eat U.S. Opioid Deaths Take a Small Dip, as Fentanyl Leaves Deadly Mark By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: U.S. Opioid Deaths Take a Small Dip, as Fentanyl Leaves Deadly MarkCategory: Health NewsCreated: 8/29/2019 12:00:00 AMLast Editorial Review: 8/30/2019 12:00:00 AM Full Article
eat Brutus & Barnaby Pig Ear Treats For Dogs Recalled By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Brutus & Barnaby Pig Ear Treats For Dogs RecalledCategory: Health NewsCreated: 8/29/2019 12:00:00 AMLast Editorial Review: 8/30/2019 12:00:00 AM Full Article
eat Best Ways to Beat the Heat By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Best Ways to Beat the HeatCategory: Health NewsCreated: 8/22/2020 12:00:00 AMLast Editorial Review: 8/24/2020 12:00:00 AM Full Article
eat Eating Disorders Cost Billions in the U.S. By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Eating Disorders Cost Billions in the U.S.Category: Health NewsCreated: 8/21/2020 12:00:00 AMLast Editorial Review: 8/24/2020 12:00:00 AM Full Article
eat Quit Smoking to Cut Risk of Death From A-Fib By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Quit Smoking to Cut Risk of Death From A-FibCategory: Health NewsCreated: 8/25/2020 12:00:00 AMLast Editorial Review: 8/25/2020 12:00:00 AM Full Article
eat Lockdowns Tough on People With Eating Disorders: Survey By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Lockdowns Tough on People With Eating Disorders: SurveyCategory: Health NewsCreated: 8/24/2020 12:00:00 AMLast Editorial Review: 8/25/2020 12:00:00 AM Full Article
eat Bee Healthy: Honey May Beat Cold Meds Against Cough By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Bee Healthy: Honey May Beat Cold Meds Against CoughCategory: Health NewsCreated: 8/24/2020 12:00:00 AMLast Editorial Review: 8/25/2020 12:00:00 AM Full Article
eat FDA Approves Wider Use of Plasma as Coronavirus Treatment By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: FDA Approves Wider Use of Plasma as Coronavirus TreatmentCategory: Health NewsCreated: 8/24/2020 12:00:00 AMLast Editorial Review: 8/25/2020 12:00:00 AM Full Article
eat Survivors' Plasma Still a Solid Option for Treating COVID-19, Experts Say By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Survivors' Plasma Still a Solid Option for Treating COVID-19, Experts SayCategory: Health NewsCreated: 8/26/2020 12:00:00 AMLast Editorial Review: 8/26/2020 12:00:00 AM Full Article
eat What Is More Deadly in the U.S.: Hot Weather or Cold? By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: What Is More Deadly in the U.S.: Hot Weather or Cold?Category: Health NewsCreated: 8/27/2020 12:00:00 AMLast Editorial Review: 8/28/2020 12:00:00 AM Full Article
eat Stop Using Ivermectin Veterinary Drug to Treat COVID, FDA Urges By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Stop Using Ivermectin Veterinary Drug to Treat COVID, FDA UrgesCategory: Health NewsCreated: 8/23/2021 12:00:00 AMLast Editorial Review: 8/23/2021 12:00:00 AM Full Article
eat Salmonella Outbreak in 17 States Tied to Italian-Style Meats By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Salmonella Outbreak in 17 States Tied to Italian-Style MeatsCategory: Health NewsCreated: 8/24/2021 12:00:00 AMLast Editorial Review: 8/25/2021 12:00:00 AM Full Article
eat 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
eat Cooler Weather Could Mean More Diabetes in Dogs By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Cooler Weather Could Mean More Diabetes in DogsCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/22/2022 12:00:00 AM Full Article
eat Michigan Officials Puzzled by Mysterious Deaths of 30 Dogs By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Michigan Officials Puzzled by Mysterious Deaths of 30 DogsCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
eat 'Stepped' Approach to Treating Diabetic Eye Disease May Be Best By www.medicinenet.com Published On :: Fri, 15 Jul 2022 00:00:00 PDT Title: 'Stepped' Approach to Treating Diabetic Eye Disease May Be BestCategory: Health NewsCreated: 7/15/2022 12:00:00 AMLast Editorial Review: 7/15/2022 12:00:00 AM Full Article
eat How Can I Keep My Baby Cool in the Car Seat? By www.medicinenet.com Published On :: Wed, 24 Aug 2022 00:00:00 PDT Title: How Can I Keep My Baby Cool in the Car Seat?Category: Health and LivingCreated: 3/17/2022 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
eat Can You Eat Raw Tofu? By www.medicinenet.com Published On :: Fri, 26 Aug 2022 00:00:00 PDT Title: Can You Eat Raw Tofu?Category: Health and LivingCreated: 8/26/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
eat Scientists Create Synthetic Mouse Embryo With Brain, Beating Heart By www.medicinenet.com Published On :: Sat, 27 Aug 2022 00:00:00 PDT Title: Scientists Create Synthetic Mouse Embryo With Brain, Beating HeartCategory: Health NewsCreated: 8/26/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
