ObjectivesLeptospirosis has been documented in slaughterhouse workers around the world. Risk factors include smoking and drinking at work, and performing tasks such as cleaning offal. This paper ...examined risk factors for leptospirosis seropositivity in slaughterhouse workers in western Kenya.MethodsThe study was conducted between May 2011 and October 2012. Questionnaires were used to collect information from workers on demographic data, health and hygiene practices in the slaughterhouse. A commercial ELISA detected antibodies to Leptospira spp. in serum samples and multilevel logistic regression analysis identified factors associated with leptospirosis seropositivity.ResultsA total of 737 workers from 142 slaughterhouses were recruited. The seroprevalence of antibodies to Leptospira spp. was 13.4% (95% CI 11.1% to 16.1%). Risk factors included: having wounds (OR 3.1; 95% CI 1.5 to 6.1); smoking (OR 1.8; 95% CI 1.1 to 2.9); eating at work (OR 2.1; 95% CI 1.2 to 3.6); cleaning the offal (OR 5.1; 95% CI 1.8 to 15.0); and having a borehole for personal water use (OR 2.3; 95% CI 1.1 to 4.7). At the slaughterhouse level, risk factors included having a roof (OR 2.6; 95% CI 1.2 to 5.6) and drawing water from a well (OR 2.2; 95% CI 1.2 to 4.0). Protective factors included working in slaughterhouses where antemortem inspection was conducted (OR 0.6; 95% CI 0.4 to 1.0) and where workers wore protective aprons (OR 0.4; 95% CI 0.2 to 0.7).ConclusionsThis is the first report of leptospirosis seropositivity in slaughterhouse workers in Kenya. Potential risk factors were identified and this information can be used to educate workers regarding their disease risks and ways to prevent or reduce transmission.
Service encounter quality is an area of growing interest to researchers and managers alike, yet little is known about the effects of face-to-face service encounter quality within a ...business-to-business setting. In this paper, a psychometrically sound measure of such service encounter quality is proposed, and consequences of this construct are empirically assessed. Both a literature review and a dyadic in-depth interview approach were used to develop a conceptual framework and a pool of items to capture service encounter quality. A mail survey of customers was undertaken, and a response rate of 36% was obtained. Data analysis was conducted via confirmatory factor analysis and structural equation modeling. Findings reveal a four-factor structure of service encounter quality, encompassing professionalism, civility, friendliness and competence dimensions. Service encounter quality was found to be directly related to customer satisfaction and service quality perceptions, and indirectly to loyalty. The importance of these findings for practitioners and for future research on service encounter quality is discussed.
Although pulmonary toxicity from sirolimus is well recognized, the biochemically homologous everolimus has until recently been thought to be free from this side effect. Emerging evidence suggests an ...association between high-dose everolimus and symptomatic pneumonitis. Toxicity at typical immunosuppressive doses has also been described. In support of these observations, we report the occurrence of clinical pneumonitis in 3 patients in association with everolimus therapy after heart transplantation in the absence of other causative factors. Typical onset consisted of dyspnea, hypoxemia, and bilateral diffuse pulmonary infiltrates beginning between 2 weeks and 6 months after commencement of the drug. Although uncommon, everolimus may cause pneumonitis and should be considered in the differential diagnosis of pulmonary infiltrates and hypoxemia in an appropriate clinical setting.
Egg‐tempera painting is a pictorial technique widely used in the Middle Ages, although poorly studied in its physico‐chemical aspects until now. Here we show how NMR relaxometry and rheology can be ...combined to probe egg‐tempera paints and shed new light on their structure and behavior. Based on recipes of the 15th century, model formulations with egg yolk and green earth have been reproduced to characterize the physicochemical properties of this paint at the mesoscopic and macroscopic scales. The rheological measurements highlight a synergetic effect between green earth and egg yolk, induced by the interactions between them and the structural organisation of the system. 1H NMR relaxometry emphasizes the presence and the structure of a network formed by the yolk and the pigment.
Crack the code of egg‐tempera paints: The macroscopic and microscopic properties of egg‐tempera paint prepared with green earth are highlighted via rheology and NMR relaxometry.
Introduction: Cytotoxic T lymphocytes (CTL) that encounter antigen proliferate from a single naïve T-cell to form a population with diverse effector function and differentiation states, that control ...and prevent infection and cancer. Antigen-specific CTL are extremely heterogeneous in terms of clonotype, differentiation state and efficacy. Factors that define CTL of superior efficacy are well explored. TCR signal strength is known to modulate the breadth and magnitude of CTL effector functions, and epigenetic marks modulate intrinsic states such as exhaustion that limit activation. It is not clear if or how TCR signal strength modulates contact-dependent killing, and TCR affinity, TCR avidity, or factors downstream of the TCR could all contribute. There is a critical period of contact when a TCR engages cognate peptide- MHC class I molecules on a target cell that determines if the cell will be killed or survive. This is important to explore as not all T-cell therapy products to treat cancer are equally efficacious despite lentiviral transduction with the same chimeric-antigen-receptor. Lack of CTL efficacy is also encountered in chronic viral infections. Indeed, antigen-specific CTL from HIV controllers suppress HIV replication in vitro unlike antigen-specific CTL from chronic progressors. Viral suppression correlates with target cell elimination suggesting a critical role for contact-dependent killing.
