Enhanced learning of proportional math through music training and spatial-temporal training

It was predicted, based on a mathematical model of the cortex, that early music training would enhance spatial-temporal reasoning. We have demonstrated that preschool children given six months of piano keyboard lessons improved dramatically on spatial-temporal reasoning while children in appropriate control groups did not improve. It was then predicted that the enhanced spatial-temporal reasoning from piano keyboard training could lead to enhanced learning of specific math concepts, in particular proportional math, which is notoriously difficult to teach using the usual language-analytic methods. We report here the development of Spatial-Temporal Math Video Game software designed to teach fractions and proportional math, and its strikingly successful use in a study involving 237 second-grade children (age range six years eight months-eight years five months). Furthermore, as predicted, children given piano keyboard training along with the Math Video Game training scored significantly higher on proportional math and fractions than children given a control training along with the Math Video Game. These results were readily measured using the companion Math Video Game Evaluation Program. The training time necessary for children on the Math Video Game is very short, and they rapidly reach a high level of performance. This suggests that, as predicted, we are tapping into fundamental cortical processes of spatial-temporal reasoning. This spatial-temporal approach is easily generalized to teach other math and science concepts in a complementary manner to traditional language-analytic methods, and at a younger age. The neural mechanisms involved in thinking through fractions and proportional math during training with the Math Video Game might be investigated in EEG coherence studies along with priming by specific music.     

Humoral and cellular immune responses to HIV-1 nef in mice DNA-immunised with non-replicating or self-replicating expression vectors.

OBJECTIVE: HIV accessory protein Nef is expressed early in the infectious cycle of the virus and has been shown to be an effective immunogen in humoral and cellular immune responses. We have used two different self-replicating pBN vectors and one non-replicating pCGal2 derived (pCG) vector expressing HIV-1 Nef in DNA immunisation of mice in order to determine their efficiency in raising humoral and cellular immune responses. DESIGN AND METHODS: The expression of Nef by the three plasmids was tested by transfections into COS-1 cells. Balb/c mice were immunised with the pBN-NEF and pCGE2-NEF constructs using gold particle bombardment. Immunoblotting and immunocytochemistry were used to detect in vitro expression of Nef. 51Cr release assay, ELISA and immunoblotting were used to detect cellular and humoral immune responses in immunised mice. RESULTS: Efficient in vitro expression of Nef was detected in pBN and pCGE2-NEF transfected cells, in pBN-NEF transfected cells the expression lasting up to three weeks. Anti-Nef antibodies in sera of 13 of 16 pBN-NEF immunised mice were detected within four weeks after the last immunisation, whereas only 2 of 12 pCGE2-NEF immunised mice had very weak anti-Nef antibodies. Twelve of the pBN-NEF immunised mice (75%) and 6 the pCGE2-NEF immunised mice (50%) showed Nef-specific cytotoxic T lymphocyte (CTL) responses within four weeks. CONCLUSIONS: We conclude that the three eukaryotic expression vectors tested are capable of inducing a cell mediated immune response towards HIV-1 Nef and should be considered as part of a genetic HIV vaccine.     

Mechanism, structure-activity studies, and potential applications of glutathione S-transferase-catalyzed cleavage of sulfonamides.

The mechanism of sulfonamide cleavage of PNU-109112, a potent HIV-1 protease inhibitor, by glutathione-S-transferase (GST) was investigated in the presence of reduced GSH. GST-catalyzed sulfonamide cleavage takes place via the nucleophilic attack of GSH on the pyridine moiety of the substrate with formation of the GS-para-CN-pyridinyl conjugate, the corresponding amine, and sulfur dioxide. Structure activity studies with a variety of sulfonamides indicate that an electrophilic center alpha to the sulfonyl group is required for cleavage. Substituents that withdraw electron density from the carbon atom alpha- to the sulfonyl group facilitate nucleophilic attack by the GS(-) thiolate bound to GST. The rate of sulfonamide cleavage is markedly affected by the nature of the electrophilic group; replacement of para-CN by para-CF(3) on the pyridine ring of PNU-109112 confers stability against sulfonamide cleavage. On the other hand, stability of sulfonamides is less dependent on the nature of the amine moiety. These principles can be applied to the synthesis of sulfonamides, labile toward cellular GST, that may serve as prodrugs for release of bioactive amines. Tumors are particularly attractive targets for these sulfonamide prodrugs as GST expression is significantly up-regulated in many cancer cells. Another potential application could be in organic synthesis, where protection of amines as the corresponding activated sulfonamides can be reversed by GST/GSH under mild conditions.     