eat What Can You Eat on a Low Cholesterol Diet? By www.medicinenet.com Published On :: Wed, 6 Jul 2022 00:00:00 PDT Title: What Can You Eat on a Low Cholesterol Diet?Category: Health and LivingCreated: 8/27/2021 12:00:00 AMLast Editorial Review: 7/6/2022 12:00:00 AM Full Article
eat AHA News: People With Dementia May Be Less Likely to Receive an Advanced Treatment For Stroke By www.medicinenet.com Published On :: Wed, 24 Aug 2022 00:00:00 PDT Title: AHA News: People With Dementia May Be Less Likely to Receive an Advanced Treatment For StrokeCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
eat Magic Mushroom Hallucinogen May Treat Problem Drinking By www.medicinenet.com Published On :: Thu, 25 Aug 2022 00:00:00 PDT Title: Magic Mushroom Hallucinogen May Treat Problem DrinkingCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
eat Brain-Eating Amoeba From River May Have Caused Child's Death By www.medicinenet.com Published On :: Fri, 19 Aug 2022 00:00:00 PDT Title: Brain-Eating Amoeba From River May Have Caused Child's DeathCategory: Health NewsCreated: 8/19/2022 12:00:00 AMLast Editorial Review: 8/19/2022 12:00:00 AM Full Article
eat Fecal Transplant Treatments Could Transmit Monkeypox, FDA Warns By www.medicinenet.com Published On :: Thu, 25 Aug 2022 00:00:00 PDT Title: Fecal Transplant Treatments Could Transmit Monkeypox, FDA WarnsCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
eat Heat Waves That Threaten Lives Will Be Common by 2100 By www.medicinenet.com Published On :: Fri, 26 Aug 2022 00:00:00 PDT Title: Heat Waves That Threaten Lives Will Be Common by 2100Category: Health NewsCreated: 8/26/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
eat What Therapeutic Options Are Available for Treating an Antiretroviral Naive Patient? By www.medicinenet.com Published On :: Thu, 16 Jun 2022 00:00:00 PDT Title: What Therapeutic Options Are Available for Treating an Antiretroviral Naive Patient?Category: Diseases and ConditionsCreated: 6/16/2022 12:00:00 AMLast Editorial Review: 6/16/2022 12:00:00 AM Full Article
eat Moving Away From Opioids to Treat Dental Pain By www.medicinenet.com Published On :: Fri, 19 Aug 2022 00:00:00 PDT Title: Moving Away From Opioids to Treat Dental PainCategory: Health NewsCreated: 8/19/2022 12:00:00 AMLast Editorial Review: 8/19/2022 12:00:00 AM Full Article
eat New Multiple Sclerosis Treatment Shows Promise in Trial By www.medicinenet.com Published On :: Fri, 26 Aug 2022 00:00:00 PDT Title: New Multiple Sclerosis Treatment Shows Promise in TrialCategory: Health NewsCreated: 8/25/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
eat Helping Older Loved Ones in a Heat Wave By www.medicinenet.com Published On :: Mon, 25 Jul 2022 00:00:00 PDT Title: Helping Older Loved Ones in a Heat WaveCategory: Health NewsCreated: 7/25/2022 12:00:00 AMLast Editorial Review: 7/25/2022 12:00:00 AM Full Article
eat Get Moving! Any Sports Can Lower Seniors' Odds of Early Death By www.medicinenet.com Published On :: Fri, 26 Aug 2022 00:00:00 PDT Title: Get Moving! Any Sports Can Lower Seniors' Odds of Early DeathCategory: Health NewsCreated: 8/25/2022 12:00:00 AMLast Editorial Review: 8/26/2022 12:00:00 AM Full Article
eat Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get Treatment By www.medicinenet.com Published On :: Wed, 10 Aug 2022 00:00:00 PDT Title: Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get TreatmentCategory: Health NewsCreated: 8/10/2022 12:00:00 AMLast Editorial Review: 8/10/2022 12:00:00 AM Full Article
eat Cold, Flu, Allergy Treatments By www.medicinenet.com Published On :: Fri, 15 Jul 2022 00:00:00 PDT Title: Cold, Flu, Allergy TreatmentsCategory: Diseases and ConditionsCreated: 9/24/1999 12:00:00 AMLast Editorial Review: 7/15/2022 12:00:00 AM Full Article
eat Most Post-Stroke Depression Still Goes Untreated By www.medicinenet.com Published On :: Mon, 25 Jul 2022 00:00:00 PDT Title: Most Post-Stroke Depression Still Goes UntreatedCategory: Health NewsCreated: 7/25/2022 12:00:00 AMLast Editorial Review: 7/25/2022 12:00:00 AM Full Article
eat Treating central sleep apnoea in heart failure: progressing one step at a time By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Extract We read with great interest the correspondence by T. Bitter and co-workers in the European Respiratory Review, about our recently published review entitled "Central sleep apnoea: not just one phenotype" [1]. We first want to express our gratefulness to the authors for their support and appreciation of our work, particularly regarding the urgent need for an increasingly differentiated view of central sleep apnoea (CSA) in the context of precision medicine. Full Article
