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Although therapies based on mesenchymal stromal cells (MSCs) are being implemented in clinical settings, many aspects regarding these procedures require further optimization. Domestic dogs suffer from numerous immune-mediated diseases similar to those found in humans. This study aimed to assess the immunomodulatory activity of canine (c) Wharton jelly (WJ)-derived MSCs and refer them to human (h) MSCs isolated from the same tissue. Canine MSC(WJ)s appeared to be more prone to in vitro aging than their human counterparts. Both canine and human MSC(WJ)s significantly inhibited the activation as well as proliferation of CD4+ and CD8+ T cells. The treatment with IFNγ significantly upregulated indoleamine-2,3-dioxygenase 1 (IDO1) synthesis in human and canine MSC(WJ)s, and the addition of poly(I:C), TLR3 ligand, synergized this effect in cells from both species. Unstimulated human and canine MSC(WJ)s released TGFβ at the same level (p > 0.05). IFNγ significantly increased the secretion of TGFβ in cells from both species (p < 0.05); however, this response was significantly stronger in human cells than in canine cells. Although the properties of canine and human MSC(WJ)s differ in detail, cells from both species inhibit the proliferation of activated T cells to a very similar degree and respond to pro-inflammatory stimulation by enhancing their anti-inflammatory activity. These results suggest that testing MSC transplantation in naturally occurring immune-mediated diseases in dogs may have high translational value for human clinical trials. [ABSTRACT FROM AUTHOR]

Background: Filiano and Kinney proposed a triple-risk model for the sudden infant death syndrome (SIDS) that involves the intersection of three risks: (1) a vulnerable infant, (2) a critical developmental period in homeostatic control, and (3) an exogenous stressor(s). The primary evidence for the role of a critical developmental period in SIDS etiology is the peak of cases around the third month of life. Independently, several studies pointed to correlation between gestational age and age at death in SIDS, but used that to assess the SIDS risk for preterm infants, ignoring further ramifications. Methods: We did a detailed analysis of CDC data spanning over two decades (1983–2011). We focused not only on the correlation between two age variables (gestational and age at death), but also on the possibility of misdiagnosis. Also, we attempted to account for potential biases in the data induced by the ICD-9/ICD-190 transition or the "Back to Sleep" campaign. Results: The peak of deaths in the third month of life, that was the main argument for the role of the critical development period, wasn't unique to SIDS. However, we confirmed an almost linear and negative correlation between gestational age and the week of death due to SIDS. This pattern (slope of correlation < 0 and significance of correlation p < 0.05) is characteristic of SIDS among all diseases analyzed in the study. Conclusions: We interpret the results as the evidence of the role of the critical development period in SIDS etiology. Possibly more attention in the future research should be put to theories that are based on homeostatic control. [ABSTRACT FROM AUTHOR]

The ability of MSCs to modulate the inflammatory environment is well recognized, but understanding the molecular mechanisms responsible for these properties is still far from complete. Prostaglandin E2 (PGE2), a product of the cyclooxygenase 2 (COX-2) pathway, is indicated as one of the key mediators in the immunomodulatory effect of MSCs. Due to the pleiotropic effect of this molecule, determining its role in particular intercellular interactions and aspects of cell functioning is very difficult. In this article, the authors attempt to summarize the previous observations regarding the role of PGE2 and COX-2 in the immunomodulatory properties and other vital functions of MSCs. So far, the most consistent results relate to the inhibitory effect of MSC-derived PGE2 on the early maturation of dendritic cells, suppressive effect on the proliferation of activated lymphocytes, and stimulatory effect on the differentiation of macrophages into M2 phenotype. Additionally, COX-2/PGE2 plays an important role in maintaining the basic life functions of MSCs, such as the ability to proliferate, migrate and differentiate, and it also positively affects the formation of niches that are conducive to both hematopoiesis and carcinogenesis. [ABSTRACT FROM AUTHOR]

