Voluntary Counselling, HIV Testing and Sexual Behaviour Among Patients with Tuberculosis in a Rural District of Malawi.

OBJECTIVES: A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi in order to 1) verify the acceptability of voluntary counselling and testing for human immunodeficiency virus (HIV) infection; 2) describe sexual behaviour and condom use; and 3) identify socio-demographic and behavioural risk factors associated with 'no condom use'. DESIGN: Cross-sectional study. METHODS: Consecutive patients diagnosed with TB between January and December 2000 were offered voluntary counselling and HIV testing (VCT) and were subsequently interviewed. RESULTS: There were 1,049 new TB patients enrolled in the study. Of these, 1,007 (96%) were pre-test counselled, 955 (91%) underwent HIV testing and 912 (87%) were post-test counselled; 43 (4%) patients refused HIV testing. The overall HIV infection rate was 77%. Of all HIV-positive TB patients, 691 (94%) were put on cotrimoxazole. There were 479 (49%) TB patients who reported sexual encounters, of whom only 6% always used condoms. Unprotected sex was associated with having TB symptoms for over 1 month, having had less than 8 years of school education, being single, divorced or widowed or having sex with the same partner. CONCLUSIONS: Offering VCT to TB patients in this setting has a high acceptance rate and provides an opportunity to strengthen and integrate TB and HIV programmes

Voluntary Counselling, HIV Testing and Adjunctive Cotrimoxazole Reduces Mortality in Tuberculosis Patients in Thyolo, Malawi.

OBJECTIVES: To assess the feasibility and effectiveness of voluntary counselling, HIV testing and adjunctive cotrimoxazole in reducing mortality in a cohort of tuberculosis (TB) patients registered under routine programme conditions in a rural district of Malawi. DESIGN: 'Before' and 'after' cohort study using historical controls. METHODS: Between 1 July 1999 and 30 June 2000 all TB patients were started on standardized anti-TB treatment, and offered voluntary counselling and HIV testing (VCT). Those found to be HIV-positive were offered cotrimoxazole at a dose of 480 mg twice daily, provided there were no contraindications. Side-effects were monitored clinically. End-of-treatment outcomes in this cohort (intervention group) were compared with a cohort registered between 1 July 1998 and 30 June 1999 in whom VCT and cotrimoxazole was not offered (control group). FINDINGS: A total of 1986 patients was registered in the study: 1061 in the intervention group and 925 in the control cohort. In the intervention group, 1019 (96%) patients were counselled pre-test, 964 (91%) underwent HIV testing and 938 (88%) were counselled post-test. The overall HIV-seroprevalence rate was 77%. A total of 693 patients were given cotrimoxazole of whom 14 (2%) manifested minor dermatological reactions. The adjusted relative risk of death in the intervention group compared with the control group was 0.81 (P < 0.001). The number needed to treat with VCT and adjunctive cotrimoxazole to prevent one death during anti-TB treatment was 12.5. INTERPRETATION: This study shows that VCT and adjunctive cotrimoxazole is feasible, safe and reduces mortality rates in TB patients under routine programme conditions

The impact of latent CMV infection on NK-cell mobilization and expression of KLRG1 and CD57 in response to acute exercise.

