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A case of stage IB2 cervical cancer at 27 weeks of pregnancy, treated with neoadjuvant chemotherapy followed by radical Cesarean hysterectomy with full pelvic and infra-mesenteric lymphadenectomy, and adjuvant chemo-radiation is described. While she remains without disease, her baby was diagnosed with acute myelogenous leukemia. We highlight the pre-operative work-up, treatment options, safety, feasibility, and outcomes for the mother and her fetus. [ABSTRACT FROM AUTHOR]

The aim of this paper is to present the relation between an evolutionary variational inequality with long-term memory and Lagrange multipliers. More precisely, we study the oligopolistic market equilibrium problem in which the profit function depends also on previous events of the market by means of a long-term memory which takes into account the previous states of the equilibrium. Moreover, thanks to the variational formulation, we are able to show existence and regularity results for equilibrium solutions. Then, we apply the infinite dimensional duality theory through which we obtain the existence of Lagrange multipliers which are great utility in order to understand the behaviour of the market. Finally, an example is provided, which allows to analyse the influence of the long-term memory on the equilibrium solution. [ABSTRACT FROM AUTHOR]

Reports on the results of a study carried out on the use of psychoactive substances in a number of patients. Methods of conducting the study; Conclusions of the study.

Gamma-hydroxybutyric acid is an allegedly benign illicit substance that is gaining increasing recognition and attention among substance abusers and athletes. Alongside foreign-made brands, the compound is also easily available, at low cost because of the facility with which it can be produced in one's kitchen. Named by some "Nature's Quaalude" or sold as a health product, it is often used with a false sense of security as it may cause serious and disabling complications, as illustrated by this clinical vignette. [ABSTRACT FROM AUTHOR]

Frequency and results of urine toxicology screens in a state-guided system of emergency rooms in a large city were compared with frequency and results of the same tests in the same population at a university-run intensive treatment psychiatric unit. Differences both in prevalence and in results were noted, with the emergency rooms testing significantly less patients than the intensive treatment unit and documenting a significantly lower rate of active substance abuse comorbidity to psychiatric disorders. Possible explanations for these differences are discussed, including clinical, attitudinal, and cost containment factors. These findings have a definite impact on treatment decision making, diagnostic precision, and validity of epidemiologic reports. [ABSTRACT FROM AUTHOR]

[Display omitted] • We propose 7 ways for nucleosome binding proteins to affect higher order structure. • Choices on nucleosomal array conditions impact protein binding and overall structure. • Chromatin phase separation is driven by a range of interactions to the nucleosome. The regulation of chromatin biology ultimately depends on the manipulation of its smallest subunit, the nucleosome. The proteins that bind and operate on the nucleosome do so, while their substrate is part of a polymer embedded in the dense nuclear environment. Their molecular interactions must in some way be tuned to deal with this complexity. Due to the rapid increase in the number of high-resolution structures of nucleosome-protein complexes and the increasing understanding of the cellular chromatin structure, it is starting to become clearer how chromatin factors operate in this complex environment. In this review, we analyze the current literature on the interplay between nucleosome-protein interactions and higher-order chromatin structure. We examine in what way nucleosomes-protein interactions can affect and can be affected by chromatin organization at the oligonucleosomal level. In addition, we review the characteristics of nucleosome-protein interactions that can cause phase separation of chromatin. Throughout, we hope to illustrate the exciting challenges in characterizing nucleosome-protein interactions beyond the nucleosome. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We evaluated the rates of response, operability and long term survival and toxicities in a large series of locally advanced cervical cancer (LACC) patients administered neoadjuvant chemotherapy (NACT) with paclitaxel, epirubicin and cisplatin (TEP) followed by radical surgery (RS). Patients and methods The study included 75 consecutive stages IB2–IVA patients administered NACT with paclitaxel (175mg/m2), epirubicin (100mg/m2) and cisplatin (100mg/m2) on day 1 of a 3-weekly cycle for 2–4cycles. Patients were evaluated for objective response by RECIST criteria and triaged to RS. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of diagnosis to recurrence/progression of disease or death, respectively. Results: Complete and partial clinical response was observed in 13 and 28 patients (56.1% objective responses); radical surgery was amenable in 52 patients (71.2%): 14 patients showed complete/microscopic response to treatment. Overall, recurrence/progression of disease was observed in 36 patients, and all of them experienced death of disease. In the whole series median PFS was 48months (5-year PFS=51.0%), and median OS was 72months (5-year OS=53.0%). Overall, 195 courses were administered; treatment was delayed in 6.7% of patients, while dose reduction was required in 36.5% of patients. Grade 3 leukopenia affected 22 patients (29.7%), while Grades 3 and 4 neutropenia was documented in 17 (22.9%) and 6 (8.1%) patients. In the whole series, we recorded 1 death whose relation with treatment-induced toxicity could not be ruled out. Conclusions: TEP provided favorable rates of response and operability in LACC patients, and allowed the obtainment of encouraging survival data without carrying out an excessive toxicity. [Copyright &y& Elsevier]

