Restricted Maximum Likelihood Model Research Articles

Global Rate of Willingness to Volunteer Among Medical and Health Students During Pandemic: Systemic Review and Meta-Analysis.

During health crises such as the COVID-19 pandemic, shortages of health care workers often occur. Recruiting students as volunteers could be an option, but it is uncertain whether the idea is well-accepted. This study aims to estimate the global rate of willingness to volunteer among medical and health students in response to the COVID-19 pandemic. A systematic search was conducted on PubMed, Embase, Scopus, and Google Scholar for studies reporting the number of health students willing to volunteer during COVID-19 from 2019 to November 17, 2023. The meta-analysis was performed using a restricted maximum-likelihood model with logit transformation. A total of 21 studies involving 26,056 health students were included in the meta-analysis. The pooled estimate of the willingness-to-volunteer rate among health students across multiple countries was 66.13%, with an I2 of 98.99% and P value of heterogeneity (P-Het)<.001. Removing a study with the highest influence led to the rate being 64.34%. Our stratified analyses indicated that those with older age, being first-year students, and being female were more willing to volunteer (P<.001). From highest to lowest, the rates were 77.38%, 77.03%, 65.48%, 64.11%, 62.71%, and 55.23% in Africa, Western Europe, East and Southeast Asia, Middle East, and Eastern Europe, respectively. Because of the high heterogeneity, the evidence from this study has moderate strength. The majority of students are willing to volunteer during COVID-19, suggesting that volunteer recruitment is well-accepted.

The effect of oral synbiotics on the gut microbiota and inflammatory biomarkers in healthy adults: a systematic review and meta-analysis

Abstract Context Prior research has explored the effect of synbiotics, the combination of probiotics and prebiotics, on the gut microbiota in clinical populations. However, evidence related to the effect of synbiotics on the gut microbiota in healthy adults has not been reviewed to date. Objective A systematic review and meta-analysis was conducted to comprehensively investigate the effect of synbiotics on the gut microbiota and inflammatory markers in populations of healthy adults. Data Sources Scopus, PubMed, Web of Science, ScienceDirect, MEDLINE, CINAHL, and The Cochrane Library were systematically searched to retrieve randomized controlled trials examining the primary outcome of gut microbiota or intestinal permeability changes after synbiotic consumption in healthy adults. Secondary outcomes of interest were short-chain fatty acids, inflammatory biomarkers, and gut microbiota diversity. Data Extraction Weighted (WMD) or standardized mean difference (SMD) outcome data were pooled in restricted maximum likelihood models using random effects. Twenty-seven articles reporting on 26 studies met the eligibility criteria (n = 1319). Data Analysis Meta-analyses of 16 studies showed synbiotics resulted in a significant increase in Lactobacillus cell count (SMD, 0.74; 95% confidence interval [CI], 0.15, 1.33; P = 0.01) and propionate concentration (SMD, 0.22; 95% CI, 0.02, 0.43; P = 0.03) compared with controls. A trend for an increase in Bifidobacterium relative abundance (WMD, 0.97; 95% CI, 0.42, 2.52; P = 0.10) and cell count (SMD, 0.82; 95% CI, 0.13, 1.88; P = 0.06) was seen. No significant differences in α-diversity, acetate, butyrate, zonulin, IL-6, CRP, or endotoxins were observed. Conclusion This review demonstrates that synbiotics modulate the gut microbiota by increasing Lactobacillus and propionate across various healthy adult populations, and may result in increased Bifidobacterium. Significant variations in synbiotic type, dose, and duration should be considered as limitations when applying findings to clinical practice. Systematic Review Registration PROSPERO no. CRD42021284033.

Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis

Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort. We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2. We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9-59·8; I2=77%), 60% (56-64; I2=35%) were women, and 80% (72-89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid β in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75-87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56-75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90-97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93-100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90-97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54-88; I2=89%), Lewy body disease (44%, 25-62; I2=77%), and cerebrovascular injury (42%, 24-60; I2=88%). These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity. None.

Willingness-to-pay for urban green space: A meta-analysis of surveys across China

Sustainable ecosystem services are increasingly recognized amid rapid regional transformation. While the rate of urbanization in China continues to rise, there is an urgent need to evaluate public preferences and their associated economic values concerning urban green space (UGS). The aim of this study was to calculate the overall willingness-to-pay (WTP) for UGS across China. Literature search was performed systematically on Scopus, Scilit, PubMed, and Google Scholar databases on 11 November 2023. Studies reporting the WTP in China were included in the analysis. Quality of the included studies were appraised by using Q-SSP tool consisting of 20-item quality of survey studies in psychology. To calculate the overall willing to pay rate and WTP, a meta-analysis was performed using restricted maximum-likelihood model on raw proportions. A total of nine studies were included comprised of 9381 valid responses with high quality according to Q-SSP (score: 70–90%). Findings from the meta-analysis indicated that the rate of willing to pay for UGS was 70.8% (95%CI: 60%, 82%; p-Het&lt;0.001, I2= 99.37%). The rate was not affected by sample size, age, gender, and education (p&gt;0.05). Among mainland Chinese population alone, the average minimum WTP was 2.97 USD/month, and increased to 3.36 USD/month if combined with Hong Kong population. A majority of over 70% Chinese population were willing to pay for UGS. Nevertheless, high heterogeneity in the pooled estimates suggest the importance of addressing contextual variables and presence of regional disparities.