Natural killer (NK) cells are cytotoxic effectors of the innate immune system that are able to distinguish healthy autologous cells from tumors and virally infected cells. NK-cells kill the targeted cells by releasing cytotoxic proteins, a process that is governed by inhibitory surface receptors, such as KLRG1. Additionally, activated NK-cells are able to proliferate in response to immunological stimuli, a process that is inhibited in NK-cells expressing the senescence marker CD57. Acute bouts of exercise are known to mobilize NK cells into the blood compartment, which could alter immunity; however, whether or not exercise alters NK-cell KLRG1 and CD57 expression has not been fully elucidated. Furthermore, as latent CMV infection is associated with an increased frequency of inhibitory NK cells, it is not known if CMV status influences NK-cell mobilization in response to acute exercise. PURPOSE: To examine the impact of latent CMV infection on the mobilization of NK-cells and their expression of KLRG1 and CD57 in response to acute exercise. METHODS: Otherwise healthy CMV seropositive (CMV+) and CMV seronegative (CMV-) males (age 23-35 years) completed a 30-min cycling protocol at 85% of maximum power. Lymphocytes isolated from whole blood before, immediately after, and one hour after exercise were surface-stained with monoclonal antibodies against CD3, CD56, KLRG1 and CD57 and analyzed by 4-color flow cytometry. RESULTS: Preliminary analysis of the data show a prodigious increase in the number of CD56 dim (mature, highly cytotoxic subset) NK-cells immediately after exercise in all subjects, which subsequently fell below pre-exercise values 1 hour later. In CMV- subjects, the proportion of CD56 bright (immature, mildly cytotoxic) NK cells was considerably higher 1 hour post-exercise than before exercise, but the number of cells changed very little suggesting that the increased proportion was due merely to the egress of CD56 dim NK cells. Interestingly, CMV seropositivity was associated with a near complete absence of CD56 bright NK cells that was unaffected by exercise. Neither exercise nor CMV status influenced the proportion of NK-cells expressing KLRG1 or CD57. CONCLUSION: Preliminary analysis of this data indicates that acute exercise preferentially mobilizes CD56 dim NK cells without altering KLRG1 and CD57 expression. Latent CMV infection is associated with a lowered proportion of CD56 bright NK-cells; however, the NK-cell response to exercise was not influenced by CMV status. Future work will examine the role of aging on NK-cell response to exercise and CMV status

Multidisciplinary treatment for chronic pain: a systematic review of interventions and outcomes

Objectives. To provide an overview of the effectiveness of multidisciplinary treatments of chronic pain and investigate about their differential effects on outcome in various pain conditions and of different multidisciplinary treatments, settings or durations. Methods. In this article, the authors performed a systematic review of all currently available randomized controlled trials (RCTs) fulfilling the inclusion criteria, by using a recently developed rating system aimed to assess the strength of evidence with regard to the methodological quality of the trials. Results. Compared with other non-disciplinary treatments, moderate evidence of higher effectiveness for multidisciplinary interventions was shown. In contrast to no treatment or standard medical treatment, strong evidence was detected in favour of multidisciplinary treatments. The evidence that comprehensive inpatient programmes were more beneficial that outpatient programmes was moderate. Fibromyalgia and chronic back pain patients tended to profit more substantially than patients with diverse origins or chronic pain diagnoses. No evidence was found that treatment variables, such as duration or programme components, were influential for the success of the intervention. Conclusion. A standard of multidisciplinary programmes should be internationally established to guarantee generally good outcomes in the treatment of chronic pain. Our results highlight the lack of quality of design, execution or reporting of many of the RCTs included in this article. Future studies should more specifically focus on differential effects of treatment components and patient variables, allowing the identification of subgroups, which most probably would profit from multidisciplinary pain programme

A spatially and temporally localized sub-laser-cycle electron source

We present an experimental and numerical study of electron emission from a sharp tungsten tip triggered by sub-8 femtosecond low power laser pulses. This process is non-linear in the laser electric field, and the non-linearity can be tuned via the DC voltage applied to the tip. Numerical simulations of this system show that electron emission takes place within less than one optical period of the exciting laser pulse, so that an 8 fsec 800 nm laser pulse is capable of producing a single electron pulse of less than 1 fsec duration. Furthermore, we find that the carrier-envelope phase dependence of the emission process is smaller than 0.1% for an 8 fsec pulse but is steeply increasing with decreasing laser pulse duration.Comment: 4 pages, 5 figure

Negative phase time for Scattering at Quantum Wells: A Microwave Analogy Experiment

