sen The fascinating truth about why common sense isn't really that common By www.newscientist.com Published On :: Tue, 24 Sep 2024 17:00:00 +0100 New research is revealing that common sense is a lot more idiosyncratic than we thought, with important implications for tackling political polarisation and the future of AI Full Article
sen Quantum time travel: The experiment to 'send a particle into the past' By www.newscientist.com Published On :: Wed, 29 May 2024 17:00:00 +0100 Time loops have long been the stuff of science fiction. Now, using the rules of quantum mechanics, we have a way to effectively transport a particle back in time – here’s how Full Article
sen Quantum holograms can send messages that disappear By www.newscientist.com Published On :: Fri, 30 Aug 2024 21:12:22 +0100 Entangled particles of light can transmit holographic images that can be selectively erased, allowing for secure communications that can also be deleted Full Article
sen Spies can eavesdrop on phone calls by sensing vibrations with radar By www.newscientist.com Published On :: Thu, 31 Oct 2024 13:52:43 +0000 An off-the-shelf millimetre wave sensor can pick out the tiny vibrations made by a smartphone's speaker, enabling an AI model to transcribe the conversation, even at a distance in a noisy room Full Article
sen The fascinating truth about why common sense isn't really that common By www.newscientist.com Published On :: Tue, 24 Sep 2024 17:00:00 +0100 New research is revealing that common sense is a lot more idiosyncratic than we thought, with important implications for tackling political polarisation and the future of AI Full Article
sen In Seniors, 'Fear of Falling' Risky in Itself By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: In Seniors, 'Fear of Falling' Risky in ItselfCategory: Health NewsCreated: 8/20/2010 10:10:00 AMLast Editorial Review: 8/23/2010 12:00:00 AM Full Article
sen Brain Protein Is a Key to 'Senior Moments,' Study Finds By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Brain Protein Is a Key to 'Senior Moments,' Study FindsCategory: Health NewsCreated: 8/28/2013 2:35:00 PMLast Editorial Review: 8/29/2013 12:00:00 AM Full Article
sen Michigan Senate OK's Medicaid Expansion By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Michigan Senate OK's Medicaid ExpansionCategory: Health NewsCreated: 8/30/2013 11:00:00 AMLast Editorial Review: 8/30/2013 12:00:00 AM Full Article
sen Sleep Apnea Treatment Helps Seniors, Study Finds By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Sleep Apnea Treatment Helps Seniors, Study FindsCategory: Health NewsCreated: 8/27/2014 12:35:00 PMLast Editorial Review: 8/28/2014 12:00:00 AM Full Article
sen Seniors More Likely to Wind Up in Hospital After Outpatient Surgery: Study By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Seniors More Likely to Wind Up in Hospital After Outpatient Surgery: StudyCategory: Health NewsCreated: 8/25/2015 12:00:00 AMLast Editorial Review: 8/26/2015 12:00:00 AM Full Article
sen Family Trumps Friends in Extending Seniors' Lives By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Family Trumps Friends in Extending Seniors' LivesCategory: Health NewsCreated: 8/21/2016 12:00:00 AMLast Editorial Review: 8/22/2016 12:00:00 AM Full Article
sen Senior Years May Truly Be Golden for Happiness By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Senior Years May Truly Be Golden for HappinessCategory: Health NewsCreated: 8/24/2016 12:00:00 AMLast Editorial Review: 8/25/2016 12:00:00 AM Full Article
sen Smoking Linked to Frailty in Seniors By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Smoking Linked to Frailty in SeniorsCategory: Health NewsCreated: 8/29/2017 12:00:00 AMLast Editorial Review: 8/30/2017 12:00:00 AM Full Article
sen Senator John McCain Dies From Brain Tumor By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Senator John McCain Dies From Brain TumorCategory: Health NewsCreated: 8/26/2018 12:00:00 AMLast Editorial Review: 8/27/2018 12:00:00 AM Full Article
sen For Seniors, 'Silent Strokes' Are Common Post-Surgery Threat: Study By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: For Seniors, 'Silent Strokes' Are Common Post-Surgery Threat: StudyCategory: Health NewsCreated: 8/26/2019 12:00:00 AMLast Editorial Review: 8/27/2019 12:00:00 AM Full Article
