PNA-based artificial nucleases as antisense and anti-miRNA oligonucleotide agents.

Because of its interesting chemical, physical and biological properties, Peptide Nucleic Acid (PNA) has attracted major attention in molecular biology, for diagnostics purposes and development of biosensors. PNAs have become candidates for gene therapeutic drugs in ANTISENSE (AO) strategy with favorable in vivo biochemical properties. Recently, antisense PNA oligonucleotides have been described in anti-miRNA approach (AMO). We propose PNA-based nucleases as AO and AMO agents. We report the design, synthesis and characterization of two kinds of artificial nucleases composed of a PEG-PNA-PEG domain conjugated to HGG·Cu (A) and DETA (B) as well known cleavage sites. Qualitative (MALDI-TOF) and quantitative (HTS) assays were planned to study nuclease activity of constructs A and B on RNA-3'-FAM target sequence. The results have highlighted the best performance of nuclease B and the relevance of the PEG spacer, in particular for conjugate A, in terms of efficiency of the cleavage, suggesting that conjugates A and B also act as potential antisense and anti-miRNA agents.

Recent progress in chemically modified siRNAs.

RNA interference technology has become a powerful laboratory tool to study gene function. Small interfering RNAs (siRNAs) have provided unprecedented opportunities for the development of new therapeutics in human diseases. Unfortunately, siRNA duplexes are not optimal drug-like molecules. The problems for their effective application are fundamentally delivery, stability and off-target effects. Chemical modification provides solutions to many of the challenges facing siRNA therapeutics. In this review, we recapitulate and discuss the development of the latest described chemical modifications of siRNAs, with a special focus on novel chemical modifications of siRNA structure, architecture and siRNA conjugates.

The in-training examination in internal medicine: resident perceptions and lack of correlation between resident scores and faculty predictions of resident performance.

PURPOSE: We sought to survey residents' perceptions regarding the In-Training Examination in Internal Medicine and to assess the ability of faculty members to evaluate the knowledge base of internal medicine residents. SUBJECTS AND METHODS: Residents were asked about the perceived utility of the In-Training Examination and related self-directed educational activities. Residents predicted their own performance on the examination (into upper, middle, or lower tertile). Faculty predicted housestaffs scores, and residents predicted the scores of interns. RESULTS: Most residents (35/36; 97%) believed that the examination was useful, and 91% modified their study habits or clinical rotation schedule based on its results. Approximately half of the residents accurately predicted into which tertile they would score. Faculty predictions of resident performance on the examination were accurate 49% of the time, and resident predictions of intern scores were accurate 38% of the time. The sensitivity ofa lower-tertile prediction by faculty was 34%, with a specificity of 90%. The sensitivity of a resident prediction of a lower-tertile intern score was 15%, with a specificity of 98%. Both faculty and residents were more likely to overestimate than underestimate examination scores. CONCLUSION: Residents believe that the In-Training Examination is useful and frequently initiate educational interventions based on results. Faculty and residents lack the ability to evaluate accurately the knowledge of trainees that they supervise. In particular, both groups may be unable to identify trainees who are deficient in this element of clinical competence.

A survey of women's health care needs on U.S. Navy ships.

A total of 628 female and 526 male U.S. military personnel completed a health survey questionnaire at the completion of four shipboard deployments lasting 10 to 180 days (mean, 57 days). During deployment, women visited clinic (sick call) at significantly higher rates than men: 189 versus 117 visits per week per 1,000 personnel. Except for generally minor gynecological conditions, women and men had similar medical problems. Upper respiratory complaints and requests for contraceptive pills were the most common reasons for clinic visits among women. The majority of sailors felt that they had received appropriate medical care, although fewer women (66%) than men (78%) were satisfied. Levels of cigarette and alcohol use and sexual activity were comparable among women and men and corresponded to those of the general U.S. population of young adults. Because of high levels of health, most medical needs of women sailors can be managed readily by providing routine gynecological care and by minor additions to the shipboard pharmacy.

Tetrasomy 8 and t(1;11)(p32;q24) in acute myelo-monocytic leukemia with extensive leukemic cutaneous involvement.

We report a case of tetrasomy 8 in a patient suffering from acute myelomonocytic leukemia with extensive leukemic cutaneous infiltration. In all metaphases analyzed t( I;11)(p32;q24) was concomitantly observed. Similarly to other cases with tetrasomy 8, the patient showed monocytic involvement and poor response to chemotherapy. We conclude that this kind of cytogenetic aberration is associated with distinct morphologic and clinical features.

Effect of splenectomy on T lymphocyte subsets in patients infected with the human immunodeficiency virus.

A case-control study was conducted at two institutions to determine whether the absolute CD4 lymphocyte count or the percentage of lymphocytes bearing the CD4 marker (i.e., the CD4 percentage) is a more accurate indicator of underlying immune status in splenectomized patients infected with human immunodeficiency virus (HIV). Each of nine splenectomized HIV-infected cases was matched with six nonsplenectomized HIV-infected controls--three matched for CD4 lymphocyte count and three for CD4 percentage. In analyses including the eight cases with an initial CD4 lymphocyte count of > 200/mm3, controlling for the CD4 count revealed differences between cases and controls in terms of CD4 percentage (range, 10%-41% and 17%-54%, respectively; P < .01) and Centers for Disease Control and Prevention (CDC) clinical stage (P = .06). Controlling for the CD4 percentage revealed a significant difference between cases and controls in terms of CD4 count (range, 396-1,040 and 55-784 cells/mm3, respectively; P < .01) but not CDC clinical stage (P > .7). These data suggest that the numerical relationship between the CD4 lymphocyte count and the CD4 percentage among splenectomized HIV-infected patients with more than 200 CD4 cells/mm3 differs from that among nonsplenectomized patients. The CD4 percentage appears to be a more accurate indicator of the underlying level of immune function in the former group of patients.