Tag: pubmed

Schweiz Arch Tierheilkd. 2023 Sep;165(9):573-584. doi: 10.17236/sat00402.

ABSTRACT

This study aimed to describe equine transportation practices and transport-related behavioural and health problems in Switzerland and to identify possible associations between them. An online survey was disseminated to Swiss equine industry members and questioned respondents’ details, transport practices (before, during, and after journeys), horse transport-related behavioural (TRPBs) and health problems (TRHPs) experienced in the previous 2 years. The survey generated 441 valid responses, analysed using descriptive statistics and logistic regression models (outcomes: TRPBs, TRHPs, injuries, diarrhea). Respondents were mainly women (79,5 %), younger than 50 years (75 %), and amateurs (80 %). Most of the respondents transported one or two horses (88,7 %), for a short (< 2 hours) journey (75,5 %). Pre-transport practices were performed by 72,1 % of respondents and horses’ fitness for travel was assessed in the majority of cases (66,5 %). During the journey, horses were tethered (92,6 %) and monitored (52,7 %). The majority of respondents (74,9 %) assessed also the horses’ fitness after travel. TRPBs were reported by 13,4 % of respondents. TRPBs’ likelihood increased when the respondents were women, performed pre-transport practices and training for transport, did not assess drinking behaviour and general health before journey, and the horses experienced also TRHPs. TRHPs were reported by 34 % of the respondents and were associated with younger respondents, use of trucks, doing pre-transport practices, wearing protections, not monitoring horses during transport and preexisting TRPBs. Among TRHPs the most frequent were injuries (72,1 %) and diarrhea (41 %). The likelihood of injuries increased with younger respondents, use of trucks, wearing protections, lack of monitoring during transport and TRPBs. While younger respondents, longer journeys, wearing protections, lack of monitoring during transport, measuring rectal temperature after journeys and TRPBs increased the odds of reporting diarrhea. Even though our findings must be interpreted with caution due to survey limitations, considering that the found associations do not always mean causation, they highlight the strengths and weaknesses of transport practices in Switzerland and report evidence to implement current regulations on the protection of horse welfare during transport.

PMID:37646097 | DOI:10.17236/sat00402

Hum Reprod. 2023 Aug 29:dead173. doi: 10.1093/humrep/dead173. Online ahead of print.

ABSTRACT

STUDY QUESTION: Does assisted hatching increase the cumulative live birth rate in subfertile couples with repeated implantation failure?

SUMMARY ANSWER: This study showed no evidence of effect for assisted hatching as an add-on in subfertile couples with repeated implantation failure.

WHAT IS KNOWN ALREADY: The efficacy of assisted hatching, with regard to the live birth rate has not been convincingly demonstrated in randomized trials nor meta-analyses. It is suggested though that especially poor prognosis women, e.g. women with repeated implantation failure, might benefit most from assisted hatching.

STUDY DESIGN, SIZE, DURATION: The study was designed as a double-blinded, multicentre randomized controlled superiority trial. In order to demonstrate a statistically significant absolute increase in live birth rate of 10% after assisted hatching, 294 participants needed to be included per treatment arm, being a total of 588 subfertile couples. Participants were included and randomized from November 2012 until November 2017, 297 were allocated to the assisted hatching arm of the study and 295 to the control arm. Block randomization in blocks of 20 participants was applied and randomization was concealed from participants, treating physicians, and laboratory staff involved in the embryo transfer procedure. Ovarian hyperstimulation, oocyte retrieval, laboratory procedures, embryo selection for transfer and cryopreservation, the transfer itself, and luteal support were performed according to local protocols and were identical in both the intervention and control arm of the study with the exception of the assisted hatching procedure which was only performed in the intervention group. The laboratory staff performing the assisted hatching procedure was not involved in the embryo transfer itself.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were eligible for inclusion in the study after having had either at least two consecutive fresh IVF or ICSI embryo transfers, including the transfer of frozen and thawed embryos originating from those fresh cycles, and which did not result in a pregnancy or as having had at least one fresh IVF or ICSI transfer and at least two frozen embryo transfers with embryos originating from that fresh cycle which did not result in a pregnancy. The study was performed at the laboratory sites of three tertiary referral hospitals and two university medical centres in the Netherlands.

MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative live birth rate per started cycle, including the transfer of fresh and subsequent frozen/thawed embryos if applicable, resulted in 77 live births in the assisted hatching group (n = 297, 25.9%) and 68 live births in the control group (n = 295, 23.1%). This proved to be statistically not significantly different (relative risk: 1.125, 95% CI: 0.847 to 1.494, P = 0.416).

LIMITATIONS, REASONS FOR CAUTION: There was a small cohort of subfertile couples that after not achieving an ongoing pregnancy, still had cryopreserved embryos in storage at the endpoint of the trial, i.e. 1 year after the last randomization. It cannot be excluded that the future transfer of these frozen/thawed embryos increases the cumulative live birth rate in either or both study arms. Next, at the start of this study, there was no international consensus on the definition of repeated implantation failure. Therefore, it cannot be excluded that assisted hatching might be effective in higher order repeated implantation failures.

WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated no evidence of a statistically significant effect for assisted hatching by increasing live birth rates in subfertile couples with repeated implantation failure, i.e. the couples which, based on meta-analyses, are suggested to benefit most from assisted hatching. It is therefore suggested that assisted hatching should only be offered if information on the absence of evidence of effect is provided, at no extra costs and preferably only in the setting of a clinical trial taking cost-effectiveness into account.

STUDY FUNDING/COMPETING INTEREST(S): None.

TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR 3387, NL 3235, https://www.clinicaltrialregister.nl/nl/trial/26138).

TRIAL REGISTRATION DATE: 6 April 2012.

DATE OF FIRST PATIENT’S ENROLMENT: 28 November 2012.

PMID:37646072 | DOI:10.1093/humrep/dead173

Neurol Clin Pract. 2023 Oct;13(5):e200180. doi: 10.1212/CPJ.0000000000200180. Epub 2023 Aug 28.

ABSTRACT

BACKGROUND AND OBJECTIVES: To develop a valid, disease-specific, patient-reported outcome (PRO) measure for adolescents and adults with Friedreich ataxia (FA) for use in therapeutic trials.

METHODS: We conducted semistructured qualitative interviews and a national cross-sectional study of individuals with FA to determine the most prevalent and burdensome symptoms and symptomatic themes to this population. These symptoms and symptomatic themes were included as questions in the first version of the Friedreich’s Ataxia-Health Index (FA-HI). We subsequently used factor analysis, beta interviews with 17 individuals with FA, and test-retest reliability assessments with 20 individuals with FA to evaluate, refine, and optimize the FA-HI. Finally, we determined the capability of the FA-HI to differentiate between subgroups of FA participants with varying levels of disease severity.

RESULTS: Participants with FA identified 18 symptomatic themes of importance to be included as subscales in the FA-HI. The FA-HI demonstrates high internal consistency and test-retest reliability, and it was identified by participants as highly relevant, comprehensive, and easy to complete. FA-HI total and subscale scores statistically differentiated between subgroups of participants with varying levels of disease burden.

DISCUSSION: Initial evaluation of the FA-HI supports its validity and reliability as a PRO for assessing how individuals with FA feel and function.

PMID:37646046 | PMC:PMC10462051 | DOI:10.1212/CPJ.0000000000200180

Front Immunol. 2023 Aug 14;14:1171176. doi: 10.3389/fimmu.2023.1171176. eCollection 2023.

