Rapid Diagnostic Algorithms as a Screening Tool for Tuberculosis: An Assessor Blinded Cross-Sectional Study

Background: A major obstacle to effectively treat and control tuberculosis is the absence of an accurate, rapid, and low-cost diagnostic tool. A new approach for the screening of patients for tuberculosis is the use of rapid diagnostic classification algorithms. Methods: We tested a previously published diagnostic algorithm based on four biomarkers as a screening tool for tuberculosis in a Central European patient population using an assessor-blinded cross-sectional study design. In addition, we developed an improved diagnostic classification algorithm based on a study population at a tertiary hospital in Vienna, Austria, by supervised computational statistics. Results: The diagnostic accuracy of the previously published diagnostic algorithm for our patient population consisting of 206 patients was 54% (CI: 47%–61%). An improved model was constructed using inflammation parameters and clinical information. A diagnostic accuracy of 86% (CI: 80%–90%) was demonstrated by 10-fold cross validation. An alternative model relying solely on clinical parameters exhibited a diagnostic accuracy of 85% (CI: 79%–89%). Conclusion: Here we show that a rapid diagnostic algorithm based on clinical parameters is only slightly improved by inclusion of inflammation markers in our cohort. Our results also emphasize the need for validation of new diagnostic algorithms in different settings and patient populations

First Search for Exclusive Diphoton Production at High Mass with Tagged Protons in Proton-Proton Collisions at root s=13 TeV

A search for exclusive two-photon production via photon exchange in proton-proton collisions, pp -> p gamma gamma p with intact protons, is presented. The data correspond to an integrated luminosity of 9.4 fb(-1) collected in 2016 using the CMS and TOTEM detectors at a center-of-mass energy of 13 TeVat the LHC. Events are selected with a diphoton invariant mass above 350 GeVand with both protons intact in the final state, to reduce backgrounds from strong interactions. The events of interest are those where the invariant mass and rapidity calculated from the momentum losses of the forward-moving protons match the mass and rapidity of the central, two-photon system. No events are found that satisfy this condition. Interpreting this result in an effective dimension-8 extension of the standard model, the first limits are set on the two anomalous four-photon coupling parameters. If the other parameter is constrained to its standard model value, the limits at 95% confidence level are vertical bar zeta(1)vertical bar < 2.9 x 10(-1)3 GeV-4 and vertical bar zeta(2)vertical bar < 6.0 x 10(-13) GeV-4.Peer reviewe

The socioeconomic impact of tuberculosis on children and adolescents : a scoping review and conceptual framework

Background: Tuberculosis (TB) has been repeatedly shown to have socioeconomic impacts in both individual-level and ecological studies; however, much less is known about this effect among children and adolescents and the extent to which being affected by TB during childhood and adolescence can have life-course implications. This paper describes the results of the development of a conceptual framework and scoping review to review the evidence on the short- and long-term socioeconomic impact of tuberculosis on children and adolescents. Objectives: To increase knowledge of the socioeconomic impact of TB on children and adolescents. Methods: We developed a conceptual framework of the socioeconomic impact of TB on children and adolescents, and used scoping review methods to search for evidence supporting or disproving it. We searched four academic databases from 1 January 1990 to 6 April 2021 and conducted targeted searches of grey literature. We extracted data using a standard form and analysed data thematically. Results: Thirty-six studies (29 qualitative, five quantitative and two mixed methods studies) were included in the review. Overall, the evidence supported the conceptual framework, suggesting a severe socioeconomic impact of TB on children and adolescents through all the postulated pathways. Effects ranged from impoverishment, stigma, and family separation, to effects on nutrition and missed education opportunities. TB did not seem to exert a different socioeconomic impact when directly or indirectly affecting children/adolescents, suggesting that TB can affect this group even when they are not affected by the disease. No study provided sufficient follow-up to observe the long-term socioeconomic effect of TB in this age group. Conclusion: The evidence gathered in this review reinforces our understanding of the impact of TB on children and adolescents and highlights the importance of considering effects during the entire life course. Both ad-hoc and sustainable social protection measures and strategies are essential to mitigate the socioeconomic consequences of TB among children and adolescents.publishedVersionPeer reviewe

Unemployment and ill health: a connection through inflammation?

