Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Non-standard errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes

Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H2O2 production (ferrous oxidation - xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H2O2, to the endothelial dysfunction associated with experimental diabetes

MONOAMINE OXIDASE IS A SOURCE OF OXIDATIVE STRESS IN OBESE PATIENTS WITH CHRONIC INFLAMMATION

Obesity is an important preventable risk factor for morbidity and mortality from cardiometabolic disease. Oxidative stress (including in visceral adipose tissue) and chronic low-grade inflammation are the major underlying pathomechanisms. Monoamine oxidase (MAO) has recently emerged as an important source of cardiovascular oxidative stress. The present study was purported to evaluate the role of MAO as contributor to reactive oxygen species (ROS) production in white adipose tissue and vessels harvested from patients undergoing elective abdominal surgery. To this aim, visceral adipose tissue and mesenteric artery branches were isolated from obese patients with chronic inflammation and used for organ bath, ROS production, qRT-PCR and immune-histology (IH) studies. The human visceral adipose tissue and mesenteric artery branches contain mainly the MAO-A isoform, as shown by the qRT-PCR and IH experiments. A significant up-regulation of MAO-A, the impairment in vascular reactivity and increase in ROS production were found in obese vs non-obese patients. Incubation of the adipose tissue samples and vascular rings with the MAO-A inhibitor (clorgyline, 30 min) improved vascular reactivity and decreased ROS generation. In conclusion, MAO-A is the predominat isoform in human abdominal adipose and vascular tissues, is overexpressed in the setting of inflammation, and contribute to the endothelial dysfunctionThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Vitamin D alleviates oxidative stress in adipose tissue and mesenteric vessels from obese patients with subclinical inflammation

Obesity is an age-independent, life-style triggered, pandemic disease associated with both endothelial and visceral adipose tissue (VAT) dysfunction leading to cardiometabolic complications mediated via increased oxidative stress and persistent chronic inflammation. The present study was aimed to assess the oxidative stress in VAT and vascular samples and the effect of in vitro administration of vitamin D. VAT and mesenteric artery branches were harvested during abdominal surgery performed in patients referred for general surgery (n= 30) that were randomized into 2 subgroups: non-obese and obese. Serum levels of C reactive protein (CRP) and vitamin D were measured. Tissue samples were treated or not with the active form of vitamin D - 1,25(OH)2D3 (100 nM, 12 h). The main findings are that in obese patients: i) a low vitamin D status was associated with increased inflammatory markers and reactive oxygen species generation in VAT and vascular samples and, ii) in vitro incubation with vitamin D alleviated oxidative stress in VAT and vascular preparations and also, improved the vascular function. We report here that serum level of vitamin D inversely correlated with the magnitude of oxidative stress in the adipose tissue. Ex vivo treatment with active vitamin D mitigated obesity-related oxidative stress.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

MONOAMINE OXIDASE INHIBITION IMPROVES VASCULAR FUNCTION IN MAMMARY ARTERIES FROM NON-DIABETIC AND DIABETIC PATIENTS WITH CORONARY HEART DISEASE

Monoamine oxidases (MAOs) are mitochondrial enzymes with 2 isoforms that have emerged as important contributors to cardiovascular oxidative stress via the constant generation of hydrogen peroxide. The present study was purported to assess whether MAO-derived H2O2 contributes to the endothelial dysfunction in mammary arteries harvested from coronary heart disease patients with/without diabetes mellitus subjected to coronary artery bypass grafting. To this aim the effects of MAO inhibition on vascular contractility to phenylephrine and endothelial-dependent relaxation (EDR) in response to acetylcholine were studied in vascular segments. Clorgyline (irreversible MAO A inhibitor), selegiline (irreversible MAO B inhibitor), and moclobemide (reversible MAO A inhibitor) were applied in the organ bath (10Âľmol/L). MAO expression was assessed by immunohistochemistry. We found a constant impairment of EDR that has been significantly attenuated in the presence of the MAO A and B inhibitors in both groups of coronary heart disease patients. MAO B was the dominant isoform in all human diseased vessels. In conclusion, in vitro inhibition of MAO significantly improved endothelium-dependent relaxation in human mammary arteries, regardless the presence of diabetes. These data suggest that MAO inhibitors might be useful in restoring endothelial response in clinical conditions associated with increased oxidative stress, such as coronary artery disease and diabetes.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Relationship between Novel Elastography Techniques and Renal Fibrosis—Preliminary Experience in Patients with Chronic Glomerulonephritis

