Expression and Activity of the NF-κB Subunits in Chronic Lymphocytic Leukaemia: A Role for RelB and Non-Canonical Signalling.

Background: Canonical NF-κB signalling by p65 (RelA) confers chemo-resistance and poor survival in chronic lymphocytic leukaemia (CLL). The role of non-canonical NF-κB signalling (leading to RelB and p52 subunit activation) in CLL is less understood, but given its importance in other B-cell tumour types, we theorised that RelB and p52 may also contribute to the pathology of CLL.

Methods: DNA binding activity of all five NF-kB subunits, p65, p50, RelB, p52, and c-Rel, was quantified using ELISA and correlated to ex vivo chemoresistance, CD40L-stimulated signalling (to mimic the lymph node microenvironment), and clinical data.

Cancer-related cognitive impairment and associated factors in a sample of older male oral-digestive cancer survivors.

Objective: This study examines the demographic and clinical variables associated with cancer-related cognitive impairment (CRCI) in a sample of older, male, oral-digestive cancer survivors at VA Medical Centers in Boston and Houston.

Methods: A two-time point, longitudinal design was used, with cognitive assessment conducted at 6 and 18 months post-diagnosis. Using ANCOVA, the cognitive functioning of 88 older adults with head and neck, esophageal, gastric, or colorectal cancers was compared with that of 88 healthy controls.

Development of a Bereavement Group in a Geriatric Mental Health Clinic for Veterans.

Objectives: This article describes the development and program evaluation of an 8-session outpatient geriatric mental health clinic bereavement group for United States military veterans who experienced the death of a loved one.

Methods: Group materials were developed based on a review of literature, with a focus on the dual process model of coping with bereavement and complicated grief treatment. Data are presented from 19 veterans who attended at least 4 of the 8 sessions across the five offerings of this group between 2013 and 2015.

Program Evaluation of Group-based Cognitive Behavioral Therapy for Insomnia: a Focus on Treatment Adherence and Outcomes in Older Adults with Co-morbidities.

Objective: To describe a program evaluation of the interrelationship of adherence and treatment outcomes in a sample of veteran older adults with co-morbidities who participated in group-based cognitive behavioral therapy for insomnia.

Methods: Retrospective data extraction was performed for 14 older adults. Adherence measures and sleep outcomes were measured with sleep diaries and Insomnia Severity Index.

Medical Abortion in Australia: What Are the Clinical and Legal Risks? Is Medical Abortion Over-regulated?

This article examines the clinical and legal risks of early medical abortion. After providing an overview of the history of mifepristone in Australia, the evidence concerning the efficacy and safety of medical abortion is discussed. It is argued that the negligible medical risks associated with mifepristone do not justify the restrictive regulatory measures imposed on medical practitioners.

PARP1 expression, activity and ex vivo sensitivity to the PARP inhibitor, talazoparib (BMN 673), in chronic lymphocytic leukaemia.

In chronic lymphocytic leukemia (CLL), mutation and loss of p53 and ATM abrogate DNA damage signalling and predict poorer response and shorter survival. We hypothesised that poly (ADP-ribose) polymerase (PARP) activity, which is crucial for repair of DNA breaks induced by oxidative stress or chemotherapy, may be an additional predictive biomarker and a target for therapy with PARP inhibitors.We measured PARP activity in 109 patient-derived CLL samples, which varied widely (192 - 190052 pmol PAR/10⁶ cells) compared to that seen in healthy volunteer lymphocytes (2451 - 7519 pmol PAR/10⁶ cells).

Valued life abilities among veteran cancer survivors.

Background: When patients have multiple chronic illnesses, it is not feasible to provide disease-based care when treatments for one condition adversely affect another. Instead, health-care delivery requires a broader person-centred treatment plan based on collaborative, patient-oriented values and goals.

Objective: We examined the individual variability, thematic content, and sociodemographic correlates of valued life abilities and activities among multimorbid veterans diagnosed with life-altering cancer.

Positive Affect and Social Anxiety Across the Lifespan: An Investigation of Age as a Moderator.

Recent literature has supported a moderate, inverse relationship between social anxiety and positive affect. It has been proposed, but not clearly established, that the inverse relationship between the constructs may be stronger in younger adults than in adults who are older. We tested this hypothesis in two archival data sets of community participants.

Cancer-related PTSD symptoms in a veteran sample: association with age, combat PTSD, and quality of life.

Objective: The diagnosis and treatment of cancer is a potentially traumatic experience that may evoke posttraumatic stress symptoms (PTSS) among survivors. This paper describes the rates of endorsement of cancer-related PTSS along with the relationship of demographic, cancer, and combat variables on PTSS and quality of life.

Methods: Veterans (N = 166) with head and neck, esophageal, gastric, or colorectal cancers were recruited through tumor registries at two regional Veterans Administration Medical Centers.

Cancer as a Criterion A Traumatic Stressor for Veterans: Prevalence and Correlates.

The diagnosis of cancer is an uncontrollable stressor posing the threat of death and disfigurement, often followed by repeated exposure to aversive reminders in the form of noxious treatments, persisting side effects, reengagement at times of surveillance, and the threat of recurrence. The phenomenon of cancer as a traumatic stressor is explored in this study, with a focus on the prevalence and correlates of posttraumatic stress disorder (PTSD) Criterion A in a sample of 170 mostly male adults who received health care at VA Medical Centers in Boston or Houston. Participants were interviewed 6 months after diagnosis with head and neck, gastro-esophageal, or colorectal cancers.

Mifepristone in South Australia -- the first 1343 tablets.

Background: Mifepristone has recently become available in Australia but its use is restricted.

