ida La gracia del evangelio: De la muerte a la vida A By feeds.gracia.org Published On :: Thu, 11 Apr 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La gracia del evangelio: De la muerte a la vida B By feeds.gracia.org Published On :: Fri, 12 Apr 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La iglesia perseguida se extiende A By feeds.gracia.org Published On :: Fri, 17 May 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La iglesia perseguida se extiende B By feeds.gracia.org Published On :: Mon, 20 May 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La clave para mantener unidad familiar By feeds.gracia.org Published On :: Thu, 01 Aug 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La armadura de Dios: El cinturón de la veracidad y la coraza de la justicia By feeds.gracia.org Published On :: Fri, 30 Aug 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La armadura de Dios: El cinturón de la veracidad y la coraza de la justicia By feeds.gracia.org Published On :: Mon, 02 Sep 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida Aprendiendo la vida cristiana By feeds.gracia.org Published On :: Mon, 16 Sep 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida Seguridades contra un mundo hostil By feeds.gracia.org Published On :: Mon, 07 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La responsabilidad del Cristiano al gobierno, 1ª parte A By feeds.gracia.org Published On :: Mon, 21 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La responsabilidad del Cristiano al gobierno, 1ª parte B By feeds.gracia.org Published On :: Tue, 22 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La responsabilidad del Cristiano al gobierno, 2ª Parte A By feeds.gracia.org Published On :: Wed, 23 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La responsabilidad del Cristiano al gobierno, 2ª Parte B By feeds.gracia.org Published On :: Thu, 24 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La responsabilidad del Cristiano al gobierno, 3ª Parte A By feeds.gracia.org Published On :: Fri, 25 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La responsabilidad del Cristiano al gobierno, 3ª Parte B By feeds.gracia.org Published On :: Mon, 28 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La responsabilidad del cristiano al gobierno, 4ª parte A By feeds.gracia.org Published On :: Tue, 29 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida La responsabilidad del cristiano al gobierno, 4ª parte B By feeds.gracia.org Published On :: Wed, 30 Oct 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
ida Spiritual Intimidation, Part 1 By feeds.gty.org Published On :: Fri, 24 May 2019 00:00:00 PST Full Article
ida Spiritual Intimidation, Part 2 By feeds.gty.org Published On :: Fri, 31 May 2019 00:00:00 PST Full Article
ida Ukraine Protests: Euromaidan Has Real Potential By Published On :: Tue, 10 Dec 2013 15:01:00 GMT Furious about its government cowing to Russia and mishandling economic challenges, Ukrainian citizens have taken to the streets in record force. Full Article
ida Ekmeleddin Ihsanoglu: Turkey's Opposition Candidate By Published On :: Tue, 08 Jul 2014 13:01:00 GMT In Turkey's upcoming presidential election, one man represents the country's two biggest opposition parties, and he is largely unknown. Full Article
ida US Candidate Amy Pope Wins Tense Contest to Run UN Migration Agency By www.voanews.com Published On :: Mon, 15 May 2023 11:25:48 -0400 Geneva — Former White House adviser Amy Pope won a vote in Geneva on Monday to head the U.N. migration agency, prevailing in a tense contest against a Portuguese incumbent who had the support of European countries. The International Organization for Migration (IOM) said Pope would become the first woman to lead the organization when she begins her five-year term on Oct. 1. Pope, who served as Deputy Director General for Management and Reform at IOM, took leave to campaign against her boss Antonio Vitorino, who has been in the position since 2018. Pope wrote on Twitter she was "humbled and honored" to be chosen by IOM's 175 member states as new director general. "I am ready to work with ALL our member states and global partners to unleash the opportunities provided by effective, orderly and humane migration," she wrote. In 2021, Pope served as Senior