Multiple Comparison Methods Research Articles

How reliable are the multiple comparison methods for odds ratio?

The homogeneity tests of odds ratios are used in clinical trials and epidemiological investigations as a preliminary step of meta-analysis. In recent studies, the severity or mortality of COVID-19 in relation to demographic characteristics, comorbidities, and other conditions has been popularly discussed by interpreting odds ratios and using meta-analysis. According to the homogeneity test results, a common odds ratio summarizes all of the odds ratios in a series of studies. If the aim is not to find a common odds ratio, but to find which of the sub-characteristics/groups is different from the others or is under risk, then the implementation of a multiple comparison procedure is required. In this article, the focus is placed on the accuracy and reliability of the homogeneity of odds ratio tests for multiple comparisons when the odds ratios are heterogeneous at the omnibus level. Three recently proposed multiple comparison tests and four homogeneity of odds ratios tests with six adjustment methods to control the type-I error rate are considered. The reliability and accuracy of the methods are discussed in relation to COVID-19 severity data associated with diabetes on a country-by-country basis, and a simulation study to assess the powers and type-I error rates of the tests is conducted.

Effect of Different Cleaning Methods on Shear Bond Strength of Resin Cement to Contaminated Zirconia

The aim of this study was to evaluate the effect of different cleaning methods on the shear bond strength (SBS) of resin cement to contaminated zirconia specimens. Eighty rectangular-shaped specimens (2 × 5 × 10 mm) were fabricated from Zirconia blocks (IPS e.max ZirCAD) and randomly divided into 8 groups (n = 10). Group A (control) was not exposed to contaminants. The following tests specimens were contaminated with saliva and silicone indicating paste. Group B was coated with ceramic primer, then subjected to contamination. Groups C, D, E, F, G, and H were contaminated; cleaned with water rinse, Ivoclean, air particle abrasion, hydrofluoric acid, KATANATM Cleaner and ZirCleanTM, respectively, and then coated with ceramic primer and bonded to dual cure resin cement cylinders. All the specimens were subjected to artificial aging and surviving specimens were subjected to the SBS test. For statistical analysis, ANOVA and multiple comparison methods at the 0.05 significance level were used. There was no statistically significant difference among Ivoclean (21.48 ± 2.90 MPa), air particle abrasion (21.92 ± 2.85 MPa), and the control group (24.68 ± 5.46). The application of ceramic primer before contamination did not preserve the SBS of resin cement to zirconia. Cleaning the contaminated zirconia surface with hydrofluoric acid (15.03 ± 3.63) or KATANATM Cleaner (17.27 ± 7.63) did not restore SBS to the uncontaminated state, but it was significantly higher than simply rinsing with water (12.46 ± 5.17) or the use of ZirCleanTM (11.59 ± 5.53). The bond strength of resin cement to zirconia was influenced by cleaning methods.

Effects of Visual Environment on Students Adjustment to Stress

The impact of stress on visual landscape perception was assessed in a photo-based survey. The survey was first performed when the student participants were expected to be stressed just prior to an important examination. The same students were asked to respond to the same questionnaire a month after the examination when they were expected to have a lower level of stress. Then respondents answered some daily activities, personal study habits, and feelings before an exam. They also provided ratings of how much a selection of environmental factors generally influence their ability to study and their academic success. In the main perceptual survey reactions to a selection of 22 landscape scenes photos were reported by ratings (1–5) of the extent to which each of six emotions was associated with each scene. Differences in emotions ratings for the represented landscapes during high-stress and low-stress periods were analyzed by multiple comparison and Pearson correlational methods using the SPSS 17.00 package. Stress tests confirmed higher stress in the first versus second survey and perceptual ratings showed significant statistical differences in emotion ratings between landscape scenes, as well as both main effects and interactions between high stress and low stress conditions. Scene ratings for each emotion were strongly positively correlated between high stress and lower stress conditions. At the same time, respondents generally gave slightly higher ratings for positive emotions -excited, relaxing, happiness-when in the high stress condition and moderately higher ratings for negative emotions -stressed, irritating, scary-, compared to their ratings when tested later under lower stress conditions. This study indicated that stress conditions affect perception, and stressed conditions gave higher emotionality overall than the unstressed condition. In general, in both stressed and unstressed conditions, the students gave the highest scores (>3.4) to convenience and the lowest score (<2) to scary. The main limitations of this study are the large number of environmental factors that influence people's perception. The strongest determiner of emotion ratings was the landscape scenes themselves. Inspection of outliers in the scatter plots and multiple comparisons articulating higher order interactions with stress conditions revealed clear differences in the patterns of emotions ratings, especially for scenes representing water surfaces, open green spaces, and seasonal plant scenes.

