"Cervicomastoid Versus Retromandibular Extension of Pre-Auricular Incision in Transmasseteric Anteroparotid Approach for Condylar Fracture Management-a Prospective Study".

Aims: Treating mandibular condylar fractures has always been a matter of debate and controversy. However, there are various approaches, but it is of utmost importance that the surgical procedure must guarantee maximum safety for the facial nerve with best cosmetic outcome and minimizing complications. This prospective study was designed to compare cervicomastoid and retromandibular extension of pre-auricular incision in transmasseteric anteroparotid approach for condylar fractures management. Patients and Methods: The study was conducted in the Department of Oral and Maxillofacial Surgery, Bapuji Dental College and Hospital, Davangere from November 2015 to May 2017, and a total of 16 condylar fractures were surgically accessed for the management and were divided into two groups, cervicomastoid (Group A) and retromandibular extension (Group B) for evaluating parameters such as to assess the access to condylar region, post-operative edema, cosmetic outcome, time taken to access and facial nerve injury. Results: Clinically the time taken was significantly less in the cervicomastoid group even though, there was no statistically significant difference regarding access to the fracture site, post-operative edema, facial nerve injury and cosmetic outcome between two groups. Conclusion: In our opinion the anteroparotid transmasseteric approach is appropriate for surgical management of mandibular condylar fractures as it provides adequate access, ensures safety of the facial nerve and is relatively easy to master. We realize that rather both incisions are good, but cervicomastoid variant is better choice in many aspects one being time taken for the surgery because of better tissue laxity of neck skin when seen in comparison.

Functional Restoration of a Midforearm Level Amputation using the Second Toe Transfer.

Unilateral midforearm level amputation is a severely debilitating situation. The present solution for this problem is either restoration of function using a prosthetic hand, or a vascularized composite allotransplant (VCA) in some very selected cases. In cases of distal forearm level amputations, even vascularized second toe transfer could be done on the radial side of the hand to achieve good functional restoration. We present a case of midforearm level amputation in which the second toe transfer has been done above the level of insertion of pronator teres muscle to achieve meaningful function. This report highlights the fact that a single toe transfer could be helpful in achieving meaningful prehension, even at this proximal.

Synthesis, Antibacterial, and Antioxidant Evaluation of Novel Series of Condensed Thiazoloquinazoline with Pyrido, Pyrano, and Benzol Moieties as Five- and Six-Membered Heterocycle Derivatives.

A novel synthesis of thiazolo[2,3-b]quinazolines 4(a-e), pyrido[2',3':4,5]thiazolo[2,3-b]quinazolines {5(a-e), 6(a-e), and 7(a-e)}, pyrano[2',3':4,5]thiazolo[2,3-b]quinazolines 8(a-e), and benzo[4,5]thiazolo[2,3-b]quinazoloine9(a-e) derivatives starting from 2-(Bis-methylsulfanyl-methylene)-5,5-dimethyl-cyclohexane-1,3-dione 2 as efficient α,α dioxoketen dithioacetal is reported and the synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the synthetic method along with a biological evaluation of these newly synthesized compounds as antioxidants and antibacterial agents against the bacterial strains, like S. aureus, E. coli, and P. aeruginosa. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 µg/mL while the others exhibited better antibacterial activity at 100 µg/mL. The results of this study showed that compound 6(c) possessed remarkable antibacterial activity, whereas compound 9(c) exhibited the highest efficacy as an antioxidant. The structures of the new synthetic compounds were elucidated by elemental analysis, IR, 1H-NMR, and 13C-NMR.

Effect of domperidone, ondansetron, olanzapine-containing antiemetic regimen on QTC interval in patients with malignancy: a prospective, observational, single-group, assessor-blinded study.

Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ2(4) = 15.629, p = 0.004; Bazett, χ2(4) = 15.910, p = 0.003); QTc on Day 1 was more than that during baseline (p < 0.001); these differences were significant in females (Fridericia, χ2(4) = 13.753, p = 0.008; Bazett, χ2 (4) = 13.278, p = 0.010) but not in males (Fridericia, χ2 (4) = 4.419, p = 0.352; Bazett, χ2(4) = 4.280, p = 0.369). Two female patients had an absolute QTc prolongation (Bazett correction) of > 500 ms. However, no clinically significant adverse events occurred. The findings show that QTc prolongation is a concern with olanzapine alone and in combination with domperidone and ondansetron, and needs to be investigated further.