sen Kitchen Essentials: Gadgets That Make Healthy Cooking Easier By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Kitchen Essentials: Gadgets That Make Healthy Cooking EasierCategory: Health NewsCreated: 8/29/2019 12:00:00 AMLast Editorial Review: 8/29/2019 12:00:00 AM Full Article
sen Stress, Anger May Worsen Heart Failure By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Stress, Anger May Worsen Heart FailureCategory: Health NewsCreated: 8/21/2020 12:00:00 AMLast Editorial Review: 8/24/2020 12:00:00 AM Full Article
sen Israeli Study Shows Pfizer Booster Gives Seniors Big Rise in Immunity By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Israeli Study Shows Pfizer Booster Gives Seniors Big Rise in ImmunityCategory: Health NewsCreated: 8/23/2021 12:00:00 AMLast Editorial Review: 8/23/2021 12:00:00 AM Full Article
sen Toppling TVs, Furniture Sending Many Young Children to ERs By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Toppling TVs, Furniture Sending Many Young Children to ERsCategory: Health NewsCreated: 8/27/2021 12:00:00 AMLast Editorial Review: 8/27/2021 12:00:00 AM Full Article
sen Alternative Medicine Popular Among Seniors, But Most Don't Tell Their Doctors About It By www.medicinenet.com Published On :: Wed, 27 Jul 2022 00:00:00 PDT Title: Alternative Medicine Popular Among Seniors, But Most Don't Tell Their Doctors About ItCategory: Health NewsCreated: 7/27/2022 12:00:00 AMLast Editorial Review: 7/27/2022 12:00:00 AM Full Article
sen Many Seniors Love Pickleball, But Injuries Can Happen By www.medicinenet.com Published On :: Mon, 8 Aug 2022 00:00:00 PDT Title: Many Seniors Love Pickleball, But Injuries Can HappenCategory: Health NewsCreated: 8/6/2022 12:00:00 AMLast Editorial Review: 8/8/2022 12:00:00 AM Full Article
sen Arsenic By www.medicinenet.com Published On :: Wed, 13 May 2020 00:00:00 PDT Arsenic: A metallic element that forms a number of poisonous compounds, arsenic is found in nature at low levels mostly in compounds with oxygen, chlorine, and sulfur. These are called inorganic arsenic compounds. Arsenic in plants and animals combines with carbon and hydrogen. This is called organic arsenic. Organic arsenic is usually less harmful than inorganic arsenic. Most arsenic compounds have no smell or special taste. Inorganic arsenic compounds are mainly used to preserve wood. They are also used to make insecticides and weed killers. Copper and lead ores contain small amounts of arsenic. When arsenic enters the environment, it does not evaporate. It gets into air when contaminated materials are burned. It settles from the air to the ground where it does not break down, but can change from one form to another. Most arsenic compounds can dissolve in water. Fish and shellfish build up organic arsenic in their tissues, but most of the arsenic in fish is not toxic. Exposure to arsenic can come from: Breathing workplace air with sawdust or burning smoke from wood containing arsenic Ingesting contaminated water, soil, or air at waste sites Ingesting contaminated water, soil, or air near areas naturally high in arsenic Inorganic arsenic is a human poison. Organic arsenic is less harmful. High levels of inorganic arsenic in food or water can be fatal. A high level is 60 parts of arsenic per million parts of food or water (60 ppm). Arsenic damages many tissues including nerves, stomach and intestines, and skin. Breathing high levels can give you a sore throat and irritated lungs. Lower levels of exposure to inorganic arsenic may cause: Nausea, vomiting, and diarrhea Decreased production of red and white blood cells Abnormal heart rhythm Blood vessel damage A "pins and needles" sensation in hands and feet Long term exposure to inorganic arsenic may lead to a darkening of the skin and the appearance of small "corns" or "warts" on the palms, soles, and torso. Direct skin contact may cause redness and swelling. Arsenic is a known carcinogen (cancer-causing agent). Breathing inorganic arsenic increases the risk of lung cancer. Ingesting inorganic arsenic increases the risk of skin cancer and tumors of the bladder, kidney, liver, and lung. Tests can measure a person's exposure to high levels of arsenic. These tests are not routinely performed in a doctor's office. Arsenic can be measured in the urine. This