Laboratory-acquired infections due to a variety of bacteria, viruses, parasites, and fungi have been described over the last century, and laboratory workers are at risk of exposure to these ...infectious agents. However, reporting laboratory-associated infections has been largely voluntary, and there is no way to determine the real number of people involved or to know the precise risks for workers. In this study, an international survey based on volunteering was conducted in biosafety level 3 and 4 laboratories to determine the number of laboratory-acquired infections and the possible underlying causes of these contaminations. The analysis of the survey reveals that laboratory-acquired infections have been infrequent and even rare in recent years, and human errors represent a very high percentage of the cases. Today, most risks from biological hazards can be reduced through the use of appropriate procedures and techniques, containment devices and facilities, and the training of personnel.
Lineage 2 West Nile virus (WNV), previously found only in sub-Saharan Africa and Madagascar, was identified in Hungary in 2004 and has rapidly expanded in Europe in the past decade. Following a ...significant outbreak of West Nile fever with neurological cases caused by lineage 1 WNV in Romania in 1996, scattered cases have been recorded in the south-east of the country in each transmission season. Another outbreak, affecting a larger area and caused by lineage 2 WNV, was recorded in 2010. We analysed human sera from neuroinvasive West Nile fever cases and mosquitoes, sampled in south-eastern Romania between 2011 and 2013, for the presence of WNV genome, and obtained partial NS5 and envelope glycoprotein sequences. Human- and mosquito-derived WNV sequences were highly similar (99%) to Volgograd 2007 lineage 2 WNV and differed from isolates previously detected in central and southern Europe. WNV was detected in one pool of Culex pipiens s.l. males, documenting vertical transmission. Lineage 4 WNV, of unknown pathogenicity to mammals, was found in the amphibian-feeding mosquito Uranotaenia unguiculata from the Danube Delta. Our results present molecular evidence for the maintenance of the same isolates of Volgograd 2007-like lineage 2 WNV in south-eastern Romania between 2011 and 2013.
Objective
To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC).
Patients and methods
Twenty-five men ...with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien–Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis.
Results
Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (
p
= 0.2). Median follow-up was 15 months (range 3–41) for the entire cohort with a median survival of 15 months (95% CI 10.1–19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62–17.23,
p
= 0.164).
Conclusion
Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome.
To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related ...symptoms.
An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments.
The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24).
The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia.
BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.
Abstract
Study question
How does the sex chromosome complement affect the transcriptome and development of oocytes during follicular growth in the mouse ovary?
Summary answer
Highly expressed ...X-linked genes adjust their transcript levels according to the X dosage. Y-linked genes affect the transcript levels of some X-linked and autosomal genes.
What is known already
Female mice carrying XO and XY chromosomes on the C57BL/6J (B6) genetic background are healthy but encounter subfertility and infertility, respectively. Our previous results have shown that the XY oocyte is defective in its cytoplasm; its replacement with that of an XX oocyte at the GV stage allows for production of healthy offspring after fertilization. Since transcription is shut down in the oocyte by the end of growth phase, the mRNAs and proteins necessary for meiotic progression and early embryonic development are accumulated during follicular growth.
Study design, size, duration
30 oocytes of 50–59 μm diameter were pooled for each genotype in biological triplicate and subjected to RNA-Sequencing. Total RNA extracted from 10–30 pooled oocytes of each size range and genotype in biological triplicate were subjected to qRT-PCR. All experiments were performed between 2019–2021.
Participants/materials, setting, methods
XY and XO females were generated by cross between B6 females with B6.YTIR and B6.XPafY males, respectively. Oocytes in the growth phase were collected at 8–18 days postpartum (dpp), whereas fully-grown oocytes were collected at 27–29 dpp after injection with equine chorionic gonadotropin. Oocytes of 50–59 μm diameter were subjected to RNA-Sequencing using a version of SmartSeq2, followed by DEG analyses. Transcript levels in the oocytes of various diameters were determined by qRT-PCR.
Main results and the role of chance
Chromatin configuration, mitochondrial distribution, and de novo transcription were largely comparable among the XX, XO, and XY oocytes smaller than 60 µm. Three way comparisons of RNA-Seq data in the oocytes of 50–59 μm revealed; (1) 13.8% of X-linked DEGs showed the transcript levels in correspond to the X chromosome dosage; (2) 9 genes on the Y short arm and 2 genes near the distal end of the Y long arm were highly expressed in XY oocytes; (3) transcript levels of X- or autosomal homologs were affected by the XY complement compared to XX and XO oocytes; and (4) 54 and 39 X-linked and autosomal genes show higher and lower transcript levels, respectively, in XY oocytes compared to XX and XO oocytes. The results of qRT-PCR of selected genes revealed distinct dynamic changes in transcript levels in the oocyte during follicular growth. Data of RNA-Seq were statistically analyzed using R Bioconductor limma package for differentially expressed genes having Benjamini-Hochberg adjusted P values lower than 0.01 and log2 fold change higher than 1. All data of qRT-PCR were statistically analyzed by one-way ANOVA followed by Tukey’s honestly significant difference (HSD) test.
Limitations, reasons for caution
In humans, most XO females die in utero and those who reach the term suffer from congenital abnormalities and infertility (Turner’s syndrome). However, the severer phenotype can be attributed to somatic cells with a greater number of genes that escape from X chromosome inactivation in humans than mice.
Wider implications of the findings: XO and XY mice provide animal models for investigating the consequence of X haplodeficiency in the female germline, independent of somatic defects. Furthermore, XY female mice provide a unique opportunity for examining whether and how Y-linked genes are transcribed outside the male germline.
