Crown ether decorated silicon photonics for safeguarding against lead poisoning.

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.

Tafasitamab and lenalidomide in large B-cell lymphoma: real-world outcomes in a multicenter retrospective study.

ABSTRACT: In this real-world evaluation of tafasitamab-lenalidomide (TL) in relapsed or refractory LBCL, patients receiving TL had higher rates of comorbidities and high-risk disease characteristics, and substantially lower progression-free survival and overall survival, compared with the L-MIND registration clinical trial for TL.

Inferior Vena Cava Filter Occlusion Causing Phlegmasia Alba Dolens.

Phlegmasia alba dolens is a rare sequela of acute extensive venothrombus of the iliofemoral segments. Rarely, phlegmasia alba dolens can also result from clotted inferior vena cava filter. A 39-year-old with protein S deficiency, and prior inferior vena cava filter placement after remote trauma presented to the emergency department with progressive bilateral lower extremity pain and swelling. Venous duplex revealed extensive bilateral deep vein thromboses from the external iliac veins to popliteal veins, as well as thrombophlebitis of the left great saphenous vein. Venography confirmed patency of the suprarenal vena cava with abrupt occlusion of the infrarenal segment at the level of the inferior vena cava filter. The filter was removed followed by endovascular thrombectomy and adjunctive venoplasty. The patient progressed well and discharged on therapeutic anticoagulation. This case illustrates that a staged endovascular approach may be utilized for acute on chronic caval thrombosis and filter removal.

Saddle Pulmonary Embolus and Simultaneous Common Carotid and Subclavian Artery Emboli.

A patent foramen ovale (PFO) is present in 27-35% of the population. Right to left cardiac shunts predispose patients to arterial emboli in the presence of venous thromboembolisms. Paradoxical embolus should be suspected in patients with deep venous thrombosis (DVT) and arterial emboli. A 45-year-old man with hypercoagulability and history of DVT presented with a week-long history of chest pain, shortness of breath, and left arm numbness. Imaging showed a saddle pulmonary embolus (PE) and emboli involving the aortic arch, left common carotid, and left subclavian artery. The patient proceeded with an endovascular thrombectomy of the pulmonary artery, followed by open thrombectomy. Echocardiogram confirmed a right to left intra-cardiac shunt consistent with a PFO. Paradoxical emboli are rare manifestations of venous thromboemboli in patients with right to left intra-cardiac shunts. Patients should be evaluated for these to help prevent further manifestations.

Examining indirect effects of advertising exposure on young adults' cannabis and nicotine vaping.

OBJECTIVE: To examine longitudinal associations between exposure to two types of advertisements (medical/recreational cannabis and e-cigarette retailers [vape shops]) and young adults' cannabis and nicotine vaping behavior. Positive and negative expectancies for cannabis and vaping nicotine were examined as mediators of these associations. METHOD: Secondary analysis of observational data from a longitudinal cohort of young adults recruited from Southern California (Wave 13: N = 2,411, 56% female, Mage = 23.6). Participants completed web-based surveys annually, reporting on advertising exposure in 2018, expectancies in 2019, and cannabis and nicotine vaping in 2020. Two path models were specified: (a) of past-month cannabis vaping only, nicotine vaping only, and co-use (vs. no vaping) and (b) of single product vaping (vs. co-use). Path analyses modeled direct and indirect associations between variables. RESULTS: Controlling for past-month cannabis and nicotine use and other covariates, there were no significant direct associations of advertising exposure with cannabis and/or nicotine vaping. However, the association between cannabis advertising exposure and vaping (cannabis only) was significantly mediated by positive cannabis expectancies (ß = 0.02, SE = 0.01, p = .03). Among those who vaped cannabis and/or nicotine in the past month at Wave 13, expectancies did not significantly mediate associations between advertising exposure and single product use (vs. co-use). CONCLUSIONS: Although exposure to cannabis advertisements may not be directly associated with young adults' cannabis vaping 2 years later, the effects of advertising exposure may be exerted indirectly by increasing positive beliefs about cannabis. Implications for public health policy are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Age-Stratified Outcomes of Mehta Casting in Idiopathic Early-Onset Scoliosis: A Multicenter Review.

