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Nevin Manimala Statistics

Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta-analysis

Biol Rev Camb Philos Soc. 2021 Mar 1. doi: 10.1111/brv.12700. Online ahead of print.

ABSTRACT

The clinical effect of sperm DNA damage in assisted reproduction has been a controversial topic during recent decades, leading to a variety of clinical practice recommendations. While the latest European Society of Human Reproduction and Embryology (ESHRE) position report concluded that DNA damage negatively affects assisted reproduction outcomes, the Practice Committee of the American Society for Reproductive Medicine (ASRM) does not recommend the routine testing of DNA damage for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Herein, our aim was to perform a systematic review and meta-analysis of studies investigating whether sperm DNA damage affects clinical outcomes in IVF and ICSI, in order to contribute objectively to a consistent clinical recommendation. A comprehensive systematic search was conducted according to PRISMA guidelines from the earliest available online indexing year until March 2020, using the MEDLINE-PubMed and EMBASE databases. We included studies analysing IVF and/or ICSI treatments performed in infertile couples in which sperm DNA damage was well defined and assessed. Studies also had to include information about pregnancy, implantation or live birth rates as primary outcomes. The NHLBI-NIH quality assessment tool was used to assess the quality of each study. Meta-analyses were conducted using the Mantel-Haenszel method with random-effects models to evaluate the Risk Ratio (RR) between high-DNA-damage and control groups, taking into account the 95% confidence intervals. Heterogeneity among studies was evaluated using the I2 statistic. We also conducted sensitivity analyses and post-hoc subgroup analyses according to different DNA fragmentation assessment techniques. We identified 78 articles that met our inclusion and quality criteria and were included in the qualitative analysis, representing a total of 25639 IVF/ICSI cycles. Of these, 32 articles had sufficient data to be included in the meta-analysis, comprising 12380 IVF/ICSI cycles. Meta-analysis revealed that, considering IVF and ICSI results together, implantation rate (RR = 0.74; 95% CI = 0.61-0.91; I2 = 69) and pregnancy rate (RR = 0.83; 0.73-0.94; I2 = 58) are negatively influenced by sperm DNA damage, although after adjustment for publication bias the relationship for pregnancy rate was no longer significant. The results showed a non-significant but detrimental tendency (RR = 0.78; 0.58-1.06; I2 = 72) on live birth rate. Meta-analysis also showed that IVF outcomes are negatively influenced by sperm DNA damage, with a statistically significant impact on implantation (RR = 0.68; 0.52-0.89; I2 = 50) and pregnancy rates (RR = 0.72; 0.55-0.95; I2 = 72), although the latter was no longer significant after correction for publication bias. While it did not quite meet our threshold for significance, a negative trend was also observed for live birth rate (RR = 0.48; 0.22-1.02; I2 = 79). In the case of ICSI, non-significant trends were observed for implantation (RR = 0.79; 0.60-1.04; I2 = 72) or pregnancy rates (RR = 0.89; 0.78-1.02; I2 = 44), and live birth rate (RR = 0.92; 0.67-1.27; I2 = 70). The current review provides the largest evidence to date supporting a negative association between sperm DNA damage and conventional IVF treatments, significantly reducing implantation and pregnancy rates. The routine use of sperm DNA testing is therefore justified, since it may help improve the outcomes of IVF treatments and/or allow a given couple to be advised on the most suitable treatment. Further well-designed controlled studies on a larger number of patients are required to allow us to reach more precise conclusions, especially in the case of ICSI treatments.

PMID:33644978 | DOI:10.1111/brv.12700

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Nevin Manimala Statistics

Correction of Artifacts Induced by B0 Inhomogeneities in Breast MRI Using Reduced-Field-of-View Echo-Planar Imaging and Enhanced Reversed Polarity Gradient Method

J Magn Reson Imaging. 2021 Mar 1. doi: 10.1002/jmri.27566. Online ahead of print.

