The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis

STUDY QUESTION: What is the risk of miscarriage among pregnant women who received any of the COVID-19 vaccines? SUMMARY ANSWER: There is no evidence that COVID-19 vaccines are associated with an increased risk of miscarriage. WHAT IS KNOWN ALREADY: In response to the COVID-19 pandemic, the mass roll-out of vaccines helped to boost herd immunity and reduced hospital admissions, morbidity and mortality. Still, many were concerned about the safety of vaccinesfor pregnancy, which may have limited their uptake among pregnant women and those planning a pregnancy. STUDY DESIGN, SIZE, DURATION: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE and Cochrane CENTRAL from inception until June 2022 using a combination of keywords and MeSH terms. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included observational and interventional studies that enrolled pregnant women and evaluated any of the available COVID-19 vaccines compared to placebo or no vaccination. We primarily reported on miscarriage in addition to ongoing pregnancy and/or live birth. MAIN RESULTS AND THE ROLE OF CHANCE: We included data from 21 studies (5 randomised trials and 16 observational studies) reporting on 149,685 women. The pooled rate of miscarriage among women who received a COVID-19 vaccine was 9% (n = 147,49/123,185, 95%CI 0.05-0.14). Compared to those who received a placebo or no vaccination, women who received a COVID-19 vaccine did not have a higher risk of miscarriage (RR 1.07, 95%CI 0.89-1.28, I2 35.8%) and had comparable rates for ongoing pregnancy or live birth (RR 1.00, 95%CI 0.97-1.03, I2 10.72%). LIMITATIONS, REASONS FOR CAUTION: Our analysis was limited to observational evidence with varied reporting, high heterogeneity and risk of bias across included studies, which may limit the generalisability and confidence in our findings. WIDER IMPLICATIONS OF THE FINDINGS: COVID-19 vaccines are not associated with an increase in the risk of miscarriage or reduced rates of ongoing pregnancy or live birth among women of reproductive age. The current evidence remains limited and larger population studies are needed to further evaluate the effectiveness and safety of COVID-19 in pregnancy. STUDY FUNDING/COMPETING INTEREST: No direct funding was provided to support this work. MPR is funded by the Medical Research Council Centre for Reproductive Heath Grant No: MR/N022556/1. BHA hold a personal development award from the National Institute of Health Research in the UK. All authors declare no conflict of interest. REGISTRATION NUMBER: CRD42021289098

Efficacy of virtual reality for pain relief in medical procedures: A systematic review and meta-analysis

BackgroundEffective pain control is crucial to optimise the success of medical procedures. Immersive virtual reality (VR) technology could offer an effective non-invasive, non-pharmacological option to distract patients and reduce their experience of pain. We aimed to evaluate the efficacy of Immersive virtual reality (VR) technology in reducing patient’s pain perception during various medical procedures by conducting a systematic review and meta-analysis.MethodsWe searched MEDLINE, EMBASE, CENTRAL, CINAHL, and SIGLE until December 2022 for all randomised clinical trials (RCT) evaluating any type of VR in patients undergoing any medical procedure. We conducted a random effect meta-analysis summarising standardised mean differences (SMD) with 95% confidence intervals (CI). We evaluated heterogeneity using I 2 and explored it using subgroup and meta-regression analyses.ResultsIn total, we included 92 RCTs (n = 7133 participants). There was a significant reduction in pain scores with VR across all medical procedures (n = 83, SMD − 0.78, 95% CI − 1.00 to − 0.57, I 2 = 93%, p = < 0.01). Subgroup analysis showed varied reduction in pain scores across trial designs [crossover (n = 13, SMD − 0.86, 95% CI − 1.23 to − 0.49, I 2 = 72%, p = < 0.01) vs parallel RCTs (n = 70, SMD − 0.77, 95% CI − 1.01 to − 0.52, I 2 = 90%, p = < 0.01)]; participant age groups [paediatric (n = 43, SMD − 0.91, 95% CI − 1.26 to − 0.56, I 2 = 87%, p = < 0.01) vs adults (n = 40, SMD − 0.66, 95% CI − 0.94 to − 0.39, I 2 = 89%, p = < 0.01)] or procedures [venepuncture (n = 32, SMD − 0.99, 95% CI − 1.52 to − 0.46, I 2 = 90%, p = < 0.01) vs childbirth (n = 7, SMD − 0.99, 95% CI − 1.59 to − 0.38, I 2 = 88%, p = < 0.01) vs minimally invasive medical procedures (n = 25, SMD − 0.51, 95% CI − 0.79 to − 0.23, I 2 = 85%, p = < 0.01) vs dressing changes in burn patients (n = 19, SMD − 0.8, 95% CI − 1.16 to − 0.45, I 2 = 87%, p = < 0.01)]. We explored heterogeneity using meta-regression which showed no significant impact of different covariates including crossover trials (p = 0.53), minimally invasive procedures (p = 0.37), and among paediatric participants (p = 0.27). Cumulative meta-analysis showed no change in overall effect estimates with the additional RCTs since 2018.ConclusionsImmersive VR technology offers effective pain control across various medical procedures, albeit statistical heterogeneity. Further research is needed to inform the safe adoption of this technology across different medical disciplines

