An important alternative to free tissue transfer in patients requiring correction of soft tissue chin defects are local and regional flaps, such as the pectoralis major myocutaneous flap and deltopectoral flap. With predictable vascular supply, potential for large size, and good aesthetic match for facial and cervical skin, the deltopectoral flap can offer the reconstructive surgeon additional options in patients who lack vessels suitable for free tissue transfer. The use of an expanded deltopectoral flap for a staged reconstruction of the chin in a patient with cancer recurrences, concomitant resections, radiation and multiple reconstructions is reported.
Chin reconstruction; Deltopectoral
Giant fibrolipomas involving the upper extremities are rare tumours. These large masses grow slowly and produce symptoms due to their size, location and compression of adjacent structures. Surgical excision usually leads to complete recovery from symptoms.
Intraneural lipomas of the ulnar nerve or its branches are rare benign tumours. Although most intraneural lipomas present as asymptomatic tumours, some may present as compression neuropathies due to their location. In the majority of cases these tumours can be enucleated without damage to the nerve fibres.
Intraneural lipoma; Ulnar nerve
Acute median nerve compression usually occurs from increased pressure within the carpal tunnel and forearm compartments. Although the hyperesthesia from burns may mimic symptoms of acute compression neuropathy, clinical diagnosis should be made from history, clinical signs and symptoms. Early recognition and decompression of the carpal tunnel either as part of the burn excision or along with escharotomy usually leads to full recovery.
Burns of hands and wrist; Median nerve compression neuropathy
The superficial branch of the radial nerve is highly vulnerable to trauma, irritation and compression due to its anatomical location. Intraneural lipomas and fibrolipomas arising from the supporting tissues of this peripheral nerve can cause compression of the adjacent nerve leading to symptoms of neuritis of the radial nerve or Wartenberg syndrome.
Intraneural lipoma; Wartenberg syndrome
Background & Objectives:
Bifidobacteria colonize the gut after the first week of life and remain an important component of the gut microbiota in infancy. This study was carried out to characterize the diversity and number of bifidobacteria colonizing the gut in Indian neonates and to investigate whether asymptomatic infection with rotavirus in the first month of life affected gut colonization by bidifobacteria.
DNA was isolated from faeces of 14 term-born neonates who were under surveillance for rotavirus infection. Bacterial and bifidobacterial diversity was evaluated by temporal temperature gradient electrophoresis (TTGE) of 16S rDNA amplified using total bacteria and bifidobacteria-specific primers. Real time PCR, targeting 16S rDNA, was used to quantitate faecal bifidobacteria and enterobacteria.
TTGE of conserved bacterial 16S rDNA showed 3 dominant bands of which Escherichia coli (family Enterobacteriaceae) and Bifidobacterium (family Bifidobacteriaceae) were constant. TTGE of Bifidobacterium genus-specific DNA showed a single band in all neonates identified by sequencing as Bifidobacterium longum subsp. infantis. Faecal bifidobacterial counts (log10 cfu/g faeces) ranged from 6.1 to 9.3 and enterobacterial counts from 6.3 to 9.5. Neonates without and with rotavirus infection in the first week of life did not show significant differences in the median count of bifidobacteria (log10 count 7.48 vs. 7.41) or enterobacteria (log10 count 8.79 vs. 7.92).
Interpretation & Conclusions:
B. longum subsp. infantis was the sole bifidobacterial species colonizing the gut of Indian neonates. Asymptomatic rotavirus infection in the first month of life was not associated with alteration in faecal bifidobacteria or enterobacteria.
Bifidobacterium; colonization; gut; neonates; rotavirus
Fractures of the pelvis associated with uncontrollable hypotension are managed by stabilization of fractures and arteriographic embolization of the bleeding vessels. Embolization of these arteries may result in necrosis of the buttocks. The use of a transverse lumbar artery-based flap can be used for repair of these defects.
Transverse lumbar flap
Soft tissue defects of the great toe that include exposed tendon and bone present a reconstructive challenge for plastic surgeons. A distally based dorsalis pedis island flap based on the first dorsal metatarsal artery, which has been successfully used to cover the soft tissue defect following wide excision of melanoma of the big toe, is reported
Dorsal metatarsal artery flap
Acute carpal tunnel syndrome is the most common compression neuropathy of the upper extremity following trauma. A rare occurence of spontaneous bleeding into the carpal tunnel, presenting as acute carpal tunnel syndrome, is presented.
