Background. Well-documented outbreaks of human toxoplasmosis infection are infrequently reported. Here, we describe a community outbreak of multivisceral toxoplasmosis that occurred in Patam, a ...Surinamese village near the French Guianan border. Methods. From the end of December 2003 through the middle of January 2004, 5 adult patients in Patam, including 2 pregnant women, were initially hospitalized for multivisceral toxoplasmosis. A French-Surinamese epidemiological investigation was conducted in the village; inquiries and clinical examinations were performed, and blood and environmental samples were obtained. For all serologically confirmed cases of toxoplasmosis, molecular analysis and mouse inoculations were performed for diagnosis and genetic characterization of Toxoplasma gondii. Results. The hospitalized patients, who did not have any immunodeficiencies, presented with an infectious disease with multivisceral involvement. Serological examination confirmed acute toxoplasmosis. One adult died, and a neonate and a fetus with congenital toxoplasmosis also died. During the investigation, 4 additional acute cases of toxoplasmosis were diagnosed among the 33 villagers. Only 3 inhabitants had serological evidence of previous T. gondii infection. In total, we reported 11 cases of toxoplasmosis: 8 multivisceral cases in immunocompetent adults, resulting in 1 death; 2 cases of lethal congenital toxoplasmosis in a neonate and a fetus; and 1 symptomatic case in a child. Molecular analysis demonstrated that identical isolates of only 1 atypical strain were responsible for at least 5 of the 11 cases of toxoplasmosis in the outbreak. No epidemiological sources could be linked to this severe community-wide outbreak of toxoplasmosis. Conclusion. This report is in agreement with the particular features of toxoplasmosis involving atypical strains that were recently described in French Guiana.
•Most tuberculosis (TB) units reported changes in their TB team operations.•TB patients diagnosed during COVID-19 showed more extended pulmonary forms.•Latent TB infections in children household ...contacts were higher in 2020.•Active TB in children household contacts were higher in 2020.
The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown.
Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected.
A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 (P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 (P = 0.001).
The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.
In haemophiliacs, the physical condition, muscular strength, aerobic resistance, anaerobic resistance and proprioception have all diminished. Muscle atrophy and instability, being more vulnerable to ...stressful motor demands, increase the risk of lesion and establish a vicious circle that is hard to break: pain, immobility, atrophy, articular instability and repeated bleeding episodes. In haemophilia, physical and/or sporting activities were not recommended until the seventies. Nowadays, the overall policy is to recommend certain physical activities, especially swimming, to improve the patient’s quality of life, thanks to prophylaxis programmes. The objective of this study is to perform a systematic review of the exercise and sporting activities recommended for haemophiliacs. Experimental and observational studies and clinical assays about rehabilitation for haemophiliacs with exercise and sporting activities have been included. The relevant studies were identified in Medline, Cinahl, Embase and SportDiscus, and key words were: haemophilia, exercise and sport (with no language restrictions). Works were independently analysed by reviewers and the following were identified: of 3603 studies, 103 were included in this review: 29 (28.15%) were experimental, 27 (26.21%) were observational and 47 (45.63%) were clinical. Physiotherapy, physical activity and sport are basic elements to improve quality of life and the physical condition, increase strength and resistance and to reduce the risk of musculoskeletal lesions and to prevent haemophilic atrophy. In general, professionals in haemophilia believe that regular exercise and rehabilitation with physiotherapy is fundamental, particularly in countries where replacement therapy is not readily available.
The pulsed electron paramagnetic resonance (EPR) methods of electron spin echo envelope modulation (ESEEM) and electron spin echo-electron nuclear double resonance (ESE-ENDOR) are used to investigate ...the structure of the Photosystem II oxygen-evolving complex (OEC), including the paramagnetic manganese cluster and its immediate surroundings. Recent unpublished results from the pulsed EPR laboratory at UC-Davis are discussed, along with aspects of recent publications, with a focus on substrate and cofactor interactions. New data on the proximity of exchangeable deuterons around the Mn cluster poised in the S
0-state are presented and interpreted. These pulsed EPR results are used in an evaluation of several recently proposed mechanisms for PSII water oxidation. We strongly favor mechanistic models where the substrate waters bind within the OEC early in the S-state cycle. Models in which the OO bond is formed by a nucleophilic attack by a Ca
2+-bound water on a strong S
4-state electrophile provide a good match to the pulsed EPR data.
To simplify and optimize the ability of EuroSCORE I and II to predict early mortality after surgery for infective endocarditis (IE).
Multicentre retrospective study (n = 775). Simplified scores, ...eliminating irrelevant variables, and new specific scores, adding specific IE variables, were created. The performance of the original, recalibrated and specific EuroSCOREs was assessed by Brier score, C-statistic and calibration plot in bootstrap samples. The Net Reclassification Index was quantified.
Recalibrated scores including age, previous cardiac surgery, critical preoperative state, New York Heart Association >I, and emergent surgery (EuroSCORE I and II); renal failure and pulmonary hypertension (EuroSCORE I); and urgent surgery (EuroSCORE II) performed better than the original EuroSCOREs (Brier original and recalibrated: EuroSCORE I: 0.1770 and 0.1667; EuroSCORE II: 0.2307 and 0.1680). Performance improved with the addition of fistula, staphylococci and mitral location (EuroSCORE I and II) (Brier specific: EuroSCORE I 0.1587, EuroSCORE II 0.1592). Discrimination improved in specific models (C-statistic original, recalibrated and specific: EuroSCORE I: 0.7340, 0.7471 and 0.7728; EuroSCORE II: 0.7442, 0.7423 and 0.7700). Calibration improved in both EuroSCORE I models (intercept 0.295, slope 0.829 (original); intercept –0.094, slope 0.888 (recalibrated); intercept –0.059, slope 0.925 (specific)) but only in specific EuroSCORE II model (intercept 2.554, slope 1.114 (original); intercept –0.260, slope 0.703 (recalibrated); intercept –0.053, slope 0.930 (specific)). Net Reclassification Index was 5.1% and 20.3% for the specific EuroSCORE I and II.
