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The aim of this study was to determine the prevalence and characteristics of postoperative pain after endodontic microsurgery and to identify potential predictors for severe pain. One hundred seventy-three patients who underwent endodontic microsurgery at a private practice were included in the study. The patients were asked to fill out a questionnaire to assess their postoperative pain levels for 5 days after surgery. The questionnaires were analyzed to record the changes in pain levels over time. The presence and size of preoperative lesions and bone thickness were determined on preoperative cone-beam computed tomographic scans. Statistical analyses were performed to identify predictors for developing severe pain after surgery. A binary logistic regression model was established to predict the occurrence of severe pain. Severe pain was most prevalent on day 1 (17.3%) and gradually decreased until a small increase on day 5. The average pain level also peaked on day 1 postoperatively and gradually decreased afterward. No significant difference was observed between patients who reported severe pain and those who did not report severe pain regarding tooth position (anterior vs posterior), lesion size, and presence of fenestration. However, sex, age, and bone thickness were all significant predictors of severe postoperative pain, with odds ratios of 2.8, 0.96, and 1.41, respectively. Severe pain was reported only in a small number of patients after endodontic microsurgery. Younger patients, females, and patients with thicker bone covering the apex are significantly more likely to develop severe pain. [ABSTRACT FROM AUTHOR]

Air pollution is a global health challenge, increasing the risk of cardiovascular diseases such as heart disease, stroke, and arrhythmias. Particulate matter (PM), particularly PM2.5 and ultrafine particles (UFP), is a key contributor to the adverse effects of air pollution on cardiovascular health. PM exposure can lead to oxidative stress, inflammation, atherosclerosis, vascular dysfunction, cardiac arrhythmias, and myocardial injury. Reactive oxygen species (ROS) play a key role in mediating these effects. PM exposure can also lead to hypertension, a significant risk factor for cardiovascular disease. The COVID-19 pandemic resulted in a significant reduction of air pollutants, leading to a decline in the incidence of heart attacks and premature deaths caused by cardiovascular diseases. This review highlights the relationship between environmental air quality and cardiovascular health, elucidating the pathways through which air pollutants affect the cardiovascular system. It also emphasizes the need for increased awareness, collective efforts to mitigate the adverse effects of air pollution, and strategic policies for long-term air quality improvement to prevent the devastating effects of air pollution on global cardiovascular health. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about the financial burden experienced by patients receiving radiation therapy. Furthermore, currently, no financial toxicity screening tools have been validated for use in radiation oncology.Methods and Materials: Physician surveys were used to gauge provider understanding of treatment costs and their willingness to adopt the use of financial toxicity screening tools. Post-treatment patient surveys were used to investigate the covariates of treatment-induced financial risk.Results: Of the 210 radiation oncologists who completed our survey, 53% reported being "very concerned" with treatment-related costs negatively affecting their patients, and 80% believed that a financial toxicity screening tool would be useful in practice. An analysis of patient surveys using logistic regression found age and cancer site to be the most important variables associated with financial toxicity. Thirty-four patients (22%) experienced financial toxicity related to treatment. The financial toxicities experienced were loss of job (28%), loss of income (24%), difficulty paying their rent or mortgage (20%), difficulty paying for transportation (15%), and difficulty paying for meals (13%).Conclusions: Financial toxicity is an important measure for patients and providers and is experienced by approximately one quarter of patients. Further studies to improve models to predict financial toxicity and how financial toxicity is related to patient outcomes and quality of life are warranted. [ABSTRACT FROM AUTHOR]