In many pharmaceuticals, a hydrogen atom or hydroxyl group is replaced by a fluorine to increase bioavailability and biostability. The fate of fluorine released from fluorine-containing drugs is not well investigated. The aim of this study was to examine possible fluorination of proteins in rat liver and brain after administration of the fluorinated drug cinacalcet. We assigned 18 Wistar rats to a control group (n = 6) and a group treated with cinacalcet (2 mg kg−1/body weight, 5 days/week), divided into 7 day (n = 6) and 21 day (n = 6) treatment subgroups. Fluorinated proteins were identified using a free proteomics approach; chromatographic separation and analysis by high-resolution mass spectrometry; peptide/protein identification using the Mascot search algorithm; manual verification of an experimentally generated MS/MS spectrum with the theoretical MS/MS spectrum of identified fluorinated peptides. Three fluorinated proteins (spectrin beta chain; carbamoyl-phosphate synthase [ammonia], mitochondrial; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1) were identified in the liver and four (spectrin beta chain, dihydropyrimidinase-related protein 4, prominin-2, dihydropyrimidinase-related protein 4) in the brain tissue after 21 days of cinacalcet treatment, but not in the control group. Introduction of fluorine into an organism by administration of fluorinated drugs results in tissue-specific fluorination of proteins. [ABSTRACT FROM AUTHOR]

Recently, the possibility of cross-kingdom gene expression regulation by miRNAs from other species ("xenomiRs"), specifically from plants, has acquired scientific meaning. Based on the one of oldest methods for dealing with inflammation via the use of cabbage leaf compresses, we investigated the effects of Brassica oleracea derived miR172a on the potential human target gene encoding FAN (Factor Associated with Neutral Sphingomyelinase Activation) protein. In vitro experiments showed a decrease in FAN protein levels in both human and mouse cells transfected with bol-miRNA172a. As the FAN protein mediates inflammatory responses, the potential of miR172a to mitigate the inflammatory process was tested in a mouse model of rheumatoid arthritis. Animal studies showed the decreased oedema of inflamed paws in mouse with rheumatoid arthritis model induced after treatment with miR172a. [ABSTRACT FROM AUTHOR]

The pathophysiology of rotator cuff tendinopathy is not fully understood, particularly in terms of the local inflammatory process. This study aimed to investigate the expression of selected molecules in the tumour necrosis factor (TNF)-α transduction pathway, including TNF-α, TNF receptor 1 (TNFR1), neutral sphingomyelinase activation associated factor (NSMAF), caspase 3 (Casp3), and interleukin (IL)-8, in patients with rotator cuff tendinopathy that had undergone surgical treatment. We included 44 participants that underwent arthroscopy, due to rotator cuff tendinopathy. Samples from the injured tendon were collected during arthroscopy, and RT-PCR was performed to determine gene expression. Pearson correlation analyses or U-Mann–Whitney test were performed to identify associations with the following parameters: sex, age at admission, body mass index, the presence of night pain, previous treatment (nonsteroidal anti-inflammatory drugs and/or steroids), medical history of the shoulder injury, upper subluxation of the humeral head, and the number of tendons injured. RT-PCR showed that the selected pro-inflammatory factors involved in the TNF-α signalling pathway expression levels were expressed in the tendon tissues. However, the levels of expression varied from patient to patient. Variations were over 250-fold for TNF-α, about 130-fold for TNFR1, NSMAF, and Casp3, and 1000-fold for IL-8. We could not confirm that any of the clinical parameters investigated were associated with the level of gene expression in the TNF-α pathway and IL-8. [ABSTRACT FROM AUTHOR]

Facilitated subcutaneous immunoglobulin (fSCIG) replacement therapy is the latest method of IgG administration; however, real-life data are limited. We retrospectively analyzed the everyday experience of fSCIG administration, particularly, the method used to switch from intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) to fSCIG and the dosing modifications required. Of the 39 adult patients with primary immunodeficiency (PID) who received fSCIG, 34 remained on the therapy at the end of the study. The median observation time was 18 (range, 3–24) months. Two patients were IgG-treatment-naïve; 23 had previously received IVIG and 14 had received SCIG. In 25 cases, a non-ramp-up dosing mode was used to switch to fSCIG (including two half-monthly doses given biweekly in 14 cases, and full monthly doses given in 11 cases), a ramp-up mode was used in six cases; other methods were used in eight cases. The median IgG trough level at baseline was 7.9 g/L (n = 38), 7.9 g/L (n = 32) at Month 6, 9.0 g/L (n = 30) at Month 12, 8.6 g/L (n = 22) at Month 18, and 9.0 g/L (n = 11) at Month 24. No serious bacterial infections or hospitalizations due to PID complications occurred. At the end of the study, 24 patients (71%) received fSCIG every 4 weeks, six (18%) received fSCIG every 3 weeks, and four (12%) received fSCIG biweekly. In conclusion, our study provides real-life evidence of clinical efficacy of personalized fSCIG treatment when switching from prior immunoglobulin replacement using various switching modes and dosing frequencies. [ABSTRACT FROM AUTHOR]

