Health care transition for cerebral palsy with intellectual disabilities: A systematic review.

OBJECTIVE: Today, most individuals with cerebral palsy are adults who need a paediatric-to-adult health care transition. However, many remain in paediatric care for treatment of adult-onset health issues. Therefore, a systematic review based on the 'Triple Aim' framework was performed to determine the status of paediatric-to-adult health care transition for people with cerebral palsy. A comprehensive evaluation of transitional care was proposed for using this framework. It consists of 'experience of care', meaning satisfaction with the care, 'population health', meaning the well-being of patients, and 'cost', meaning cost-effectiveness. METHOD: Electronic database (PubMed) searches were performed. The inclusion criteria were original articles published between 1990 and 2020. The search terms used in this study were ('cerebral palsy' AND 'transition to adult health care') OR ('cerebral palsy' AND 'transition'). The study type had to be epidemiological, case report, case-control, and cross-sectional, but not qualitative. The outcomes of the studies were categorised into 'care experience', 'population health', and 'cost', according to the Triple Aim framework. RESULTS: Thirteen articles met the abovementioned inclusion criteria. Few studies have examined the effect of the intervention of transition for young adults with cerebral palsy. Participants in some studies had no intellectual disability. Young adults were dissatisfied with the 'care experience', 'population health', and 'cost' and had unmet health needs and inadequate social participation. INTERPRETATION: Further transition intervention studies with a comprehensive assessment and proactive involvement of individuals are warranted. The presence of an intellectual disability should be considered.

Interferon Beta-1b may reverse axonal dysfunction in multiple sclerosis.

Progression of the disability of multiple sclerosis (MS) is thought to be related to axonal damage that is seen even in normal appearing white matter (NAWM) of patients' brains. Interferon beta (IFNß) treatment for MS reduces the frequency of clinical exacerbations and the appearance of new inflammatory demyelinating lesions on magnetic resonance imaging (MRI). However, the effect of IFNß treatment on axonal damage in MS is not known. The present study aimed to assess the effect of IFNß on axonal function by comparing the data from localised single voxel proton MR spectroscopy (MRS) performed on eight MS patients given IFNß-1b treatment and 11 untreated patients. Brain MRI and MRS were performed before the initiation of IFNß-1b treatment and 24 months after treatment initiation. Levels of N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine (Cr) were calculated as the areas under their peaks shown on MRS and the ratios of NAA/Cr and Cho/Cr were calculated. In the patients treated with IFNß-1b there was a significant increase in the ratio of NAA/Cr in NAWM (p=0.028) at 24 months after the initiation of treatment. In contrast, there was no significant change in the NAA/Cr ratio in the untreated patients. These results suggest that IFNß-1b treatment might recover axonal function in NAWM of MS patients.

Novel amplifier expression vectors producing higher levels of IL-2 led to slower tumor growth and longer survival in vivo.

Sufficient levels of gene expression are required for effective gene therapy. One of the major obstacles in gene therapy is the low transgene expression obtained from currently available vector systems. To address this issue, we employed a transcriptional amplifier strategy in a single construct to enhance transgene expression. In the amplifier vectors (pHi-1 and pHi-2), the strong CMV promoter was used to drive a transcriptional factor, Tat, which could transactivate a second promoter (HIV1 LTR or HIV2 LTR) located in the same construct driving the gene of interest. Using the human interleukin-2 (IL-2) cytokine gene, our data showed that the pHi-1/2 amplifier vectors could produce significantly higher IL-2 levels in human lung cancer cells (A549) and breast cancer cells (MCF-7) than that obtained by directly using the CMV promoter alone. Injection of pHi-2-IL-2-modified Lewis Lung (LL/2) tumor clones led to significantly slower tumor growth and longer survival in mice compared to those injected with either CMV promoter driven IL-2 clones or the parental tumor cells. Our results demonstrated that the transcriptional amplifier-based expression cassettes could be very useful in applications where high levels of gene expression are difficult to achieve.

Glufosinate ammonium induces convulsion through N-methyl-D-aspartate receptors in mice.

Glufosinate ammonium, a broad-spectrum herbicide, causes convulsion in rodents and humans. Because of the structural similarities between glufosinate and glutamate, the convulsion induced by glufosinate ammonium may be ascribed to glutamate receptor activation. Three N-methyl-D-asparate (NMDA) receptor antagonists, dizocilpine, LY235959, and Compound 40, and an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist, NBQX, were coadministrated with glufosinate ammonium (80 mg/kg, intraperitoneally) in mice. Statistical analyses showed that the NMDA receptor antagonists markedly inhibited the convulsions, while the AMPA/kainate receptor antagonist had no effect on the convulsion. These results suggest that the convulsion caused by glufosinate ammonium is mediated through NMDA receptors.

[Effects of positive end-expiratory pressure, tidal volume and perflubron doses on gas exchange during partial liquid ventilation].