A study of fractional order dual-phase-lag bioheat transfer model.

In this study, we have established a space-time fractional DPL bioheat transfer model in the presence of temperature-dependent metabolic and space-time dependent electromagnetic heat sources. Applying the Legendre wavelet collocation method, the fractional order partial differential equation is reduced into the system of algebraic equations, which has been solved using the Newton iteration method. The error bound as well as stability analysis and numerical scheme validation are provided. The time to achieve for the position of hyperthermia is discussed in three cases: the DPL model, the time-fractional DPL model, and the space-time-fractional DPL model. The effect of variability of time and space fractional derivative orders (α and ß), transmitted power (P) and lagging times on the temperature profile in biological tissue at a different time are discussed in detail. We conclude that a suitable value of α, ß, τT, τq, and P provides a desirable temperature at a particular time in thermal therapies. Such knowledge will be very useful in the clinical therapeutic application.

A study of heat transfer during cryosurgery of lung cancer.

In this study, a mathematical model describing two-dimensional bio-heat transfer during cryosurgery of lung cancer is developed. The lung tissue is cooled by a cryoprobe by imposing its surface at a constant temperature or a constant heat flux or a constant heat transfer coefficient. The freezing starts and the domain is distributed into three stages namely: unfrozen, mushy and frozen regions. In stage I where the only unfrozen region is formed, our problem is an initial-boundary value problem of the hyperbolic partial differential equation. In stage II where mushy and unfrozen regions are formed, our problem is a moving boundary value problem of parabolic partial differential equations and in stage III where frozen, mushy, and unfrozen regions are formed, our problem is a moving boundary value problem of parabolic partial differential equations. The solution consists of the three-step procedure: (i) transformation of problem in non-dimensional form, (ii) by using finite differences, the problem converted into ordinary matrix differential equation and moving boundary problem of ordinary matrix differential equations, (iii) applying Legendre wavelet Galerkin method the problem is transferred into the generalized system of Sylvester equations which are solved by applying Bartels-Stewart algorithm of generalized inverse. The complete analysis is presented in the non-dimensional form. The consequence of the imposition of boundary conditions on moving layer thickness and temperature distribution are studied in detail. The consequence of Stefan number, Kirchoff number and Biot number on moving layer thickness are also studied in specific.

A Correlative Study of N-Cadherin Expression with Different Grades of Oral Squamous Cell Carcinoma Projecting as a Marker of Epithelial to Mesenchymal Transition in Tumor Progression.

Background: Epithelial cells typically express E-cadherin where as N-cadherin expressed by mesenchymal cells. The epithelial to mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT is typical for carcinoma cells during tumor progression and correlate with the local invasiveness and metastatic potential of the tumor. Oral squamous cell carcinoma is a malignant neoplasm arising from the mucosal epithelium of the oral cavity. It can be classified as well; moderate and poor depends on a tumor cells resemblance to its tissue of origin. Materials and Methods: A total of 130 cases of histopathologically diagnosed as OSCC were selected for the study, out of which 66,38 and 26 were well, moderate and poorly differentiated respectively. One section was stained with Haematoxylin and Eosin and the other section for N-cadherin immunohistochemical study. Then the N-cadherin expression was correlated histopathologically with different grades of OSCC. Statistical analysis was carried out mainly by Chi-Square analysis. Results: Among the 66 cases of WDSCC mean value of N-cadherin expression was 1.79, 38 cases of MDSCC mean value of N-cadherin expression was 4.16 and among the 26 cases of PDSCC the mean value was 6.38.That means the value of N- cadherin expression was progressively increasing with decreased differentiation of the tumor cells. The statistical analysis also shown it was highly significant (P<0.001). Conclusion: A correlative study of N-cadherin expression with different grades of OSCC will be useful to predict the state of tumor progression and also it may give accuracy for histopathogical grading of the tumor.

A study of cryosurgery of lung cancer using Modified Legendre wavelet Galerkin method.