ABSTRACT

Decades of research have probed the molecular and cellular mechanisms that control the immune response to malaria. Yet many studies offer conflicting results on the functional impact of innate immunity for controlling parasite replication early in infection. We conduct a meta-analysis to seek consensus on the effect of innate immunity on parasite replication, examining three different species of rodent malaria parasite. Screening published studies that span four decades of research we collate, curate, and statistically analyze infection dynamics in immune-deficient or -augmented mice to identify and quantify general trends and reveal sources of disagreement among studies. Additionally, we estimate whether host factors or experimental methodology shape the impact of immune perturbations on parasite burden. First, we detected meta-analytic mean effect sizes (absolute Cohen’s h) for the difference in parasite burden between treatment and control groups ranging from 0.1475 to 0.2321 across parasite species. This range is considered a small effect size and translates to a modest change in parasitaemia of roughly 7-12% on average at the peak of infection. Second, we reveal that variation across studies using P. chabaudi or P. yoelii is best explained by stochasticity (due to small sample sizes) rather than by host factors or experimental design. Third, we find that for P. berghei the impact of immune perturbation is increased when young or female mice are used and is greatest when effector molecules (as opposed to upstream signalling molecules) are disrupted (up to an 18% difference in peak parasitaemia). Finally, we find little evidence of publication bias suggesting that our results are robust. The small effect sizes we observe, across three parasite species, following experimental perturbations of the innate immune system may be explained by redundancy in a complex biological system or by incomplete (or inappropriate) data reporting for meta-analysis. Alternatively, our findings might indicate a need to re-evaluate the efficiency with which innate immunity controls parasite replication early in infection. Testing these hypotheses is necessary to translate understanding from model systems to human malaria.

PMID:37646037 | PMC:PMC10461630 | DOI:10.3389/fimmu.2023.1171176

Front Immunol. 2023 Aug 14;14:1211980. doi: 10.3389/fimmu.2023.1211980. eCollection 2023.

ABSTRACT

BACKGROUND: Clinically, some patients whose HBsAg becomes negative owing to antiviral therapy or spontaneously still show a low level of HBV DNA persistence in serum. T-lymphocyte subsets, cytokine levels and HBV S gene sequences were analyzed in this study.

METHODS: A total of 52 HBsAg-negative and HBV DNA-positive patients(HBsAg-/HBV DNA+ patients), 52 persistently HBsAg-positive patients(HBsAg+/HBV DNA+ patients) and 16 healthy people were evaluated. T-lymphocyte subsets of these patients were detected by flow cytometry, serum cytokines and chemokines were detected by the Luminex technique, and the HBV S region was evaluated by Sanger sequencing. T%, T-lymphocyte, CD8+ and CD4+T lymphocyte were lower in the HBsAg-negative group than in the HC group. Compared with the HBsAg-positive group, the HBsAg-negative group had lower levels in T lymphocyte %, CD8+T lymphocyte %, CD8+T lymphocyte and CD4/CD8. These difference were statistically significant (P<0.05). Serum IFN-γ, IFN-α and FLT-3L levels were significantly higher in the HBsAg-negative group than in the HBsAg-positive group (P<0.05). However, levels of many cytokines related to inflammation (i.e., IL-6, IL-8, IL10, IL-12, IL-17A) were lower in the HBsAg-negative group. Fifty-two HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., Y100C, S114T, C124Y, P127L, G130R, T131N, M133T, C137S, G145A) and TMD region substitutions (i.e., E2K/R/D, G7D/R, G10D, A17R, F20L/S, L21V, L22V).

CONCLUSIONS: According to the results of T-lymphocyte subsets and serum cytokines, it can be deduced that the cellular immune function of HBsAg-negative patients is superior to that of HBsAg-positive patients, with attenuation of liver inflammation. HBsAg-negative patients may show a variety of mutations and amino acid replacement sites at high frequency in the HBV S region, and these mutations may lead to undetectable HBsAg, HBsAg antigenic changes or secretion inhibition.

PMID:37646026 | PMC:PMC10461097 | DOI:10.3389/fimmu.2023.1211980

Front Immunol. 2023 Aug 14;14:1235914. doi: 10.3389/fimmu.2023.1235914. eCollection 2023.