Background. Healthcare-associated infections could affect the rate of morbidity, mortality and postdischarge hospitalization among patients. They are also dangerous to healthcare professionals and generate significant cost to the healthcare system. Objectives. The aim of this study was to evaluate the occurrence rate of colonization with various antibioticresistant (AR) bacteria among patients admitted to the Department of Immunology, Transplantology and Internal Diseases. Material and methods. The study used retrospective analysis of patients (n = 280) with no clinical signs of infection admitted into the department between November 2015 and May 2017. The observational period lasted until January 2019. Collected data included sex, age at admission, location directly prior to current hospitalization, and medical history. Nasal and rectal swabs were collected, and stool and urine samples were obtained on the day of admission. Specimens were cultured according to standard microbiological procedures. In all cases, the appropriate bioMerieux (Marcy-l'Étoile, France) media were used. Isolates were identified using mass spectrometer (Vitek MS; bioMerieux). Results. One-hundred ninety-one (68.2%) of patients were colonized with AR bacteria. The incidence of colonization was not influenced by age or sex. The risk of colonization was associated with admission from another hospital and history of kidney transplantation (p = 0.0136 and p < 0.001, respectively). The number of hospitalizations during the whole observational period was higher in the group of colonized patients compared to non-colonized (2.76 ±2.4 vs 2.07 ±1.68, p = 0.0099). The number of hospitalizations correlated positively with the number of positive cultures obtained from the same patients (rho = 0.18, p = 0.0274). Conclusions. The rate of colonization at admission to the ward could be high, depending on previous hospitalization and medical history. Colonization significantly increased post-discharge hospitalization rate. [ABSTRACT FROM AUTHOR]

Background: There are many doubts with regards to accepting deceased kidneys with acute kidney injury (AKI) for transplantation. Purpose: The aim of this study was to present the 5-years outcome of kidney transplantation cases where deceased donors developed AKI before organ procurement. Methods: Two hundred twenty-six deceased renal transplants were analyzed. Data regarding donors and recipients were collected. Terminal AKI was defined as terminal serum creatinine concentration higher than 1.99 mg/dL and 66 such cases were diagnosed. All kidney transplant recipients were followed for 60 months. Results: AKI group presented more episodes of delayed graft function (DGF) compared to the non-AKI group (56% vs 35%, p <.05). No differences were observed between the groups in the rate of acute rejection episodes, kidney function as well as patient and graft survival. Conclusions: Transplants with AKI present more often DGF and comparable graft survival to transplants without AKI. Kidneys with AKI can be a valuable source of organs provided attentive selection and appropriate care of deceased donors. [ABSTRACT FROM AUTHOR]

Liver transplantation remains the only therapeutic method in end-stage liver disease. Cardiovascular system diseases, including arterial hypertension, are considered one of the main risk factors increasing mortality in this population. The aim of the study was the evaluation of circadian blood pressure patterns in liver transplant recipients. In a group of 107 liver transplant recipients, a 24-hour ambulatory blood pressure monitoring (ABPM) was performed. The ABPM revealed arterial hypertension in 88.79% and unsatisfactory blood pressure (BP) control in 71.03% of the study participants. The abnormal circadian BP pattern was observed in 90.65% of liver recipients. The subgroup of patients with preserved BP circadian rhythm was characterized by higher standard deviation (SD) and coefficient of variation (CV) values for 24-hour systolic, diastolic and mean arterial blood pressure (SBP, DBP, and MAP). There were no such differences for other short-term blood pressure variability (ST BPV) parameters: SD and CV of day-time and night-time SBP, DBP and MAP values. Arterial hypertension and circadian BP abnormalities are present in a majority of liver transplant recipients. BP circadian rhythm is not associated with ST BPV parameters assessed separately during awake and sleep period which suggests that both groups of parameters could reflect different cardiovascular phenomena after liver transplantation. [ABSTRACT FROM AUTHOR]