If a quantum mechanical particle is scattered by a potential well, the wave function of the particle can propagate with negative phase time. Due to the analogy of the Schr\"odinger and the Helmholtz equation this phenomenon is expected to be observable for electromagnetic wave propagation. Experimental data of electromagnetic wells realized by wave guides filled with different dielectrics confirm this conjecture now.Comment: 10 pages, 6 figure

The Impact of Latent Herpesvirus Infections on the Mobilization of Recent Thymic Emigrants and Extrathymic T-cells in Response to Acute Aerobic Exercise in Man

T-cells typically mature in the thymus gland, which eventually succumbs to age-related atrophy, resulting in a decreased naïve T-cell repertoire in middle to later years. Aged individuals and those with persistently reactivating herpesvirus infections have an increased reliance on the extrathymic maturation of T-cells due to the shrinking effects that age and latent viral infection has on the naïve T-cell repertoire. Acute bouts of aerobic exercise are known to mobilize T-cells that exhibit both a naïve and late-stage differentiation phenotype into the blood compartment; however, it is not known if recent thymic emigrants (RTE) or extrathymic T-cells contribute to the lymphocytosis associated with exercise. PURPOSE: To examine the impact of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection on the mobilization of RTE and extrathymic T-cells in response to acute exercise. METHODS: Otherwise healthy CMV or EBV seropositive (CMV+ or EBV+) and CMV or EBV seronegative (CMV- or EBV-) males (age 23-35y) completed a 30-min cycling protocol at 85% of maximum power. Lymphocytes isolated from whole blood before, immediately after, and one hour after exercise were surface stained with monoclonal antibodies to identify phenotypes of RTE (CD103+/CD62L-) and extrathymic T-cells believed to mature in the liver (CD3+/CD25-/CD122+) and the epithelium of the small intestine (CD3+/CD4-/CD8-; TCRγδ+/ CD8αα+; CD3-/CD2+/CD7+). Cell populations were analyzed by flow cytometry and antibodies against CMV and EBV were determined in serum by ELISA. RESULTS: Preliminary analyses show that the proportion of RTE among the total CD3+/CD4+ or CD3+/CD8+ T-cell subsets did not change immediately after exercise, but was elevated above baseline 1h later due to the preferential egress of late stage differentiated T-cells. Neither CMV nor EBV status influenced the proportions of RTE in blood in response to exercise. T-cells mainly found in intestinal mucosa (i.e. CD3+/CD4-/CD8- and CD3-/CD2+/CD7+) were found to increase in blood immediately after exercise; an effect that appeared to be more pronounced in EBV but not CMV-infected subjects. CONCLUSION: An acute bout of aerobic exercise elicits the mobilization of T-cells exhibiting phenotype characteristics of extrathymically matured T-cells, suggesting that extrathymic T-cell mobilization contributes to the lymphocytosis associated with acute exercise. This effect appears to be amplified in subjects carrying a latent EBV but not CMV infection. Future research should attempt to establish the impact of long-term exercise and latent herpesvirus infections on the frequency of RTE and extrathymic T-cells in the aged, as this could have significant implications for age-associated immune dysfunction

