Advances and future challenges in adenoviral vector pharmacology and targeting

Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multifaceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral "sinks" must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology is deduced from the most commonly used serotypes, Ad5 and Ad2. However, these serotypes may not represent all adenoviruses, and may not even represent the most useful vectors for all purposes. Chimeras between Ad serotypes may become useful in engineering vectors that can selectively evade substantial viral traps, such as Kupffer cells, while retaining the robust qualities of Ad5. Similarly, vectorizing other Ad serotypes may become useful in avoiding immunity against Ad5 altogether. Taken together, this research on basic adenovirus biology will be necessary in developing vectors that interact more strategically with the host for the most optimal therapeutic effect.     

To Evaluate the Effect of Various Surface Treatments on the Shear Bond Strength of Three Different Intraoral Ceramic Repair Systems: An In Vitro Study

Fractures of metal-ceramic restoration pose an esthetic and functional dilemma both for patient and the dentist. Intraoral repair systems eliminate the remake and removal of restoration. Many intraoral repair materials and surface treatments are available to repair intraorally fractured metal-ceramic restoration. Bond strength data of various materials and specific technique used for repair are necessary for predicting the success of a given repair system. This study evaluated the shear bond strength of three different intraoral repair systems for metal-ceramic restorations applied on exposed metal and porcelain surface. One hundred and twenty metal discs (20 mm in diameter × 0.7 mm thick) were fabricated with nickel–chromium alloy (Mealloy, Dentsply, USA). Feldspathic porcelain (Duceram, Degudent, Germany) were applied over one test surface of the discs in the thickness of 1.8 mm followed by conventional firing. The defect, which simulates clinical failures were created in 1/4th area of the metal-ceramic discs. The metal-ceramic discs samples were divided into ceramic substrate (Group I, n = 60) and metal substrate (Group II, n = 60), according to the defect location. Then, samples of ceramic substrate (Group I) and metal substrate (Group II) were subdivided into A, B according to the surface treatments (A; roughening with diamond bur and B; abraded with 50 μ Al₂O₃) and repaired with one of the intraoral repair systems tested (a. Ceramic repair system, Ivoclar Vivadent; b. Clearfil repair system, Kurary, c; Porcelain repair system, 3 M ESPE). All the repaired samples were stored in distilled water at 37 °C for 24 h. After thermocycling at 6–60° C, all the samples were stored at 37 °C for additional 7 days. Shear bond strength of all the samples were calculated by using Universal testing machine. The mean shear bond strength values for the group I (A/B) were as follows: Ceramic repair system (9.47 ± 1.41/14.03 ± 2.54 MPa), Clearfil repair system (14.03 ± 2.32/14.64 ± 2.28 MPa), and Porcelain repair system (14.41 ± 3.96/14.86 ± 3.10 MPa). The mean shear bond strength values for the group II (A/B) were as follows: Ceramic repair system (9.42 ± 1.44/18.61 ± 2.60 MPa), Clearfil repair system (14.44 ± 3.23/14.98 ± 2.73 MPa), and Porcelain repair system (11.86 ± 2.24/13.24 ± 2.72 MPa). Air abrasion with 50 μm aluminum oxide particles is the preferred surface treatment. Porcelain repair system showed the highest shear bond with air abrasion for ceramic substrate and for metal substrate Ceramic repair system showed the highest bond strength with air abrasion as a surface treatment. This study suggest that the three repair systems tested are adequate for intraoral chairside repair of metal-ceramic restoration when air abrasion is used for surface treatment of the substrate (Ceramic repair system, Ivoclar Vivadent, Germany; Clearfil repair system, Kurary, Japan; Porcelain repair system, 3M ESPE, Germany).     

3‐D imaging in post‐traumatic malformation and eruptive disturbance in permanent incisors: a case report

Abstract – Injury to the primary dentition is one of the common problems of childhood. Disturbances during crown development of the permanent teeth result in morphologic alterations. This case report highlights the role of 3‐D imaging when conventional dental radiographs are not enough to answer our clinical questions regarding future eruptive disturbances. 3‐D imaging can many times give us a definitive diagnosis and improve the treatment planning after early injuries in the deciduous dentition. The current status of multislice computed tomography (CT) and cone beam CT (CBCT) as diagnostic tools in pediatric dental population is also discussed briefly.     

Revision Total Hip Arthroplasty Using Imageless Navigation With the Concept of Combined Anteversion

Background

The purpose of the study was to evaluate the implant positions and clinical results of revision total hip arthroplasty (THA) using an imageless navigation with the concept of combined anteversion.

