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1.
Nat Immunol ; 25(4): 607-621, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38589621

ABSTRACT

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.


Subject(s)
Biomedical Research , COVID-19 , Humans , Post-Acute COVID-19 Syndrome , Hospitalization , Immunoglobulin G
2.
Cell ; 184(23): 5699-5714.e11, 2021 11 11.
Article in English | MEDLINE | ID: mdl-34735795

ABSTRACT

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.


Subject(s)
COVID-19 Vaccines/immunology , Vaccines, Synthetic/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , BNT162 Vaccine , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Cross-Priming/immunology , Dose-Response Relationship, Immunologic , Ethnicity , Female , Humans , Immunity , Immunoglobulin G/immunology , Linear Models , Male , Middle Aged , Reference Standards , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Treatment Outcome , Young Adult , mRNA Vaccines
3.
Nature ; 625(7993): 134-147, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38093007

ABSTRACT

Scientific evidence regularly guides policy decisions1, with behavioural science increasingly part of this process2. In April 2020, an influential paper3 proposed 19 policy recommendations ('claims') detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to behavioural interventions also had strong empirical support, as did appealing to social consensus or bipartisan agreement. Targeted language in messaging yielded mixed effects and there were no effects for highlighting individual benefits or protecting others. No available evidence existed to assess any distinct differences in effects between using the terms 'physical distancing' and 'social distancing'. Analysis of 463 papers containing data showed generally large samples; 418 involved human participants with a mean of 16,848 (median of 1,699). That statistical power underscored improved suitability of behavioural science research for informing policy decisions. Furthermore, by implementing a standardized approach to evidence selection and synthesis, we amplify broader implications for advancing scientific evidence in policy formulation and prioritization.


Subject(s)
Behavioral Sciences , COVID-19 , Evidence-Based Practice , Health Policy , Pandemics , Policy Making , Humans , Behavioral Sciences/methods , Behavioral Sciences/trends , Communication , COVID-19/epidemiology , COVID-19/ethnology , COVID-19/prevention & control , Culture , Evidence-Based Practice/methods , Leadership , Pandemics/prevention & control , Public Health/methods , Public Health/trends , Social Norms
4.
J Virol ; 98(7): e0007224, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38814066

ABSTRACT

Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in gag evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants.IMPORTANCEDespite increased coverage in antiretroviral therapy for the prevention of perinatal transmission, paediatric HIV-1 infection remains a significant public health concern, especially in areas of high HIV-1 prevalence. Understanding HIV-1 transmission and the subsequent virus adaptation from the mother to the infant's host environment, as well as the viral factors that affect disease outcome, is important for the development of early immune-directed interventions for infants. This study advances our understanding of vertical HIV-1 transmission, and how infant immune selection pressure is shaping the intra-host evolutionary dynamics of HIV-1.


Subject(s)
Evolution, Molecular , HIV Infections , HIV-1 , Infectious Disease Transmission, Vertical , Mutation , T-Lymphocytes, Cytotoxic , gag Gene Products, Human Immunodeficiency Virus , nef Gene Products, Human Immunodeficiency Virus , Humans , HIV-1/genetics , HIV-1/immunology , T-Lymphocytes, Cytotoxic/immunology , HIV Infections/virology , HIV Infections/immunology , HIV Infections/transmission , Infant , Female , gag Gene Products, Human Immunodeficiency Virus/genetics , gag Gene Products, Human Immunodeficiency Virus/immunology , nef Gene Products, Human Immunodeficiency Virus/genetics , nef Gene Products, Human Immunodeficiency Virus/immunology , Immune Evasion/genetics , Infant, Newborn , Phylogeny , Male , Longitudinal Studies , Pregnancy , Adult
5.
Immunity ; 44(2): 368-79, 2016 Feb 16.
Article in English | MEDLINE | ID: mdl-26885859

