Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
Journal of Clinical Oncology ; JOUR:418, 40(28 Supplement).
Article in English | EMBASE | ID: covidwho-2098621

ABSTRACT

Background: Pain affects 40-90% of patients with advanced cancer. Supplementing pharmacologic therapy with behavioral skills may improve pain outcomes. We sought to evaluate patients' perspectives of a pain-cognitive behavioral therapy (CBT) mobile health intervention for cancer pain. Method(s): We recruited patients from the Dana-Faber Cancer Institute outpatient palliative care clinic to review the pain-CBT mHealth intervention. Eligible patients were >21 years old, had an incurable solid malignancy, chronic pain related to cancer, and were using opioids for cancer. We excluded hospitalized patients and those with pain from a recent surgery, dementia/delirium, or an opioid use disorder. In individual, qualitative interviews patients reviewed pain-CBT content modified for advanced cancer and mHealth delivery, and provided feedback on the relevance of the content in the context of their own pain. Result(s): Patients (n = 14) reviewed pain-CBT app content and wireframes. Most rated the content and user interface as highly usable, informative, aesthetically pleasing, convenient, and relevant to their experiences. Suggested improvement included revising technical content to increase clarity/ reduce literacy, shortening length of texts, and including additional tracking for daily opioid use. Six subthemes regarding patients' current pain management approaches were identified. Individuals endorsed using physical coping skills including engaging in physical activity and at times struggling to recognize physical limits. Many endorsed utilizing psychological coping such as accepting their pain, reframing thoughts about pain, and using distraction or relaxation to cope. Social support was relevant to coping for almost all patients, and many described COVID-19 distancing guidelines as disruptive. Patients endorsed complex relationships with opioids including guilt related to use or difficulty understanding prescription instructions. Most patients emphasized the relationship between sleep, stress, and pain as central to their pain management, and that they wished their clinicians reviewed the relationship between pain and stress earlier. Conclusion(s): MHealth delivery was viewed as an attractive method to both integrate and deliver behavioral pain management skills with opioid support to alleviate cancer pain. A future pilot study will evaluate the app's feasibility and acceptability in patients with advanced cancer.

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-337987

ABSTRACT

Pregnant women are an at-risk group for severe COVID-19, though the majority experience mild/asymptomatic disease. Although severe COVID-19 has been shown to be associated with immune activation at the maternal-fetal interface even in the absence of active viral replication, the immune response to asymptomatic/mild COVID-19 remains unknown. Here, we assessed immunological adaptations in both blood and term decidua from 9 SARS-exposed pregnant women with asymptomatic/mild disease and 15 pregnant SARS-naive women. In addition to selective loss of tissue-resident decidual macrophages, we report attenuation of antigen presentation and type I IFN signaling but upregulation of inflammatory cytokines and chemokines in blood monocyte derived decidual macrophages. On the other hand, infection was associated with remodeling of the T cell compartment with increased frequencies of activated CD69+ tissue-resident T cells and decreased abundance of Tregs. Interestingly, frequencies of cytotoxic CD4 and CD8 T cells increased only in the blood, while CD8 effector memory T cells were expanded in the decidua. In contrast to decidual macrophages, signatures of type I IFN signaling were increased in decidual T cells. Finally, T cell receptor diversity was significantly reduced with infection in both compartments, albeit to a much greater extent in the blood. The resulting aberrant immune activation in the placenta, even with asymptomatic disease may alter the exquisitely sensitive developing fetal immune system, leading to long-term adverse outcomes for offspring.