Aims: The efficacy of cell therapy in patients with stress urinary incontinence (SUI) is lower than expected. The aim of this study was to determine the injection accuracy rate both with transurethral and periurethral route. Methods: Autologous intraurethral cell transplantation was performed in female goats. The cells were injected either periurethrally (PERI group, two depots/animal, n = 8) or transurethrally (TRANS group, eight depots/animal, n = 11). Transurethral injections were performed under endoscopic guidance. The number and distribution of cell depots in urethras were analyzed in the three‐step protocol: 1) screening of whole explants by in vivo imaging system; 2) systematic microscopic analysis of raw 10 μm cross‐sections; 3) immunohistochemistry. As control, four urethras collected 1 day after transurethral transplantation were used. Episodes of cell suspension leakages after needle withdrawal were noted. Results: In all experimental animals depots were identified in the urethral wall 28 days after transplantation. The mean percentage of depots located in the urethral wall in relation to all performed injections amounted to 68.7% and 67.0% for PERI and TRANS groups, respectively. The mean proportions of depots which were identified in external urethral sphincter (EUS) amounted 18.8% and 17.1%, respectively. Suspension leakage was observed in 19% of transurethral injections. Conclusions: Although majority of cell depots were administrated accurately into the urethral wall, the precise delivery of cells into EUS is limited regardless of injection method. The insufficient accuracy of cell delivery into EUS and cell suspension leakage can contribute to the low efficacy of cell therapy in human patients with SUI. [ABSTRACT FROM AUTHOR]

In our work, we have built models predicting whether a patient will lose an organ after a liver transplant within a specified time horizon. We have used the observations of bilirubin and creatinine in the whole first year after the transplantation to derive predictors, capturing not only their static value but also their variability. Our models indeed have a predictive power that proves the value of incorporating variability of biochemical measurements, and it is the first contribution of our paper. As the second contribution we have identified that full-complexity models such as random forests and gradient boosting lack sufficient interpretability despite having the best predictive power, which is important in medicine. We have found that generalized additive models (GAM) provide the desired interpretability, and their predictive power is closer to the predictions of full-complexity models than to the predictions of simple linear models. [ABSTRACT FROM AUTHOR]

Currently, the majority of neonates born to organ recipient mothers on chronic immunosuppressive therapy are formula fed. However, over the past few years, evidence has grown, suggesting that breastfeeding might be possible and beneficial. We designed a study assessing the transfer of tacrolimus into the colostrum of posttransplant mothers. We assessed the amount of tacrolimus and its metabolites, M-1 and M-3, that would be ingested by the breastfed neonates. Concentrations of tacrolimus and its metabolites were measured in colostrum from 14 posttransplant mothers as well as in venous cord blood and venous blood of the neonates. Test material analysis was performed by liquid chromatography coupled with mass spectrometry (LC/MS). The amount of ingested formula was registered, which allowed for estimation of the amount of tacrolimus and its metabolites that would be ingested by breastfed infants. The mean amount of tacrolimus that would be ingested by the neonates in maternal milk was 151.4 ng/kg/24 h (standard deviation SD ± 74.39); metabolite M-1: 23.80 ng/kg/24 h (SD ± 14.53); and metabolite M-3: 13.25 ng/kg/24 h (SD ± 9.05). The peak level of tacrolimus and metabolite M-1 in colostrum was noted 8 h after an oral dose (3.219 ng/mL SD ± 2.22 and 0.56 ng/mL SD ± 0.60, respectively) and metabolite M-3 after 6 h (0.29 ng/mL SD ± 0.22). Low concentrations of tacrolimus and its metabolites, M-1 and M-3, in colostrum show that neonates will ingest trace amounts of the drug. Further studies are required to fully assess the safety of breastfeeding by posttransplant mothers. [ABSTRACT FROM AUTHOR]