The comparative effects of mGlu5 receptor positive allosteric modulators VU0409551 and VU0360172 on cognitive deficits and signalling in the sub-chronic PCP rat model for schizophrenia

The metabotropic glutamate receptor mGlu5 has been implicated in the neuropathology of several debilitating disorders. In schizophrenia, mGlu5 receptor hypofunction has been linked with neuropathology and cognitive deficits, making it an attractive therapeutic target. The cognitive impairment associated with schizophrenia remains an unmet clinical need, with existing antipsychotics primarily targeting positive symptoms and failing to induce consistent, substantial improvements in cognition, thus providing incomplete treatment. Using the sub-chronic phencyclidine (scPCP) rat model, widely shown to mimic the cognitive impairment and neuropathology of schizophrenia, we have investigated two mGlu5 receptor positive allosteric modulators (PAMs), VU0409551 and VU0360172. We compared the efficacy of these compounds in restoring cognitive deficits and, since these two PAMs have reportedly distinct signalling mechanisms, changes in mGlu5 receptor signalling molecules AKT and MAPK in the prefrontal cortex. Although not effective at 0.05 and 1mg/kg, cognitive deficits were significantly alleviated by both PAMs at 10 and 20 mg/kg. The compounds appeared to have differential effects on the scPCP-induced increases in AKT and MAPK phosphorylation: VU0409551 induced a significant decrease in expression of p-AKT, whereas VU0360172 had this effect on p-MAPK levels. Thus, the beneficial effects of PAMs on scPCP-induced cognitive impairment are accompanied by at least partial reversal of scPCP-induced elevated levels of p-MAPK and p-AKT, dysfunction of which is strongly implicated in schizophrenia pathology. These promising data imply an important role for mGlu5 receptor signalling pathways in improving cognition in the scPCP model and provide support for mGlu5 receptor PAMs as a possible therapeutic intervention for schizophrenia

A Novel Approach of Using Electrostatic Field to Reduce Thawing Time and Improve Frozen Beef Quality

Objective:The objective of this study was to evaluate the impact of applying an electrostatic field (EF) on thawing characteristics, such as thawing speed and purge loss, as well as its impact on quality attributes during subsequent aging and retail display of beef. Study Description:Striploins from both sides of USDA Choice carcasses (n = 12) were collected and portioned into four equal parts (n = 48). Portions were vacuum packaged and frozen at -40°F for 14 days and randomly assigned to one of four EF thawing treatments: 0 kV (control), 2.5 kV (EF-2.5), 5 kV (EF-5), and 10 kV (EF-10). Within each EF treatment, half of the striploin portions were thawed in an inside cooler (32°F) and half in an outside cooler (36°F). The thawing process was considered complete when all striploin portions reached 30.2°F. After thawing, striploin portions were weighed and purge was collected for analysis, and portions were fabricated into steaks. One steak was used for histological analysis to assess muscle fiber damage and remaining steaks were vacuum packaged and subjected to either 0 or 14 days of aging. After the aging, steaks were placed on Styrofoam trays, overwrapped with polyvinyl chloride, and retail displayed for either 0 or 7 days. Steaks were evaluated daily for objective color as well as subjective evaluation of discoloration. After completion of the designated aging and display period, steaks were utilized for Warner-Bratzler shear force (WBSF), sarcomere length, lipid oxidation, pH, and myofibrillar protein degradation analysis. Results: There was an increase in purge loss for all EF samples compared to the control in the outside cooler location (P\u3c0.05). Application of EF did not reduce thawing times (P\u3e0.05), with EF-10 taking longer to reach the targeted 30.2°F (P\u3c0.05). All EF treatments reduced purge aerobic plate count (P\u3c0.01) in the outside cooler location. The EF-10 had lower WBSF (P\u3c0.05), and EF-10 samples from the outside cooler location tended to have greater muscle fiber spacing (P= 0.09). For the 0-day aged samples, EF-5 on day 7 resulted in more discoloration than the rest of the treatments (P\u3c0.05). In samples aged for 14 days, the EF-5 and EF-2.5 had less discoloration than the control and EF-10 (P\u3c0.05). When looking at the impact of EF on a* (redness), EF-5 had higher a* values (more redness) than the control and EF-2.5 on days 4 and 5 of retail display (P\u3c0.05). The EF applications did not alter myofibrillar protein degradation, sarcomere length, lipid oxidation, and purge protein concentrations (P\u3e0.05). The Bottom Line:The application of EF during thawing did not reduce purge loss and thawing times but showed potential as an antimicrobial intervention and color stabilizer