Trial registration number
Not applicable
A correct diagnosis determined in the case of peformance athletes has a great importance in training management. In this context, modern and non-invasive tests are used more frequently, thus ...obtaining complex information referring to the metabolic typology, to the type of answer the body gives when it is subject to stress, as well as to the presence of toxic and nutritive minerals inside the body. Purpose: the determination of absolute levels of the main nutritious minerals, compared to ideal values and to the average interval, and the determination of the relations between them, with the purpose of assessing C. D.’s health condition, athlete member of the national racewalking team. Theories: performing the tissue mineral testing in our athlete’s case may therefore change her food diet and her effort and recovery medication, through diet recommendation. Methods: tissue mineral testing (TMT) was used as test screening, which makes possible the assessment of minerals that are vital to health and of the main toxic metals that may exist inside the body. Results: abnormal mineral levels were found and these deficiencies affect the athlete’s endocrine system. Conclusions: one can also make diet and treatment suggestions which could correct the mineral imbalance.
2230 patients from Bucharest with genital infections were investigated (1988-1996) to identify the chlamydial etiology. The rate of isolation of Chlamydia trachomatis was of 33.8%. The highest ...percentages were reported in patients clinically diagnosed with cervicitis (56.2%) and non-gonococcal urethritis (36%); as well as in patients aged 31-35 years, single, who had genital urinary infections in history.
The evolution of the Carpathians is in its final stage with intermediate seismic activity (70–200 km, Mw = 4–7.7) localized beneath its southeastern salient (Vrancea zone). Our analysis, in the ...transition area between south Carpathians and east Carpathians, reveals that the termination of convergence is characterized by a clockwise rotation of the Carpathian belt transport direction. Using structural maps and cross sections, we show that this change of convergence direction had several structural consequences including (1) the Pliocene‐Quaternary activation of out‐of‐sequence structures in the southern east Carpathians and (2) the creation of dextral strike‐slip faults bounding the mobile belt to the west, in the south Carpathians. Our fracture analysis in syntectonic deposits allows us to distinguish and stratigraphically date two fanning stress patterns, corresponding to the two last transport directions of the Carpathian system (1) a Burdigalian to early Tortonian stress field with compression directions rotating along with the Carpathian curved orogenic belt but with transpression (NW–SE compression) and a low‐strain partitioning along east trending internal strike‐slip faults in the south Carpathians and (2) a late Tortonian to Pleistocene rotated and smaller radial stress pattern, with N–S compression in the south Carpathians. The rotation of the convergence direction is interpreted as the result of the Miocene migration and progressive collision of the Carpathian system with the thick crust of the NW trending Tornquist‐Teisseyre line and its prolongation in Romania. The area able to subduct, determined by thickness of crust entering the subduction zone, was progressively restricted to a foreland corner in front of the southeastern Carpathians. The progressive collision forced the convergence to slow down and rotate from eastward to southeastward in late Miocene. The Dobrogea hills in front of the latest migrating system may represent the late Neogene NE–SW flexural bulge of the subducting foreland panel. This clockwise rotation of the transport direction can be compared with the clockwise rotation that occurred in other subduction systems (Tyrrhenian subduction, Caribbean subduction, etc.) which were controlled by the location of oceanic versus continental crust in front of the orogenic belt.
Abstract
Background: Inter- and intra-tumour heterogeneity underlies variability in therapeutic response. Although targeting of the epidermal growth factor receptor (EGFR) in breast cancer has failed ...to demonstrate clinical efficacy at the population level, complete and durable responses have been reported at low frequencies. The molecular determinants of these responses are unknown, but are of importance in the era of precision medicine.
Results: We performed a patient-derived xenograft (PDX) clinical trial with gefitinib in a breast cancer PDX cohort. Consistent with clinical trial data, gefitinib exhibited limited efficacy across most models. One PDX, however, demonstrated a complete and durable (>6 months) clinical response, and was subject to deep molecular profiling to identify determinants of response. Exome sequencing revealed no single nucleotide variants or copy number alterations in EGFR pathway members. EGFR was differentially expressed between the two major cellular subpopulations identified by single-cell RNAseq and this cellular heterogeneity in EGFR expression was validated immunohistochemically. Fluorescence-activated cell sorting of the EGFRhi subpopulation revealed cells with enhanced stem-like properties, including ALDH activity, sphere-forming capacity in vitro, ability to form tumours in vivo and seeding lung micrometastases from orthotopically transplanted tumours. Tumourspheres derived from EGFRhi cells developed into mixed EGFRhi and EGFRlo subpopulations, as did macrometastases, supporting that EGFRhi subpopulation can self-renew and re-populate. Analysis of expressed SNVs in the single-cell RNAseq data, filtered by variants identified from exome sequencing, showed no clonal segregation, supporting a non-clonal origin of the functionally distinct EGFRhi and EGFRlo subpopulations. This EGFR-driven tumour initiating cell program was observed in independent PDX models, some which showed growth inhibition in response to gefitinib.
Conclusions: Using bulk and single-cell genomic profiling, we identified and functionally validated an EGFR-driven tumour-initiating program in a subset of aggressive breast tumours, which may be predictive of gefitinib sensitivity. This contradicts traditional beliefs that good therapeutic targets are homogenously expressed, in that we show that a target displaying intra-tumour heterogeneity can be effective so long that it is expressed in the tumour-initiating population.
Citation Format: Savage P, Saleh SMI, Wang Y-C, Revil T, Badescu D, Liu L, Iacucci E, Zuo D, Bertos N, Munoz-Ramos V, Asselah J, Meterissian S, Omeroglu A, Hébert S, Kleinman C, Park M, Ragoussis J. A targetable EGFR-driven tumor-initiating program in breast cancer abstract. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-06-11.
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