Advisor on Migration to U.S. President Joe Biden, who publicly backed her candidacy. "As IOM's largest bilateral donor, the United States strongly supports Ms. Pope's vision and looks forward to working with her to implement the critical reforms necessary to create a more effective, inclusive IOM," U.S. Secretary of State Antony Blinken said in a statement. More than 100 million people are forcibly displaced around the world and IOM seeks to ensure humane and orderly migration and intervenes where needed. Vitorino, a former European Commissioner who is close to his compatriot United Nations Secretary General Antonio Guterres, had touted an increase in the body's annual budget among his successes. Asked about the contest earlier this year, Vitorino described it as unprecedented. "We have never happened to have an incumbent director general that faces a competition with one of his deputy generals. Let's call it an innovation," Vitorino told journalists in March. He said at the time he had Portugal's backing as well as the "strong encouragement" of the European Union. Full Article World News
ida Guterres Congratulates Nihon Hidankyo For Nobel Prize For Efforts To Rid Humanity of Nuclear Weapons By www.ipsnews.net Published On :: Fri, 11 Oct 2024 14:48:50 +0000 The United Nations Secretary General António Guterres congratulated grassroots Japanese organization Nihon Hidankyo on being awarded the 2024 Nobel Peace Prize. “The atomic bomb survivors from Hiroshima and Nagasaki, also known as the hibakusha, are selfless, soul-bearing witnesses of the horrific human cost of nuclear weapons,” he said in a statement. “While their numbers grow smaller each […] Full Article Active Citizens Civil Society Editors' Choice Featured Global Headlines Human Rights IPS UN: Inside the Glasshouse Nuclear Disarmament Nuclear Energy - Nuclear Weapons Peace TerraViva United Nations IPS UN Bureau IPS UN Bureau Report Nuclear Abolition 2024
ida Viewpoints: Is Tax Avoidance Destroying America? By Published On :: Sat, 14 May 2016 17:23:00 GMT Why don't the rich pay their fair share in taxes? Full Article
ida BIR to monitor online sellers' tax compliance during holiday season By business.inquirer.net Published On :: Wed, 13 Nov 2024 14:14:09 +0800 MANILA, Philippines – The Bureau of Internal Revenue (BIR) will closely monitor the tax compliance of online marketplaces and online sellers during the holiday season, Commissioner Romeo Lumagui Jr. has said. In a statement Wednesday, Lumagui warned that online businesses violating tax laws would be blocked. Section 115 of the National Internal Revenue Code, as […]...Keep on reading: BIR to monitor online sellers' tax compliance during holiday season Full Article
ida Kate Middleton seizes opportunity for Royal guidance, after Meghan's alleged snub By www.thenews.com.pk Published On :: Tue, 12 Nov 2024 19:50:00 +0500 Princess Kate has found a trusted mentor in the Duchess of Edinburgh, Sophie, 59, as she adjusts to her new role as Princess of Wales. Royal biographer Claudia Joseph revealed that Kate "jumped at the chance" to be mentored by Sophie, describing her as a "tower of strength" and a reliable... Full Article
ida to wire electric fans 89 toyota cressida By english.al-akhbar.com Published On :: to wire electric fans 89 toyota cressida Full Article
ida Scientists Shock Spuds in Bid to Boost Antioxidants By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Scientists Shock Spuds in Bid to Boost AntioxidantsCategory: Health NewsCreated: 8/23/2010 2:10:00 PMLast Editorial Review: 8/24/2010 12:00:00 AM Full Article
ida Bottled Teas May Not Deliver on Antioxidants By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Bottled Teas May Not Deliver on AntioxidantsCategory: Health NewsCreated: 8/23/2010 12:10:00 PMLast Editorial Review: 8/24/2010 12:00:00 AM Full Article
ida Black Rice Is Cheap Way to Get Antioxidants By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Black Rice Is Cheap Way to Get AntioxidantsCategory: Health NewsCreated: 8/27/2010 10:06:00 AMLast Editorial Review: 8/27/2010 10:06:13 AM Full Article
ida Five More Cases of Local Zika Infection Reported in Florida By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Five More Cases of Local Zika Infection Reported in FloridaCategory: Health NewsCreated: 8/24/2016 12:00:00 AMLast Editorial Review: 8/24/2016 12:00:00 AM Full Article
