Comparison of Measured and Monte Carlo Calculated Dose Distributions from Indigenously Developed 6 MV Flattening Filter Free Medical Linear Accelerator.

PURPOSE: Monte Carlo simulation was carried out for a 6 MV flattening filter-free (FFF) indigenously developed linear accelerator (linac) using the BEAMnrc user-code of the EGSnrc code system. The model was benchmarked against the measurements. A Gaussian distributed electron beam of kinetic energy 6.2 MeV with full-width half maximum of 1 mm was used in this study. METHODS: The simulation of indigenously developed linac unit has been carried out by using the Monte Carlo-based BEAMnrc user-code of the EGSnrc code system. Using the simulated model, depth and lateral dose profiles were studied using the DOSXYZnrc user-code. The calculated dose data were compared against the measurements using an RFA dosimertic system made by PTW, Germany (water tank MP3-M and 0.125 cm3 ion chamber). RESULTS: The BEAMDP code was used to analyze photon fluence spectra, mean energy distribution, and electron contamination fluence spectra. Percentage depth dose (PDD) and beam profiles (along both X and Y directions) were calculated for the field sizes 5 cm × 5 cm - 25 cm × 25 cm. The dose difference between the calculated and measured PDD and profile values were under 1%, except for the penumbra region where the maximum deviation was found to be around 3%. CONCLUSIONS: A Monte Carlo model of indigenous FFF linac (6 MV) has been developed and benchmarked against the measured data.

Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing.

In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of "fitter" clones may be anticipated. However, an imbalanced distribution of multiple myeloma is frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into the spatial clonal architecture. We demonstrate spatial genomic heterogeneity in more than 75% of patients, including inactivation of CDKN2C and TP53, and mutations affecting mitogen-activated protein kinase genes. We show that the extent of spatial heterogeneity is positively associated with the size of biopsied focal lesions consistent with regional outgrowth of advanced clones. The results support a model for multiple myeloma progression with clonal sweeps in the early phase and regional evolution in advanced disease. We suggest that multi-region investigations are critical to understanding intra-patient heterogeneity and the evolutionary processes in multiple myeloma.In multiple myeloma, malignant cells expand within bone marrow. Here, the authors use multi-region sequencing in patient samples to analyse spatial clonal architecture and heterogeneity, providing novel insight into multiple myeloma progression and evolution.

A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve.

OBJECTIVE: Neural reflexes regulate immune responses and homeostasis. Advances in bioelectronic medicine indicate that electrical stimulation of the vagus nerve can be used to treat inflammatory disease, yet the understanding of neural signals that regulate inflammation is incomplete. Current interfaces with the vagus nerve do not permit effective chronic stimulation or recording in mouse models, which is vital to studying the molecular and neurophysiological mechanisms that control inflammation homeostasis in health and disease. We developed an implantable, dual purpose, multi-channel, flexible 'microelectrode' array, for recording and stimulation of the mouse vagus nerve. APPROACH: The array was microfabricated on an 8 µm layer of highly biocompatible parylene configured with 16 sites. The microelectrode was evaluated by studying the recording and stimulation performance. Mice were chronically implanted with devices for up to 12 weeks. MAIN RESULTS: Using the microelectrode in vivo, high fidelity signals were recorded during physiological challenges (e.g potassium chloride and interleukin-1ß), and electrical stimulation of the vagus nerve produced the expected significant reduction of blood levels of tumor necrosis factor (TNF) in endotoxemia. Inflammatory cell infiltration at the microelectrode 12 weeks of implantation was limited according to radial distribution analysis of inflammatory cells. SIGNIFICANCE: This novel device provides an important step towards a viable chronic interface for cervical vagus nerve stimulation and recording in mice.

The haptoglobin beta subunit sequesters HMGB1 toxicity in sterile and infectious inflammation.