The efficacy of gas exchange during partial liquid ventilation (PLV) may be affected by positive end-expiratory pressure (PEEP), tidal volume (TV) and perflubron (PFOB) dose. The purpose of the present study was to clarify which factors were important for improving gas exchange during PLV. Fourteen rabbits were anesthetized and tracheostomized. Lung was introduced with intravenous oleic acid combined with saline lung lavage. After obtaining control data, PFOB 7.5 ml.kg-1 was instilled into the trachea, and ventilation settings were changed sequentially [1. TV: 10 ml.kg-1 (mTV), 2. mTV with PEEP, 3. TV: 15 ml.kg-1 (hTV), 4. hTV with PEEP]. PEEP level was set to the lower inflection point. The PFOB dose was increased to 15 ml.kg-1 and measurements were repeated under each ventilation setting. PEEP increased PaO2 in all ventilation settings. In hTV ventilation settings, incremental dose of PFOB significantly increased PaO2. The PaO2 values of all hTV ventilation settings were significantly higher than those of corresponding ventilation setting of mTV. Pulmonary compliance was significantly decreased with PEEP in hTV ventilation in addition to 15 ml.kg-1 PFOB. The results suggested that adequate gas tidal volume was the most important factor for improving gas exchange during PLV. However, PEEP or larger dose of PFOB should be avoided because they may decrease pulmonary compliance.

Bone-targeted Src SH2 inhibitors block Src cellular activity and osteoclast-mediated resorption.

Src, a nonreceptor tyrosine kinase, is an important regulator of osteoclast-mediated resorption. We have investigated whether compounds that bind to the Src SH2 domain inhibit Src activity in cells and decrease osteoclast-mediated resorption. Compounds were examined for binding to the Src SH2 domain in vitro using a fluorescence polarization binding assay. Experiments were carried out with compounds demonstrating in vitro binding activity (nmol/L range) to determine if they inhibit Src SH2 binding and Src function in cells, demonstrate blockade of Src signaling, and lack cellular toxicity. Cell-based assays included: (1) a mammalian two-hybrid assay; (2) morphological reversion and growth inhibition of cSrcY527F-transformed cells; and (3) inhibition of cortactin phosphorylation in csk-/- cells. The Src SH2 binding compounds inhibit Src activity in all three of these mechanism-based assays. The compounds described were synthesized to contain nonhydrolyzable phosphotyrosine mimics that bind to bone. These compounds were further tested and found to inhibit rabbit osteoclast-mediated resorption of dentine. These results indicate that compounds that bind to the Src SH2 domain can inhibit Src activity in cells and inhibit osteoclast-mediated resorption.

[Propofol anesthesia combined with thoracic epidural anesthesia for thymectomy for myasthenia gravis--a report of eleven cases].

We report 11 cases of thymectomy for myasthenia gravis using propofol and thoracic epidural anesthesia. Considering the influence of nitrous oxide to environment and muscular relaxation of volatile anesthetics, we selected this anesthetic method. By proper sedation with propofol and sufficient analgesia with epidural anesthesia, the hemodynamics during operation was stable and the emergence was rapid. The patients were extubated early after operation except in one case in which oxygenation was not good because of sputum. We conclude that our anesthetic method is useful. Moreover, we applied Fuchu hospital scoring system for prediction of the need of postoperative mechanical ventilation in patients with myasthenia gravis to the present 11 cases. These predictions corresponded well with the results. Therefore Fuchu hospital scoring system is useful for managing these patients by our anesthetic method.

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Anti-HPA-5b-induced neonatal alloimmune thrombocytopenia: antibody titre as a predictor. Collaborative Study Group.

Anti-HPA-5b is the most commonly found platelet-specific antibody among pregnant women, but it does not cause severe fetal-neonatal alloimmune thrombocytopenia in the majority of affected infants. However, as the sequelae of the affected children may become severe, it is necessary to identify the risk factors for neonatal alloimmune thrombocytopenia. Of 21 354 consecutive pregnant women, 138 [0.65%; 95% confidence interval (CI) 0.54-0.75%], corresponding to 13.2% of the 1049 HPA-5b- women calculated by the gene frequency, were positive for anti-HPA-5b at the first trimester. Anti-HPA-5b was titrated in specimens obtained at the third trimester and antibody-positive women and their neonates were HPA-5 genotyped. Platelet counts in cord blood and 3 d after birth were assessed in the infants born to these mothers. Chi-square analysis showed no significant relationship between the titres of maternal antibody to HPA-5b and the number of pregnancies. There was a significant difference in platelet counts at d 3 between neonates who were compatible (267 x 109/l) or incompatible (220 x 109/l, P < 0.05) with maternal anti-HPA-5b. HPA-5b antibody titres >/= 64 were related to the development of thrombocytopenia (< 150 x 109/l) in neonates 1 d and 3 d after birth. A high titre (>/= 64) had a positive predictive value of 50% for thrombocytopenia 3 d after birth when the infant was HPA-5b+ and a negative predictive value of 100%. These results indicate that a high titre (>/= 64) of anti-HPA-5b is associated with a higher risk of neonatal thrombocytopenia, even if anti-HPA-5b-induced severe thrombocytopenia rarely develops.

Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti.

The complete nucleotide sequence of the genome of a symbiotic bacterium Mesorhizobium loti strain MAFF303099 was determined. The genome of M. loti consisted of a single chromosome (7,036,071 bp) and two plasmids, designated as pMLa (351,911 bp) and pMLb (208, 315 bp). The chromosome comprises 6752 potential protein-coding genes, two sets of rRNA genes and 50 tRNA genes representing 47 tRNA species. Fifty-four percent of the potential protein genes showed sequence similarity to genes of known function, 21% to hypothetical genes, and the remaining 25% had no apparent similarity to reported genes. A 611-kb DNA segment, a highly probable candidate of a symbiotic island, was identified, and 30 genes for nitrogen fixation and 24 genes for nodulation were assigned in this region. Codon usage analysis suggested that the symbiotic island as well as the plasmids originated and were transmitted from other genetic systems. The genomes of two plasmids, pMLa and pMLb, contained 320 and 209 potential protein-coding genes, respectively, for a variety of biological functions. These include genes for the ABC-transporter system, phosphate assimilation, two-component system, DNA replication and conjugation, but only one gene for nodulation was identified.

Identification of three distinct regions of deletion on the long arm of chromosome 11 in childhood acute lymphoblastic leukemia.

Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identified deletions of chromosome arm 11q. These observations led us to analyse the loss of heterozygosity (LOH) of chromosome arm 11q in 113 primary childhood ALL samples using 14 microsatellite markers. LOH was found in 18 (16%) patients. Detailed examination identified three distinct regions of deletion. The first region is flanked by D11S901 and D11S1391 at 11q22-23 containing the ATM gene. Mutational analysis suggested that the altered gene in this region is not the ATM gene. The second region is flanked by D11S614 and D11S924 at 11q23 containing the MLL gene. The third region is flanked by D11S1356 and D11S614 at 11q23 containing the MLL gene. All the cases with LOH at MLL locus lacked detectable MLL gene rearrangements. In addition, 20 children have been studied both at initial diagnosis and relapse; none of the individuals who relapsed acquired LOH of 11q, suggesting that 11q deletions were infrequently involved in the progression of childhood ALL. Children with 11q LOH had a good response to induction chemotherapy (P=0.015). These data suggest that alterations of putative tumor suppressor genes on 11q are important events in development of childhood ALL. Our map provides important information toward cloning putative tumor suppressor genes associated with childhood ALL.

[Neonatal Streptococcus pyogenes meningitis and sagittal sinus thrombosis: case report]. / Meningite neonatal por Streptococcus pyogenes e trombose de seio sagital. Relato de caso.

We report a case of Streptococcus pyogenes meningitis in a 18 days year-old-girl with clinical course complicated by sagittal sinus thrombosis. Some aspects of the pathogenesis, treatment and follow-up of the disease are discussed. The world increase of serious streptococcal infections in the last 10 years, probably will become neonatal Streptococcus pyogenes meningitis more frequent in the future and it is important to be alert for the precocious diagnosis and the possible complications of that potentially lethal infection.

New taxanes as highly efficient reversal agents for multidrug resistance in cancer cells.

New non-cytotoxic taxanes synthesized from 10-deacetylbaccatin III and special hydrophobic acylating agents show remarkable MDR reversal activity (< or = 99.8%) against drug-resistant human breast cancer cells when co-administered with paclitaxel or doxorubicin. This activity is ascribed to the highly efficient blocking of P-glycoprotein efflux by these new taxanes.

Syntheses and structure-activity relationships of taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III.

A series of new taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III was synthesized by means of the beta-lactam synthon method. Most of the new taxoids thus synthesized possess excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines, and several of these taxoids show subnanomolar IC50 values which are severalfold to 1 order of magnitude better than those of paclitaxel and docetaxel. Modifications at the 3'- and 3'-N-positions exert marked effects on the activity. For the substituents at C-3', the cytotoxicity decreases in the order 2-furyl approximately 2-methyl-1-propenyl > or = 2-methylpropyl > (E)-1-propenyl > or = n-propyl > phenyl > > 2,2-dimethylpropyl. For the 3'-N substituents, the activity decreases in the order t-BuOCO > Ph > n-hexanoyl. A significant increase in the cytotoxicity against the doxorubicin-resistant human breast cancer cell line MCF7-R that expresses the multidrug resistance (MDR) phenotype is observed by the proper modification of the substituent at C-10. The observed remarkable effects of the substituents at C-10 on the activity against MCF7-R can be ascribed to the effective inhibition of the binding of these new taxoids to P-glycoprotein that is responsible for MDR.