Carpal tunnel syndrome; Spontaneous bleeding
Pancreatic cancer is the fourth leading cause of cancer-related death in the world. The etiology of pancreatic cancer is heterogeneous with a wide range of alterations that have already been reported at the level of the genome, transcriptome, and proteome. The past decade has witnessed a large number of experimental studies using high-throughput technology platforms to identify genes whose expression at the transcript or protein levels is altered in pancreatic cancer. Based on expression studies, a number of molecules have also been proposed as potential biomarkers for diagnosis and prognosis of this deadly cancer. Currently, there are no repositories which provide an integrative view of multiple Omics data sets from published research on pancreatic cancer. Here, we describe the development of a web-based resource, Pancreatic Cancer Database (http://www.pancreaticcancerdatabase.org), as a unified platform for pancreatic cancer research. PCD contains manually curated information pertaining to quantitative alterations in miRNA, mRNA, and proteins obtained from small-scale as well as high-throughput studies of pancreatic cancer tissues and cell lines. We believe that PCD will serve as an integrative platform for scientific community involved in pancreatic cancer research.
biomarker; body fluids; chronic pancreatitis; secreted
Marine actinobacteria are known to be a rich source for novel metabolites with diverse biological activities. In this study, a potential extracellular L-asparaginase was characterised from the Streptomyces griseus NIOT-VKMA29. Box-Behnken based optimization was used to determine the culture medium components to enhance the L-asparaginase production. pH, starch, yeast extract and L-asparagine has a direct correlation for enzyme production with a maximum yield of 56.78 IU mL−1. A verification experiment was performed to validate the experiment and more than 99% validity was established. L-Asparaginase biosynthesis gene (ansA) from Streptomyces griseus NIOT-VKMA29 was heterologously expressed in Escherichia coli M15 and the enzyme production was increased threefold (123 IU mL−1) over the native strain. The ansA gene sequences reported in this study encloses several base substitutions with that of reported sequences in GenBank, resulting in altered amino acid sequences of the translated protein.
Dengue and chikungunya are rapidly expanding viruses transmitted by mosquitoes of the genus Aedes. Few epidemiological studies have examined the extent of transmission of these infections in South India despite an increase in the number of reported cases, and a high suitability for transmission.
Methods and findings
We conducted a household-based seroprevalence survey among 1010 individuals aged 5-40 years living in fifty randomly selected spatial locations in Chennai, Tamil Nadu. Participants were asked to provide a venous blood sample and to complete a brief questionnaire with basic demographic and daily activity information. Previous exposure to dengue and chikungunya was determined using IgG indirect ELISA (Panbio) and IgG ELISA (Novatec), respectively. We used this data to estimate key transmission parameters (force of infection and basic reproductive number) and to explore factors associated with seropositivity. While only 1% of participants reported history of dengue and 20% of chikungunya, we found that 93% (95%CI 89-95%) of participants were seropositive to dengue virus, and 44% (95%CI 37-50%) to chikungunya. Age-specific seroprevalence was consistent with long-tem, endemic circulation of dengue and suggestive of epidemic chikungunya transmission. Seropositivity to dengue and chikungunya were significantly correlated, even after adjusting for individual and household factors. We estimate that 23% of the susceptible population gets infected by dengue each year, corresponding to approximately 228,000 infections. This transmission intensity is significantly higher than that estimated in known hyperendemic settings in Southeast Asia and the Americas.
These results provide unprecedented insight into the very high transmission potential of dengue and chikungunya in Chennai and underscore the need for enhanced surveillance and control methods.
Despite a recent increase in the number of cases, little data exist on the extent of dengue and chikungunya transmission in Indian cities. We conducted a household-based serosurvey conducted in randomly selected spatial locations across the metropolis of Chennai. We tested samples for evidence of previous infection by dengue and chikungunya viruses and used this data to estimate key transmission parameters (force of infection and basic reproductive number) and to explore factors associated with seropositivity. We found that 93% of participants had been exposed to dengue virus, and 44% to chikungunya. We estimate that 23% of the susceptible population gets infected by dengue virus each year, corresponding to approximately 228,000 infections per year. This transmission intensity is almost three times larger than that in traditionally hyperendemic district in Thailand, and suggests an extremely large proportion of asymptomatic/sub-clinical disease, a lack of recognition of the disease and/or under-reporting.