Rapid review and meta-analysis of serial intervals for SARS-CoV-2 Delta and Omicron variants

BackgroundThe serial interval is the period of time between symptom onset in the primary case and symptom onset in the secondary case. Understanding the serial interval is important for determining transmission dynamics of infectious diseases like COVID-19, including the reproduction number and secondary attack rates, which could influence control measures. Early meta-analyses of COVID-19 reported serial intervals of 5.2 days (95% CI: 4.9–5.5) for the original wild-type variant and 5.2 days (95% CI: 4.87–5.47) for Alpha variant. The serial interval has been shown to decrease over the course of an epidemic for other respiratory diseases, which may be due to accumulating viral mutations and implementation of more effective nonpharmaceutical interventions. We therefore aggregated the literature to estimate serial intervals for Delta and Omicron variants.MethodsThis study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A systematic literature search was conducted of PubMed, Scopus, Cochrane Library, ScienceDirect, and preprint server medRxiv for articles published from April 4, 2021, through May 23, 2023. Search terms were: (“serial interval” or “generation time”), (“Omicron” or “Delta”), and (“SARS-CoV-2” or “COVID-19”). Meta-analyses were done for Delta and Omicron variants using a restricted maximum-likelihood estimator model with a random effect for each study. Pooled average estimates and 95% confidence intervals (95% CI) are reported.ResultsThere were 46,648 primary/secondary case pairs included for the meta-analysis of Delta and 18,324 for Omicron. Mean serial interval for included studies ranged from 2.3–5.8 days for Delta and 2.1–4.8 days for Omicron. The pooled mean serial interval for Delta was 3.9 days (95% CI: 3.4–4.3) (20 studies) and Omicron was 3.2 days (95% CI: 2.9–3.5) (20 studies). Mean estimated serial interval for BA.1 was 3.3 days (95% CI: 2.8–3.7) (11 studies), BA.2 was 2.9 days (95% CI: 2.7–3.1) (six studies), and BA.5 was 2.3 days (95% CI: 1.6–3.1) (three studies).ConclusionsSerial interval estimates for Delta and Omicron were shorter than ancestral SARS-CoV-2 variants. More recent Omicron subvariants had even shorter serial intervals suggesting serial intervals may be shortening over time. This suggests more rapid transmission from one generation of cases to the next, consistent with the observed faster growth dynamic of these variants compared to their ancestors. Additional changes to the serial interval may occur as SARS-CoV-2 continues to circulate and evolve. Changes to population immunity (due to infection and/or vaccination) may further modify it.

Interleukin-1 beta treatment alters prostaglandin-related mRNA expression and cytokine abundance in equine endometrial culture

Interleukin-1β (IL-1β) is a proinflammatory cytokine that modulates the immunoinflammatory response and induces prostaglandin synthesis. IL-1β has a variety of roles in the endometrium during inflammation, decidualization, pregnancy, and post-partum. It can cause changes in endometrial gene expression and may affect cytokine, chemokine, and prostaglandin-related pathways. The relationship between IL-1β, prostaglandins, and downstream inflammatory responses in the equine uterine environment is not fully known. Our objective was to determine the effect that IL-1β has on prostaglandin-related gene expression, as well as cytokine and chemokine abundance, in endometrial cell culture. Light breed mares (n=8) were examined daily by transrectal ultrasound until ovulation. An endometrial biopsy was collected at day 11 post ovulation, and used for primary endometrial cell culture. Cells were cultured in DMEM with 10% FBS. At 80% confluence, cells were either not supplemented or supplemented with: 100 nM Progesterone (Prog); 1 nM Estradiol-17β (Est); or 100 nM Prog and 1 nM Est (P+E). After 24 hours, cells were treated with recombinant equine IL-1β at either 10 ng/mL (Low) or 1000 ng/mL (High), or 0.2% DMSO as an untreated control. Twenty-four hours post-treatment, supernatant was collected, and a bead-based multiplex assay was used to quantify concentration of twelve cytokines and chemokines. Total RNA was extracted from the cells and mRNA expression was evaluatedfor 10 prostaglandin-related genes, using the ΔCT method with ACTB as the reference gene. Data analysis was performed using JMP Pro 16, using a restricted maximum likelihood model with treatment and supplementation as factors, and mare as a random factor. Treatment with IL-1β High resulted in increased levels of CCL2, CCL5, and CCL11 (p<0.001) in cell culture supernatant, as well as increased mRNA expression of PTGS2 (p<0.02), regardless of supplementation. Cells supplemented with Prog or P+E and treated with IL-1β High had increased expression of IL1R1, IL1RAP, PTGS1, and PTGES compared to non-supplemented cells (p<0.05). IL-1β High treatment increased LiF expression in cells supplemented with Prog or P+E compared to untreated cells (p<0.05). IL-1β likely acts to modulate inflammatory pathways in the endometrium, altering chemokine levels and activating expression of PTGS2, leading to changes in downstream prostaglandin synthesis and other related pathways. Progesterone appears to increase expression of several target genes when compared to non-supplemented cells. Progesterone has been shown to be involved in the suppression of several inflammatory pathways, and investigation into the ovarian steroid regulation of genes and proteins in the equine endometrium is warranted. Further studies on the effect of IL-1β on molecular pathways and prostaglandin regulation could lead to a greater understanding of the uterine environment in the pregnant and non-pregnant mare.