BACKGROUND: This study provides age-stratified outcomes of cast treatment for idiopathic early-onset scoliosis. METHODS: This is a multicenter, retrospective review of patients with idiopathic early-onset scoliosis treated with Mehta casting at 4 tertiary children's hospitals between 2001 and 2016. The inclusion criteria were idiopathic early-onset scoliosis and a minimum follow-up of 2 years after casting ended. The exclusion criteria were <2 casts, >3 casts at an outside facility, and a major curve of <20° pre-treatment. Subjects were grouped by age at first cast: <18 months, 18 to <24 months, 2 to <3 years, 3 to <4 years, and ≥4 years. RESULTS: There were 134 patients with a mean follow-up of 5.2 years (95% confidence interval [CI], 4.8 to 5.5 years) after casting. Prior to treatment, the major curve was not significantly different between the various age groups and was a mean of 50.4° (95% CI, 48.0° to 52.8° [range, 22° to 109°]). Of the <18-month group (n = 59), at the final follow-up at a mean of 7.4 years (95% CI, 6.8 to 8.1 years) of age, 75% had scoliosis of <15°, and 6.8% had undergone a surgical procedure or had a major curve of ≥50°. The results declined in the 18 to <24-month group (n = 30), with a major curve of <15° at the final follow-up at 8.5 years (95% CI, 7.3 to 9.7 years) of age in 33% (p < 0.001), and 17% having undergone a surgical procedure or had a major curve of ≥50°, with results nearly identical in the 2 to <3-year group (n = 21). The results continued to decline with increasing age; 23% of the 3 to <4-year group had a major curve of <15° at the final follow-up, and 31% had undergone a surgical procedure or had scoliosis of ≥50°. Of the ≥4-year group, just 9.1% had scoliosis of <15° (p < 0.0001 compared with the <18-month group), and 64% had undergone a surgical procedure or had scoliosis of ≥50°. CONCLUSIONS: Children who underwent casting prior to 18 months of age were more likely to have a major curve of <15° at a minimum 2-year follow-up after casting. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

A novel cell line panel reveals non-genetic mediators of platinum resistance and phenotypic diversity in high grade serous ovarian cancer.

OBJECTIVES: Resistance to cancer therapy is an enduring challenge and accurate and reliable preclinical models are lacking. We interrogated this unmet need using high grade serous ovarian cancer (HGSC) as a disease model. METHODS: We created five in vitro and two in vivo platinum-resistant HGSC models and characterised the entire cell panel via whole genome sequencing, RNASeq and creation of intraperitoneal models. RESULTS: Mutational signature analysis indicated that platinum-resistant cell lines evolved from a pre-existing ancestral clone but a unifying mutational cause for drug resistance was not identified. However, cisplatin-resistant and carboplatin-resistant cells evolved recurrent changes in gene expression that significantly overlapped with independent samples obtained from multiple patients with relapsed HGSC. Gene Ontology Biological Pathways (GOBP) related to the tumour microenvironment, particularly the extracellular matrix, were repeatedly enriched in cisplatin-resistant cells, carboplatin-resistant cells and also in human resistant/refractory samples. The majority of significantly over-represented GOBP however, evolved uniquely in either cisplatin- or carboplatin-resistant cell lines resulting in diverse intraperitoneal behaviours that reflect different clinical manifestations of relapsed human HGSC. CONCLUSIONS: Our clinically relevant and usable models reveal a key role for non-genetic factors in the evolution of chemotherapy resistance. Biological pathways relevant to the extracellular matrix were repeatedly expressed by resistant cancer cells in multiple settings. This suggests that recurrent gene expression changes provide a fitness advantage during platinum therapy and also that cancer cell-intrinsic mechanisms influence the tumour microenvironment during the evolution of drug resistance. Candidate genes and pathways identified here could reveal therapeutic opportunities in platinum-resistant HGSC.