BACKGROUND: Extra-corpuscular haemoglobin is an endogenous factor enhancing inflammatory tissue damage, a process counteracted by the haemoglobin-binding plasma protein haptoglobin composed of alpha and beta subunits connected by disulfide bridges. Recent studies established that haptoglobin also binds and sequesters another pro-inflammatory mediator, HMGB1, via triggering CD163 receptor-mediated anti-inflammatory responses involving heme oxygenase-1 expression and IL-10 release. The molecular mechanism underlying haptoglobin-HMGB1 interaction remains poorly elucidated. METHODS: Haptoglobin ß subunits were tested for HMGB1-binding properties, as well as efficacy in animal models of sterile liver injury (induced by intraperitoneal acetaminophen administration) or infectious peritonitis (induced by cecal ligation and puncture, CLP, surgery) using wild-type (C57BL/6) or haptoglobin gene-deficient mice. RESULTS: Structural-functional analysis demonstrated that the haptoglobin ß subunit recapitulates the HMGB1-binding properties of full-length haptoglobin. Similar to HMGB1-haptoglobin complexes, the HMGB1-haptoglobin ß complexes also elicited anti-inflammatory effects via CD163-mediated IL-10 release and heme oxygenase-1 expression. Treatment with haptoglobin ß protein conferred significant protection in mouse models of polymicrobial sepsis as well as acetaminophen-induced liver injury, two HMGB1-dependent inflammatory conditions. CONCLUSIONS: Haptoglobin ß protein offers a novel therapeutic approach to fight against various inflammatory diseases caused by excessive HMGB1 release.

Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker.

The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.

Ni(II) and Zn(II) Complexes Containing Alkynyl Functionalized Salicylaldimine Ligand and Heterocyclic Coligand: Synthesis, Characterization and Luminescence Properties.

Some nickel(II) and zinc(II) complexes of the type [Ni(L)(phen/bipy)]X (1a-6a) and [Zn(L) (phen/bipy)]X (1b-6b) (where L = 2-{(E)-[(4-trimethylsilylethynylphenyl)imino]methyl}-4-(4-nitro phenylethynyl)phenol; phen = 1, 10-phenanthroline, bipy = 2, 2´-bipyridine; X = ClO4-, BF4-, PF6-) have been prepared and characterized on the basis of elemental analyses, FTIR, 1H NMR and mass spectral studies. The molecular structure of L was determined by single crystal X-ray diffraction studies. The electrochemical behaviour of the Ni(II) complexes indicate that the phen complexes appears at more positive potential as compared to those for bipy complexes, as a consequence of its strong π-acidic character. TGA was carried out to study the thermal behavior of the complexes. Room temperature luminescence is observed for all complexes corresponds to π â†’ π* ILCT transition. The size of the counter anion and heterocyclic coligands phen and bipy shows marked effect on emission properties of the complexes.

Comparison of rocuronium at two different doses and succinylcholine for endotracheal intubation in adult patients for elective surgeries.

BACKGROUND: The effects of rocuronium at two different doses, that is, 0.6 mg/kg (2 × ED95) and 0.9 mg/kg (3 × ED95), were compared with succinylcholine (2 mg/kg) when used for endotracheal intubation in adult patients for elective surgeries under general anesthesia. MATERIALS AND METHODS: Ninety patients were divided into three groups of 30 each. Groups A, B received injection rocuronium at 0.6 mg/kg, 0.9 mg/kg respectively and Group C received succinylcholine at 2 mg/kg. Onset of action of relaxant, intubation conditions, time taken to intubate and duration of action were compared. STATISTICAL ANALYSIS USED: To compare the statistical difference in the age, weight, height of the study subjects, onset of action of relaxant, intubation conditions, time taken to intubate, and duration of action analysis of variance and unpaired t-test were used. RESULTS: The onset time was considerably shorter with rocuronium 0.9 mg/kg than 0.6 mg/kg. The onset time of rocuronium 0.9 mg/kg was found to be significantly longer than succinylcholine 2 mg/kg. Time taken to intubate was shortest with succinylcholine 2 mg/kg. The time taken to intubate with the rocuronium 0.9 mg/kg was found to be comparable to that of rocuronium 0.6 mg/kg. Intubation score of rocuronium 0.9 mg/kg was the best (17.75), which was comparable with succinylcholine. However, the intubation score obtained with rocuronium 0.6 mg/kg was inferior. Duration of action was shortest with succinylcholine. The duration of action is prolonged when the dose of rocuronium is increased from 0.6 to 0.9 mg/kg. CONCLUSION: Rapid sequence induction of anesthesia with propofol and fentanyl, succinylcholine allowed a more rapid endotracheal intubation sequence and created superior intubation conditions than rocuronium. However, the technique of using a large dose of rocuronium to achieve perfect conditions for tracheal intubation may have application whenever succinylcholine is relatively contraindicated.

S100A7 has an oncogenic role in oral squamous cell carcinoma by activating p38/MAPK and RAB2A signaling pathway.

