The ssDNA Theory of BRCAness and Genotoxic Agents

Cancers that are deficient in BRCA1 or BRCA2 are thought to be hypersensitive to genotoxic agents because they cannot prevent or repair DNA double strand breaks, but observations in patients suggest this dogma may no longer agree with experiment. Here, we propose that single stranded DNA underlies the hypersensitivity of BRCA deficient cancers, and that defects in double strand break repair and prevention do not. Specifically, in BRCA deficient cells, ssDNA gaps developed because replication was not effectively restrained in response to stress. In addition, we observed gaps could be suppressed by either restored fork restraint or by gap filling, both of which conferred therapy resistance in tissue culture and BRCA patient tumors. In contrast, restored double strand break repair and prevention did not confer therapy resistance when gaps were present. Critically, double strand breaks were not detected after therapy when apoptosis was inhibited, supporting a framework in which double strand breaks are not directly induced by genotoxic agents, but instead are created by cell death nucleases and are not fundamental to genotoxic agents. Together, these data indicate that ssDNA replication gaps underlie the BRCA cancer phenotype, BRCAness, and we propose are fundamental to the mechanism-of-action of genotoxic chemotherapy

Preliminary results on the preferences of Callosobruchus maculatus on Apulian germplasm of Cicer arietinum

The susceptibility of six genotypes of Cicer arietinum L. (Fabaceae) to Callosobruchus maculatus (Fabr.) (Coleoptera: Bruchidae) was evaluated through comparative laboratory bioassays. The egg-laying amount, pattern of adult emergence, median development time and pre-adult mortality were assessed under free-choice and no-choice bioassays on three local genotypes (Altamura, Grumo Appula White and Grumo Appula Black) and three commercial varieties (Barraco, Sultano and standard of large-scale retail trade as control). Trials were performed on a completely randomized experimental design under artificial conditions with the release of males and females (ratio 1:3), at the most 24-h old. Among the assayed genotypes, the local one provided with a black coat (Grumo Appula Black) was significantly (

Psychological Distress and Affective, Behavioral and Cognitive Experiences of Stuttering

Adults who stutter (AWS) are vulnerable to the development of various psychopathological symptoms, although prevalence data are mixed, and even less clarity exists as it relates to the factors that potentially influence their occurrence. The current study sought to shed light on the prevalence of self-reported psychopathology in AWS and aimed to identify relationships between affective, behavioral and cognitive (ABC) experiences of stuttering and psychological distress. This was based on AWS\u27 reports of speech situation-specific anxiety and speech disruption, the use of behaviors to avoid or escape stuttering, and one\u27s communication attitude. The self-reports administered to 40 AWS via Qualtrics, an online survey software, were subtests of the Behavior Assessment Battery for Adults who Stutter (BAB; Vanryckeghem & Brutten, 2018) and the Brief Symptom Inventory-18 (Deragotis, 2001). Participants\u27 BAB scores approximated the normative data suggesting that the current sample corresponded to the psychosocial profile of AWS. Participants\u27 indications of psychological distress were not found to differ from that of a non-clinical normative sample. Ten percent of participants met clinical thresholds for what is considered clinically significant distress. Overall, the current data provide evidence that, as a group, levels of psychopathology in this population approximate community samples, highlighting the existence of psychologically distressed subgroups of AWS. Regression analyses uncovered that the ABC factors of stuttering positively predicted participants\u27 reports of levels of psychopathology. Among these factors, speech situation-specific anxiety had the strongest relationship to psychological distress, followed closely by one\u27s report of situation-specific speech disruption. To a lesser, but still significant extent, a PWS\u27 communication attitude predicted psychopathology. Finally, a weaker and less clear positive relationship between PWS\u27 use of coping behaviors to avoid and/or escape stuttering and their levels of psychological distress was found

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET)

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in "in Vitro" Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed

Inflammatory Cytokines During Cardiac Rehabilitation After Heart Surgery and Their Association to Postoperative Atrial Fibrillation

Inflammation is associated with atrial fibrillation (AF), but little is known about the association of AF with the inflammatory serum cytokines after the acute postoperative phase. Thus, we aimed to explore how plasma cytokines concentrations modify during a 3-week cardiac rehabilitation after heart surgery, comparing patients who developed postoperative AF (POAF) and those with permanent AF with patients free from AF (NoAF group). We enrolled 100 consecutive patients and 40 healthy volunteers as a control group. At the beginning of cardiac rehabilitation, 11 days after surgery, serum levels of MPO, PTX3, ADAM17, sST2, IL-25, and IL-33 were dramatically higher, whereas TNFa and IL-37 levels were much lower in NoAF, POAF, and permanent AF patients than in the healthy volunteers. After rehabilitation, most of the cytokines changed tending towards normalization. POAF patients (35% of the total) had higher body mass index and abdominal adiposity than NoAF patients, but similar general characteristics and risk factors for POAF. However, ADAM-17 and IL-25 were always lower in POAF than in NoAF patients, suggesting a protective role of IL-25 and ADAM 17 against POAF occurrence. This finding could impact on therapeutic strategies focusing on the postoperative prophylactic antiarrhythmic interventions