The use of simplified EuroSCORE I and EuroSCORE II models in IE with the addition of specific variables may lead to simpler and more accurate models.
Gated mesoporous silica nanoparticles can deliver payload upon the application of a predefined stimulus, and therefore are promising drug delivery systems. Despite their important role, relatively ...low emphasis has been placed on the design of gating systems that actively target carbohydrate tumor cell membrane receptors. We describe herein a new Lewis X (Le
) antigen-targeted delivery system comprising mesoporous silica nanoparticles (MSNs) loaded with ATTO 430LS dye, functionalized with a Le
derivative (1) and capped with a fucose-specific carbohydrate-binding protein (Aleuria aurantia lectin (AAL)). This design takes advantage of the affinity of AAL for Le
overexpressed receptors in certain cancer cells. In the proximity of the cells, AAL is detached from MSNs to bind Le
, and selectins in the cells bind Le
in the gated MSNs, thereby inducing cargo delivery. Gated MSNs are nontoxic to colon cancer DLD-1 cells, and ATTO 430LS dye delivered correlated with the amount of Le
antigen overexpressed at the DLD-1 cell surface. This is one of the few examples of MSNs using biologically relevant glycans for both capping (via interaction with AAL) and targeting (via interaction with overexpressed Le
at the cell membrane).
Normal tissue complication probability (NTCP) models can be useful to estimate the risk of fibrosis after breast-conserving surgery (BCS) and radiotherapy (RT) to the breast. However, they are ...subject to uncertainties. We present the impact of contouring variation on the prediction of fibrosis.
280 breast cancer patients treated BCS-RT were included. Nine Clinical Target Volume (CTV) contours were created for each patient: i) CTV_crop (reference), cropped 5 mm from the skin and ii) CTV_skin, uncropped and including the skin, iii) segmenting the 95% isodose (Iso95%) and iv) 3 different auto-contouring atlases generating uncropped and cropped contours (Atlas_skin/Atlas_crop). To illustrate the impact of contour variation on NTCP estimates, we applied two equations predicting fibrosis grade ≥ 2 at 5 years, based on Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) models, respectively, to each contour. Differences were evaluated using repeated-measures ANOVA. For completeness, the association between observed fibrosis events and NTCP estimates was also evaluated using logistic regression.
There were minimal differences between contours when the same contouring approach was followed (cropped and uncropped). CTV_skin and Atlas_skin contours had lower NTCP estimates (−3.92%, IQR 4.00, p < 0.05) compared to CTV_crop. No significant difference was observed for Atlas_crop and Iso95% contours compared to CTV_crop. For the whole cohort, NTCP estimates varied between 5.3% and 49.5% (LKB) or 2.2% and 49.6% (RS) depending on the choice of contours. NTCP estimates for individual patients varied by up to a factor of 4. Estimates from “skin” contours showed higher agreement with observed events.
Contour variations can lead to significantly different NTCP estimates for breast fibrosis, highlighting the importance of standardising breast contours before developing and/or applying NTCP models.
•Differences in breast radiotherapy contouring after breast-conserving surgery influence the estimated probability of normal tissue complications.•For individual patients, the estimated risk of grade ≥ 1 breast fibrosis at five years after radiotherapy varies by up to factor of 4.•It is essential to define and standardise contours when developing/applying NTCP models.
Issue/problem
Leptospirosis is an endemic disease which is mandatorily notifiable in Spain. It is associated with occupational activities in which workers come into contact with rat urine. In our ...region, this disease's rates of prevalence and incidence are highest among red swamp crayfish collectors (Procambarus clarkii) (RSCC). The increase in outbreaks of leptospirosis over the last 7 years has motivated us to design and implement a Clinical Practice Guide (CPG) for health workers, informational material for the general population, and ID cards and specific information aimed at RSCCs, as a means of reducing the incidence rate. The guide may also serve as a useful tool in other regions and countries with activities associated with Leptospira-infected wetlands.
Description of the problem
The material we have designed is the result of a research project funded by the Consejería de Salud de Andalucía to identify leptospirosis incidence, prevalence, and risk factors among wetland RSCCs. Hardly any CPGs or informational material exist about this disease. The GPC and the educational material designed may be very useful in other environments with a high risk of leptospirosis.
Results
Prevalence of the disease was higher among RSCCs than among the general population (9.8% vs 3.1%) (OR: 3.4; CI 95%: 1.1-12.7) and accumulated incidence was 17.4%. Less than half of the workers adopted appropriate individual preventive measures.
Lessons
The risk of contracting leptospirosis is 3.4 times greater for the RSCC population than it is for the general population. Early detection and antibiotic therapy prevent aggravation of the disease in serious cases and may even prevent deaths. Education and the promotion of preventive measures among RSCCs reduces the risk of infection. The training of health professionals and the design of decision algorithms shorten and improve the quality of treatment for leptospirosis patients.
Key messages
Early detection and antibiotic therapy reduce the incidence of severe forms of leptospirosis.
The material designed will help the risk population to adopt preventive measures and seek medical attention.
Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends ...testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.
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