Comparative in vitro activity of l-ofloxacin and FK037 to other agents against 10,040 fresh clinical isolates

Fresh clinical isolates collected from November 1, 1992 through November 1, 1993, were tested by agar dilution against 26 different antimicrobial agents including FK037 and l-ofloxacin. Among the 10 040 organisms tested were Staphylococcus aureus (n = 1222), methicillin-resistant Staphylococcus aureus (MRSA, n = 455), Staphylococcus epidermidis (n = 533), Staphylococcus hominis (n = 90), Staphylococcus hemolyticus (n = 89), Streptococcus pneumoniae (n = 144), Escherichia coli (n = 2326), Klebsiella pneumoniae (n = 745), Enterobacter cloacae (n = 258), Proteus mirabilis (n = 445), Pseudomonas aeruginosa (n = 998), and Stenotrophomonas (Xanthomonas) maltophilia (n = 102). Both l-ofloxacin and FK037 inhibited 98% of S. aureus strains at 4 mug/ml. FK037 was at least 4 times more effective than the third generation cephalosporins against MRSA, inhibiting 79% of the strains at 16 mug/ml. While the potency of these agents looks promising, their clinical utility will depend in part upon the maximal dosage that can be safely administered.     

Bronchoscopic findings in post-obstructive pulmonary oedema

Purpose

To present the first photographed bronchoscopic findings associated with negative pressure pulmonary oedema (NPPE).

Clinical features

A previously healthy patient underwent anterior C₃–C₄ disc removal and arthrodesis. Following tracheal extubation he developed acute respiratory distress manifested as stridor, tachypnoea, restlessness, and desaturation. Once the trachea was reintubated, he displayed the classic findings of pulmonary oedema. Bronchoscopy was performed to confirm tracheal tube position and to rule out tracheal injury secondary to surgical manipulation. Diffuse punctate haemorrhages were noted throughout the visualised tracheobronchial tree.

Conclusion

We believe that these haemorrhages represent disruption of the bronchial vasculature and may contribute to the clinical presentation of NPPE.     

Cytomegalovirus as a risk factor in renal transplantation

A prospective study of 276 patients that were greater than 12 years old and received transplants between October 1, 1977 and September 30, 1979 has been undertaken. Any patient with clinical findings compatible with overt cytomegalovirus (CMV) disease was placed on a "CMV disease diagnostic protocol." All diagnosed cases of CMV occurring before November 15, 1979 have been analyzed. Eighty patients (29%) had overt CMV disease. Seventy-two (90%) of them contracted CMV within the first 3 months post-transplant. The incidence of overt CMV varied with donor type. Eight percent (4 of 49), 17% (8 of 48), 20% (5 of 25), 40% (46 of 115) and 43% (15 of 35) of HLA-identical (ID) siblings, non-ID siblings, child donor, cadaveric donor, and parental donor, respectively, contracted CMV disease. Overt clinical CMV disease influenced the graft function and patient survival rates significantly (P < 0.01). Several risk factors have been considered as possible indicators of CMV disease. These include age, sex, diabetic status, time of onset of CMV, donor and recipient CMV complement-fixing (CF) and indirect fluorescence (IF) titers. The same variables were analyzed to determine whether they might also predict the severity of the disease. Donor CF is the single most important risk factor. Recipient serology alone was not found to be a significant risk factor but 15 of 27 (56%) persons who had a negative titer and received a kidney from a donor with a positive CF titer contracted overt CMV. Nine of those 15 (60%) had moderate, severe, or lethal illness.