ABSTRACT

Humans that are heterozygous for the common S180L polymorphism in the Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous for the allele are at increased risk. The reason for this difference in susceptibility is not clear. We report that Mal has a TLR-independent role in interferon-gamma (IFN-γ) receptor signaling. Mal-dependent IFN-γ receptor (IFNGR) signaling led to mitogen-activated protein kinase (MAPK) p38 phosphorylation and autophagy. IFN-γ signaling via Mal was required for phagosome maturation and killing of intracellular Mycobacterium tuberculosis (Mtb). The S180L polymorphism, and its murine equivalent S200L, reduced the affinity of Mal for the IFNGR, thereby compromising IFNGR signaling in macrophages and impairing responses to TB. Our findings highlight a role for Mal outside the TLR system and imply that genetic variation in TIRAP may be linked to other IFN-γ-related diseases including autoimmunity and cancer.


Subject(s)
Interferon-gamma/metabolism , Macrophages/physiology , Membrane Glycoproteins/metabolism , Mycobacterium tuberculosis/immunology , Receptors, Interleukin-1/metabolism , Tuberculosis, Pulmonary/immunology , Animals , Autophagy/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , HEK293 Cells , Humans , Immunity, Innate/genetics , MAP Kinase Signaling System/genetics , Macrophages/microbiology , Membrane Glycoproteins/genetics , Mice , Mice, Knockout , Polymorphism, Genetic , Protein Binding/genetics , RNA, Small Interfering/genetics , Receptors, Interferon/metabolism , Receptors, Interleukin-1/genetics , Tuberculosis, Pulmonary/genetics , Interferon gamma Receptor
6.
Proc Natl Acad Sci U S A ; 119(38): e2203385119, 2022 09 20.
Article in English | MEDLINE | ID: mdl-36095174

ABSTRACT

Managing agricultural landscapes to support biodiversity conservation requires profound structural changes worldwide. Often, discussions are centered on management at the field level. However, a wide and growing body of evidence calls for zooming out and targeting agricultural policies, research, and interventions at the landscape level to halt and reverse the decline in biodiversity, increase biodiversity-mediated ecosystem services in agricultural landscapes, and improve the resilience and adaptability of these ecosystems. We conducted the most comprehensive assessment to date on landscape complexity effects on nondomesticated terrestrial biodiversity through a meta-analysis of 1,134 effect sizes from 157 peer-reviewed articles. Increasing landscape complexity through changes in composition, configuration, or heterogeneity significatively and positively affects biodiversity. More complex landscapes host more biodiversity (richness, abundance, and evenness) with potential benefits to sustainable agricultural production and conservation, and effects are likely underestimated. The few articles that assessed the combined contribution of linear (e.g., hedgerows) and areal (e.g., woodlots) elements resulted in a near-doubling of the effect sizes (i.e., biodiversity level) compared to the dominant number of studies measuring these elements separately. Similarly, positive effects on biodiversity are stronger in articles monitoring biodiversity for at least 2 y compared to the dominant 1-y monitoring efforts. Besides, positive and stronger effects exist when monitoring occurs in nonoverlapping landscapes, highlighting the need for long-term and robustly designed monitoring efforts. Living in harmony with nature will require shifting paradigms toward valuing and promoting multifunctional agriculture at the farm and landscape levels with a research agenda that untangles complex agricultural landscapes' contributions to people and nature under current and future conditions.


Subject(s)
Biodiversity , Conservation of Natural Resources , Farms , Conservation of Natural Resources/methods
7.
Proc Natl Acad Sci U S A ; 119(29): e2205498119, 2022 07 19.
Article in English | MEDLINE | ID: mdl-35858344

ABSTRACT

HLA class I (HLA-I) allotypes vary widely in their dependence on tapasin (TAPBP), an integral component of the peptide-loading complex, to present peptides on the cell surface. We identified two single-nucleotide polymorphisms that regulate TAPBP messenger RNA (mRNA) expression in Africans, rs111686073 (G/C) and rs59097151 (A/G), located in an AP-2α transcription factor binding site and a microRNA (miR)-4486 binding site, respectively. rs111686073G and rs59097151A induced significantly higher TAPBP mRNA expression relative to the alternative alleles due to higher affinity for AP-2α and abrogation of miR-4486 binding, respectively. These variants associated with lower Plasmodium falciparum parasite prevalence and lower incidence of clinical malaria specifically among individuals carrying tapasin-dependent HLA-I allotypes, presumably by augmenting peptide loading, whereas tapasin-independent allotypes associated with relative protection, regardless of imputed TAPBP mRNA expression levels. Thus, an attenuated course of malaria may occur through enhanced breadth and/or magnitude of antigen presentation, an important consideration when evaluating vaccine efficacy.