Hybrid gold nanostructures seeded into nanotextured zinc oxide (ZnO) nanoflowers (NFs) were created for novel biosensing applications. The selected ‘spotted NFs’ had a 30-nm-thick gold nanoparticle (AuNP) layer, chosen from a range of AuNP thicknesses, sputtered onto the surface. The generated nanohybrids, characterized by morphological, physical and structural analyses, were uniformly AuNP-seeded onto the ZnO NFs with an average length of 2–3 μm. Selective capture of molecular probes onto the seeded AuNPs was evidence for the specific interaction with DNA from pathogenic Leptospirosis-causing strains via hybridization and mis-match analyses. The attained detection limit was 100 fM as determined via impedance spectroscopy. High levels of stability, reproducibility and regeneration of the sensor were obtained. Selective DNA immobilization and hybridization were confirmed by nitrogen and phosphorus peaks in an X-ray photoelectron spectroscopy analysis. The created nanostructure hybrids illuminate the mechanism of generating multiple-target, high-performance detection on a single NF platform, which opens a new avenue for array-based medical diagnostics.
The performance of sensing surfaces highly relies on nanostructures to enhance their sensitivity and specificity. Herein, nanostructured zinc oxide (ZnO) thin films of various thicknesses were coated on glass and p-type silicon substrates using a sol-gel spin-coating technique. The deposited films were characterized for morphological, structural, and optoelectronic properties by high-resolution measurements. X-ray diffraction analyses revealed that the deposited films have a c-axis orientation and display peaks that refer to ZnO, which exhibits a hexagonal structure with a preferable plane orientation (002). The thicknesses of ZnO thin films prepared using 1, 3, 5, and 7 cycles were measured to be 40, 60, 100, and 200 nm, respectively. The increment in grain size of the thin film from 21 to 52 nm was noticed, when its thickness was increased from 40 to 200 nm, whereas the band gap value decreased from 3.282 to 3.268 eV. Band gap value of ZnO thin film with thickness of 200 nm at pH ranging from 2 to 10 reduces from 3.263eV to 3.200 eV. Furthermore, to evaluate the transducing capacity of the ZnO nanostructure, the refractive index, optoelectric constant, and bulk modulus were analyzed and correlated. The highest thickness (200 nm) of ZnO film, embedded with an interdigitated electrode that behaves as a pH-sensing electrode, could sense pH variations in the range of 2-10. It showed a highly sensitive response of 444 μAmM-1cm-2 with a linear regression of R2 =0.9304. The measured sensitivity of the developed device for pH per unit is 3.72μA/pH.
The deposition of the amyloid β protein (Aβ) in the brain is a hallmark of Alzheimer's disease (AD). Removal of Aβ by Aβ-antibody treatment has been developed as a potential treatment strategy against AD. First clinical trials showed neither a stop nor a reduction of disease progression. Recently, we have shown that the formation of soluble and insoluble Aβ aggregates in the human brain follows a hierarchical sequence of three biochemical maturation stages (B-Aβ stages). To test the impact of the B-Aβ stage on Aβ immunotherapy, we treated transgenic mice expressing human amyloid precursor protein (APP) carrying the Swedish mutation (KM670/671NL; APP23) with the Aβ-antibody β1 or phosphate-buffered saline (PBS) beginning 1) at 3 months, before the onset of dendrite degeneration and plaque deposition, and 2) at 7 months, after the start of Aβ plaque deposition and dendrite degeneration.
At 5 months of age, first Aβ aggregates in APP23 brain consisted of non-modified Aβ (representing B-Aβ stage 1) whereas mature Aβ-aggregates containing N-terminal truncated, pyroglutamate-modified AβN3pE and phosphorylated Aβ (representing B-Aβ stage 3) were found at 11 months of age in both β1- and PBS-treated animals. Protective effects on commissural neurons with highly ramified dendritic trees were observed only in 3-month-old β1-treated animals sacrificed at 5 months. When treatment started at 7 months of age, no differences in the numbers of healthy commissural neurons were observed between β1- and PBS-treated APP23 mice sacrificed with 11 months.
