Efficacy of Autogenous Split Thickness Calvarial Graft in the Management of Residual Cranial Defect

Introduction

The patients with cranial deformity suffer from headache, dizziness, irritability, loss of concentration, depression, anxiety, intolerance to noise and vibration and neuromotor weakness. It is therefore essential to restore the calvarium.

Material and Method

This study was conducted in the Department of Oral and Maxillofacial Surgery, Armed Forces Medical College, Pune between Oct 2010 and Mar 2012. The study population was selected from the outpatient department and from the referred cases. The aim was to study the uptake of split thickness calvarial graft in the management of residual cranial defect. After applying the inclusion and exclusion criterions, ten cases were selected with residual cranial deformity, operated for cranioplasty using split thickness calvarial graft and evaluated.

Conclusion

It was concluded that cranioplasty using autogenous split thickness calvarial graft for restoring cranial defects is a useful technique and this procedure allows the surgeon to reconstruct a moderate-to-large cranial defect, without breaching the inner cortical plate.     

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.     

Three differentiation states risk-stratify bladder cancer into distinct subtypes

Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes, on the basis of their differentiation states: basal, intermediate, and differentiated, where only the most primitive tumor cell subpopulation within each subtype is capable of generating xenograft tumors and recapitulating downstream populations. We found that keratin 14 (KRT14) marks the most primitive differentiation state that precedes KRT5 and KRT20 expression. Furthermore, KRT14 expression is consistently associated with worse prognosis in both univariate and multivariate analyses. We identify here three distinct BC subtypes on the basis of their differentiation states, each harboring a unique tumor-initiating population.     

Metal oxide QD based ultrasensitive microsphere fluorescent sensor for copper,chromium and iron ions in water

Herein we developed a rapid, cheap, and water-soluble ultra-sensitive ZnO quantum dot (QD) based metal sensor for detecting different hazardous metal ions up to the picomolar range in water. Various spectroscopic and microscopic techniques confirmed the formation of 2.15 ± 0.46 μm of ZnO QD conjugated CMC microspheres (ZCM microspheres) which contain 5.5 ± 0.5 nm fluorescent zinc oxide (ZnO) QDs. Our system, as a promising sensor, exhibited excellent photostability and affinity towards various heavy metal ions. The detection limits were calculated to be 16 pM for Cu²⁺ and 0.18 nM for Cr⁶⁺ ions which are better than previously reported values. The simple fluorescence ‘turn off’ property of our ZCM microsphere sensor system can serve a two-in-one purpose by not only detecting the heavy metals but also quantifying them. Nonetheless, pattern recognition for different heavy metals helped us to detect and identify multiple heavy metal ions. Finally, their practical applications on real samples also demonstrated that the ZCM sensor can be effectively utilized for detection of Cr⁶⁺, Fe³⁺, Cu²⁺ present in the real water samples. This study may inspire future research and design of target fluorescent metal oxide QDs with specific functions.

Herein we developed a rapid, cheap, and water-soluble ultra-sensitive ZnO quantum dot (QD) based metal sensor for detecting different hazardous metal ions up to the picomolar range in water.     

Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals

Introduction

Human APOBEC3G/F (hA3G/F) restricts retroviral replication through G-to-A hypermutations, which can generate drug-resistant progenies in vitro. The clinical relevance is still inconclusive. To bridge this gap, we aim to study the role of these hypermutations in evolution of drug resistance; we characterised hA3G/F-mediated hypermutations in the RT region of the pol gene of patients with or without antiretroviral therapy (ART).

Methods

In 88 HIV-1-positive individuals, drug resistance genotyping was carried out in plasma virus and provirus by population sequencing. Hypermutations were determined by three different approaches using Hypermut 2.0 software, cluster analysis and APOBEC3G-mediated defectives indices. Clinical and demographic characteristics of these individuals were studied in relation to these hypermutations.

Results

hA3G/F-mediated hypermutated sequences in proviral DNA, but not in plasma virus, were identified in 11.4% (10/88) subjects. Proviral hypermutations were observed more frequently in patients with ART failure than in ART-naïve individuals (p=0.03). In therapy failure patients, proviral hypermutation were associated with greater intra-compartmental genetic diversity (p<0.001). In therapy-naïve individuals, hypermutated proviral DNA with M184I and M230I mutations due to the editing of hA3G, had stop codons in the open reading frames and the same mutations were absent in the plasma virus. Only a limited concordance was found between the drug resistance mutations in plasma RNA and proviral DNA.