Nucleosomes are a crucial platform for the recruitment and assembly of protein complexes that process the DNA. Mechanistic and structural in vitro studies typically rely on recombinant nucleosomes that are reconstituted using artificial, strong-positioning DNA sequences. To facilitate such studies on native, genomic nucleosomes, there is a need for methods to produce any desired DNA sequence in an efficient manner. The current methods either do not offer much flexibility in choice of sequence or are less efficient in yield and labor. Here, we show that ramified rolling circle amplification (RCA) can be used to produce milligram amounts of a genomic nucleosomal DNA fragment in a scalable, one-pot reaction overnight. The protocol is efficient and flexible in choice of DNA sequence. It yields 10-fold more product than PCR, and rivals production using plasmids. We demonstrate the approach by producing the genomic DNA from the human LIN28B locus and show that it forms functional nucleosomes capable of binding pioneer transcription factor Oct4. Image 1 • A method is introduced to efficiently produce nucleosomal DNA of flexible sequence. • The rRCA approach is scalable and can yield multi-milligrams of DNA. • rRCA produced LIN28B DNA yields functional nucleosomes capable of binding Oct4. [ABSTRACT FROM AUTHOR]

Background & Aims: Several antibiotic treatments aiming to prevent spontaneous bacterial peritonitis (SBP) in cirrhotic patients with low‐protein content in ascitic fluid have been tested; however, there are limited data on the comparative efficacy of these regimens. We assessed their comparative efficacy through a network meta‐analysis and using GRADE criteria to appraise quality of evidence. Methods: Through literature review through October 2018, we identified 10 randomized controlled trials comparing antibiotic treatments (norfloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole and rifaximin) with each other or placebo. Primary outcome was SBP occurrence, with mortality rate and rate of other infections as secondary outcomes. Results: In comparison with placebo, moderate quality evidence supports the use of norfloxacin and ciprofloxacin in primary prophylaxis of SBP (risk ratio 0.23; 95% CI, 0.09‐0.56; P = 0.001 and 0.23; 0.07‐0.79; P = 0.02 respectively) while only low quality evidence suggests superiority of rifaximin (risk ratio 0.15; 0.05‐0.42). When antimicrobial agents were compared to each other, no significant difference was found. With regard to mortality, moderate quality supports the superiority of norfloxacin over placebo (risk ratio, 0.68; 95% CI, 0.47‐0.99; P = 0.04), while ciprofloxacin and rifaximin showed only a non‐significant benefit and no significant difference was found in the other comparisons. None of the tested antibiotics proved to significantly decrease the rate of other infections. Conclusions: Norfloxacin appears to have significant benefit both in terms of SBP prevention and mortality; ciprofloxacin represents a valuable option although without a clear survival benefit. Rifaximin shows interesting results but needs to be tested in further trials. [ABSTRACT FROM AUTHOR]

Unrepairable comminuted fractures of the radial head Mason type III or type IV have poor outcomes when treated by open reduction and internal fixation. Radial head resection has been proposed as good option for surgical treatment, while in the last decades, the development of technology and design in radial head prosthesis has increased efficacy in prosthetic replacement. The present review was conducted to determine the best surgical treatment for comminuted radial head when ORIF is not possible. Better outcomes are reported for radial head arthroplasty in terms of elbow stability, range of motion, pain, and fewer complications compared to radial head excision. Nevertheless, radial head resection still can be considered an option of treatment in isolated radial head fractures with no associated ligament injuries lesion of ligaments or in case of older patients with low demanding function. [ABSTRACT FROM AUTHOR]