Aβ antibody treatment was capable of protecting neurons from dendritic degeneration as long as Aβ aggregation was absent or represented B-Aβ stage 1 but had no protective or curative effect in later stages with mature Aβ aggregates (B-Aβ stage 3). These data indicate that the maturation stage of Aβ aggregates has impact on potential treatment effects in APP23 mice.
Electronic supplementary material
The online version of this article (doi:10.1186/s40478-015-0217-z) contains supplementary material, which is available to authorized users.
Amyloid; Immunization; Antibody; Protofibrils; Fibrils; Clearance
use of hybrid hemoglobin (Hb), with mesoheme substituted for
protoheme, allows separate monitoring of the α or β hemes
along the allosteric pathway. Using resonance Raman (rR) spectroscopy
in silica gel, which greatly slows protein motions, we have observed
that the Fe–histidine stretching frequency, νFeHis, which
is a monitor of heme reactivity, evolves between frequencies characteristic
of the R and T states, for both α or β chains, prior to
the quaternary R–T and T–R shifts. Computation of νFeHis,
using QM/MM and the conformational search program PELE, produced remarkable
agreement with experiment. Analysis of the PELE structures showed
that the νFeHis shifts resulted from heme distortion and, in
the α chain, Fe–His bond tilting. These results support
the tertiary two-state model of ligand binding (Henry et al., Biophys. Chem.2002, 98, 149).
Experimentally, the νFeHis evolution is faster for β than
for α chains, and pump–probe rR spectroscopy in solution
reveals an inflection in the νFeHis time course at 3 μs
for β but not for α hemes, an interval previously shown
to be the first step in the R–T transition. In the α
chain νFeHis dropped sharply at 20 μs, the final step
in the R–T transition. The time courses are fully consistent
with recent computational mapping of the R–T transition via
conjugate peak refinement by Karplus and co-workers (Fischer et al., Proc. Natl. Acad. Sci. U. S. A.2011, 108, 5608). The effector molecule IHP was found to lower
νFeHis selectively for α chains within the R state, and
a binding site in the α1α2 cleft
Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. The search for targeted treatments has been hampered by the lack of relevant animal models for the genetically diverse subsets of HCC, including the 20-40% of HCCs that are defined by activating mutations in the gene encoding β-catenin. To address this chemotherapeutic challenge, we created and characterized transgenic zebrafish expressing hepatocyte-specific activated β-catenin. By 2 months post fertilization (mpf), 33% of transgenic zebrafish developed HCC in their livers, and 78% and 80% of transgenic zebrafish showed HCC at 6 and 12 mpf, respectively. As expected for a malignant process, transgenic zebrafish showed significantly decreased mean adult survival compared to non-transgenic control siblings. Using this novel transgenic model, we screened for druggable pathways that mediate β-catenin-induced liver growth and identified two c-Jun N-terminal kinase (JNK) inhibitors and two antidepressants (one tricyclic antidepressant, amitriptyline, and one selective serotonin reuptake inhibitor) that suppressed this phenotype. We further found that activated β-catenin was associated with JNK pathway hyperactivation in zebrafish and in human HCC. In zebrafish larvae, JNK inhibition decreased liver size specifically in the presence of activated β-catenin. The β-catenin-specific growth-inhibitory effect of targeting JNK was conserved in human liver cancer cells. Our other class of hits, antidepressants, has been used in patient treatment for decades, raising the exciting possibility that these drugs could potentially be repurposed for cancer treatment. In support of this proposal, we found that amitriptyline decreased tumor burden in a mouse HCC model. Our studies implicate JNK inhibitors and antidepressants as potential therapeutics for β-catenin-induced liver tumors.
Liver cancer is a leading cause of cancer-related death. Genetic analysis of liver cancer has enabled classification of these tumors into subsets with unique genetic, clinical, and prognostic features. The search for targeted liver cancer treatments has been hampered by the lack of relevant animal models for these genetically diverse subsets, including liver cancers that are defined by activating mutations in the gene encoding β-catenin, an integral component of the Wnt signaling pathway. Here we describe the generation and characterization of genetically modified zebrafish expressing hepatocyte-specific activated β-catenin. We used this new zebrafish model to screen for drugs that suppress β-catenin-induced liver growth, and identified two classes of hits, c-Jun N-terminal kinase (JNK) inhibitors and antidepressants, that suppressed this phenotype. Our findings provide insights into the mechanisms by which β-catenin promotes liver tumor formation and implicate JNK inhibitors and antidepressants as potential treatments for a subset of human liver cancers.