LC–MS/MS methods to measure ribociclib in mouse plasma and Ringer’s solution were successfully developed and validated. Reverse phase chromatography was performed with gradient elution using C18 (100A, 50 × 4.6 mm, 3 μ) and C8-A (50 × 2.0 mm, 5 μ) columns for plasma and Ringer’s samples, respectively. Mouse plasma samples were extracted using solid phase extraction method, whereas no extraction was required for the Ringer’s solution samples. Analytes were detected using positive ion MRM mode. The precursor to product ions (Q1 → Q3) selected for ribociclib and d6-ribociclib were ( m / z ) 435.2 → 252.1 and 441.2 → 252.1, respectively. The linear range of quantification of ribociclib was 62.5–10,000 ng/ml for plasma method and 0.1–100 ng/ml for Ringer’s solution method. The results for the inter-day and intra-day accuracy and precision of quality control samples were within the acceptable range. The lower limit of quantitation (LLOQ) for plasma and Ringer’s samples were 62.5 ng/ml (S/N > 30) and 0.1 ng/ml (S/N > 13), respectively, whereas the limit of detection (LOD) was 6.9 ng/ml (S/N > 7) and 0.05 ng/ml (S/N > 3), respectively. The developed methods were successfully applied to the analysis of ribociclib in mouse plasma and dialysate samples collected during a cerebral microdialysis study of ribociclib in a non-tumor bearing mouse. [ABSTRACT FROM AUTHOR]

Abdominal computed tomography (CT) showed a 1.35-cm proximal superior mesenteric artery (SMA) pseudoaneurysm with hemoperitoneum (Fig 1). Engaging the SMA and using the power injector for visceral angiography at this point is controversial, as the manipulation of the SMA and/or the force of the contrast agent injection may have caused the SMA injury. Graph: Figure 1 Contrast-enhanced abdominal CT of a patient with EDS-IV with an SMA pseudoaneurysm. [Extracted from the article]

Upon initial discovery in late 2019, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, has managed to spread across the planet. A plethora of symptoms affecting multiple organ systems have been described, with the most common being nonspecific upper respiratory symptoms: cough, dyspnea, and wheezing. However, the cardiovascular system is also at risk following COVID-19 infection. Numerous cardiovascular complications have been reported by physicians globally, in particular cardiac tamponade Physicians must hold a high index of suspicion in identifying and treating patients with cardiac tamponade who may have contracted the novel coronavirus. This review will describe the current epidemiology and pathophysiology of SARS-CoV-2 and cardiac tamponade, highlighting their clinical course progression and the implications it may have for the severity of both illnesses. The paper will also review published case reports of cardiac tamponade, clinical presentation, and treatment of this complication, as well as the disease as a whole. [ABSTRACT FROM AUTHOR]

Our institution's multidisciplinary Prevention of Amputation in Veterans Everywhere (PAVE) program allocates veterans with critical limb threatening ischemia (CLTI) to immediate revascularization, conservative care, primary amputation, or palliative limb care according to previously reported criteria. These four groups align with the approaches outlined by the global guidelines for the management of CLTI. In the present study, we have delineated the natural history of the palliative limb care group of patients and quantified the procedural risks and outcomes. Veterans prospectively enrolled into the palliative limb cohort of our PAVE program from January 2005 to January 2020 were analyzed. The primary outcome was mortality. The secondary outcomes included overall and limb-related readmissions, limb loss, and wound healing. The clinical frailty scale (CFS) score was calculated, and the 5-year expected mortality was estimated using the Veterans Affairs Quality Enhancement Research Initiative tool. Regression analysis was performed to establish associations among the following variables: mortality, wound, ischemia, and foot infection (WIfI) score, CFS score, overall admissions, and limb-related admissions. The PAVE program enrolled 1158 limbs during 15 years. Of the 1158 limbs, 157 (13.5%) in 145 patients were allocated to the palliative limb care group. The overall mortality of the group was 88.2% (median interval, 3.5 months; range, 0-91 months). Of the 128 patients who had died, 64 (50%) had died within 3 months of enrollment. The predicted 5-year mortality for the group was 66%. The average CFS score for the group was 6.2, denoting persons moderately to severely frail. Using the CFS score, 106 patients were considered frail and 39 were considered not frail. No differences were found in mortality between the frail and nonfrail patients. However, a statistically significant difference was found in early (<3 months) mortality (56.2% vs 37.5%; P =.032). The 30-day limb-related readmission rate was 4.7%. Eventual major amputation was necessary for 18 limbs (11.5%). Wound healing occurred in 30 patients (20.6%). Regression analysis demonstrated no association between the CFS score and mortality (r = 0.55; P =.159) or between the WIfI score and mortality (r = 0.0165; P =.98). However, a significant association was found between the WIfI score and limb-related admissions (r = 0.97; P <.001). Frail patients with CLTI had high early mortality and a low risk of limb-related complications. They also had a low incidence of deferred primary amputation or limb-related readmissions. In our cohort, the vast majority of patients had died within a few months of enrollment without requiring an amputation. A comprehensive approach to the treatment of CLTI patients should include a palliative limb care option because a significant proportion of these patients will have limited survival and can potentially avoid unnecessary surgery and major amputation. [ABSTRACT FROM AUTHOR]

