Impact of macronutrients and salinity stress on biomass and biochemical constituents in Monoraphidium braunii to enhance biodiesel production.

Microalgal lipids are precursors to the production of biodiesel, as well as a source of valuable dietary components in the biotechnological industries. So, this study aimed to assess the effects of nutritional (nitrogen, and phosphorus) starvations and salinity stress (NaCl) on the biomass, lipid content, fatty acids profile, and predicted biodiesel properties of green microalga Monoraphidium braunii. The results showed that biomass, biomass productivity, and photosynthetic pigment contents (Chl. a, b, and carotenoids) of M. braunii were markedly decreased by nitrogen and phosphorus depletion and recorded the maximum values in cultures treated with full of N and P concentrations (control, 100%). These parameters were considerably increased at the low salinity level (up to 150 mM NaCl), while an increasing salinity level (up to 250 mM NaCl) reduces the biomass, its productivity, and pigment contents. Nutritional limitations and salt stress (NaCl) resulted in significantly enhanced accumulation of lipid and productivity of M. braunii, which represented more than twofold of the control. Furthermore, these conditions have enhanced the profile of fatty acid and biodiesel quality-related parameters. The current study exposed strategies to improve M. braunii lipid productivity for biodiesel production on a small scale in vitro in terms of fuel quality under low nutrients and salinity stress.

Ras Association Domain Family 1A Gene Promoter Methylation as a Biomarker for Chronic Viral Hepatitis C-related Hepatocellular Carcinoma.

Background One of the most prevalent aberrant epigenetic modifications found in hepatocellular carcinoma (HCC) is abnormal DNA methylation. Our study aimed to evaluate serum Ras association domain family 1A (RASSF1A) gene promoter methylation in patients with chronic viral hepatitis C (HCV)-associated liver cirrhosis with and without HCC as a potential new marker for the early detection of HCC. Methodology The 60 participants who participated in the trial were divided into the following three groups: 20 patients with newly diagnosed primary HCC on top of HCV-related liver cirrhosis, 20 patients with HCV-related liver cirrhosis, and 20 age- and sex-matched healthy individuals as a control group. All participants underwent methylation-specific polymerase chain reaction testing to detect the blood level of the RASSF1A gene's methylated promoter. Results Methylated RASSF1A was found in 30% of patients with liver cirrhosis caused by HCV and in 65% of patients with HCC, but not in any of the controls. It was discovered that the serum methylation RASSF1A had an accuracy of 82.50% and an area under the curve (AUC) of 0.825 for separating HCC patients from healthy controls. With an AUC of 0.675 and an accuracy of 67.50%, it was able to differentiate patients with HCC from those with HCV-related liver cirrhosis. Additionally, there was no statistically significant association between RASSF1A methylation status and HCC mass size (p = 0.449). Conclusions Serum RASSF1A promoter methylation status detection could be useful for detecting HCC early, especially in high-risk individuals such as those with HCV.

Coupling wastewater treatment, biomass, lipids, and biodiesel production of some green microalgae.

This study demonstrates the combination of wastewater treatment and green microalgae cultivation for the low-cost production of lipids as a feedstock for biodiesel production. Three green microalgal species were used: Chlamydomonas reinhardtii, Monoraphidium braunii, and Scenedesmus obliquus. Nutrient, heavy metals and minerals removal, biomass productivity, carbohydrate, protein, proline, lipid, and fatty acids methyl ester (FAMEs) contents besides biodiesel properties were evaluated. The results showed that all algal species were highly efficient and had the potential to reduce nitrate, ammonia, phosphate, sulfate, heavy metals (Zn2+, Cu2+, Mn2+, and Fe2+), calcium, magnesium, sodium, and potassium after 10 days of algal treatment compared to initial concentrations. The removal efficiency of these parameters ranged from 12 to 100%. The growth rates of M. braunii and S. obliquus cultivated in wastewater were significantly decreased compared to the control (synthetic medium). In contrast, C. reinhardtii showed the highest growth rate when cultivated in sewage water. Wastewater could decrease the soluble carbohydrates and protein content in all tested algae and increase the proline content in M. braunii and S. obliquus. In wastewater culture, M. braunii had the highest lipid productivity of 5.26 mg L-1 day-1. The fatty acid profiles of two studied species (C. reinhardtii and M. braunii) revealed their suitability as a feedstock for biodiesel production due to their high content of saturated fatty acids, representing 80.91% and 68.62% of the total fatty acid content, respectively, when cultivated in wastewater. This study indicated that wastewater could be used to modify biomass productivity, lipid productivity, and the quantity of individual fatty acids in some algae that affect biodiesel quality to achieve international biodiesel standards.