Characterization of interferons in the equine conceptus and endometrium

Interferons (IFN) are involved in the maintenance and establishment of pregnancy in a variety of species. There are three types of IFNs, which include type I (IFN-α, β, ε, τ, and δ), type II (IFN-γ), and type III (IFN-λ1, λ2 and λ3). In the horse, IFNA, IFND and IFNO are expressed in the equine trophoblast, and IFNE is expressed in higher abundance in equine endometrium during the luteal phase. However, investigation of IFNs and their receptors during early equine pregnancy is still lacking. Our objective was to investigate the expression of IFN types I and II and their receptors, and other IFN related genes in equine conceptuses and endometrium during early pregnancy. Mares were examined daily by transrectal ultrasound when in estrus until the day (D) of ovulation (OV). Pregnant (P) group mares were bred using artificial insemination by a single fertile stallion. Conceptuses were detected and measured via transrectal ultrasound and collected via uterine lavage using 0.9% NaCl through a transcervical bivona catheter. Following conceptus retrieval, an endometrial biopsy was collected. Endometrial samples from nonpregnant (NP) mares were collected at D11 (NP11; n=6) and D13 (NP13; n=7), while endometrium and conceptuses were collected from pregnant mares at D11 (P11; n=7), D13 (P13; n=8), and D16 (P16; n=6). As the majority of nonpregnantmares would have undergone luteolysis, a D16 sample was not included in this study. Total RNA was isolated and evaluated for expression of interferon-related genes using Real-time PCR. The mean threshold cycle was determined and then normalized to the mean of the reference genes (GAPDH and ACTB) (ΔCT). A restricted maximum likelihood model was performed in JMP Pro 16 (Cary, NC) with mare as a random factor with significance set at P<0.05. There was no amplification for IFNB and IFND in the endometrium, and no amplification of IFNG, IFNB and IFNAR2 in the conceptus. In the endometrium, IFNAR1 and IFNGR1 had higher expression in P11 compared to P13 (P<0.02). Expression of endometrial IFNG mRNA was higher in P11 and P16 compared to P13 (P<0.004). There was no difference in the mRNA relative abundance of endometrial ISG15 and IFITM1 between groups or days. In the conceptus, IFNA, IFNO, and IFNGR2 expression were higher in D16 compared to other ages (P<0.05). D11 and D16 conceptuses had higher expression of IFNAR1 compared to D13 (P<0.0002), while IFNGR1 was higher in D16 compared to D11 (P<0.004). The role of interferons during maternal recognition of pregnancy in the horse is unknown. Unlike the pig, the horse embryo does not seem to express IFNG. Further investigation is underway.

Differential gene expression in the equine endometrium and conceptus from Day 11 to 16 post-ovulation

Mobility of the equine conceptus is essential for maternal recognition of pregnancy (MRP) and is regulated by the conceptus's own derived prostaglandin secretion. Our objective was to compare prostaglandin-related genes and other genes of interest during the expected MRP time. Light breed mares were examined daily by transrectal ultrasound when in estrus until the day (D) of ovulation. Mares in the pregnant (P) group were bred by artificial insemination with >500 million progressively motile normal sperm from one fertile stallion until D0. Conceptuses were detected and measured via transrectal ultrasound and collected via uterine lavage using 0.9% NaCl through a transcervical bivona catheter. Endometrium was collected via a transcervical biopsy punch following conceptus retrieval. Endometrium of non-pregnant (NP) mares was collected at: D11 (NP11; n=6) and D13 (NP13; n=7), while endometrium from the pregnant horn and conceptuses was collected at D11 (P11; n=7), D13 (P13; n=8), and D16 (P16; n=6). Total RNA from trophoblast and endometrial samples was isolated and evaluated for expression of PTGS2, PTGES, mPGES2, PTGER4, PTGER2, PTGIS, PTGIR, HPGD, SLCO2A1, CRTC2, NR3C1, CBR1, CREB, NF-Kβ, SPP1, IGFBP1, ESR1 and DNTTIP2 using Real-time PCR. Mean threshold cycle was determined and normalized to the reference gene (GAPDH and ACTB) (ΔCT). Statistical analyses were performed using JMP Pro 16, and data was ranked, transformed if necessary, followed by a restricted maximum likelihood model with mare as arandom factor to test differences between Groups and Day. Regarding endometrial mRNA, NP11 had higher expression for NF-Kβ, PTGIS, PTGIR and CBR1 compared to NP13 (p<0.007). ESR1, mPGES2, PTGIS, and CBR1 mRNA were higher in P11 compared to P16 (p<0.05), while CRTC2 was higher in P16 compared to P11 (p<0.06). Lastly, NF-Kβ, PTGIR and CBR1 were higher in P11 compared to P13 (p<0.01), but NF-Kβ P13 was lower compared to P16 (p<0.04). Regarding the conceptuses, CREB and PTGFR expressions were higher in D16 compared to D11 (p<0.003), while CRTC2, NR3C1, NF-Kβ and SPP1 were higher in D16 compared to D11 and 13 (p<0.02). D13 conceptuses had lower expression of HPGD compared to D11 and 16 (p<0.02). Lastly, D11 conceptuses had higher expression of mPGES2, PTGIS and PTGER4 compared to D13 and D16 (p<0.03). Higher expression of D11 PTGIS from both tissues may increase nutrient and blood flow to the endometrium in support of the early conceptus. The upregulation of endometrial NF-Kβ at D11 may be a result of endometrial receptivity through the regulation of inflammation, and the up-regulation of HPGD may function to regulate PGE2 during early pregnancy. Understanding embryonic and endometrial prostaglandin regulation during MRP may help to develop future therapies to ameliorate pregnancy loss in the horse.

