2,143 results match your criteria: "United Kingdom (S.S.); and Clinical Pharmacology and Quantitative Pharmacology[Affiliation]"

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Neurol Genet

December 2024

From the Division of Neurology (A.H.T., S.-Y.L.), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Programa de Pós-Graduação em Ciências Médicas da Universidade Federal do Rio Grande do Sul (P.S.-A.), Clínica Santa María, Santiago, Chile; Departamento de Farmacologia (A.F.S.S.), Universidade Federal do Rio Grande do Sul; Serviço de Neurologia (A.F.S.S.), Hospital de Clínicas de Porto Alegre, Brazil; Institute of Neurogenetics (H.M., M.L.D., C.K.), University of Lübeck, Germany; Department of Biomedical Science (A.A.-A.), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; The Michael J. Fox Foundation for Parkinson's Research (J.S., B.F.), New York; Department of Medical and Molecular Genetics (C.E.W.), Indiana University, Indianapolis; Department of Neuroscience and Brain Health (M.L.D.), Metropolitan Medical Center, Manila, Philippines; Centre for Preventive Neurology (S.D., M.T.P., A.J.N.), Wolfson Institute of Population Health, Queen Mary University of London, United Kingdom; Unidad de Trastornos del Movimiento (M.T.P.), Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain; Laboratory of Neurogenetics (M.B.M.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical and Movement Neurosciences (M.B.M., H.R.M.), UCL Queen Square Institute of Neurology, University College London, United Kingdom; Department of Neurology (R.N.A.), Columbia University Irving Medical Center, New York; Movement Disorders Division (R.N.A.), Neurological Institute, Tel Aviv Sourasky Medical Center and Tel Aviv School of Medicine, Tel Aviv University, Israel; Molecular Medicine Laboratory and Neurology Department (K.R.K.), Concord Clinical School, Concord Repatriation General Hospital, The University of Sydney; Translational Neurogenomics Group (K.R.K.), Genomic and Inherited Disease Program, Garvan Institute of Medical Research; and St Vincent's Healthcare Campus (K.R.K.), Faculty of Medicine, UNSW Sydney, Darlinghurst, New South Wales, Australia.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

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Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

N Engl J Med

December 2024

From the Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University (J.H., X.L.), and the State Key Laboratory of Organ Failure Research, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangdong Institute of Hepatology, Nanfang Hospital (J.H.), Guangzhou, the Department of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University (W.Z.), the Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine (Q.X.), Roche Holding (Q.B., E.C.), Roche Research and Development Center (C.C., Y.H.), and Takeda APAC Biopharmaceutical Research and Development (Q.B.), Shanghai, the Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, First Hospital of Jilin University, Changchun (R.H.), the Center of Infectious Diseases, Laboratory of Infectious and Liver Disease, Institute of Infectious Diseases, West China Hospital, Sichuan University, Chengdu (H.T.), and the Department of Medicine and State Key Laboratory of Liver Research, Queen Mary Hospital, University of Hong Kong, Hong Kong (M.-F.Y.) - all in China; the Division of Infectious Diseases, University Hospital Álvaro Cunqueiro, Galicia Sur Health Research Institute, Servizo Galego de Saúde-Universidade de Vigo, Vigo, Spain (L.E.M.A.); the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital (S.-S.Y.), and the Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University (C.-Y.P.), Taichung, the Department of Internal Medicine, Changhua Christian Hospital, Changhua (W.-W.S.), Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung (W.-L.C.), and National Taiwan University Hospital, Taipei (J.-H.K.) - all in Taiwan; the Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea (D.J.K.); the HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Center and the Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok (A.A.), and the Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai (A.L.) - both in Thailand; Université de Paris-Cité, Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Centre de Recherche sur l'Inflammation, INSERM Unité Mixte de Recherche 1149, Paris (T.A.); F. Hoffmann-La Roche, Basel, Switzerland (F. Canducci, M.T.C., F. Chughlay, K.G., N.G., P.K., R.K., M.T.); Roche Products, Welwyn Garden City (S.D., V.P., B.S., R.U., C.W.), and ID Pharma Consultancy, Yelverton (C.W.) - both in the United Kingdom; Enthera Pharmaceuticals, Milan (F. Canducci); Parexel International, Hyderabad, India (A.P.); and the New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand (E.G.).

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

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Penile Reconstruction with Radial Forearm Free Flap-Present State of the Art.

Indian J Plast Surg

December 2024

Department of Plastic and Reconstructive Surgery, Amrita Hospital, Faridabad, Haryana, India.

