Evaluation Of Gingival Biotype And Recession Following Non-Surgical Periodontal Treatment Using 3-Dimensional Scan Methods.

The study evaluated the position of gingival margins in anterior teeth using clinical and 3-dimensional (3D) optical scanning method among patients subjected to non surgical periodontal treatment (NSPT). A single arm, longitudinal study was undertaken at the Archway Dental Center, University of Manchester, UK. History and clinical examination were done. Gingival recession, attachment loss (AL), and periodontal probing depth (PD) were recorded at baseline and 12-weeks follow-up. NSPT was done using hand and ultrasonic instruments. Impressions were made, the resultant gypsum models were scanned to generate 3D images. The change in the gingival level and thickness of facial gingiva were assessed. Out of eight patientsrecruited, three were lost to follow up. The 3D scan showed a poor correlation with the clinical assessment of gingival recession in anterior teeth following NSPT (r=- 0.0089). Recession did not improve after NSPT (p= 0.20).

A placebo-controlled randomized clinical trial of antibiotics versus probiotics as an adjuvant to nonsurgical periodontal treatment among smokers with Stage III, Grade C generalized periodontitis.

BACKGROUND: Probiotics are viable microorganisms, which if delivered in appropriate dose can provide health benefits. Lactobacillus reuteri (DM17938+ATCC PTA 5289) has been recommended as a safe choice for probiotics. The objective of this study is to compare the improvement in the periodontal parameters amongst smokers with generalized periodontitis with Stage III, Grade C treated with nonsurgical periodontal treatment (NSPT) to which either an antibiotics or probiotics were given as an adjuvant. METHODS: Sixty smokers with Stage III, Grade C generalized periodontitis were randomized in two groups after taking informed consent. Periodontal parameters including bleeding on probing (BOP), probing depth (PD), attachment loss (AL), gingival index (GI), and plaque index (PI) were recorded. Group 1 received (after NSPT and oral hygiene instructions) amoxicillin and metronidazole for 7 days and a placebo for probiotics for 30 days. Group 2 was provided (after NSPT and oral hygiene instructions) with one tablet of Lactobacillus reuteri probiotics (2 × 108 CFU) twice daily for 30 days and placebo antibiotics for 7 days. The periodontal parameters were recorded again at 1- and 3-month follow-ups as outcome variables. Mean, standard deviation, and confidence interval were reported using SPSS 20.0. RESULTS: A statistically significant clinical improvement in the PD, BOP, PI, and GI were observed in both the groups at 3-month follow-up. However, the AL remained unchanged in both the groups. CONCLUSIONS: Administration of probiotics and antibiotics along with NSPT yield statistically significant differences in PD and BOP from baseline to 3-month follow-up. However, between the group differences were not statistically significant for the periodontal parameters (AL, PD, and BOP).

Perceptions of health care workers on maternal and child health services in Pakistan during COVID-19: A cross-sectional study.

Background: Maternal and child healthcare service delivery in vulnerable and fragile health systems has suffered a tremendous impact owing to the shift in focus to curtail the COVID-19 pandemic. We aimed to evaluate the impact of the COVID-19 pandemic on maternal and child healthcare services to inform policy advice for a more resilient maternal and child healthcare service delivery in Pakistan. Methods: A descriptive cross-sectional study was conducted. A structured and validated questionnaire was transformed into an online version and a link was first sent to about 300 healthcare professionals to achieve a sample size of 203, including medical doctors, nurses, and other paramedical staff working in public sector health facilities of the four provinces of Pakistan. The questionnaire was responded to by 195 participants. The Chi-Square test was used to determine the statistical differences between the categorical variables. Results: Although about two-thirds of the participants reported a moderate adherence to protocols and procedures to prevent COVID-19 in their health facilities, the maternal and child health service delivery-related indicators declined during the pandemic. For instance, 66.8% and 62.4% of the participants, respectively, did not agree that a Neonatal Intensive Care Unit and an Intensive Care Unit to admit sick newborns and women with obstetric complications during the COVID-19 pandemic were available during the COVID-19 pandemic. In addition, 23% and 20% of the participants, respectively, reported that staff availability and the provision of cesarean section were moderate to extremely affected. The association between job designation and the impact of COVID-19 was statistically significant (χ2 p = 0.038). Conclusions: The study suggests that maternal and child healthcare services including C-Section, perinatal care, and inpatient care of newborns in Pakistan may have been moderately affected by the COVID-19 pandemic.