Investigation of cytokines in equine serum, conceptuses and endometrium in early pregnancy

Cytokines and their receptor systems are present at the fetomaternal interface of some species and regulate trophoblast biology. The cytokine and chemokine systems are key in the communication between fetal derived trophoblast cells and the maternal tissue. However, evidence for the presence of cytokines and their receptors during early equine pregnancy is lacking. Our objective was to investigate interleukins, chemokine ligands, dendritic cells and TNFα in equine serum, conceptuses and endometrium during early pregnancy. Daily transrectal ultrasound examinations of the mares were performed when in estrus until the day (D) of ovulation (OV). An endometrial biopsy was taken from non-pregnant (NP) mares at: D11 (NP11; n=6) or D13 (NP13; n=7). Mares in the pregnant (P) group were bred by artificial insemination from a single fertile stallion, and transrectal ultrasound was performed to detect and measure conceptuses. On the day of sample collection, conceptuses were collected through a transcervical bivona catheter and uterine lavage using 0.9% NaCl, and this was followed by an endometrial biopsy. Pregnant mares’ conceptuses and endometrial biopsies were retrieved at D11 (P11; n=7), D13 (P13; n=8), or D16 (P16; n=6). A D16 sample was not obtained for NP group. A Bradford assay was performed on extracted endometrium and conceptus tissue to determine total protein concentration,followed by a bead-based equine validated multiplex assay (Luminex Corp. Austin, TX) to quantify concentration of the following equine specific inflammatory markers: IL-4, IL-17, IL-10, IL-1β, CCL2, CCL3, CCL5, CCL11, sCD-14 and TNFα. A restricted maximum likelihood model was performed to compare the protein concentration between groups and days in JMP Pro 16 (Cary, NC) with the mare as a random factor and significance set at p<0.05. Cytokine and chemokine serum concentrations were similar between groups and days of collection. Regarding the endometrium, IL-17 U/mg was higher (p<0.05) in group NP13 [median (interquartile)] [11.4 (8.2, 21.7)] than NP11 [4.1 (2.6, 5.3)]. In pregnant mares, endometrial IL-17 was higher in P13 group [6.3 (3.4, 13.9)] compared to group P16 [2.5 (2.1, 4.8)] (p<0.05). In conceptuses, D11 had significantly higher concentrations of CCL2 [1350.2 (793, 1839.5); p<0.03], CCL3 [1990.9 (998.6, 3083.8); p<0.01], CCL5 [363.2 (149.6, 480.6); p<0.006] and CCL11[3143.7 (1764.2, 5221.9); p<0.01 compared to D16 [66.7 (38.8, 644.8); 67.8 (43, 572.30); 9.1 (6.6, 96.3); 196.2 (150.9, 1436.6)], respectively. Higher chemokine concentrations in the earlier embryos may reflect the recruitment of endometrial leukocytes. Further investigation into the role of cytokines and chemokines in early equine pregnancy is warranted.

Mesenchymal stromal cell conditioned media is immunomodulatory in the equine endometrium