is the most reliable test for arsenic exposure. Since arsenic stays in the body only short time, one must have the test soon after exposure. Tests on hair or fingernails can measure exposure to high levels of arsenic over the past 6-12 months. These tests are not very useful for low level exposures. These tests do not predict whether you will have any harmful health effects. The US Environmental Protection Agency (EPA) sets limits on the amount of arsenic that industrial sources can release. It restricted or canceled many uses of arsenic in pesticides and may restrict more. EPA set a limit of 0.05 parts per million (ppm) for arsenic in drinking water. EPA may lower this further. The US Occupational Safety and Health Administration (OSHA) established a maximum permissible exposure limit for workplace airborne arsenic of 10 micrograms per cubic meter (µg/m³).MedTerms (TM) is the Medical Dictionary of MedicineNet.com.We Bring Doctors' Knowledge To You Full Article
sen Having Ideal Heart Health May Lessen the Risk for Brain Vessel Disease By www.medicinenet.com Published On :: Thu, 18 Aug 2022 00:00:00 PDT Title: Having Ideal Heart Health May Lessen the Risk for Brain Vessel DiseaseCategory: Health NewsCreated: 8/17/2022 12:00:00 AMLast Editorial Review: 8/18/2022 12:00:00 AM Full Article
sen Does Menopause Make You More Sensitive to Pain? By www.medicinenet.com Published On :: Wed, 11 May 2022 00:00:00 PDT Title: Does Menopause Make You More Sensitive to Pain?Category: Diseases and ConditionsCreated: 5/11/2022 12:00:00 AMLast Editorial Review: 5/11/2022 12:00:00 AM Full Article
sen Menopause Might Worsen Jaw Pain in Women By www.medicinenet.com Published On :: Tue, 17 May 2022 00:00:00 PDT Title: Menopause Might Worsen Jaw Pain in WomenCategory: Health NewsCreated: 5/17/2022 12:00:00 AMLast Editorial Review: 5/17/2022 12:00:00 AM Full Article
sen Senior Sex: Tips for Senior Citizens By www.medicinenet.com Published On :: Mon, 11 Jul 2022 00:00:00 PDT Title: Senior Sex: Tips for Senior CitizensCategory: Health and LivingCreated: 7/11/2022 12:00:00 AMLast Editorial Review: 7/11/2022 12:00:00 AM Full Article
sen Being Social May Be Key to 'Sense of Purpose' as You Age By www.medicinenet.com Published On :: Tue, 12 Jul 2022 00:00:00 PDT Title: Being Social May Be Key to 'Sense of Purpose' as You AgeCategory: Health NewsCreated: 7/12/2022 12:00:00 AMLast Editorial Review: 7/12/2022 12:00:00 AM Full Article
sen 'Virtual' Museum Visits Are Good Medicine for Seniors By www.medicinenet.com Published On :: Tue, 16 Aug 2022 00:00:00 PDT Title: 'Virtual' Museum Visits Are Good Medicine for SeniorsCategory: Health NewsCreated: 8/16/2022 12:00:00 AMLast Editorial Review: 8/16/2022 12:00:00 AM Full Article
sen 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
sen Salicylate Sensitivity Causes, Symptoms, and Foods to Avoid By www.medicinenet.com Published On :: Fri, 8 Jul 2022 00:00:00 PDT Title: Salicylate Sensitivity Causes, Symptoms, and Foods to AvoidCategory: Health and LivingCreated: 7/8/2022 12:00:00 AMLast Editorial Review: 7/8/2022 12:00:00 AM Full Article
sen CDC Panel Urges Seniors to Get New, More Potent Flu Shot This Fall By www.medicinenet.com Published On :: Thu, 23 Jun 2022 00:00:00 PDT Title: CDC Panel Urges Seniors to Get New, More Potent Flu Shot This FallCategory: Health NewsCreated: 6/23/2022 12:00:00 AMLast Editorial Review: 6/23/2022 12:00:00 AM Full Article
sen How Childhood Abuse Can Haunt the Senior Years By www.medicinenet.com Published On :: Fri, 8 Jul 2022 00:00:00 PDT Title: How Childhood Abuse Can Haunt the Senior YearsCategory: Health NewsCreated: 7/8/2022 12:00:00 AMLast Editorial Review: 7/8/2022 12:00:00 AM Full Article
