should be considered when assessing HIV-associated cognitive impairment in clinical care or research studies

A new health care index predicts short term mortality for TB and HIV co-infected people

BACKGROUND: Using 2004–2007 TB:HIV Study data from Europe and Latin America, we previously generated a health care index (HCI) for TB and HIV co-infected people. With improvements in diagnostic and management practices, we have now updated the HCI with new data. METHODS: We evaluated nine aspects of health care in Cox proportional hazards models on time from TB diagnosis to death. Kaplan-Meier methods were used to estimate the probability of death by HCI quartile. RESULTS: Of 1396 eligible individuals (72% male, 59% from Eastern Europe), 269 died within 12 months. Use of rifamycin/isoniazid/pyrazinamide-based treatment (HR 0.67, 95% CI 0.50–0.89), TB drug susceptibility testing (DST) and number of active TB drugs (DST + <3 drugs (HR 1.09, 95% CI 0.80–1.48), DST + ≥3 drugs (HR 0.49, 95% CI 0.35–0.70) vs. no DST), recent HIV-RNA measurement (HR 0.64, 95% CI 0.50–0.82) and combination antiretroviral therapy use (HR 0.72, 95% CI 0.53–0.97) were associated with mortality. These factors contributed respectively 5, –1, 8, 5 and 4 to the HCI. Lower HCI was associated with an increased probability of death; 30% (95% CI 26–35) vs. 9% (95% CI 6–13) in the lowest vs. the highest quartile. CONCLUSION: We found five potentially modifiable health care components that were associated with mortality among TB-HIV positive individuals. Validation of our HCI in other TB cohorts could enhance our findings

Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study

BACKGROUND: Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study. METHODS: Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models. FINDINGS: Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001). INTERPRETATION: Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe. FUNDING: EU Seventh Framework Programme

A Model of Free Tissue Transfer: The Rat Epigastric Free Flap

Free tissue transfer has been increasingly used in clinical practice since the 1970s, allowing reconstruction of complex and otherwise untreatable defects resulting from tumor extirpation, trauma, infections, malformations or burns. Free flaps are particularly useful for reconstructing highly complex anatomical regions, like those of the head and neck, the hand, the foot and the perineum. Moreover, basic and translational research in the area of free tissue transfer is of great clinical potential. Notwithstanding, surgical trainees and researchers are frequently deterred from using microsurgical models of tissue transfer, due to lack of information regarding the technical aspects involved in the operative procedures. The aim of this paper is to present the steps required to transfer a fasciocutaneous epigastric free flap to the neck in the rat. This flap is based on the superficial epigastric artery and vein, which originates from and drain into the femoral artery and vein, respectively. On average the caliber of the superficial epigastric vein is 0.6 to 0.8 mm, contrasting with the 0.3 to 0.5 mm of the superficial epigastric artery. Histologically, the flap is a composite block of tissues, containing skin (epidermis and dermis), a layer of fat tissue (panniculus adiposus), a layer of striated muscle (panniculus carnosus), and a layer of loose areolar tissue. Succinctly, the epigastric flap is raised on its pedicle vessels that are then anastomosed to the external jugular vein and to the carotid artery on the ventral surface of the rat's neck. According to our experience, this model guarantees the complete survival of approximately 70 to 80% of epigastric flaps transferred to the neck region. The flap can be evaluated whenever needed by visual inspection. Hence, the authors believe this is a good experimental model for microsurgical research and training.info:eu-repo/semantics/publishedVersio

Abstract P-27: The 30S Ribosomal Subunit Assembly Factor Rbfa Plays a Key Role in the Formation of the Central Pseudoknot and in the Correct Docking of Helix 44 of the Decoding Center