Endometritis is a common and costly disorder in horses that results in poor reproductive performance. Current therapies are supportive, and the industry suffers from a paucity of immunomodulatory treatment modalities for this disease that is characterized by inflammatory dysregulation. Recently, mesenchymal stromal cell conditioned media (MSC-CM) is being explored as a treatment option for various inflammatory conditions due to its immunoregulatory, antimicrobial, biofilm disruption, and tissue repair properties. Our objective was to evaluate changes in the endometrial inflammatory response after treatment with MSC-CM in vitro. We hypothesized that endometrial cells in culture would have altered cytokine expression and production. Five estrous mares were biopsied to establish primary endometrial cell cultures. After cell dissociation, endometrial cells were cultured in DMEM supplemented with 10% FBS and 1% antibiotic antimycotic solution (Sigma Aldrich) at 37°C with 5% CO2. At 80% confluence, cultures were hormonally supplemented with 1nM Estradiol-17β, 100 nM Progesterone, or no supplementation; and 24 hours later, treated with MSC-CM or DMSO as control. Supernatants from the cell cultures were analyzed for cytokine expression using an equine cytokine Multiplex assay (Luminex Corp. Austin, TX) quantifying inflammatory biomarkers including IFN-α, IFN-γ, IL-4, IL-17, IL-10, IL1-β, CCL2, CCL3, CCL5, CCL11, TNF-α, and sCD14. In parallel, cells were lysed and RNA extracted for Real-time PCR using the ΔCT method with ACTB as the reference gene for geneexpression of IL-6, IL-8, PTGS2, PTGES, PTGIS, TNFα, TGFB, and NFKb. Data analysis was performed with JMP Pro 16 with level of significant p<0.05. A restricted maximum likelihood model with treatment, supplementation and their interaction and mare as a random factor was used. There was no effect of hormone supplementation on supernatant cytokine concentrations, but treatment with MSC-CM altered their concentration. MSC-CM treatment increased the concentration of CCL2 pg/ml [median (interquartile)] [1862554 (32482, 240080) (p≤0.02); and decreased CCL3 [66 (0.1, 99)] (p≤ 0.01) and IL-10 [6.5 (0.1, 9.5)] (p≤0.007) compared to DMSO control [3114 (2398.5, 7483); 109 (0.1, 154); and 13 (0.1, 17)], respectively. Gene expression analysis showed that MSC-CM-treated cells had increased expression of IL-6 (p≤0.001), IL-8 (p≤0.001), PTGS2 (p≤0.002), PTGES (p≤0.0012), and NFKb (p≤0.01). Additionally, gene expression analysis revealed an effect of hormone supplementation, with increased expression of IL-8 (p≤0.027) and PTGS2 (p≤0.0443) in estrogen or progesterone supplemented cultures compared to no supplementation. Taken together, treatment with MSC-CM resulted in increased inflammatory marker production and greater gene expression of inflammatory cytokines and prostaglandin-related genes. These results are supportive of the potential role of MSC-CM in equine endometrial immunomodulation. Further studies in vivo are warranted to investigate the clinical outcome of this immunomodulatory effect after intrauterine infusion.

Genetic parameters and selection of mango genotypes using the FAI-BLUP multitrait index

Mango (Mangifera indica L.) presents phenotypic diversity in relation to fruit quality. Due to this diversity, studies on performance and evaluation of genotypes help in the selection of new cultivars. The aim of this study was to select superior mango genotypes for fruit quality using a mixed model selection index. The fruit quality of two hundred and forty six different hybrids and four commercial cultivars (Ataulfo, Kent, Palmer and Tommy Atkins) was evaluated in three consecutive harvests. Estimates of variance components and predictions of phenotypic and genotypic values were obtained, as well as principal component analysis, factor analysis and genotype-ideotype distance (FAI-BLUP). Permanent variance among plants represented the largest portion of phenotypic variance for most traits. Estimates of the repeatability coefficient ranged from 0.09 to 0.96, being high for most variables. The selective accuracy predicted by the restricted maximum likelihood model (REML) ranged from 0.48 to 0.99, revealing a good degree of confidence in the inferences. Eigenvalue estimates revealed five principal components responsible for 77.72% of the total genetic variability. The greatest positive genetic gains were for fruit weight (37.29%), soluble solids/titratable acidity ratio (35.02%), b* (23.02%), pulp firmness (20.99%), ventral diameter (12.18%), transverse diameter (11.80%), skin luminosity (8.08%), soluble solids content (6.97%), length (4.28%), c* (3.08%), pulp luminosity (2.18%) and h* (0.88%). Negative genetic gains were observed for titratable acidity (-26.04%) and a* (-12.82%). Twenty-five genotypes were selected as the most promising based on factor analysis and FAI-BLUP index, promoting improvement and genetic gain in several traits. Between commercial cultivars, Ataulfo was the highest ranked genotype (29th), followed by Kent (36th), Palmer (243th) and Tommy Atkins (247th). The genotypes selected should be included in the next stages of the mango breeding program for high-quality fruits under irrigated cultivation in the Brazilian semiarid region.

Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?

Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother–child pairs, and 6,222 father–child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes.

Influence of the abutment height on marginal bone level changes around two-piece dental implants: Meta-analysis and trial sequential analysis of randomized clinical trials.