Salivary proteins are an important source for developing marker-based assays for oral cancers. To get an insight into the proteins present in human saliva, we applied multiple strategies involving affinity-based depletion of abundant proteins, fractionation of the resulting proteins or their tryptic peptides followed by LC–MS/MS analysis, using high resolution mass spectrometry. By integrating the protein identifications observed by us with those from similar workflows employed in earlier investigations, we compiled an updated salivary proteome. We have mapped the salivary proteome to the published data on differentially expressed proteins from oral cancer tissues and also for their secretory features using prediction tools, SignalP 4.1, TMHMM 2c and Exocarta. Proteotypic peptides for the subset of proteins implicated in oral cancer and mapped to any two of the prediction tools for secretory potential have been listed. The data here are related to the research article “Human saliva proteome – a resource of potential biomarkers for oral cancer” in the Journal of Proteomics .
The in-vitro study compared the shear bond strength (SBS) of three recently introduced dual-cure resin based core build-up materials namely ParaCore, FluoroCore, and MultiCore.
Materials and Methods:
One hundred twenty extracted permanent human mandibular molar teeth were taken and sectioned horizontally beneath the dentinoenamel junction to expose the coronal dentin. The specimens obtained were divided into three main groups based on the materials used and then further divided into four sub-groups based on time interval with ten samples each. The dentin surface was treated with the respective adhesives of the groups and then bulk filled with core build-up materials. The attained samples were than subjected to shear loading in Instron Universal Testing Machine. The data were tabulated and statistically analyzed using analysis of variance (ANOVA), Tukey's HSD, and Levene's test.
The mean SBS was highest in MultiCore at all time periods as compared to FluoroCore and ParaCore and was also higher at 48 h thermocycling in all three groups studied.
MultiCore dual-cure resin based core build-up material showed the highest mean SBS as compared to FluoroCore and ParaCore. SBS was not negatively affected by thermocycling.
Core build-up; dual-cure resin; shear bond strength; thermocycling
DNA tumor viruses including members of the polyomavirus, adenovirus, papillomavirus, and herpes virus families are presently the subject of intense interest with respect to the role that epigenetics plays in control of the virus life cycle and the transformation of a normal cell to a cancer cell. To date, these studies have primarily focused on the role of histone modification, nucleosome location, and DNA methylation in regulating the biological consequences of infection. Using a wide variety of strategies and techniques ranging from simple ChIP to ChIP-chip and ChIP-seq to identify histone modifications, nuclease digestion to genome wide next generation sequencing to identify nucleosome location, and bisulfite treatment to MeDIP to identify DNA methylation sites, the epigenetic regulation of these viruses is slowly becoming better understood. While the viruses may differ in significant ways from each other and cellular chromatin, the role of epigenetics appears to be relatively similar. Within the viral genome nucleosomes are organized for the expression of appropriate genes with relevant histone modifications particularly histone acetylation. DNA methylation occurs as part of the typical gene silencing during latent infection by herpesviruses. In the simple tumor viruses like the polyomaviruses, adenoviruses, and papillomaviruses, transformation of the cell occurs via integration of the virus genome such that the virus's normal regulation is disrupted. This results in the unregulated expression of critical viral genes capable of redirecting cellular gene expression. The redirected cellular expression is a consequence of either indirect epigenetic regulation where cellular signaling or transcriptional dysregulation occurs or direct epigenetic regulation where epigenetic cofactors such as histone deacetylases are targeted. In the more complex herpersviruses transformation is a consequence of the expression of the viral latency proteins and RNAs which again can have either a direct or indirect effect on epigenetic regulation of cellular expression. Nevertheless, many questions still remain with respect to the specific mechanisms underlying epigenetic regulation of the viruses and transformation.
