Search

Abstract The risk of developing age-related macular degeneration (AMD) is influenced by genetic background. In 2016, the International AMD Genomics Consortium (IAMDGC) identified 52 risk variants in 34 loci, and a polygenic risk score (PRS) from these variants was associated with AMD. The Israeli population has a unique genetic composition: Ashkenazi Jewish (AJ), Jewish non-Ashkenazi, and Arab sub-populations. We aimed to perform a genome-wide association study (GWAS) for AMD in Israel, and to evaluate PRSs for AMD. Our discovery set recruited 403 AMD patients and 256 controls at Hadassah Medical Center. We genotyped individuals via custom exome chip. We imputed non-typed variants using cosmopolitan and AJ reference panels. We recruited additional 155 cases and 69 controls for validation. To evaluate predictive power of PRSs for AMD, we used IAMDGC summary-statistics excluding our study and developed PRSs via clumping/thresholding or LDpred2. In our discovery set, 31/34 loci reported by IAMDGC were AMD-associated (P

Purpose: To assess the safety and efficacy of a ciliary neurotrophic factor (CNTF) intraocular implant on neuroprotection and neuroenhancement in glaucoma. Design: Open-label, prospective, phase I clinical trial. Participants: A total of 11 participants were diagnosed with primary open-angle glaucoma (POAG). One eye of each patient was assigned as the study (implant) eye. Methods: The study eye was implanted with a high-dose CNTF-secreting NT-501 implant, whereas the other eye served as a control. All patients were followed up for 18 months. Analysis was limited to descriptive statistics. Main Outcome Measures: Primary outcome was safety through 18 months after implantation assessed by serial eye examinations, structural and functional testing, and adverse events (AEs) recording. Parameters measured included visual acuity (VA), Humphrey visual field (HVF), pattern electroretinogram, scanning laser polarimetry with variable corneal compensation (GDx VCC), and OCT. These parameters were also used for secondary analysis of efficacy outcome. Results: All NT-501 implants were well tolerated with no serious AEs associated with the implant. The majority of AEs were related to the implant placement procedure and were resolved by 12 weeks after surgery. Foreign-body sensation was the most commonly reported AE and was self-limited to the postoperative period. The most common implant-related AE was pupil miosis; no patients underwent explant. Visual acuity and contrast sensitivity decreased more in fellow eyes than in study eyes (VA, −5.82 vs. −0.82 letters; and contrast sensitivity, −1.82 vs. −0.37 letters, for fellow vs. study eyes, respectively). The median HVF visual field index and mean deviation measurements worsened (decreased) in fellow eyes (−13.0%, −3.9 dB) and improved (increased) in study eyes (2.7%, 1.2 dB). Implanted eyes showed an increase in retinal nerve fiber layer thickness measured by OCT and by GDx VCC (OCT, 2.66 μm vs. 10.16 μm; and GDx VCC, 1.58 μm vs. 8.36 μm in fellow vs. study eyes, respectively). Conclusions: The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements suggesting biological activity, supporting the premise for a randomized phase II clinical trial of single and dual NT-501 CNTF implants in patients with POAG, which is now underway. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

T cell-based immunotherapies have exhibited promising outcomes in tumor control; however, their efficacy is limited in immune-excluded tumors. Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the tumor microenvironment and modulating immune infiltration. Despite the identification of distinct CAF subtypes using single-cell RNA-sequencing (scRNA-seq), their functional impact on hindering T-cell infiltration remains unclear, particularly in soft-tissue sarcomas (STS) characterized by low response rates to T cell-based therapies. In this study, we characterize the STS microenvironment using murine models (in female mice) with distinct immune composition by scRNA-seq, and identify a subset of CAFs we termed glycolytic cancer-associated fibroblasts (glyCAF). GlyCAF rely on GLUT1-dependent expression of CXCL16 to impede cytotoxic T-cell infiltration into the tumor parenchyma. Targeting glycolysis decreases T-cell restrictive glyCAF accumulation at the tumor margin, thereby enhancing T-cell infiltration and augmenting the efficacy of chemotherapy. These findings highlight avenues for combinatorial therapeutic interventions in sarcomas and possibly other solid tumors. Further investigations and clinical trials are needed to validate these potential strategies and translate them into clinical practice., (© 2024. The Author(s).)