Background: Abnormal function in reward circuitry in cocaine addiction could predate drug use as a risk factor, follow drug use as a consequence of substance-induced alterations, or both. Methods: We used a functional magnetic resonance imaging monetary incentive delay task (MIDT) to investigate reward-loss neural response differences among 42 current cocaine users, 35 former cocaine users, and 47 healthy subjects who also completed psychological measures and tasks related to impulsivity and reward. Results: We found various reward processing-related group differences in several MIDT phases. Across task phases we found a control > current user > former user activation pattern, except for loss outcome, where former compared with current cocaine users activated ventral tegmental area more robustly. We also found regional prefrontal activation differences during loss anticipation between cocaine-using groups. Both groups of cocaine users scored higher than control subjects on impulsivity, compulsivity and reward-punishment sensitivity factors. In addition, impulsivity-related factors correlated positively with activation in amygdala and negatively with anterior cingulate activation during loss anticipation. Conclusions: Compared with healthy subjects, both former and current users displayed abnormal brain activation patterns during MIDT performance. Both cocaine groups differed similarly from healthy subjects, but differences between former and current users were localized to the ventral tegmental area during loss outcome and to prefrontal regions during loss anticipation, suggesting that long-term cocaine abstinence does not normalize most reward circuit abnormalities. Elevated impulsivity-related factors that relate to loss processing in current and former users suggest that these tendencies and relationships may pre-exist cocaine addiction. [Copyright &y& Elsevier]

Abstract: Adipose tissue is now well established as an endocrine organ and multiple hormones termed ‘adipokines’ are released from it. With the rapidly increasing obese population and the increased risk mortality from prostate cancer within the obese population we looked to investigate the role of the adipokine visfatin in LNCaP and PC3 prostate cancer cell lines. Using immunohistochemistry and immunocytochemistry we demonstrate visfatin expression in LNCaP (androgen-sensitive) and PC3 (androgen-insensitive) human prostate cancer cell lines as well as human prostate cancer tissue. Additionally, we show that visfatin increases PC3 cell proliferation and demonstrate the activation of the MAPKs ERK-1/2 and p38. Moreover we also demonstrate that visfatin promotes the expression and activity of MMP-2/9 which are important proteases involved in the breakdown of the extracellular matrix, suggesting a possible role for visfatin in prostate cancer metastases. These data suggest a contributory and multifunctional role for visfatin in prostate cancer progression, with particular relevance and emphasis in an obese population. [Copyright &y& Elsevier]