Oral cancer consists of squamous cell carcinoma within the oral cavity or on the lip. The clinical prognosis of this cancer is mostly poor owing to delayed diagnosis and a lack of appropriate early detection biomarkers to identify the disease. In the current study, we investigated the role of the S100A7 calcium-binding protein in oral squamous cell carcinoma as an activator of the p38/MAPK and RAB2A signaling pathway. The aim of the present study was to determine whether S100A7 and RAB2A have a role in tumor progression and to assess their potential as early detection biomarkers for oral cancer. This study elucidated the functional and molecular mechanisms of S100A7 and RAB2A activity in oral cancer, leading us to conclude that S100A7 is the major contributing factor in the occurrence of oral cancer and promotes local tumor progression by activating the MAPK signaling pathway via the RAB2A pathway. We hypothesize that S100A7 affects cell motility and invasion by regulating the RAB2A-associated MAPK signaling cascades. Also, the downregulation of S100A7 expression by RNA interference-mediated silencing inhibits oral cancer cell growth, migration and invasion.

Monte Carlo based investigations of electron contamination from telecobalt unit head in build up region and its impact on surface dose.

A Telecobalt unit has wide range of applications in cancer treatments and is used widely in many countries all around the world. Estimation of surface dose in Cobalt-60 teletherapy machine becomes important since clinically useful photon beam consist of contaminated electrons during the patient treatment. EGSnrc along with the BEAMnrc user code was used to model the Theratron 780E telecobalt unit. Central axis depth dose profiles including surface doses have been estimated for the field sizes of 0×0, 6×6, 10×10, 15×15, 20×20, 25×25, 30×30cm2 and at Source-to-surface distance (SSD) of 60 and 80cm. Surface dose was measured experimentally by the Gafchromic RTQA2 films and are in good agreement with the simulation results. The central axis depth dose data are compared with the data available from the British Journal of Radiology report no. 25. Contribution of contaminated electrons has also been calculated using Monte Carlo simulation by the different parts of the Cobalt-60 head for different field size and SSD's. Moreover, depth dose curve in zero area field size is calculated by extrapolation method and compared with the already published data. They are found in good agreement.

Copper(I) Complexes of N-(2-{[(2E)-2-(4-Nitrobenzylidenyl)Hydrazinyl]Carbonyl}Phenyl)Benzamide and Triphenylphosphine: Synthesis, Characterization and Luminescence Properties.

Copper(I) complexes of the formula [Cu(L)(PPh3)2]X (1-4) (X = Cl(1), ClO4(2), BF4(3) and PF6(4)) [where L = N-(2-{[(2E)-2-(4-nitrobenzylidenyl)hydrazinyl]carbonyl}phenyl)benzamide; PPh3 = triphenylphosphine] have been prepared by the condensation of N-[2-(hydrazinocarbonyl)phenyl]benzamide with 4-nitrobenzaldehyde followed by the reaction with CuCl, [Cu(MeCN)4]ClO4, [Cu(MeCN)4]BF4 and [Cu(MeCN)4]PF6 in presence of triphenylphosphine as a coligand. Complexes 1-4 were then characterized by elemental analyses, FTIR, UV-visible and 1H NMR spectroscopy. Mononuclear copper(I) complexes 1-4 were formed with L in its keto form by involvement of azomethine nitrogen and the carbonyl oxygen along with two PPh3 groups. A single crystal X-ray diffraction study of the representative complex [(Cu(L)(PPh3)2]CIO4 (2) reveals a distorted tetrahedral geometry around Cu(I). Crystal data of (2): space group = C2/c, a = 42.8596 (9) Å, b = 14.6207 (3) Å, c = 36.4643 (7) Å, V = 20,653.7 (7) Å3, Z = 16. Complexes 1-4 exhibit quasireversible redox behaviour corresponding to a Cu(I)/Cu(II) couple. All complexes show blue-green emission as a result of fluorescence from an intra-ligand charge transition (ILCT), ligand to ligand charge transfer transition (LLCT) or mixture of both. Significant increase in size of the counter anion shows marked effect on quantum efficiency and lifetime of the complexes in solution.

Technology for the manufacture of Diabetic Rosogolla.

