The rehabilitation of clinical assessment for the diagnosis of pulmonary embolism

Pulmonary angiography is the gold standard for diagnosis of segmental pulmonary embolism, but no longer for subsegmental pulmonary embolism because the inter-observer agreement for angiographically documented subsegmental pulmonary embolism is only 60%. A normal rapid ELISA VIDAS D-dimer test result and a normal perfusion scan exclude pulmonary embolism with a negative predictive value of >99%, irrespective of clinical score. The positive predictive value for pulmonary embolism of a high probability VP-scan compared to pulmonary angiography is 87% indicating that 13% of patients with a high probability VP-scan do not have pulmonary embolism. The combination of a negative CUS, a low clinical score, and a non-diagnostic VP-scan safely excludes pulmonary embolism. Patients with a non-diagnostic VP-scan, a negative CUS, but a moderate to high clinical score are candidates for pulmonary angiography. The positive predictive value of helical spiral CT is >95 to 99%. The combination of a negative CUS, a low clinical score, and the presence of a clear alternative diagnosis is predicted to safely exclude pulmonary embolism. Helical spiral CT detects all clinical relevant pulmonary emboli and a large number of alternative diagnoses in symptomatic patients with a non-diagnostic or a high-probability VP-scan. The negative predictive value during 3 months followup after a negative spiral CT for pulmonary embolism in 4 retrospective studies and 1 prospective management study was >99%. Only a small group of patients (1-2%) with a non-diagnostic spiral CT are candidates for pulmonary angiography. Therefore, it is predicted that the spiral CT will replace both VP-scanning and pulmonary angiography to safely exclude or diagnose pulmonary emboli in patients with suspected pulmonary embolism.     

Forty-one near full-length HIV-1 sequences from Kenya reveal an epidemic of subtype A and A-containing recombinants

OBJECTIVE: To further define the genetic diversity of HIV-1 in Kenya using approaches that clearly distinguish subtypes from inter-subtype recombinants. DESIGN: Near full genome sequencing and analysis were used, including sensitive new tools for detection and mapping of recombinants. METHODS: Purified peripheral blood mononuclear cell DNA from 41 HIV-1 positive blood donations collected from six hospitals across southern Kenya was used to amplify near full-length genomes by nested PCR. These were sequenced on an ABI 3100 automated sequencer and analyzed phylogenetically. RESULTS: Among 41 near full-length genomes, 25 were non-recombinant (61%) and 16 were recombinant (39%). Of the 25 pure subtypes, 23 were subtype A, one was subtype C and one was subtype D. Most recombinants consisted of subtype A and either subtype C or subtype D; a few contained A2, a recently identified sub-subtype. Two A2/D recombinants had identical breakpoints and may represent a circulating recombinant form. A third A2/D recombinant had the same structure as a previously described Korean isolate, and these may constitute a second A2-containing circulating recombinant form. CONCLUSIONS: In Kenya, 93% of HIV-1 genomes were subtype A or A-containing recombinant strains. Almost 40% of all strains were recombinant. Vaccine candidates tested in Kenya should be based on subtype A strains, but the methods used for evaluation of breakthrough infections during future vaccine trials should be capable of identifying non-A subtypes, the A2 sub-subtype, and recombinants.     

HIV Prevalence Among Hospitalized Patients at the Main Psychiatric Referral Hospital in Botswana

We examined HIV prevalence among patients 18–49 year olds admitted to a psychiatric hospital in Botswana in 2011 and 2012. The retrospective study analyzed females (F) and males (M) separately, comparing proportions with Chi square test and continuous variables with Wilcoxon rank-sum test, assessing significance at the 5% level. HIV seroprevalence among hospitalized psychiatric patients was much more common among females (53%) compared with males (19%) (p < 0.001). These women also appeared more vulnerable to infection compared with females in the general population (29%) (p < 0.017). Among both women and men, HIV-infection appeared most common among patients with organic mental disorders (F:68%, M:41%) and neurotic, stress related and somatoform disorders (F:68%, M:42%). The largest proportion of HIV infections co-occurred among patients diagnosed with schizophrenia, schizotypal and other psychotic disorders (F:48%; M:55%), mood (affective) disorders (F:21%; M:16%) and neurotic, stress-related and somatoform disorders (F:16%; M:20%). Interventions addressing both mental health and HIV among women and men require development.     

