Instruction prioritization in task-based balance training for individuals with idiopathic Parkinson’s disease

The objective of the study was to evaluate the effect of prioritization of instruction in balance training for individuals with Parkinson’s disease (PD). Thirty-six participants were evaluated before and after the training using the Berg Balance Scale, Dynamic Gait Index, and Geriatric Depression Scale. Results show that dual task training with variable priority instruction is as effective as single task training in improving the balance performance of individuals with idiopathic PD.     

Prognostic potential of <Emphasis Type="Italic">KLOTHO</Emphasis> and <Emphasis Type="Italic">SFRP1</Emphasis> promoter methylation in head and neck squamous cell carcinoma

Hypermethylation in the CpG island promoter regions of tumor suppressors is known to play a significant role in the development of HNSCC and the detection of which can aid the classification and prognosis of HNSCC. This study aims to profile the methylation patterns in a panel of key genes including CDKN2A, CDKN2B, KLOTHO (KL), RASSF1A, RARB, SLIT2, and SFRP1, in a group of HNSCC samples from Saudi Arabia. The extent of methylation in these genes is determined using the MethyLight assay and correlated with known clinicopathological parameters in our samples of 156 formalin-fixed and paraffin-embedded HNSCC tissues. SLIT2 methylation had the highest frequency (64.6%), followed by RASSF1A (41.3%), RARB (40.7%), SFRP1 (34.9), KL (30.7%), CKDN2B (29.6%), and CKDN2A (29.1%). KL and SFRP1 methylation were more predominant in nasopharyngeal tumors (P = 0.001 and P = 0.031 respectively). Kaplan Meier analysis showed that patients with moderately differentiated tumors who display SFRP1 methylation have significantly worse overall survival in comparison with other samples. In contrast, better clinical outcomes were seen in patients with KL methylation. In conclusion, our findings suggest that the detection of frequent methylation in SFRP1 and KL genes’ promoters could serve as prognostic biomarkers for HNSCC.     

MSDsite: a database search and retrieval system for the analysis and viewing of bound ligands and active sites

The three-dimensional environments of ligand binding sites have been derived from the parsing and loading of the PDB entries into a relational database. For each bound molecule the biological assembly of the quaternary structure has been used to determine all contact residues and a fast interactive search and retrieval system has been developed. Prosite pattern and short sequence search options are available together with a novel graphical query generator for inter-residue contacts. The database and its query interface are accessible from the Internet through a web server located at: http://www.ebi.ac.uk/msd-srv/msdsite.     

Nectarin IV, a potent endoglucanase inhibitor secreted into the nectar of ornamental tobacco plants. Isolation, cloning, and characterization

We have isolated and characterized the Nectarin IV (NEC4) protein that accumulates in the nectar of ornamental tobacco plants (Nicotiana langsdorffii x Nicotiana sanderae var LxS8). This 60-kD protein has a blocked N terminus. Three tryptic peptides of the protein were isolated and sequenced using tandem mass spectroscopy. These unique peptides were found to be similar to the xyloglucan-specific fungal endoglucanase inhibitor protein (XEGIP) precursor in tomato (Lycopersicon esculentum) and its homolog in potato (Solanum tuberosum). A pair of oligonucleotide primers was designed based on the potato and tomato sequences that were used to clone a 1,018-bp internal piece of nec4 cDNA from a stage 6 nectary cDNA library. The remaining portions of the cDNA were subsequently captured by 5' and 3' rapid amplification of cDNA ends. Complete sequencing of the nec4 cDNA demonstrated that it belonged to a large family of homologous proteins from a wide variety of angiosperms. Related proteins include foliage proteins and seed storage proteins. Based upon conserved identity with the wheat (Triticum aestivum) xylanase inhibitor TAXI-1, we were able to develop a protein model that showed that NEC4 contains additional amino acid loops that are not found in TAXI-1 and that glycosylation sites are surface exposed. Both these loops and sites of glycosylation are on the opposite face of the NEC4 molecule from the site that interacts with fungal hemicellulases, as indicated by homology to TAXI-I. NEC4 also contains a region homologous to the TAXI-1 knottin domain; however, a deletion in this domain restructures the disulfide bridges of this domain, resulting in a pseudoknottin domain. Inhibition assays were performed to determine whether purified NEC4 was able to inhibit fungal endoglucanases and xylanases. These studies showed that NEC4 was a very effective inhibitor of a family GH12 xyloglucan-specific endoglucanase with a K(i) of 0.35 nm. However, no inhibitory activity was observed against other family GH10 or GH11 xylanases. The patterns of expression of the NEC4 protein indicate that, while expressed in nectar at anthesis, it is most strongly expressed in the nectary gland after fertilization, indicating that inhibition of fungal cell wall-degrading enzymes may be more important after fertilization than before.     

