Numerical treatment and global error estimation for thermal electro-osmosis effect on non-Newtonian nanofluid flow with time periodic variations.

The essential purpose of this study is to discuss the impact of time-periodic variations on mixed convection heat transfer for MHD Eyring-Powell nanofluid. The fluid flows through a non-Darcy porous medium over an infinite vertical plate. The effects of viscous dissipation, Ohmic dissipation, electro-osmosis force, heat source, thermal radiation, Dufour feature, and chemical reaction are presumed. The system of partial differential equations which governs the problem is transformed into a system of non-linear algebraic equations and then an explicit finite difference approach is espoused to solve these nonlinear algebraic equations. The numerical results for the velocity, temperature, and nanoparticles concentration distributions are computed and displayed through a set of graphs. Also, the skin friction coefficient, reduced Nusselt number, and Sherwood number are computed numerically for various values of the physical parameters. It is found that the velocity becomes greater with an elevation in the value of the Helmholtz-Smoluchowski velocity. Meanwhile, it enlarges with rising in the value of the electro-osmotic parameter. The rise in the value of the thermal radiation parameter causes a dwindling influence on both temperature and nanoparticles concentration. Investigations of these effects together are very useful due to their important vital applications in various scientific fields, especially in medicine and medical industries, such as endoscopes, respirators, and diverse medical implementations, as nanoparticles can be utilized in the remedy of cancer tumors. Additionally, electroosmotic flow is important due to its ability to control fluid movement and enhance mass transport, making it valuable in various application such as sample separation, drug delivery, and DNA analysis, offering enhanced efficiency and sensitivity.

Computational simulation for MHD peristaltic transport of Jeffrey fluid with density-dependent parameters.

This study aimed to give a new theoretical recommendation for non-dimensional parameters depending on the fluid temperature and concentration. This suggestion came from the fact of fluid density may change with the fluid temperature ([Formula: see text]) and concentration ([Formula: see text]). So, a newly released mathematical form of Jeffrey fluid with peristalsis through the inclined channel is constructed. The problem model defines a mathematical fluid model which converts using non-dimensional values. A sequentially used technique called the Adaptive shooting method for finding the problem solutions. Axial velocity behavior has become a novel concern to Reynolds number. In contradiction to different values of parameters, the temperature and concentration profiles are designated/sketched. The results show that the high value of the Reynolds number acts as a fluid temperature damper, while it boosts the concentration of the fluid particle. The non-constant fluid density recommendation makes the Darcy number controls with a fluid velocity which is virtually significant in drug carries applications or blood circulation systems. To verify the obtained results, a numerical comparison for obtained results has been made with a trustful algorithm with aid of AST using wolfram Mathematica version 13.1.1.

Intravitreous chemotherapy as adjuvant rteatment for vitreous seeding in retinoblastoma: A Philippine tertiary hospital experience

Background@#Intravitreal chemotherapy has been an effective addition in treating vitreous seeding in retinoblastoma. However, it was only in 2020 that it was used in the Philippines. There is no literature on its use in multiple Filipino retinoblastoma patients. @*Objectives@#To describe the clinical course of the four patients who are the first to undergo intravitreal chemotherapy for vitreous seeding of retinoblastoma in the Philippine tertiary hospital.@*Methods@#A case series of four eyes of four patients with retinoblastoma who underwent intravitreous injection of melphalan and topotecan for vitreous seeding at the Department of Ophthalmology and Visual Sciences of a Philippine tertiary hospital. @*Results@#Two eyes, with International Intraocular Retinoblastoma Classification (IIRC) Group C with vitreous seeding, responded well to intravitreous melphalan and topotecan. One eye had recurrent vitreous seeding despite 10 intravitreal injections. One eye with IIRC Group E, did not respond to intravitreous chemotherapy and was eventually enucleated. This is the first case series on the local use of intravitreous chemotherapy in the country for vitreous seeding in retinoblastoma. The control of 50% achieved in this case series is lower than in other series due to longer treatment interval from poor follow-up and the presence of advanced disease.@*Conclusion@#The use of intravitreous melphalan and topotecan can be an effective adjuvant for systemic chemotherapy in controlling vitreous seeding in eyes with IIRC Group C. It is not effective in controlling IIRC Group E disease.

Influence of variable velocity slip condition and activation energy on MHD peristaltic flow of Prandtl nanofluid through a non-uniform channel.