Introduction: A renal biopsy represents the gold standard in the diagnosis, prognosis, and management of patients with glomerulonephritis. So far, non-invasive elastographic techniques have not confirmed their utility in replacing a biopsy; however, the new and improved software from Hologic Supersonic Mach 30 is a promising method for assessing the renal tissue’s stiffness and viscosity. We investigated whether this elastography technique could reveal renal tissue fibrosis in patients with chronic glomerulonephritis. Materials and methods: Two-dimensional-shear wave elastography (SWE) PLUS and viscosity plane-wave ultrasound (Vi PLUS) assessments were performed in 40 patients with chronic glomerulopathies before being referred for a renal biopsy. For each kidney, the mean values of five stiffness and viscosity measures were compared with the demographic, biological, and histopathological parameters of the patients. Results: In total, 26 men and 14 women with a mean age of 52.35 ± 15.54 years, a mean estimated glomerular filtration rate (eGFR) of 53.8 ± 35.49 mL/min/1.73m2, and a mean proteinuria of 6.39 ± 7.42 g/24 h were included after providing their informed consent. Out of 40 kidney biopsies, 2 were uninterpretable with inappropriate material and were divided into four subgroups based on their fibrosis percentage. Even though these elastography techniques were unable to differentiate between separate fibrosis stages, when predicting between the fibrosis and no-fibrosis group, we found a cut-off value of <20.77 kPa with the area under the curve (AUC) of 0.860, a p < 0.001 with 88.89% sensitivity, and a 75% specificity for the 2D SWE PLUS measures and a cut-off value of <2.8 Pa.s with an AUC of 0.792, a p < 0.001 with 94% sensitivity, and a 60% specificity for the Vi PLUS measures. We also found a cut-off value of <19.75kPa for the 2D SWE PLUS measures (with an AUC of 0.789, p = 0.0001 with 100% sensitivity, and a 74.29% specificity) and a cut-off value of <1.28 Pa.s for the Vi PLUS measures (with an AUC 0.829, p = 0.0019 with 60% sensitivity, and a 94.29% specificity) differentiating between patients with over 40% fibrosis and those with under 40%. We also discovered a positive correlation between the glomerular filtration rate (eGFR) and 2D-SWE PLUS values (r = 0.7065, p < 0.0001) and Vi PLUS values (r = 0.3637, p < 0.0211). C reactive protein (CRP) correlates with the Vi PLUS measures (r = -0.3695, p = 0.0189) but not with the 2D SWE PLUS measures (r = −0.2431, p = 0.1306). Conclusion: Our findings indicate that this novel elastography method can distinguish between individuals with different stages of renal fibrosis, correlate with the renal function and inflammation, and are easy to use and reproducible, but further research is needed for them to be employed routinely in clinical practice

Histomorphometrical and CBCT Evaluation of Tissue Loss Progression Induced by Consecutive, Alternate Ligatures in Experimental Peri-Implantitis in a Dog Model: A Pilot Study

Objectives: Soft and hard tissue breakdown was histologically and radiologically assessed around implants with alternate, consecutively placed ligatures on the same edentulous dog hemimandible. The influence of ligatured implants (LI) on adjacent non-ligatured implants (NLI, as a possible naturally induced peri-implantitis) was also evaluated. Material and Methods: Three months after tooth extraction, five dental implants were placed in the dog hemimandible. Two months after abutment placement, ligatures were placed subsequently two months apart on alternate implants, while both intermediate implants were left without ligatures. Ligatures were kept in place during the entire experiment, and no plaque control measures were taken. Eleven months post-implantation, the animal was sacrificed. Undecalcified ground sections were cut, stained with Masson Goldner and MOVAT Pentachrome and evaluated by light microscopy. Soft and hard tissue loss was assessed using histomorphometric and CBCT parameters. Results: All NLI presented deep false peri-implant pockets on the oral aspect and pronounced vertical bone resorption on the buccal aspect. After 2, 4 and 6 months, during the breakdown period, more than 30% of the bone was lost in LI in all directions, while, despite immediate vicinity, NLI displayed less destruction. Intense inflammation, typical for induced peri-implantitis, was present, with similar intensity in LI as NLI, but in different parts of the lesions. Morphometry confirmed intense soft tissue inflammation, more bone resorption and higher amounts of infiltrated connective tissue in LI when compared with NLI. Conclusion: Within the limits of the present pilot study, the adequacy of the experimental dog model based on ligature-induced peri-implantitis was able to be successfully challenged by non-ligature models of spontaneously occurring peri-implant inflammation, while meeting the requirements for experimental designs with a very small numbers of animals. The influence of implants with severe peri-implantitis on adjacent implants resulted in less than expected tissue loss in the latter accession numbers