Subject(s)
Histocompatibility Antigens Class I , Malaria, Falciparum , Membrane Transport Proteins , Plasmodium falciparum , Binding Sites , Genetic Variation , Histocompatibility Antigens Class I/immunology , Humans , Malaria, Falciparum/genetics , Malaria, Falciparum/immunology , Malaria, Falciparum/parasitology , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , MicroRNAs/metabolism , Peptides/immunology , Plasmodium falciparum/immunology , RNA, Messenger/genetics , Transcription Factor AP-2/metabolism
8.
Curr Opin Hematol ; 31(1): 16-23, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37823547

ABSTRACT

PURPOSE OF REVIEW: Models of arterial thrombus formation represent a vital experimental tool to investigate platelet function and test novel antithrombotic drugs. This review highlights some of the recent advances in modelling thrombus formation in vitro and suggests potential future directions. RECENT FINDINGS: Microfluidic devices and the availability of commercial chips in addition to enhanced accessibility of 3D printing has facilitated a rapid surge in the development of novel in-vitro thrombosis models. These include progression towards more sophisticated, 'vessel on a chip' models which incorporate vascular endothelial cells and smooth muscle cells. Other approaches include the addition of branches to the traditional single channel to yield an occlusive model; and developments in the adhesive coating of microfluidic chambers to better mimic the thrombogenic surface exposed following plaque rupture. Future developments in the drive to create more biologically relevant chambers could see a move towards the use of human placental vessels, perfused ex-vivo. However, further work is required to determine the feasibility and validity of this approach. SUMMARY: Recent advances in thrombus formation models have significantly improved the pathophysiological relevance of in-vitro flow chambers to better reflect the in-vivo environment and provide a more translational platform to test novel antithrombotics.


Subject(s)
Endothelial Cells , Thrombosis , Female , Pregnancy , Humans , Placenta , Thrombosis/etiology , Arteries , Hemostasis
9.
HIV Med ; 25(2): 223-232, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37804064

ABSTRACT

OBJECTIVES: Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels. METHODS: Individuals aged 6-19 years with HIV-associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo-controlled randomized trial investigating the effect of 48-week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels. RESULTS: In total, 172 participants were included in this sub-study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow-up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03-1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)-3, -7, and -10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72-1.03, p = 0.103). CONCLUSION: Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV-associated chronic lung disease needs further investigation.


Subject(s)
HIV Infections , Lung Diseases , Child , Humans , Azithromycin/therapeutic use , Biomarkers , Breath Tests , HIV Infections/complications , HIV Infections/drug therapy , Inflammation , Lung Diseases/etiology , Nitric Oxide/analysis , Zimbabwe , Adolescent , Young Adult
11.
Plant Physiol ; 193(2): 966-979, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37265110

ABSTRACT

There is a limited understanding of the carbon assimilation capacity of nonfoliar green tissues and its impact on yield and seed quality since most photosynthesis research focuses on leaf photosynthesis. In this study, we investigate the photosynthetic efficiency of soybean (Glycine max) pods and seeds in a field setting and evaluate its effect on mature seed weight and composition. We demonstrate that soybean pod and seed photosynthesis contributes 13% to 14% of the mature seed weight. Carbon assimilation by soybean pod and seed photosynthesis can compensate for 81% of carbon loss through the respiration of the same tissues, and our model predicts that soybean pod and seed photosynthesis contributes up to 9% of the total daily carbon gain of the canopy. Chlorophyll fluorescence (CF) shows that the operating efficiency of photosystem II in immature soybean seeds peaks at the 10 to 100 mg seed weight stage, while that of immature pods peaks at the 75 to 100 mg stage. This study provides quantitative information about the efficiency of soybean pod and seed photosynthesis during tissue development and its impact on yield.