Angiographically Occult Subarachnoid Hemorrhage: Yield of Repeat Angiography, Influence of Initial CT Bleed Pattern, and Sources of Diagnostic Error in 242 Consecutive Patients.

BACKGROUND AND PURPOSE: Nearly 20% of patients with spontaneous SAH have no definitive source on initial DSA. The purpose of this study was to investigate the timing and yield of repeat DSA, to clarify the influence of initial CT bleed pattern, and to characterize sources of diagnostic error in this scenario. MATERIALS AND METHODS: We evaluated the yield of repeat DSA and clinical outcomes stratified by hemorrhage pattern on CT in consecutive patients with nontraumatic SAH with negative initial DSA findings at a referral center. Cases in which the culprit lesion was subsequently diagnosed were classified as physiologically occult (ie, undetectable) on the initial DSA, despite adequate technique and interpretation or misdiagnosed due to operator-dependent error. RESULTS: Two hundred forty-two of 1163 (20.8%) patients with spontaneous SAH had negative initial DSA findings between 2009 and 2018. The SAH CT pattern was nonperimesencephalic (41%), perimesencephalic (36%), sulcal (18%), and CT-negative (5%). Repeat DSA in 135/242 patients (55.8%) revealed a source in 10 patients (7.4%): 4 saccular aneurysms, 4 atypical aneurysms, and 2 arteriovenous shunts. The overall yield of repeat DSA was 11.3% with nonperimesencephalic and 2.2% for perimesencephalic patterns. The yield of the second and third DSAs with a nonperimesencephalic pattern was 7.7% and 12%, respectively. Physiologically occult lesions accounted for 6/242 (2.5%) and operator-dependent errors accounted for 7/242 (2.9%) of all angiographically occult lesions on the first DSA. CONCLUSIONS: Atypical aneurysms and small arteriovenous shunts are important causes of SAH negative on angiography. Improving DSAs technique can modestly reduce the need for repeat DSA; however, a small fraction of SAH sources remain occult despite adequate technique. These findings support the practice of repeating DSA in patients with a nonperimesencephalic SAH pattern.

A stem cell journey in ophthalmology: From the bench to the clinic.

Debilitating diseases of the eye represent a large unmet medical need potentially addressable with stem cell-based approaches. Over the past decade, the California Institute for Regenerative Medicine (CIRM) has funded and supported the translation, from early research concepts to human trials, of therapeutic stem cell approaches for dry age-related macular degeneration, retinitis pigmentosa, and limbal stem cell deficiency. This article chronicles CIRM's journey in the ophthalmology field and discusses some key challenges and questions that were addressed along the way as well as questions that remain.

Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software.

BACKGROUND AND PURPOSE: Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast. MATERIALS AND METHODS: We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA ± CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (>6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of <30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (<8 hours before CTP) for a separate imaging study. RESULTS: The recent IV contrast and contrast-naïve cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12-0.96; P = .04). CONCLUSIONS: Patients who received IV iodinated contrast in proximity (<8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naïve patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration.

Interrater Reliability in the Measurement of Flow Characteristics on Color-Coded Quantitative DSA of Brain AVMs.

BACKGROUND AND PURPOSE: Hemodynamic features of brain AVMs may portend increased hemorrhage risk. Previous studies have suggested that MTT is shorter in ruptured AVMs as assessed on quantitative color-coded parametric DSA. This study assesses the interrater reliability of MTT measurements obtained using quantitative color-coded DSA. MATERIALS AND METHODS: Thirty-five color-coded parametric DSA images of 34 brain AVMs were analyzed by 4 neuroradiologists with experience in interventional neuroradiology. Hemodynamic features assessed included MTT of the AVM and TTP of the dominant feeding artery and draining vein. Agreement among the 4 raters was assessed using the intraclass correlation coefficient. RESULTS: The interrater reliability among the 4 raters was poor (intraclass correlation coefficient = 0.218; 95% CI, 0.062-0.414; P value = .002) as it related to MTT assessment. When the analysis was limited to cases in which the raters selected the same image to analyze and selected the same primary feeding artery and the same primary draining vein, interrater reliability improved to fair (intraclass correlation coefficient = 0.564; 95% CI, 0.367-0.717; P < .001). CONCLUSIONS: Interrater reliability in deriving color-coded parametric DSA measurements such as MTT is poor so minor differences among raters may result in a large variance in MTT and TTP results, partly due to the sensitivity and 2D nature of the technique. Reliability can be improved by defining a standard projection, feeding artery, and draining vein for analysis.

