Assessment of predicted enzymatic activity of α‐N‐acetylglucosaminidase variants of unknown significance for CAGI 2016

The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α‐N‐acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to .61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population‐scale analysis of disease epidemiology and rare variant association analysis.     

Outcomes of root canal treatment and restoration, implant-supported single crowns, fixed partial dentures, and extraction without replacement: a systematic review

STATEMENT OF PROBLEM: Dentists and patients are regularly confronted by a difficult treatment question: should a tooth be saved through root canal treatment and restoration (RCT), be extracted without any tooth replacement, be replaced with a fixed partial denture (FPD) or an implant-supported single crown (ISC)? PURPOSE: The purpose of this systematic review was to compare the outcomes, benefits, and harms of endodontic care and restoration compared to extraction and placement of ISCs, FPDs, or extraction without tooth replacement. MATERIAL AND METHODS: Searches performed in MEDLINE, Cochrane, and EMBASE databases were enriched by hand searches, citation mining, and expert recommendation. Evidence tables were developed following quality and inclusion criteria assessment. Pooled and weighted mean success and survival rates, with associated confidence intervals, were calculated for single implant crowns, fixed partial dentures, and initial nonsurgical root canal treatments. Data related to extraction without tooth replacement and psychosocial outcomes were evaluated by a narrative review due to literature limitations. RESULTS: The 143 selected studies varied considerably in design, success definition, assessment methods, operator type, and sample size. Direct comparison of treatment types was extremely rare. Limited psychosocial data revealed the traumatic effect of loss of visible teeth. Economic data were largely absent. Success rates for ISCs were higher than for RCTs and FPDs, respectively; however, success criteria differed greatly among treatment types, rendering direct comparison of success rates futile. Long-term survival rates for ISCs and RCTs were similar and superior to those for FPDs. CONCLUSIONS: Lack of comparative studies with similar outcomes criteria with comparable time intervals limited comparison of these treatments. ISC and RCT treatments resulted in superior long-term survival, compared to FPDs. Limited data suggested that extraction without replacement resulted in inferior psychosocial outcomes compared to alternatives. Long-term, prospective clinical trials with large sample sizes and clearly defined outcomes criteria are needed.     

Significance of hepatic xanthine oxidase and uric acid in aged and dietary restricted rats

Xanthine oxidase (XOD), one of the major intracellular sources of superoxide production, is well characterized as a causative factor in ischemia/reperfusion related damage. In the present study, we investigated age-effect on the status of XOD, an enzyme interconvertible with xanthine dehydrogenase (XDH) under oxidative stress. We also examined the modulation of the enzyme using the anti-oxidative action of dietary restriction (DR). We obtained evidence showing XOD activity to be significantly increased by DR, peaking at 24 months, although no progressive, age-related changes were noticed. On the other hand, while XDH activity decreased in ad libitum fed rats with age, DR maintained higher activity levels at 18 and 24 months of age. During aging, the conversion of XDH to XOD was slightly increased, as indicated by the XOD/XDH ratio. One novel finding of the present study is DR’s ability to elevate the uric acid level, which likely augments the anti-oxidative defense system, thereby buffering against oxidatively stressed conditions during aging. Based on what is known about the antioxidative abilities of DR and uric acid, we propose that the high uric acid levels we observed in DR rats may well serve as part of a defense strategy to protect redox balance.     

Polysaccharide-Based Nanocomposites for Food Packaging Applications

The article presents a review of the literature on the use of polysaccharide bionanocomposites in the context of their potential use as food packaging materials. Composites of this type consist of at least two phases, of which the outer phase is a polysaccharide, and the inner phase (dispersed phase) is an enhancing agent with a particle size of 1–100 nm in at least one dimension. The literature review was carried out using data from the Web of Science database using VosViewer, free software for scientometric analysis. Source analysis concluded that polysaccharides such as chitosan, cellulose, and starch are widely used in food packaging applications, as are reinforcing agents such as silver nanoparticles and cellulose nanostructures (e.g., cellulose nanocrystals and nanocellulose). The addition of reinforcing agents improves the thermal and mechanical stability of the polysaccharide films and nanocomposites. Here we highlighted the nanocomposites containing silver nanoparticles, which exhibited antimicrobial properties. Finally, it can be concluded that polysaccharide-based nanocomposites have sufficient properties to be tested as food packaging materials in a wide spectrum of applications.     