Traffic flow forecasting using natural selection based hybrid Bald Eagle Search-Grey Wolf optimization algorithm.

In a fast-moving world, transportation consumes most of the time and resources. Traffic prediction has become a thrust application for machine learning algorithms to overcome the hurdles faced by congestion. Its accuracy determines the selection and existence of machine learning algorithms. The accuracy of such an algorithm is improved better by the proper tuning of the parameters. Support Vector Regression (SVR) is a well-known prediction mechanism. This paper exploits the Hybrid Grey Wolf Optimization-Bald Eagle Search (GWO-BES) algorithm for tuning SVR parameters, wherein the GWO selection methods are of natural selection. SVR-GWO-BES with natural selection has error performance increases by 48% in Mean Absolute Percentage Error and Root Mean Square Error, with the help of Caltrans Performance Measurement System (PeMS) open-source data and Chennai city traffic data for traffic forecasting. It is also shown that the increasing population of search agents increases the performance.

Novel metaheuristic based on multiverse theory for optimization problems in emerging systems.

Finding an optimal solution for emerging cyber physical systems (CPS) for better efficiency and robustness is one of the major issues. Meta-heuristic is emerging as a promising field of study for solving various optimization problems applicable to different CPS systems. In this paper, we propose a new meta-heuristic algorithm based on Multiverse Theory, named MVA, that can solve NP-hard optimization problems such as non-linear and multi-level programming problems as well as applied optimization problems for CPS systems. MVA algorithm inspires the creation of the next population to be very close to the solution of initial population, which mimics the nature of parallel worlds in multiverse theory. Additionally, MVA distributes the solutions in the feasible region similarly to the nature of big bangs. To illustrate the effectiveness of the proposed algorithm, a set of test problems is implemented and measured in terms of feasibility, efficiency of their solutions and the number of iterations taken in finding the optimum solution. Numerical results obtained from extensive simulations have shown that the proposed algorithm outperforms the state-of-the-art approaches while solving the optimization problems with large feasible regions.

Dynamic Performance of Partially Orifice Porous Aerostatic Thrust Bearing.

The aerostatic thrust bearing's performance under vibration brings certain changes in stiffness and stability, especially in the range of 100 to 10,000 Hz, and it is accompanied by significant increase in fluctuations due to the changes in frequency, and the size of the gas film damping. In this research work, an analysis is carried out to evaluate the impact of throttling characteristics of small size orifice on stiffness and stability optimization of aerostatic thrust bearings. There are two types of thrust bearing orifices such as: partial porous multiple orifice and porous thrust bearings and their effects on variations in damping and dynamic stiffness are evaluated. A simulation based analysis is carried out with the help of the perturbation analysis model of an aerostatic thrust bearing simulation by using FLUENT software (CFD). Therefore, two models of aerostatic thrust bearings-one with the porous and other with partial porous orifice are developed-are simulated to evaluate the effects of perturbation frequencies on the damping and dynamic stiffness. The results reveal a decrease in the amplitude of dynamics capacity with an increase in its frequency, as well as a decrease in the damping of partial porous aerostatic thrust bearings with an increase in the number of orifices. It also reveals an increase in the radius of an orifice with an increment of damping of bearing at the same perturbation frequency and, with an increase in orifice height, a corresponding decrease in the damping characteristics of bearings and in the dynamic stiffness and coefficient of damping of bearing film in the frequency range less than 100 Hz.

Development and validation of scale for self evaluation of soft skills in postgraduate dental students.