ABSTRACT

BACKGROUND: Diffusion-weighted (DW) echo-planar imaging (EPI) is prone to geometric distortions due to B0 inhomogeneities. Both prospective and retrospective approaches have been developed to decrease and correct such distortions.

PURPOSE: The purpose of this work was to evaluate the performance of reduced-field-of-view (FOV) acquisition and retrospective distortion correction methods in decreasing distortion artifacts for breast imaging. Coverage of the axilla in reduced-FOV DW magnetic resonance imaging (MRI) and residual distortion were also assessed.

STUDY TYPE: Retrospective.

POPULATION/PHANTOM: Breast phantom and 169 women (52.4 ± 13.4 years old) undergoing clinical breast MRI.

FIELD STRENGTH/SEQUENCE: A 3.0 T/ full- and reduced-FOV DW gradient-echo EPI sequence.

ASSESSMENT: Performance of reversed polarity gradient (RPG) and FSL topup in correcting breast full- and reduced-FOV EPI data was evaluated using the mutual information (MI) metric between EPI and anatomical images. Two independent breast radiologists determined if coverage on both EPI data sets was adequate to evaluate axillary nodes and identified residual nipple distortion artifacts.

STATISTICAL TESTS: Two-way repeated-measures analyses of variance and post hoc tests were used to identify differences between EPI modality and distortion correction method. Generalized linear mixed effects models were used to evaluate differences in axillary coverage and residual nipple distortion.

RESULTS: In a breast phantom, residual distortions were 0.16 ± 0.07 cm and 0.22 ± 0.13 cm in reduced- and full-FOV EPI with both methods, respectively. In patients, MI significantly increased after distortion correction of full-FOV (11 ± 5% and 18 ± 9%, RPG and topup) and reduced-FOV (8 ± 4% both) EPI data. Axillary nodes were observed in 99% and 69% of the cases in full- and reduced-FOV EPI images. Residual distortion was observed in 93% and 0% of the cases in full- and reduced-FOV images.

DATA CONCLUSION: Minimal distortion was achieved with RPG applied to reduced-FOV EPI data. RPG improved distortions for full-FOV images but with more modest improvements and limited correction near the nipple.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

PMID:33644939 | DOI:10.1002/jmri.27566

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Evaluation of some predictive parameters for baked-milk tolerance in children with cow’s milk allergy

Allergol Immunopathol (Madr). 2021 Mar 1;49(2):53-59. doi: 10.15586/aei.v49i2.64. eCollection 2021.

ABSTRACT

BACKGROUND: Inclusion of baked-milk products to the diet appears to markedly accelerate tolerance to unheated milk compared to a strict avoidance diet.

OBJECTIVE: : The present study aims to investigate the predictors of baked-milk tolerance in children with Immunoglobulin E (IgE)-mediated cow’s milk (CM) allergy.

METHODS: The study included 80 patients diagnosed with IgE-mediated CM allergy upon oral food challenge (OFC) testing at our clinic. Patients who developed and did not develop reactions during OFC with baked milk were compared considering clinical and laboratory parameters.

RESULTS: Eighty patients with CM allergy comprised 48 male and 32 female infants with an average age of 7.25 ± 2.45 (3-13) months. We found that 62.5% of them showed tolerance to baked milk in the OFC test performed with cakes containing 2.6-g milk protein. When the patients who tolerated and could not tolerate baked-milk products were compared for test results, we detected a statistically significant intergroup difference regarding diameter of wheal in skin prick test (SPT) performed with muffin slurry, levels of specific Immunoglobulin E (sIgE) in CM, sheep’s milk (SM), goat’s milk (GM), casein, and the amount of unheated milk consumed until a reaction developed in the OFC test performed with unheated milk (P < 0.05).

CONCLUSION: We defined novel decision points based on CM, SM, GM, casein sIgE levels, wheal diameter in SPT with muffin slurry, and the amount of milk ingested during OFC performed with unheated milk that may be useful in predicting outcomes of baked-milk ingestion.

