Chromatin dynamics governed by a set of nuclear structural proteins

Abstract

During the past three decades, the study of nuclear and chromatin organization has become of great interest. The organization and dynamics of chromatin are directly responsible for many functions including gene regulation, genome replication, and maintenance. In order to better understand the details of these mechanisms, we need to understand the role of specific proteins that take part in these processes.

The genome in the nucleus is organized in different length scales, ranging from the bead‐like nucleosomes through topological associated domains (TADs) up to chromosome territories. The mechanisms that maintain these structures, however, remain to be fully elucidated. Previous works highlighted the significance of lamin A, an important nucleoplasmic protein; however, there are other nuclear structural proteins that are also important for chromatin organization. Studying the organizational aspects of the nucleus is a complex task, and different methods have been developed and adopted for this purpose, including molecular and imaging methods.

Here we describe the use of the live‐cell imaging method and demonstrate that the dynamics of the nucleus is strongly related to its organizational mechanisms. We labeled different genomic sites in the nucleus and measured the effect of nuclear structural proteins on their dynamics. We studied lamin A, BAF, Emerin, lamin B, CTCF, and Cohesin and discuss how each of them affect chromatin dynamics. Our findings indicate that lamin A and BAF have a significant effect on chromosomes dynamics, while other proteins mildly affect the type of the diffusion while the volume of motion is not affected.

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Outcomes and prognostic factors in intermediate-risk prostate cancer: multi-institutional analysis of the Spanish RECAP database

Abstract

Purpose

To retrospectively assess outcomes and to identify prognostic factors in patients diagnosed with intermediate-risk (IR) prostate cancer (PCa) treated with primary external beam radiotherapy (EBRT).

Materials and methods

Data were obtained from the multi-institutional Spanish RECAP database, a population-based prostate cancer registry in Spain. All IR patients (NCCN criteria) who underwent primary EBRT were included. The following variables were assessed: age; prostate-specific antigen (PSA); Gleason score; clinical T stage; percentage of positive biopsy cores (PPBC); androgen deprivation therapy (ADT); and radiotherapy dose. The patients were stratified into one of three risk subcategories: (1) favourable IR (FIR; GS 6, ≤ T2b or GS 3 + 4, ≤ T1c), (2) marginal IR (MIR; GS 3 + 4, T2a–b), and (3) unfavourable IR (UIR; GS 4 + 3 or T2c). Biochemical relapse-free survival (BRFS), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed.

Results

A total of 1754 patients from the RECAP database were included and stratified by risk group: FIR, n = 781 (44.5%); MIR, n = 252 (14.4%); and UIR, n = 721 (41.1%). Mean age was 71 years (range 47–86). Mean PSA was 10.4 ng/ml (range 6–20). The median radiotherapy dose was 74 Gy, with mean doses of 72.5 Gy (FIR), 73.4 Gy (MIR), and 72.8 Gy (UIR). Most patients (88%) received ADT for a median of 7.1 months. By risk group (FIR, MIR, UIR), ADT rates were, respectively, 88.9, 86.5, and 86.9%. Only patients with ≥ 24 months of follow-up post-EBRT were included in the survival analysis (n = 1294). At a median follow-up of 52 months (range 24–173), respective 5- and 10-year outcomes were: OS 93.6% and 79%; BRFS 88.9% and 71.4%; DFS 96.1% and 89%; CSS 98.9% and 94.6%. Complication rates (≥ grade 3) were: acute genitourinary (GU) 2%; late GU 1%; acute gastrointestinal (GI) 2%; late GI 1%. There was no significant association between risk group and BRFS or OS. However, patients with favourable-risk disease had significantly better 5- and 10-year DFS than patients with UIR: 98.7% vs. 92.4% and 92% vs. 85.8% (p = 0.0005). CSS was significantly higher (p = 0.0057) in the FIR group at 5 (99.7% vs. 97.3%) and 10 years (96.1% vs. 93.4%). On the multivariate analyses, the following were significant predictors of survival: ADT (BRFS and DFS); dose ≥ 74 Gy (BRFS); age (OS).

Conclusions

This is the first nationwide study in Spain to report long-term outcomes of patients with intermediate-risk PCa treated with EBRT. Survival outcomes were good, with a low incidence of both acute and late toxicity. Patients with unfavourable risk characteristics had significantly lower 5- and 10-year disease-free survival rates. ADT and radiotherapy dose ≥ 74 Gy were both significant predictors of treatment outcomes.