Multicenter Postmarket Analysis of the Neuroform Atlas Stent for Stent-Assisted Coil Embolization of Intracranial Aneurysms.

BACKGROUND AND PURPOSE: The Neuroform Atlas is a new microstent to assist coil embolization of intracranial aneurysms that recently gained FDA approval. We present a postmarket multicenter analysis of the Neuroform Atlas stent. MATERIALS AND METHODS: On the basis of retrospective chart review from 11 academic centers, we analyzed patients treated with the Neuroform Atlas after FDA exemption from January 2018 to June 2019. Clinical and radiologic parameters included patient demographics, aneurysm characteristics, stent parameters, complications, and outcomes at discharge and last follow-up. RESULTS: Overall, 128 aneurysms in 128 patients (median age, 62 years) were treated with 138 stents. Risk factors included smoking (59.4%), multiple aneurysms (27.3%), and family history of aneurysms (16.4%). Most patients were treated electively (93.7%), and 8 (6.3%) underwent treatment within 2 weeks of subarachnoid hemorrhage. Previous aneurysm treatment failure was present in 21% of cases. Wide-neck aneurysms (80.5%), small aneurysm size (<7 mm, 76.6%), and bifurcation aneurysm location (basilar apex, 28.9%; anterior communicating artery, 27.3%; and middle cerebral artery bifurcation, 12.5%) were common. A single stent was used in 92.2% of cases, and a single catheter for both stent placement and coiling was used in 59.4% of cases. Technical complications during stent deployment occurred in 4.7% of cases; symptomatic thromboembolic stroke, in 2.3%; and symptomatic hemorrhage, in 0.8%. Favorable Raymond grades (Raymond-Roy occlusion classification) I and II were achieved in 82.9% at discharge and 89.5% at last follow-up. mRS ≤2 was determined in 96.9% of patients at last follow-up. The immediate Raymond-Roy occlusion classification grade correlated with aneurysm location (P < .0001) and rupture status during treatment (P = .03). CONCLUSIONS: This multicenter analysis provides a real-world safety and efficacy profile for the treatment of intracranial aneurysms with the Neuroform Atlas stent.

Challenges of scale-up to dolutegravir-based regimens in sub-Saharan Africa.

OBJECTIVE: Evaluate the potential effectiveness of the implementation of dolutegravir (DTG)-based regimens in patients on failing current antiretroviral treatment (ART) given the high levels of nucleoside reverse transcriptase inhibitor (NRTI) resistance in Togo. DESIGN: Patients on ART attending health facilities for routine follow-up visits and for whom HIV viral load test was performed were consecutively included. METHODS: Protease, reverse transcriptase and integrase fragments were sequenced and analyzed for presence of drug resistance mutations for patients with viral load more than 1000 copies/ml. RESULTS: Among 1681 patients, 320 (19.04%) had viral load more than 1000 copies/ml and 200 were tested for drug resistance mutations. Reverse transcriptase gene was successfully sequenced for 181/200 (90.5%) patients; 140/181 (77.4%) were resistant to NRTIs and non-NRTIs, 4/181 (2.2%) to NRTIs only and 18/181 (9.9%) to non-NRTIs only. Many viral strains accumulated mutations predicting resistance to NRTIs recommended in first and second-line DTG-based ART regimens. ART switch to a DTG-based regimen after viral load testing (viral load >1000 copies/ml) or blind switch without prior viral load testing to a new DTG-based first line, estimated 31% and 47.6% of patients to be potentially on functional DTG monotherapy respectively. CONCLUSION: Overall, our results predict that, at the scale of sub-Saharan Africa a significant proportion of patients could be on functional monotherapy. To achieve the third 90 of UNAIDS objectives, implementation of DTG-based regimens should be accompanied with an accelerated scaling up of access to viral load. Studies designed to quantify the implications of use of suboptimal DTG-based regimens are also needed.