eat Treating central sleep apnoea in heart failure: is positive airway pressure and adaptive servo-ventilation in particular the gold standard? By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Extract We read with great interest the review article by Randerath et al. [1] recently published in the European Respiratory Review. We would like to congratulate the authors on this clearly structured review, which emphasises the urgent need for an increasingly differentiated view of central sleep apnoea (CSA) in the context of precision medicine. Full Article
eat Breathing techniques to reduce symptoms in people with serious respiratory illness: a systematic review By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Background In adults with serious respiratory illness, breathlessness is prevalent and associated with reduced health-related quality of life. The aim of this review was to assess the impact of breathing techniques on breathlessness in adults with serious respiratory illness. Methods Electronic databases were searched to identify randomised controlled trials testing breathing techniques (techniques that aim to alter the respiratory pattern, excluding respiratory muscle training) in people with serious respiratory illness. The primary outcome was breathlessness and secondary outcomes were health-related quality of life and adverse events. Two authors independently screened for inclusion, evaluated risk of bias and extracted data. Results 73 randomised controlled trials were included with 5479 participants, most with COPD or asthma. Breathing exercises (pursed lip and/or diaphragmatic breathing) reduced breathlessness measured by the modified Medical Research Council scale compared to usual care (mean difference (MD) –0.40 points, 95% CI –0.70– –0.11, eight studies, n=323), although the effect did not exceed the minimal important difference. Yoga breathing also improved modified Medical Research Council score compared to usual care (MD –1.05 points, 95% CI –2.45–0.35, three studies, n=175). Breathing techniques consistently improved health-related quality of life in people with COPD and asthma on multiple health-related quality of life measures in comparison to usual care, with effects that generally exceeded the minimal important difference. No adverse events related to breathing techniques were reported. Conclusion Breathing techniques may improve breathlessness, and consistently improve health-related quality of life, in people with serious respiratory illness. These findings support the use of breathing exercises in the care of people with serious respiratory illness. Full Article
eat Headache Treatment Options By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Family medicine physicians often see headache as the chief complaint when meeting patients within their practice. The goal is to try different treatment modalities without having to send the patient to a specialist. Headaches affect different individuals during their lifetime. Before any treatment begins, it is best that one rules out possible causes of the headache, for example, drug interactions or structural cerebrum conditions. Nonpharmacological treatment is recommended first before attempting a stepwise approach to cost-effective pharmacological treatment options. Pharmacological treatment options should include preventive and on-demand options. A family physician has all the resources to assist patients with different types of headaches. Full Article
eat Supporting Evidence For Pulmonary Rehabilitation in the Treatment of Long COVID By rc.rcjournal.com Published On :: 2024-10-25T05:44:13-07:00 Full Article
eat Feasibility of Delivering 5-Day Normobaric Hypoxia Breathing in a Hospital Setting By rc.rcjournal.com Published On :: 2024-10-25T05:44:12-07:00 BACKGROUND:Beneficial effects of breathing at FIO2 < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with FIO2 as low as 0.11 in 5 healthy volunteers.METHODS:All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from FIO2 of 0.16 on the first day to FIO2 of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' SpO2, heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments.RESULTS:Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased SpO2 and increased heart rate. At FIO2 of 0.14, the mean SpO2 was 92%; at FIO2 of 0.13, the mean SpO2 was 93%; at FIO2 of 0.12, the mean SpO2 was 88%; at FIO2 of 0.11, the mean SpO2 was 85%; and, finally, at an FIO2 of 0.21, the mean SpO2 was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension.CONCLUSIONS:Results of the current physiologic study suggests that, within a hospital setting, delivering FIO2 as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested. Full Article