Lateral diffusion of membrane lipids and proteins during the cell cycle of neuroblastoma cells.

The fluorescence photobleaching recovery method has been used to determine the lateral mobilities of membrane lipids and proteins during the cell cycle of synchronized C1300 mouse neuroblastoma cells (clone Neuro-2A). As probes for lipid mobility, 3,3'-dioctadecylindocarbocyanine iodide and a fluorescein-labeled analog of ganglioside GM1 were used. Membrane proteins were labeled with rhodamine-labeled rabbit antibodies against mouse E14 cells. For both lipid probes the diffusion coefficients reach a minimum in mitosis, increase 2- to 3-fold during G1, remain constant at maximal values during S, and decrease again shortly before mitosis. Membrane proteins also exhibit minimum diffusion coefficients in mitosis, followed by a similar rise in G1. However, as cells proceed through S and G2, the lateral mobility of the membrane proteins gradually decreases. It is argued that lipid mobility is controlled by the fluidity of the membrane lipid matrix whereas protein mobility is governed also by other constraints.     

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Leukemia cells exhibit a dysregulated developmental program as the result of genetic and epigenetic alterations. Overexpression of the RNA-binding protein Musashi2 (MSI2) has been previously shown to predict poor survival in leukemia. Here, we demonstrated that conditional deletion of Msi2 in the hematopoietic compartment results in delayed leukemogenesis, reduced disease burden, and a loss of LSC function in a murine leukemia model. Gene expression profiling of these Msi2-deficient animals revealed a loss of the hematopoietic/leukemic stem cell self-renewal program and an increase in the differentiation program. In acute myeloid leukemia patients, the presence of a gene signature that was similar to that observed in Msi2-deficent murine LSCs correlated with improved survival. We determined that MSI2 directly maintains the mixed-lineage leukemia (MLL) self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc, and Ikzf2 mRNAs. Moreover, depletion of MLL target Ikzf2 in LSCs reduced colony formation, decreased proliferation, and increased apoptosis. Our data provide evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and suggest MSI2 as a potential therapeutic target for myeloid leukemia.     

Well‐Being and Personal Growth in Mothers of Full‐Term and Pre‐Term Singletons and Twins

The present study examined well‐being and personal growth in mothers (n = 414) 1 year after childbirth. We examined the contribution of the event characteristics (birth of singletons or twins, full‐ or pre‐term babies, first or non‐first child, spontaneous pregnancy or fertility treatments and infant temperament), internal resources (attachment anxiety and avoidance) and external resources (marital quality and maternal grandmother's support). Regressions indicated that having a first child, child's easier temperament, lower attachment anxiety and avoidance, grandmother's emotional support and some aspects of the spousal relationships contributed to well‐being. Personal growth was found to be related to the birth of a pre‐term baby or babies, positively associated with maternal grandmother's support, and the marital quality of parenthood, and negatively with mothers' education. Beyond the findings that well‐being and personal growth are related to the availability of certain resources, the current study demonstrates that the two outcomes are separate phenomena that reveal different patterns of associations with other variables. Several explanations for the findings are proposed, and practical implications are discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Distinct Haplotype in Non-Ashkenazi Gaucher Patients with N370S Mutation

ABSTRACT: A new polymorphism, in intron 7 of glucocerebrosidase gene, has been identified in Gaucher Disease patients. It seems to appear only in Pv1.1^-alleles bearing the N370S mutation. This new sub-haplotype was only identified in Portuguese patients, of origins spanning all of the Portuguese continental territory. This finding indicates that, in the Portuguese, mutation N370S has existed in the context of two slightly different haplotypes and thus must be relatively ancient.