This study is carried out to analyze the problem of mixed convection magnet nanoflow of Prandtl fluid through a non-uniform channel with peristalsis. The external influences of activation energy and non-constant velocity slip are given full consideration. The mentioned fluid is expressed as a governing equations system, and then these equations are converted with non-dimensional parameter values to a system of ordinary differential equations. The converted system of equations is solved in terms of y and then graphs and sketches are offered using the generalized differential transform method. Graphs and results for volume friction as well as velocity profile, concentration, and temperature distributions are obtained. Results show development in the velocity profile of fluid distribution through high values of the non-constant velocity slip effect. The present study is alleged to deliver more opportunities to advance the applications of the drug-carrying system in hypoxic tumor areas with aid of identifying the flow mechanisms.

Prediction of Immunotherapy Response in Melanoma through Combined Modeling of Neoantigen Burden and Immune-Related Resistance Mechanisms.

PURPOSE: While immune checkpoint blockade (ICB) has become a pillar of cancer treatment, biomarkers that consistently predict patient response remain elusive due to the complex mechanisms driving immune response to tumors. We hypothesized that a multi-dimensional approach modeling both tumor and immune-related molecular mechanisms would better predict ICB response than simpler mutation-focused biomarkers, such as tumor mutational burden (TMB). EXPERIMENTAL DESIGN: Tumors from a cohort of patients with late-stage melanoma (n = 51) were profiled using an immune-enhanced exome and transcriptome platform. We demonstrate increasing predictive power with deeper modeling of neoantigens and immune-related resistance mechanisms to ICB. RESULTS: Our neoantigen burden score, which integrates both exome and transcriptome features, more significantly stratified responders and nonresponders (P = 0.016) than TMB alone (P = 0.049). Extension of this model to include immune-related resistance mechanisms affecting the antigen presentation machinery, such as HLA allele-specific LOH, resulted in a composite neoantigen presentation score (NEOPS) that demonstrated further increased association with therapy response (P = 0.002). CONCLUSIONS: NEOPS proved the statistically strongest biomarker compared with all single-gene biomarkers, expression signatures, and TMB biomarkers evaluated in this cohort. Subsequent confirmation of these findings in an independent cohort of patients (n = 110) suggests that NEOPS is a robust, novel biomarker of ICB response in melanoma.

Analysis of Factors That Interrupt With INR Control in the First Anticoagulation Clinic Monitoring Jordanian Patients.

Multiple factors such as vitamin K consumption, drug interactions, herbs interactions, disease states, and alcohol intake affect international normalized ratio (INR) values and thus warfarin dosing. These variables have been described in general and for all patients in the literature. In contrast, the factors that affect INR control in a specific population are rarely studied. Being aware of these factors contributes a lot in maintaining an INR control and avoiding the supratherapeutic or subtherapeutic anticoagulation and the associated risks of hemorrhage or thromboembolism. The aim of this study is to recognize the specific population factors in Jordanian patients that interrupt INR control. Such recognition provides clinical pharmacists managing the anti-coagulation clinic (ACC) with necessary tools and predictors of dose adjustment, nontarget INR handling, and points to add on to the educational session. A total of 2788 patients were referred to the first clinical pharmacists managed ACC at Queen Alia Heart Institute-the only official referral hospital for cardiac patients in Jordan-for education and monitoring between November 1, 2013, and November 1, 2016. We evaluated specific population factors that interrupt INR control using a pretested, structured clinical data collection form. The patients were followed up regularly for achieving target INR (TINR). For patients who were not achieving TINR, the possible cause was examined thoroughly by reviewing the patient's medical file for recent medication intake, comorbidities, and laboratory results. Then the patients or their caregiver were asked direct questions regarding their diet, food supplements, cigarette smoking, shisha smoking, alcohol intake, herbs, and complementary medicine use and compliance, in addition to performing pharmacogenetic testing (polymorphisms of vitamin K-epoxide reductase complex [VKORC1] and cytochrome P450 2C9 [CYP2C9] genes) in special cases. For a total of 2788 patients, 89 488 INR values were included in the study. Of all, 20 365 (22.8%) were non-TINR values, 13 145 (14%) were subtherapeutic, and 7220 (8.1%) were supratherapeutic. All patients included in the study had a non-TINR at least 3 times (n = 65, 2.3%) and as frequent as 50 times (n = 21, 0.8%) during the study period. Non-TINR values ranged from 1 to 11. Serious side effects reported in 7 patients with uncontrolled INR, 6 were bleeding, which required hospitalization (2 upper gastrointestinal [GI] bleeding, 3 nasal bleeding, and 1 eye bleeding), 1 was cerebrovascular accident (CVA thrombolytic). Factors that interrupted INR control in our population, arranged in descending sequence, were concurrent medication use 46.9% (mainly Salicylates and Amiodarone), smoking cigarettes and shisha 17% (represented the most frequent single factor that caused non-TINR in the present study), a nonbalanced dietary vitamin K intake 16.88% caused changes in INR (lower) was related to an increase in the intake of vitamin K-rich food, were noticed to be much more in the spring season in Jordan (end of March and April mainly), herbal supplements 15.02%; Hawthorn (Crataegus, الزعرور) is an herb that lives widely in Jordan, and shockingly we found that it is used very commonly in our ACC patients and corresponded to an elevated INR <8 in 11 patients, and serious bleeding events that required hospitalization in 2 cases), noncompliance 1.49%, comorbid diseases 1%, malabsorption 0.53%, alcohol intake 0.39%, and VKORC1 A/G and CYP2C9 *1*1 genotype 0.15%. The analysis of factors that interrupted with INR control in our patients were both predicted and distinctive; most of these factors were reported previously by other researchers. On the other hand, many of the previously reported factors were not frequently detected in our patients, and the frequency of each of the realized factors was contributed differently to non-TINR in our population. Alarming factors causing non-TINR detected in our study include smoking both cigarettes and shisha, herbal use (Hawthorn and Ginseng), increased intake of vitamin K rich food in the spring season, and concurrent medication use (Salicylates, Amiodarone, Ciprofloxacin, nonsteroidal anti-inflammatory drugs [NSAIDS], Azithromycin, Clarithromycin: although the use of these drugs is mandatory sometimes, it can be replaced by an alternative, eg, antibiotics or monitored closely together with warfarin).