Subject(s)
Carbon , Glycine max , Photosynthesis , Plant Leaves , Seeds
12.
Clin Genet ; 106(1): 13-26, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38685133

ABSTRACT

The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diagnostic procedures was published in 2012. With the increasing complexity of the genetics of FSHD1 and 2, the increase of genetic testing centers, and the start of clinical trials for FSHD, it is crucial to provide an update on our knowledge of the genetic features of the FSHD loci and renew the international consensus on the molecular testing recommendations. To this end, members of the FSHD European Trial Network summarized the evidence presented during the 2022 ENMC meeting on Genetic diagnosis, clinical outcome measures, and biomarkers. The working group additionally invited genetic and clinical experts from the USA, India, Japan, Australia, South-Africa, and Brazil to provide a global perspective. Six virtual meetings were organized to reach consensus on the minimal requirements for genetic confirmation of FSHD1 and FSHD2. Here, we present the clinical and genetic features of FSHD, specific features of FSHD1 and FSHD2, pros and cons of established and new technologies (Southern blot in combination with either linear or pulsed-field gel electrophoresis, molecular combing, optical genome mapping, FSHD2 methylation analysis and FSHD2 genotyping), the possibilities and challenges of prenatal testing, including pre-implantation genetic testing, and the minimal requirements and recommendations for genetic confirmation of FSHD1 and FSHD2. This consensus is expected to contribute to current clinical management and trial-readiness for FSHD.


Subject(s)
Genetic Testing , Muscular Dystrophy, Facioscapulohumeral , Muscular Dystrophy, Facioscapulohumeral/genetics , Muscular Dystrophy, Facioscapulohumeral/diagnosis , Humans , Genetic Testing/standards , Genetic Testing/methods , Practice Guidelines as Topic
13.
Nicotine Tob Res ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38452212

ABSTRACT

INTRODUCTION: Recruiting special populations to smoking cessation trials is challenging and approaches beyond in-clinic recruitment may be beneficial. This secondary analysis of data from a smoking cessation RCT for individuals with a history of cervical cancer or cervical intraepithelial neoplasia (CIN) explored differences associated with in-clinic vs. online recruitment. METHODS: Participants were recruited from clinics within a university-based NCI-designated cancer center (n=87) and online nationally via Facebook (n=115). Baseline measures included sociodemographics, smoking history, and cancer or CIN history. Study retention and smoking abstinence were assessed 12 months post-baseline. Group differences in baseline characteristics were evaluated. Retention and abstinence were evaluated while controlling for group differences and predictors. RESULTS: Participants recruited online (vs. in-clinic) had higher educational attainment (p=.01) and health literacy (p=.003). They were more likely to have CIN vs. cancer, to be further from the time of diagnosis, and to have completed active treatment (p values<.001). While controlling for these group differences and independent predictors, retention was higher among participants recruited online (log-likelihood χ2(1)=11.41, p<.001). There were no recruitment differences in self-reported (p=.90) or biochemically confirmed smoking abstinence (p=.18). CONCLUSIONS: Compared to individuals recruited in-person, individuals recruited online were more educated, had higher health literacy, and presented with a different clinical profile (i.e., more likely to have CIN vs. cancer and to have completed active treatment). There were few differences in participant characteristics between recruitment approaches, and no differences on any smoking-related variables. Online recruitment has the potential to improve enrollment of cancer survivors to smoking cessation trials. IMPLICATIONS: People with a history of CIN or cervical cancer recruited to a smoking cessation RCT online (vs. in-clinic) were more likely to have a diagnosis of CIN vs. cancer and were more educated and health literate. Participants recruited online were more likely to be retained in the study and there were no differences in smoking abstinence rates at 12-months. Incorporating online recruitment increased the reach of tobacco treatment efforts to a larger and more diverse sample. This could reduce the burden of tobacco-related disease, improve CIN and cancer treatment outcomes, and reduce secondary malignancies and morbidity among this underserved group.

