Isolation, structure, and synthesis of novel 4-quinolinone alkaloids from Esenbeckia leiocarpa

Two new biocidal quinolinone alkaloids, 3-methoxy-1-methyl-2-propyl-4-quinolone [1] and 2(1'-ethylpropyl)-1-methyl-4-quinolone [2], were efficiently isolated using reversed-phase recycling hplc from the leaves of Esenbeckia leiocarpa. The structures were determined through spectroscopic data and confirmed by total synthesis. These alkaloids have antifeedant activities against the pink bollworm, Pectinophora gossypiella.     

The genomes of three North American <Emphasis Type="Italic">orthopoxviruses</Emphasis>

The complete genomes of a skunkpox, volepox, and raccoonpox virus were sequenced and annotated. Phylogenetic analysis of these genomes indicates that although these viruses are all orthopoxviruses, they form a distinct clade to the other known species. This supports the ancient divergence of the North American orthopoxviruses from other members of the orthopoxviruses. Only two open reading frames appear to be unique to this group of viruses, but a relatively small number of insertions/deletions contribute to the varied gene content of this clade. The availability of these genomes will help determine whether skunkpox and volepox viruses share the characteristics that make raccoonpox a useful vaccine vector.     

The pathway to grandparenting stress: trauma,relational conflict,and emotional well-being

Objectives: This paper examines the mediating effect of child–grandparent conflict on the relationship between child trauma exposure and grandparenting stress.

Methods: Data was collected from a sample of custodial grandparents who participated in kinship care or relative caregiving programs (n = 251). Grandparenting stress was measured with Parenting Stress Scale (Berry &; Jones, 1995 Berry, J.O., &; Jones, W.H. (1995). The Parental Stress Scale: Initial psychometric evidence. Journal of Social and Personal relationships, 12, 463–472.[Crossref], [Web of Science ®] , [Google Scholar]) modified for grandparents. A series of regression models and structural equation models (SEM) were used to test the relationship between the number of different types of child trauma exposures and grandparenting stress, and to examine the mediating effect of child–grandparent conflicts on the relationship.

Results: Almost three-fourths (72%) of children had experienced at least one type of traumatic exposure. The SEM model shows that child's trauma exposure indirectly affected grandparenting stress, mediated by child–grandparenting conflicts though no direct path between the child's trauma exposure variable and grandparenting stress was found. A higher level of child–grandparent conflicts was also associated with a lower level of emotional well-being among custodial grandparents.

Conclusion: Based on these findings, recommendations are made about how to tailor a trauma-informed approach to the needs of custodial grandparents.     

Disproportionately large, communicating fourth ventricle. Case report]

A 39-year-old male was admitted because of slowly progressive disturbance of consciousness, diplopia, and ataxia after laparotomy. Ventriculoperitoneal shunting and removal of an arteriovenous malformation had been performed previously. Neurological examination on admission revealed drowsiness, rotatory nystagmus, Parinaud's sign, and truncal ataxia. Computed tomography scan revealed extraordinary dilatation of the fourth ventricle compared with other dilated ventricles, and old low-density areas in the cerebellar hemispheres. After an external ventricular drainage (EVD) was inserted, all the ventricles decreased in size and the symptoms disappeared. The authors confirmed the patency of the aqueductal canal. One week later, the EVD was replaced by a ventriculoperitoneal shunt. A disproportionately large, communicating fourth ventricle (DLCFV) should be differentiated from an isolated fourth ventricle, which consists of marked enlargement of the fourth ventricle with obstruction of both the inlet and outlet of the fourth ventricle. The authors propose the importance of the fragility to pressure of the brain parenchyma and cerebellar hemispheres around the fourth ventricle as the mechanism of producing DLCFV.     

Anti-B4-blocked ricin: a phase II trial of 7 day continuous infusion in patients with multiple myeloma

This phase II trial was undertaken to determine the toxicities, response rate, pharmacokinetics and frequency of human anti-mouse antibody (HAMA) and anti-ricin antibody (HARA) when the B-cell restricted immunotoxin anti-B4-bR was administered to patients with previously treated multiple myeloma (MM).
Five patients with MM were scheduled to receive a 7 d continuous infusion of anti-B4-bR. The initial four patients received therapy at 40 μg/kg lean body weight (LBW)/d. Two patients received a 7 d infusion, one patient received 6 d, and another patient 5 d of therapy. The fifth patient was treated for 7 d at a lower dose of 30 μg/kg LBW/d because of the side-effects observed in the initial patients.
Pharmacokinetic studies demonstrated a peak serum level >2.6 n M in three of the patients. Side-effects of therapy included hepatic transaminase elevations, myalgias, thrombocytopenia, nausea, vomiting, decrease in performance status, and capillary leak syndrome. One patient developed HAMA and two patients HARA. One patient developed neurologic toxicity with akinetic mutism, and died following therapy. No patient demonstrated a significant decline in M-component during therapy.
We concluded that anti-B4-bR can be administered by continuous infusion to patients with multiple myeloma, although immunotoxin levels >3 n M were associated with increased incidence of toxicity and required dose adjustment. Future trials using anti-B4-bR in MM will be needed to determine the optimal dose and administration schedule in this patient population, and to determine whether there is evidence of biologic activity.