Aim The study was conducted to investigate secretory activity and define the paracrine potential of mesenchymal stem cells from human umbilical cord and amniotic membrane (UC-MSCs and AM-MSCs, respectively). Methods UC-MSCs ( n = 6) were obtained from tissue explants using an adherent method after two weeks of incubation. AM-MSCs ( n = 6) were obtained by digestion with tripsin and collagenase. MSC phenotype was confirmed in vitro by performing flow cytometry, differentiation assays and vimentin staining. Supernatants were collected after 48 h culturing in serum-free conditions and the following concentrations were determined: epidermal growth factor (EGF), interleukin (IL)-6, IL-10, tumor necrosis factor-α, transforming growth factor-β (TGF-β), vascular endothelial growth factor-α (VEGF-α) and metalloproteinase (MMP) 1, 8 and 13, using multiplex supernatant cytokine assay. Data were compared with adipose tissue derived MSCs (AD-MSCs, n = 6). Results Both UC-MSC and AM-MSC populations were positively identified as MSCs by flow cytometry and differentiation potential into bone, cartilage and adipose tissue. Using a multiple cytokine detection assay, we proved that both UC-MSCs and AM-MSCs show high secretive capacity. However, the secretion profile differed between cells from various sources. UC-MSCs showed significantly higher production of TGF-β and lower production of VEGF-α, compared to AD-MSCs ( P = 0.004) and AM-MSCs ( P = 0.039) and lower levels of EGF ( P = 0005). AM-MSCs showed significantly lower levels of MMP-8 than UC-MSCs ( P = 0.024); however, there was no difference in levels of released cytokines compared to AD-MSCs. Conclusion AM-MSCs show similar IL production as AD-MSCs, while UC-MSCs have a significantly different profile, which suggests diverse biological potential of both cell types for immunomodulative and regenerative therapy. [ABSTRACT FROM AUTHOR]

Introduction: Despite spectacular progress in cellular transplantology, there are still many concerns about the fate of transplanted cells. More preclinical studies are needed, especially on large animal models, to bridge the translational gap between basic research and the clinic. Herein, we propose a novel approach in analysis of cell transplantation effects in large animals explants using in vivo imaging system (IVIS®) or similar equipment. Material and methods: In the in vitro experiment cells labeled with fluorescent membrane dyes: DID (far red) or PKH26 (orange) were visualized with IVIS®. The correlation between the fluorescence signal and cell number with or without addition of minced muscle tissue was calculated. In the ex vivo study urethras obtained from goats after intraurethral cells (n = 9) or PBS (n = 4) injections were divided into 0.5 cm cross-slices and analyzed by using IVIS®. Automatic algorithm followed or not by manual setup was used to separate specific dye signal from tissue autofluorescence. The results were verified by systematic microscopic analysis of standard 10 μm specimens prepared from slices before and after immunohistochemical staining. Comparison of obtained data was performed using diagnostic test function. Results: Fluorescence signal strength in IVIS® was directly proportional to the number of cells regardless of the dye used and detectable for minimum 0.25x106 of cells. DID-derived signal was much less affected by the background signal in comparison to PKH26 in in vitro test. Using the IVIS® to scan explants in defined arrangement resulted in precise localization of DID but not PKH26 positive spots. Microscopic analysis of histological specimens confirmed the specificity (89%) and sensitivity (80%) of IVIS® assessment relative to DID dye. The procedure enabled successful immunohistochemical staining of specimens derived from analyzed slices. Conclusions: The IVIS® system under appropriate conditions of visualization and analysis can be used as a method for ex vivo evaluation of cell transplantation effects. Presented protocol allows for evaluation of cell delivery precision rate, enables semi-quantitative assessment of signal, preselects material for further analysis without interfering with the tissue properties. Far red dyes are appropriate fluorophores to cell labeling for this application. [ABSTRACT FROM AUTHOR]