Factors Affecting Slip Progression After In Situ Screw Fixation of Stable Slipped Capital Femoral Epiphysis.

BACKGROUND: Slip progression after in situ fixation of slipped capital femoral epiphysis (SCFE) has been reported as occurring in up to 20% of patients. We review SCFE treated with in situ single screw fixation performed at 2 hospitals over a 15-year period to determine the factors associated with slip progression. METHODS: This case-control study reviews SCFE treated with in situ single cannulated screw fixation with minimum follow up of 1 year and full closure of the affected physis. Slip progression (failure) was defined as worsening of the Southwick slip angle of 10 or more degrees or revision surgery for symptomatic slip progression. Univariate and multivariate analyses were performed comparing success and failure groups for patient characteristics, screw type and position, and radiographic measurements. RESULTS: Ninety three patients with 108 slips met all criteria, with 15 hips (14%) classified as having slip progression (failure). All failures had 3 threads or fewer across the physis. Five hips had 2 threads across the physis, and 4 of the 5 were classified as failures. Lower modified Oxford bone scores were found in the failure group, though the difference was small (0.9, P=0.013). Failure was also associated with partially threaded screws (P=0.001). Failed hips were associated with lower initial Southwick angles (32.8 degrees) than successful hips (40.4 degrees) (P=0.047). In the stepwise model for multivariate regression, 4 factors were identified as significant, with lower initial number of threads (P<0.0001), mild initial Southwick category (P=0.0050), male sex (P=0.0061), and partially threaded screw type (P=0.0116) predicting failure. CONCLUSION: This study is the largest to date evaluating risk factors for slip progression after SCFE fixation, and the first to consider revision surgery for symptomatic slip progression. For stable SCFE, we demonstrate that 4 threads across the physis with a fully threaded screw of 6.5 mm diameter or greater was sufficient to avoid slip progression. We provide a risk stratification for progression of slip showing that in some cases 3 threads across the physis may be sufficient. LEVEL OF EVIDENCE: Level III-case-control study.

Peer selection and influence for marijuana use in a complete network of first-year college students.

BACKGROUND: Marijuana is the most frequently used illicit drug among college students, and there is a need to understand the social processes that contribute to young adults' marijuana use. Substance use behaviors tend to be more similar (homophilous) among individuals with social ties to one another. However, little is known about whether marijuana use homophily within young adult relationships is due to social selection (seeking out ties with similar marijuana use to one's own) or social influence (adopting similar marijuana use behaviors as one's ties), or both. METHODS: Students (N = 1,489; 54.6% female; Mage = 18.6 years) at one University completed online surveys in their first three semesters of college. Surveys assessed participant characteristics, marijuana use, and ties to up to 10 other students in the whole (sociocentric) network of first-year college students. Stochastic-actor oriented models (SAOMs) were used to analyze the co-evolution of marijuana use and social ties over time. RESULTS: Participants were more likely to select peers with similar past 30-day marijuana use as themselves. Concurrently, students' past 30-day marijuana use became more similar to their peers' use over time. DISCUSSION: Evidence for selection and influence effects were highly significant after controlling for network structure and other covariates indicating these processes may work in tandem to increase marijuana use homophily over the first year of college. This highlights the importance of relationships made early in the first-year of college, as these initial peer ties are likely to reinforce marijuana use behaviors that occur within these relationships.

Inpatient Exergames for Children with Cerebral Palsy following Lower Extremity Orthopedic Surgery: A Feasibility Study.