The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with fluorescence activated cell sorting (FACS) and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ATP-binding cassette (ABC) and solute carrier (SLC) transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

How frequently and when do patients undergo cholecystectomy after bariatric surgery?

BACKGROUND: Rapid weight loss after bariatric surgery is associated with gallstone formation, and cholecystectomy is required in up to 15% of patients. Prophylactic cholecystectomy or prophylactic ursodiol administration in the postoperative period have been suggested to address this problem. The objectives of this study were to investigate the frequency and timing of cholecystectomies after bariatric surgery and to determine the associated risk factors in patients who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic adjustable gastric band (LAGB), or laparoscopic sleeve gastrectomy (LSG). METHODS: Data prospectively collected in an institutional database were analyzed. Differences among the 3 procedures and the effects of ursodiol administration, patient demographic characteristics, postoperative weight loss, and individual surgeon practices on cholecystectomy rates were examined. Survival analysis and proportional hazard models were used. RESULTS: Of 1398 patients, 109 (7.8%) underwent cholecystectomy with a median follow-up of 49 (range 12-103) months. Cholecystectomy frequency was 10.6% after LRYGB, significantly higher than 2.9% after LAGB (P < .001), and 3.5% after LSG (P = .004). The frequency was highest within the first 6 months (3.7%), but declined over time to < 1% per year after 3 years. Ursodiol administration did not affect cholecystectomy rates (P = .97), and significant intersurgeon variability was noted. Excess weight loss (EWL)>25% within the first 3 months was the strongest predictor of postoperative cholecystectomy (P<.001). Cox hazards model revealed 1.25 odds ratio per 10% EWL within 3 months, and odds ratio .77 per decade of life. In addition, white patients had 1.45 times higher cholecystectomy rates than did black patients. Preoperative body mass index, gender, and surgeon did not affect cholecystectomy rates. CONCLUSION: Bariatric surgery is associated with a low frequency of postoperative cholecystectomy, which is highest early after surgery and mainly determined by the amount of EWL within the first 3 months. The results of the present study do not support routine prophylactic cholecystectomy at the time of bariatric surgery in asymptomatic patients.

Drosophila as a model for intractable epilepsy: gilgamesh suppresses seizures in para(bss1) heterozygote flies.

Intractable epilepsies, that is, seizure disorders that do not respond to currently available therapies, are difficult, often tragic, neurological disorders. Na(+) channelopathies have been implicated in some intractable epilepsies, including Dravet syndrome (Dravet 1978), but little progress has been forthcoming in therapeutics. Here we examine a Drosophila model for intractable epilepsy, the Na(+) channel gain-of-function mutant para(bss1) that resembles Dravet syndrome in some aspects (parker et al. 2011a). In particular, we identify second-site mutations that interact with para(bss1), seizure enhancers, and seizure suppressors. We describe one seizure-enhancer mutation named charlatan (chn). The chn gene normally encodes an Neuron-Restrictive Silencer Factor/RE1-Silencing Transcription factor transcriptional repressor of neuronal-specific genes. We identify a second-site seizure-suppressor mutation, gilgamesh (gish), that reduces the severity of several seizure-like phenotypes of para(bss1)/+ heterozygotes. The gish gene normally encodes the Drosophila ortholog of casein kinase CK1g3, a member of the CK1 family of serine-threonine kinases. We suggest that CK1g3 is an unexpected but promising new target for seizure therapeutics.