sen Rapid SARS-CoV-2 surveillance using clinical, pooled, or wastewater sequence as a sensor for population change [METHODS] By genome.cshlp.org Published On :: 2024-10-29T06:46:08-07:00 The COVID-19 pandemic has highlighted the critical role of genomic surveillance for guiding policy and control. Timeliness is key, but sequence alignment and phylogeny slow most surveillance techniques. Millions of SARS-CoV-2 genomes have been assembled. Phylogenetic methods are ill equipped to handle this sheer scale. We introduce a pangenomic measure that examines the information diversity of a k-mer library drawn from a country's complete set of clinical, pooled, or wastewater sequence. Quantifying diversity is central to ecology. Hill numbers, or the effective number of species in a sample, provide a simple metric for comparing species diversity across environments. The more diverse the sample, the higher the Hill number. We adopt this ecological approach and consider each k-mer an individual and each genome a transect in the pangenome of the species. Structured in this way, Hill numbers summarize the temporal trajectory of pandemic variants, collapsing each day's assemblies into genome equivalents. For pooled or wastewater sequence, we instead compare days using survey sequence divorced from individual infections. Across data from the UK, USA, and South Africa, we trace the ascendance of new variants of concern as they emerge in local populations well before these variants are named and added to phylogenetic databases. Using data from San Diego wastewater, we monitor these same population changes from raw, unassembled sequence. This history of emerging variants senses all available data as it is sequenced, intimating variant sweeps to dominance or declines to extinction at the leading edge of the COVID-19 pandemic. Full Article
sen Impact of COVID-19 on Chronic Ambulatory-Care-Sensitive Condition Emergency Department Use Among Older Adults By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Background: The COVID-19 pandemic social distancing requirements encouraged patients to avoid public spaces including in-office health care visits. Ambulatory-care-sensitive conditions (ACSCs) represent conditions that can be managed with quality primary care and when access is limited, these conditions can lead to avoidable emergency department (ED) visits. Methods: Using national data on ED visits from 2019 to 2021 in the National Hospital Ambulatory Care Survey, we examined the impact of COVID-19 pandemic on ACSC ED visits among older adults (aged ≥65). Results: The proportion of ED visits among older adults that were for ACSCs increased between 2019 (17.4%) and 2021 (18.5%). The trend in both rural (26.4%–28.6%) and urban areas (15.4%–16.8%) shows a significant jump from 2019 to 2021 (P < .001). Conclusions: This rise in ACSC ED use is consistent with a delay in normal primary care during the pandemic. Full Article
sen 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
sen Could cough hypersensitivity symptom profile differentiate phenotypes of chronic cough? By beta.openres.ersjournals.com Published On :: 2024-11-11T01:50:25-08:00 Background Recently, cough reflex hypersensitivity has been proposed as a common underlying feature of chronic cough in adults. However, symptoms and clinical characteristics of cough hypersensitivity have not been studied amongst phenotypes of chronic cough. This study aimed to compare symptom features, such as cough triggers and associated throat sensations, of cough hypersensitivity in patients with asthmatic chronic cough and those with refractory chronic cough (RCC). Methods Patients with chronic cough from the Korean Chronic Cough Registry were prospectively evaluated over 6 months. Physicians determined the aetiological diagnosis based on clinical evaluations and responses to treatment at the 6-month follow-up visit. Symptoms of cough hypersensitivity and cough-specific quality of life were assessed using the Cough Hypersensitivity Questionnaire (CHQ) and the Leicester Cough Questionnaire (LCQ), respectively. Results The analysis included 280 patients who completed the follow-up: 79 with asthmatic cough (cough variant asthma or eosinophilic bronchitis) and 201 with RCC. Baseline CHQ scores were similar between the groups (8.3±3.7 in asthmatic cough versus 8.9±3.9 in RCC; p=0.215, adjusted for age, sex and LCQ score). There were no significant between-group differences in the LCQ and cough severity Visual Analog Scale scores. Both groups showed a similar negative correlation with LCQ scores (asthmatic cough: r=–0.427, p<0.001; RCC: r=–0.306, p<0.001). Conclusions The symptoms of cough hypersensitivity may not distinguish between asthmatic cough and RCC. This suggests that chronic cough is the primary diagnosis in both phenotypes. It indicates a shared mechanism in their cough pathogenesis, despite having potentially different treatable traits. Full Article