Objective: Evaluate the feasibility of implementing cycling-based exergames for children with cerebral palsy (CP) following lower extremity orthopedic surgery and explore its impact on pain and well-being.Methods: Ten children with CP were recruited; the first five received physiotherapy (comparison) and next five received fifteen exergame sessions over 3 weeks and physiotherapy (case) (NCT0376907). Feasibility indicators evaluated recruitment, questionnaire and exergame completion. Faces Pain Scale-Revised (FPS-R), PROMIS Pediatric Pain Interference Scale (PPIS), and KIDSCREEN-27 were administered. Wilcoxon signed-rank and effect size (r) tests evaluated within-group differences and between-group differences were assessed using Mann-Whitney U tests.Results: All feasibility indicators were met. Large effects for improved case group pain were identified (FPS-R r = 0.60, PPIS r = 0.58), as well as significant improvement in KIDSCREEN-27 total (U = 0.50, p = .05) and psychological well-being (U = 3.00, p = .01) scores, favoring the case group.Conclusions: Incorporating pediatric exergames is feasible and demonstrates potential for improving pain and well-being.

The budding yeast transition to quiescence.

A subset of Saccharomyces cerevisiae cells in a stationary phase culture achieve a unique quiescent state characterized by increased cell density, stress tolerance, and longevity. Trehalose accumulation is necessary but not sufficient for conferring this state, and it is not recapitulated by abrupt starvation. The fraction of cells that achieve this state varies widely in haploids and diploids and can approach 100%, indicating that both mother and daughter cells can enter quiescence. The transition begins when about half the glucose has been taken up from the medium. The high affinity glucose transporters are turned on, glycogen storage begins, the Rim15 kinase enters the nucleus and the accumulation of cells in G1 is initiated. After the diauxic shift (DS), when glucose is exhausted from the medium, growth promoting genes are repressed by the recruitment of the histone deacetylase Rpd3 by quiescence-specific repressors. The final division that takes place post-DS is highly asymmetrical and G1 arrest is complete after 48 h. The timing of these events can vary considerably, but they are tightly correlated with total biomass of the culture, suggesting that the transition to quiescence is tightly linked to changes in external glucose levels. After 7 days in culture, there are massive morphological changes at the protein and organelle level. There are global changes in histone modification. An extensive array of condensin-dependent, long-range chromatin interactions lead to genome-wide chromatin compaction that is conserved in yeast and human cells. These interactions are required for the global transcriptional repression that occurs in quiescent yeast.

Growth-friendly Spinal Instrumentation in Marfan Syndrome Achieves Sustained Gains in Thoracic Height Amidst High Rates of Implant Failure.

BACKGROUND: There are few reports on the surgical management of early-onset scoliosis (EOS) associated with Marfan syndrome (MFS). Affected patients tend to have more rapid curve progression than those with idiopathic EOS, and their course is further complicated by medical comorbidities. As surgical techniques and implants for growing spines become more widely applied, this study seeks to better delineate the safety and efficacy of growth-friendly spinal instrumentation in treating this population. METHODS: A prospective registry of children treated for EOS was queried for MFS patients treated between 1996 and 2016. Forty-two patients underwent rib-based or spine-based growing instrumentation and were assessed on preoperative, surgical, and postoperative clinical and radiographic parameters including complications and reoperations. Subgroup analysis was performed based on spine-based versus rib-based fixation. RESULTS: Patients underwent their index surgery at a mean age of 5.5 years, when the major coronal curve and kyphosis measured 77 and 50 degrees, respectively. Over half were treated with traditional growing rods. Patients underwent 7.2 total surgical procedures-4.7 lengthening and 1.9 revision surgeries not including conversion to fusion-over a follow-up of 6.5 (±4.1) years. Radiographic correction was greatest at index surgery but maintained over time, with a final thoracic height measuring 23.8 cm. Patients experienced a mean of 2.6 complications over the course of the study period; however, a small group of 6 patients experienced ≥6 complications while over half of patients experienced 0 or 1. Implant failures represented 42% of all complications with infection and pulmonary complications following. CONCLUSIONS: This is the largest report on patients with EOS and MFS. All subtypes of growth-friendly constructs reduced curve progression in this cohort, but complications and reoperations were nearly universal; patients were particularly plagued by implant failure and migration. Further collaborations are needed to enhance understanding of optimal timing and fixation constructs for those with MFS and other connective tissue diseases.