<p>Abstract</p> <p>Background</p> <p>Unemployment is a source of acute and long-term psychosocial stress. Acute and chronic psychosocial stress can induce pronounced changes in human immune responses. In this study we tested our hypothesis that stress-induced low-grade tissue inflammation is more prevalent among the unemployed.</p> <p>Methods</p> <p>We determined the inflammatory status of 225 general population subjects below the general retirement age (65 years in Finland). Those who had levels of both interleukin-6 (≥ 0.97 pg/mL) and high-sensitivity C-reactive protein (≥ 1.49 mg/L) above the median were assessed to have an elevated inflammatory status (n = 72).</p> <p>Results</p> <p>An elevated inflammatory status was more common among the unemployed than among other study participants (59% versus 30%, p = 0.011). In the final multivariate model, those who were unemployed had over five-fold greater odds for having an elevated inflammatory status (OR 5.20, 95% CI 1.55-17.43, p = 0.008).</p> <p>Conclusion</p> <p>This preliminary finding suggests that stress-induced low-grade inflammation might be a link between unemployment and ill health.</p

Common MicroRNA Signatures in Cardiac Hypertrophic and Atrophic Remodeling Induced by Changes in Hemodynamic Load

BACKGROUND: Mechanical overload leads to cardiac hypertrophy and mechanical unloading to cardiac atrophy. Both conditions produce similar transcriptional changes including a re-expression of fetal genes, despite obvious differences in phenotype. MicroRNAs (miRNAs) are discussed as superordinate regulators of global gene networks acting mainly at the translational level. Here, we hypothesized that defined sets of miRNAs may determine the direction of cardiomyocyte plasticity responses. METHODOLOGY/PRINCIPAL FINDINGS: We employed ascending aortic stenosis (AS) and heterotopic heart transplantation (HTX) in syngenic Lewis rats to induce mechanical overloading and unloading, respectively. Heart weight was 26±3% higher in AS (n = 7) and 33±2% lower in HTX (n = 7) as compared to sham-operated (n = 6) and healthy controls (n = 7). Small RNAs were enriched from the left ventricles and subjected to quantitative stem-loop specific RT-PCR targeting a panel of 351 miRNAs. In total, 153 miRNAs could be unambiguously detected. Out of 72 miRNAs previously implicated in the cardiovascular system, 40 miRNAs were regulated in AS and/or HTX. Overall, HTX displayed a slightly broader activation pattern for moderately regulated miRNAs. Surprisingly, however, the regulation of individual miRNA expression was strikingly similar in direction and amplitude in AS and HTX with no miRNA being regulated in opposite direction. In contrast, fetal hearts from Lewis rats at embryonic day 18 exhibited an entirely different miRNA expression pattern. CONCLUSIONS: Taken together, our findings demonstrate that opposite changes in cardiac workload induce a common miRNA expression pattern which is markedly different from the fetal miRNA expression pattern. The direction of postnatal adaptive cardiac growth does, therefore, not appear to be determined at the level of single miRNAs or a specific set of miRNAs. Moreover, miRNAs themselves are not reprogrammed to a fetal program in response to changes in hemodynamic load

Depressive symptoms during rehabilitation period predict poor outcome of lumbar spinal stenosis surgery: A two-year perspective

<p>Abstract</p> <p>Background</p> <p>Previous research has shown an association between preoperative depressive symptoms and a poorer surgery outcome in lumbar spinal stenosis (LSS). It is not known whether depressive symptoms throughout the recovery period are relevant to the outcome of surgery in LSS. In this prospective clinical study the predictive value of preoperative and postoperative depressive symptoms with respect to the surgery outcome is reported.</p> <p>Methods</p> <p>96 patients (mean age 62 years) with symptomatic lumbar spinal stenosis underwent decompressive surgery. They completed the same set of questionnaires preoperatively and 3 months, 6 months, 1 year and 2 years postoperatively. Depressive symptoms were assessed with the 21-item Beck Depression Inventory. Physical functioning and pain were assessed with the Oswestry Disability Index, the Stucki Questionnaire, self-reported walking ability and VAS rating. Logistic regression analyses were used to examine the predictive value of preoperative and postoperative depressive symptoms regarding the surgery outcome. A "good" outcome was defined in two ways: first, by gaining a 30% improvement in relation to the preoperative disability and pain, and second, by having a score at or below the median value for disability and pain on 2-year follow-up.</p> <p>Results</p> <p>Having elevated depressive symptoms particularly on 3-month follow-up was predictive of a poorer surgery outcome regarding pain and disability: when the outcome was defined as less than 30% improvement from the baseline, the OR's (with 95% confidence intervals) were 2.94 (1.06-8.12), <0.05 for Oswestry and 3.33 (1.13-9.79), <0.05 for VAS. In median split approach the OR was 4.11 (1.27-13.32), <0.05 for Oswestry. Predictive associations also emerged between having depressive symptoms on 6-month and 1-year follow-ups and a poorer outcome regarding disability. The predictive value of elevated depressive symptoms particularly with respect to 2-yeard disability was evident whether the outcome was defined as a 30% improvement compared to the preoperative status or as belonging to the better scoring half of the study population on 2-year follow-up.</p> <p>Conclusions</p> <p>Preoperative and postoperative depressive symptoms may indicate those patients at greater risk of a poorer postoperative functional ability. For these patients, further clinical evaluation should be carried out, especially during postoperative stages.</p