Sperm motility is an essential selection criteria by embryologists at the time of intracytoplasmic sperm injection (ICSI). One method of testing sperm viability is to induce sperm motility by increasing cyclic adenosine monophosphate (cAMP) levels by treating a semen sample with phosphodiesterase inhibitors (PDEIs), such as theophylline and pentoxifylline. It explores the implications of PDEI in medical care, reflecting on its effects in clinical settings and recognizing potential topics for future exploration. This analysis revealed that by incorporating stimulants that activate movements, the time it took to single out sperms was markedly reduced, and consequently, the sperms were safeguarded from a prolonged period of oxidative stress. Furthermore, theophylline was found to advance sperm motility, consequently resulting in several initially immobile spermatozoa displaying rapid progressive motility. Higher fertilization rate, cleavage rate, good quality embryos (grade I), and higher biochemical and clinical pregnancy rates were found with artificial sperm activation (ASA) using pentoxifylline and theophylline. This review emphasizes the need for more research to evaluate the drug's long-term safety and investigate the effects of theophylline and pentoxifylline on postfertilization parameters, such as embryo development, implantation, and pregnancy outcomes. These areas of investigation are important for understanding the complete impact of these agents and to ensure their safe and effective implementation in clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gala et al.)

The COVID-19 pandemic necessitated the understanding of the infodemic for making informed decisions. Limiting the spread of health misinformation and disinformation was the primary goal of the health informatics project. The project became the recipient of the ASIS&T "Chapter Innovation of the Year Award 2021". A repertoire of online and offline initiatives was carried out with 9 well-researched videos for promoting health informatics. Since August 2021, thousands of academics, librarians, teachers, parents, and students from 16 countries and regions were invited to be science communicators to create and disseminate accurate health information in their areas through an international digital story writing competition. In this paper, we will discuss the strategies of responding to the information crisis, including employing interventions that protect against the infodemic and mitigate its harmful effects, to strengthen the resilience of individuals and communities in dealing with it in an information-resilient society., (85th Annual Meeting of the Association for Information Science & Technology | Oct. 29 – Nov. 1, 2022 | Pittsburgh, PA. Author(s) retain copyright, but ASIS&T receives an exclusive publication license.)

The fight against the COVID-19 pandemic is as much an information war as it is a medical war. Members from South Asia and the Asia Pacific countries share their experiences and challenges faced with collaborative responses for the ASIS&T Special Chapter funded project on "Dealing with COVID-19 and saving people's lives in South Asia (SA) areas & beyond-A Health Informatics Promotion Project" awarded to the South Asia Chapter in 2021. The panel discusses the challenges faced within the context of geopolitical, socio-economic, religious, and cultural conditions prevalent within their countries. In the first 40 minutes, panel members narrate their own experiences by sharing their personal stories about this collaborative project and share the challenges of content creation and promotion from within the context of their respective countries. The next 30 minutes will be facilitated by the panel chair inviting a discussion between panel members and the audience to engage and come up with innovative ideas, discuss challenges in creating multilingual content and suggestions for improving the project outcome as well as shed light on initiating future health informatics project in similar regions. The last 20 minutes will culminate with the summarization of these collaborative experiences., (85th Annual Meeting of the Association for Information Science & Technology | Oct. 29 – Nov. 1, 2022 | Pittsburgh, PA. Author(s) retain copyright, but ASIS&T receives an exclusive publication license.)

Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance., (© 2021. The Author(s).)

Transradial access for cardiac catheterization is a safe and viable approach with significantly lower incidence of major access-related complications compared with the transfemoral approach. As this form of access is getting wider acceptance among interventional cardiologists, awareness of its complications is of vital importance. Asymptomatic radial artery occlusion, non-occlusive radial artery injury and radial artery spasm are commonly reported complication of this approach. Symptomatic radial arterial occlusion, pseudoaneurysm and radial artery perforation are rarely reported complications of transradial approach. Early identification of these uncommon complications and their urgent management is of significant importance. We present the case of an 80-year-old lady who developed pseudoaneurysm a week after transradial cardiac catheterization managed with surgical excision with no long-term sequela., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Transradial access for cardiac catheterization is now widely accepted among the invasive cardiology community as a safe and viable approach with a markedly reduced incidence of major access-related complications compared with the transfemoral approach. As this access technique is now being used more commonly for cardiac catheterization, it is of paramount importance to be aware of its complications and to understand their prevention and management. Some of the common complications of transradial access include asymptomatic radial artery occlusion, nonocclusive radial artery injury and radial artery spasm. Among these complications, radial artery spasm is still a significant challenge. Symptomatic radial arterial occlusion, pseudoaneurysm and radial artery perforation are rarely reported complications of the transradial approach. Early identification of these rare complications and their immediate management is of vital importance. Arteriovenous fistula, minor nerve damage and complex regional pain syndrome are very rare but have been reported. Recently, granulomas have been reported to be associated with the use of a particular brand of hydrophilic sheaths during the procedure. Generally, access-site complications can be minimized by avoiding multiple punctures, selection of smaller sheaths, gentle catheter manipulation, adequate anticoagulation, use of appropriate compression devices and avoiding prolonged high-pressure compression. In addition, careful observation for any ominous signs such as pain, numbness and hematoma formation during and in the immediate postprocedure period is essential in the prevention of catastrophic hand ischemia.

