Elucidating the roles of ASPM isoforms reveals a novel prognostic marker for pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide. Late diagnosis, desmoplastic tissue and intrinsic resistance to therapy are among the main reasons for its aggressive phenotype. In addition, it is now appreciated that cancer stem cells – a rare subpopulation of tumor cells highly resistant to therapy – are crucial players in PDAC initiation, progression and resistance to therapy. In a recent article in The Journal of Pathology, Hsu et al elucidated the specific roles of abnormal spindle-like, microcephaly-associated protein (ASPM) isoforms in PDAC. The authors reported that ASPM isoform I (ASPM-iI) is mainly expressed in the cytoplasm of PDAC cells. Its expression is associated with the Wnt signaling pathway, which promotes stemness and maintains the cancer stem cell niche. Clinically, expression of ASPM-iI correlates with poor survival in PDAC patients. Thus, this study revealed a novel prognostic marker as well as a potential therapeutic target for PDAC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults

This study evaluated the efficacy of paroxetine for symptoms and associated features of chronic posttraumatic stress disorder (PTSD), interpersonal problems, and dissociative symptoms in an urban population of mostly minority adults. Adult outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of single-blind placebo (N = 70). Those not rated as significantly improved were then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks, with a flexible dosage design (maximum 60 mg by week 7). Significantly more patients treated with paroxetine were rated as responders (14/21, 66.7%) on the Clinical Global Impression-Improvement Scale (CGI-I) compared to patients treated with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also superior to placebo on reduction of dissociative symptoms [Dissociative Experiences Scale (DES) score] and reduction in self-reported interpersonal problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week maintenance phase, paroxetine response continued to improve, but placebo response did not. Paroxetine was well tolerated and superior to placebo in ameliorating the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms, and interpersonal problems in the first trial conducted primarily in minority adults.     

Verbal and physical aggression in World War II former prisoners of war: role of posttraumatic stress disorder and depression

This study examined the relationship among posttraumatic stress disorder (PTSD), depression, and intimate partner relationship aggression in a community sample of World War II (WWII) male military former prisoners of war (POWs). Sixty percent of these POWs reported verbal aggression in their marriages, and 12% endorsed physical aggression. Both verbal and physical aggression were significantly correlated to the severity of captivity trauma and to PTSD symptoms. Posttraumatic stress disorder symptoms significantly mediated the relationship between severity of trauma and both verbal and physical aggression. Depression was a significant moderator of the relationship between PTSD and both physical and verbal aggression. Theoretical and clinical implications are suggested.     

Escharotomy using an enzymatic debridement agent for treating experimental burn-induced compartment syndrome in an animal model

BACKGROUND: In patients with deep circumferential burns, adequate resolution of burn-induced compartment syndrome (BICS) is achieved by surgical escharotomy. Surgical escharotomy is traumatic, may cause considerable blood loss, does nothing toward debridement of the burn wound, and entails possible morbidity and complications. Debridase is a Bromelain derived enzymatic preparation capable of lysing the burn eschar within 4 hours, obviating the need for surgical debridement. It has an affinity to burned necrotic tissue and does not damage healthy skin. In our clinical assessment of the Debridase efficacy, we found in several cases of deep burns of the limbs that the measured IC pressure subsided after 2-4 hours of Debridase application and none of the enzymatic escharotomy treated patients suffering from circumferential burns developed BICS. To confirm these observations we conducted this controlled study. AIM: to assess the efficacy of Debridase for treating BICS in an animal model. MATERIALS AND METHODS: A model for BICS was developed by making circumferential burns to pig legs and monitoring the anterior compartment the legs. BICS was induced in the legs of 5 pigs, 20 legs. 10 legs were treated with Debridase and 10 served as nontreated controls, treated by surgical escharotomy at the conclusion of the experiment. RESULTS: Debridase reduced BICS within 30 minutes from application. Debridase was as effective as a standard surgical escharotomy. CONCLUSION: Escharectomy using an effective enzymatic debriding agent is potentially an adequate, simple, fast and effective procedure to treat BICS, it has the added benefit of burn debridement without surgical escharotomy.