eat NEAT1 promotes genome stability via m6A methylation-dependent regulation of CHD4 [Research Papers] By genesdev.cshlp.org Published On :: 2024-10-16T07:18:56-07:00 Long noncoding (lnc)RNAs emerge as regulators of genome stability. The nuclear-enriched abundant transcript 1 (NEAT1) is overexpressed in many tumors and is responsive to genotoxic stress. However, the mechanism that links NEAT1 to DNA damage response (DDR) is unclear. Here, we investigate the expression, modification, localization, and structure of NEAT1 in response to DNA double-strand breaks (DSBs). DNA damage increases the levels and N6-methyladenosine (m6A) marks on NEAT1, which promotes alterations in NEAT1 structure, accumulation of hypermethylated NEAT1 at promoter-associated DSBs, and DSB signaling. The depletion of NEAT1 impairs DSB focus formation and elevates DNA damage. The genome-protective role of NEAT1 is mediated by the RNA methyltransferase 3 (METTL3) and involves the release of the chromodomain helicase DNA binding protein 4 (CHD4) from NEAT1 to fine-tune histone acetylation at DSBs. Our data suggest a direct role for NEAT1 in DDR. Full Article
eat The treatment of latent tuberculosis infection in migrants in primary care versus secondary care By erj.ersjournals.com Published On :: 2024-11-07T00:35:56-08:00 Extract With a disproportionate burden of tuberculosis (TB) amongst migrants in Europe [1], Burman et al. [2] have highlighted the pressing need for alternative approaches to make TB infection (TBI) screening comprehensive and accessible. Across high-income Organisation for Economic Co-operation and development countries, a median of 52% of TB cases occur in foreign-born individuals, who are at their highest risk of developing TB disease within the first 5 years of migration [3]. Molecular epidemiological studies indicate that the majority of these cases occur as a result of TBI reactivation, often acquired overseas [4]. Within the UK, overseas-born migrants have a 14-fold higher TB incidence than UK-born individuals [5]. The World Health Organization therefore recommends that migrants from countries with a high TB burden may be prioritised for TBI screening [6, 7]. Full Article
eat Treatment of latent tuberculosis infection in migrants in primary care versus secondary care By erj.ersjournals.com Published On :: 2024-11-07T00:35:55-08:00 Background Control of latent tuberculosis infection (LTBI) is a priority in the World Health Organization strategy to eliminate TB. Many high-income, low TB incidence countries have prioritised LTBI screening and treatment in recent migrants. We tested whether a novel model of care, based entirely within primary care, was effective and safe compared to secondary care. Methods This was a pragmatic cluster-randomised, parallel group, superiority trial (ClinicalTrials.gov: NCT03069807) conducted in 34 general practices in London, UK, comparing LTBI treatment in recent migrants in primary care to secondary care. The primary outcome was treatment completion, defined as taking ≥90% of antibiotic doses. Secondary outcomes included treatment acceptance, adherence, adverse effects, patient satisfaction, TB incidence and a cost-effectiveness analysis. Analyses were performed on an intention-to-treat basis. Results Between September 2016 and May 2019, 362 recent migrants with LTBI were offered treatment and 276 accepted. Treatment completion was similar in primary and secondary care (82.6% versus 86.0%; adjusted OR (aOR) 0.64, 95% CI 0.31–1.29). There was no difference in drug-induced liver injury between primary and secondary care (0.7% versus 2.3%; aOR 0.29, 95% CI 0.03–2.84). Treatment acceptance was lower in primary care (65.2% (146/224) versus 94.2% (130/138); aOR 0.10, 95% CI 0.03–0.30). The estimated cost per patient completing treatment was lower in primary care, with an incremental saving of GBP 315.27 (95% CI 313.47–317.07). Conclusions The treatment of LTBI in recent migrants within primary care does not result in higher rates of treatment completion but is safe and costs less when compared to secondary care. Full Article
eat Factors Influencing the Central Nervous System (CNS) Distribution of the Ataxia Telangiectasia Mutated and Rad3-Related Inhibitor Elimusertib (BAY1895344): Implications for the Treatment of CNS Tumors [Metabolism, Transport, and Pharmacogenetics] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited. SIGNIFICANCE STATEMENT This study examined the disconnect between the in vitro synergy and in vivo efficacy of elimusertib/temozolomide combination therapy by exploring systemic and central nervous system (CNS) distributional pharmacokinetics. Results indicate that the lack of improvement in in vivo efficacy in glioblastoma (GBM) patient-derived xenograft (PDX) models could be attributed to inadequate exposure of pharmacologically active drug concentrations in the CNS. These observations can guide further exploration of elimusertib for the treatment of GBM or other CNS tumors. Full Article
eat First-in-Human Total-Body PET/CT Imaging Using 89Zr-Labeled MUC5AC Antibody in a Patient with Pancreatic Adenocarcinoma By jnm.snmjournals.org Published On :: 2024-11-01T04:25:31-07:00 Full Article