Dowling-Degos disease (DDD) is a rare genodermatosis, which was first described by Dowling and Freudenthal in 1938 and then by Degos and Ossipowski in 1954. GLO:DF2/01dec19:ced13914-fig-0001.jpg PHOTO (COLOR): (a) Dowling-Degos disease of the mother's vulva: multiple hyperpigmented brownish macules showing dark brown to black macules in both solitary and confluent patterns. GLO:DF2/01dec19:ced13914-fig-0002.jpg PHOTO (COLOR): (a) Dowling-Degos disease of the daughter's vulva: the macules were lighter in colour (light brown) and fewer in number than in the mother. [Extracted from the article]

Background:The NGR-hTNF (asparagine-glycine-arginine-human tumour necrosis factor) is able to promote antitumour immune responses and to improve the intratumoural doxorubicin uptake by selectively damaging tumour blood vessels.Methods:Patients progressing after 1 platinum/taxane-based regimen received NGR-hTNF 0.8 μg m−2 and doxorubicin 60 mg m−2 every 3 weeks. Primary endpoint was a Response Evaluation Criteria in Solid Tumors-defined response rate with a target of more than 6 out of 37 responding patients.Results:A total of 37 patients with platinum-free interval lower than 6 months (PFI<6; n=25), or between 6 and 12 months (PFI=6-12; n=12) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6 per ml (interquartile range, 1.2-2.1). In all, 18 patients (49%) received more than 6 cycles. Febrile neutropaenia was registered in one patient (3%). Among 35 assessable patients, 8 (23%; 95% CI 12-39%) had partial response (2 with PFI<6; 6 with PFI=6-12) and 15 (43%) had stable disease (10 with PFI<6; 5 with PFI=6-12). Median progression-free survival (PFS) was 5.0 months for all patients, 3.8 months for patients with PFI<6, and 7.8 months for patients with PFI=6-12. Median overall survival (OS) was 17.0 months. Patients with baseline PBLC higher than the first quartile had improved PFS (P=0.01) and OS (P=0.001).Conclusion:Tolerability and activity of this combination warrant further randomised testing in patients with PFI<6. The role of PBLC as a blood-based biomarker deserves further investigation. [ABSTRACT FROM AUTHOR]

Fluorescence fish embryo, will be 2.15 Fish embryo Fluorescence Fluorescence blood smear, will be 2.16 Blood Smear Fluorescence (17) In legend figure 5, it says 52 h post fertilization, it should be 52 h post fertilization. [Extracted from the article]

• Structure-based calculations on the nucleosome surface interaction shows that NBPeps induce specific atomic fluctuations of the nucleosome structure. • In vitro studies shows that NBPeps may affect the stability of the nucleosome structure. • Cell-based assays shows that the NBPeps may penetrate the cell and localizes at the nuclear environment. • Fish embryo toxicity (FET) test shows that the NBPeps can cause tissue modifications, such as defects in pigmentation and induction of earlier hatching. • H4 peptide shows to be highly specific for targeting the nucleosome, with important effects on the final nucleosome structure and robust in vivo effects. Chromatin state is highly dependent on the nucleosome binding proteins. Herein, we used a multipronged approach employing biophysical and in vivo experiments to characterize the effects of Nucleosome Binding Peptides (NBPeps) on nucleosome and cell activity. We performed a series of structure-based calculations on the nucleosome surface interaction with GMIP1 (a novel NBPep generated in silico), and HMGN2 (nucleosome binding motif of HMGN2), which contains sites that bind DNA and the acid patch, and also LANA and H4pep (nucleosome binding motif of H4 histone tail) that only bind to the acidic patch. Biochemical assays shows that H4pep, but not HMGN2, GMIP1 and LANA, is highly specific for targeting the nucleosome, with important effects on the final nucleosome structure and robust in vivo effects. These findings suggest that NBPeps might have important therapeutic implications and relevance as tools for chromatin investigation. [ABSTRACT FROM AUTHOR]