sen Multidisciplinary management of adult patients with chylothorax: a consensus statement By erj.ersjournals.com Published On :: 2024-11-07T00:35:55-08:00 The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research. Full Article
sen Comparison of the CYP3A Selective Inhibitors CYP3cide, Clobetasol, and Azamulin for Their Potential to Distinguish CYP3A7 Activity in the Presence of CYP3A4/5 [Articles] By dmd.aspetjournals.org Published On :: 2024-10-16T09:02:03-07:00 The CYP3A7 enzyme accounts for ~50% of the total cytochrome P450 (P450) content in fetal and neonatal livers and is the predominant P450 involved in neonatal xenobiotic metabolism. Additionally, it is a key player in healthy birth outcomes through the oxidation of dehydroepiandrosterone (DHEA) and DHEA-sulfate. The amount of the other hepatic CYP3A isoforms, CYP3A4 and CYP3A5, expressed in neonates is low but highly variable, and therefore the activity of individual CYP3A isoforms is difficult to differentiate due to their functional similarities. Consequently, a better understanding of the contribution of CYP3A7 to drug metabolism is essential to identify the risk that drugs may pose to neonates and developing infants. To distinguish CYP3A7 activity from CYP3A4/5, we sought to further characterize the selectivity of the specific CYP3A inhibitors CYP3cide, clobetasol, and azamulin. We used three substrate probes, dibenzylfluorescein, luciferin-PPXE, and midazolam, to determine the IC50 and metabolism-dependent inhibition (MDI) properties of the CYP3A inhibitors. Probe selection had a significant effect on the IC50 values and P450 inactivation across all inhibitory compounds and enzymes. CYP3cide and azamulin were both identified as MDIs and were most specific for CYP3A4. Contrary to previous reports, we found that clobetasol propionate (CP) was not an MDI of CYP3A5 but was more selective for CYP3A5 over CYP3A4/7. We further investigated CYP3cide and CP’s ability to differentiate CYP3A7 activity in an equal mixture of recombinant CYP3A4, CYP3A5, and CYP3A7, and our results provide confidence of CYP3cide’s and CP’s ability to distinguish CYP3A7 activity in the presence of the other CYP3A isoforms. SIGNIFICANCE STATEMENT These findings provide valuable insight regarding in vitro testing conditions to investigate the metabolism of new drug candidates and help determine drug safety in neonates. The results presented here also clearly demonstrate the effect that probe selection may have on CYP3A cytochrome P450 inhibition studies. Full Article
sen Can the International Conference on Population and Development Programme of Action and Cairo Consensus Normalize the Discourse on Population? By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 Full Article
sen Capacity-Building Through Digital Approaches: Evaluating the Feasibility and Effectiveness of eLearning to Introduce Subcutaneous DMPA Self-Injection in Senegal and Uganda By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 ABSTRACTTraining health workers is one of the biggest challenges and cost drivers when introducing a new contraceptive method or service delivery innovation. PATH developed a digital training curriculum for family planning providers who are learning to offer subcutaneous DMPA (DMPA-SC), including through self-injection, as an option among a range of contraceptive methods. The DMPA-SC eLearning course for health workers includes 10 lessons with an emphasis on informed choice counseling and training clients to self-inject. In partnership with Ministries of Health in Senegal and Uganda, the course was rolled out in select areas in 2019–2020, including during the COVID-19 pandemic when physical distancing requirements restricted in-person training. We conducted evaluations in both countries to assess the practical application of this digital training approach for contraceptive introduction. The evaluation consisted of a post-training survey, an observational assessment conducted during post-training supportive supervision, and an estimation of training costs.In both countries, a majority (88.6% in Uganda and 64.3% in Senegal) scored above 80% on a DMPA-SC knowledge test following the training. In Senegal, where there was a comparison group of providers trained in person, those providers scored similar on the post-test to eLearners. Providers in both groups and in both countries felt more prepared to administer DMPA-SC or offer self-injection to clients after receiving a supervision visit (93%–98% of eLearners felt very prepared after supervision as compared to 45%–72% prior). The evaluation results suggest that digital approaches offer a number of benefits, can be cost-effective, and are most optimal when blended with in-person training and/or supportive supervision. Full Article