14.
Br J Sports Med ; 58(10): 538-547, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38637135

ABSTRACT

OBJECTIVES: To determine if physiotherapists can deliver a clinically effective very low energy diet (VLED) supplementary to exercise in people with knee osteoarthritis (OA) and overweight or obesity. METHODS: 88 participants with knee OA and body mass index (BMI) >27 kg/m2 were randomised to either intervention (n=42: VLED including two daily meal replacement products supplementary to control) or control (n=46: exercise). Both interventions were delivered by unblinded physiotherapists via six videoconference sessions over 6 months. The primary outcome was the percentage change in body weight at 6 months, measured by a blinded assessor. Secondary outcomes included BMI, waist circumference, waist-to-hip ratio, self-reported measures of pain, function, satisfaction and perceived global change, and physical performance tests. RESULTS: The intervention group lost a mean (SD) of 8.1% (5.2) body weight compared with 1.0% (3.2) in the control group (mean (95% CI) between-group difference 7.2% (95% CI 5.1 to 9.3), p<0.001), with significantly lower BMI and waist circumference compared with control group at follow-up. 76% of participants in the intervention group achieved ≥5% body weight loss and 37% acheived ≥10%, compared with 12% and 0%, respectively, in the control group. More participants in the intervention group (27/38 (71.1%)) reported global knee improvement than in the control group (20/42 (47.6%)) (p=0.02). There were no between-group differences in any other secondary outcomes. No serious adverse events were reported. CONCLUSION: A VLED delivered by physiotherapists achieved clinically relevant weight loss and was safe for people with knee OA who were overweight or obese. The results have potential implications for future service models of care for OA and obesity. TRIAL REGISTRATION NUMBER: NIH, US National Library of Medicine, Clinicaltrials.gov NCT04733053 (1 February 2021).


Subject(s)
Body Mass Index , Obesity , Osteoarthritis, Knee , Weight Loss , Humans , Osteoarthritis, Knee/rehabilitation , Male , Female , Middle Aged , Obesity/diet therapy , Obesity/therapy , Aged , Exercise Therapy/methods , Overweight/diet therapy , Overweight/therapy , Diet, Reducing , Caloric Restriction , Waist Circumference , Weight Reduction Programs/methods , Waist-Hip Ratio
15.
Qual Health Res ; : 10497323241251984, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39030700

ABSTRACT

Public health restrictions to protect physical health during the COVID-19 pandemic had unintended effects on mental health, which may have disproportionately affected some potentially vulnerable groups. This scoping review of qualitative research provides a narrative synthesis of new mothers' perspectives on their mental health during COVID-19 pandemic restrictions through pregnancy to the postpartum period. Database searches in PubMed, CINAHL, and PsycINFO sought primary research studies published until February 2023, which focused on new mothers' self-perceived mental health during the pandemic (N = 55). Our synthesis found that new mothers' mental health was impacted by general public health restrictions resulting in isolation from family and friends, a lack of community support, and impacts on the immediate family. However, public health restrictions specific to maternal and infant healthcare were most often found to negatively impact maternal mental health, namely, hospital policies prohibiting the presence of birthing partners and in-person care for their infants. This review of qualitative research adds depth to previous reviews that have solely examined the quantitative associations between COVID-19 public health restrictions and new mothers' mental health. Here, our review demonstrates the array of adverse impacts of COVID-19 public health restrictions on new mothers' mental health throughout pregnancy into the postpartum period, as reported by new mothers. These findings may be beneficial for policy makers in future public health emergency planning when evaluating the impacts and unintended consequences of public health restrictions on new mothers.

16.
Int J Mol Sci ; 25(2)2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38256024

ABSTRACT

Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced (p < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen (p < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis.


Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Thrombosis , Humans , Biglycan , Decorin , Extracellular Matrix Proteins , Aspirin , Collagen Type I
17.
Int J Mol Sci ; 25(14)2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39062849

ABSTRACT

A key step in platelet production is the migration of megakaryocytes to the vascular sinusoids within the bone marrow. This homing is mediated by the chemokine CXCL12 and its receptor CXCR4. CXCR4 is also a positive regulator of platelet activation and thrombosis. Pim-1 kinase has been shown to regulate CXCR4 signalling in other cell types, and we have previously described how Pim kinase inhibitors attenuate platelet aggregation to CXCL12. However, the mechanism by which Pim-1 regulates CXCR4 signalling in platelets and megakaryocytes has yet to be elucidated. Using human platelets, murine bone marrow-derived megakaryocytes, and the megakaryocyte cell line MEG-01, we demonstrate that pharmacological Pim kinase inhibition leads to reduced megakaryocyte and platelet function responses to CXCL12, including reduced megakaryocyte migration and platelet granule secretion. Attenuation of CXCL12 signalling was found to be attributed to the reduced surface expression of CXCR4. The decrease in CXCR4 surface levels was found to be mediated by rapid receptor internalisation, in the absence of agonist stimulation. We demonstrate that pharmacological Pim kinase inhibition disrupts megakaryocyte and platelet function by reducing constitutive CXCR4 surface expression, decreasing the number of receptors available for agonist stimulation and signalling. These findings have implications for the development and use of Pim kinase inhibitors for the treatment of conditions associated with elevated circulating levels of CXCL12/SDF1α and increased thrombotic risk.


Subject(s)
Blood Platelets , Chemokine CXCL12 , Megakaryocytes , Proto-Oncogene Proteins c-pim-1 , Receptors, CXCR4 , Signal Transduction , Receptors, CXCR4/metabolism , Blood Platelets/metabolism , Blood Platelets/drug effects , Megakaryocytes/metabolism , Megakaryocytes/drug effects , Megakaryocytes/cytology , Humans , Signal Transduction/drug effects , Animals , Proto-Oncogene Proteins c-pim-1/metabolism , Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors , Chemokine CXCL12/metabolism , Mice , Protein Kinase Inhibitors/pharmacology , Cell Movement/drug effects , Cell Line
18.
Vet Surg ; 53(1): 122-130, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37462406

ABSTRACT

OBJECTIVE: To compare mortality of dogs undergoing partial staphylectomy using conventional incisional, carbon dioxide (CO2 ) laser, and bipolar vessel sealing device (BVSD) techniques for the treatment of brachycephalic obstructive airway syndrome (BOAS). STUDY DESIGN: Retrospective multicenter cohort study. ANIMALS: A total of 606 client-owned English bulldogs, French bulldogs, and pugs. METHODS: Medical records from 2011 to 2021 were reviewed for signalment, history, surgical technique, length of hospitalization, and complications. Multivariate statistical analysis was performed to compare odds of mortality between the three techniques of staphylectomy. RESULTS: The overall mortality rate was 24/606 (4.0%). Of those 24 dogs, staphylectomy was performed with BVSD technique in 13 cases, with CO2 laser in nine, and using conventional incisional technique in two. Nine dogs were graded II or III laryngeal collapse, 14 were graded I, and one was unknown. BVSD technique was associated with mortality prior to discharge compared to the other two techniques (OR = 6.0, 95% CI: 1.3-28.4, p = .023). No differences were detected between conventional incisional and CO2 laser techniques. Concurrent higher grade (stage II or III) laryngeal collapse was independently associated with mortality prior to discharge (OR = 4.6, 95% CI: 1.8-11.8, p = .002). CONCLUSION: The use of BVSD and grade of laryngeal collapse were associated with a higher risk of perioperative mortality. CLINICAL SIGNIFICANCE: Clinical studies using a randomized trial design should be conducted to further determine the putative influence of surgical instrumentation in the perioperative mortality rate following multilevel surgery in dogs with BOAS.


