Engineering fibrinogen-binding VSV-G envelope for spatially- and cell-controlled lentivirus delivery through fibrin hydrogels

We recently demonstrated that fibrin hydrogels can be used as vehicles for efficient lentivirus gene delivery. Gene transfer in fibrin gels was strongly dependent on matrix degradation by target cells but a fraction of lentiviral particles diffused out of the gels over time compromising spatial control of gene transfer. To overcome this challenge, we engineered lentiviral particles that bind covalently to fibrin during polymerization. To this end, we fused into the viral envelope glycoprotein (VSV-G) peptide domains that are recognized by factor XIII and protease cleavage sites that are recognized by plasmin. Lentivirus pseudotyped with the modified envelopes bound to fibrinogen in a factor XIII dose dependent manner and was released upon plasmin treatment. The peptide/VSV-G fusion envelope variants did not compromise the transduction efficiency of the resulting virus except when lacking any flexible linkers separating the peptide from the VSV-G envelope. Diffusion of virus from the gels decreased dramatically, especially at high concentrations of FXIII, even for fibrin gels with low fibrinogen concentration that were loaded with high titer virus. Lentivirus arrays prepared with fibrin-conjugated lentivirus yielded highly efficient gene transfer that was confined to virus-containing fibrin spots. As a result, signal/noise ratio increased and cross-contamination between neighboring sites was minimal. Finally, in addition to lentivirus microarrays this strategy may be used to achieve spatially-controlled gene transfer for therapeutic applications.     

Association of bilirubin and protein thiols in relation to copper and ceruloplasmin in hyperbilirubinemic patients

Objective： Bilirubin is a double edged sword in biological system, acting as a toxic molecule and cytoprotectant. Unconjugated bilirubin is proved to show antioxidant activity in vitro and in vivo. In the current work we tried to know the relationship between both conjugated and uneonjugated bilirubin with copper and protein thiols in patients with hyperbilirubihernia. Methods： Study was conducted on 56 hyperbilirubinemie eases and 56 healthy controls. Serum copper, ceruloplasmin, protein thiols, total bilirubin, conjugated and unconjugated bilirubin, uneonjugated bilirubin/albumin ratio, total protein, albumin, AST, ALT and ALP were estimated. Results： There was significant increase in serum copper, total biliruhin, conjugated and uneonjugated bilirubin, uneonjugated bilirubin/albumin ratio, AST, ALT, and ALP, and decrease in serum ceruloplasmin, protein thiols, total protein, and albumin in hyperbilirubinemie cases when compared to healthy controls. Conjugated bilirubin correlated positively with liver enzymes AST and ALP, and negatively with protein thiols, total protein and albumin. Uneonjugated bilirubin correlated positively with ALT. Protein thiols correlated negatively with copper and positively with eeruloplasmin, and also correlated negatively with liver enzymes like AST, ALT and ALP, and positively with total protein and albumin. Conclusion： Combination of elevated levels of trace elements like copper and availability of reducing agent like bilirubin may prove deleterious by generating free radicals.     

Late-infantile neuronal ceroid lipofuscinosis (CLN2/Jansky-Bielschowsky type) in Oman

This study was conducted to see the pattern of neuronal ceroid lipofuscinosis in Oman. Eleven children (10 male) with late-infantile neuronal ceroid lipofuscinosis were seen in 5 families. Most of the patients, 9 of 11 (81.8%), were CLN2 type (late-infantile neuronal ceroid lipofuscinosis or Jansky-Bielschowsky), and 2 patients were the atypical type. Five children were seen in 1 extended family. All children had onset with seizures except in 1 family. The majority had onset between ages 1 to 4 years. Nine and of the 11 children had onset with myoclonic seizures. Neuroregression and microcephaly were noted in all. All children had brain volume reduction and typical cerebellar atrophy. Ophthalmological examination was abnormal in all. Clinical features, histological findings, and genetic study reveal that CLN2 type is the most common form of neuronal ceroid lipofuscinosis. There is male predominance of 90.1% in this part of the Arab world.     

Trends in hepatitis B virus infection among blood donors in Kelantan, Malaysia: a retrospective study

The objective of this study was to determine the prevalence and trends in hepatitis B infection among blood donors attending the Transfusion Medicine Unit at the Hospital Universiti Sains Malaysia, Kelantan, Malaysia. A retrospective study was carried out by reviewing the results of HBsAg among blood donors for the years 2000 to 2004. During this period, 44,658 blood donors were studied. We noted that there was a significant difference in the prevalence of hepatitis B infection between regular and first time donors. There was also a decreasing trend noticed in both study groups. The mean prevalence was significantly different between first time (1.83%) and regular donors (0.45%) (p < 0.005). There is a need to improve public awareness programs to lower the incidence of hepatitis B infection in the general population and consequently first time blood donors. Future studies are also required to determine the trends and outcomes of these programs.     