Abstract: Introduction: There is wide variability in the responses of individual patients to aspirin and clopidogrel. Polymorphisms of several platelet receptors have been related to increased platelet aggregation. We therefore aimed to evaluate whether these polymorphisms are related to altered response to aspirin or clopidogrel. Materials and methods: Patients (n =120) undergoing percutaneous coronary intervention who received aspirin for ≥1week but not clopidogrel were included. Blood samples were drawn at baseline and 20–24h after a 300-mg clopidogrel dose. Aspirin insensitivity was defined as 5μM ADP-induced aggregation ≥70% and 0.5mg/mL arachidonic acid-induced aggregation ≥20%. Clopidogrel insensitivity was defined as baseline minus post-treatment aggregation ≤10% in response to 5 and 20μM ADP. PlA polymorphism of glycoprotein IIIa, T744C polymorphism of the P2Y12 gene and the 1622A>G polymorphism of the P2Y1 gene were genotyped by polymerase chain reaction. Results: There were no differences in polymorphism frequencies between drug-insensitive vs. drug-sensitive patients. There were also no significant differences in response to aspirin (assessed by arachidonic acid-induced aggregation) or to clopidogrel (assessed by ADP-induced aggregation or activation markers) when patients were grouped according to genotype. The only trend observed was lower reduction in PAC-1 binding following clopidogrel in PlA2 carriers (P =0.065). Conclusions: We did not find an association between polymorphisms in the platelet receptors GP IIIa, P2Y12 or P2Y1 and response to aspirin or clopidogrel in cardiac patients. These findings suggest that the variability in response to anti-platelet drugs is multi-factorial and is not caused only by single gene mutations. [Copyright &y& Elsevier]

The hydrolysis of triglyceride (TG) stored in the lipid droplets of the insect fat body is under hormonal regulation by the adipokinetic hormone (AKH), which triggers a rapid activation cAMP-dependent kinase cascade (protein kinase A (PKA)). The role of phosphorylation on two components of the lipolytic process, the TG-lipase and the lipid droplet, was investigated in fat body adipocytes. The activity of purified TG-lipase determined using in vivo TG-radiolabeled lipid droplets was unaffected by the phosphorylation of the lipase. However, the activity of purified lipase was 2.4-fold higher against lipid droplets isolated from hormone-stimulated fat bodies than against lipid droplets isolated from unstimulated tissue. In vivo stimulation of lipolysis promotes a rapid phosphorylation of a lipid droplet protein with an apparent mass of 42-44 kDa. This protein was identified as ‘Lipid Storage Droplet Protein 1’ (Lsdp1). In vivo phosphorylation of this protein reached a peak ∼10 min after the injection of AKH. Supporting a role of Lsdp1 in lipolysis, maximum TG-lipase activity was also observed with lipid droplets isolated 10 min after hormonal stimulation. The activation of lipolysis was reconstituted in vitro using purified insect PKA and TG-lipase and lipid droplets. In vitro phosphorylation of lipid droplets catalyzed by PKA enhanced the phosphorylation of Lsdp1 and the lipolytic rate of the lipase, demonstrating a prominent role PKA and protein phosphorylation on the activation of the lipid droplets. AKH-induced changes in the properties of the substrate do not promote a tight association of the lipase with the lipid droplets. It is concluded that the lipolysis in fat body adipocytes is controlled by the activation of the lipid droplet. This activation is achieved by PKA-mediated phosphorylation of the lipid droplet. Lsdp1 is the main target of PKA, suggesting that this protein is a major player in the activation of lipolysis in insects. [ABSTRACT FROM AUTHOR]

Background: Improvements in angiographic imaging systems technology provide options to decrease radiation exposure. The effect of these variations on image resolution is unknown.Methods: Using an American National Standards Institution phantom, a high-contrast (line-pair) and low contrast (Gammex 151) phantoms, 5 second images were acquired using a Phillips Allure angiographic suite, using fluoroscopic capture (FC) as well as cineangiography (CA) in posterior anterior (PA) and left anterior oblique (LAO) projections as well as high and low table positions. Image resolutions were measured as ranked by three independent trained observers blinded to the purpose of the assessments. Comparative analyses were performed. Interobserver agreement was evaluated.Results: High contrast image resolution was significantly lower with FC compared to CA (median [interquartile range], 1.69 [1.52-1.69] mm, vs 2.09 [1.88-2.09] mm, P < 0.001). No significant differences were observed in between PA and LAO projections as well as low and high table positions. Low contrast resolution was also lower with FC compared to CA (5 [6.5-5] vs 3 [5-3] mm, P < 0.001). No significant differences in high-contrast or low-contrast resolution were noted between PA and LAO projections, or high and low table positions. Both low and high-contrast image resolution improved with higher radiation exposure. Good interobserver agreement was noted (Fleiss-Kappa ranging from 0.69-0.74).Conclusion: Image resolution was perceived to be better with CA compared to FC, although not significantly affected by beam angulation or table height. Aligning resolution needs with imaging modality and maximizing table height may improve procedural efficacy and safety. [ABSTRACT FROM AUTHOR]