eat uPAR Immuno-PET in Pancreatic Cancer, Aging, and Chemotherapy-Induced Senescence By jnm.snmjournals.org Published On :: 2024-11-01T04:25:31-07:00 Identifying cancer therapy resistance is a key time-saving tool for physicians. Part of chemotherapy resistance includes senescence, a persistent state without cell division or cell death. Chemically inducing senescence with the combination of trametinib and palbociclib (TP) yields several tumorigenic and prometastatic factors in pancreatic cancer models with many potential antibody-based targets. In particular, urokinase plasminogen activator receptor (uPAR) has been shown to be a membrane-bound marker of senescence in addition to an oncology target. Methods: Here, 2 antibodies against murine uPAR and human uPAR were developed as immuno-PET agents to noninvasively track uPAR antigen abundance. Results: TP treatment increased cell uptake both in murine KPC cells and in human MiaPaCa2 cells. In vivo, subcutaneously implanted murine KPC tumors had high tumor uptake with the antimurine uPAR antibody independently of TP in young mice, yet uPAR uptake was maintained in aged mice on TP. Mice xenografted with human MiaPaCa2 tumors showed a significant increase in tumor uptake on TP therapy when imaged with the antihuman uPAR antibody. Imaging with either uPAR antibody was found to be more tumor-selective than imaging with [18F]FDG or [18F]F-DPA-714. Conclusion: The use of radiolabeled uPAR-targeting antibodies provides a new antibody-based PET imaging candidate for pancreatic cancer imaging as well as chemotherapy-induced senescence. Full Article
eat 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
eat Diffusion Analysis of Intracranial Epidermoid, Head and Neck Epidermal Inclusion Cyst, and Temporal Bone Cholesteatoma [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Intracranial epidermoids temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are typically slow-growing, benign conditions arising from ectodermal tissue. They exhibit increased signal on DWI. While much of the imaging literature describes these lesions as showing diffusion restriction, we investigated these qualitative signal intensities and interpretations of restricted diffusion with respect to normal brain structures. This study aimed to quantitatively evaluate the ADC values and histogram features of these lesions. MATERIALS AND METHODS: This retrospective study included children with histologically confirmed diagnoses of intracranial epidermoids, temporal bone cholesteatomas, or head and neck epidermal inclusion cysts. Lesions were segmented, and voxelwise calculation of ADC values was performed along with histogram analysis. ADC calculations were validated with a second analysis software to ensure accuracy. Normal brain ROIs—including the cerebellum, white matter, and thalamus—served as normal comparators. Correlational analysis and Bland-Altman plots assessed agreement among software tools for ADC calculations. Differences in the distribution of values between the lesions and normal brain tissues were assessed using the Wilcoxon rank sum and Kruskal-Wallis tests. RESULTS: Forty-eight pathology-proved cases were included in this study. Among them, 13 (27.1%) patients had intracranial epidermoids 14 (29.2%) had head and neck epidermal inclusion cysts, and 21 (43.7%) had temporal bone cholesteatomas. The mean age was 8.67 (SD, 5.30) years, and 27 (56.3%) were female. The intraclass correlation for absolute agreement for lesional ADC between the 2 software tools was 0.997 (95% CI, 0.995–0.998). The intracranial epidermoid head and neck epidermal inclusion cyst, and temporal bone cholesteatoma median ADC values were not significantly different (973.7 versus 875.7 versus 933.2 x 10–6 mm2/s, P = .265). However, the ADCs of the 3 types of lesions were higher than those of 3 normal brain tissue types (933 versus 766, x 10–6 mm2/s, P < .001). CONCLUSIONS: The ADC values of intracranial epidermoids, temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are higher than those of normal brain regions. It is not accurate to simply classify these lesions as exhibiting restricted diffusion or reduced diffusivity without considering the tissue used for comparison. The observed hyperintensity on DWI compared with the brain is likely attributable to a relatively higher contribution of the T2 shinethrough effect. Full Article
eat ITPR1-associated spinocerebellar ataxia with craniofacial features--additional evidence for germline mosaicism [RESEARCH ARTICLE] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome. Full Article
eat Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions. Full Article
eat Correction to "Opioid-related emergency department visits and deaths after a harm-reduction intervention: a retrospective observational cohort time series analysis" By www.cmajopen.ca Published On :: 2024-06-18T06:21:04-07:00 Full Article