In this paper, we have developed a new mathematical model describing bio-heat transfer during cryosurgery of lung cancer. The lung tissue cooled by a flat probe whose temperature decreases linearly with time. The freezing process occurs in three stages and the whole region is divided into solid, mushy and liquid region. The heat released in the mushy region is considered as discontinuous heat generation. The model is an initial-boundary value problem of the hyperbolic partial differential equation in stage 1 and moving boundary value problem of parabolic partial differential equations in stage 2 and 3. The method of the solution consists of four-step procedure as transformation of problem in dimensionless form, the problem of hyperbolic partial differential equation converted into ordinary matrix differential equation and the moving boundary problem of parabolic partial differential equations converted into moving boundary problem of ordinary matrix differential equations by using finite differences in space, transferring the problem into the generalized system of Sylvester equations by using Legendre wavelet Galerkin method and the solution of the generalized system of Sylvester equation are solved by using Bartels-Stewart algorithm of generalized inverse. The whole analysis is presented in dimensionless form. The effect of cryoprobe rate on temperature distribution and the effect of Stefan number on moving layer thickness is discussed in detail.

Monocyte as an Emerging Tool for Targeted Drug Delivery: A Review.

Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocytes can be used as a carrier for delivery of active agents into tissues, where other carriers have no significant access. Targeting monocytes is possible both through passive and active targeting, the former one is simply achieved by enhanced permeation and retention effect while the later one by attachment of ligands on the surface of the lipid-based particulate system. Monocytes have many receptors e.g., mannose, scavenger, integrins, cluster of differentiation 14 (CD14) and cluster of differentiation 36 (CD36). The ligands used against these receptors are peptides, lectins, antibodies, glycolipids, and glycoproteins. This review encloses extensive introduction of monocytes as a suitable carrier system for drug delivery, the design of lipid-based carrier system, possible ways for delivery of therapeutics to monocytes, and the role of monocytes in the treatment of life compromising diseases such as cancer, inflammation, stroke, etc.

Numerical simulation of time fractional dual-phase-lag model of heat transfer within skin tissue during thermal therapy.

In this paper, we investigated the thermal behavior in living biological tissues using time fractional dual-phase-lag bioheat transfer (DPLBHT) model subjected to Dirichelt boundary condition in presence of metabolic and electromagnetic heat sources during thermal therapy. We solved this bioheat transfer model using finite element Legendre wavelet Galerkin method (FELWGM) with help of block pulse function in sense of Caputo fractional order derivative. We compared the obtained results from FELWGM and exact method in a specific case, and found a high accuracy. Results are interpreted in the form of standard and anomalous cases for taking different order of time fractional DPLBHT model. The time to achieve hyperthermia position is discussed in both cases as standard and time fractional order derivative. The success of thermal therapy in the treatment of metastatic cancerous cell depends on time fractional order derivative to precise prediction and control of temperature. The effect of variability of parameters such as time fractional derivative, lagging times, blood perfusion coefficient, metabolic heat source and transmitted power on dimensionless temperature distribution in skin tissue is discussed in detail. The physiological parameters has been estimated, corresponding to the value of fractional order derivative for hyperthermia treatment therapy.

Evaluation of Mandibular Condylar Changes in Patients Following Orthognathic Surgery: A Retrospective Study.

BACKGROUND: Condylar resorption as a cause of relapse after orthognathic surgery is well known. Several authors have presented evidence of the relation between orthognathic surgery and condylar remodeling and resorption. This study was done to appraise the condylar changes along with the form and function following orthognathic surgery, as well as to assess what factors may have contributed to the problems. METHODOLOGY: A diagnosis of progressive condylar resorption (PCR) was made by comparison of preoperative and postoperative radiographs (cephalometric radiograms), as well as clinical evaluations. The radiographs were taken for each patient preoperatively and postoperatively, which include immediately after osteotomy, at 6 months and 24 months. Additional radiographs were taken when required. Then, preoperative and postoperative tracings were compared at 24 months postoperatively. RESULTS AND CONCLUSION: It can be concluded from this study that females of relative low age (<18 years) appeared to be a high-risk factor for the occurrence of condylar alteration including PCR. A steep mandibular plane angle, the low facial height ratio (post/ant), and magnitude of surgery were also significantly related to the occurrence of condylar alteration, but the multivariance regression showed that these parameters had only limited value.

Leukemia-cell proliferation and disease progression in patients with early stage chronic lymphocytic leukemia.