To identify potential barriers to care, this study examined the general psychiatry outpatient new appointment availability in the US, including in-person and telepsychiatry appointments, comparing results between insurance types (Medicaid vs. private insurance), states, and urbanization levels. This mystery shopper study investigated 5 US states selected according to Mental Health America Adult Ranking and geography to represent the US mental health care system. Clinics across five selected states were stratified sampled by county urbanization levels. Calls were made during 05/2022–07/2022. Collected data included contact information accuracy, appointment availability, wait time (days), and related information. Altogether, 948 psychiatrists were sampled in New York, California, North Dakota, Virginia, and Wyoming. Overall contact information accuracy averaged 85.3%. Altogether, 18.5% of psychiatrists were available to see new patients with a significantly longer wait time for in-person than telepsychiatry appointments (median = 67.0 days vs median = 43.0 days, p < 0.01). The most frequent reason for unavailability was provider not taking new patients (53.9%). Mental health resources were unevenly distributed, favoring urban areas. Psychiatric care has been severely restricted in the US with low accessibility and long wait times. Transitioning to telepsychiatry represents a potential solution for rural disparities in access. • <20% of psychiatrists were available to see new patients. • Median wait times for in-person and telepsychiatry appointments were 67 days and 43 days. • Fewer local mental health resources were available in rural areas compared to urban areas. • Psychiatric care has been restricted in the US with low accessibility and long wait times. • Barriers to timely psychiatric care need to be identified and addressed. [ABSTRACT FROM AUTHOR]

l -ribose and d -tagatose are biochemically synthesized using sugar isomerases. The l -arabinose isomerase gene from Shigella flexneri (Sf-AI) was cloned and expressed in Escherichia coli BL-21. Sf-AI was applied for the bioproduction of d -tagatose from d -galactose. l -ribose synthesis was performed by two step isomerization using Sf-AI and d -lyxose/ribose isomerase from Cohnella laevoribosii . The overall 22.3% and 25% conversion rate were observed for d -tagatose and l -ribose production from d -galactose and l -arabinose respectively. In the present manuscript, synthesis of rare sugars from naturally available sugars is discussed along with the biochemical characterization of Sf-AI and its efficiency. [ABSTRACT FROM AUTHOR]

Abstract: Fatty acids stored as triglycerides (TG) in the fat body serve as precursor in multiple processes including energy production and synthesis of cellular components. Mobilization of fatty acids from TG depends on the action of lipases. The fat body triglyceride lipase from Manduca sexta, MsTGL, is the only insect lipase that has been purified and characterized, so far. A TGL cDNA from M. sexta fat body encoding a 649 amino acid protein was cloned and its identity confirmed by mass spectrometry and Edman sequencing data of the purified protein. The protein sequence has conserved domains and residues of potential importance for the function and regulation of TGL activity. The expression of TGL and the lipase activity of fat body homogenates were studied in several developmental stages of M. sexta. TG-hydrolase activity of fat body increased as larva grew to the last instar and, then, decreased to minimal levels during pupa stage. Lipase activity was progressively restored in adult insects and reached maximum values at this stage. The fat body lipase activity from adult insects, 1–2 day after emergence, was 9-fold higher than that from 2 to 3 days old 5th-instar larvae. A good correlation was found between the abundance of TGL protein and the lipase activity of fat body homogenates. This correlation and the expression pattern of TGL throughout development are consistent with the notion that TGL is the main fat body TG lipase of M. sexta. [Copyright &y& Elsevier]