Subject(s)
Airway Obstruction , Craniosynostoses , Dog Diseases , Larynx , Lasers, Gas , Humans , Dogs , Animals , Lasers, Gas/therapeutic use , Carbon Dioxide , Cohort Studies , Dog Diseases/therapy , Airway Obstruction/surgery , Airway Obstruction/veterinary , Craniosynostoses/veterinary , Syndrome , Retrospective Studies
19.
Vet Anaesth Analg ; 51(3): 235-243, 2024.
Article in English | MEDLINE | ID: mdl-38413340

ABSTRACT

OBJECTIVE: To investigate if preoperative ondansetron reduces postoperative nausea associated with laparoscopic gastropexy and castration in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Twenty client-owned, healthy male dogs. METHODS: Dogs were premedicated with dexmedetomidine (2-5 mcg kg-1) and methadone (0.2-0.5 mg kg-1) intramuscularly. General anesthesia was induced with propofol and maintained with an inhalant anesthetic agent. Dogs were randomized into group S (saline 0.1 mL kg-1, intravenously) or group O (ondansetron 0.2 mg kg-1, intravenously). Plasma and serum were collected before premedication and 3 hours postextubation to measure arginine vasopressin (AVP) and cortisol concentrations. Nausea scoring occurred before and 10 minutes after premedication, immediately after extubation, and at 1, 2 and 3 hours postextubation. Data were analyzed by mixed and split-plot anova with Bonferroni adjustment for the number of group comparisons. Significance was set at p < 0.05. RESULTS: Nausea scores increased over time at 1 (p = 0.01) and 2 (p < 0.001) hours postextubation in both groups compared with before premedication. Median nausea score (0-100 mm) for groups S and O before premedication were 2.5 and 0.5 mm, respectively. At 1 and 2 hours postextubation, group S scored 7.5 and 4.0 mm and group O scored 6.0 and 5.0 mm, respectively. No significant differences in nausea scores within or between groups were observed before premedication and 3 hours postextubation. Cortisol concentrations increased significantly 3 hours postextubation in both groups (p < 0.001) compared with before premedication, with no differences between groups. AVP concentrations showed no significant differences within or between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative intravenous administration of ondansetron (0.2 mg kg-1) did not impact postoperative nausea after laparoscopic gastropexy and castration. Investigation of higher doses of ondansetron on the incidence of postoperative nausea and vomiting in dogs after surgery is warranted.


Subject(s)
Antiemetics , Gastropexy , Laparoscopy , Ondansetron , Orchiectomy , Postoperative Nausea and Vomiting , Dogs , Animals , Male , Ondansetron/administration & dosage , Postoperative Nausea and Vomiting/veterinary , Postoperative Nausea and Vomiting/prevention & control , Laparoscopy/veterinary , Antiemetics/administration & dosage , Orchiectomy/veterinary , Orchiectomy/adverse effects , Gastropexy/veterinary , Dog Diseases/surgery , Prospective Studies , Preoperative Care/veterinary , Preoperative Care/methods
20.
Aust Occup Ther J ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38702985

ABSTRACT

INTRODUCTION: The Sensory Processing Measure 2 (SPM2) and the Sensory Profile 2 (SP2) are two sensory processing scales often used by occupational therapists. The SPM2 and SP2 both claim to assess aspects of children's sensory processing. This cross-sectional study examined the convergent validity of the SPM2-Home Form (SPM2-HF) and Child SP2 for school-aged neurotypical children. METHODS: Thirty parents/caregivers of neurotypical children aged 7 to 12 completed the SPM2-HF and the Child SP2 about their child. Spearman rho's correlation coefficient with bootstrapping was used to investigate the correlations among the sensory, behavioural, and quadrant scores of the Child SP2 and SPM2-HF subscale scores. CONSUMER AND COMMUNITY INVOLVEMENT: Given the topic, consumers and community members were not involved in the design, execution, or write up of the study results. RESULTS: Several statistically significant correlations were found between the sensory and quadrant subscales of the Child SP2 with the SPM-HF. Strong to moderate correlations were established between the sensory subscales of the Child SP2 and the SPM2-HF, ranging from 0.40 to 0.74 (p < 0.05). Additionally, correlations between the quadrant subscales of the Child SP2 and the subscales of the SPM2-HF ranged from weak (0.38) to strong (0.77) correlations (p < 0.05). CONCLUSION: These results provide evidence of convergent validity between the SPM2-HF and Child SP2 for neurotypical school-aged children. Further research on the psychometric properties of the SPM2-HF and Child SP2 is recommended.

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