OBJECTIVE: To develop and validate a soft skills questionnaire, and to use it for self-evaluation by postgraduate dentistry students. METHODS: The cross-sectional descriptive study was conducted at University College of Dentistry, , University of Lahore, Lahore, Pakistan, from February 2020 to April 2020 and comprised of residents from first to final year of training for either Masters in Dental Surgery or Fellowship of the College of Physicians and Surgeons Pakistan programmes. A soft skills questionnaire was generated and was validated through exploratory factor analysis of the elements and items of the questionnaire using SPSS 23. RESULTS: Of the 60 subjects, 37(61.7%) were MDS residents and 23(38.3%) were Fellowship residents. The mean age of the sample was 29.650±2.815 years, and 26(43.3%) subjects were males. The questionnaire was validated (p<0.001). Three domains measured the attitude of dentists, with 7 scenarios having 5 items per scenario. Both categories of trainees had high agreement in understanding and application of non-technical skills, with the exception of leadership skills. However, the difference between the groups was non-significant (p>0.05). CONCLUSIONS: A self-generated questionnaire was successfully validated.

Association of hard and soft tissue factors with gingival recession in orthodontically treated patients: A retrospective study.

INTRODUCTION: Orthodontic treatment is thought as a contributory factor in the development of recession. The objective of this study was to determine the factors associated with a gingival recession in patients who underwent orthodontic mechano-therapy. MATERIAL AND METHODS: A retrospective chart review of 72 post-orthodontic cases done at the dental clinics of Aga Khan University hospital that were treated from 2009 to 2017. After evaluating dental records patients were recruited based on inclusion and exclusion criteria. Patients were divided into two groups based on the presence or absence of gingival recession on posttreatment photographs. Patients in each group were further assessed on the following factors: (1) Lower incisor inclination (IMPA). (2) Tissue thickness on the facio-lingual dimension. (3) Alveolar bone height. (4) Alveolar bone thickness. RESULTS: The mean age of patients at the start of treatment was 16.56±5.66years. Gingival recession was found in 40.3% of our patients while 59.7% of patients had no recession found after orthodontic treatment. Univariable logistic regression was applied for factors associated with a gingival recession following orthodontic treatment which showed that the odds ratio of gingival recession in thin gingival biotype are 14.4 times more than in thick gingival biotype. Multivariable regression analysis showed that the cases had 10.2 times more recession in thin biotype than those in the thick gingival biotype while adjusting for pre- and posttreatment alveolar heights following orthodontic treatment and with a confidence interval [95% CI=2.69 to 38.40]. CONCLUSIONS: It was concluded from this study that 40% of patients developed gingival recession in one or more teeth during orthodontic treatment. Among different factors pre-treatment, gingival biotype of patients and male gender were the factors that were more associated with the development of gingival recession.

COVID-19 Optimizer Algorithm, Modeling and Controlling of Coronavirus Distribution Process.

The emergence of novel COVID-19 is causing an overload on public health sector and a high fatality rate. The key priority is to contain the epidemic and reduce the infection rate. It is imperative to stress on ensuring extreme social distancing of the entire population and hence slowing down the epidemic spread. So, there is a need for an efficient optimizer algorithm that can solve NP-hard in addition to applied optimization problems. This article first proposes a novel COVID-19 optimizer Algorithm (CVA) to cover almost all feasible regions of the optimization problems. We also simulate the coronavirus distribution process in several countries around the globe. Then, we model a coronavirus distribution process as an optimization problem to minimize the number of COVID-19 infected countries and hence slow down the epidemic spread. Furthermore, we propose three scenarios to solve the optimization problem using most effective factors in the distribution process. Simulation results show one of the controlling scenarios outperforms the others. Extensive simulations using several optimization schemes show that the CVA technique performs best with up to 15%, 37%, 53% and 59% increase compared with Volcano Eruption Algorithm (VEA), Gray Wolf Optimizer (GWO), Particle Swarm Optimization (PSO) and Genetic Algorithm (GA), respectively.

Neural minimization methods (NMM) for solving variable order fractional delay differential equations (FDDEs) with simulated annealing (SA).

To enrich any model and its dynamics introduction of delay is useful, that models a precise description of real-life phenomena. Differential equations in which current time derivatives count on the solution and its derivatives at a prior time are known as delay differential equations (DDEs). In this study, we are introducing new techniques for finding the numerical solution of fractional delay differential equations (FDDEs) based on the application of neural minimization (NM) by utilizing Chebyshev simulated annealing neural network (ChSANN) and Legendre simulated annealing neural network (LSANN). The main purpose of using Chebyshev and Legendre polynomials, along with simulated annealing (SA), is to reduce mean square error (MSE) that leads to more accurate numerical approximations. This study provides the application of ChSANN and LSANN for solving DDEs and FDDEs. Proposed schemes can be effortlessly executed by using Mathematica or MATLAB software to get explicit solutions. Computational outcomes are depicted, for various numerical experiments, numerically and graphically with error analysis to demonstrate the accuracy and efficiency of the methods.