Approaches to resource management of a modern university in the context of digitalisation

The article considers the evolution of university models, examines in detail the model of a digital university and pays special attention to changing the paradigm of university resource management in the context of digitalization. The transition from managing university resources to managing access to them is substantiated. This problem is relevant, since the Russian economy is faced with the task of overcoming technological dependence in the current conditions of restrictions and Western sanctions. The development of universities of a new quality, integrated with the real sector of the economy, operating on the basis of digital technologies and providing competitive innovative development, could be a solution to this problem. The purpose of the article is to propose a new methodology for the development of the university and the management of its resources in the context of digitalization. In the course of the study the authors solved the following tasks: they analyzed global trends and external risks for higher education; revealed the phenomenon of the digital university; substantiated the new principles of digital university resource management that meet the requirements of the fourth industrial revolution; proposed an approach to the digital development of the university based on the harmonization of the interests and requirements of stakeholders; considered the concepts of infrastructure logic and the strategy of digital transformation of the university. The article used both general scientifc research methods and special ones: frstly, statistical analysis of indicators of global innovation trends in the feld of digitalization of education and the economy; secondly, an institutional approach aimed at identifying effective institutions (rules of the game) that can increase the overall motivation of internal and external stakeholders of the university to ensure an effective digital transformation process; thirdly, the method of multiple thematic comparisons to analyze the scientifc literature and ofcial sources on the digital development of the university and the innovative economy. As a result of the study, the authors formulated a set of recommendations for developing a strategy for the digital transformation of Russian universities based on the author’s methodology for resource management in the digital age for integration into the global innovation process and obtaining leadership positions in global university rankings.

Condylar Changes after Maxillary Expansion in Children with Cleft Lip and Palate-A Three-Dimensional Retrospective Study.

Background: The presence of posterior crossbite can trigger aesthetic and functional changes as mandibular asymmetry in individuals, contributing to asymmetrical muscle function. Mandibular asymmetry and respective condyle adaptation may be an etiological factor in temporomandibular disorder. This study aims to evaluate the effects of maxillary expansion on the position and angulation of the condyles as well as the intercondylar distance in children with cleft lip and palate. Methods: Twenty-five individuals with cleft lip and palate who underwent maxillary expansion were selected. Condylar changes were evaluated by cone beam computed tomography using the Pullinger and Hollender formula. To determine the statistically significant differences between the variables, the Student t-test and the Benjamini–Hochberg correction method for multiple comparisons were used. Results: No statistically significant differences between angulation and condylar position before and after maxillary expansion were found. The intercondylar distance tended to increase in growing individuals with cleft lip and palate after maxillary expansion. Conclusions: Intercondylar distance shows a tendency to increase after expansion regardless of the cleft phenotype. No differences were found in angulation and condylar position with the changes in occlusion resulting from maxillary expansion.

Should methods of correction for multiple comparisons be applied in pharmacovigilance?


 Purpose. In pharmacovigilance, spontaneous reporting databases are devoted to the early detection of adverse event ‘signals’ of marketed drugs. A common limitation of these systems is the wide number of concurrently investigated associations, implying a high probability of generating positive signals simply by chance. However it is not clear if the application of methods aimed to adjust for the multiple testing problems are needed when at least some of the drug-outcome relationship under study are known. To this aim we applied a robust estimation method for the FDR (rFDR) particularly suitable in the pharmacovigilance context.
 Methods. We exploited the data available for the SAFEGUARD project to apply the rFDR estimation methods to detect potential false positive signals of adverse reactions attributable to the use of non-insulin blood glucose lowering drugs. Specifically, the number of signals generated from the conventional disproportionality measures and after the application of the rFDR adjustment method was compared.
 Results. Among the 311 evaluable pairs (i.e., drug-event pairs with at least one adverse event report), 106 (34%) signals were considered as significant from the conventional analysis. Among them 1 resulted in false positive signals according to rFDR method.
 Conclusions. The results of this study seem to suggest that when a restricted number of drug-outcome pairs is considered and warnings about some of them are known, multiple comparisons methods for recognizing false positive signals are not so useful as suggested by theoretical considerations.

