Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) ...complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine-associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.
Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt ...five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A voltammetric method for phenolic compounds determination detected differences between
Gossypium hirsutum
and
Gossypium barbadense
, injured or not by caterpillars.
G. barbadense
seeds collected in ...Amazon were multiplied and compared to a commercial Brazilian variety (
G. hirsutum
). Plants were conducted in a net protected house for two assays where: i) floral buds were inoculated with boll weevil eggs and ii) leaves were infested with
Spodoptera cosmioides
(Walker) and leaf phenolic compounds determined by a voltammetric method based on the differential pulse technique and glassy carbon electrode. The proportion of emerging boll weevils was greater in
G. hirsutum
(0.24) than in
G. barbadense
(0.14).
G. hirsutum
non infested older leaves presented a higher amount of total phenolics than the younger leaves. For the infested plants, total phenolic levels were similar in both developmental stages and to the not infested younger leaves. The most intense current peak in the voltammetric profile was at the oxidation potential of 0.5 V for all samples, and more intense for
G. hirsutum
older leaves. Another less intense current peak at 0.8 V, found at all profiles, was great for
G. barbadense
attacked by caterpillars. Compounds coincident with these peaks may be related to insect tolerance.
Enduring sustainability challenges requires a new model of collective leadership that embraces critical reflection, inclusivity and care. Leadership collectives can support a move in academia from ...metrics to merits, from a focus on career to care, and enact a shift from disciplinary to inter- and trans-disciplinary research. Academic organisations need to reorient their training programs, work ethics and reward systems to encourage collective excellence and to allow space for future leaders to develop and enact a radically re-imagined vision of how to lead as a collective with care for people and the planet.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Monitoring phenylalanine (Phe) concentrations is critical for the management of phenylketonuria (PKU). This can be done in dried blood spots (DBS) or in EDTA plasma derived from capillary or venous ...blood. Different techniques are used to measure Phe, the most common being flow-injection analysis tandem mass spectrometry (FIA-MS-MS) and ion exchange chromatography (IEC). Significant differences have been reported between Phe concentrations in various sample types measured by different techniques, the cause of which is not yet understood. We measured Phe concentrations in 240 venous blood samples from 199 patients with hyperphenylalaninemia in dried blood spots, EDTA plasma and erythrocytes by FIA-MS-MS and IEC. Phe concentrations were significantly lower in erythrocytes than in plasma leading to about 19% lower Phe DBS concentrations compared with plasma independent from the method used for quantification. As most therapy recommendations for PKU patients are based on plasma concentrations reliable conversion of DBS into plasma concentrations is necessary. Variances of Phe concentrations in plasma and DBS are not linear but increases with higher concentrations indicating heteroscedasticity. We therefore suggest the slope of the 75th percentile from quantile regression as a correction factor.
Background
The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position ...paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe.
Objective
To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa.
Methods
As part of the @IT.2020 multi‐center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility.
Results
The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days).
Conclusion
The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.
Depending on the criteria used, the length of a pollen season can vary dramatically. EAACI criteria generate very extended pollen seasons in Southern Europe, which also include many days/weeks with no/low pollen counts. The exclusion of “intercurrent periods” with no/low pollen counts (“fragmented pollen season” method) improves the accuracy of EAACI criteria.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Early mobilization after surgery is a cornerstone of the Enhanced Recovery After Surgery (ERAS) programs in total hip arthroplasty (THA) or total knee arthroplasty (TKA). Our goal was to determine ...the time to mobilization after this surgery and the factors associated with early mobilization.
This was a predefined substudy of the POWER.2 study, a prospective cohort study conducted in patients undergoing THA and TKA at 131 Spanish hospitals. The primary outcome was the time until mobilization after surgery as well as determining those perioperative factors associated with early mobilization after surgery.
A total of 6093 patients were included. The median time to achieve mobilization after the end of the surgery was 24.áhours 16.Çô30. 4,222 (69.3%) patients moved in .ëñ 24.áhours after surgery. Local anesthesia OR.á=.á0.80 (95% confidence interval CI: 0.72.Çô0.90); p.á=.á0.001, surgery performed in a self-declared ERAS center OR = 0.57 (95% CI: 0.55.Çô0.60); p.á<.á0.001, mean adherence to ERAS items OR.á=.á0.93 (95% CI: 0.92.Çô0.93); p.á<.á0.001, and preoperative hemoglobin OR.á=.á0.97 (95% CI: 0.96.Çô0.98); p.á<.á0.001 were associated with shorter time to mobilization.
Most THA and TKA patients mobilize in the first postoperative day, early time to mobilization was associated with the compliance with ERAS protocols, preoperative hemoglobin, and local anesthesia, and with the absence of a urinary catheter, surgical drains, epidural analgesia, and postoperative complications. The perioperative elements that are associated with early mobilization are mostly modifiable, so there is room for improvement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
The number of HIV‐infected individuals from developed countries travelling to tropical and subtropical areas has increased as a result of the clinical and survival benefits of combination ...antiretroviral therapy. The aim of our study was to describe the traveler population in the SHCS and to determine the frequency of viral rebound in virologically suppressed individuals after a travel episode to the tropics compared to non‐travelers.