The clinical course of patients with recently diagnosed early stage chronic lymphocytic leukemia (CLL) is highly variable. We examined the relationship between CLL-cell birth rate and treatment-free survival (TFS) in 97 patients with recently diagnosed, Rai stage 0-II CLL in a blinded, prospective study, using in vivo 2H2O labeling. Birth rates ranged from 0.07 to 1.31% new cells per day. With median follow-up of 4.0 years, 33 subjects (34%) required treatment by NCI criteria. High-birth rate was observed in 44% of subjects and was significantly associated with shorter TFS, unmutated IGHV status and expression of ZAP70 and of CD38. In multivariable modeling considering age, gender, Rai stage, expression of ZAP70 or CD38, IGHV mutation status and FISH cytogenetics, only CLL-cell birth rate and IGHV mutation status met criteria for inclusion. Hazard ratios were 3.51 (P=0.002) for high-birth rate and 4.93 (P<0.001) for unmutated IGHV. The association between elevated birth rate and shorter TFS was observed in subjects with either mutated or unmutated IGHVs, and the use of both markers was a better predictor of TFS than either parameter alone. Thus, an increased CLL birth rate in early stage disease is a strong predictor of disease progression and earlier treatment.

Synthesis and biological evaluation of novel isoxazolines linked via piperazine to 2- benzoisothiazoles as potent apoptotic agents.

Synthesis of 3-(4-((3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl)piperazin-1-yl) benzoisothiazole derivatives (5a-i), which constitute a new class of isoxazolines, has been accomplished in regio-selective manner. These derivatives have been prepared by employing the reaction between substituted aldoximes (4a-i) and 3-(4-Allylpiperazin-1-yl) benzoisothiazole in presence of chloramine-T which afforded in good yields. These compounds were screened for cytotoxic activity on tumor cells. Four among the nine synthesized compounds were found to exhibit potent cytotoxic and antineoplastic activities in comparison to tumor necrosis factor-related apoptosis inducing ligand (TRAIL) protein in mammalian cancer cells. The rest of the derivatives showed moderate activity.

A study on thermal damage during hyperthermia treatment based on DPL model for multilayer tissues using finite element Legendre wavelet Galerkin approach.

Hyperthermia is a process that uses heat from the spatial heat source to kill cancerous cells without damaging the surrounding healthy tissues. Efficacy of hyperthermia technique is related to achieve temperature at the infected cells during the treatment process. A mathematical model on heat transfer in multilayer tissues in finite domain is proposed to predict the control temperature profile at hyperthermia position. The treatment technique uses dual-phase-lag model of heat transfer in multilayer tissues with modified Gaussian distribution heat source subjected to the most generalized boundary condition and interface at the adjacent layers. The complete dual-phase-lag model of bioheat transfer is solved using finite element Legendre wavelet Galerkin approach. The present solution has been verified with exact solution in a specific case and provides a good accuracy. The effect of the variability of different parameters such as lagging times, external heat source, metabolic heat source and the most generalized boundary condition on temperature profile in multilayer tissues is analyzed and also discussed the effective approach of hyperthermia treatment. Furthermore, we studied the modified thermal damage model with regeneration of healthy tissues as well. For viewpoint of thermal damage, the least thermal damage has been observed in boundary condition of second kind. The article concludes with a discussion of better opportunities for future clinical application of hyperthermia treatment.

Non-linear dual-phase-lag model for analyzing heat transfer phenomena in living tissues during thermal ablation.

In this article, a non-linear dual-phase-lag (DPL) bio-heat transfer model based on temperature dependent metabolic heat generation rate is derived to analyze the heat transfer phenomena in living tissues during thermal ablation treatment. The numerical solution of the present non-linear problem has been done by finite element Runge-Kutta (4,5) method which combines the essence of Runge-Kutta (4,5) method together with finite difference scheme. Our study demonstrates that at the thermal ablation position temperature predicted by non-linear and linear DPL models show significant differences. A comparison has been made among non-linear DPL, thermal wave and Pennes model and it has been found that non-linear DPL and thermal wave bio-heat model show almost same nature whereas non-linear Pennes model shows significantly different temperature profile at the initial stage of thermal ablation treatment. The effect of Fourier number and Vernotte number (relaxation Fourier number) on temperature profile in presence and absence of externally applied heat source has been studied in detail and it has been observed that the presence of externally applied heat source term highly affects the efficiency of thermal treatment method.

A study on DPL model of heat transfer in bi-layer tissues during MFH treatment.