Results: To identify factors that define superior CTL efficacy downstream of the TCR, we generated TCR-identical CD8+ CTL clones specific for a single epitope, HIV-1 FLKEKGGL (FL8) Nef (90-97) restricted by HLA B*0801, from individuals with HLA B*08-FL8 tetramer specific responses dominated by the use of a single TCR. Remarkably, clones that used the same TCR and bound tetramer with identical avidity, indicating the same surface expression of TCR, had distinct abilities to suppress HIV-1 in vitro. The mechanism of in vitro suppression correlated with target cell elimination demonstrating TCR-identical CTL clones can have distinct contact-dependent killing efficiency. Effective clones were highly responsive at low antigen densities, as might be encountered during physiological viral infection, with more rapid onset of signalling demonstrated by higher phospho-ERK MFI after 10 minutes of stimulation, faster onset of degranulation, and a higher final proportion of cells responding with CD107a expression, a marker of degranulation, at one hour. These novel distinctions in a reductionist in vitro model enabled us to dissect virus suppressive activity beyond initial TCR-antigen contact. On transcriptome examination we identified novel putative coreceptors containing ITAM (XX receptor to be revealedXX) or ITIM (XX two receptors to be revealed XX) motifs that were consistently over or under expressed on CTL clones that demonstrated superior contact-dependent killing.
Furthermore, ex vivo RT-PCR analysis of TCR-identical single cells sorted from the HLA B*08-FL8 tetramer positive population from which the CTL clones were generated, identified two populations of CTL, defined by expression of these novel ITAM and ITIM receptors. Lentiviral transduction of Jurkat cells with the novel ITAM receptor enhanced MFI phospho-ERK expression at 10 minutes when activated using plate bound OKT3, to generate a TCR signal, suggesting that this ITAM receptor may act as a TCR co-stimulatory molecule. T-cell poise may be critical to efficient contact-dependent killing, particularly if antigen or CTL cell numbers are limiting, by modulation of the probability of target cell death during each CTL-TCR engagement with its cognate peptide- MHC complex. We also demonstrated that TCR-identical CTL clones from one individual had distinct epigenetic regulation of TNF secretion.
Conclusion: Our results suggest that poise of the signalling cascade and intrinsic ontogenetic regulation of functions are critical to antiviral activity and identify putative novel check-point targets for therapeutic development.
Mead:BMS: Honoraria; Pfizer: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau.
A substantial proportion of the population with congestive heart failure (CHF) has concomitant airway disease. Little information exists on the tolerability of carvedilol in patients with chronic ...obstructive pulmonary disease (COPD). In this study, we assessed the tolerability and efficacy of carvedilol in patients with CHF and concomitant COPD or asthma.
Between 1996 and 2000, a total of 487 patients began receiving open-label carvedilol. Forty-three (9%) had COPD (
n = 31) or asthma (
n = 12). Spirometry supported clinical diagnosis in all, and full pulmonary function testing supported diagnosis in 71%. Sixty percent began carvedilol therapy in the hospital and underwent measurement of peak expiratory flow rates (PEFR) before and after dosing.
In patients with COPD, mean forced expiratory volume in one second (FEV
1) was 62% ± 13% predicted, reversibility was 4% ± 4% with bronchodilators, and FEV
1/FVC was 62% ± 8%. Mean PEFR was 325 ± 115 liter/min before the dose and increased by 17% 2 hours after the carvedilol dose (
p = 0.04). In patients with asthma, mean FEV
1 was 80% ± 17% predicted, reversibility was 13% ± 7% , and FEV
1/FVC was 74% ± 11%. Mean PEFR was 407 ± 161 liter/min before the dose with no significant change 2 hours after the dose. Carvedilol was introduced safely in 84% of patients with COPD, with only 1 patient withdrawn from therapy for wheezing. In contrast, only 50% of patients with asthma tolerated carvedilol. Survival at 2.5 years was 72%. In survivors, left ventricular end-diastolic diameter decreased from 76 ± 11 mm to 72 ± 14 mm (
p = 0.01), left ventricular end-systolic diameter decreased from 65 ± 13 mm to 60 ± 15 mm (
p = 0.01), and fractional shortening increased from 14% ± 7% to 17% ± 7% (
p = 0.05) at 12 months.
Patients with CHF and COPD tolerated carvedilol well with no significant reversible airflow limitation, but patients with CHF and asthma tolerated carvedilol poorly. The effect of carvedilol on left ventricular dimensions and function in patients with concomitant airway diseases was similar to that seen in our general group of patients. Asthma remains a contraindication to β-blockade.
Three hundred forty-three pigs slaughtered and marketed in western Kenya were subjected to lingual examination and HP10 Ag-ELISA for the serological detection of Taenia solium antigen. When estimates ...were adjusted for the sensitivity and specificity of the diagnostic assays, prevalence of T. solium cysticercosis estimated by lingual exam and HP10 Ag-ELISA was between 34.4 % (95 % confidence interval (CI) 19.4–49.4 %) and 37.6 % (95 % CI 29.3–45.9 %), respectively. All pigs, however, were reported to have passed routine meat inspection. Since T. solium poses a serious threat to public health, these results, if confirmed, indicate that the introduction of control strategies may be appropriate to ensure the safety of pork production in this region.
Bone loss is most rapid in the immediate period after cardiac or lung transplantation. This randomized study compared the efficacy of 6 months of treatment with either calcitriol ...(1,25‐dihydroxyvitamin D3; 0.5 μg/day) or two cycles of etidronate plus calcium in preventing bone loss in 41 patients undergoing cardiac or lung transplantation. Patients were followed for 18 months after cessation of treatment. Bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry (DXA). There were no significant differences between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporin over the 2 years. Bone loss did not differ between groups after 6 months and, despite 6 months prophylaxis with either agent, bone loss was significant in both groups at 6 months and 12 months. However, compared with an untreated reference group, both therapies offered significant protection at 6 months and etidronate provided significant protective carryover after therapy had been discontinued. These data suggest short‐term prophylaxis with calcitriol or cyclical etidronate is partially effective in reducing bone loss after cardiac or lung transplantation but treatment needs to be continued for a longer term.
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