Validity and Relative Validity of Alternative Methods of Assessing Physical Activity in Epidemiologic Studies: Findings From the Men's Lifestyle Validation Study.

In the Men's Lifestyle Validation Study (2011-2013), we examined the validity and relative validity of a physical activity questionnaire (PAQ), a Web-based 24-hour recall (Activities Completed Over Time in 24 Hours (ACT24)), and an accelerometer by multiple comparison methods. Over the course of 1 year, 609 men completed 2 PAQs, two 7-day accelerometer measurements, at least 1 doubly labeled water (DLW) physical activity level (PAL) measurement (n=100 with repeat measurements), and 4 ACT24s; they also measured their resting pulse rate. A subset (n=197) underwent dual-energy x-ray absorptiometry (n=99 with repeated measurements). The method of triads was used to estimate correlations with true activity using DLW PAL, accelerometry, and the PAQ or ACT24 as alternative comparison measures. Estimated correlations of the PAQ with true activity were 0.60 (95% confidence interval (95% CI): 0.52, 0.68) for total activity, 0.69 (95% CI: 0.61, 0.79) for moderate-to-vigorous physical activity (MVPA), and 0.76 (95% CI: 0.62, 0.93) for vigorous activity. Corresponding correlations for total activity were 0.53 (95% CI: 0.45, 0.63) for the average of 4 ACT24s and 0.68 (95% CI: 0.61, 0.75) for accelerometry. Total activity and MVPA measured by PAQ, ACT24, and accelerometry were all significantly correlated with body fat percentage and resting pulse rate, which are physiological indicators of physical activity. Using a combination of comparison methods, we found the PAQ and accelerometry to have moderate validity for assessing physical activity, especially MVPA, in epidemiologic studies.

Respuesta de la intensidad de luces LED sobre la producción de lechuga en una granja vertical casera

On the market there are several LED lamps that were not designed to produce lettuce, however, they can be purchased at a low cost. In Mexico there is a lack of research on its use in small-scale vertical farms and hydroponic established in urban agriculture. The objective of this work was to measure the response of three commercial lamps with LED lights on the growth and morphogenesis of sangria lettuce grown in a low-cost home vertical farm. The sangria lettuce was subjected to three light intensities with different spectra and photoperiod after 30 days of growth the plant height, leaf length, leaf width, number of leaves and fresh weight were measured, and a one-way analysis of variance (ANOVA) and Duncan's multiple comparison method was used through an algorithm designed in Python. According to the results, the highest fresh weight is made for a light intensity of 5700 lux. In the 2100 lux treatment, the highest height of the plant is performed and it was the treatment with the highest energy consumption. The production of lettuce at home is technically feasible, however, in addition to the light intensity, it is necessary to evaluate the quality (wavelengths) from the agronomic point of view.

Correlation of organic acid tolerance and genotypic characteristics of Listeria monocytogenes food and clinical isolates