HIRA directly targets the enhancers of selected cardiac transcription factors during in vitro differentiation of mouse embryonic stem cells.

HIRA is a histone chaperone known to modulate gene expression through the deposition of H3.3. Conditional knockout of Hira in embryonic mouse hearts leads to cardiac septal defects. Loss of function mutation in HIRA, together with other chromatin modifiers, was found in patients with congenital heart diseases. However, the effects of HIRA on gene expression at earlier stages of cardiogenic mesoderm differentiation have not yet been studied. Differentiation of mouse embryonic stem cells (mESCs) towards cardiomyocytes mimics some of these early events and is an accepted model of these early stages. We performed RNA-Seq and H3.3-HA ChIP-seq on both WT and Hira-null mESCs and early cardiomyocyte progenitors of both genotypes. Analysis of RNA-seq data showed differential down regulation of cardiovascular development-related genes in Hira-null cardiomyocytes compared to WT cardiomyocytes. We found HIRA-dependent H3.3 deposition at these genes. In particular, we observed that HIRA influenced directly the expression of the transcription factors Gata6, Meis1 and Tbx2, essential for cardiac septation, through H3.3 deposition. We therefore identified new direct targets of HIRA during cardiac differentiation.

CIRM Alpha Stem Cell Clinics: Collaboratively Addressing Regenerative Medicine Challenges.

The California Institute for Regenerative Medicine (CIRM) Alpha Stem Cell Clinic (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA-regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Here, we describe our multi-center experiences addressing current and future challenges.

Spectrophotometric determination of fenoprofen calcium drug in pure and pharmaceutical preparations. Spectroscopic characterization of the charge transfer solid complexes.

Simple, accurate and robust spectrophotometric method was developed for determination of fenoprofen calcium drug (FPC). The proposed method was based on the charge transfer (CT) reaction of FPC drug (as n-electron donor) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 2,4,6-trinitrophenol (picric acid, PA) or 1,2,5,8-tetrahydroxyanthraquinone (Quinalizarin, QZ) (as π-acceptors) to give highly colored charge transfer complexes. Different variables affecting the reaction such as reagent concentration, temperature and time have been carefully optimized to achieve the highest sensitivity. Beer's law was obeyed over the concentration ranges of 2-60, 0.6-90 and 4-30µgmL-1 using DDQ, PA and QZ CT reagents, respectively, with correlation coefficients of 0.9986, 0.9989 and 0.997 and detection limits of 1.78, 0.48 and 2.6µgmL-1 for the CT reagents in the same order. Elucidation of the chemical structure of the solid CT complexes formed via reaction between the drug under study and π-acceptors was done using elemental, thermal analyses, IR, 1H NMR and mass spectrometry. X-ray diffraction was used to estimate the crystallinity of the CT complexes. Their biological activities were screened against different bacterial and fungal organisms. The method was applied successfully with satisfactory results for the determination of FPC drug in fenoprofen capsules. The method was validated with respect to linearity, limit of detection and quantification, inter- and intra-days precision and accuracy. The proposed method gave comparable results with the official method.

Genetic diversity and transmission networks of HIV-1 strains among men having sex with men (MSM) in Lomé, Togo.

