16 research outputs found

    Biodistribution, clearance, and long‐term fate of clinically relevant nanomaterials

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    Realization of the immense potential of nanomaterials for biomedical applications will require a thorough understanding of how they interact with cells, tissues, and organs. There is evidence that, depending on their physicochemical properties and subsequent interactions, nanomaterials are indeed taken up by cells. However, the subsequent release and/or intracellular degradation of the materials, transfer to other cells, and/or translocation across tissue barriers are still poorly understood. The involvement of these cellular clearance mechanisms strongly influences the long-term fate of used nanomaterials, especially if one also considers repeated exposure. Several nanomaterials, such as liposomes and iron oxide, gold, or silica nanoparticles, are already approved by the American Food and Drug Administration for clinical trials; however, there is still a huge gap of knowledge concerning their fate in the body. Herein, clinically relevant nanomaterials, their possible modes of exposure, as well as the biological barriers they must overcome to be effective are reviewed. Furthermore, the biodistribution and kinetics of nanomaterials and their modes of clearance are discussed, knowledge of the long-term fates of a selection of nanomaterials is summarized, and the critical points that must be considered for future research are addressed

    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

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    Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

    Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA‐Epilepsy study

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    Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross‐sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA‐Epilepsy working group. Methods: A state‐of‐the‐art deep learning‐based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( η ρ max 2 ηρmax2 \eta {\mathit{\mathsf{\rho}}}_{\mathsf{max}}^{\mathsf{2}} = .05) and longer epilepsy duration ( η ρ max 2 ηρmax2 \eta {\mathit{\mathsf{\rho}}}_{\mathsf{max}}^{\mathsf{2}} = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE‐HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy

    Large Bowel Obstruction Subsequent to Resected Lobular Breast Carcinoma: An Unconventional Etiology of Malignant Obstruction

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    Introduction. Breast cancer metastasis to the gastrointestinal tract is rare and mostly limited to case reports which recommend consideration of metastasis when breast cancer patients particularly those with invasive lobular carcinoma present with new gastrointestinal complaints. Presentation of case. We report a 50-year-old female who presented with gastrointestinal symptoms of nausea and vomiting determined to be the result of large bowel obstruction secondary to rectosigmoid metastasis and carcinomatosis of breast invasive lobular carcinoma. She was treated with diverting loop sigmoid colostomy for her large bowel obstruction. Discussion. Our case reflects the importance of gastrointestinal surveillance of patients with a history of breast cancer. Current National Comprehensive Cancer Network (NCCN) guidelines for stage I-II breast cancer suggest posttreatment lab and imaging evaluation for metastasis only if new symptoms present. Conclusion. We observed an unusually rapid disease progression, requiring evaluation of new gastrointestinal symptoms. Assessment for GI tract metastatic involvement should be done as early as progression to symptomatic disease can result in need for further invasive surgery in advanced stages of cancer

    What Happened to PhilRice’s Microtiller? A Scaling Study

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    This study inquires on the outscaling of the microtiller, a machine developed by the Philippine Rice Research Institute (PhilRice) in the 1990s to address the tedious rice land cultivation in the Cordillera highlands of the Philippines. Stakeholders of the project were interviewed, particularly staff members of PhilRice and the Department of Agriculture; representatives of the Central Cordillera Agricultural Programme, PhilRice’s partner organization in developing and promoting the microtiller; and manufacturers and farmers in the area. It was found that while the machine offered a solution to the highly tedious land preparation issue, four key factors affected its scaling: absence of private sector engagement, lack of a business plan for scaling, lack of extension services, and the presence of a more versatile and cheaper competitor. This study provides empirical evidence of the usability of the set of scaling ingredients developed by PPPLab and the International Maize and Wheat Improvement Center to facilitate analysis of scaling of innovations. The findings may inform scaling opportunities and strategies for farm machines by agricultural research and development institutions across the globe
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