Article Synopsis
  • Patients with penile defects, whether congenital or acquired, experience significant psychological distress, and the free radial artery forearm flap method has emerged as a preferred technique for reconstruction.
  • A retrospective study over 16 years reviewed various cases, modifying the initial design to enhance urethral function and stability in the procedure.
  • Results indicated that most patients regained sensation and could urinate standing; however, some experienced complications, and aesthetic outcomes varied, highlighting the technique's potential for effective rehabilitation.
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Insecticide resistance escalation is decreasing the efficacy of vector control tools. Monitoring vector resistance is paramount in order to understand its evolution and devise effective counter-solutions. In this study, we monitored insecticide resistance patterns, vector population bionomics and genetic variants associated with resistance over 3 years from 2021 to 2023 in Uganda.

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Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia.

Circ Res

December 2024

Cardiovascular Research Center, Massachusetts General Hospital, Boston. (C.C., P.X., Z.Y., Y.S., E.S.L., J.D.R., M.C.H.).

Background: Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction. The pathophysiology of preeclampsia remains incompletely understood. This study used human venous endothelial cell (EC) transcriptional profiling to investigate potential novel mechanisms underlying EC dysfunction in preeclampsia.

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Genetic Variants Associated With Preeclampsia and Maternal Serum sFLT1 Levels.

Hypertension

December 2024

Department of Obstetrics and Gynaecology, School of Clinical Medicine, University of Cambridge, United Kingdom. (J.A.M., U.S., F.G., E.C., D.S.C.-J., G.C.S.S.).

Background: Elevated maternal serum sFLT1 (soluble fms-like tyrosine kinase 1) has a key role in the pathophysiology of preeclampsia. We sought to determine the relationship between the maternal and fetal genome and maternal levels of sFLT1 at 12, 20, 28, and 36 weeks of gestational age (wkGA).

Methods: We studied a prospective cohort of nulliparous women (3968 mother-child pairs).

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Aims: Sudden arrhythmic death syndrome (SADS) refers to a sudden death, which remains unexplained despite comprehensive post-mortem examination and a toxicological screen. We aimed to investigate the impact of age and sex on the overall diagnostic yield and underlying aetiology in decedents with SADS using a combined approach of familial evaluation (FE) and molecular autopsy (MA).

Methods And Results: Consecutive referrals to a single centre for FE only, MA only or both, following a SADS death were included.

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The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential.

Int J Mol Sci

December 2024

Centre for Liver and Gastrointestinal Research, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham B15 2TT, UK.

Hepatocellular carcinoma (HCC) represents a significant clinical burden globally and is predicted to continue to increase in incidence for the foreseeable future. The treatment of HCC is complicated by the fact that, in the majority of cases, it develops on a background of advanced chronic inflammatory liver disease. Chronic inflammation can foster an immunosuppressive microenvironment that promotes tumour progression and metastasis.

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Owing to their rapid cooling rate and hence loss-limited propagation distance, cosmic-ray electrons and positrons (CRe) at very high energies probe local cosmic-ray accelerators and provide constraints on exotic production mechanisms such as annihilation of dark matter particles. We present a high-statistics measurement of the spectrum of CRe candidate events from 0.3 to 40 TeV with the High Energy Stereoscopic System, covering 2 orders of magnitude in energy and reaching a proton rejection power of better than 10^{4}.

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Studies have reported the potential role of Boswellic acids (BAs), bioactive pentacyclic triterpenes from (BS), in treating rheumatoid arthritis (RA). However, poor water solubility and limited oral absorption are restricting factors for its better therapeutic efficacy. Based on these assumptions, the current study aimed to develop naturosomal delivery of BAs to boost their extremely low bioavailability, colloidal stability, and water solubility.

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Microplastic (MP) pollution poses a global threat to urban and rural environments and can have negative effects on a range of organisms. Mosquito larvae often breed in water contaminated with MPs, and given their important role as disease vectors, understanding the effects of larval exposure to MPs is critical for understanding the potential impact on their life history traits and subsequent methods for their control. Here, we have exposed first instar larvae of Anopheles gambiae s.

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Cost-effectiveness of radiofrequency echographic multi-spectrometry for the diagnosis of osteoporosis in the United States.

JBMR Plus

January 2025

Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, 6229 GT, The Netherlands.

Radiofrequency echographic multi-spectrometry (REMS) is an innovative, non-ionizing diagnostic technique that has shown high accuracy and precision, making it a promising alternative to DXA for osteoporosis diagnosis in clinical settings. With economic considerations playing an increasingly crucial role in healthcare decisions, this study aims to evaluate the cost-effectiveness and economic impact of improved osteoporosis diagnosis using REMS followed by treatment in the United States. A microsimulation-based Markov model was constructed to estimate the cost per quality-adjusted life year (QALY) gained (in US$2022) for REMS followed by treatment vs no diagnosis and treatment in US women aged 50 yr and older with osteoporosis.