Background: Ribosome biogenesis is a complicated multi-stage process. In the cell, 30S ribosomal subunit assembly is fast and efficient, proceeding with the help of numerous assembly protein factors. The exact role of most assembly factors and mechanistic details of their operation remain unclear. The combination of genetic modification with cryo-EM analysis is widely used to identify the role of protein factors in assisting specific steps of the ribosome assembly process. The strain with knockout of a single assembly factor gene accumulates immature ribosomal particles which structural characterization reveals the information about the reactions catalyzed by the corresponding factor. Methods: We isolated the immature 30S subunits (pre-30S subunits) from the Escherichia coli strain lacking the rbfA gene (ΔrbfA) and characterized them by cryo-electron microscopy (cryo-EM). Results: Deletion of the assembly factor RbfA caused a substantial distortion of the structure of an important central pseudoknot which connects three major domains of 30S subunit and is necessary for ribosome stability. It was shown that the relative order of the assembly of the 3′ head domain and the docking of the functionally important helix 44 depends on the presence of RbfA. The formation of the central pseudoknot may promote stabilization of the head domain, likely through the RbfA-dependent maturation of the neck helix 28. The cryo-EM maps for pre-30S subunits were divided into the classes corresponding to consecutive assembly intermediates: from the particles with completely unresolved head domain and unfolded central pseudoknot to almost mature 30S subunits with well-resolved body, platform, and head domains and with partially distorted helix 44. Cryo-EM analysis of ΔrbfA 30S particles revealing the accumulation of two predominant classes of early and late intermediates (obtained at 2.7 Å resolutions) allowed us to suggest that RbfA participate in two stages of the 30S subunit assembly and is deeper involved in the maturation process than previously thought. Conclusion: In summary, RbfA acts at two distinctive 30S assembly stages: early formation of the central pseudoknot including the folding of the head, and positioning of helix 44 in the decoding center at a later stage. An update to the model of factor-dependent 30S maturation was proposed, suggesting that RfbA is involved in most of the subunit assembly process

Laser photoplethysmography in integrated evaluation of collateral circulation of lower extremities

The paper evaluated the diagnostic value of laser photoplethysmography when examining patients with chronic lower limb ischemia. A statistical analysis of the research results was made, and diagrams of relationship between the degrees of ischemia and blood flow are presented

Feasibility and effectiveness of indicator condition-guided testing for HIV: results from HIDES I (HIV indicator diseases across Europe study)

Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009- February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% [95% CI: 1.42-2.34]; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe

Quantitative analysis of ribosome–mRNA complexes at different translation stages

Inhibition of primer extension by ribosome–mRNA complexes (toeprinting) is a proven and powerful technique for studying mechanisms of mRNA translation. Here we have assayed an advanced toeprinting approach that employs fluorescently labeled DNA primers, followed by capillary electrophoresis utilizing standard instruments for sequencing and fragment analysis. We demonstrate that this improved technique is not merely fast and cost-effective, but also brings the primer extension inhibition method up to the next level. The electrophoretic pattern of the primer extension reaction can be characterized with a precision unattainable by the common toeprint analysis utilizing radioactive isotopes. This method allows us to detect and quantify stable ribosomal complexes at all stages of translation, including initiation, elongation and termination, generated during the complete translation process in both the in vitro reconstituted translation system and the cell lysate. We also point out the unique advantages of this new methodology, including the ability to assay sites of the ribosomal complex assembly on several mRNA species in the same reaction mixture

Multicenter European Prevalence Study of Neurocognitive Impairment and Associated Factors in HIV Positive Patients

We conducted a cross-sectional study in 448 HIV positive patients attending five European outpatient clinics to determine prevalence of and factors associated with neurocognitive impairment (NCI) using computerized and pen-and-paper neuropsychological tests. NCI was defined as a normalized Z score ≤-1 in at least 2 out of 5 cognitive domains. Participants' mean age was 45.8 years; 84% male; 87% white; 56% university educated; median CD4 count 550 cells/mm(3); 89% on antiretroviral therapy. 156 (35%) participants had NCI, among whom 26 (17%; 5.8% overall) reported a decline in activities of daily living. Prevalence of NCI was lower in those always able to afford basic needs (adjusted prevalence ratio [aPR] 0.71, 95% confidence interval [CI] 0.54-0.94) or with a university education (aPR 0.72, 95% CI 0.54-0.97) and higher in those with severe depressive symptoms (aPR 1.53, 95% CI 1.09-2.14) or a significant comorbid condition (aPR 1.40, 95% CI 1.03-1.90)