sen Sensory-Motor Neuropathy in Mfn2 T105M Knock-in Mice and Its Reversal by a Novel Piperine-Derived Mitofusin Activator [Neuropharmacology] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Mitochondrial dysfunction is a hallmark of many genetic neurodegenerative diseases, but therapeutic options to reverse mitochondrial dysfunction are limited. While recent studies support the possibility of improving mitochondrial fusion/fission dynamics and motility to correct mitochondrial dysfunction and resulting neurodegeneration in Charcot-Marie-Tooth disease (CMT) and other neuropathies, the clinical utility of reported compounds and relevance of preclinical models are uncertain. Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2 A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse. We further demonstrate that daily oral treatment with a novel mitofusin activator derived from the natural product piperine can reverse these neurologic phenotypes. Piperine derivative 8015 promoted mitochondrial fusion and motility in Mfn2-deficient cells in a mitofusin-dependent manner and reversed mitochondrial dysfunction in cultured fibroblasts and reprogrammed motor neurons from a human CMT2A patient carrying the MFN2 T105M mutation. Like previous mitofusin activators, 8015 exhibited stereospecific functionality, but the more active stereoisomer, 8015-P2, is unique in that it has subnanomolar potency and undergoes entero-hepatic recirculation which extends its in vivo half-life. Daily administration of 8015-P2 to Mfn2 T105M knock-in mice for 6 weeks normalized neuromuscular and sensory dysfunction and corrected histological/ultrastructural neurodegeneration and neurogenic myoatrophy. These studies describe a more clinically relevant mouse model of CMT2A and an improved mitofusin activator derived from piperine. We posit that 8015-P2 and other piperine derivatives may benefit CMT2A or other neurodegenerative conditions wherein mitochondrial dysdynamism plays a contributory role. SIGNIFICANCE STATEMENT Mitochondrial dysfunction is widespread and broadly contributory in neurodegeneration, but difficult to target therapeutically. Here, we describe 8015-P2, a new small molecule mitofusin activator with ~10-fold greater potency and improved in vivo pharmacokinetics versus comparators, and demonstrate its rapid reversal of sensory and motor neuron dysfunction in an Mfn2 T105M knock-in mouse model of Charcot-Marie-Tooth disease type 2 A. These findings further support the therapeutic approach of targeting mitochondrial dysdynamism in neurodegeneration. Full Article
sen 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
sen Low-Field (64 mT) Portable MRI for Rapid Point-of-Care Diagnosis of Dissemination in Space in Patients Presenting with Optic Neuritis [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Low-field 64 mT portable brain MRI has recently shown diagnostic promise for MS. This study aimed to evaluate the utility of portable MRI (pMRI) in assessing dissemination in space (DIS) in patients presenting with optic neuritis and determine whether deploying pMRI in the MS clinic can shorten the time from symptom onset to MRI. MATERIALS AND METHODS: Newly diagnosed patients with optic neuritis referred to a tertiary academic MS center from July 2022 to January 2024 underwent both point-of-care pMRI and subsequent 3T conventional MRI (cMRI). Images were evaluated for periventricular (PV), juxtacortical (JC), and infratentorial (IT) lesions. DIS was determined on brain MRI per 2017 McDonald criteria. Test characteristics were computed by using cMRI as the reference. Interrater and intermodality agreement between pMRI and cMRI were evaluated by using the Cohen . Time from symptom onset to pMRI and cMRI during the study period was compared with