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Background: PRAME (eferentially expressed ntigen in lanoma) is a cancer-testis antigen expressed in several tumor indications, representing an attractive anticancer target. However, its intracellular location limits targeting by traditional methods. PRAME peptides are presented on the surface of tumor cells by human leukocyte antigen (HLA) molecules, indicating that a T cell receptor (TCR)-based strategy that redirects T cells to kill PRAME tumors could be a novel immunotherapeutic option.

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Over the past two decades there has been increased interest in orphan drug development for rare diseases. However, hurdles to clinical trial design for these disorders remain. This phase 1a/1b study addressed several challenges, while evaluating the safety and tolerability of the novel oral molecule KL1333 in healthy volunteers and subjects with primary mitochondrial disease.

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Background: White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease.

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Background: Sex may impact clinical outcomes in patients with stroke treated with dual antiplatelet therapy (DAPT). We aimed to investigate the sex differences in the short-term outcomes of DAPT within a real-world population of patients with noncardioembolic mild-to-moderate ischemic stroke or high-risk transient ischemic attack.

Methods: We performed a propensity score-matched analysis from a prospective multicentric cohort study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]) by including patients with noncardioembolic mild-to-moderate stroke (National Institutes of Health Stroke Scale score of 0-10) or high-risk transient ischemic attack (age, blood pressure, clinical features, duration of transient ischemic attack, presence of diabetes [ABCD] ≥4) who initiated DAPT within 48 hours of symptom onset.

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Neuroimaging Correlates of 3 Distinct Physical-Cognitive Phenotypes in Cognitively Normal Older Adults: The Gothenburg H70 Cohort Study.

Neurology

January 2025

From the Department of Physical Activity and Health (R.W.), the Swedish School of Sport and Health Sciences, GIH, Stockholm; Division of Clinical Geriatrics (R.W., A.M., O.L., S.S., M.S., M.K., E.W.), Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden; Wisconsin Alzheimer's Disease Research Center (R.W.), University of Wisconsin School of Medicine and Public Health, Madison; Centre for Ageing and Health (AgeCap) (J.S., O.L., T.R.S., S.K., A.Z., I.S.), Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; Department of Psychology (J.S.), University of Gothenburg, Göteborg; Neuro Division (J.B.P.), Department of Clinical Neurosciences, Karolinska Institute, Stockholm; FINGERS Brain Health Institute (M.K.), Stockholm; Medical Unit Aging (M.K.), Karolinska University Hospital, Solna, Sweden; Ageing Epidemiology (AGE) Research Unit (M.K.), School of Public Health, Imperial College London, Medical School Building, St Mary's Hospital, United Kingdom; Institute of Public Health and Clinical Nutrition and Institute of Clinical Medicine (M.K.), Neurology, University of Eastern Finland, Kuopio; Aging Research Center (T.R.S.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University; and Department of Psychiatry Cognition and Old Age Psychiatry (I.S.), Sahlgrenska University Hospital, Region Västra Götaland, Mölndal, Sweden.

Background And Objectives: Individuals aged 70 and older frequently experience an increased risk of deficits in both physical and cognitive functions. However, the natural progression and interrelationship of these deficits, as well as their neurologic correlates, remain unclear. We aimed to classify the data-driven physical-cognitive phenotypes and then investigate their associations with neuroimaging markers.

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Background: Residual malaria transmissions in Africa may be associated with improved coverage of insecticide-treated nets, house features, and livestock husbandry. These human-land use activities may drive the ecology and behaviour of malaria vectors which sustain residual malaria transmission. This study was conducted to assess changes in the ecology and behaviour of Anopheles funestus and Anopheles arabiensis in villages with high coverage of insecticide-treated nets to guide the selection of complementary vector control strategies against residual malaria transmission.

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Low Penetrance Sarcomere Variants Contribute to Additive Risk in Hypertrophic Cardiomyopathy.

Circulation

December 2024

Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor. (E.D.S., Y.-C.T., B.E., A.B., O.M., S.S., A.S.H.).

Article Synopsis
  • - Hypertrophic cardiomyopathy (HCM) was traditionally seen as caused by rare, high-risk single-gene changes, but new research indicates common low-risk variants (LowSVs) also play a significant role in the disease.
  • - In a study of over 6000 patients, 12 LowSVs were discovered, which are relatively common in the general population and more prevalent in HCM patients, suggesting they may influence disease severity and risk.
  • - While LowSVs alone are linked to a later onset of HCM and fewer complications, their presence alongside more severe genetic variants increases health risks significantly.
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Inappropriate Therapy and Shock Rates Between the Subcutaneous and Transvenous Implantable Cardiac Defibrillator: A Secondary Analysis of the PRAETORIAN Trial.