A collection of Listeria monocytogenes isolates from various food products, food processing environments and clinical sources (n = 153) were evaluated for their tolerance to acetic, lactic and propionic acids. A large variation in tolerance was observed amongst isolates under mildly acidic conditions (pH 5.3) for acetic (5–20 mM undissociated acid) and propionic acid (2–10 mM undissociated acid) but there was less variation for lactic acid (3–6 mM undissociated acid). Analysis of the isolate genome sequences for a complement of genes previously shown to have a role in acid tolerance revealed that thiT, gadT2, gadD2 and gadD3 genes were linked to higher acetic acid tolerance (P < 0.05) while lisRK was linked to higher tolerance to propionic acid (P = 1 × 10−11). An absence of plasmid genes was also linked with isolates showing higher tolerance for all acids. Scoary GWAS analysis revealed that a total of 333, 207, and 333 genes were associated with acid tolerance for acetic, lactic, and propionic acid, respectively (P < 0.05). However, the p-value adjusted with Bonferroni's method for multiple comparisons did not reveal any significant associations. Isolates were grouped into clonal complexes (CC) using Multi Locus Sequence Typing (MLST) and MIC values for the three acids were determined for representative strains. One complex, CC18, showed significantly higher (P ≤ 0.05) acetic and propionic acid MIC values than other groups, whereas only CC7 type isolates revealed significantly higher (P ≤ 0.001) lactic acid MIC values. The results demonstrate that MLST typing could be linked to acid tolerance phenotypic traits which is important in predicting the behaviour of L. monocytogenes in food products.

A study of acoustic characteristics of voluntary expiratory sounds produced before and immediately after swallowing

To evaluate the expiratory sounds produced during swallowing recorded simultaneously with videofluorographic examination of swallowing (VF) using fast Fourier transform (FFT), and to examine the relationship between dysphagia and its acoustic characteristics. A total of 348 samples of expiratory sounds were collected from 61 patients with dysphagia whose expiratory sounds were recorded during VF. The VF results were evaluated by one dentist and categorized into three groups: safe group (SG), penetration group (PG), and aspiration group (AG). The duration and maximum amplitude of expiratory sounds produced were measured as the domain characteristics on the time waveform of these sounds and compared among the groups. Time window-length appropriate for FFT and acoustic discriminate values (AD values) of SG, PG, and AG were also investigated. The groups were analyzed using analysis of variance and Scheffé's multiple comparison method. The maximum amplitude of SG was significantly smaller than those of PG and AG. The mean duration in SG (2.05 s) was significantly longer than those in PG (0.84 s) and AG (0.96 s). The AD value in SG was significantly lower than those in PG and AG. AD value detects penetration or aspiration, and can be useful in screening for dysphagia.

Reproducibility, Validity, and Relative Validity of Self-Report Methods for Assessing Physical Activity in Epidemiologic Studies: Findings From the Women’s Lifestyle Validation Study

Among 683 participants in the Women's Lifestyle Validation Study (2010-2012), we evaluated the performance of a self-administered physical activity questionnaire (PAQ) and Web-based 24-hour recalls (Activities Completed Over Time in 24 Hours (ACT24)) using multiple comparison methods. Two PAQs, 4 ACT24s, two 7-day accelerometer measurements, 1 doubly labeled water (DLW) physical activity level (PAL) measure (repeated; n=90), and 4 resting pulse rate measurements were collected over 15 months. The deattenuated correlation between the PAQ and DLW PAL was 0.41 (95% confidence interval (CI): 0.33, 0.49) for total physical activity (PA) and 0.40 (95% CI: 0.31, 0.48) for moderate-to-vigorous PA (MVPA). These correlations were similar when using accelerometry as the comparison method. Single and averaged ACT24 measurements had lower correlations with DLW and accelerometry as comparison methods. The PAQ showed inverse correlations with DLW body fat percentage and resting pulse rate. Using the method of triads, the estimated correlation of the PAQ with true total PA was 0.54 (95% CI: 0.47, 0.62) and that with true MVPA was 0.60 (95% CI: 0.52, 0.69). For averaged ACT24, the estimated correlations were 0.50 (95% CI: 0.43, 0.59) for total PA and 0.47 (95% CI: 0.39, 0.58) for MVPA, and for averaged accelerometry, these estimated correlations were 0.72 (95% CI: 0.64, 0.81) and 0.62 (95% CI: 0.53, 0.71), respectively. The PAQ provided reasonable validity for total PA and MVPA.