PMID:33641294 | DOI:10.15586/aei.v49i2.64

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Nevin Manimala Statistics

The CXCR5 T follicular helper cell compartment in children with antibody deficiencies-in search of a prognostic marker of childhood hypogammaglobulinemia

Allergol Immunopathol (Madr). 2021 Mar 1;49(2):113-121. doi: 10.15586/aei.v49i2.34. eCollection 2021.

ABSTRACT

BACKGROUND: Novel immunodiagnostic markers are required in order to discriminate between mild hypogammaglobulinemia and severe humoral primary immune deficiencies in children. The efficacy of an antibody response to infections and vaccines is underpinned by T follicular helper (Tfh) cells, activating an immunoglobulin class switch recombination, somatic hypermutations, and affinity maturation.

OBJECTIVE: To determine the formation of the Tfh cells in antibody deficient children and to define their importance as prognostic markers helpful in defining the severity of hypogammaglobulinemia.

METHODS: We retrospectively reviewed medical records of 200 children aged from 2 months to 10 years, in whom hypogammaglobulinemia was assessed, from January to December 2019. In all the children studied, a flow cytometric analysis of the Tfh cell compartment was performed.

RESULTS: In young infants aged from 2 to 9 months, the mean relative frequency of the Tfh population was lower than in the control population. Concomitantly, the relative values of Tfh cells, corresponding with the 95th percentile, were below the reference values in all age groups.

CONCLUSIONS: A deficiency of Tfh cells in young infants mirrors the immaturity of the humoral immune response, whereas in older children Tfh cells are proposed as a prognostic marker facilitating to distinguish between mild hypogammaglobulinemia and the developing common variable immunodeficiency.

PMID:33641302 | DOI:10.15586/aei.v49i2.34

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Rapid weight gain in early life is associated with severity of respiratory syncytial virus (RSV) bronchiolitis in children

Allergol Immunopathol (Madr). 2021 Mar 1;49(2):23-30. doi: 10.15586/aei.v49i2.51. eCollection 2021.

ABSTRACT

OBJECTIVES: This study aimed to investigate whether rapid weight gain in early life was associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children.

METHODS: We retrospectively reviewed 190 patients (1-24 months) hospitalized for RSV bronchiolitis. Parameters of bronchiolitis severity were compared between rapid (change in weight z-score from birth >0.67, n = 65) and normal weight gain groups (n = 125). We assessed for correlations between bronchiolitis severity and weight gain. Linear regression was performed to predict for bronchiolitis severity based on weight gain, controlling for covariates. SPSS was used for statistical analyses.

RESULTS: The rapid weight gain group had longer mean durations of tachypnea (2.3±2.0 vs. 1.7±1.8 days, P = 0.027), wheezing (3.2±2.5 vs. 1.6±1.8 days, P < 0.001), and chest retractions (1.5±2.2 vs. 0.6±1.3 days, P = 0.007). Correlations of weight gain with tachypnea (r = 0.146), wheezing (r = 0.279), and chest retractions (r = 0.179) were statistically significant. Weight gain predicted for tachypnea (B = 0.485, P = 0.013) and wheezing (B = 0.846, P = 0.001) durations after adjusting for covariates of severity (age, sex, current weight, RSV type, coinfection, recurrent bronchiolitis, hospital stay, fever, oxygen supplementation, maximal respiratory and heart rates, and laboratory indices).

CONCLUSIONS: Our findings suggest an association between weight gain and severity of RSV bronchiolitis in young children. Weight gain was significantly associated with the durations of tachypnea and wheezing. The trajectory of weight gain in early life may play a significant role in the clinical course of RSV bronchiolitis.

PMID:33641290 | DOI:10.15586/aei.v49i2.51

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Antibodies to Der p 1 and Der p 2 in allergic patients

Allergol Immunopathol (Madr). 2021 Mar 1;49(2):46-52. doi: 10.15586/aei.v49i2.59. eCollection 2021.