4.
Modern Pathology ; 35(SUPPL 2):815-816, 2022.
Article in English | EMBASE | ID: covidwho-1857624

ABSTRACT

Background: Although there are many studies examining the clinical outcomes of women and their infants diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, during pregnancy, the reasons causing the possible adverse outcomes remain unclear1. This study examines placental pathology from women who contracted COVID-19 during pregnancy at this university hospital institution. Design: This study was centered around all 19 placenta specimens from patients infected with COVID-19 at this university hospital. The American College of Obstetricians and Gynecologists (ACOG) allow for the judgement of the Obstetrics physician to be the predominant factor in the decision of sending the placenta specimen for pathology evaluation. Therefore ACOG and CRICO (a risk retention group for medical practitioners) work in conjunction to recommend that placentas be sent for pathology evaluation when clinically indicated. All 19 placenta specimens that were submitted in this study met at least one of these recommendations and therefore 19 age matched controls without COVID-19 infection were reviewed in order to outline any significant clinical trends. The age matched controls were selected within the same time frame as the COVID-19 specimens, which was June 2020 to August 2021. Results: The interval of initial COVID-19 diagnosis and time of placenta evaluation was documented in each case, with the median time interval being 2 days (minimum 1day to maximum 91 days). The gestational age for each patient was calculated, and the average gestational age was a full term pregnancy of 37.2 weeks. 90% of the patients were identified to be of Hispanic ethnicity and heritage, while the other two patients were of Caucasian descent. 63% of the placental weights from the COVID specimens were 25th percentile or lower, whereas only 21% of the age matched controls were 25th percentile or lower. 63% of the cases were recognized to contain histopathological abnormalities, 10.5% in aged matched controls. 4 cases were found to have intra-placental infarction (figure 1), 2 cases were identified to have chorangiosis, 1 case of villous ischemic change, 1 case of decidual laminar necrosis, 1 case of meconium, and 2 cases of acute chorioamnionitis. Conclusions: In this study on average the placenta weight was identified to be lower than age matched controls and placental abnormalities were identified more often in patients infected with COVID 19 (63% vs. 10.5%). (Table Presented).

5.
Journal of Pain ; 23(5):28-29, 2022.
Article in English | EMBASE | ID: covidwho-1849569

ABSTRACT

Individuals experience variable degrees of severity and interference from chronic pain. While clinical diagnosis and pain symptomology may importantly inform treatment options, person-level characteristics may also impact treatment efficacy. The biopsychosocial model of pain includes several pain-modulatory factors which may inform meaningful categorization, or clustering, of individuals with chronic pain, and help predict pain outcomes. In this observational, longitudinal study conducted approximately shortly after the onset of social distancing, patients with chronic pain (N=94) completed validated assessments of known psychosocial (depression, stress, sleep, catastrophizing) pain modulators and pain intensity, which were used to empirically cluster patients into 3 groups using a two-step hierarchical approach. Subsequently, at 1 year later, degree of pain interference, loneliness, social support, mindfulness, and optimism were compared between these 3 groups using ANOVAs. Participants clustered empirically into three groups: 1) Global Elevation Symptoms (GES), characterized by high psychological distress and moderate pain intensity;2) Pain Intensity Predominant (PIP), characterized by high pain intensity, but average psychological distress;and 3) Less Elevated Symptoms (LES), characterized by low pain intensity and psychological distress. At the 1-year follow-up, patients in the GES cluster reported significantly greater pain interference than the other two clusters, as well as greater feelings of loneliness and lower mindfulness and optimism compared to the LES cluster. This study supports prior research suggesting that psychosocial-based clustering of patients can be used to identify distinct groups of chronic pain patients. In particular, patients identified as belonging to the GES cluster (high psychological distress, high pain intensity early after onset of social distancing) were at greater risk of suffering from pain a year later, as well as loneliness and less mindfulness and optimism. Patient clustering techniques may help identify high risk patients and suggest behavioral interventions to improve pain by addressing psychosocial modulators of pain. Grant support from 5R35GM128691-02.

6.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333740

ABSTRACT

New SARS-CoV-2 variants that have accumulated multiple mutations in the spike (S) glycoprotein enable increased transmission and resistance to neutralizing antibodies. Here, we study the antigenic and structural impacts of the S protein mutations from four variants, one that was involved in transmission between minks and humans, and three that rapidly spread in human populations and originated in the United Kingdom, Brazil or South Africa. All variants either retained or improved binding to the ACE2 receptor. The B.1.1.7 (UK) and B.1.1.28 (Brazil) spike variants showed reduced binding to neutralizing NTD and RBD antibodies, respectively, while the B.1.351 (SA) variant showed reduced binding to both NTD- and RBD-directed antibodies. Cryo-EM structural analyses revealed allosteric effects of the mutations on spike conformations and revealed mechanistic differences that either drive inter-species transmission or promotes viral escape from dominant neutralizing epitopes. HIGHLIGHTS: Cryo-EM structures reveal changes in SARS-CoV-2 S protein during inter-species transmission or immune evasion.Adaptation to mink resulted in increased ACE2 binding and spike destabilization.B.1.1.7 S mutations reveal an intricate balance of stabilizing and destabilizing effects that impact receptor and antibody binding.E484K mutation in B.1.351 and B.1.1.28 S proteins drives immune evasion by altering RBD conformation.S protein uses different mechanisms to converge upon similar solutions for altering RBD up/down positioning.