The focused question was: "In systemically healthy individuals with at least one two-piece dental implant, what is the efficacy of long (≥2 mm; intervention) compared with short (<2 mm; comparison) shoulder height abutments in peri-implant marginal bone level (MBL) changes at <1 year and ≥1 year reported by randomized controlled clinical trials?" An electronic and hand search was conducted to identify RCTs published up to August 2022. The primary outcome variable was changed in MBL from implant surgery to subsequent follow-ups. Mean values and standard deviations for each study were extracted. Weighted mean differences and 95% confidence intervals were calculated. Meta-analysis for MBL changes was performed through a random-effect restricted maximum-likelihood model at early (<1year) and late (≥1year) stages of bone remodeling. Publication bias and sensitivity tests were also applied. Subgroup analysis was performed to further explore possible sources of heterogeneity in the estimated treatment effect. Trial sequential analysis was performed to assess the required information and false-positive results. Six randomized clinical trials fulfilled the inclusion/exclusion criteria and were included in the qualitative and quantitative analysis with a follow-up range from 6 to 36 months after implant surgery. Meta-analysis revealed that long abutments significantly exhibited 0.27 mm (CI 95% -0.60, 0.06) and 0.33 mm (CI 05% -0.50, -0.16) lower MBL changes compared with short ones at <1year and≥1year, respectively. Subgroup meta-analysis revealed that studies with implants placed in a more subcrestal position significantly exhibited less differences in MBL changes between long and short abutments. No meta-analysis was conducted for peri-implant clinical parameters, and soft-tissue changes provided that reported data were scarce. Trial sequential analysis revealed insufficient information size to provide a definitive answer on the effect of abutment height in MBL. It might be cautiously concluded that two-piece implants with long abutments (≥2 mm) may display a protective role against marginal bone loss when compared with short ones (<2 mm) at <1year and ≥1year. A more subcrestal implant position seemed to minimize the effect of the abutment height in terms of MBL.

Incidence of Cerebral Venous Thrombosis: A Population-Based Study, Systematic Review, and Meta-Analysis.

Studying the baseline incidence of cerebral venous thrombosis (CVT) prior to COVID-19 and the limitations of how this has been previously reported in the literature will help improve understanding of this disease and how risks may have changed in the post-COVID era. We examined CVT incidence using linked administrative data in British Columbia, Canada (population 5.2 million). To contextualize our findings, we also examined CVT incidence in the published literature and searched MEDLINE and EMBASE for article titles and abstracts up to Nov 2, 2021 on CVT incidence in adults. We performed abstract screening and full-text review prior to data extraction and explored associations between CVT incidence and year of study, geographic location, and study quality with meta-analyses and meta-regression. A random-effects restricted maximum likelihood model was used. Publication bias was assessed using the Egger tests and using visual inspection of the funnel plot for symmetry. There were 554 unique CVT cases (mean age 50.9 years, 55.4% women) in British Columbia from 2000 to 2017; overall annual incidence was 8.7 (95%CI' 8.0-9.4) per million. Incidence increased over time in men across the entire study period, and from 2011 to 2017 in women. We identified 22 other studies on CVT incidence before 2020 (21/23 total studies included in meta-analysis). Annual incidence overall was 12.1 (95% CI' 9.9-14.3) per million with significant between-study heterogeneity (I2 98.8%, Qp-value<0.001). There were no significant associations on meta-regression between incidence and study year, study quality score, or gross national income per capita of the study country. Visual inspection of the funnel plot and a significant Egger test (z=2.8, P<0.01) suggested possible publication bias. Incidence of CVT in Canadian data increased over time but remained lower than in other population-based studies. Significant heterogeneity exists in the literature, which may be subject to publication bias.

Effects of Environmental Temperature and Humidity on Milk Composition, Microbial Load, and Somatic Cells in Milk of Holstein Dairy Cows in the Northeast Regions of Iran.

Simple SummaryLivestock performance is influenced by different elements due to the complex interactions between the individual animals and environmental conditions such as temperature and humidity. Hence, the influence of environmental temperature and humidity on milk production quality parameters needs to be investigated. The objective of this study is to elucidate the effect of environmental temperature and humidity on milk composition, microbial load, and somatic cells in the milk of Holstein dairy cows. Our findings reveal that, when temperature increased from 6.2 °C to 31.3 °C, the milk protein, fat, solids-not-fat (SNF), and somatic cell count (SCC) significantly decreased. In contrast, the microbial count in milk significantly increased, by approximately 13.7%. When humidity increased from 54% to 82%, the milk protein, fat, SNF, and SCC significantly increased. However, under the same increase in humidity, the microbial count in milk significantly decreased, by approximately 16.3%. The results indicate that there exists a correlation between different months of the year, temperature, and humidity of the environment, in terms of milk components and somatic cells. Our findings reveal that the optimum performance, in terms of milk composition, occurred in the first quarter of the year, while milk quality decreased as temperature increased and humidity decreased.The present study aims to examine the relationships between temperature and humidity and milk composition, microbial load, and somatic cells in the milk of Holstein dairy cows. For this purpose, the temperature–humidity index, ambient temperature, and relative humidity data were obtained from the nearest weather stations. Production data were obtained from four dairy farms in Golestan province, Iran, collected from 2016 to 2021. The traits investigated were protein, fat, solids-not-fat (SNF), microbial load, and somatic cell count (SCC) in milk. The effects of the environmental temperature, humidity, month, and season on the milk composition, microbial load, and somatic cells were analyzed through analysis of variance. The effects of environmental temperature, humidity, month, and season on the milk composition, microbial load, and somatic cell composition were analyzed using a mixed procedure with a restricted maximum likelihood model. Although our findings revealed that there were significant differences in fat, protein, SNF, and SCC among the different months of the year (p < 0.01), no significant difference was observed in the total microbial count in milk. Environmental temperature presented significant impacts on fat, protein, SNF, SCC, and total microbial count within various temperature ranges (p < 0.01). When the temperature increased from 6.2 °C to 31.3 °C, the milk protein, fat, SNF, and somatic cell count significantly decreased, by approximately 4.09%, 5.75%, 1.31%, and 16.8%, respectively; meanwhile, the microbial count in milk significantly increased, by approximately 13.7%. Humidity showed an influence on fat, protein, non-fat solids, somatic cells, and total microbial count within different temperature ranges (p < 0.01). When the humidity increased from 54% to 82%, the milk protein, fat, SNF, and SCC significantly increased, by approximately 3.61%, 4.84%, 1.06%, and 10.2%, respectively; meanwhile, the microbial count in milk significantly decreased, by approximately 16.3%. The results demonstrate that there is a negative correlation between different months of the year, temperature, and the humidity of the environment, in terms of milk components and SCC. Our findings demonstrate that the optimum performance, in terms of milk composition, occurred in the first quarter of the year. As temperature increases and humidity decreases, milk quality decreases. Therefore, the adverse effects of environmental conditions on agricultural profits are not negligible, and strategies to better deal with the negative environmental effects are needed in order to improve milk quality in dairy cows.