ida New Case of Local Zika Infection Reported in Florida By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: New Case of Local Zika Infection Reported in FloridaCategory: Health NewsCreated: 8/25/2016 12:00:00 AMLast Editorial Review: 8/26/2016 12:00:00 AM Full Article
ida Serious Problems at Florida Stem Cell Clinic By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Serious Problems at Florida Stem Cell ClinicCategory: Health NewsCreated: 8/29/2017 12:00:00 AMLast Editorial Review: 8/29/2017 12:00:00 AM Full Article
ida Major Study Gives Women More Guidance on Hormone Therapy During Menopause By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Major Study Gives Women More Guidance on Hormone Therapy During MenopauseCategory: Health NewsCreated: 8/29/2019 12:00:00 AMLast Editorial Review: 8/30/2019 12:00:00 AM Full Article
ida Record High COVID Cases and Deaths Reported in Florida By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Record High COVID Cases and Deaths Reported in FloridaCategory: Health NewsCreated: 8/26/2021 12:00:00 AMLast Editorial Review: 8/26/2021 12:00:00 AM Full Article
ida Metronidazole (Flagyl) vs. Fluconazole (Diflucan) By www.medicinenet.com Published On :: Wed, 24 Aug 2022 00:00:00 PDT Title: Metronidazole (Flagyl) vs. Fluconazole (Diflucan)Category: MedicationsCreated: 11/27/2018 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
ida Development and Validation of a Customized Amplex UltraRed Assay for Sensitive Hydrogen Peroxide Detection in Pharmaceutical Water By journal.pda.org Published On :: 2024-10-22T08:20:35-07:00 For clean-room technologies such as isolators and restricted access barrier systems (RABS), decontamination using hydrogen peroxide (H2O2) is increasingly attractive to fulfill regulatory requirements. Several approaches are currently used, ranging from manual wipe disinfection to vapor phase hydrogen peroxide (VPHP) or automated nebulization sanitization. Although the residual airborne H2O2 concentration can be easily monitored, detection of trace H2O2 residues in filled products is rather challenging. To simulate the filling process in a specific clean room, technical runs with water for injection (WfI) are popular. Thus, the ability to detect traces of H2O2 in water is an important prerequisite to ensure a safe and reliable use of H2O2 for isolator or clean room decontamination. The objective of this study was to provide a validated quantitative, fluorometric Amplex UltraRed assay, which satisfies the analytical target profile of quantifying H2O2 in WfI at low nanomolar to low micromolar concentrations (ppb range) with high accuracy and high precision. The Amplex UltraRed technology provides a solid basis for this purpose; however, no commercial assay kit that fulfills these requirements is available. Therefore, a customized Amplex UltraRed assay was developed, optimized, and validated. This approach resulted in an assay that is capable of quantifying H2O2 in WfI selectively, sensitively, accurately, precisely, and robustly. This assay is used in process development and qualification approaches using WfI in H2O2-decontaminated clean rooms and isolators. Full Article
ida Consolidating roles of neuroimmune reflexes: specificity of afferent, central, and efferent signals in homeostatic immune networks [Special Section: Symposium Outlook] By genesdev.cshlp.org Published On :: 2024-10-16T07:18:56-07:00 Neural reflexes occupy a central role in physiological homeostasis. The vagus nerve is a major conduit for transmitting afferent and efferent signals in homeostatic reflex arcs between the body and the brain. Recent advances in neuroscience, immunology, and physiology have revealed important vagus nerve mechanisms in suppressing inflammation and treating rheumatoid arthritis and other autoimmune conditions. Numerous clinical trials indicate that there is significant benefit to vagus nerve stimulation therapy. Although many questions are still unanswered, it will be important, even necessary, to pursue answers that will be useful in guiding interventions to modulate immunological and physiological homeostasis. Full Article