Understanding the HIV epidemic in key populations is important. Today only scarce information is available on HIV-1 strains that circulate in men having sex with men (MSM) in sub-Saharan Africa. Here, we studied for the first time the genetic diversity of HIV-1 strains circulating in the MSM population in Lomé, the capital city from Togo. The overall subtype/CRF distribution in pol (protease and/or partial reverse transcriptase (RT)) among the 79 HIV-1 strains from MSM was as follows: CRF02_AG (72%, n=57), subtype G (2.5%, n=2), sub-subtype A3 (1.3%, n=1), and unique recombinant forms (URF) (24%, n=19). Among the 19 URFs four different mosaic structures were observed, annotated as URF1 to URF4. Fifteen sequences (URF1) had the same mosaic structure in pol (G/CRF02_AG) and could represent a new circulating recombinant form (CRF). Phylogenetic analysis of the RT sequences showed that there were several introductions of CRF02_AG strains in the MSM population, however half of the CRF02_AG and all URF1 strains formed a separate, well-supported cluster suggesting one major introduction of CRF02_AG in the MSM population followed by efficient transmission and emergence of a possible new CRF. At least 40% of the strains fell into recent transmission chains involving two to seven MSM. Comparison with >950 HIV-1 sequences from previous studies in Togo showed intermixing of the HIV-1 epidemics between MSM and the general population. Moreover, an HIV-1 strain from a recently HIV-1 infected male patient from Germany, fell within a cluster of HIV-1 strains from MSM from Togo, illustrating recent exchange between MSM from Africa and people from other geographic regions. With growing evidence of the importance of MSM in the dynamic of the HIV epidemic in Africa there is an urgent need for appropriate interventions to limit HIV transmission in this population group.

High Rates of Drug Resistance Among Newly Diagnosed HIV-infected Children in the National Prevention of Mother-to-child Transmission Program in Togo.

BACKGROUND: Prevention of mother-to-child transmission (PMTCT) programs have been largely scaled-up, but data on infant HIV drug resistance from PMTCT programs implemented in resource-limited countries are lacking. METHODS: Remnant dried blood spots from HIV-infected children (aged <18 months) tested through the Togo national early infant diagnosis program during 2012 and 2013 were collected and assessed for HIV drug resistance. Pol-RT (reverse transcriptase) region was amplified, sequenced and analyzed for the presence of drug resistance mutations (DRMs). RESULTS: Overall, 121 of 201 (60.2%) newly diagnosed children had detectable DRMs. Among the 131 of 201 (65.2%) children with reported exposure to maternal and/or infant antiretrovirals (ARVs), DRMs were detected in 99 children (75.6%). Importantly, in 41 of 201 children for whom no exposure to ARVs was reported, DRMs were detected in 11 children (26.8%). For 29 children, no data on ARV exposure were available. For the 121 of 201 children with DRMs, 99 of 121 (81.8%) had only nonnucleoside reverse transcriptase inhibitor DRMs detected but 21 of 121 (17.3%) had both nonnucleoside reverse transcriptase inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) DRMs. Among breast-fed children, drug resistance was more frequent when mothers were on antiretroviral therapy (ART), 61 of 75 (81.3%) versus 14 of 39 (35.9%) when mothers were not on ART (P < 0.001). Nucleoside reverse transcriptase inhibitor resistance was more common when mothers were on ART. CONCLUSIONS: Scale-up and improvement of PMTCT strategies resulted in a global decrease of pediatric HIV infections, but our study shows high rates of drug resistance in infants for whom prevention failed.

High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo.

INTRODUCTION: Antiretroviral treatment (ART) has been scaled up over the last decade but compared to adults, children living with HIV are less likely to receive ART. Moreover, children and adolescents are more vulnerable than adults to virological failure (VF) and emergence of drug resistance. In this study we determined virological outcome in perinatally HIV-1-infected children and adolescents receiving ART in Togo. METHODS: HIV viral load (VL) testing was consecutively proposed to all children and adolescents who were on ART for at least 12 months when attending HIV healthcare services for their routine follow-up visit (June to September 2014). Plasma HIV-1 VL was measured using the m2000 RealTime HIV-1 assay (Abbott Molecular, Des Plaines, IL, USA). Genotypic drug resistance was done for all samples with VL>1000 copies/ml. RESULTS AND DISCUSSION: Among 283 perinatally HIV-1-infected children and adolescents included, 167 (59%) were adolescents and 116 (41%) were children. The median duration on ART was 48 months (interquartile range: 28 to 68 months). For 228 (80.6%), the current ART combination consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine and lamivudine) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine or efavirenz). Only 28 (9.9%) were on a protease inhibitor (PI)-based regimen. VL was below the detection limit (i.e. 40 copies/ml) for 102 (36%), between 40 and 1000 copies/ml for 35 (12.4%) and above 1000 copies/ml for 146 (51.6%). Genotypic drug-resistance testing was successful for 125/146 (85.6%); 110/125 (88.0%) were resistant to both NRTIs and NNRTIs, 1/125 (0.8%) to NRTIs only, 4/125 (3.2%) to NNRTIs only and three harboured viruses resistant to reverse transcriptase and PIs. Overall, 86% (108/125) of children and adolescents experiencing VF and successfully genotyped, corresponding thus to at least 38% of the study population, had either no effective ART or had only a single effective drug in their current ART regimen. CONCLUSIONS: Our study provided important information on virological outcome on lifelong ART in perinatally HIV-1-infected children and adolescents who were still on ART and continued to attend antiretroviral (ARV) clinics for follow-up visits. Actual conditions for scaling up and monitoring lifelong ART in children in resource-limited countries can have dramatic long-term outcomes and illustrate that paediatric ART receives inadequate attention.