Choice of recipient vessels in delayed TRAM flap breast reconstruction after radiotherapy

This study compared the use of the internal mammary and thoracodorsal recipient vessels in a uniform group of patients who underwent delayed TRAM flap reconstruction after radiotherapy, focusing on usability rates and outcomes. The authors identified 123 delayed TRAM flap patients who had undergone postmastectomy radiotherapy from a prospective database (1990 to 2001). Recipient vessel unusability rates were calculated on the basis of reports of inspection of a vessel, either by direct intraoperative dissection or by findings from color Doppler examination (internal mammary vessels only). Charts were reviewed for outcomes including flap loss, vascular complications, fat necrosis, and lymphedema; t-test and chi-square analyses were performed to compare outcomes and unusability rates, and multiple regression analysis was performed to determine factors influencing outcome. Of the 123 planned free TRAM flaps, 106 were completed as free flaps and 17 were performed as pedicled flaps because of unusable recipient vessels. Of the free flaps, 45 were anastomosed to the internal mammary vessels, 55 to the thoracodorsal vessels, and six to other vessels. The internal mammary and thoracodorsal groups did not differ significantly in body mass index, abdominal scars, smoking history, time delay between irradiation and TRAM flap reconstruction, or flap ischemia time. Radiation doses to the axilla (thoracodorsal), internal mammary chain, and supraclavicular fossa were similar between the groups. The internal mammary vessels were rejected in 11 (20 percent) of 56 cases, and the thoracodorsal vessels were rejected in 19 (26 percent) of 74 cases (p = 0.42). In cases with unusable internal mammary vessels, 46 percent (n = 5) had inadequate veins, 27 percent (n = 3) had inadequate arteries, and in 27 percent (n = 3) both vessels were inadequate. In the 19 cases with unusable thoracodorsal vessels, 84 percent (n = 16) were excessively scarred, 11 percent (n = 2) had inadequate vessels, and 5 percent (n = 1) were absent. Outcomes were similar regardless of recipient vessels used (internal mammary versus thoracodorsal): total flap loss, 0 percent versus 4 percent (p = 0.20); vascular complications, 6.7 percent versus 11 percent (p = 0.46); arm lymphedema, 4.4 percent versus 9 percent (p = 0.37); partial flap loss, 9 percent versus 6 percent (p = 0.54); and fat necrosis, 18 percent versus 15 percent (p = 0.69). Multivariate analysis revealed a trend for higher complication rates in smokers and with the use of the thoracodorsal vessels as the recipients. Overall, no discernible unusability or outcome differences were detected between the internal mammary and thoracodorsal groups.     

Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and congestive heart failure

Strong expression of the inducible form of nitric oxide synthase (NOS II) has been shown in the myocardium of patients with myocardial infarction (MI). We hypothesized that NOS II plays an important role in the development of MI and subsequent heart failure and that inhibition of NOS II may beneficially alter the course of the disease. Long-term administration (2 mo) of the selective NOS II inhibitor S-methylisothiourea (SMT) to rats with MI significantly improved cardiac function. A significant drop in mortality, lung water content, infarct size, and cardiomyocyte hypertrophy was also associated with the use of SMT. Plasma concentration of nitrite and nitrate was also reduced by SMT. Short-term administration of SMT (first 2 wk only) significantly reduced infarct size; however, it did not improve cardiac dysfunction measured 2 mo after MI. These findings demonstrate that induction of NOS II during MI exerts negative effects on cardiac function and structure. Long-term administration of a selective NOS II inhibitor may prove to be beneficial in the treatment of MI and congestive heart failure.     