ida A circular split nanoluciferase reporter for validating and screening putative internal ribosomal entry site elements [METHOD] By rnajournal.cshlp.org Published On :: 2024-10-16T07:18:13-07:00 Internal ribosomal entry sites (IRESs) recruit the ribosome to promote translation, typically in an m7G cap-independent manner. Although IRESs are well-documented in viral genomes, they have also been reported in mammalian transcriptomes, where they have been proposed to mediate cap-independent translation of mRNAs. However, subsequent studies have challenged the idea of these "cellular" IRESs. Current methods for screening and discovering IRES activity rely on a bicistronic reporter assay, which is prone to producing false positive signals if the putative IRES sequence has a cryptic promoter or cryptic splicing sites. Here, we report an assay for screening IRES activity using a genetically encoded circular RNA comprising a split nanoluciferase (nLuc) reporter. The circular split nLuc reporter is less susceptible to the various sources of false positives that adversely affect the bicistronic IRES reporter assay and provides a streamlined method for screening IRES activity. Using the circular split nLuc reporter, we find that nine reported cellular IRESs have minimal IRES activity. Overall, the circular split nLuc reporter offers a simplified approach for identifying and validating IRESs and exhibits reduced propensity for producing the types of false positives that can occur with the bicistronic reporter assay. Full Article
ida Longitudinal validation of King's Sarcoidosis Questionnaire in a prospective cohort with mild sarcoidosis By beta.openres.ersjournals.com Published On :: 2024-11-11T01:50:25-08:00 Background Quality of life is impaired in patients with sarcoidosis. The King's Sarcoidosis Questionnaire (KSQ) is a brief questionnaire assessing health-related quality of life in patients with sarcoidosis, comprising subdomains of General Health Status (GHS), Lung, Medication, Skin and Eyes. The aim of this study was to enhance the validation of the KSQ, incorporating longitudinal validation and known-groups validity in a cohort with mild sarcoidosis. Methods The KSQ was linguistically validated according to guidelines. Patients with sarcoidosis completed KSQ and other questionnaires at baseline, after 2 weeks and at 12 months. Forced vital capacity (FVC) was measured. Concurrent validity, reliability and responsiveness were assessed. Results In patients (n=150), the KSQ had moderate to strong correlations with the Short Form-12 (Mental Component Summary), the King's Brief Interstitial Lung Disease questionnaire and the Fatigue Assessment Scale (r=0.30–0.70) and weak correlations with the Short Form-12 (Physical Component Summary) and FVC (r=0.01–0.29). The KSQ GHS and Lung domains were able to discriminate between groups of patients stratified according to fatigue, treatment and FVC. The KSQ had high internal consistency (Cronbach's α=0.73–0.90) and repeatability (interclass correlation coefficients 0.72–0.81). Correlations to comparable questionnaires at baseline were moderate or strong for the GHS, Lung and GHS–Lung subdomains and weak or moderate for FVC. The KSQ was responsive to changes over time. Conclusion This study strengthened the validation of the KSQ by introducing known-groups validity and assessments of responsiveness over 12 months in patients with mild sarcoidosis. Full Article
ida Cannabinoid 2 Receptor Activation Protects against Diabetic Cardiomyopathy through Inhibition of AGE/RAGE-Induced Oxidative Stress, Fibrosis, and Inflammasome Activation [Special Section: Cannabinoid Signaling in Human Health and Disease] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Oxidative stress, fibrosis, and inflammasome activation from advanced glycation end product (AGE)–receptor of advanced glycation end product (RAGE) interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of β-caryophyllene (BCP) on activating cannabinoid type 2 receptors (CB2Rs) against diabetic complication, mainly cardiomyopathy and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding a high-fat diet with streptozotocin injections. After the development of diabetes, the animals received a 12-week oral BCP treatment at a dose of 50 mg/kg/body weight. BCP treatment showed significant improvement in glucose tolerance and insulin resistance and