17α‐Ethynylestradiol‐induced changes in Brassica rapa during the seedling growth stage

AbstractEstrogens and estrogen‐like compounds are considered contaminants of emerging concern due to their endocrine disrupting capability and potential to build up in soil and aquatic environments, although little is known about the effects of estrogenic compounds on plant life. This research aims to understand the effect of the synthetic hormone 17‐α ethynylestradiol (EE2) on Brassica rapa L. (field mustard) root and shoot vigor at the seedling stage. Endpoints considered included: plant height; root, shoot, and total dry biomass; number of leaves and inflorescences; leaf carbon and nitrogen; root growth traits (length, surface area, diameter, and volume); and root developmental parameters (tips, forks, and crossings). Tukey's method for multiple comparisons was used to determine the significance of pairwise differences between treatment means for each endpoint. 17‐α Ethynylestradiol acted generally as a biostimulant at the concentrations considered (0, 0.5, 1, 5, 10, and 15 μg L−1), with the most pronounced differences occurring in seedlings treated with 1 μg L−1 EE2. Although number of leaves and biomass appeared to be inhibited at EE2 concentrations of ≥5 μg L−1 and ≥10 μg L−1, respectively, all other traits in estrogen‐treated plants were similar or improved compared with the control plants. Study results suggest that at certain concentrations, EE2 contributes to more structured root systems, triggering vigorous plant development that may potentially enhance a successful seedling establishment.

Anticarcinogenic Efficacy of Fucoxanthin on HepG2 Cell Lines

Introduction: Hepatocellular Carcinoma (HCC) is considered one of the deadliest cancers which grow rapidly worldwide. Fucoxanthin can be acquired from edible brown seaweeds, reported that fucoxanthin has numerous physiological functions and biological abilities, and various medicinal properties. Aim: To evaluate the anti-carcinogenic efficiency of fucoxanthin against the Human Hepatoma Cell Line (HepG2). Materials and Methods: This in-vitro examination and research was carried from June 2018 to August 2018, at Alagappa University, Karaikudi, Tamil Nadu, India. Fucoxanthin at different concentrations was taken to demonstrate its antiproliferative potential and its cytotoxic effect. In this present examination, based on the outcome of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl2H-tetrazolium bromide (MTT) assay, 80 µM and 100µM were chosen for further in-vitro studies. It was noted that remarkable leakage of Lactate Dehydrogenase (LDH) and a noteworthy decrease in the Glutathione (GSH) content of 80µ M and 100µM of fucoxanthin treated HepG2 cells. Under light and fluorescence microscopic examination, there was a significant reduction in cell growth and cell proliferation in the fucoxanthin-treated HepG2 cells. Data were presented as the mean±standard deviation. The one-way analysis of variance (ANOVA) and Tukey’s multiple comparison method were used to find the level of significance. Results: The human HepG2 to be studied and analysed were divided into group I: control group; group II: comprising those cells treated with fucoxanthin in concentration of 80 µM; group III: comprising those cells treated with fucoxanthine in concentration of 100 µM. The results of the MTT assay put forward that fucoxanthin has the cytotoxic and anti-proliferative potential against HepG2 further fucoxanthin significantly alter the marker enzymes level (p-value &lt;0.05). The therapeutic efficiency of fucoxanthin might be due to the antioxidant effect of the bioactive compound. In this present investigation, the results of in-vitro studies, fucoxanthin strongly put forward that it has potential anticarcinogenic efficacy against the hepatic tumour (p-value &lt;0.05). Conclusion: The results of this analysis undoubtedly symbolise that fucoxanthin has anti-oxidant activity and anti-carcinogenic efficacy against primary liver cancer HCC. Due to their therapeutic efficacy, may be considered as an excellent candidate against HCC.

Differential diagnosis of pure ground glass nodules in lung with spectral CT imaging