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Multiple factors bias chromosome micronucleation

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Surgeon Experience and Medicare Expenditures for Laparoscopic Compared to Open Colectomy

Objective: To quantify the extent to which payments for laparoscopic and open colectomy are influenced by a surgeon's experience with laparoscopy. Background: Numerous studies suggest that healthcare costs for laparoscopic colectomy are lower than open surgery. None have assessed the importance of surgeon experience on the relative financial benefits of laparoscopy. Methods: We conducted a study of 182,852 national Medicare beneficiaries undergoing laparoscopic or open colectomy between 2010 and 2012. Using instrumental variable methods to account for selection bias, we compared Medicare payments for laparoscopic and open colectomy. We stratified our analysis by surgeons' annual experience with laparoscopic colectomy to determine the influence of provider experience on payments. Results: In the fully adjusted analysis, average episode payments per patient were $2640 [95% confidence interval (CI) −$4091 to −$1189] lower with the laparoscopic approach versus open. Surgeons in the highest quartile of laparoscopic experience demonstrated an average payment savings of $5456 per patient (CI −$7918 to −$2994) in their laparoscopic versus open cases. Among surgeons in the lowest quartile of laparoscopic experience, there was, however, no difference between laparoscopic and open cases (difference: $954, 95% CI −$731 to $2639). Differences in payments were explained by differences in complications rates. Both groups had similar rates of complications for open procedures (least experience, 21%, most experience, 21%; P = 0.45), but differed significantly on rates of complications for laparoscopic cases (least experience, 28%, most experience, 15%; P

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Prognosis of autoimmune hemolytic anemia in critically ill patients

Abstract

Patients with autoimmune hemolytic anemia (AIHA) may require intensive care unit (ICU) admission. In order to describe the characteristics of AIHA patients in ICU and identify prognosis factors, clinical and biological data from 44 patients admitted in one ICU between 2002 and 2015 were retrospectively analyzed. The main reasons for ICU admission were profound anemia without any organ failure in 19 patients (either for safer transfusion or continuous monitoring only). Twenty-five (57%) patients had a past history of hemopathy. Twenty patients presented with a direct anti-globulin test (DAT) positive for immunoglobulin G (DAT-IgG) only (46%), 8 with a DAT positive for both IgG and complement (DAT-IgG+C) (36%), and 16 with a DAT positive for complement only (DAT-IgG+C) (18%). Corticosteroids and rituximab were administered to respectively 44 (100%) and 12 (25%) patients. Red blood cell transfusion was required in 28 (64%) patients. Ten (23%) patients received vasopressors. Renal replacement therapy was necessary in 14 (31.8%) patients. Thirteen (30%) patients died in the ICU. There was no difference between survivors and non-survivors regarding associated comorbidities like hemopathy (18/31 [58%] vs. 7/13 [54%], p = 0.80). In decedents, age was higher (72 years [57.8–76.3] vs. 50 years [34.3–64], p < 0.01) and organ dysfunctions were more severe at day 1 (SOFA 8 [7–11] vs. 5.5 [3–7], p < 0.01). Patients with a DAT-IgG displayed poorer outcome in comparison with patients with DAT-IgG+C/C (hospital mortality 69% vs. 36%, p = 0.04). Mortality rate of AIHA patients requiring ICU admission is consequential and appears to be impacted by age, organ failures, and DAT-IgG.

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A lethal case of hoarding due to the combination of traumatic and confined space asphyxia

Abstract

Hoarding is defined as the acquisition of, and failure to discard, possessions of little use or value to others, usually associated with a significant degree of clutter in the individual's home. We describe a case of a woman who died from a combined traumatic and confined space asphyxia, after being trapped under some of the objects amassed in her apartment. The event was considered to be accidental; by taking into account the information gathered during assessment of the scene, we believe that the accident took place while entering or exiting the apartment. It appears that the woman, who was trying to open or close the door, could have been using her leg to keep the objects piled behind the door from falling. Unfortunately the pile of hoarded objects collapsed and the woman was fatally trapped underneath them. The age and strength of the woman played an important role in the fatal incident, she was too old and weak to remove the items that had collapsed over her body. The scarcity of space between the collapsed objects and the woman, as well as the absence of external or internal signs of violent asphyxiation, or other causes of death, allowed us to establish that the death resulted from a combined mechanism of both the traumatic and the confined space asphyxiation.

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Utilizing ticks as forensic indicators in a livestock investigation

Abstract

Although forensic parasitology remains in its infancy compared with more developed fields like forensic entomology, parasites can be useful forensic indicators. We present the case of an individual who disobeyed animal health legislation and crossed animal quarantine boundaries and two state lines with a cattle tick (Rhipicephalus australis) infested horse. Following recognition of the infestation by animal health officers, the individual asserted that the infestation had occurred either during transport or upon arrival at the site of discovery, and that they had not contravened quarantine legislation. Utilizing ticks as forensic indicators, knowledge of the life cycle and minimum age of ticks on the infested horse indicated that the individual's assertions were false, and that they had in fact transported the tick infested horse from a cattle tick endemic region across state lines and quarantine zones.

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