Methods
Swiss HIV Cohort Study participants with at least one follow‐up visit between 1 January 1989 and 28 February 2015 were eligible for inclusion in the study. The primary outcome was the occurrence of viral rebound (viral load > 200 HIV‐1 RNA copies/mL) after a travel episode compared with a nontravel episode in previously suppressed individuals (≤ 200 copies/mL). All virologically suppressed patients contributed multiple travel or nontravel episodes to the analysis. Logistic regression was performed including factors associated with viral rebound.
Results
We included 16 635 patients in the study, of whom 6084 (36.5%) had ever travelled to the tropics. Travel frequency increased over time, with travellers showing better HIV parameters than nontravellers less advanced Centers for Disease Control and Prevention (CDC) stage and higher CD4 count nadir. Viral rebound was seen in 477 (3.9%) of 12 265 travel episodes and in 5121 (4.5%) of 114 884 nontravel episodes unadjusted odds ratio (OR) 0.87; 95% confidence interval (CI) 0.78–0.97. Among these 477 post‐travel viral rebounds, 115 had a resistance test performed and 51 (44%) of these showed new resistance mutations. Compared with European and North American patients, the odds for viral rebound were significantly lower in Southeast Asian (OR 0.67; 95% CI 0.51–0.88) and higher in sub‐Saharan African (SSA) patients (OR 1.41; 95% CI 1.22–1.62). Travel further increased the odds of viral rebound in SSA patients (OR 2.00; 95% CI 1.53–2.61).
Conclusions
Region of origin is the main risk factor for viral rebound rather than travel per se. Pre‐travel adherence counselling should focus on patients of SSA origin.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Acute childhood stroke is an emergency requiring a high level of awareness among first-line healthcare providers. This survey serves as an indicator of the awareness of, the interest in, and ...knowledge of childhood stroke of German pediatricians.
Thousand six hundred and ninety-seven physicians of pediatric in- and outpatient facilities in Bavaria, Germany, were invited via email to an online-survey about childhood stroke.
The overall participation rate was 14%. Forty-six percent of participants considered a diagnosis of childhood stroke at least once during the past year, and 47% provide care for patients who have suffered childhood stroke. The acronym FAST (Face-Arm-Speech-Time-Test) was correctly cited in 27% of the questionnaires. Most commonly quoted symptoms of childhood stroke were hemiparesis (90%), speech disorder (58%), seizure (44%), headache (40%), and impaired consciousness (33%). Migraine (63%), seizure (39%), and infections of the brain (31%) were most frequently named as stroke mimics. Main diagnostic measures indicated were magnetic resonance imaging (MRI) (96%) and computer tomography (CT) (55%). Main therapeutic strategies were thrombolysis (80%), anticoagulation (41%), neuroprotective measures, and thrombectomies (15% each). Thirty-nine percent of participants had taken part in training sessions, 61% studied literature, 37% discussed with colleagues, and 25% performed internet research on childhood stroke. Ninety-three percent of participants approve skill enhancement, favoring training sessions (80%), publications (43%), and web based offers (35%). Consent for offering a flyer on the topic to caregivers in facilities was given in 49%.
Childhood stroke constitutes a topic of clinical importance to pediatricians. Participants demonstrate a considerable level of comprehension concerning the subject, but room for improvement remains. A multi-modal approach encompassing an elaborate training program, regular educational publications in professional journals, and web based offers could reach a broad range of health care providers. Paired with a public adult and childhood stroke awareness campaign, these efforts could contribute to optimize the care for children suffering from stroke.
Abstract This article reports the rationale for the Brazilian Cardioprotective Nutritional Program (BALANCE Program) Trial. This pragmatic, multicenter, nationwide, randomized, concealed, controlled ...trial was designed to investigate the effects of the BALANCE Program in reducing cardiovascular events. The BALANCE Program consists of a prescribed diet guided by nutritional content recommendations from Brazilian national guidelines using a unique nutritional education strategy, which includes suggestions of affordable foods. In addition, the Program focuses on intensive follow-up through one-on-one visits, group sessions, and phone calls. In this trial, participants 45 years or older with any evidence of established cardiovascular disease will be randomized to the BALANCE or control groups. Those in the BALANCE group will receive the afore mentioned program interventions, while controls will be given generic advice on how to follow a low-fat, low-energy, low-sodium, and low-cholesterol diet, with a view to achieving Brazilian nutritional guideline recommendations. The primary outcome is a composite of death (any cause), cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, or hospitalization for unstable angina. A total of 2468 patients will be enrolled in 34 sites and followed up for up to 48 months. If the BALANCE Program is found to decrease cardiovascular events and reduce risk factors, this may represent an advance in the care of patients with cardiovascular disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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