ABSTRACT

INTRODUCTION: SARS-CoV-2 elicits a hyper-inflammatory response that contributes to increased morbidity and mortality in patients with COVID-19. In the case of HIV infection, despite effective anti-retroviral therapy, people living with HIV (PLWH) experience chronic systemic immune activation, which renders them particularly vulnerable to the life-threatening pulmonary, cardiovascular and other complications of SARS-CoV-2 co-infection. The focus of the study was a comparison of the concentrations of systemic indicators of innate immune dysfunction in SARS-CoV-2-PCR-positive patients (n=174) admitted with COVID-19, 37 of whom were co-infected with HIV.

METHODS: Participants were recruited from May 2020 to November 2021. Biomarkers included platelet-associated cytokines, chemokines, and growth factors (IL-1β, IL-6, IL-8, MIP-1α, RANTES, PDGF-BB, TGF-β1 and TNF-α) and endothelial associated markers (IL-1β, IL-1Ra, ICAM-1 and VEGF).

RESULTS: PLWH were significantly younger (p=0.002) and more likely to be female (p=0.001); median CD4+ T-cell count was 256 (IQR 115 -388) cells/μL and the median HIV viral load (VL) was 20 (IQR 20 -12,980) copies/mL. Fractional inspired oxygen (FiO2) was high in both groups, but higher in patients without HIV infection (p=0.0165), reflecting a greater need for oxygen supplementation. With the exception of PDGF-BB, the levels of all the biomarkers of innate immune activation were increased in SARS-CoV-2/HIV-co-infected and SARS-CoV-2/HIV-uninfected sub-groups relative to those of a control group of healthy participants. The magnitudes of the increases in the levels of these biomarkers were comparable between the SARS-CoV-2 -infected sub-groups, the one exception being RANTES, which was significantly higher in the sub-group without HIV. After adjusting for age, sex, and diabetes in the multivariable model, only the association between HIV status and VEGF was statistically significant (p=0.034). VEGF was significantly higher in PLWH with a CD4+ T-cell count >200 cells/μL (p=0.040) and those with a suppressed VL (p=0.0077).

DISCUSSION: These findings suggest that HIV co-infection is not associated with increased intensity of the systemic innate inflammatory response during SARS-CoV-2 co-infection, which may underpin the equivalent durations of hospital stay, outcome and mortality rates in the SARS-CoV-2/HIV-infected and -uninfected sub-groups investigated in the current study. The apparent association of increased levels of plasma VEGF with SARS-CoV-2/HIV co-infection does, however, merit further investigation.

PMID:37646024 | PMC:PMC10461055 | DOI:10.3389/fimmu.2023.1235914

HGG Adv. 2023 Aug 1;4(4):100228. doi: 10.1016/j.xhgg.2023.100228. eCollection 2023 Oct 12.

ABSTRACT

Clinician bias negatively impacts the healthcare received by marginalized communities. In this study, we explored factors that influence clinician and trainee bias against individuals with intellectual disabilities and its impact on clinical judgment in prenatal genetic testing settings. Specifically, we examined bias toward a fetus with a higher chance of developing a disability. We compared genetics specialists with their non-expert counterparts. This web-based study included clinical vignettes, implicit association tests (IATs), and an educational module. 595 participants were recruited via their institution or professional society. We conducted statistical analyses, including regression models controlling for key demographic characteristics, to analyze recommendation patterns and degree of change after the module. Genetics expertise strongly correlated with appropriate testing recommendation when the patient would not consider pregnancy termination (r = 1.784 pre-module, r = 1.502 post-module, p < 0.01). Factors that influenced pre-module recommendation to test include increased age (r = -0.029, p < 0.05), high religiosity (r = 0.525, p < 0.05), and participant personal preference against testing (r = 1.112, p < 0.01). Responses among participants without genetics expertise improved after the educational module (Z = -4.435, p < 0.01). 42% of non-experts who answered inappropriately changed their answer to match guidelines after the module. Individual bias, along with structural and institutional bias, permeates family planning encounters and significantly decreases quality of care. We demonstrate here that anti-bias training is effective, particularly for non-expert providers, and it can improve the care provided to individuals with intellectual disability. Evidence-based training such as this one can help providers make appropriate genetic counseling recommendations.