enhanced serum insulin levels in diabetic animals. BCP treatment effectively reversed the heart remodeling and restored the phosphorylated troponin I and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a expression. Ultrastructural examination showed reduced myocardial cell injury in DCM mice treated with BCP. The preserved myocytes were found to be associated with reduced expression of AGE/RAGE in DCM mice hearts. BCP treatment mitigated oxidative stress by inhibiting expression of NADPH oxidase 4 and activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2–related factor 2 (Nrf2) signaling. Also, BCP suppressed cardiac fibrosis and endothelial-to-mesenchymal transition in DCM mice by inhibiting transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) signaling. Further, BCP treatment suppressed nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation in DCM mice and alleviated cellular injury to the pancreatic tissues evidenced by significant elevation of the number of insulin-positive cells. To demonstrate a CB2R-dependent mechanism of BCP, another group of DCM mice were pretreated with AM630, a CB2R antagonist. AM630 was observed to abrogate the beneficial effects of BCP in DCM mice. Taken together, BCP demonstrated the potential to protect the myocardium and pancreas of DCM mice mediating CB2R-dependent mechanisms. SIGNIFICANCE STATEMENT BCP, a CB2R agonist, shows protection against DCM. BCP attenuates oxidative stress, inflammation, and fibrosis in DCM via activating CB2Rs. BCP mediating CB2R activation favorably modulates AGE/RAGE, PI3K/AKT/Nrf2β and TGF-β/Smad and (NLRP3) inflammasome in diabetic cardiomyopathy. Full Article
ida Low-Efficacy Mu Opioid Agonists as Candidate Analgesics: Effects of Novel C-9 Substituted Phenylmorphans on Pain-Depressed Behavior in Mice [Behavioral Pharmacology] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Low-efficacy mu opioid receptor (MOR) agonists may serve as novel candidate analgesics with improved safety relative to high-efficacy opioids. This study used a recently validated assay of pain-depressed behavior in mice to evaluate a novel series of MOR-selective C9-substituted phenylmorphan opioids with graded MOR efficacies. Intraperitoneal injection of dilute lactic acid (IP acid) served as a noxious stimulus to depress locomotor activity by mice in an activity chamber composed of two compartments connected by an obstructed door. Behavioral measures included (1) crosses between compartments (vertical activity over the obstruction) and (2) movement counts quantified as photobeam breaks summed across compartments (horizontal activity). Each drug was tested alone and as a pretreatment to IP acid. A charcoal-meal test and whole-body-plethysmography assessment of breathing in 5% CO2 were also used to assess gastrointestinal (GI) inhibition and respiratory depression, respectively. IP acid produced a concentration-dependent depression in crosses and movement that was optimally alleviated by intermediate- to low-efficacy phenylmorphans with sufficient efficacy to produce analgesia with minimal locomotor disruption. Follow-up studies with two low-efficacy phenylmorphans (JL-2-39 and DC-1-76.1) indicated that both drugs produced naltrexone-reversible antinociception with a rapid onset and a duration of ~1 h. Potency of both drugs increased when behavior was depressed by a lower IP-acid concentration, and neither drug alleviated behavioral depression by a non-pain stimulus (IP lithium chloride). Both drugs produced weaker GI inhibition and respiratory depression than fentanyl and attenuated fentanyl-induced GI inhibition and respiratory depression. Results support further consideration of selective, low-efficacy MOR agonists as candidate analgesics. SIGNIFICANCE STATEMENT This study used a novel set of mu opioid receptor (MOR)-selective opioids with graded MOR efficacies to examine the lower boundary of MOR efficacy sufficient to relieve pain-related behavioral depression in mice. Two novel low-efficacy opioids (JL-2-39, DC-1-76.1) produced effective antinociception with improved safety relative to higher- or lower-efficacy opioids, and results support further consideration of these and other low-efficacy opioids as candidate analgesics. Full Article