Autologous breast reconstruction with the extended latissimus dorsi flap

The extended latissimus dorsi myocutaneous flap can provide autogenous tissue replacement of breast volume without an implant. Nevertheless, experience with the extended latissimus dorsi flap for breast reconstruction is relatively limited. In this study, the authors evaluated their experience with the extended latissimus dorsi flap for breast reconstruction to better understand its indications, limitations, complications, and clinical outcomes. All patients who underwent breast reconstruction with extended latissimus dorsi flaps at the authors' institution between January of 1990 and December of 2000 were reviewed. During the study period, 75 extended latissimus dorsi flap breast reconstructions were performed in 67 patients. Bilateral breast reconstructions were performed in eight patients, and 59 patients underwent unilateral breast reconstruction. There were 45 immediate and 30 delayed reconstructions. Mean patient age was 51.5 years. Mean body mass index was 31.8 kg/m2. Flap complications developed in 21 of 75 flaps (28.0 percent), and donor-site complications developed in 29 of 75 donor sites (38.7 percent). Mastectomy skin flap necrosis (17.3 percent) and donor-site seroma (25.3 percent) were found to be the most common complications. There were no flap losses. Patients aged 65 years or older had higher odds of developing flap complications compared with those 45 years or younger (p = 0.03). Patients with size D reconstructed breasts had significantly higher odds of flap complications compared with those with size A or B reconstructed breasts (p = 0.05). Obesity (body mass index greater than or equal to 30 kg/m2) was associated with a 2.15-fold increase in the odds of developing donor-site complications compared with patients with a body mass index less than 30 kg/m2 (p = 0.01). No other studied factors had a significant relationship with flap or donor-site complications. In most patients, the extended latissimus dorsi flap alone, without an implant, can provide good to excellent autologous reconstruction of small to medium sized breasts. In selected patients, larger breasts may be reconstructed with the extended latissimus dorsi flap alone. This flap's main disadvantage is donor-site morbidity with prolonged drainage and risk of seroma. Patients who are obese are at higher risk of developing these donor-site complications. In conclusion, the extended latissimus dorsi flap is a reliable method for total autologous breast reconstruction in most patients and should be considered more often as a primary choice for breast reconstruction.     

Analysis of pharyngocutaneous fistula following free jejunal transfer for total laryngopharyngectomy

The development of a pharyngocutaneous fistula is the most common and troublesome complication in the early postoperative period following free jejunal transfer for total laryngopharyngectomy. However, many aspects of this complication remain unclear. In this study, the authors analyzed their experience with the pharyngocutaneous fistula formation following free jejunal transfers to evaluate its clinical behavior, determine the significance of the anastomotic technique used, and evaluate the role of preoperative radiation therapy on its formation and management. Of 168 patients who underwent free jejunal transfers following total laryngopharyngectomy at the authors' institution between July of 1988 and March of 2000, 23 patients (13.7 percent) with postoperative fistulas were identified. The mean onset of fistula formation was 16 days. Of the 23 fistulas, 13 (56.5 percent) occurred at the proximal and 10 (43.5 percent) at the distal anastomoses. Whereas the majority of the proximal fistulas (69.2 percent) developed near the mesenteric side of the jejunal flap, most of the distal fistulas (90 percent) were located anteriorly. The incidence of proximal fistula formation was higher in patients with a single-layer repair than in patients with a two-layer repair of a proximal anastomosis (80 percent versus 38.5 percent, p = 0.09). The incidence of fistula formation was greater in patients who received preoperative radiation therapy than in those who did not (16.3 percent versus 11.4 percent, p = 0.36). In addition, whereas a majority of fistulas (80 percent) occurred at the proximal anastomosis in patients who did not receive preoperative radiation therapy, most fistulas (61.5 percent) occurred at the distal anastomosis in patients who did receive radiation therapy (p = 0.09). The fistulas closed spontaneously in 15 patients (65 percent). On average, spontaneous closure occurred in 7.4 weeks. Proximal fistulas had a significantly higher rate of spontaneous closure compared with distal fistulas (85 percent versus 40 percent, p = 0.04). The rate of spontaneous fistula closure was higher in patients who had not received preoperative radiation therapy than in those who had (90 percent versus 46 percent, p = 0.07). Surgical closure of the fistula was required in five patients. The fistulas were not repaired in three patients because of recurrent tumor. Twenty patients (87 percent) resumed oral feeding after the closure of the fistula, with 17 (85 percent) of 20 patients tolerating a regular diet and three (15 percent) of 20 a liquid diet only.In conclusion, most fistulas occur at the proximal anastomosis and near the mesenteric side of the jejunal flap, and the use of a two-layer anastomotic technique seems to be associated with a lower incidence of fistula formation at the proximal suture line. Most fistulas close spontaneously, especially ones that occur proximally. Preoperative radiotherapy does seem to increase the risk of fistula formation, especially at the distal anastomotic site and make subsequent resolution of the fistulas more difficult. Most patients are able to resume oral feeding once the fistula is closed.     

Glucopyranosides derived from 6-aryl-5-cyano-2-(methylthio)pyrimidin-4(3H)ones

The reaction of 2,3.4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide with a 6-aryl-5-cyano-2-(methylthio)pyrimidin-4(3H)one in aqueous acetone in the presence of KOH furnishes a 4-(beta-D-glucopyranosyloxy)pyrimidine and a 3-(beta-D-glucopyranosyl)pyrimidine as the major and minor product. respectively.