Objective: To evaluate the differential diagnostic performance of quantitative parameters derived from the spectral CT imagingin pure ground-glass nodules. Methods: A total of 44 patients with pure ground glass nodules underwent chest energy spectrum CT and with known subsequently pathological findings in the Imaging Department of the Second Affiliated Hospital of Soochow University from August 2017 to September 2019 were retrospectively analyzed. Among them, there are 18 males and 26 females, aged from 26 to 79 (51±12) years. They were divided into as the inflammatory group (n=12), pre-invasive adenocarcinoma group (n=17) and invasive adenocarcinoma group (n=15). The aforementioned three groups were further reclassified as non-invasive adenocarcinoma group (inflammatory lesion+pre-invasive lesion) and invasive adenocarcinoma group in order to evaluating the values of water concentration (WC) for the determination of adenocarcinoma infiltration status. The values of WC derived from the arterial and venous phase of the lesion, iodine concentration (IC), standardized iodine concentration (NIC) were measured respectively.The slope of the energy spectral curve (K40-70KeV) derived from the arterial and venous phase of the lesion was also calculated. One-way ANOVA analysis was performed to compare the differences of the three groups and the multiple comparison method was used for further comparing. Intraclass correlation efficient (ICC) was used to assess the consistency of the three times of measurements. The area under curve(AUC) of Receiver Operating Characteristic (ROC) was conducted to evaluate the diagnostic performance of water based values. Results: The values of WC in the arterial and venous phases were significantly different. As in the inflammatory group, the pre-invasive lesion group and the invasive adenocarcinoma group, the values of WC was (291.95±58.66) mg/cm3, (297.61±63.96) mg/cm3and (374.52±60.62) mg/cm3 of the arterial phase, and (277.07±33.78) mg/cm3, (291.74±50.49) mg/cm3 and (373.33±75.12) mg/cm3 of the venous phase, respectively(all P<0.05). Further comparison demonstrated that no significant difference was observed for the values of WC derived from the arterial phases and venous phases between the inflammatory lesion group and the pre-invasive lesion group (all P>0.05).There were an significant differences between the invasive adenocarcinoma group, the inflammatory lesion group and the pre-invasive lesion group (all P<0.05). The values of WC derived from the venous phase achieved the largest AUC (0.770) for differentiating invasive adenocarcinoma from non-invasive adenocarcinoma (inflammatory lesions+pre-invasive lesions) in the pure ground glass nodules. The sensitivity and specificity were 66.67% and 93.10%, respectively, when using 349.31 mg/cm³ as the optimal threshold. The slope of the spectral curve and iodine-related parameters (IC, NIC) derived from arterial or venous phases among the three groups were not significantly different (all P>0.05). Conclusion: The values of WC derived from the spectral CT can better distinguish inflammatory, pre-invasive lesions and invasive adenocarcinoma, which is helpful for the qualitative analysis for pure ground glass nodules.

Variability of milk urea, milk urea nitrogen, and ammonia emission from dairy Simmental and Holstein cows based on the milk recording month

The subject of this paper was to define the variability of milk urea, milk urea nitrogen, and ammonia emission from dairy Simmental and Holstein cows relating to months of milk recording through the precision farming methodology. Test-day records of dairy cows used in the statistical analysis were collected over five years. Regarding the parity, the animals were divided into four classes; regarding the recording date, test-day records were divided into twelve recording months, from January to December. The analysis was performed separately for each breed. The significance of the differences between the recording months was tested by the Scheffe’s method of multiple comparisons (using the PROC GLM procedure in SAS). In terms of results, lower ammonia emission per cow was determined in the winter, while the ammonia emission was higher in the summer. Also, higher values of milk urea, milk urea nitrogen, as well as higher ammonia emission per animal, were determined in the Holstein than in Simmental cows.

Maternal intake restriction programs the energy metabolism, clock circadian regulator and mTOR signals in the skeletal muscles of goat offspring probably via the protein kinase A-cAMP-responsive element-binding proteins pathway.