Alternative approaches to assessing intervention effectiveness in randomized trials: application in a colorectal cancer screening study

Background  

Previous analysis of a randomized community-based trial of a multi-component intervention to increase colorectal cancer (CRC) screening among Filipino Americans (n = 548) found significantly higher screening rates in the two intervention groups compared to the control group, when using intent-to-treat analysis and self-reported screening as the outcome. This report describes more nuanced findings obtained from alternative approaches to assessing intervention effectiveness to inform future intervention implementation.     

A case of atypical teratoid/rhabdoid tumor in an adult, with long survival

Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant tumor that mostly occurs in early childhood and has poor prognosis despite aggressive therapy. Adult cases are rare and, as far as we are aware, only 30 cases have been reported to date. Here we present the case of a 27-year-old female with left parietal AT/RT with the chief complaint of numbness of the right superior limb. First, the tumor was surgically removed and the diagnosis was grade II glioma. With additional radiotherapy, the clinical course after surgery was favorable. After 6 years, she had an operation for recurrence and the diagnosis was grade III glioma. Temozolomide was prescribed, and a disease-free period of 2 years followed. Surgery was performed for a third time for second recurrence with histology of diffuse growth of rhabdoid cells. Immunohistochemistry was partially positive for vimentin and epithelial membrane antigen. Ki-67 labeling index was extremely high and tumor cells showed no staining of INI1 suggestive of diagnosis of AT/RT. We re-evaluated past specimens and none had immunoreactivity of INI1. Ki-67 labeling index and O-6 methylguanine DNA methyltransferase (MGMT) staining were also re-examined and both increased gradually. She is still alive without recurrence for more than 1 year. As far as we are aware, this is the second longest survival of an adult with AT/RT.     

Tobacco use among South Asians: results of a community-university collaborative study

OBJECTIVE: Although South Asians (individuals from India, Pakistan, Sri Lanka, Bangladesh, Nepal, Bhutan, and the Maldives) are the third largest Asian group in the USA, relatively little data are available to document their use of tobacco. We collected data from a community sample of 344 South Asian adults to assess rates of smokeless tobacco product use and smoking and examine demographic predictors of use. DESIGN: Non-random sample; cross-sectional survey. RESULTS: Close to a third of the sample (28%) reported current use of smokeless tobacco products. In multivariate analyses, gender and ethnicity were significant predictors of use of smokeless tobacco products. Men and Bangladeshis were more likely to use smokeless tobacco. The overall rate of daily cigarette/bidi smoking observed in our sample (9%) was similar to that observed in the population of California (10%); however, the rates among men (19%) and some ethnic subgroups (16% for Pakistanis) were significantly higher. Gender, ethnicity and years in the USA emerged as significant predictors of daily smoking with men and Pakistanis being significantly more likely to smoke. Length of stay in the USA was inversely related to daily smoking. CONCLUSION: These findings emphasize the need to disaggregate data for South Asians and suggest that tobacco control interventions should target specific segments of the population (men, Bangladeshis, Pakistanis). Interventions to decrease use of smokeless tobacco products are especially warranted for South Asians.     

Klippel-Trenaunay-Weber syndrome with partial motor seizures and hemimegalencephaly

A girl with Klippel-Trenaunay-Weber syndrome with partial motor seizures is reported. She had hemimegalencephaly and band heterotopia on MRI of the brain.     

Severe psychiatric problems in right hepatic lobe donors for living donor liver transplantation

BACKGROUND: The morbidity and mortality from donation of a right hepatic lobe for living donor liver transplantation (LDLT) is an important issue for this procedure. We report the prevalence of severe psychiatric postoperative complications from the Adult-to-Adult Living Donor Liver Transplantation Cohort study (A2ALL), which was established to define the risks and benefits of LDLT for donors and recipients. METHODS: Severe psychiatric complications were evaluated in all donors from the A2ALL study who were evaluated between 1998 and February 2003. RESULTS: Of the 392 donors, 16 (4.1%) had one or multiple psychiatric complications, including three severe psychiatric complications (suicide, accidental drug overdose, and suicide attempt). CONCLUSIONS: Despite extensive preoperative screening, some donors experience severe psychiatric complications, including suicide, after liver donation. Psychiatric assessment and monitoring of liver donors may help to understand and prevent such tragic events.