ida Validation of an Artificial Intelligence-Based Prediction Model Using 5 External PET/CT Datasets of Diffuse Large B-Cell Lymphoma By jnm.snmjournals.org Published On :: 2024-11-01T04:25:31-07:00 The aim of this study was to validate a previously developed deep learning model in 5 independent clinical trials. The predictive performance of this model was compared with the international prognostic index (IPI) and 2 models incorporating radiomic PET/CT features (clinical PET and PET models). Methods: In total, 1,132 diffuse large B-cell lymphoma patients were included: 296 for training and 836 for external validation. The primary outcome was 2-y time to progression. The deep learning model was trained on maximum-intensity projections from PET/CT scans. The clinical PET model included metabolic tumor volume, maximum distance from the bulkiest lesion to another lesion, SUVpeak, age, and performance status. The PET model included metabolic tumor volume, maximum distance from the bulkiest lesion to another lesion, and SUVpeak. Model performance was assessed using the area under the curve (AUC) and Kaplan–Meier curves. Results: The IPI yielded an AUC of 0.60 on all external data. The deep learning model yielded a significantly higher AUC of 0.66 (P < 0.01). For each individual clinical trial, the model was consistently better than IPI. Radiomic model AUCs remained higher for all clinical trials. The deep learning and clinical PET models showed equivalent performance (AUC, 0.69; P > 0.05). The PET model yielded the highest AUC of all models (AUC, 0.71; P < 0.05). Conclusion: The deep learning model predicted outcome in all trials with a higher performance than IPI and better survival curve separation. This model can predict treatment outcome in diffuse large B-cell lymphoma without tumor delineation but at the cost of a lower prognostic performance than with radiomics. Full Article
ida Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET By jnm.snmjournals.org Published On :: 2024-11-01T04:25:31-07:00 Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [11C]UCB-J PET. Methods: Participants included 31 older adults with AD and 16 with normal cognition. The distribution volume ratio (DVR) using simplified reference tissue model 2 was compared with SUVR at short scan windows using a whole-cerebellum reference region. Results: Synaptic density was reduced in AD participants using DVR or SUVR. SUVR using later scan windows (60–90 or 70–90 min) was minimally biased, with the strongest correlation with DVR. Effect sizes using SUVR at these late time windows were minimally reduced compared with effect sizes with DVR. Conclusion: A simplified tissue-to-reference method may be useful for multicenter and longitudinal studies seeking to measure synaptic density in AD. Full Article
ida Glatiramer Acetate for the Treatment of Multiple Sclerosis: From First-Generation Therapy to Elucidation of Immunomodulation and Repair [Review Article] By pharmrev.aspetjournals.org Published On :: 2024-10-16T07:40:25-07:00 Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis. Extensive clinical trials and long-term assessments established the efficacy and the safety of GA. Furthermore, studies of the therapeutic processes induced by GA in animal models and in MS patients indicate that GA affects various levels of the innate and the adaptive immune response, generating deviation from proinflammatory to anti-inflammatory pathways. This includes competition for binding to antigen presenting cells; driving dendritic cells, monocytes, and B-cells toward anti-inflammatory responses; and stimulating T-helper 2 and T-regulatory cells. The immune cells stimulated by GA reach the CNS and secrete in situ anti-inflammatory cytokines alleviating the pathological processes. Furthermore, cumulative findings reveal that in addition to its immunomodulatory effect, GA promotes neuroprotective repair processes such as neurotrophic factors secretion, remyelination, and neurogenesis. This review aims to provide an overview of MS pathology diagnosis and treatment as well as the diverse mechanism of action of GA. Significance Statement Understanding the complex MS immune pathogenesis provided multiple targets for therapeutic intervention, resulting in a plethora of agents, with various mechanisms of action, efficacy, and safety profiles. However, promoting repair beyond the body’s limited spontaneous extent is still a major challenge. GA, one of the first approved disease-modifying therapies, induces diverse immunomodulatory effects. Furthermore, GA treatment results in elevated neurotrophic factors secretion, remyelination and neurogenesis, supporting the notion that immunomodulatory treatment can support in situ a growth-promoting and repair environment. Full Article