The biological mechanism by which maternal undernutrition increases the metabolic disorder risk of skeletal muscles in offspring is not fully understood. We hypothesize that maternal intake restriction influences metabolic signals in the skeletal muscles of offspring via a glucagon-mediated pathway. Twenty-four pregnant goats were assigned to the control group (100% of the nutrients requirement, n = 12) and restricted group (60% of the control feed allowance from pregnant days 45 to 100, n = 12). Blood and Longissimus thoracis muscle were sampled from dams (100 d of gestation), fetuses (100 d of gestation), and kids (90 d after birth) in each group. The data were analyzed using the linear MIXED model, with the multiple comparison method of SIDAK applied. Intake restriction reduced (P < 0.05) the total blood protein of dams and fetuses. Maternal restriction decreased (P < 0.05) the cAMP-responsive element-binding protein 1 (CREB1), CREB-binding protein (CREBBP), protein kinase A (PKA), aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1), protein kinase B (AKT1), mammalian target of rapamycin (mTOR), and regulatory-associated protein of mTOR (RPTOR) mRNA expression in the fetuses, and reduced (P < 0.05) the CREBBP, nuclear receptor subfamily 1 group H member 3 (NR1H3), D-box binding PAR bZIP transcription factor (DBP) and PKA mRNA levels in the kids, but increased (P < 0.05) the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1A) and tuberous sclerosis 2 (TSC2) mRNA levels in the fetuses. The mRNA expression of clock circadian regulator (CLOCK) and TSC2 genes was increased (P < 0.05) in the restricted kids. The protein expression of total PKA and phosphorylated PKA in the restricted fetuses and kids were downregulated (P < 0.05), and the protein expression of total mTOR and phosphorylated mTOR were reduced (P < 0.05) in the restricted fetuses and kids. Maternal intake restriction regulated fat oxidation, protein synthesis, and circadian clock expression in the muscles of the offspring probably via the glucagon-mediated PKA-CREB pathway, which reveals a noteworthy molecular pathway that maternal undernutrition leads to metabolic adaptation of skeletal muscle in offspring.

Renal function and lipid metabolism are major predictors of circumpapillary retinal nerve fiber layer thickness\u2014the LIFE-Adult Study

BackgroundCircumpapillary retinal nerve fiber layer thickness (cpRNFLT) as assessed by spectral domain optical coherence tomography (SD-OCT) is a new technique used for the detection and evaluation of glaucoma and other optic neuropathies. Before translating cpRNFLT into clinics, it is crucially important to investigate anthropometric, biochemical, and clinical parameters potentially affecting cpRNFLT in a large population-based dataset.MethodsThe population-based LIFE-Adult Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. All participants underwent standardized systemic assessment of various cardiometabolic risk markers and ocular imaging, including cpRNFLT measurement using SD-OCT (Spectralis, Heidelberg Engineering). After employing strict SD-OCT quality criteria, 8952 individuals were analyzed. Multivariable linear regression analyses were used to evaluate the independent associations of various cardiometabolic risk markers with sector-specific cpRNFLT. For significant markers, the relative strength of the observed associations was compared to each other to identify the most relevant factors influencing cpRNFLT. In all analyses, the false discovery rate method for multiple comparisons was applied.ResultsIn the entire cohort, female subjects had significantly thicker global and also sectoral cpRNFLT compared to male subjects (p < 0.05). Multivariable linear regression analyses revealed a significant and independent association between global and sectoral cpRNFLT with biomarkers of renal function and lipid profile. Thus, thinner cpRNFLT was associated with worse renal function as assessed by cystatin C and estimated glomerular filtration rate. Furthermore, an adverse lipid profile (i.e., low high-density lipoprotein (HDL) cholesterol, as well as high total, high non-HDL, high low-density lipoprotein cholesterol, and high apolipoprotein B) was independently and statistically significantly related to thicker cpRNFLT. In contrast, we do not observe a significant association between cpRNFLT and markers of inflammation, glucose homeostasis, liver function, blood pressure, or obesity in our sector-specific analysis and globally.ConclusionsMarkers of renal function and lipid metabolism are predictors of sectoral cpRNFLT in a large and deeply phenotyped population-based study independently of previously established covariates. Future studies on cpRNFLT should include these biomarkers and need to investigate whether incorporation will improve the diagnosis of early eye diseases based on cpRNFLT.

HLA Loci and Recurrence of Focal Segmental Glomerulosclerosis in Pediatric Kidney Transplantation.