ABSTRACT

INTRODUCTION AND OBJECTIVES: Atopic individuals are characterized by increased IgE production and Th2 response if exposed to certain antigens. It is known that the mother transfers anti-mite antibodies to the fetus and newborn, IgG thru the placenta, and IgA thru breastfeeding, but it is not clear whether there is a protective mechanism mediated by them concerning the development of future allergies. This study aimed to compare the levels of IgA, IgG, and IgE antibodies specific to Der p 1 and Der p 2 between atopic and healthy individuals.

METHODS: Serum samples of 98 patients and 44 healthy controls were subjected to quantification for specific IgE, IgG, and IgA antibodies against Der p 1 and Der p 2 by ImmunoCap® and ELISA, and subjected to statistical analysis as indicated.

RESULTS: Atopic patients had higher serum levels of IgE, IgG, and IgA specific to Der p 1 and Der p 2. The correlation was more robust between IgE and IgG antibodies.

CONCLUSIONS: Allergic patients produce higher levels of antibodies against Der p 1 and Der p 2 compared with healthy individuals. The mechanisms involved still require detailed studies.

PMID:33641293 | DOI:10.15586/aei.v49i2.59

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Erythema-directed digital photography and colorimeter scores correlate with rosacea erythema evaluation in patients under treatment with topical ivermectin

Dermatol Ther. 2021 Feb 28:e14920. doi: 10.1111/dth.14920. Online ahead of print.

ABSTRACT

Inflammatory rosacea is clinically characterized by persistent erythema and inflammatory lesions. Its severity is generally based on clinical observation that may be cumbersome. The aim of this study was to assess if erythema-directed digital photography (EEDP) and colorimeter (COL) correlate and are concordant with clinical evaluation of erythema degree of rosacea under topical treatment. Thirty naïve patients with mild/moderate inflammatory rosacea were instructed to apply ivermectin cream for 8 weeks. Erythema degree was performed at baseline, and at 2, 4, 6 and 8 weeks by clinician erythema assessment based on 5-point severity scale (from 0=no erythema to 4=fiery redness), and by instrumental evaluation by EDDP using the same 5-point scale of clinical assessment and by COL using a 5-point scale (from 0=<1 units=no erythema to 4>12 units=fiery redness). Concordance and correlation analysis were performed using Cohen’s Kappa coefficient and Correlation Coefficient test respectively. At baseline a statistically significant concordance/correlation value between EDDP/COL was observed. At 2 weeks, the statistical concordance/correlation value between instrumentals were both increased, along with a slight significant concordance between clinical assessment and erythema-directed digital photography. At 4, 6 and 8 weeks, a statistically significant increase of concordance/correlation value among all the considered parameters from baseline was found. The results of our study showed that at baseline and during the early treatment stage both EDDP and COL were able to appreciate more accurately the erythema grade compared to clinical observation supporting the use of non-invasive techniques for a more objective evaluation of erythema in rosacea. This article is protected by copyright. All rights reserved.

PMID:33641260 | DOI:10.1111/dth.14920

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Self-medication among pregnant women attending outpatients’ clinics in northern Jordan-a cross-sectional study

Pharmacol Res Perspect. 2021 Apr;9(2):e00735. doi: 10.1002/prp2.735.

ABSTRACT

Self-medication can facilitate patients’ access to medicinal products, save time, and reduce financial and health-care service use burden. On the other hand, irresponsible use of self-medications can result in adverse consequences. Self-medication is common among different demographic groups including pregnant women. In general, medicinal products might have harmful effects on mothers and baby. This study aimed to assess self-medication practices among pregnant women in the northern region of Jordan. A cross-sectional study was conducted on pregnant women attending outpatient clinics in the northern region of Jordan. Self-medication practices among the target population were assessed using a survey questionnaire that was administered through interviewer-assisted mode. Data were collected between December 2019 and September 2020, and descriptive statistics and inferential analysis were applied. A total of 1,313 pregnant women were surveyed (response rate = 95.50%). Self-medication and the use of herbal remedies were practiced by 33.10% and 32.14% of the participant, respectively. Headaches and general pains were the most frequently reported conditions treated by self-medication practice with either conventional medicinal products or herbal remedies. The gravidity (≥4) and the gestational stage (≥28 weeks) were the predictors of self-medication practice. This study showed that self-medication was not widely practiced by pregnant women in the northern region of Jordan. Disease simplicity and previous history were the main motives for self-medicating. Efforts should be made by health-care providers to address pregnant women and educate them to increase their awareness about the unsafe use of medicines and the harmful effects on fetus.