The nuclear envelope (NE) LINC complex, in mammals comprised of SUN domain and nespnn proteins, provides a direct connection between the nuclear lamina and the cytoskeleton, which contributes to nuclear positioning and cellular rigidity. SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2, and it remains unclear how SUN1 is anchored. Here, we identify emerin and short nesprin-2 isoforms as novel nucleoplasmic binding partners of SUN1/2. These have overlapping binding sites distinct from the lamin A binding site. However, we demonstrate that tight association of SUN! with the nuclear lamina depends upon a short motif within residues 209 -228, a region that does not interact significantly with known SUN! binding partners. Moreover, SUN! localizes correctly in cells lacking emerin. Importantly then, the major determinant of SUN1 NE localization has yet to be identified. We further find that a subset of lamin A mutations, associated with laminopathies Emery-Dreifuss muscular dystrophy (EDMD) and Hutchinson-Gilford progeria syndrome (HGPS), disrupt lamin A interaction with SUN1 and SUN2. Despite this, NE localization of SUN1 and SUN2 is not impaired in cell lines from either class of patients. Intriguingly, SUN2 expression at the NE is instead enhanced in a significant proportion of HGPS but not EDMD cells and strongly correlates with pre-lamin A accumulation due to preferential interaction of SUN1 with pre-lamin A. We propose that these different perturbations in lamin A-SUN protein interactions may underlie the opposing effects of EDMD and HGPS mutations on nuclear and cellular mechanics. [ABSTRACT FROM AUTHOR]

Background: Duplex Doppler ultrasonography (USG) remains the gold standard for evaluation of radial artery occlusion (RAO) after transradial access (TRA). The diagnostic accuracy of digital plethysmography, which is cheaper and widely available, for evaluation of RAO after TRA is not known.Methods: Patients undergoing TRA were prospectively studied. After undergoing TRA for diagnostic or interventional coronary procedure and obtaining radial artery hemostasis, the radial artery was evaluated for presence or absence of RAO using digital plethysmography of the ipsilateral index finger and the thumb using modified reverse Barbeau's test (MRBT) and USG. Sensitivity, specificity, predictive values, likelihood ratios and other metrics of evaluation of diagnostic performance of MRBT in reference to USG, the current gold standard, were evaluated.Results: 503 patients who underwent TRA for coronary procedures were studied. MRBT demonstrated a sensitivity = 96.2%, specificity = 99.8%, positive predictive value = 96.1, negative predictive value = 99.8, likelihood ratio (+) = 481, likelihood ratio (-) = 0.38, diagnostic accuracy = 99.6, diagnostic odds ratio = 11,904, Youden's index = 0.96, receiver operator characteristic derived c-statistic = 0.98 and Cohen's k = 0.98 when compared to USG. MRBT performed using the ipsilateral index finger and the thumb was no different. Agreement between absence of ipsilateral radial artery pulsation and RAO was weak (Cohen's k = 0.69).Conclusions: MRBT using ipsilateral digital plethysmography performs comparably to USG for assessment of presence of RAO after TRA. There is no significant difference between MRBT performed using the ipsilateral thumb or the index finger. [ABSTRACT FROM AUTHOR]

Objectives: Evaluation of plethysmography as a reliable triage tool to access collateral circulation in the hand prior to transradial access.Background: Hand plethysmographic testing has been used for access site triage prior to cardiac catheterization despite a lack of data supporting its result's stability.Methods: Cohort of consecutive outpatients presenting for evaluation prior to cardiac catheterization underwent hand plethysmographic testing at the beginning of the office visit and before discharge. Demographics and clinical data was recorded.Results: Hands (N = 887) in 445 patients were evaluated using the Barbeau plethysmography technique. Barbeau Test (BT) patterns A, B, C, and D were observed in 58%, 30%, 8% and 4% on initial evaluation. On preliminary evaluation, 780 (88%) hands had a "low-risk" pattern (A or B) and 107 (12%) hands had a "high-risk" pattern (C or D). Repeat evaluation performed 50 ± 26 min later revealed a 'low-risk' pattern in 809 (91%) hands with 78 (9%) of hands showing a persistent "high risk" pattern. In 29 (27%) high-risk hands, spontaneous conversion to pattern B within <1 h occurred. Reverse Barbeau Test (RBT) at baseline showed pattern A, B, C and D in 95.9%, 2.8%, 1% and .4% respectively. There was no significant change in RBT upon follow-up evaluation. Strength of the radial artery pulsation was significantly associated with the pattern of RBT and the strength of ulnar pulsation was associated with the results of the BT.Conclusions: Plethysmographic testing of forearm circulation demonstrates variability over short intervals suggesting poor reliability for access site triage. [ABSTRACT FROM AUTHOR]