7.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333537

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 has escalated into a global crisis. The spike (S) protein that mediates cell entry and membrane fusion is the current focus of vaccine and therapeutic antibody development efforts. The S protein, like many other viral fusion proteins such as HIV-1 envelope (Env) and influenza hemagglutinin, is glycosylated with both complex and high mannose glycans. Here we demonstrate binding to the SARS-CoV-2 S protein by a category of Fab-dimerized glycan-reactive (FDG) HIV-1-induced broadly neutralizing antibodies (bnAbs). A 3.1 A resolution cryo-EM structure of the S protein ectodomain bound to glycan-dependent HIV-1 bnAb 2G12 revealed a quaternary glycan epitope on the spike S2 domain involving multiple protomers. These data reveal a new epitope on the SARS-CoV-2 spike that can be targeted for vaccine design. HIGHLIGHTS: Fab-dimerized, glycan-reactive (FDG) HIV-1 bnAbs cross-react with SARS-CoV-2 spike.3.1 A resolution cryo-EM structure reveals quaternary S2 epitope for HIV-1 bnAb 2G12.2G12 targets glycans, at positions 709, 717 and 801, in the SARS-CoV-2 spike.Our studies suggest a common epitope for FDG antibodies centered around glycan 709.

8.
Modern Pathology ; 35(SUPPL 2):815-816, 2022.
Article in English | Web of Science | ID: covidwho-1782155
9.
Journal of Virology ; 96(4):16, 2022.
Article in English | Web of Science | ID: covidwho-1755961

ABSTRACT

Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not ex-hibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited antiviral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, similar to 50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine (Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19) and cytokine (Ifn-lambda and Tnf-alpha) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Micro-glia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work dem-onstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

11.
Circulation ; 144(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1629550

ABSTRACT

Introduction: The corona virus disease-2019 (COVID-19) pandemic has been associated with decrease in the rate of myocardial infarction (MI), and this is likely related to patients delaying seeking care due to COVID-19 concerns. Methods: In this retrospective observational study, we compared all patient encounters who presented with MI to Ascension Saint Agnes Hospital, Baltimore, MD from March to December 2020 with a cohort of patient encounters who presented with MI during an equivalent period in 2019. We analyzed the data using Statistical Package for Social Sciences (SPSS) and used two sample t-test and Chi-square x to compare the outcomes between the two cohorts as appropriate. Results: We had 275 MI admissions that met our inclusion criteria. When comparing MI encounters in 2020 with encounters in 2019, there were no significant differences in mortality (2.1% vs. 4.5%, p=0.274), acute renal failure(14.9% vs. 18.7%, p=0.403), or intensive care unit admission (7.1% vs. 7.5%, p=0.892). There were no significant differences in modalities of treatment including cardiac catheterization (94.3% vs. 95.5%, p=0.652), or medical treatment alone (13.5% vs. 18.7%, p=0.241) in 2020 vs. 2019. Referrals for coronary artery bypass graft surgery (CABG) were significantly higher in 2020 than in 2019 (8.5% vs. 3.0%, p=0.050). When comparing patients who presented during the first 5 months of the pandemic (March-July) with patients who presented in the last 5 months of the pandemic in 2020 (August-December);there were significant decrease in rate of cardiac catheterization (90.5% vs. 98.5%, p = 0.041), and significant increase in rate of medical treatment alone (18.9% vs. 7.5%, p = 0.047) in the first 5 months. Conclusions: The first five months of the pandemic were associated with a significant decrease in rates of pursuing cardiac catheterization along with an increase rates of medical treatment alone compared with the following five months.