PMID:37646012 | PMC:PMC10461018 | DOI:10.1016/j.xhgg.2023.100228

bioRxiv. 2023 Aug 17:2023.05.03.539321. doi: 10.1101/2023.05.03.539321. Preprint.

ABSTRACT

Intuitively, combining multiple sources of evidence should lead to more accurate decisions than considering single sources of evidence individually. In practice, however, the proper computation may be difficult, or may require additional data that are inaccessible. Here, based on the concept of conditional independence, we consider expressions that can serve either as recipes for integrating evidence based on limited data, or as statistical benchmarks for characterizing evidence integration processes. Consider three events, A, B , and C . If A and B are conditionally independent with respect to C , then the probability that C occurs given that both A and B are known, P ( C | A, B ), can be easily calculated without the need to measure the full three-way dependency between A, B , and C . This simplified approach can be used in two general ways: to generate predictions by combining multiple (conditionally independent) sources of evidence, or to test whether separate sources of evidence are functionally independent of each other. These applications are demonstrated with four computer-simulated examples, which include detecting a disease based on repeated diagnostic testing, inferring biological age based on multiple biomarkers of aging, discriminating two spatial locations based on multiple cue stimuli (multisensory integration), and examining how behavioral performance in a visual search task depends on selection histories. Besides providing a sound prescription for estimating outcomes, this methodology may be useful for analyzing experimental data of many types.

PMID:37646001 | PMC:PMC10461915 | DOI:10.1101/2023.05.03.539321

bioRxiv. 2023 Aug 14:2023.08.14.553219. doi: 10.1101/2023.08.14.553219. Preprint.

ABSTRACT

Sequencing of viral infections has become increasingly common over the last decade. Deep sequencing data in particular have proven useful in characterizing the roles that genetic drift and natural selection play in shaping within-host viral populations. They have also been used to estimate transmission bottleneck sizes from identified donor-recipient pairs. These bottleneck sizes quantify the number of viral particles that establish genetic lineages in the recipient host and are important to estimate due to their impact on viral evolution. Current approaches for estimating bottleneck sizes exclusively consider the subset of viral sites that are observed as polymorphic in the donor individual. However, allele frequencies can change dramatically over the course of an individual’s infection, such that sites that are polymorphic in the donor at the time of transmission may not be polymorphic in the donor at the time of sampling and allele frequencies at donor-polymorphic sites may change dramatically over the course of a recipient’s infection. Because of this, transmission bottleneck sizes estimated using allele frequencies observed at a donor’s polymorphic sites may be considerable underestimates of true bottleneck sizes. Here, we present a new statistical approach for instead estimating bottleneck sizes using patterns of viral genetic variation that arose de novo within a recipient individual. Specifically, our approach makes use of the number of clonal viral variants observed in a transmission pair, defined as the number of viral sites that are monomorphic in both the donor and the recipient but carry different alleles. We first test our approach on a simulated dataset and then apply it to both influenza A virus sequence data and SARS-CoV-2 sequence data from identified transmission pairs. Our results confirm the existence of extremely tight transmission bottlenecks for these two respiratory viruses, using an approach that does not tend to underestimate transmission bottleneck sizes.

PMID:37645981 | PMC:PMC10462048 | DOI:10.1101/2023.08.14.553219

Res Sq. 2023 Aug 17:rs.3.rs-3242375. doi: 10.21203/rs.3.rs-3242375/v1. Preprint.

ABSTRACT

In this note, we present an innovative approach called “homologous hypothesis tests” that focuses on cross-sectional comparisons of average tumor volumes at different time-points. By leveraging the correlation structure between time-points, our method enables highly efficient per time-point comparisons, providing inferences that are highly efficient as compared to those obtained from a standard two-sample $t$-test. The key advantage of this approach lies in its user-friendliness and accessibility, as it can be easily employed by the broader scientific community through standard statistical software packages.

PMID:37645958 | PMC:PMC10462185 | DOI:10.21203/rs.3.rs-3242375/v1