Effect of Apical Patency on Postoperative Pain: A Meta-analysis.

INTRODUCTION: This systematic review and meta-analysis assessed the available evidence regarding the effect of apical patency versus nonpatency on postendodontic pain in adult patients. METHODS: The study adhered strictly to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Scopus, MEDLINE via Ovid, Google Scholar, and the Web of Science databases were searched up to April 2018 to retrieve the most relevant studies. Two authors evaluated the studies for eligibility criteria and assessed the risk of bias using the Cochrane tool. The weighted means were calculated using a fixed effects model. When statistically significant (P < .1) heterogeneity was detected, a random effects model was used to assess the significance of treatment effects. RESULTS: Five studies were identified for this systematic review; 4 were included in the meta-analyses. Two studies revealed a low risk of bias, whereas 3 studies revealed a high risk of bias. Because of the significant heterogeneity between studies, a random effects model was used. The meta-analysis showed that the apical patency resulted in less postoperative pain compared with nonpatency, but the difference was not statistically significant. Moreover, no statistically significant difference was found with regard to analgesic consumption. CONCLUSIONS: Considering the limitations of this study, it was concluded that maintaining apical patency during routine endodontic treatment was not associated with an increased incidence of postoperative pain in adult patients.

Standardized programming to reduce the burden of inappropriate therapies in implantable cardioverter defibrillators - Single centre follow up results.

BACKGROUND: Current algorithms and device morphology templates have been proposed in current Implantable Cardioverter-Defibrillators (ICDs) to minimize inappropriate therapies (ITS), but this has not been completely successful. AIM: Assess the impact of a deliberate strategy of using an atrial lead implant with standardized parameters; based on all current ICD discriminators and technologies, on the burden of ITS. METHOD: A retrospective single-centre analysis of 250 patients with either dual chamber (DR) ICDs or biventricular ICDs (CRTDs) over a (41.9 ± 27.3) month period was performed. The incidence of ITS on all ICD and CRTD patients was chronicled after the implementation of standardized programming. RESULTS: 39 events of anti-tachycardial pacing (ATP) and/or shocks were identified in 20 patients (8% incidence rate among patients). The total number of individual therapies was 120, of which 34% were inappropriate ATP, and 36% were inappropriate shocks. 11 patients of the 250 patients received ITS (4.4%). Of the 20 patients, four had ICDs for primary prevention and 16 for a secondary prevention. All the episodes in the primary indication group were inappropriate, while seven patients (43%) of the secondary indication group experienced inappropriate therapies. CONCLUSIONS: The burden of ITS in the population of patients receiving ICDs was 4.4% in the presence of atrial leads. The proposed rationalized programming criteria seems an effective strategy to minimize the burden of inappropriate therapies and will require further validation.

A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle.

P-wave pseudonormalization after iatrogenic coronary sinus isolation.

We report a case of a 58 year old gentleman with prior history of catheter ablation for persistent atrial fibrillation (AF). His baseline ECG showed sinus rhythm with a broad and notched P-wave in lead II and biphasic P-wave (positive/negative) in leads III and aVF previously described as advanced interatrial block. A redo ablation procedure was performed due to AF recurrence. An iatrogenic isolation of the coronary sinus (CS) was observed during ablation with marked narrowing and loss of the terminal negative component of the P-wave on the surface ECG.

Advanced Interatrial Block Predicts New Onset Atrial Fibrillation in Patients with Severe Heart Failure and Cardiac Resynchronization Therapy.