The Impact of Long Duration Spaceflight on Plasma Antimicrobial Proteins

Introduction: Robust immunity is essential for further human exploration of the solar system beyond Earth’s orbit. Spaceflight has been associated with immune perturbations and latent viral reactivation. However, logistical constraints have restricted many of these studies to simple pre- and post-flight measures, which are greatly confounded by the stressors associated with launch, landing and re-adaptation to the 1G environment. More in-flight immune data are required particularly during long-duration (3-6 months) spaceflight missions. This study examined the effects of spaceflight on plasma antimicrobial proteins (AMPs) and reactivation of latent herpesviruses. Methods: Plasma, saliva and urine samples were obtained from 20 crewmembers who spent ~6-months on the International Space Station (ISS). Samples were collected 180 and 45-days before launch, in-flight (at ‘early, ‘mid’ and ‘late’ stages of the mission), immediately upon return to Earth (R+0) and 30 days following return (R+30). Plasma LL-37, HNP 1-3 and lysozyme concentrations were determined by ELISA. Saliva Epstein-Barr virus (EBV), varicella zoster virus (VZV) and urine cytomegalovirus (CMV) DNA levels were quantified by Real-Time PCR. Maximum likelihood linear mixed models (LMM) were used to determine main effects of time (pre-flight, in-flight, R+0 and R+30), and EBV, VZV and CMV viral shedding status (shedding or non-shedding) on the concentration of each AMPs. Results: Lower plasma levels of LL-37 were found at R+0, compared to pre-flight, in-flight and R+30 (-80.6%, -80.2% and -73.49% respectively; p \u3c 0.01). Plasma HNP 1-3 levels were elevated above pre-flight level during flight, at R+0 and R+30 (+24%, +40% and +17% respectively; p \u3c 0.01). Only those crewmembers found to shed CMV had a significant reduction in plasma LL-37 at R+0 (p \u3c 0.05). Similarly, crewmembers found to shed VZV at R+0 had lower HNP 1-3 concentrations than crewmembers who did not shed VZV (-68.9%; p \u3c 0.01). Finally, only those crewmembers who shed EBV had increased plasma levels of HNP 1-3 at R+0 (p \u3c 0.01). Plasma lysozyme levels were unaffected by spaceflight or latent viral shedding. Conclusion: Long-duration spaceflight alters plasma LL-37 and HNP 1-3 levels and are linked to the reactivation of latent herpesviruses. The in-flight changes observed for HNP 1-3 indicate that certain immune perturbations may be independent of launch/landing stress. Future studies are required to determine if spaceflight induced immune dysregulation increases the risk of an adverse health event before exploration-class planetary missions (i.e. to Mars) can be considered

Diagnosis and management of anaemia and iron deficiency in patients with haematological malignancies or solid tumours in France in 2009-2010: the AnemOnHe study

OBJECTIVE: To describe the management of anaemia in 2009-2010 in France in patients with haematological malignancies (HM) or solid tumours (ST). METHODS: Retrospective observational study in 57 centres, enrolling adult patients with HM or ST treated for an episode of anaemia (duration of the episode &gt;/= 3 months occurring in the last 12 months). RESULTS: 220 patients with ST (breast, 18%; lung, 18%) and 56 with HM (lymphoma, 60%) were included (median age, 68 years; female, 53%). Mean haemoglobin level at anaemia diagnosis was 9.3 +/- 1.4 g/dL (&lt;8 g/dL for 16%) and 9.8 +/- 1.1g/dL (&lt;8 g/dL for 6%) in HM and ST patients, respectively. At least one parameter of iron deficiency (ferritin, transferrin saturation) was assessed in 26% of HM and 19% of ST patients. Treatment of anaemia included erythropoiesis-stimulating agents (ESA) for 98% of HM and 89% of ST patients. Iron was prescribed to 14% (oral, 12%; intravenous, 2%) of HM patients and to 42% (oral, 17%; intravenous, 25%) of ST patients. The rates of blood transfusions were high: 70% in HM and 46% in ST patients; transfusions alone or administrated with ESA were more frequent in patients with Hb &lt;8 g/dL. CONCLUSION: Although recent guidelines recommend evaluating iron deficiency and correcting anaemia by using intravenous iron, our study in cancer patients evidenced that ESA and blood transfusions are still frequently used as the treatment of anaemia in cancer patients. Iron deficiency is insufficiently assessed (only one patient among five) and as a consequence iron deficiency is most likely insufficiently treated

Lorentz Invariant Superluminal Tunneling

It is shown that superluminal optical signalling is possible without violating Lorentz invariance and causality via tunneling through photonic band gaps in inhomogeneous dielectrics of a special kind.Comment: 10 pages revtex, no figure, more discussions added, submitted to Phys. Rev.