TB being one of the deadliest diseases and second most common infectious cause of deaths, poses the severe threat to global health. The extended duration of therapy owing to resistance and its upsurge in immune-compromised patients have been the driving force for the development of novel of anti-TB scaffolds. Recently, we have compiled the account of anti-mycobacterial scaffolds published during 2015–2020 and updated them in 2021. The present work involves the insights on the anti-mycobacterial scaffolds reported in 2022 with their mechanism of action, structure activity relationships, along with the key perceptions for the design of newer anti-TB agents for the broader interests of medicinal chemists. [Display omitted] • Organized coverage of diversified scaffolds with anti-tubercular profile reported in 2022. • Novel heterocycles reported for anti-TB profile along with their merits and demerits. • Focused need for novel drug candidates against drug resistant strains. • Highlighted with mode of anti-TB action against M. tuberculosis strains. • Insightful discussion on their in silico , in vitro or in vivo anti-tuberculosis potential, if reported. [ABSTRACT FROM AUTHOR]

Summary The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors. [ABSTRACT FROM AUTHOR]

Abstract: Background context: After spinal fusion surgery, postoperative management often includes imaging with either computed tomography (CT) or magnetic resonance imaging (MRI) to assess the spinal canal and nerve roots. The metallic implants used in the fusion can cause artifact that interferes with this imaging, reducing their diagnostic value. Stainless steel is known to produce large amounts of artifact, whereas titanium is known to produce significantly less. Other alloys such as vitallium are now being used in spinal implants, but their comparison to titanium and stainless steel has not been well documented in the orthopedic literature. Titanium is a desirable metal because of its light weight and lower production of artifact on imaging, although it is not as stiff as stainless steel. Vitallium is proposed as a replacement for titanium because it has stiffness similar to stainless steel, while still being as light as titanium. Purpose: The purpose of this study was to compare the amount of artifact produced on MRI and CT by three types of spinal implants: stainless steel, titanium, and vitallium. Study design: A prospective experimental design was used to compare three types of spinal implants used in posterior spinal fusion surgery. Outcome measures: The resulting images were evaluated by a radiologist to measure the amount of artifact (in millimeters) and by an orthopedic surgeon to assess the diagnostic quality (on a Likert scale). Methods: A porcine torso was used for repeated MRI and CT scans before and after implantation with pedicle screws and rods made of the three metals being studied. Results: Images produced after the insertion of vitallium rods and titanium screws as well as those with titanium rods and screws were found to have less artifact and a better overall diagnostic quality than those produced with stainless steel implants. Overall, there was not a difference between the amount of artifact in the spinal images with vitallium and titanium rods, with the exception of a few trials that showed small but statistically significant differences between the two metals, where titanium had slightly better images. Conclusions: If vitallium rods are used in posterior spinal surgery in place of implants made of titanium or stainless steel, any postoperative imaging of the spine using MRI or CT should have amounts of artifact that are similar to titanium and better than stainless steel. [Copyright &y& Elsevier]

New chiral Mn(III) salen epoxidation catalysts 1 and 2 (a catalyst loading in the range of 2.0–0.4 mol%) have been investigated for enantioselective epoxidation of chromene derivatives to chromene epoxides using pyridine N-oxide as a proximal ligand with excellent conversions and chiral induction. [Copyright &y& Elsevier]

Describes the immediate and short-term transesophageal echocardiographic results of catheter closure of small- and large-sized secundum atrial septal defect (ASD) in children and adults using the AGA Medical Corp. septal occluder (ASO). Features of the ASO; Complications encountered during and immediately after procedure.