Background.Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation accounts for the majority of allograft failures in children with primary FSGS. Although current research focuses on FSGS pathophysiology, a common etiology and mechanisms of disease recurrence remain elusive.Methods.We performed a retrospective review of the Scientific Registry of Transplant Recipients to determine the association of specific HLA recurrence of FSGS. Kidney transplants recipients under the age of 19 who were diagnosed with FSGS, who were transplanted after January 1, 2000, and who had complete HLA data were included in the study. We performed simple logistic regression on all HLA A, B, C, DR, and DQ represented in the dataset and FSGS recurrence and then determined those associated with recurrence using the Benjamini–Hochberg method for multiple comparisons. For those HLAs that were associated with recurrence, we further determined the effect of matching recipient and donor HLA with recurrence.Results.HLA DR7, DR53, DQ2, DR52, and DQ7 were associated with increased or decreased risk of recurrent disease after transplantation. We identified a risk haplotype consisting of HLA-DR7, DR53, and DQ2 that was consistently associated with an increased risk of recurrence (odds ratio 1.91; 95% confidence interval, 1.44-2.54, P < 0.001). We also found that donor/recipient concordance for HLA-DQ7 was associated with a decreased risk of recurrence (odds ratio 0.42; 95% confidence interval, 0.37-0.53, P = 0.009).Conclusions.HLA profiles may be used for risk stratification of recurrence of FSGS in pediatric kidney transplant recipients and deserves further study.

Antifungal activity of boric acid, triclosan and zinc oxide against different clinically relevant Candida species.

The genus Candida includes about 200 different species, but only a few are able to produce disease in humans. The species responsible for the highest proportion of human infections is Candida albicans. However, in the last two decades there has been an increase in the proportion of infections caused by other Candida species, including C.glabrata (Nakaseomyces glabrata), C.parapsilosis, C.tropicalis, C.krusei (Pichia kudriavzevi) and more recently C.auris. Decolonisation of patients has been used as an infection control strategy for bacterial infections, but information about decolonisation products used in clinical practice for Candida and other fungal pathogens is limited. Compounds with antimicrobial activity, such as triclosan (TR), boric acid (BA) and zinc oxide (ZO), are mainly used in personal care products. These products can be used for long periods of time without an abrasive skin effect and are a possible alternative for patient decolonisation in healthcare settings. The aim of this study was to evaluate the antifungal activity of boric acid (BA), triclosan (TR) and zinc oxide (ZO), individually and combined, against clinically relevant Candida species. Compounds to be screened for antifungal activity were evaluated at different concentrations, alone, and combined, using a well diffusion assay. The statistical evaluation was performed using analysis of variance (ANOVA) and a post hoc analysis using the multiple comparisons method. Individually, BA and TR showed antifungal activity against all Candida species evaluated but ZO did not show any antifungal activity. Mixtures of BA [5%]-TR [0.2%]; BA [5%]-TR [0.3%]; BA [5%]-TR [0.2%]-ZO [8.6%]; and BA [5%]-TR [0.2%]-ZO [25%] yielded the highest antifungal activity. An increased antifungal effect was observed in some mixtures when compared with individual compounds. We demonstrated antifungal activity of BA and TR against multiple Candida species, including against a clade of the emerging healthcare-associated pathogen C.auris. Additionally, this study shows enhancement of the antifungal effect and no antagonism among the mixtures of these compounds. Further research is needed to determine whether these compounds can reduce the burden of Candida on skin.

Where to find needles in a haystack?

In many existing methods of multiple comparison, one starts with either Fisher’s p value or the local fdr. One commonly used p value, defined as the tail probability exceeding the observed test statistic under the null distribution, fails to use information from the distribution under the alternative hypothesis. The targeted region of signals could be wrong when the likelihood ratio is not monotone. The oracle local fdr based approaches could be optimal because they use the probability density functions of the test statistic under both the null and alternative hypotheses. However, the data-driven version could be problematic because of the difficulty and challenge of probability density function estimation. In this paper, we propose a new method, Cdf and Local fdr Assisted multiple Testing method (CLAT), which is optimal for cases when the p value based methods are optimal and for some other cases when p value based methods are not. Additionally, CLAT only relies on the empirical distribution function which quickly converges to the oracle one. Both the simulations and real data analysis demonstrate the superior performance of the CLAT method. Furthermore, the computation is instantaneous based on a novel algorithm and is scalable to large data sets.