Cancer; Epigenetics; Methylation; Transformation; Virus
In rapidly developing countries such as India, the ubiquity of air pollution sources in urban and rural communities often results in ambient and household exposures significantly in excess of health-based air quality guidelines. Few efforts, however, have been directed at establishing quantitative exposure–response relationships in such settings. We describe study protocols for The Tamil Nadu Air Pollution and Health Effects (TAPHE) study, which aims to examine the association between fine particulate matter (PM2.5) exposures and select maternal, child and adult health outcomes in integrated rural–urban cohorts.
Methods and analyses
The TAPHE study is organised into five component studies with participants drawn from a pregnant mother–child cohort and an adult cohort (n=1200 participants in each cohort). Exposures are assessed through serial measurements of 24–48 h PM2.5 area concentrations in household microenvironments together with ambient measurements and time-activity recalls, allowing exposure reconstructions. Generalised additive models will be developed to examine the association between PM2.5 exposures, maternal (birth weight), child (acute respiratory infections) and adult (chronic respiratory symptoms and lung function) health outcomes while adjusting for multiple covariates. In addition, exposure models are being developed to predict PM2.5 exposures in relation to household and community level variables as well as to explore inter-relationships between household concentrations of PM2.5 and air toxics. Finally, a bio-repository of peripheral and cord blood samples is being created to explore the role of gene–environment interactions in follow-up studies.
Ethics and dissemination
The study protocols have been approved by the Institutional Ethics Committee of Sri Ramachandra University, the host institution for the investigators in this study. Study results will be widely disseminated through peer-reviewed publications and scientific presentations. In addition, policy-relevant recommendations are also being planned to inform ongoing national air quality action plans concerning ambient and household air pollution.
air pollution; cohorts; India; exposure-response; particulate matter; air toxics
Bulk insulators with strong spin orbit coupling exhibit metallic surface states possessing topological order protected by the time reversal symmetry. However, experiments show vulnerability of topological states to aging and impurities. Different studies show contrasting behavior of the Dirac states along with plethora of anomalies, which has become an outstanding problem in material science. Here, we probe the electronic structure of Bi2Se3 employing high resolution photoemission spectroscopy and discover the dependence of the behavior of Dirac particles on surface terminations. The Dirac cone apex appears at different binding energies and exhibits contrasting shift on Bi and Se terminated surfaces with complex time dependence emerging from subtle adsorbed oxygen-surface atom interactions. These results uncover the surface states behavior of real systems and the dichotomy of topological and normal surface states important for device fabrication as well as realization of novel physics such as Majorana Fermions, magnetic monopole, etc.
The complete genome sequence of the ALL-03 strain of rat cytomegalovirus (RCMV) has been determined. The RCMV genome has a length of 197,958 bp and is arranged as a single unique sequence flanked by 504-bp terminal direct repeats. This strain is closely related to the English strain of RCMV in terms of genetic arrangement but differs slightly in size.
Adenovirus infections of immunocompromised patients can develop into deadly multiorgan or systemic disease. The virus is especially threatening for pediatric allogeneic hematopoietic stem cell transplant recipients; according to some studies, 10% or more of these patients succumb to disease resulting from adenovirus infection. At present, there is no drug approved for the treatment or prevention of adenovirus infections. Compounds that are approved to treat other virus infections are used off-label to combat adenovirus, but only anecdotal evidence of the efficacy of these drugs exists. Ganciclovir, a drug approved for the treatment of herpesvirus infection, was previously reported to be effective against human adenoviruses in vitro. To model adenovirus infections in immunocompromised humans, we examined ganciclovir's efficacy in immunosuppressed Syrian hamsters intravenously infected with type 5 human adenovirus (Ad5). This animal model is permissive for Ad5 replication, and the animals develop symptoms similar to those seen in humans. We demonstrate that ganciclovir suppresses Ad5 replication in the liver of infected hamsters and that it mitigates the consequences of Ad5 infections in these animals when administered prophylactically or therapeutically. We show that ganciclovir inhibits Ad5 DNA synthesis and late gene expression. The mechanism of action for the drug is not clear; preliminary data suggest that it exerts its antiadenoviral effect by directly inhibiting the adenoviral DNA polymerase. While more extensive studies are required, we believe that ganciclovir is a promising drug candidate to treat adenovirus infections. Brincidofovir, a drug with proven activity against Ad5, was used as a positive control in the prophylactic experiment.