Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) ...prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia (formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival.
Background and purpose
Specific respiratory tract infections, including COVID‐19, may cause smell and/or taste disorders (STDs) with increased frequency. The aim was to determine whether new‐onset ...STDs are more frequent amongst COVID‐19 patients than influenza patients.
Method
This was a case–control study including hospitalized patients of two tertiary care centres. Consecutive patients positive for COVID‐19 polymerase chain reaction (cases) and patients positive for influenza polymerase chain reaction (historical control sample) were assessed during specific periods, employing a self‐reported STD questionnaire.
Results
Seventy‐nine cases and 40 controls were included. No significant differences were found in basal features between the two groups. New‐onset STDs were significantly more frequent amongst cases (31, 39.2%) than in the control group (5, 12.5 %) adjusted odds ratio 21.4 (2.77–165.4, P = 0.003). COVID‐19 patients with new‐onset STDs were significantly younger than COVID‐19 patients without STDs (52.6 ± 17.2 vs. 67.4 ± 15.1, P < 0.001). Amongst COVID‐19 patients who presented STDs, 22 (70.9%) recalled an acute onset and it was an initial manifestation in 11 (35.5%). Twenty‐five (80.6%) presented smell disorders (mostly anosmia, 14, 45.2%) and 28 (90.3%) taste disorders (mostly ageusia, 14, 45.2%). Only four (12.9 %) reported concomitant nasal obstruction. The mean duration of STD was 7.5 ± 3.2 days and 12 patients (40%) manifested complete recovery after 7.4 ± 2.3 days of onset.
Conclusion
New‐onset STDs were significantly more frequent amongst COVID‐19 patients than influenza patients; they usually had an acute onset and were commonly an initial manifestation. The use of STD assessment in anamnesis as a hint for COVID‐19 and to support individuals’ self‐isolation in the current epidemic context is suggested.
This is the first study to report the prevalence of general obesity and abdominal obesity (AO) in the adult population of Spain based on measurements of weight, height and waist circumference. The ...data are taken from the ENRICA study, a cross‐sectional study carried out between June 2008 and October 2010 in 12,883 individuals representative of the non‐institutionalized population on Spain aged 18 years and older. Anthropometry was performed under standardized conditions in the households by trained interviewers. Overweight was considered as body mass index (BMI) 25–29.9 kg m−2, and obesity as BMI ≥ 30 kg m−2. AO was defined as waist circumference >102 cm in men and >88 cm in women. The prevalence of obesity was 22.9% (24.4% in men and 21.4% in women). About 36% of adults had AO (32% of men and 39% of women). The frequency of obesity and of AO increased with age and affected, respectively, 35 and 62% of persons aged 65 and over. The frequency of obesity and AO decreased with increasing educational level. For example, 29% of women with primary education or less had obesity vs. only 11% of those with university studies. The prevalence of obesity was very high in the Canary Islands and in the south of Spain.
There is a strong rationale to therapeutically target the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in breast cancer since it is highly ...deregulated in this disease and it also mediates resistance to anti-HER2 therapies. However, initial studies with rapalogs, allosteric inhibitors of mTORC1, have resulted in limited clinical efficacy probably due to the release of a negative regulatory feedback loop that triggers AKT and ERK signaling. Since activation of AKT occurs via PI3K, we decided to explore whether PI3K inhibitors prevent the activation of these compensatory pathways. Using HER2-overexpressing breast cancer cells as a model, we observed that PI3K inhibitors abolished AKT activation. However, PI3K inhibition resulted in a compensatory activation of the ERK signaling pathway. This enhanced ERK signaling occurred as a result of activation of HER family receptors as evidenced by induction of HER receptors dimerization and phosphorylation, increased expression of HER3 and binding of adaptor molecules to HER2 and HER3. The activation of ERK was prevented with either MEK inhibitors or anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors. Combined administration of PI3K inhibitors with either HER2 or MEK inhibitors resulted in decreased proliferation, enhanced cell death and superior anti-tumor activity compared with single agent PI3K inhibitors. Our findings indicate that PI3K inhibition in HER2-overexpressing breast cancer activates a new compensatory pathway that results in ERK dependency. Combined anti-MEK or anti-HER2 therapy with PI3K inhibitors may be required in order to achieve optimal efficacy in HER2-overexpressing breast cancer. This approach warrants clinical evaluation.
Microgastrine wasps are among the most species‐rich and numerous parasitoids of caterpillars (Lepidoptera). They are often host‐specific and thus are extensively used in biological control efforts ...and figure prominently in trophic webs. However, their extraordinary diversity coupled with the occurrence of many cryptic species produces a significant taxonomic impediment. We present and release the results of 8 years (2004–2011) of DNA barcoding microgastrine wasps. Currently they are the best represented group of parasitoid Hymenoptera in the Barcode of Life Data System (BOLD), a massive barcode storage and analysis data management site for the International Barcoding of Life (iBOL) program. There are records from more than 20 000 specimens from 75 countries, including 50 genera (90% of the known total) and more than 1700 species (as indicated by Barcode Index Numbers and 2% MOTU). We briefly discuss the importance of this DNA data set and its collateral information for future research in: (1) discovery of cryptic species and description of new taxa; (2) estimating species numbers in biodiversity inventories; (3) clarification of generic boundaries; (4) biological control programmes; (5) molecular studies of host‐parasitoid biology and ecology; (6) evaluation of shifts in species distribution and phenology; and (7) fostering collaboration at national, regional and world levels. The integration of DNA barcoding with traditional morphology‐based taxonomy, host records, and other data has substantially improved the accuracy of microgastrine wasp identifications and will significantly accelerate further studies on this group of parasitoids.
Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis ...with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.
In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before ...autologous stem-cell transplantation (ASCT).
This was a multicenter, open-label, phase I–II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT.
A total of 66 patients were recruited (median age 36 years; range 18–66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3–4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3–4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12–33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%).
BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.
We present results from the most comprehensive radio monitoring campaign towards the closest star to our Sun, Proxima Centauri. We report 1.1–3.1 GHz observations with the Australia Telescope Compact ...Array over 18 consecutive days in April 2017. We detected radio emission from Proxima Centauri for most of the observing sessions, which spanned ~1.6 orbital periods of the planet Proxima b. The radio emission is stronger at the low-frequency band, centered around 1.6 GHz, and is consistent with the expected electron-cyclotron frequency for the known star’s magnetic field intensity of ~600 gauss. The 1.6 GHz light curve shows an emission pattern that is consistent with the orbital period of the planet Proxima b around the star Proxima, with its maxima of emission happening near the quadratures. We also observed two short-duration flares (a few minutes) and a long-duration burst (about three days) whose peaks happened close to the quadratures. We find that the frequency, large degree of circular polarization, change in the sign of circular polarization, and intensity of the observed radio emission are all consistent with expectations from electron cyclotron-maser emission arising from sub-Alfvénic star–planet interaction. We interpret our radio observations as signatures of interaction between the planet Proxima b and its host star Proxima. We advocate for monitoring other dwarf stars with planets to eventually reveal periodic radio emission due to star–planet interaction, thus opening a new avenue for exoplanet hunting and the study of a new field of exoplanet–star plasma interaction.
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