PMID:33641261 | DOI:10.1002/prp2.735

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Nevin Manimala Statistics

When driving hurts: characterizing the experience and impact of driving with back pain

Scand J Pain. 2021 Feb 23. doi: 10.1515/sjpain-2020-0108. Online ahead of print.

ABSTRACT

OBJECTIVES: Driving is one of the most widespread aspects of daily living to people in the United States and is an active process that requires various cognitive functions, such as attention. Chronic low back pain (CLBP) is one of the more prevalent and costly health conditions in the world, with individuals who report CLBP also reporting significant impairment across different domains of daily life both physically and cognitively. However, despite the prevalence of these two constructs, research detailing the experience of driving in pain remains largely underrepresented. This cross-sectional study sought to characterize the driving experience of people who experience CLBP, focusing on the psychological constructs related to chronic pain like pain catastrophizing, affective responses (irritability, anxiety, fear), and self-reported driving behaviors and outcomes.

METHODS: This study distributed an online questionnaire measuring pain, disability, and other psychological constructs commonly associated with CLBP like pain catastrophizing through M-turk to 307 U.S. participants with recurring CLBP and regular driving activity. Participants also answered questions regarding driving in pain, affective responses to driving in pain (i.e., irritability, anxiety, and fear), driving behaviors and violations, driving avoidance habits as a result of pain, opioid use, using pain medication while driving, and recent vehicle collisions within the past three years. Bivariate correlations were used to compare study variables, and one-way ANOVA’s were used to compare means between participants with and without a collision history within the past three years.

RESULTS: Findings demonstrated significant positive associations not only between the psychological factors commonly associated with chronic pain, such as pain intensity, pain disability, pain catastrophizing, and the cognitive intrusion by pain, but also statistically significant relationships between these measures and pain intensity while driving, affective responses to driving in pain, driving violations, and driving avoidance habits. Additionally, in comparison to participants with no collision history within the past three years, participants who had been driving during a vehicle collision reported greater pain catastrophizing and cognitive intrusion by pain scores.

CONCLUSIONS: To our knowledge, the current study is the first to characterize driving experience specifically among individuals with CLBP, with attention to the relationship among key sensory, affective, and cognitive psychological metrics as well as self-reported driving history and behavior. The current findings reinforce multiple associations between pain and cognitive-affective variables that have been observed in literature outside the driving context, including pain intensity, anger, inattention, and behavioral disruption. Given that driving is a pervasive, potentially risky behavior that requires some form of cognitive focus and control, the current findings point to a continued need to examine these associations within this specific life context.We believe we have laid a groundwork for research considering the role of psychological pain variables in a driving performance. However, the nature of our analyses prevents any sort of causality from being inferred, and that future experimental research is warranted to better understand and explain these mechanisms underlying driving in pain while accounting for participant bias and subject interpretation.

PMID:33641275 | DOI:10.1515/sjpain-2020-0108

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Prenylflavonoids isolated from Macaranga tanarius stimulate odontoblast differentiation of human dental pulp stem cells and tooth-root formation via the mitogen-activated protein kinase and protein kinase B pathways

Int Endod J. 2021 Feb 28. doi: 10.1111/iej.13503. Online ahead of print.

ABSTRACT

AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation.

METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3′-geranyl-naringenin (GN), and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analyzed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and western blot analysis. The molecular mechanism was investigated with western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analyzed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student’s t-test. The data were considered to have statistical significance when the p-value was less than 0.05.

RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (p<0.001) and induced the expression of odontogenic marker genes (p<0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (p<0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (p<0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (p<0.05).

CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signaling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.

PMID:33641170 | DOI:10.1111/iej.13503