Gene therapy of glioblastoma multiforme via combined expression of suicide and cytokine genes: a pilot study in humans.

Retrovirus-mediated gene therapy is a particularly attractive approach for glioblastoma multiforme (GBM), given the poor prognosis of this tumour and its localized proliferation in post-mitotic tissue. In this study we assessed, for the first time in humans, the therapeutic potential of a newly designed bicistronic Moloney vector (pLIL-2-TK), combining the expression of a suicide gene (thymidine kinase, tk) with an immunomodulatory gene (human interleukin 2, IL-2). Evidence of transgene activity in the treated tumours is presented.     

Use of PCR to identify enteroaggregative Escherichia coli as an important cause of acute diarrhoea among children living in Calcutta, India.

The importance of enteroaggregative Escherichia coli (EAggEC) as a possible aetiological agent of acute diarrhoea among children in Calcutta, India, was investigated. Simultaneously the use of a previously described PCR diagnostic system was assessed for its ability to identify EAggEC infection. E. coli strains isolated during a 1-year case-control study from faecal samples of 388 children aged <5 years, with or without diarrhoea, were examined for EAggEC by HeLa cell adherence assay in parallel with a PCR assay with primers generated from an EAggEC DNA probe. A blind comparison was made between the two methods to determine their diagnostic potential. E. coli isolates that adhered to HeLa cells in an aggregative pattern were the sole isolates significantly more often in 254 cases (9%) than in 134 control (2%) children. Age stratification showed that EAggEC were isolated more frequently from children aged <36 months. The EAggEC isolates belonged to several O serogroups and showed multiple drug resistance. Both methods were positive for 26 samples, nine samples were positive by PCR alone and seven samples were positive by culture alone, thus indicating a 78% sensitivity and 97% specificity for the PCR assay. EAggEC is an important aetiological agent of acute diarrhoea among infants in and around Calcutta, and the PCR diagnostic system may be useful to identify such infection in epidemiological studies.     

Beneficial Effects of Aluminum on the Progression of Lead‐Induced Nephropathy in Rats

We studied the effect of aluminum on lead‐induced nephropathy in male albino rats. Five groups of male albino rats were given either water only or lead acetate (125 mg/kg body weight) and/or aluminum chloride (50 mg/kg body weight or 100 mg/kg body weight) for a period of 90 days. Aluminum was found to prevent the lead‐induced increase in the relative organ (kidney) weight in a dose‐dependent manner. Aluminum also prevented lead‐induced increase in plasma creatinine levels of the treated animals. Estimation of lead concentration in kidneys of different treatment groups revealed that the net deposition of lead was lower in animals which were given both lead acetate and aluminum chloride simultaneously. The results showed that aluminum offers some protection against lead‐induced nephrotoxicity in a time‐ and dose‐dependent manner.     

Medical Therapy for Eisenmenger Syndrome: A Case Report and Review of Literature

Eisenmenger syndrome (ES) is defined as the process in which a long-standing left-to-right cardiac shunt caused by a congenital heart defect is eventually reversed into a cyanotic right-to-left shunt. It is crucial to recognize this grave pathology at the earliest because once it develops, treatment by medical or surgical means becomes even more challenging. In past decades, various therapeutic options have been developed that address the specific pathophysiological aspects of the disease and have shown to improve functional capacity and quality of life. There are three major therapeutic pathways in pulmonary hypertension treatment - endothelin receptor antagonists, phosphodiesterase type-5 inhibitors, and prostacyclin derivatives. These therapies not only improve hemodynamic parameters and exercise capacity but they also improve prognosis with various form of Pulmonary hypertension including ES. We report a case of a 35-year-old female of ostium secundum atrial septal defect with ES, started on upfront combination therapy of ambrisentan and tadalafil who demonstrated marked improvement after 3 months of medical therapy.