the preceding 1.5 years before pMRI implementation by using Kruskal-Wallis with post hoc Dunn tests. RESULTS: Twenty patients (median age: 32.5 years [interquartile range {IQR}, 28–40]; 80% women) were included, of whom 9 (45%) and 5 (25%) had DIS on cMRI and pMRI, respectively. Median time interval between pMRI and cMRI was 7 days (IQR, 3.5–12.5). Interrater agreement was very good for PV (95%, = 0.89), and good for JC and IT lesions (90%, = 0.69 for both). Intermodality agreement was good for PV (90%, = 0.80) and JC (85%, = 0.63), and moderate for IT lesions (75%, = 0.42) and DIS (80%, = 0.58). pMRI had a sensitivity of 56% and specificity of 100% for DIS. The median time from symptom onset to pMRI was significantly shorter (8.5 days [IQR 7–12]) compared with the interval to cMRI before pMRI deployment (21 days [IQR 8–49], n = 50) and after pMRI deployment (15 days [IQR 12–29], n = 30) (both P < .01). Time from symptom onset to cMRI in those periods was not significantly different (P = .29). CONCLUSIONS: In patients with optic neuritis, pMRI exhibited moderate concordance, moderate sensitivity, and high specificity for DIS compared with cMRI. Its integration into the MS clinic reduced the time from symptom onset to MRI. Further studies are warranted to evaluate the role of pMRI in expediting early MS diagnosis and as an imaging tool in resource-limited settings. Full Article
sen NeuroMix with MRA: A Fast MR Protocol to Reduce Head and Neck CTA for Patients with Acute Neurologic Presentations [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Overuse of CT-based cerebrovascular imaging in the emergency department and inpatient settings, notably CTA of the head and neck for minor and nonfocal neurologic presentations, stresses imaging services and exposes patients to radiation and contrast. Furthermore, such CT-based imaging is often insufficient for definitive diagnosis, necessitating additional MR imaging. Recent advances in fast MRI may allow timely assessment and a reduced need for head and neck CTA in select populations. MATERIALS AND METHODS: We identified inpatients or patients in the emergency department who underwent CTAHN (including noncontrast and postcontrast head CT, with or without CTP imaging) followed within 24 hours by a 3T MRI study that included a 2.5-minute unenhanced multicontrast sequence (NeuroMix) and a 5-minute intracranial time of flight MRA) during a 9-month period (April to December 2022). Cases were classified by 4 radiologists in consensus as to whether NeuroMix and NeuroMix + MRA detected equivalent findings, detected unique findings, or missed findings relative to CTAHN. RESULTS: One hundred seventy-four cases (mean age, 67 [SD, 16] years; 56% female) met the inclusion criteria. NeuroMix alone and NeuroMix + MRA protocols were determined to be equivalent or better compared with CTAHN in 71% and 95% of patients, respectively. NeuroMix always provided equivalent or better assessment of the brain parenchyma, with unique findings on NeuroMix and NeuroMix + MRA in 35% and 36% of cases, respectively, most commonly acute infarction or multiple microhemorrhages. In 8/174 cases (5%), CTAHN identified vascular abnormalities not seen on the NeuroMix + MRA protocol due to the wider coverage of the cervical arteries by CTAHN. CONCLUSIONS: A fast MR imaging protocol consisting of NeuroMix + MRA provided equivalent or better information compared with CTAHN in 95% of cases in our population of patients with an acute neurologic presentation. The findings provide a deeper understanding of the benefits and challenges of a fast unenhanced MR-first approach with NeuroMix + MRA, which could be used to design prospective trials in select patient groups, with the potential to reduce radiation dose, mitigate adverse contrast-related patient and environmental effects, and lessen the burden on radiologists and health care systems. Full Article
sen De novo TRPM3 missense variant associated with neurodevelopmental delay and manifestations of cerebral palsy [RESEARCH ARTICLE] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp). Full Article
sen Leukemic presentation and progressive genomic alterations of MCD/C5 diffuse large B-cell lymphoma (DLBCL) [RESEARCH ARTICLE] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance. Full Article