Diabetic Rosogolla was manufactured by using low-fat cow milk. Six different combinations viz. type of chhana and two different concentrations (40° and 50° Brix) of cooking medium. All of the experimental samples and control were analyzed for physico-chemical, textural, and sensory properties. A 40° Brix concentration of cooking medium was preferred to give a highly acceptable Diabetic Rosogolla. The average composition of Diabetic Rosogolla is moisture-52.20%, fat-4.46%, protein-12.78%, sorbitol-29.66%, and ash-0.89%. Similarly, the rheological properties were hardness-7.85 N, cohesiveness-0.54, springiness-6.06 mm, gumminess-3.8 N, chewiness-26.07 Nmm, fracture force-4.1 N, adhesiveness-0.0272 Nmm, and stiffness-2.17 N/mm. This protocol can be adopted at commercial level and be used to serve the customers who desire fewer calories but cannot resist having the sweets after their meal.

Copper(II) complexes of N-(2-{[(2E)-2-(2-Hydroxy-(5-substituted)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide ligands and heterocyclic coligands.

Some copper(II) complexes of the type [Cu(L1-3)(phen]·CH2Cl2 (1a-3a) and [Cu(L1-3) (bipy)]·CH2Cl2 (1b-3b) (where L1=N-(2-{[(2E)-2-(2-Hydroxy-benzylidene)-hydrazino]carbonyl}phenyl)benzamide, L2=N-(2-{[(2E)-2-(2-Hydroxy-(5-bromo)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide, L3=N-(2-{[(2E)-2-(2-Hydroxy-(5-methoxy)-benzylidene)-hydrazino]carbonyl}phenyl)benzamide; phen=1,10-phenanthroline, bipy=2,2'-bipyridine) have been prepared and characterized on the basis of elemental analyses, IR, UV-Vis and EPR spectral studies. IR spectra indicate that the ligand L1-3 exists in the keto form in the solid state, while at the time of complexation, it tautomerises into enol form. The single crystal X-ray diffraction study of the representative complex [Cu(L1) (phen)]·CH2Cl2 (1a) reveals the distorted square pyramidal geometry around copper(II). Crystal data of (1a): space group=P21/n, a=11.5691(16) Å, b=11.0885(15) Å, c=24.890(4) Å, V=3166.2(8) Å(3), Z=4. The electrochemical behavior of all the complexes indicate that the phen complexes appears at more positive potential as compared to those for bipy complexes, as a consequence of its stronger π acidic character. All the complexes exhibit blue-green emission as a result of the fluorescence from the intra-ligand (π→π(*)) emission excited state.

The morphology of lumbar sympathetic trunk in humans: a cadaveric study.

The vasospastic diseases and chronic pain related to lower limb have been successfully treated by surgical ablation of lumbar sympathetic trunk for last 80 years.Precise knowledge of anatomy of lumbar sympathetic trunk and its adjoining structures is mandatory for safe and uncomplicated lumbar and spinal surgeries.We aim to study the detailed anatomy of entry and exit of lumbar sympathetic trunk, the number, dimensions and location of lumbar ganglia in relation to lumbar vertebra. Thorough dissection was carried out in 30 formalin embalmed cadavers available in the Department of Anatomy, Pravara Institute of Medical Sciences (PIMS), Rural Medical College (RMC), Loni, Maharashtra. A total of 238 ganglia were observed in 60 lumbar sympathetic trunks. The sympathetic trunk traversed dorsal to the crus of diaphragm in 72.6% and in 13.3% it entered dorsal to the medial arcuate ligament. The most common site of the location of lumbar ganglia was in relation to the second lumbar vertebra, sometimes extending up to the L2-L3 vertebral disc. There was a medial shift of sympathetic trunk in lumbar region and it coursed over sacral promontory to reach the pelvic region in 96% of specimens. These variations should be kept in mind in order to prevent hazardous complications like accidental avulsion of first lumbar ganglia and genitofemoral neuritis.

HMGB1 mediates splenomegaly and expansion of splenic CD11b+ Ly-6C(high) inflammatory monocytes in murine sepsis survivors.