Background: In the setting of myocardial infarction (MI) or acute coronary syndrome (ACS), current guidelines recommend early and aggressive lipid lowering therapy with statins, irrespective of the baseline lipoprotein levels. Takotsubo cardiomyopathy (TCM) patients have a clinical presentation similar to myocardial infarction and thus receive early and aggressive statin therapy during their initial hospitalization. However, the pathology of TCM is not atherosclerotic coronary artery disease and hence we assumed the lipid profiles in TCM would be healthier than coronary artery disease patients., Methods: In this retrospective study, we assessed fasting serum lipoprotein levels of ten TCM patients and compared them with forty, age and sex-matched myocardial infarction (MI) patients., Results: Comparing serum lipoprotein levels of TCM with MI group, there was no significant difference in mean total cholesterol between the two groups (174.5 mg/dL vs. 197.6 mg/dL, p = 0.12). However, in the TCM group, mean HDL-C was significantly higher (66.87 mg/dL vs. 36.5 mg/dL, p = 0.008), the mean LDL-C was significantly lower (89.7 mg/dL vs. 128.9 mg/dL, p = 0.0002), and mean triglycerides was also significantly lower (65.2 mg/dL vs. 166.8 mg/dL, p < 0.0001)., Conclusions: In this study, TCM patients in comparison to MI patients had significantly higher levels of HDL-C, lower levels of LDL-C levels and triglycerides. The lipid profiles in TCM were consistent with the underlying pathology of non-atherosclerotic, non-obstructive coronary artery disease. As lipoproteins in most TCM patients were within the optimal range, we recommend an individual assessment of lipid profiles along with their coronary heart disease risk factors for considering long term lipid-lowering therapy. A finding of hyperalphalipoproteinemia or hypotriglyceridemia in 40% of TCM patients is novel but this association needs to be confirmed in future studies with larger sample sizes. These findings may provide clues in understanding the pathogenesis of takotsubo cardiomyopathy.

Very late stent thrombosis is defined as in-stent thrombosis occurring after 1 year of an intra-coronary artery stent placement. Drug eluting stents have lately been criticized for increased reports of very late stent thrombosis. The exact cause of these very late stent thromboses is not clearly understood. Virchow's triad describes the three main factors of thrombus formation to be stasis of blood flow, endothelial injury and hypercoagulability. Based on Virchow's triad, we propose the cause of very late stent thrombosis to be formation of a de novo atherosclerotic lesion in the proximal segment of a stented artery. The de novo atherosclerotic lesion narrows the vessel lumen and causes stasis of blood flow in the distal stent. The de novo lesion can also cause myocardial ischemia creating a prothrombotic environment in the stented region. Stasis of blood flow and prothrombotic environment in the stented region can lead to the formation of very late stent thrombosis. Since atherosclerosis is a dynamic aging process in humans, we propose de novo proximal lesions in the coronary arteries can predispose to very late stent thrombosis., (Published by Elsevier Ltd.)