BACKGROUND: Advanced interatrial block (aIAB) on the surface electrocardiogram (ECG), defined as a P-wave duration ≥120 milliseconds with biphasic (±) morphology in inferior leads, is frequently associated with atrial fibrillation (AF). The aim of this study was to determine whether preoperative aIAB could predict new-onset AF in patients with severe congestive heart failure (CHF) requiring cardiac resynchronization therapy (CRT). METHODS: Retrospective analysis of consecutive patients with CHF and no prior history of AF undergoing CRT for standard indications. A baseline 12-lead ECG was obtained prior to device implantation and analyzed for the presence of aIAB. ECGs were scanned at 300 DPI and maximized 8×. Semiautomatic calipers were used to determine P-wave onset and offset. The primary outcome was the occurrence of AF identified through analyses of intracardiac electrograms on routine device follow-up. RESULTS: Ninety-seven patients were included (74.2% male, left atrial diameter 45.5 ± 7.8 mm, 63% ischemic). Mean P-wave duration was 138.5 ± 18.5 milliseconds and 37 patients (38%) presented aIAB at baseline. Over a mean follow-up of 32 ± 18 months, AF was detected in 29 patients (30%) and the incidence was greater in patients with aIAB compared to those without it (62% vs 28%; P < 0.003). aIAB remained a significant predictor of AF occurrence after multivariate analysis (OR 4.1; 95% CI, 1.6-10.7; P < 0.003). CONCLUSION: The presence of aIAB is an independent predictor of new-onset AF in patients with severe CHF undergoing CRT.

An adaptive handover prediction scheme for seamless mobility based wireless networks.

We propose an adaptive handover prediction (AHP) scheme for seamless mobility based wireless networks. That is, the AHP scheme incorporates fuzzy logic with AP prediction process in order to lend cognitive capability to handover decision making. Selection metrics, including received signal strength, mobile node relative direction towards the access points in the vicinity, and access point load, are collected and considered inputs of the fuzzy decision making system in order to select the best preferable AP around WLANs. The obtained handover decision which is based on the calculated quality cost using fuzzy inference system is also based on adaptable coefficients instead of fixed coefficients. In other words, the mean and the standard deviation of the normalized network prediction metrics of fuzzy inference system, which are collected from available WLANs are obtained adaptively. Accordingly, they are applied as statistical information to adjust or adapt the coefficients of membership functions. In addition, we propose an adjustable weight vector concept for input metrics in order to cope with the continuous, unpredictable variation in their membership degrees. Furthermore, handover decisions are performed in each MN independently after knowing RSS, direction toward APs, and AP load. Finally, performance evaluation of the proposed scheme shows its superiority compared with representatives of the prediction approaches.

Advanced mobility handover for mobile IPv6 based wireless networks.

We propose an Advanced Mobility Handover scheme (AMH) in this paper for seamless mobility in MIPv6-based wireless networks. In the proposed scheme, the mobile node utilizes a unique home IPv6 address developed to maintain communication with other corresponding nodes without a care-of-address during the roaming process. The IPv6 address for each MN during the first round of AMH process is uniquely identified by HA using the developed MN-ID field as a global permanent, which is identifying uniquely the IPv6 address of MN. Moreover, a temporary MN-ID is generated by access point each time an MN is associated with a particular AP and temporarily saved in a developed table inside the AP. When employing the AMH scheme, the handover process in the network layer is performed prior to its default time. That is, the mobility handover process in the network layer is tackled by a trigger developed AMH message to the next access point. Thus, a mobile node keeps communicating with the current access point while the network layer handover is executed by the next access point. The mathematical analyses and simulation results show that the proposed scheme performs better as compared with the existing approaches.

PP2A-dependent control of transcriptionally active FOXO3a in CD8(+) central memory lymphocyte survival requires p47(phox).