sen Cross-Sectional Study of Cesarean Delivery and Safety Culture by Family Medicine Presence [Annals Journal Club] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article
sen PBRNs: Past, Present, and Future: A NAPCRG Report on the Practice-Based Research Network Conference. [Family Medicine Updates] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article
sen A Few Doctors Will See Some of You: The Critical Role of Underrepresented in Medicine (URiM) Family Physicians in the Care of Medicaid Beneficiaries [Original Research] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 PURPOSE Despite being key to better health outcomes for patients from racial and ethnic minority groups, the proportion of underrepresented in medicine (URiM) physicians remains low in the US health care system. This study linked a nationally representative sample of family physicians (FPs) with Medicaid claims data to explore the relative contributions to care of Medicaid populations by FP race and ethnicity. METHODS This descriptive cross-sectional study used 2016 Medicaid claims data from the Transformed Medicaid Statistical Information System and from 2016-2017 American Board of Family Medicine certification questionnaire responses to examine the diversity and Medicaid participation of FPs. We explored the diversity of FP Medicaid patient panels and whether they saw ≥150 beneficiaries in 2016. Using logistic regression models, we controlled for FP demographics, practice characteristics, and characteristics of the communities in which they practiced. RESULTS Of 13,096 FPs, Latine, Hispanic, or of Spanish Origin (LHS) FPs and non-LHS Black FPs saw more Medicaid beneficiaries compared with non-LHS White and non-LHS Asian FPs. The patient panels of URiM FPs had a much greater proportion of Medicaid beneficiaries from racial and ethnic minority groups. Overall, non-LHS Black and LHS FPs had greater odds of seeing ≥150 Medicaid beneficiaries in 2016. CONCLUSIONS These findings clearly show the critical role URiM FPs play in caring for Medicaid beneficiaries, suggesting physician race and ethnicity are correlated with Medicaid participation. Diversity in the health care workforce is essential for addressing racial health inequities. Policies need to address problems in pathways to medical education, including failures to recruit, nurture, and retain URiM students. Full Article
sen Family Medicine Presence on Labor and Delivery: Effect on Safety Culture and Cesarean Delivery [Original Research] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 PURPOSE Currently, 40% of counties in the United States do not have an obstetrician or midwife, and in rural areas the likelihood of childbirth being attended to by a family medicine (FM) physician is increasing. We sought to characterize the effect of the FM presence on unit culture and a key perinatal quality metric in Iowa hospital intrapartum units. METHODS Using a cross-sectional design, we surveyed Iowa physicians, nurses, and midwives delivering intrapartum care at hospitals participating in a quality improvement initiative to decrease the incidence of cesarean delivery. We linked respondents with their hospital characteristics and outcomes data. The primary outcome was the association between FM physician, obstetrician (OB), or both disciplines’ presence on labor and delivery and hospital low-risk, primary cesarean delivery rate. Unit culture was compared by hospital type (FM-only, OB-only, or Both). RESULTS A total of 849 clinicians from 39 hospitals completed the survey; 13 FM-only, 11 OB-only, and 15 hospitals with both. FM-only hospitals were all rural, with <1,000 annual births. Among hospitals with <1,000 annual births, births at FM-only hospitals had an adjusted 34.3% lower risk of cesarean delivery (adjusted incident rate ratio = 0.66; 95% CI, 0.52-.0.98) compared with hospitals with both. Nurses endorsed unit norms more supportive of vaginal birth and stronger safety culture at FM-only hospitals (P <.05). CONCLUSIONS Birthing hospitals staffed exclusively by FM physicians were more likely to have lower cesarean rates and stronger nursing-rated safety culture. Both access and quality of care provide strong arguments for reinforcing the pipeline of FM physicians training in intrapartum care. Full Article