Virological outcome among HIV-1 infected patients on first-line antiretroviral treatment in semi-rural HIV clinics in Togo.

BACKGROUND: Access to antiretroviral treatment (ART) in resource-limited countries has increased significantly but scaling-up ART into semi-rural and rural areas is more recent. Information on treatment outcome in such areas is still very limited notably due to additional difficulties to manage ART in these areas. RESULTS: 387 HIV-1 infected adults (≥18 years) were consecutively enrolled when attending healthcare services for their routine medical visit at 12 or 24 months on first-line ART in five HIV care centers (four semi-rural and one rural). Among them, 102 patients were on first-line ART for 12 ± 2 months (M12) and 285 for 24 ± 2 months (M24). Virological failure was observed in 70 (18.1 %) patients ranging from 13.9 to 31.6 % at M12 and from 8.1 to 22.4 % at M24 across the different sites. For 67/70 patients, sequencing was successful and drug resistance mutations were observed in 65 (97 %). The global prevalence of drug resistance in the study population was thus at least 16.8 % (65/387). Moreover, 32 (8.3 %) and 27 (6.9 %) patients were either on a completely ineffective ART regime or with only a single drug active. Several patients accumulated high numbers of mutations and developed also cross-resistance to abacavir, didanosine or the new NNRTI drugs like etravirine and rilpivirine. CONCLUSION: The observations on ART treatment outcome from ART clinics in semi-rural areas are close to previous observations in Lomé, the capital city suggesting that national ART-programme management plays a role in treatment outcome.

Alarming rates of virological failure and drug resistance in patients on long-term antiretroviral treatment in routine HIV clinics in Togo.

Information on efficacy of long-term antiretroviral treatment (ART) exposure in resource-limited countries is still scarce. In 767 patients attending routine HIV centers in Togo and receiving first-line ART for more than four years, 42% had viral load greater than 1000 copies/ml and either were on a completely ineffective ART regime or were with only a single drug active. The actual conditions to ensure lifelong ART in resource-limited countries can have dramatic long-term outcomes.

Computational modeling of flow-altering surgeries in basilar aneurysms.

In cases where surgeons consider different interventional options for flow alterations in the setting of pathological basilar artery hemodynamics, a virtual model demonstrating the flow fields resulting from each of these options can assist in making clinical decisions. In this study, image-based computational fluid dynamics (CFD) models were used to simulate the flow in four basilar artery aneurysms in order to evaluate postoperative hemodynamics that would result from flow-altering interventions. Patient-specific geometries were constructed using MR angiography and velocimetry data. CFD simulations carried out for the preoperative flow conditions were compared to in vivo phase-contrast MRI measurements (4D Flow MRI) acquired prior to the interventions. The models were then modified according to the procedures considered for each patient. Numerical simulations of the flow and virtual contrast transport were carried out in each case in order to assess postoperative flow fields and estimate the likelihood of intra-aneurysmal thrombus deposition following the procedures. Postoperative imaging data, when available, were used to validate computational predictions. In two cases, where the aneurysms involved vital pontine perforator arteries branching from the basilar artery, idealized geometries of these vessels were incorporated into the CFD models. The effect of interventions on the flow through the perforators was evaluated by simulating the transport of contrast in these vessels. The computational results were in close agreement with the MR imaging data. In some cases, CFD simulations could help determine which of the surgical options was likely to reduce the flow into the aneurysm while preserving the flow through the basilar trunk. The study demonstrated that image-based computational modeling can provide guidance to clinicians by indicating possible outcome complications and indicating expected success potential for ameliorating pathological aneurysmal flow, prior to a procedure.