Estimates of Genetic Parameters for Shape Space Data in Franches-Montagnes Horses.

Simple SummaryEquine breeding is often based on conformation traits, describing the proportions, shape and joint angles of a horse. These conformations traits are, however, mostly subjectively judged and not measured objectively, affecting the response of selection through lower heritabilities and precision. In this study, we measured joint angles, quantified the variation in shape of 608 Swiss Franches-Montagnes (FM) horses and estimated the heritability of these traits. We found that the poll angle had the highest heritability of all joint angles (h2 = 0.37), and variation in shape describing the type (heavy–light) was also fairly heritable (h2 = 0.36–0.37). Furthermore, the shape of the FM stallions has clearly evolved towards a lighter type from 1940 to 2018 without stabilisation in recent years, risking the loss of the light draught horse type. Phenotyping based on photographs allowed us to improve the accuracy of certain joint angle traits, and to monitor the conformational development of the FM breed.Conformation traits such as joint angles are important selection criteria in equine breeding, but mainly consist of subjective evaluation scores given by breeding judges, showing limited variation. The horse shape space model extracts shape data from 246 landmarks (LM) and objective joint angle measurements from triplets of LM on standardized horse photographs. The heritability was estimated for 10 joint angles (seven were measured twice with different LM placements), and relative warp components of the whole shape, in 608 Franches-Montagnes (FM) horses (480 stallions, 68 mares and 60 geldings born 1940–2018, 3–25 years old). The pedigree data comprised 6986 horses. Genetic variances and covariances were estimated by restricted maximum likelihood model (REML), including the fixed effects birth year, age (linear and quadratic), height at withers (linear and quadratic), as well as postural effects (head, neck, limb position and body alignment), together with a random additive genetic animal component and the residual effect. Estimated heritability varied from 0.08 (stifle joint) to 0.37 (poll). For the shape, the type was most heritable (0.36 to 0.37) and evolved from heavy to light over time. Image-based phenotyping can improve the selection of horses for conformation traits with moderate heritability (e.g., poll, shoulder and fetlock).

Precision-based exercise in people with anxiety and stress related disorders: Are there interindividual differences in anxiolytic effects? An ancillary meta-analysis of randomized controlled trials

Interest in the individualized responses to exercise has been growing within mental health care and psychiatry. This meta-analysis examined if true interindividual differences (IIDs) in anxiolytic effects of exercise exist among adults with anxiety- and stress-related disorders. Data were extracted from a previous meta-analysis of randomized controlled trials (RCTs) and searches in CINAHL, Embase and Medline were updated (8 arms from 7 original studies, n participants=322). Change outcome standard deviations treated as point estimates for anxiety were extracted to calculate true IIDs. Inverse variance heterogeneity and restricted maximum likelihood models were used. Aerobic exercise and resistance training showed significant anxiolytic effects. No significant pooled IIDs were found for aerobic exercise nor resistance training demonstrating that there is currently a lack of convincing evidence to support the notion that true IIDs exist for the anxiolytic effects of exercise among adults with anxiety- and stress-related disorders. Consequently, clinical practice can focus on general population physical activity guidelines for patients with anxiety- and stress-related disorders rather than aiming for highly specific, individualized recommendations. Future research could prioritize investigating how to motivate patients with anxiety- and stress-related disorders to meet general population physical activity guidelines.