Circ Arrhythm Electrophysiol

December 2024

Department of Cardiology, Amsterdam UMC Location University of Amsterdam, Heart Center, Amsterdam Cardiovascular Sciences Heart failure and Arrhythmias, the Netherlands (L.R.A.O.N., S.P., L.V.A.B., T.F.B., A.-F.B.E.Q., W.v.d.S., L.S., J.A.d.V., J.G.P.T., N.R.B., J.R.d.G., K.M.K., A.d.W., A.A.M.W., R.E.K.).

Article Synopsis
  • Inappropriate therapy (IAT) is a significant issue associated with implantable cardiac defibrillator (ICD) therapy, particularly highlighted in early subcutaneous ICD (S-ICD) studies which showed high rates of inappropriate shocks (IAS).
  • The PRAETORIAN trial, an international study with 849 patients, found no major differences in IAT and IAS rates between S-ICD and transvenous ICD (TV-ICD) groups, as both groups had similar cumulative incidences.
  • Key predictors for IAT varied between the two groups, with TV-ICD patients experiencing IAT mainly from supraventricular tachycardias, while S-ICD patients faced issues from cardiac oversensing
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Objectives: The UK has recently established subscription-payment agreements for two antimicrobials: cefiderocol and ceftazidime-avibactam. This article summarises the novel value assessments that informed this process and lessons learned for future pricing and funding decisions.

Methods: The evaluations used decision modelling to predict population incremental net health effects (INHEs), informed by systematic reviews, evidence syntheses, national surveillance data and structured expert elicitation.

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Background: Though epidemiological studies show increased cardiovascular disease (CVD) risks among individuals with psychiatric disorders, findings on sex differences in comorbidity have been inconsistent.

Methods: This genetic epidemiology study examined the sex-specific association between the genetic risk of 3 psychiatric disorders (major depression [MD], schizophrenia, and bipolar disorder), estimated using polygenic scores (PGSs), and risks of 3 CVDs (atrial fibrillation [AF], coronary artery disease [CAD], and heart failure [HF]) in 345 169 European-ancestry individuals (UK Biobank), with analyses replicated in an independent BioVU cohort (n=49 057). Mediation analysis was conducted to determine whether traditional CVD risk factors could explain any observed sex difference.

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Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia.

N Engl J Med

December 2024

From the Cancer Institute, University College London (C.R., K.S.P., M.P.), University College London Hospitals NHS Foundation Trust (C.R.), King's College Hospital NHS Foundation Trust (D.Y.), and Autolus Therapeutics (P.L.-S., Y.Z., W.B., E.B., M.P.), London, Manchester Royal Infirmary, Manchester (E.T.), University Hospitals Birmingham NHS Foundation Trust, Birmingham (S.C.), University Hospitals Bristol NHS Foundation Trust, Bristol (K.H.), Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle (T.M.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (R.M.) - all in the United Kingdom; City of Hope National Medical Center, Duarte (K.S.S.), the Hematology, Blood and Marrow Transplant, and Cellular Therapy Program, University of California, San Francisco, San Francisco (A.C.L.), and UC Davis Medical Center, Sacramento (M.A.) - all in California; the Sarah Cannon Transplant and Cellular Therapy Program, Methodist Hospital, San Antonio (P.S.), and the University of Texas M.D. Anderson Cancer Center, Houston (E.J.) - both in Texas; Hospital Universitari Vall d'Hebron-Universitat Autónoma de Barcelona, Barcelona (P.B.), and Hospital Universitari i Politècnic La Fe, Valencia (M.G.) - both in Spain; Washington University School of Medicine, St. Louis (A.G.); the Sarah Cannon Transplant and Cellular Therapy Program, TriStar Centennial Medical Center, Nashville (J.M.P.); the University of Maryland Medical Center, Baltimore (J.A.Y.); Miller School of Medicine, University of Miami, Miami (A.M.B.), and Moffitt Cancer Center, Tampa (B.D.S.) - both in Florida; Winship Cancer Institute of Emory University, Atlanta (M.L.A.); Colorado Blood Cancer Institute, Denver (L.M.); the University of Rochester Medical Center, Rochester (K.M.O.), and Memorial Sloan Kettering Cancer Center, New York (J.H.P.) - both in New York; the David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago (M.R.B.); and Dana-Farber Cancer Institute, Boston (D.J.D.).

Article Synopsis
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