Background: Cirrhotic cardiomyopathy has been reported to be a major cause of morbidity and mortality in liver transplant recipients. However, there is scant data from Asia. With liver transplantation programs gradually being established in the region, Asian hepatologists are bound to face this entity., Methods: Thirty patients with alcoholic cirrhosis and 30 with cirrhosis of nonalcoholic etiology were enrolled, after excluding those with recent bleeding, gross ascites, severe anemia and other conditions which could alter cardiovascular status. Thirty healthy subjects without cardiovascular risk factors were enrolled as controls. Hepatic function status was assessed by biochemical tests and prothrombin time. Cardiac structural and functional assessment was performed non-invasively using transthoracic echocardiography., Results: Deceleration time was significantly (P < 0.05) prolonged in both the cirrhotic groups (235.03 +/- 44.23 ms and 255.87 +/- 46.16 ms) compared to controls (185.83 +/- 25.04 ms), indicative of diastolic dysfunction in cirrhotic patients. Other parameters, viz. ejection fraction, E : A ratio, left ventricular relative wall thickness, interventricular septal thickness and left ventricular systolic as well as diastolic chamber dimensions did not show statistically significant difference between any of the groups. Cardiac structural and functional parameters were not correlated with the severity of liver dysfunction. There was no statistically significant difference between the alcoholic and nonalcoholic groups., Conclusions: Asian patients with cirrhosis do have evidence of diastolic dysfunction. Cardiac structural and functional parameters did not correlate with the severity of liver dysfunction. Cardiac dysfunction seemed to be the consequence of cirrhosis itself, rather than of alcohol.

Background and Objective: Investigators have documented an increase in renal artery resistance in cirrhotic patients. We studied the hepatic and renal hemodynamics by color Doppler in patients with liver cirrhosis in relation to the presence and severity of ascites., Methods: A prospective study was carried out in a large public hospital on 33 patients with cirrhosis of liver and 11 healthy control subjects. Eleven patients had no ascites, 12 had diuretic-responsive ascites and 10 had refractory ascites. The resistance index (RI) of the hepatic artery was measured by color Doppler on its main branch and renal artery RI was measured on the main renal, interlobar and cortical arteries of the right kidney., Results: Considering intraobserver variabilities, coefficient of variation for RI was 2.3%-7.8% (mean [SD] 4.2% [1.8%]). Hepatic artery RI were 0.68 (0.07), 0.68 (0.1), 0.81 (0.04), 1.0 (0.12) in control subjects and cirhotics with no ascites, responsive ascites and refractory ascites, respectively. Renal RI was significantly higher than in control subjects at all three levels in patients with responsive and refractory ascites, being higher in those with refractory than responsive ascites. Renal RI decreased from hilum towards the outer parenchyma, in cirrhotics with no ascites and responsive ascites but not in refractory ascites., Conclusion: Hepatic artery RI is higher in cirrhotics and is related to presence and severity of ascites. In control subjects and patients with no ascites or responsive ascites the renal RI decreased from hilum to the outer parenchyma.

Background: Color Doppler is a noninvasive method for assessing portal hemodynamics. Laser Doppler velocimetry is useful in assessment of microcirculatory abnormalities in portal hypertensive gastropathy (PHG)., Aims: To study portal hemodynamics by color Doppler and gastric mucosal blood flow (GMBF) by laser Doppler velocimetry in patients with cirrhosis., Methods: Twenty-eight patients with cirrhosis of liver (24 men) and 10 healthy subjects (7 men) were studied. Portal venous blood flow (PVBF) and portal flow velocity (PFV) were assessed by color Doppler at the level where the hepatic artery crosses the portal vein, and GMBF was measured by laser Doppler velocimetry., Results: PVBF (379.5 [102.9] mL/min), PFV (5.3 [1.1] cm/sec) and GMBF (3.5 [0.8] volts) were significantly lower in patients with cirrhosis than in controls. PVBF and PFV were significantly lower in patients in Child class B and C than those in class A. Patients with ascites had significantly lower PVBF, PFV and GMBF than those without; values were also lower in patients with PHG than in those without. History of bleeding had no relation with PVBF and PFV. GMBF showed good correlation with PVBF (r=0.58, p<0.001) and with PFV (r=0.48, p<0.01)., Conclusions: In cirrhosis of liver, PVBF, PFV and GMBF are significantly lower, and the changes increase with increasing severity of liver disease.

Kinetic methodology was applied for the first time to the determination of gliadin proteins by using a stopped-flow mixing technique. The method is based on two simultaneous processes: the reaction between gliadins and sodium dodecyl sulfate and the elimination of the quenching caused by this surfactant of the fluorescence of Cresyl Violet. Thus, the increase in fluorescence intensity with time is directly related to gliadin concentration. The use of this oxazine dye allows dynamic fluorescence measurements at long wavelengths, which avoids potential interferences from the sample matrix. The reaction rate is measured within 5 s, so the method is very suitable for the routine determination of gliadins in food samples. The dynamic range of the calibration graph was 0.5-50 micrograms ml-1 and the LOD was 0.25 microgram ml-1. The RSD was 1.6%. The method was applied to different food samples and the analytical recoveries were 88-107%.