BACKGROUND: More than 500,000 hospitalized patients survive severe sepsis annually in the USA. Recent epidemiological evidence, however, demonstrated that these survivors have significant morbidity and mortality, with 3-year fatality rates higher than 70%. To investigate the mechanisms underlying persistent functional impairment in sepsis survivors, here we developed a model to study severe sepsis survivors following cecal ligation and puncture (CLP). METHODS: Sepsis was induced in mice by CLP and survivors were followed for twelve weeks. Spleen and blood were collected and analyzed at different time points post-sepsis. RESULTS: We observed that sepsis survivors developed significant splenomegaly. Analysis of the splenic cellular compartments revealed a major expansion of the inflammatory CD11b+ Ly-6CHigh pool. Serum high-mobility group box 1 (HMGB1) levels in the sepsis surviving mice were significantly elevated for 4-6 weeks after post-sepsis, and administration of an anti-HMGB1 monoclonal antibody significantly attenuated splenomegaly as well as splenocyte priming. Administration of recombinant HMGB1 to naive mice induced similar splenomegaly, leukocytosis and splenocyte priming as observed in sepsis survivors. Interestingly analysis of circulating HMGB1 from sepsis survivors by mass spectroscopy demonstrated a stepwise increase of reduced form of HMGB1 (with known chemo-attractant properties) during the first 3 weeks, followed by disulphide form (with known inflammatory properties) 4-8 weeks after CLP. DISCUSSION: Our results indicate that prolonged elevation of HMGB1 is a necessary and sufficient mediator of splenomegaly and splenocyte expansion, as well as splenocyte inflammatory priming in murine severe sepsis survivors.

Chitinolytic enzymes: an appraisal as a product of commercial potential.

Chitin, its deacetylated form, chitosan and chitinolytic enzymes viz. endo-chitinase, N-acetylglucosaminidase, chitosanase, chitin deacetylase (CDA) are gaining importance for their biotechnological applications. Presently, chitin degrading enzymes constitute high-cost low-volume products in human health care and associated research. Indeed chitinases and CDA-chitosanase complex possesss tremendous potential in agriculture to control plant pathogenic fungi and insects. The success in exploring chitinases especially for agriculture, i.e. as a high-volume low-cost product, depends on the availability of highly active preparations with a reasonable cost. Therefore, a reconsideration in terms of understanding the roles of chitinolytic enzymes in applications, e.g. host-pathogen interaction for biocontrol, different mechanisms of chitin degradation, and identification of new enzymes with varying specificities, may make them more useful in a variety of commercial processes in the near future. The possible issues and challenges encountered in the translation of proof of concept into a commercial product will be appraised in this review.

Multidisciplinary treatment approach with one piece implants for congenitally missing maxillary lateral incisors: a case report.

Congenitally missing lateral incisors are a common clinical occurrence. Dental Implants have become a primary treatment option for replacement of these teeth. Many times in prosthodontic treatment planning a multidisciplinary approach is needed for a comprehensive out come. Prosthodontic treatment planning is needed prior to the patient's consultation and following treatment acceptance; the prosthodontist may need to coordinate treatment needs with other specialists, including an orthodontist and an implant surgeon. This article describes multidisciplinary management of a case presenting with spaced maxillary anteriors due to the congenitally missing lateral incisors. Treatment consisted of initial orthodontic space management to obtain adequate space for missing lateral incisors. Single piece, narrow diameter implants were placed in edentulous spaces on both sides. Aesthetic crown lengthening procedure was performed with all anterior teeth along with tissues surrounding the implants. Metal-ceramic crowns were given as definitive restorations, resulting into an acceptable aesthetic outcome.

Design of 6Mev linear accelerator based pulsed thermal neutron source: FLUKA simulation and experiment.

The 6MeV LINAC based pulsed thermal neutron source has been designed for bulk materials analysis. The design was optimized by varying different parameters of the target and materials for each region using FLUKA code. The optimized design of thermal neutron source gives flux of 3×10(6)ncm(-2)s(-1) with more than 80% of thermal neutrons and neutron to gamma ratio was 1×10(4)ncm(-2)mR(-1). The results of prototype experiment and simulation are found to be in good agreement with each other.

Central venous catheter-related blood stream infection rate in critical care units in a tertiary care, teaching hospital in Mumbai.

Blood stream infections related to central venous catheterization are one of the major device-associated infections reported. Patients admitted in critical care units requiring central venous catheterization and presenting with signs of septicemia during catheterization period were investigated for catheter-related blood stream infections (CRBSI). The CRBSI rate was 9.26 per 1000 catheter days in general with highest rate in neonatal intensive care unit (27.02/1000 days). Site of insertion of catheter and duration of catheterization did not show the influence on the CRBSI rate. Coagulase-negative Staphylococci were the predominant cause. Mortality of 33% was observed in patients with CRBSI. Since central venous catheters are increasingly being used in the critical care, regular surveillance for infection associated them are essential.