Unusual cause of Fournier's gangrene: colorectal-genitourinary tract fistulae status post brachytherapy.

There are few reports of radiation associated colorectal-genitourinary tract (CRGU) fistulae causing Fournier's gangrene (FG). We describe a case of FG in a patient with possibly two CRGU fistulae in the context of previous high-dose brachytherapy and external beam radiation therapy for prostate cancer. Unfortunately, CRGU fistulae are not well classified as significant risk factors for the development of FG. Our case demonstrates the rationale for maintaining a broad differential in patients presenting with recurrent urinary tract symptoms or necrotising soft tissue infections to include undiagnosed fistulae.

Sub-kHz linewidth, hybrid III-V/silicon wavelength-tunable laser diode operating at the application-rich 1647-1690†nm.

The wavelength region about of 1650 nm enables pervasive applications. Some instances include methane spectroscopy, free-space/fiber communications, LIDAR, gas sensing (i.e. C2H2, C2H4, C3H8), surgery and medical diagnostics. In this work, through the hybrid integration between an III-V optical amplifier and an extended, low-loss wavelength tunable silicon Vernier cavity, we report for the first time, a III-V/silicon hybrid wavelength-tunable laser covering the application-rich wavelength region of 1647-1690 nm. Room-temperature continuous wave operation is achieved with an output power of up to 31.1 mW, corresponding to a maximum side-mode suppression ratio of 46.01 dB. The laser is ultra-coherent, with an estimated linewidth of 0.7 kHz, characterized by integrating a 35 km-long recirculating fiber loop into the delayed self-heterodyne interferometer setup. The laser linewidth is amongst the lowest in hybrid/heterogeneous III-V/silicon lasers.

Application of a Novel Instantized Glycerol Monooleate Ingredient in a Protein-Stabilized Oil-In-Water Emulsion.

Glycerol monooleate (GMO), casein and whey proteins are surfactants that can stabilize emulsion systems. This study investigates the impact of instantized GMO powders on creaming stability and oxidative stability in protein-stabilized emulsions. Model emulsions with bulk GMO, two instantized GMO powders, and two controls (without GMO) were produced by microfluidization. The droplet size, ζ-potential, viscosity, and creaming index of the emulsions were measured, while oxidative stability was evaluated by analysis of volatile compounds during storage (28 days, 45 °C) using gas chromatography mass spectrometry. Emulsions with GMO produced smaller average droplet sizes (180.0 nm) with a narrower distribution (polydispersity index of 0.161) compared to the controls (197.6 nm, 0.194). The emulsion stability of instantized emulsions was as good as bulk GMO, which were both better than controls. Based on the relative abundance of 3-octen-2-one, 2,4-heptadienal isomer 2, and 3,5-octadien-2-one isomer 1, the oxidative stability of the instantized emulsions was not significantly different from controls; however, bulk GMO emulsion showed significantly lower stability than controls. Instantized GMO powders can successfully produce physically stable protein-stabilized emulsions with good oxidative stability in a convenient powdered format.

Polysubstance use among youth experiencing homelessness: The role of trauma, mental health, and social network composition.

BACKGROUND: Substance use is common among youth experiencing homelessness (YEH). However, less is known about the use of multiple substances (polysubstance use), or factors associated with polysubstance use among YEH. The present study sought to identify subgroups of YEH based on their recent polysubstance use behavior, and investigate traumatic experiences, mental health and social network composition as predictors. METHODS: YEH (N = 1,032; Mage = 21.3) from three drop-in centers in Los Angeles completed an in-person survey and social network interview between October 2011 and June 2013. Latent class analysis (LCA) was used to identify subgroups of youth based on nine types of substance use in the past 30 days; latent class logistic regression was used to identify variables associated with class membership. RESULTS: Five polysubstance use classes were identified: heavy alcohol and marijuana (33.6 %), illicit drug use (4.9 %), high all polysubstance use (14.9 %), primarily marijuana (18.1 %), and low use (28.5 %). Relative to the low use class, traumatic experiences were associated with membership in every polysubstance use class. Suicide attempts were associated with membership in the high all class (OR = 9.41). Number of substance-using, homeless network members was associated with membership in the heavy alcohol and marijuana use class (OR = 1.35). Number of non-substance-using network members (homeless [OR = 0.29] and housed [OR = 0.73]) was associated with lower odds of membership in the high all class. CONCLUSIONS: Distinct groups of YEH can be identified by their recent polysubstance use patterns. Traumatic experiences, suicidality, and social network composition are important correlates of polysubstance use among YEH.