12.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-293060

ABSTRACT

Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited anti-viral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ~50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine ( Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19 ) and cytokine ( Ifn-lambda and Tnf-alpha ) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. Importance: Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

13.
Monthly Labor Review ; : 1-45, 2021.
Article in English | Web of Science | ID: covidwho-1315110
14.
2020 Ieee Pes & Ias Powerafrica Conference ; 2020.
Article in English | Web of Science | ID: covidwho-1271185

ABSTRACT

Excessive electrical consumption within buildings is a common issue across all sectors. Each sector responds to this differently, and the Higher Education (HE) sector is no exception, where energy-intensive laboratories are prevalent in most universities. The COVID-19 crisis has meant that these laboratories have either closed or reduced their opening hours;hereby, this offers an excellent opportunity to assess how shutdown periods impact on electrical consumption. This research assesses unregulated electrical consumption within a single laboratory building, which functions as a research engineering building. An Energy-Management System (EMS) was used to collect the room-level data, primarily electrical consumption. This study found that unregulated electricity consumption typically reduced rapidly during the shutdown period with a percentage reduction of 46.61% between the week before lockdown and the week during the lockdown.

15.
Cell ; 184(11): 2955-2972.e25, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1237636

ABSTRACT

Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.


Subject(s)
Antibodies, Neutralizing/immunology , HIV-1/immunology , Immunoglobulin Fab Fragments/immunology , Polysaccharides/immunology , SARS-CoV-2/immunology , Simian Immunodeficiency Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , env Gene Products, Human Immunodeficiency Virus/immunology , Animals , B-Lymphocytes/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/immunology , Dimerization , Epitopes/immunology , Glycosylation , HIV Antibodies/immunology , HIV Infections/immunology , Humans , Immunoglobulin Fab Fragments/chemistry , Macaca mulatta , Polysaccharides/chemistry , Receptors, Antigen, B-Cell/chemistry , Simian Immunodeficiency Virus/genetics , Vaccines/immunology , env Gene Products, Human Immunodeficiency Virus/chemistry , env Gene Products, Human Immunodeficiency Virus/genetics
16.
Journal of Pain ; 22(5):611-612, 2021.
Article in English | EMBASE | ID: covidwho-1226308

ABSTRACT

The COVID-19 pandemic social distancing mandates have increased levels of social isolation, a change which appears to have impacted some chronic pain patients more than others. Previous research suggests that feelings of loneliness and sleep disturbance may importantly modulate pain. In the present study, we examined whether the personality trait of introversion served as a protective factor against worsening pain interference during conditions of social isolation, and whether this was related to differences in sleep disturbance and loneliness. Chronic pain patients in Massachusetts (n=150) completed electronic questionnaires 4-8 weeks after the state-wide social distancing mandate. Validated questionnaires included the Brief Pain Inventory (BPI), Myers-Briggs introversion/extroversion subscale (1-10), UCLA Loneliness and PROMIS Sleep Disturbance short forms. Change scores were calculated by subtracting recalled scores from current scores. Linear regression was used to assess association between factors, and mediation analyses were used to assess the degree to which other factors mediated the relationship between introversion and change in pain interference. Introversion scores were inversely related to increased pain interference since social distancing (Rho=-0.194, p=0.017), such that patients with higher introversion scores showed little to no change in pain interference, compared to more extroverted patients. Higher introversion was also associated with lower increases in sleep disturbance (Rho=-0.163, p=0.046) and loneliness (Rho=-0.279, p=0.001) since social distancing. Multiple simple mediation analyses revealed that the relationship between introversion and change in pain interference was partially mediated by differential changes in sleep disturbance and loneliness. Chronic pain patients experience varying degrees of worsening of pain interference with social distancing, which may be partially explained by their degree of introversion/extroversion. In particular, more introverted patients appeared to be partially protected, experiencing less of an increase in loneliness and sleep disturbance and, in turn, less of an increase in pain interference. 5R35GM128691-02.

SELECTION OF CITATIONS
SEARCH DETAIL