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells

BACKGROUND: Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1+/MAGE-A4-), which fail to differentiate to pre-spermatogonia (POU5F1-/MAGE-A4+) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to investigate the role of Gankyrin in progression from gonocyte to pre-invasive GCNIS and subsequent invasive TGCC. METHODS: We determined Gankyrin expression in human fetal testicular tissue (gestational weeks 9-20; n = 38), human adult testicular tissue with active spermatogenesis (n = 9), human testicular tissue with germ cell maturation delay (n = 4), testicular tissue from patients with pre-invasive GCNIS (n = 6), and invasive TGCC including seminoma (n = 6) and teratoma (n = 7). Functional analysis was performed in-vitro by siRNA knock-down of Gankyrin in the NTera2 cells (derived from embryonal carcinoma). RESULTS: Germ cell expression of Gankyrin was restricted to a sub-population of prespermatogonia in human fetal testes. Nuclear Gankyrin was also expressed in GCNIS cells of childhood and adult pre-invasive TGCC patients, and in GCNIS from seminoma and non-seminoma patients. Cytoplasmic expression was observed in seminoma tumour cell

Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species–season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds

Importance of proximity to resources, social support, transportation and neighborhood security for mobility and social participation in older adults: results from a scoping study

ABSTRACT: Background: Since mobility and social participation are key determinants of health and quality of life, it is important to identify factors associated with them. Although several investigations have been conducted on the neighborhood environment, mobility and social participation, there is no clear integration of the results. This study aimed to provide a comprehensive understanding regarding how the neighborhood environment is associated with mobility and social participation in older adults.Methods: A rigorous methodological scoping study framework was used to search nine databases from different fields with fifty-one keywords. Data were exhaustively analyzed, organized and synthesized according to the International Classification of Functioning, Disability and Health (ICF) by two research assistants following PRISMA guidelines, and results were validated with knowledge users.Results: The majority of the 50 selected articles report results of cross-sectional studies (29; 58 %), mainly conducted in the US (24; 48 %) or Canada (15; 30 %). Studies mostly focused on neighborhood environment associations with mobility (39; 78 %), social participation (19; 38 %), and occasionally both (11; 22 %). Neighborhood attributes considered were mainly 'Pro ducts and technology' (43; 86) and 'Services, systems and policies' (37; 74 %), but also 'Natural and human- made changes' (27; 54 %) and 'Support and relationships' (21; 42 %). Mobility and social participation were both positively associated with Proximity to resources and recreational facilities, Social support, Having a car or driver's license, Public transportation and Neighborhood security, and negatively associated with Poor user-friendliness of the walking environment and Neighborhood insecurity. Attributes of the neighborhood environment not covered by previous research on mobility and social participation mainly concerned 'Attitudes', and 'Services, systems and policies'.Conclusion: Results from this comprehensive synthesis of empirical studies on associations of the neighborhood environment with mobility and social participation will ultimately support best practices, decisions and the development of innovative inclusive public health interventions including clear guidelines for the creation of age-supportive environments. To foster mobility and social participation, these interventions must consider Proximity to resources and to recreational facilities, Social support, Transportation, Neighborhood security and User-friendliness of the walking environment. Future studies should include both mobility and social participation, and investigate how they are associated with 'Attitudes', and 'Services, systems and policies' in older adults, including disadvantaged older adults