Can computerized cognitive training reverse the diagnosis of HIV‐associated neurocognitive disorder? A research protocol

Nearly 50% of adults with HIV have some form of HIV‐associated neurocognitive disorder (HAND), ranging from subtle to symptoms that interfere with everyday functioning and quality of life. HAND is diagnosed when a person performs more than 1 standard deviation below his or her normative mean on standardized measures in two or more cognitive domains (e.g., attention, speed of processing, verbal memory, executive functioning). As adults age with HIV, they are more likely to develop comorbidities such as cardiovascular disease, hypertension, and insulin resistance that may further contribute to poorer cognitive functioning and HAND. Certain computerized cognitive training programs may be able to improve specific cognitive domains in those with HIV. Such programs may be effective in changing the diagnosis of HAND in cognitively vulnerable adults. In this article, we describe the design and methods of TOPS—the Training On Purpose Study. In this on‐going experimental study, 146 older adults (50+) with HAND are randomized to either: (i) an Individualized‐Targeted Cognitive Training group, or (ii) a no‐contact control group. This study targets those cognitive domains in which participants experience a deficit and trains participants with the corresponding computerized cognitive training program for that domain. An Individualized Targeted Cognitive Training approach using cognitive‐domain‐specific cognitive training programs may offer symptom relief to those individuals diagnosed with HAND, which may actually reverse this diagnosis. Given that these cognitive training programs are commercially available, this approach represents a potential paradigm shift in how HAND is considered and treated.     

Preferential expression of double-stranded ribonucleic acid in tumor versus normal cells: biological and clinical implications

In an effort to develop a new tumor marker suitable for flow cytometric analysis, we examined the value of double-stranded ribonucleic acid (ds- RNA) measurements using propidium iodide after DN'ase treatment. Cellular ds-RNA content was evaluated both in experimental cell lines and in clinical specimens. Higher levels of ds-RNA were present in tumor cells as compared with normal cells. In tumor cells, fluorescence was intensely localized in the nucleolus and was more diffuse in the cytoplasm. Change of less than 10% in the ds-RNA levels was observed in cell lines as a function of cytokinetic determinants such as cycle phase, culture age, and cycle traverse rate. Tumor differentiation by dimethylsulfoxide resulted in a significant decrease in cellular ds-RNA content. For quantitative comparison of clinical material, a ds-RNA excess was defined in relationship to normal peripheral blood lymphocytes. ds-RNA excess greater than 30% was observed in only one of 34 normal tissues (3%) as compared with 124 of 201 neoplastic tissue samples (62%). This incidence was higher in patients with acute leukemia (76%), high-grade and intermediate-grade lymphoma (75%), and high tumor stage myeloma (83%), as compared with chronic leukemia (20%), low-grade lymphoma (25%), and intermediate or low tumor mass myeloma (43%). Prognostically, a high pretreatment ds-RNA excess in myeloma was associated with a lower remission rate. The persistence of ds-RNA excess in the bone marrow of patients with acute myelogenous leukemia in remission predicted for a shorter remission duration (seven v 22 months; P = .05). We conclude that ds-RNA excess, as readily measured objectively and quantitatively by flow cytometry, may have important diagnostic and prognostic implications for the management of patients with malignant disease.     

Prognosis in critically ill children requiring continuous renal replacement therapy

We performed an observational prospective study in 53 critically ill children to analyze the prognostic factors of children requiring continuous renal replacement therapy. Pediatric index of mortality (PIM), pediatric risk of mortality score (PRISM), multi-organ failure score, serum lactate levels, blood pressure, vasoactive drugs, renal function and characteristics of renal replacement therapy were analyzed. The mortality was 32.1%, with multi-organ failure being the most frequent cause of death (59%). The children who died presented a significantly lower blood pressure and required more doses of vasoactive drugs, dopamine and epinephrine than did the survivors. The PRISM and PIM scores and the serum lactate levels and the number of organs suffering failure were significantly higher in the patients who died than in the survivors. However, the PRISM and PIM scores underestimated the risk of mortality. The age, sex, urea and creatinine levels, type of pump and volume of ultrafiltrate did not affect the prognosis. The association of a mean BP<55 mmHg and epinephrine dose >0.6 g/kg/min was predictive of mortality in 76% of the patients. We conclude that the prognosis in children requiring renal replacement therapy depends on the severity of the clinical state at the time of starting therapy, principally on the hemodynamic situation.     

Screening of Tanzanian medicinal plants for anti-Candida activity

Background  

Candida albicans has become resistant to the already limited, toxic and expensive anti-Candida agents available in the market. These factors necessitate the search for new anti-fungal agents.