Leisure-time physical activity, cardiorespiratory fitness and feelings of hopelessness in men

<p>Abstract</p> <p>Background</p> <p>Leisure-time physical activity (LTPA) and cardiorespiratory fitness contribute to mental health. Hopelessness has been linked to impaired mental health, cardiovascular events and mortality. Previous studies have focused on physical exercise and depression. We examined the associations of LTPA and cardiorespiratory fitness with feelings of hopelessness.</p> <p>Methods</p> <p>In this cross-sectional study leisure-time physical activity, maximal oxygen uptake (VO_2max), hopelessness and cardiovascular risk factors were assessed in a population-based cohort of 2428 men aged 42 – 60 years old at baseline.</p> <p>Results</p> <p>Men feeling more hopeless about their future and reaching goals were less physically active, less fit and had a higher prevalence of many cardiovascular risk factors than men with lower levels of hopelessness. In a logistic regression model adjusted for age, smoking, alcohol consumption, cardiovascular disease and socioeconomic status, men engaging in less than 60 min/week of moderate-to-vigorous LTPA were 37% (95% CI 11 – 67%) more likely to feel hopeless than those engaging in at least 2.5 h/wk of LTPA. After further adjusting for elevated depressive symptoms the association of LTPA and hopelessness remained significant. VO_2maxwas also associated with hopelessness, but not after adjustment for depressive symptoms.</p> <p>Conclusion</p> <p>Moderate and vigorous LTPA and cardiorespiratory fitness were inversely associated with hopelessness in these middle-aged men. These findings suggest that physical inactivity and poor cardiorespiratory fitness is an important associate of hopelessness, a distinct element of low subjective well-being.</p

The stability of life satisfaction in a 15-year follow-up of adult Finns healthy at baseline

BACKGROUND: While physical health has improved considerably over recent decades in Finland, the disease burden of mental health, especially that of depression, has become increasingly demanding. However, we lack long-term data on the natural course of subjective well-being in the general population. The aim of this study was to investigate the long-term course of self-reported life satisfaction. METHODS: This was a 15-year prospective cohort study on a nationwide sample of adult Finnish twins (N = 9679), aged 18–45 and healthy at baseline, who responded to postal questionnaires in 1975, 1981 and 1990 including a 4-item life satisfaction scale (happiness/easiness/interest in life and feelings of loneliness). Life satisfaction score (range: 4–20) was classified into three categories: satisfied (4–6), intermediate (7–11) and dissatisfied group (12–20). The associations between life satisfaction scores during the follow-up were studied with linear/logistic regression. RESULTS: Moderate stability and only a slight effect of age or birth-cohort on mean life satisfaction score (LS) were detected. In 1990, 56% of all and 31% of the dissatisfied remained in the same LS category as at baseline. Only 5.9% of the study subjects changed from being satisfied to dissatisfied or vice versa. Correlations between continuous scores (1975, 1981 and 1990) were 0.3–0.4. Baseline dissatisfaction (compared to satisfaction) predicted dissatisfaction in 1981 (OR = 10.4; 95%CI 8.3–13.1) and 1990 (5.6; 4.6–6.8). Multiple adjustments decreased the risk only slightly. CONCLUSIONS: Life satisfaction in adult Finns was moderately stable during 15 years. Among an identifiable group (i.e. the dissatisfied) life dissatisfaction may become persistent, which places them at a greater risk of adverse health outcomes