ida Cyclic Aspiration in Mechanical Thrombectomy: Influencing Factors and Experimental Validation [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Mechanical thrombectomy is a fundamental intervention for acute ischemic stroke treatment. While conventional techniques are effective, cyclic aspiration (CyA) shows potential for better recanalization rates. We aim to investigate factors affecting CyA and compare them with static aspiration (StA). MATERIALS AND METHODS: StA setup consisted of an aspiration pump connected to pressure transducer. CyA was tested with 5 subsequent iterations: single solenoid valve with air plus saline (i1) or saline alone (i2) as aspiration medium; 2 solenoid valves with air plus saline (i3) as aspiration medium; complete air removal and saline feeding (i4); and pressurized saline feeding (i5). To assess the efficacy of clot ingestion, the pressure transducer was replaced with a distal aspiration catheter. Moderately stiff clot analogs (15 mm) were used to investigate the ingestion quantified as clot relative weight loss. Additionally, the aspiration flow rate was assessed for each setup. RESULTS: With CyA i1, the amplitude of the achieved negative pressure waves declined with increasing frequencies but progressively increased with each subsequent iteration, achieving a maximum amplitude of 81 kPa for i5 at 1 Hz. Relative clot weight loss was significantly higher with i5 at 5 Hz than with StA (100% versus 37.8%; P = .05). Aspiration flow rate was lower with CyA than with StA (i5 at 5 Hz: 199.8 mL/min versus StA: 311 mL/min; P < .01). CONCLUSIONS: CyA with the appropriate setup may represent an encouraging innovation in mechanical thrombectomy, offering a promising pathway for improving efficacy in clot ingestion and recanalization. The observed benefits warrant confirmation in a clinical setting. Full Article
ida Healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality: a longitudinal community-based study By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises. Full Article
ida Guidance and Resources for Family Medicine Scholarship [Family Medicine Updates] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article
ida [PERSPECTIVES] The Complex Roles of Redox and Antioxidant Biology in Cancer By perspectivesinmedicine.cshlp.org Published On :: 2024-11-01T07:17:20-07:00 Redox reactions control fundamental biochemical processes, including energy production, metabolism, respiration, detoxification, and signal transduction. Cancer cells, due to their generally active metabolism for sustained proliferation, produce high levels of reactive oxygen species (ROS) compared to normal cells and are equipped with antioxidant defense systems to counteract the detrimental effects of ROS to maintain redox homeostasis. The KEAP1-NRF2 system plays a major role in sensing and regulating endogenous antioxidant defenses in both normal and cancer cells, creating a bivalent contribution of NRF2 to cancer prevention and therapy. Cancer cells hijack the NRF2-dependent antioxidant program and exploit a very unique metabolism as a trade-off for enhanced antioxidant capacity. This work provides an overview of redox metabolism in cancer cells, highlighting the role of the KEAP1-NRF2 system, selenoproteins, sulfur metabolism, heme/iron metabolism, and antioxidants. Finally, we describe therapeutic approaches that can be leveraged to target redox metabolism in cancer. Full Article
ida New research to better understand the biological factors of suicidal behaviour By www.heraldscotland.com Published On :: Tue, 12 Nov 2024 06:30:00 +0000 New research to better understand the biological factors of suicidal behaviour Researchers at the University of Glasgow are embarking on two new PhD projects to better understand the impact that biological factors may have on suicidal behaviour. Full Article