Forkhead box O3a (FOXO3a) transcription factor is regulated by complex post-translational modifications that allow for transcriptional control of various apoptosis factors including pro-apoptotic Bim. Although it has been shown that kinases phosphorylate FOXO3a in memory T cells, the role of protein phosphatases in the control of memory T lymphocyte FOXO3a function is less clear. Here, we report that FOXO3a is dephosphorylated (activated) by a protein phosphatase 2A (PP2A)-dependent mechanism in CD8(+) memory lymphocytes (Tm) during Listeria monocytogenes (Lm) infection, which allows for enhanced Bim transcription in nicotinamide adenine dinucleotide phosphate-oxidase p47(phox)-deficient (p47(phox-/-)) Tm. Consequently, CD8(+) Tm from Lm-infected p47(phox-/-) mice express significantly higher levels of each pro-apoptotic Bim protein isoform. Furthermore, there was a profound reduction in the accumulation of CD8(+) T central memory (Tcm) cells in infected p47(phox-/-) spleens, and 65% p47(phox-/-) mouse moribundity following secondary Lm reinfection compared with 25% in wild-type mice. Notably, blocking PP2A activity attenuated FOXO3 activation and Bim transcription in p47(phox-/-) CD8(+) memory lymphocytes. Our findings indicate a critical role for p47(phox) in a dynamic interplay between PP2A and FOXO3a that regulates pro-apoptotic Bim transcription in CD8(+) memory lymphocytes during infection.

p47(phox) directs murine macrophage cell fate decisions.

Macrophage differentiation and function are pivotal for cell survival from infection and involve the processing of microenvironmental signals that determine macrophage cell fate decisions to establish appropriate inflammatory balance. NADPH oxidase 2 (Nox2)-deficient chronic granulomatous disease (CGD) mice that lack the gp91(phox) (gp91(phox-/-)) catalytic subunit show high mortality rates compared with wild-type mice when challenged by infection with Listeria monocytogenes (Lm), whereas p47(phox)-deficient (p47(phox-/-)) CGD mice show survival rates that are similar to those of wild-type mice. We demonstrate that such survival results from a skewed macrophage differentiation program in p47(phox-/-) mice that favors the production of higher levels of alternatively activated macrophages (AAMacs) compared with levels of either wild-type or gp91(phox-/-) mice. Furthermore, the adoptive transfer of AAMacs from p47(phox-/-) mice can rescue gp91(phox-/-) mice during primary Lm infection. Key features of the protective function provided by p47(phox-/-) AAMacs against Lm infection are enhanced production of IL-1α and killing of Lm. Molecular analysis of this process indicates that p47(phox-/-) macrophages are hyperresponsive to IL-4 and show higher Stat6 phosphorylation levels and signaling coupled to downstream activation of AAMac transcripts in response to IL-4 stimulation. Notably, restoring p47(phox) protein expression levels reverts the p47(phox)-dependent AAMac phenotype. Our results indicate that p47(phox) is a previously unrecognized regulator for IL-4 signaling pathways that are important for macrophage cell fate choice.

Combinatorial antileukemic disruption of oxidative homeostasis and mitochondrial stability by the redox reactive thalidomide 2-(2,4-difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione (CPS49) and flavopiridol.

2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione (CPS49) is a member of a recently identified class of redox-reactive thalidomide analogs that show selective killing of leukemic cells by increasing intracellular reactive oxygen species (ROS) and targeting multiple transcriptional pathways. Flavopiridol is a semisynthetic flavonoid that inhibits cyclin-dependent kinases and also shows selective lethality against leukemic cells. The purpose of this study is to explore the efficacy and mechanism of action of the combinatorial use of the redox-reactive thalidomide CPS49 and the cyclin-dependent kinase inhibitor flavopiridol as a selective antileukemic therapeutic strategy. In combination, CPS49 and flavopiridol were found to induce selective cytotoxicity associated with mitochondrial dysfunction and elevations of ROS in leukemic cells ranging from additive to synergistic activity at low micromolar concentrations. Highest synergy was observed at the level of ROS generation with a strong correlation between cell-specific cytotoxicity and reciprocal coupling of drug-induced ROS elevation with glutathione depletion. Examination of the transcriptional targeting of CPS49 and flavopiridol combinations reveals that the drugs act in concert to initiate a cell specific transcriptional program that manipulates nuclear factor-kappaB (NF-kappaB), E2F-1, and p73 activity to promote enhanced mitochondrial instability by simultaneously elevating the expression of the proapoptotic factors BAX, BAD, p73, and PUMA while depressing expression of the antiapoptotic genes MCL1, XIAP, BCL-xL, SURVIVIN, and MDM2. The coadministration of CPS49 and flavopiridol acts through coordinate targeting of transcriptional pathways that enforce selective mitochondrial dysfunction and ROS elevation and is therefore a promising new therapeutic combination that warrants further preclinical exploration.