Conclusions

hA3G lethal hypermutation was significantly associated with ART failure in Indian HIV-1 subtype C patients. It is unlikely that viral variants, which exhibit hypermutated sequences and M184I and/or M230I, will mature and expand in vivo.     

Traumatic abdominal wall hernia: Delayed repair: Advantageous or taxing

INTRODUCTIONTraumatic abdominal wall hernia (TAWH) is a rare entity. Most cases occur in children, following an injury from the bicycle handle bar. In adults, it usually results from road traffic accidents (RTA). We present one of the largest reported cases of TAWH following RTA managed by delayed mesh repair.PRESENTATION OF CASEA 35 yr old obese male with RTA was diagnosed with TAWH with 19 cm × 15 cm defect in left flank. As there were no intra abdominal injuries and overlying skin was abraded, he was planned for elective repair after 6 months. On exploration a defect of 30 cm × 45 cm was found extending from midline anteriorly to 8 cm short of midline posteriorly in transverse axis and costal margin to iliac crest in craniocaudal axis. After restoration of bowel into abdominal cavity, primary closure or even approximation of muscular defect was not possible thus a mesh closure using 60 cm × 60 cm prolene mesh in subcutaneous plane was done. After 4 months follow up, patient is healthy and has no recurrence.DISCUSSIONEmergent surgical management of TAWH is usually favoured due to high incidence of associated intra abdominal injuries. Delayed repair may be undertaken in selected cases.CONCLUSIONTAWH, although rare, should be suspected in cases of RTA with abdominal wall swellings. With time, the hernia defect may enlarge and muscles may undergo atrophy making delayed repair difficult.     

Synthesis and antimicrobial screening of some novel chalcones and flavanones substituted with higher alkyl chains

As a part of our program to generate some novel flavonoid frameworks substituted with higher alkyl groups as possible antimicrobial agents, we have in total synthesized twelve novel chalcones (11–16) and their corresponding flavanones (17–22) substituted with either nonyl or dodecyl chains in ring B in very good to excellent yields. The synthesized compounds have been screened for their antimicrobial potential against six bacterial and four fungal strains. The tested compounds, in general, showed significant antibacterial and comparable antifungal activities. While the chalcone (16) with a dodecyl chain showed highly promising antibacterial activity against almost all the organisms tested, the chalcone (13) with nonyl chain showed promising antifungal activity against Candida rugosa and Aspergillus niger strains.     

Chemopreventive potential of Apium leptophyllum (Pers.) against DMBA induced skin carcinogenesis model by modulatory influence on biochemical and antioxidant biomarkers in Swiss mice

Aim:

The study was designed to investigate the chemopreventive potential of flavonoidal fractions of Apium leptophyllum fruits (FFALF) on Swiss mice.

Materials and Methods:

Skin tumor or papilloma was developed by topical application of DMBA (25 μg in 0.1 ml acetone) on intrascapular region of mice, twice weekly for 8 weeks. The animals were divided into six groups: Group I (vehicle control); group II (FFALF control, 5 mg/kg); group III (carcinogenic control, DMBA treated initially for 8 weeks); and group IV, V and VI as pre-treated group (FFALF 5, 10 and 20 mg/kg respectively for 16 weeks along with DMBA treatment). After the 16^th week of treatment; the tumor morphology, skin histopathology, and biochemical and antioxidant biomarkers were measured and compared with carcinogenic control as well as vehicle control.

Results:

The co-administration of FFALF with DMBA-treated groups showed significant (P ≤ 0.001) prevention against skin papilloma and normalized the status of lipid peroxidation with antioxidant biomarkers in a dose-dependent manner as compared to carcinogenic control.

Conclusions:

Thus, the present study suggests that the FFALF is non-carcinogenic and has chemopreventive potential on DMBA-induced carcinogenesis in mouse, which may be due to the modulation of cutaneous lipid peroxidation or enhancement of total antioxidant capacity.KEY WORDS: Apium leptophyllum, antioxidant biomarker, chemoprevention, DMBA, skin papilloma