Objective: To describe the use of mifepristone in South Australia in the period 2009-2010 and to explore options that may become available to general practitioners.

Discussion: Mifepristone has been added to regimens for early and second trimester abortions - both medical and surgical abortions.

Therapeutic potential of poly(ADP-ribose) polymerase inhibitor AG014699 in human cancers with mutated or methylated BRCA1 or BRCA2.

Background: Mutations in BRCA1 and BRCA2 (BRCA1/2), components of the homologous recombination DNA repair (HRR) pathway, are associated with hereditary breast and ovarian cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors are selectively cytotoxic to animal cells with defective HRR, but results in human cancer cells have been contradictory. We undertook, to our knowledge, the first comprehensive in vitro and in vivo investigations of the antitumor activity of the PARP inhibitor AG014699 in human cancer cells carrying mutated or epigenetically silenced BRCA1/2.

Central nervous system penetration and enhancement of temozolomide activity in childhood medulloblastoma models by poly(ADP-ribose) polymerase inhibitor AG-014699.

Background: Temozolomide shows activity against medulloblastoma, the most common malignant paediatric brain tumour. Poly(ADP-ribose) polymerase (PARP) inhibitors enhance temozolomide activity in extracranial adult and paediatric human malignancies.

Methods: We assessed the effect of AG-014699, a clinically active PARP inhibitor, on temozolomide-induced growth inhibition in human medulloblastoma models.

6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance.

Familial breast and ovarian cancers are often defective in homologous recombination (HR) due to mutations in the BRCA1 or BRCA2 genes. Cisplatin chemotherapy or poly(ADP-ribose) polymerase (PARP) inhibitors were tested for these tumors in clinical trials. In a screen for novel drugs that selectively kill BRCA2-defective cells, we identified 6-thioguanine (6TG), which induces DNA double-strand breaks (DSB) that are repaired by HR.

Differential binding of Escherichia coli McrA protein to DNA sequences that contain the dinucleotide m5CpG.

The Escherichia coli McrA protein, a putative C(5)-methylcytosine/C(5)-hydroxyl methylcytosine-specific nuclease, binds DNA with symmetrically methylated HpaII sequences (Cm5CGG), but its precise recognition sequence remains undefined. To determine McrA's binding specificity, we cloned and expressed recombinant McrA with a C-terminal StrepII tag (rMcrA-S) to facilitate protein purification and affinity capture of human DNA fragments with m5C residues. Sequence analysis of a subset of these fragments and electrophoretic mobility shift assays with model methylated and unmethylated oligonucleotides suggest that N(Y > R) m5CGR is the canonical binding site for rMcrA-S.

Characterisation of adult green lacewing (Chrysoperla carnea) digestive physiology: impact of a cysteine protease inhibitor and a synthetic pyrethroid.

Background: In spite of concern regarding potential non-target effects of GM crops, few studies have compared GM pest control with conventional methods. The impacts of cypermethrin and oilseed rape expressing oryzacystatin-1 (OC-1) were compared in this study on the predator Chrysoperla carnea (Stephens).

Results: Adults fed purified rOC-1 showed a subtle shift in digestive protease profile, with an increasing reliance on serine proteases (chymotrypsin), increase in aspartic proteases and a slight reduction in elastase activity.

Treatment of suction termination of pregnancy-retained products with misoprostol markedly reduces the repeat operation rate.

A six-year audit of clinical outcomes following the treatment of suction termination of pregnancy-retained products of conception symptoms with 200 microg of misoprostol orally or sublingually three times a day for six doses showed that it was 93% effective and it reduced the repeat dilation and curettage rate by 79.6% (P < 0.001).

Comparison of four perioperative misoprostol regimens for surgical termination of first-trimester pregnancy.

Objective: To compare the outcomes of 4 different perioperative misoprostol regimens for surgical termination of first-trimester pregnancy.

Methods: Retrospective analysis of the records of 4000 women (4 cohorts of 1000 each) who underwent surgical termination of pregnancy. The 4 cohorts received: no misoprostol; 200 microg of oral misoprostol 30 minutes preoperatively; 200 microg of sublingual misoprostol 30 minutes preoperatively; or 200 microg of oral misoprostol 3 hours preoperatively plus 200 microg of vaginal misoprostol postoperatively.

Effective sensitization of temozolomide by ABT-888 is lost with development of temozolomide resistance in glioblastoma xenograft lines.

Resistance to temozolomide and radiotherapy is a major problem for patients with glioblastoma but may be overcome using the poly(ADP-ribose) polymerase inhibitor ABT-888. Using two primary glioblastoma xenografts, the efficacy of ABT-888 combined with radiotherapy and/or temozolomide was evaluated. Treatment with ABT-888 combined with temozolomide resulted in significant survival prolongation (GBM12: 55.

Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma.

Purpose: High-risk neuroblastoma is characterized by poor survival rates, and the development of improved therapeutic approaches is a priority. Temozolomide and topotecan show promising clinical activity against neuroblastoma. Poly(ADP-ribose) polymerase-1 (PARP-1) promotes DNA repair and cell survival following genotoxic insult; we postulated that its inhibition may enhance the efficacy of these DNA-damaging drugs in pediatric cancers.

Cloning, purification and initial characterization of E. coli McrA, a putative 5-methylcytosine-specific nuclease.

Expression strains of Escherichia coli BL21(DE3) overproducing the E. coli m(5)C McrA restriction protein were produced by cloning the mcrA coding sequence behind a T7 promoter. The recombinant mcrA minus BL21(DE3) host produces active McrA as evidenced by its acquired ability to selectively restrict the growth of T7 phage containing DNA methylated in vitro by HpaII methylase.