Impact of neuroimaging in the pretreatment evaluation of early stage non-small cell lung cancer.

BACKGROUND: There are limited data and conflicting guideline recommendations regarding the role of neuroimaging in the pretreatment evaluation of non-small cell lung cancer (NSCLC). METHODS: We performed a retrospective, pragmatic cohort study of patients with NSCLC diagnosed between January 1 and December 31, 2015. Eligible patients were identified from an institutional tumor registry. We collected all records of pretreatment neuroimaging within 12 weeks of diagnosis, including CT head (CT) and MRI brain (MRI). We abstracted the indication for neuroimaging, presence of central neurologic symptoms and cancer stage (with and without neuroimaging findings) from the tumor registry and the electronic health record. RESULTS: We identified 216 evaluable patients with newly diagnosed NSCLC. 157 of 216 patients (72.7%) underwent neuroimaging as part of initial staging, and 41 (26%) were found to have brain metastases. Of 43 patients with central neurologic symptoms at the time of neuroimaging, 28 (67%) had brain metastasis. In patients without central neurologic symptoms, brain metastases were discovered in 0 of 33 patients with clinical stage I or II, 4 of 36 (11%) with clinical stage III and 9 of 45 (20%) with clinical stage IV disease. CONCLUSIONS: In patients with early stage NSCLC (i.e. clinical stage I and II) without central neurologic symptoms, brain metastases are unlikely. The continued use of neuroimaging in the pretreatment evaluation of clinical stage I patients without central neurologic symptoms is not needed.

Novel, provable algorithms for efficient ensemble-based computational protein design and their application to the redesign of the c-Raf-RBD:KRas protein-protein interface.

The K* algorithm provably approximates partition functions for a set of states (e.g., protein, ligand, and protein-ligand complex) to a user-specified accuracy ε. Often, reaching an ε-approximation for a particular set of partition functions takes a prohibitive amount of time and space. To alleviate some of this cost, we introduce two new algorithms into the osprey suite for protein design: fries, a Fast Removal of Inadequately Energied Sequences, and EWAK*, an Energy Window Approximation to K*. fries pre-processes the sequence space to limit a design to only the most stable, energetically favorable sequence possibilities. EWAK* then takes this pruned sequence space as input and, using a user-specified energy window, calculates K* scores using the lowest energy conformations. We expect fries/EWAK* to be most useful in cases where there are many unstable sequences in the design sequence space and when users are satisfied with enumerating the low-energy ensemble of conformations. In combination, these algorithms provably retain calculational accuracy while limiting the input sequence space and the conformations included in each partition function calculation to only the most energetically favorable, effectively reducing runtime while still enriching for desirable sequences. This combined approach led to significant speed-ups compared to the previous state-of-the-art multi-sequence algorithm, BBK*, while maintaining its efficiency and accuracy, which we show across 40 different protein systems and a total of 2,826 protein design problems. Additionally, as a proof of concept, we used these new algorithms to redesign the protein-protein interface (PPI) of the c-Raf-RBD:KRas complex. The Ras-binding domain of the protein kinase c-Raf (c-Raf-RBD) is the tightest known binder of KRas, a protein implicated in difficult-to-treat cancers. fries/EWAK* accurately retrospectively predicted the effect of 41 different sets of mutations in the PPI of the c-Raf-RBD:KRas complex. Notably, these mutations include mutations whose effect had previously been incorrectly predicted using other computational methods. Next, we used fries/EWAK* for prospective design and discovered a novel point mutation that improves binding of c-Raf-RBD to KRas in its active, GTP-bound state (KRasGTP). We combined this new mutation with two previously reported mutations (which were highly-ranked by osprey) to create a new variant of c-Raf-RBD, c-Raf-RBD(RKY). fries/EWAK* in osprey computationally predicted that this new variant binds even more tightly than the previous best-binding variant, c-Raf-RBD(RK). We measured the binding affinity of c-Raf-RBD(RKY) using a bio-layer interferometry (BLI) assay, and found that this new variant exhibits single-digit nanomolar affinity for KRasGTP, confirming the computational predictions made with fries/EWAK*. This new variant binds roughly five times more tightly than the previous best known binder and roughly 36 times more tightly than the design starting point (wild-type c-Raf-RBD). This study steps through the advancement and development of computational protein design by presenting theory, new algorithms, accurate retrospective designs, new prospective designs, and biochemical validation.

