Fisher profiles and perceptions of sea turtle-fishery interactions: case study of East Coast Peninsular Malaysia

The paper focuses on coastal fisheries, particularly examining sea turtle-fishery interactions and determining the socioeconomic profile and perception of local fishers about sea turtle issues along the East Coast of Peninsular Malaysia.Turtle fisheries, Nature conservation, Coastal fisheries, Man-induced effects, ISEW, Malaysia, Malaya, Pahang, Malaysia, Malaya, Kelantan, Malaysia, Malaya, Terengganu,

Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling

Stenodactylin, a highly toxic type 2 ribosome-inactivating protein purified from the caudex of Adenia stenodactyla Harms, is a potential anticancer drug candidate. Previous studies demonstrated that stenodactylin induces apoptosis and necroptosis in treated cells, involving the production of reactive oxygen species. We analyzed the effect of stenodactylin on Raji and Ramos (Human Burkitt’s lymphoma cells) and MOLM-13 (acute myeloid leukemia cells). Moreover, we focused on the early events in MOLM-13 cells that characterize the cellular response to the toxin by whole-genome microarray analysis of gene expression. Treatment with stenodactylin induced the depurination of 28S rRNA within 4 h and increased the phosphorylation of p38 and JNK. A time-dependent activation of caspase 1, 2, 8, 9, 3/7 was also observed. Genome-wide gene expression microarray analysis revealed early changes in the expression of genes involved in the regulation of cell death, inflammation and stress response. After 4 h, a significant increase of transcript level was detectable for ATF3, BTG2, DUSP1, EGR1, and JUN. Increased upstream JUN signaling was also confirmed at protein level. The early response to stenodactylin treatment involves inflammatory and apoptotic signaling compatible with the activation of multiple cell death pathways. Because of the above described properties toward acute myeloid leukemia cells, stenodactylin may be a promising candidate for the design of new immunoconjugates for experimental cancer treatment

Validation and reliability of the Chichewa translation of the EQ-5D quality of life questionnaire in adults with orthopaedic injuries in Malawi

Background: The EQ-5D is a standardised instrument that measures health-related quality-of-life and explores cost-effectiveness of treatments. Malawi is a low-resource country that would benefit from assessment of quality-of-life among individuals living with chronic conditions. Chichewa is the official native language of Malawi. The Chichewa version of the EQ-5D-3L developed by EuroQoL group has not been validated with Chichewa speakers. The purpose of this study was to evaluate the clinimetric properties of the Chichewa EQ-5D-3L.Methods: Patients with orthopaedic conditions were recruited in the outpatient orthopaedic clinics and wards at Queen Elizabeth Central Hospital, Blantyre, Malawi. Fifty-three patients with various musculoskeletal problems were administered the Chichewa EQ-5D-3L and World Health Organization quality of life (WHO-QOL) questionnaires. To assess repeatability, a separate test–retest population of 20 patients were also selected from orthopaedic clinics and wards to fill out the questionnaire twice.Results: Convergence validity was determined, with each of the WHO-QOL domains and the EQ-5D descriptive index and visual analogue scale (VAS) having good to moderate correlation (r = 0.3–0.7). Internal consistency was measured for the descriptive index, and the Cronbach’s alpha was 0.7. The ceiling effect for the descriptive index and the VAS were 9.4% and 0%, respectively. No respondents reached floor effect for the descriptive index or the VAS. The test retest intraclass correlation coefficient reliability at 14 days was 0.984 for the VAS and 1 for the descriptive index, with all 20 respondents providing the same responses.Conclusions: The EuroQoL translated version of the Chichewa EQ-5D-3L was found to demonstrate adequate validity, internal consistency, floor/ ceiling effects, and reliability

Fixation of the fully hydroxyapatite-coated Corail stem implanted due to femoral neck fracture: 38 patients followed for 2 years with RSA and DEXA

Background Today, dislocated femoral neck fractures are commonly treated with a cemented hip arthroplasty. However, cementing of the femoral component may lead to adverse effects and even death. Uncemented stems may lower these risks and hydroxyapatite (HA) coating may enhance integration, but prosthetic stability and clinical outcome in patients with osteoporotic bone have not been fully explored. We therefore studied fixation and clinical outcome in patients who had had a femoral neck fracture and who had received a fully HA-coated stem prosthesis. Patients and methods 50 patients with a dislocated femoral neck fracture were operated with the fully HA-coated Corail total or hemiarthroplasty. 38 patients, mean age 81 (70-96) years, were followed for 24 months with conventional radiographs, RSA, DEXA, and for clinical outcome. Results 31 of the 38 implants moved statistically significantly up to 3 months, mainly distally, mean 2.7 mm (max. 20 mm (SD 4.3)), and rotated into retroversion mean 3.3 (-1.8 to 17) (SD 4.3) and then appeared to stabilize. Distal stem migration was more pronounced if the stem was deemed to be too small. There was no correlation between BMD and stem migration. The migration did not result in any clinically adverse effects. Interpretation The fully hydroxyapatite-coated Corail stem migrates during the first 3 months, but clinical outcome appears to be good, without any adverse events

Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

Background: Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods: Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results: Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions: Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration: ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT0182971

Being Grateful for My Stupid Little Life : Why We Need Movies

More and more I’m convinced the current cultural paradigm leaves us too thin. The practical and objective approach to reality doesn’t attend to the complexity and mystery of the created world; it doesn’t attend to the complexity and mystery of our humanity. Posting about how movies help make sense of our experiences from In All Things - an online hub committed to the claim that the life, death, and resurrection of Jesus Christ has implications for the entire world. http://inallthings.org/being-grateful-for-my-stupid-little-life-why-we-need-movies

GRP94 rewires and buffers the FLT3-ITD signaling network and promotes survival of acute myeloid leukemic stem cells

Not available

Cyclic AMP induces IPC leukemia cell apoptosis via CRE-and CDK-dependent Bim transcription

The IPC-81 cell line is derived from the transplantable BNML model of acute myelogenic leukemia (AML), known to be a reliable predictor of the clinical efficiency of antileukemic agents, like the first-line AML anthracycline drug daunorubicin (DNR). We show here that cAMP acted synergistically with DNR to induce IPC cell death. The DNR-induced death differed from that induced by cAMP by (1) not involving Bim induction, (2) being abrogated by GSK3β inhibitors, (3) by being promoted by the HSP90/p23 antagonist geldanamycin and truncated p23 and (4) by being insensitive to the CRE binding protein (CREB) antagonist ICER and to cyclin-dependent protein kinase (CDK) inhibitors. In contrast, the apoptosis induced by cAMP correlated tightly with Bim protein expression. It was abrogated by Bim (BCL2L11) downregulation, whether achieved by the CREB antagonist ICER, by CDK inhibitors, by Bim-directed RNAi, or by protein synthesis inhibitor. The forced expression of BimL killed IPC-81WT cells rapidly, Bcl2-overexpressing cells being partially resistant. The pivotal role of CREB and CDK activity for Bim transcription is unprecedented. It is also noteworthy that newly developed cAMP analogs specifically activating PKA isozyme I (PKA-I) were able to induce IPC cell apoptosis. Our findings support the notion that AML cells may possess targetable death pathways not exploited by common anti-cancer agents