In this paper, dual-phase-lag bioheat transfer model subjected to Fourier and non-Fourier boundary conditions for bi-layer tissues has been solved using finite element Legendre wavelet Galerkin method (FELWGM) during magnetic fluid hyperthermia. FELWGM localizes small scale variation of solution and fast switching of functional bases. It has been observed that moderate hyperthermia temperature range (41-46°C) can be better achieved in spherical symmetric coordinate system and treatment method will be independent of the Fourier and non-Fourier boundary conditions used. The effect of phase-lag times has been observed only in tumor region. FCC FePt magnetic nano-particle produces more effective treatment with respect to other magnetic nano-particles. The effect of variability of magnetic heat source parameters (magnetic induction, frequency, diameter of magnetic nano-particles, volume fractional of magnetic nano-particles and ligand layer thickness) has been investigated. The physical property of these parameters has been described in detail during magnetic fluid hyperthermia (MFH) treatment and also discussed the clinical application of MFH in Oncology.

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases.

The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a recently identified hereditary cancer syndrome. Germline mutations in this tumor suppressor gene predispose families to the development of various malignancies. The molecular functions of the gene as well as the clinical phenotype of the syndrome are still being clarified. We sought to conduct a comprehensive review of published research into BAP1-TPDS to more thoroughly delineate the clinical implications of germline BAP1 mutations. We also report two additional families with germline BAP1 mutations. Current evidence demonstrates that germline BAP1 mutations predispose families to uveal melanoma, renal cell carcinoma, malignant mesothelioma, cutaneous melanoma, and possibly to a range of other cancers as well. Some of these cancers tend to be more aggressive, have a propensity to metastasize, and onset earlier in life in patients with BAP1 mutations as compared to non-predisposed patients with equivalent cancers. Although further research is necessary, this information can aid in the management, diagnosis, and therapy of these patients and their families, and highlights the importance of genetic counseling.

Cytoplasmic myosin-exposed apoptotic cells appear with caspase-3 activation and enhance CLL cell viability.

The degree of chronic lymphocytic leukemia (CLL) B-cell antigen receptor (BCR) binding to myosin-exposed apoptotic cells (MEACs) correlates with worse patient outcomes, suggesting a link to disease activity. Therefore, we studied MEAC formation and the effects of MEAC binding on CLL cells. In cell line studies, both intrinsic (spontaneous or camptothecin-induced) and extrinsic (FasL- or anti-Fas-induced) apoptosis created a high percent of MEACs over time in a process associated with caspase-3 activation, leading to cytoplasmic myosin cleavage and trafficking to cell membranes. The involvement of common apoptosis pathways suggests that most cells can produce MEACs and indeed CLL cells themselves form MEACs. Consistent with the idea that MEAC formation may be a signal to remove dying cells, we found that natural IgM antibodies bind to MEACs. Functionally, co-culture of MEACs with CLL cells, regardless of immunoglobulin heavy-chain variable region gene mutation status, improved leukemic cell viability. Based on inhibitor studies, this improved viability involved BCR signaling molecules. These results support the hypothesis that stimulation of CLL cells with antigen, such as those on MEACs, promotes CLL cell viability, which in turn could lead to progression to worse disease.

BTK inhibition results in impaired CXCR4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia.

Bruton's tyrosine kinase (BTK) is involved in the regulation of B-cell growth, migration and adhesion. The importance of BTK in cell trafficking is emphasized by the clonal contraction proceeded by lymphocytosis typical for the enzyme inhibitor, ibrutinib, in B-cell malignancies, including chronic lymphocytic leukemia (CLL). Here, we investigated BTK regulation of leukemic B-cell trafficking in a mouse model of aggressive TCL1 CLL-like disease. Inhibiting BTK by ibrutinib reduced surface membrane (sm) levels of CXCR4 but not CXCR5, CD49d and other adhesion/homing receptors. Decreased smCXCR4 levels resulted from blocking receptor signal transduction, which in turn aborted cycling from and to the membrane. This resulted in rapid re-distribution of CLL cells from spleens and lymph nodes into the circulation. CLL cells with impaired smCXCR4 from BTK inhibition failed to home to spleens. These functional changes mainly resulted from inhibition of CXCR4 phosphorylation at Ser339, mediated directly by blocking BTK enzymatic activity and indirectly by affecting the function of downstream targets PLCγ2 and PKCµ, and eventually synthesis of PIM-1 and BTK itself. Our data identify CXCR4 as a key regulator in BTK-mediated CLL-cell retention and have elucidated a complex set of not previously described mechanisms responsible for these effects.