Interferon‐Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) as a Prognostic Marker for Local Control in T1‐2 N0 Breast Cancer Treated with Breast‐Conserving Surgery and Radiation Therapy (BCS + RT)

Interferon‐induced protein with tetratricopeptide repeats 1 (IFIT1) expression, involved in the regulation of translation, has been implicated to mediate resistance to chemotherapy and radiation in cancer cells in vitro. The purpose of this study was to evaluate the prognostic significance of IFIT1 protein expression in patients with breast cancer treated with Breast‐Conserving Surgery and Radiation Therapy (BCS + RT). A tissue microarray was constructed with specimens from 282 women with node‐negative, early‐stage (I/II) breast cancer who were treated with BCS + RT. Immunohistochemistry was used to stain for the IFIT1 protein. Cytoplasmic IFIT1 protein expression levels were correlated with clinicopathologic factors, local relapse‐free survival (LRFS), disease‐free survival (DFS), and overall survival (OS). IFIT1 positivity was found in 123 (49%) of cases. The median follow‐up time was 7.3 years. Eighty percent of the patients had T1 disease, 88% were human epidermal growth factor receptor 2 (HER2) negative, and 20% had triple‐negative breast cancer (TNBC). IFIT1 positivity was associated with estrogen receptor negative status (p = 0.002), progesterone receptor negative status (p = 0.02), TNBC (p = 0.01), and HER2‐positive status (p = 0.006). In univariate and multivariate analysis, IFIT1 positivity was associated with improved LRFS (p = 0.055 and p = 0.04, respectively). Using a log‐rank test, IFIT1 positivity was found to be associated with improved LRFS (94% versus 85%, p = 0.046) but not DFS or OS at 10 years. On subset analysis of the TNBC patients, IFIT1 positivity was found to correlate with improved LRFS (100% versus 53%, p = 0.004) and DFS in (87% versus 49%, p = 0.048) at 10 years. Elevated IFIT1 protein expression is associated with improved LRFS. In addition, our data suggest that IFIT1 expression may help risk stratify patients with TNBC who may benefit from more aggressive therapy. As there is limited data on IFIT1 in breast cancer, additional work is needed to ascertain its significance.     

Case report: retroperitoneoscopic nephrectomy in pyonephrotic nonfunctioning moiety of horseshoe kidney

Laparoscopic removal of the pyonephrotic moiety of a horseshoe kidney is challenging because of inflammation, aberrant vasculature, abnormal kidney location, and the renal isthmus. We herein report retroperitoneoscopic nephrectomy of the nonfunctioning pyonephrotic right moiety of a horseshoe kidney.     

Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons

The regulation of metal ion transport within neurons is critical for normal brain function. Of particular importance is the regulation of redox metals such as iron (Fe), where excess levels can contribute to oxidative stress and protein aggregation, leading to neuronal death. The divalent metal transporter 1 (DMT1) plays a central role in the regulation of Fe as well as other metals; hence, failure of DMT1 regulation is linked to human brain pathology. However, it remains unclear how DMT1 is regulated in the brain. Here, we show that DMT1 is regulated by Ndfip1 (Nedd4 family-interacting protein 1), an adaptor protein that recruits E3 ligases to ubiquitinate target proteins. Using human neurons we show the Ndfip1 is upregulated and binds to DMT1 in response to Fe and cobalt (Co) exposure. This interaction results in the ubiquitination and degradation of DMT1, resulting in reduced metal entry. Induction of Ndfip1 expression protects neurons from metal toxicity, and removal of Ndfip1 by shRNAi results in hypersensitivity to metals. We identify Nedd4–2 as an E3 ligase recruited by Ndfip1 for the ubiquitination of DMT1 within human neurons. Comparison of brains from Ndfip1^−/− with Ndfip1^+/+ mice exposed to Fe reveals that Ndfip1^−/− brains accumulate Fe within neurons. Together, this evidence suggests a critical role for Ndfip1 in regulating metal transport in human neurons.     

A Clinico-Bacteriological Study of Pyodermas at a Tertiary Health Center in Southwest Rajasthan

Background:

The spectrum of pyoderma changes constantly, and so does the antibiotic susceptibility pattern.

Aims:

This study was done to assess the magnitude and clinical patterns of pyodermas, their causative micro-organisms, and the antibiotic susceptibility patterns.

Materials and Methods:

Five hundred consecutive, clinically diagnosed and untreated cases of pyoderma, attending the Dermatology OPD of RNT Medical College and MB Government Hospital, Udaipur, from October 2010 to September 2011 were the subjects of this study. A detailed clinical examination, and relevant investigations including bacterial culture and sensitivity, were carried out and recorded.

Statistical Analysis:

For statistical analysis of data, the software ‘EPI-INFO Version 6’ was used, and Chi-square (χ²) test was applied.

Results:

Of 19576 cases attending skin OPD during the study period, pyoderma was seen in 500 patients; the incidence being 2.55%. Males outnumbered females. The highest number of cases (109; 21.8%) was observed in 1st decade. Lower extremities were the commonest site of predilection. Primary pyodermas outnumbered secondary pyodermas. Furuncle (136; 27.2%) and infectious eczematoid dermatitis (62; 12.4%) were the commonest entities among primary and secondary pyoderma respectively. Staphylococcus aureus was the commonest causative agent in both primary and secondary pyoderma. It showed high susceptibility to amoxycillin + sulbactam, aminoglycosides and cefoperazone, moderate susceptibility to linezolid, while low susceptibility to fluoroquinolones and cephalexin.

Conclusion:

Such studies help to assess the changing trend of bacterial infections, their causative organisms and antibiotic susceptibility pattern.     

Viscoexpression of anterior chamber cysticercus cellulosae

We report a case of anterior chamber Cysticercus cellulosae that was removed by viscoexpression.