A Systematic Literature Review of Health Utility Values in Breast Cancer

BackgroundHealth utility values (HUVs) are important inputs to the cost-utility analysis of breast cancer interventions.PurposeProvide a catalog of breast cancer–related published HUVs across different stages of breast cancer and treatment interventions.Data SourcesSystematic searches of MEDLINE, MEDLINE In-Process, EMBASE, Web of Science, CINAHL, PsycINFO, EconLit, and Cochrane databases (2005–2017).Study SelectionStudies published in English that reported mean or median HUVs using direct or indirect methods of utility elicitation for breast cancer.Data ExtractionIndependent reviewers extracted data on a preestablished and piloted form; disagreements were resolved through discussion.Data AnalysisMixed-effects meta-regression using restricted maximum likelihood modeling was conducted for intervention type, stage of breast cancer, and typical clinical and treatment trajectory of breast cancer patients to assess the effect of study characteristics (i.e., sample size, utility elicitation method, and respondent type) on HUVs.Data SynthesisSeventy-nine studies were included in the review. Most articles (n = 52, 66%) derived HUVs using the EQ-5D. Patients with advanced-stage breast cancer (range, 0.08 to 0.82) reported lower HUVs as compared with patients with early-stage breast cancer (range, 0.58 to 0.99). The meta-regression analysis found that undergoing chemotherapy and surgery and radiation, being diagnosed with an advanced stage of breast cancer, and recurrent cancer were associated with lower HUVs. The members of the general public reported lower HUVs as compared with patients.LimitationsThere was considerable heterogeneity in the study population, health states assessed, and utility elicitation methods.ConclusionThis review provides a catalog of published HUVs related to breast cancer. The substantial heterogeneity in the health utility studies makes it challenging for researchers to choose which HUVs to use in cost-utility analyses for breast cancer interventions.

Genomic Selection for Milk Production Traits in Xinjiang Brown Cattle.

Simple SummaryMilk production is an important trait in the breeding and genetic improvement of Xinjiang Brown cattle. To obtain the best strategy for improving the reliability of the breeding value estimation for each trait, we used single-trait and multitrait models based on the A-array pedigree-based best linear unbiased prediction (PBLUP) and H-array single-step genomic best linear unbiased prediction (ssGBLUP) to perform the genetic evaluation of different strategies using the restricted maximum likelihood (REML) and Bayesian methods. Upon comparison, the ssGBLUP calculation results of the multitrait models obtained using the REML and Bayesian methods were better than those of other strategies. Considering the calculation time, the multitrait model REML method is recommended for ssGBLUP calculation to accurately predict the breeding value of young animals; thus, this strategy should be used for the early breeding selection of Xinjiang Brown cattle.One-step genomic selection is a method for improving the reliability of the breeding value estimation. This study aimed to compare the reliability of pedigree-based best linear unbiased prediction (PBLUP) and single-step genomic best linear unbiased prediction (ssGBLUP), single-trait and multitrait models, and the restricted maximum likelihood (REML) and Bayesian methods. Data were collected from the production performance records of 2207 Xinjiang Brown cattle in Xinjiang from 1983 to 2018. A cross test was designed to calculate the genetic parameters and reliability of the breeding value of 305 daily milk yield (305 dMY), milk fat yield (MFY), milk protein yield (MPY), and somatic cell score (SCS) of Xinjiang Brown cattle. The heritability of 305 dMY, MFY, MPY, and SCS estimated using the REML and Bayesian multitrait models was approximately 0.39 (0.02), 0.40 (0.03), 0.49 (0.02), and 0.07 (0.02), respectively. The heritability and estimated breeding value (EBV) and the reliability of milk production traits of these cattle calculated based on PBLUP and ssGBLUP using the multitrait model REML and Bayesian methods were higher than those of the single-trait model REML method; the ssGBLUP method was significantly better than the PBLUP method. The reliability of the estimated breeding value can be improved from 0.9% to 3.6%, and the reliability of the genomic estimated breeding value (GEBV) for the genotyped population can reach 83%. Therefore, the genetic evaluation of the multitrait model is better than that of the single-trait model. Thus, genomic selection can be applied to small population varieties such as Xinjiang Brown cattle, in improving the reliability of the genomic estimated breeding value.

Prevalence and Predisposing Factors for Recurrence after Hallux Valgus Surgery: A Systematic Review and Meta-Analysis.

Recurrence is a frequent and undesirable outcome after hallux valgus (HV) surgery. However, the prevalence of HV recurrence and the pre- and postoperatory factors associated with it have not been adequately studied. This study aimed to quantify the prevalence rate of HV recurrence and to analyze its predisposing factors. MEDLINE and EMBASE databases were systematically searched for observational studies including individuals undergoing HV surgical correction. The random-effects restricted maximum likelihood model was used to estimate the pooled effect size (correlation coefficient (r)). Twenty-three studies were included, yielding a total of 2914 individuals. Pooled prevalence of HV recurrence was 24.86% (95% confidence interval (CI), 19.15 to 30.57, I2 = 91.92%, p = 0.00). Preoperative HV angle (HVA) (r = 0.29; 95% CI, 0.14 to 0.43) and preoperative intermetatarsal angle (IMA) (r = 0.13; 95% CI, 0.00 to 0.27) showed a moderate positive relationship with recurrence. Postoperative HVA (r = 0.57; 95% CI, 0.21 to 0.94) and sesamoid position (r = 0.46; 95% CI, 0.31 to 0.60) showed strong relationships with recurrence. In conclusion, preoperative HVA, IMA, and postoperative HVA and sesamoid position are significant risk factors for HV recurrence, and the association of these factors with recurrence is affected by age.