Impaired Delivery of Cholesterol Effluxed From Macrophages to Hepatocytes by Serum From CKD Patients May Underlie Increased Cardiovascular Disease Risk.

INTRODUCTION: Although chronic kidney disease (CKD) is associated with increased risk for coronary artery disease (CAD), the underlying mechanisms are not completely defined. In the present study, we tested the hypothesis that flux of cholesterol from macrophage foam cells to liver is impaired in subjects with CKD. METHODS: Consecutive healthy patients, patients with at least 1 CAD risk factor, patients with established CAD, and patients with CKD stages G3 to G5 (n ≥ 15/group) were recruited prospectively. The ability of total patient serum without any modifications to (i) facilitate efflux of cholesterol from human THP1-macrophage foam cells under physiological conditions (cholesterol efflux capacity [CEC]) and (ii) to deliver this effluxed cholesterol to primary hepatocytes with physiological expression of high-density lipoprotein (HDL) receptor SR-BI (capacity to deliver cholesterol to hepatocytes [CDCH]) was evaluated. RESULTS: Although healthy patients, patients with at least 1 CAD risk factor, and patients with established CAD all showed similar CEC, patients with CKD showed significantly higher CEC. CDCH was significantly lower in all groups compared with the healthy patients; however, when corrected for higher CEC, CDCH in patients with CKD was significantly lower than in patients with CAD. CDCH correlated with age, body mass index, metabolic parameters, inflammatory markers, and kidney function markers (estimated glomerular filtration rate [eGFR], serum creatinine, and serum cystatin C). CONCLUSIONS: These results suggest that aberrations in delivery of cholesterol effluxed from macrophage foam cells to liver for final elimination or the last step of reverse cholesterol transport, may underlie the increased risk of CAD in patients with CKD.

Management of Early-Onset Scoliosis-From Mehta Casts to Magnetically Expandable Rods: State of the Art in 2019.

Early-onset scoliosis (EOS) encompasses a wide variety of challenging to treat spinal deformities occurring in children before 10 years of age. The Classification of Early-Onset Scoliosis (C-EOS) has emerged as a useful classification for both clinical and research purposes, as have similar classifications of surgery and complications in the EOS population. Approaches to both nonsurgical and surgical management of EOS have changed dramatically in recent years. There has been a resurgence of interest in nonsurgical management of EOS following several reports of success with serial Mehta cast treatment. Distraction-based surgical approaches, whether rib- or spine-based, remain the mainstay of surgical treatment. The introduction and widespread adoption of magnetically controlled growing rods (MCGR) has altered the need for repeat surgeries for lengthening in distraction based surgery. However, it remains unclear whether overall complication and unplanned revision surgery rates will be improved over historical traditional growing rods or rib-based distraction. Conversion of growth-friendly instrumentation to a final fusion remains a challenging procedure, with high rates of complications and revision surgeries.