Comparison of Type I and Type III Collagen Concentration between <i>Oreochromis mossambicus</i> and <i>Oreochromis niloticus</i> in Relation to Skin Scaffolding

Background and Objectives: Skin scaffolding can be done using allografts and autografts. As a biological allograft, the skin of Oreochromis niloticus (ON) has been used due to its high type I and III collagen content. Oreochromis mossambicus (OM) is also a member of the Oreochromis family, but not much is known regarding its collagen content. As such, this study aimed to assess and compare the collagen content of the two fish species. Materials and Methods: This is a crossover study comparing the skin collagen contents of the two fish. Young fish were chosen, as they tend to have higher collagen concentrations. The skin samples were sterilized in chlorhexidine and increasing glycerol solutions and analyzed histochemically with Sirius red picrate under polarized light microscopy. Results: 6 young ON and 4 OM specimens were used. Baseline type I collagen was higher for OM, but at maximum sterilization it was higher for ON, with no differences in between Type III collagen was higher for OM across all comparisons with the exception of the last stage of sterilization. Generally, collagen concentrations were higher in highly sterilized samples. Conclusions: OM skin harvested from young fish, with its greater collagen III content may be a better candidate for use as a biological skin scaffold in the treatment of burn wounds, compared to ON

Relationship between Novel Elastography Techniques and Renal Fibrosis—Preliminary Experience in Patients with Chronic Glomerulonephritis

Introduction: A renal biopsy represents the gold standard in the diagnosis, prognosis, and management of patients with glomerulonephritis. So far, non-invasive elastographic techniques have not confirmed their utility in replacing a biopsy; however, the new and improved software from Hologic Supersonic Mach 30 is a promising method for assessing the renal tissue’s stiffness and viscosity. We investigated whether this elastography technique could reveal renal tissue fibrosis in patients with chronic glomerulonephritis. Materials and methods: Two-dimensional-shear wave elastography (SWE) PLUS and viscosity plane-wave ultrasound (Vi PLUS) assessments were performed in 40 patients with chronic glomerulopathies before being referred for a renal biopsy. For each kidney, the mean values of five stiffness and viscosity measures were compared with the demographic, biological, and histopathological parameters of the patients. Results: In total, 26 men and 14 women with a mean age of 52.35 ± 15.54 years, a mean estimated glomerular filtration rate (eGFR) of 53.8 ± 35.49 mL/min/1.73m2, and a mean proteinuria of 6.39 ± 7.42 g/24 h were included after providing their informed consent. Out of 40 kidney biopsies, 2 were uninterpretable with inappropriate material and were divided into four subgroups based on their fibrosis percentage. Even though these elastography techniques were unable to differentiate between separate fibrosis stages, when predicting between the fibrosis and no-fibrosis group, we found a cut-off value of p p p = 0.0001 with 100% sensitivity, and a 74.29% specificity) and a cut-off value of p = 0.0019 with 60% sensitivity, and a 94.29% specificity) differentiating between patients with over 40% fibrosis and those with under 40%. We also discovered a positive correlation between the glomerular filtration rate (eGFR) and 2D-SWE PLUS values (r = 0.7065, p r = 0.3637, p p = 0.0189) but not with the 2D SWE PLUS measures (r = −0.2431, p = 0.1306). Conclusion: Our findings indicate that this novel elastography method can distinguish between individuals with different stages of renal fibrosis, correlate with the renal function and inflammation, and are easy to use and reproducible, but further research is needed for them to be employed routinely in clinical practice