Objective:Studies on the regulation of human blood flow revealed several modes of oscillations with frequencies ranging from 0.005 to 1 Hz. Several mechanisms were proposed that might influence these oscillations, such as the activity of vascular endothelium, the neurogenic activity of vessel wall, the intrinsic activity of vascular smooth muscle, respiration, and heartbeat. These studies relied typically on non-invasive techniques, for example, laser Doppler flowmetry. Oscillations of biochemical markers were rarely coupled to blood flow. Methods:The redox potential difference between the artery and the vein was measured by platinum electrodes placed in the parallel homonymous femoral artery and the femoral vein of ventilated anesthetized pigs. Results:Continuous measurement at 5 Hz sampling rate using a digital nanovoltmeter revealed fluctuating signals with three basic modes of oscillations: ∼ 1, ∼ 0.1 and ∼ 0.01 Hz. These signals clearly overlap with reported modes of oscillations in blood flow, suggesting coupling of the redox potential and blood flow. Discussion:The amplitude of the oscillations associated with heart action was significantly smaller than for the other two modes, despite the fact that heart action has the greatest influence on blood flow. This finding suggests that redox potential in blood might be not a derivative but either a mediator or an effector of the blood flow control system. [ABSTRACT FROM PUBLISHER]

Aim Retention of indoxyl sulphate and p-cresol sulphate is associated with many diseases. The aim of the present study was to examine serum levels of indoxyl sulphate and p-cresol sulphate, the dynamics of their changes according to age, and their precursors. Methods The study included 180 healthy individuals aged 20-90 years ( n = 180), divided into subgroups by decade ( n = 30 in each subgroup) and into subgroups of ≥65 years ( n = 42) or <65 years ( n = 138). Serum indoxyl sulphate and p-cresol sulphate, tryptophan, and tyrosine were measured using high-performance liquid chromatography-mass spectrometry. Results The 70-90 years age group had higher indoxyl sulphate than the 50-59 years age group ( P = 0.033). The 70-90 years age group had higher p-cresol sulphate than the 20-29 years ( P < 0.001), 30-39 years ( P < 0.001), 40-49 years ( P = 0.007) and 50-59 years ( P = 0.001) age groups; the 60-69 years age group had higher p-cresol sulphate than the 20-29 years ( P = 0.043) and 30-39 years ( P = 0.011) age groups. Indoxyl sulphate and p-cresol sulphate serum levels were higher in those aged ≥65 years. Indoxyl sulphate and p-cresol sulphate serum levels correlated positively with age, but not with tryptophan and tyrosine, respectively. Conclusions Healthy aging is associated with indoxyl sulphate and p-cresol sulphate serum level increases, which are not linked to tryptophan and tyrosine serum levels. Geriatr Gerontol Int 2017; 17: 1022-1026. [ABSTRACT FROM AUTHOR]

Background/aim: Mesenchymal stem cells (MSCs) are gaining rising interest in gynecology and obstetrics. MSCs immunomodulatory properties are suitable enough to reduce perinatal morbidity caused by inflammation in premature neonates. The aim of this study was to evaluate and compare the ability to inhibit allo-activated lymphocytes proliferation by MSCs derived from different sources: amniotic membrane (AM), umbilical cord (UC) and adipose tissue (AT).Methods: MSCs were isolated from AM (n = 7) and UC (n = 6) and AT (n = 6) of healthy women. Cells were characterized by flow cytometry and differentiation assay. To evaluate the potential of fetal and adult MSCs to diminish immunological response, mixed lymphocytes reaction (MLR) was performed.Results: Amnion and UC-derived cells displayed typical MSCs characteristics. Addition of MSCs to MLR significantly inhibited the proliferation of stimulated lymphocytes. The effect was observed regardless of the MSCs type used (p < 0.01 in all groups). Comparative analysis revealed no significant differences in this action between tested MSCs types. Additionally, no type of MSCs significantly stimulated allogeneic lymphocytes.Conclusion: The results prove the immunosuppressive capacities of fetal-derived MSCs in vitro. In the future, they may be potentially used to treat premature newborn as well as in immunomodulation in post-transplant therapy. [ABSTRACT FROM AUTHOR]

Background: Cell-based therapy is a treatment method in tendon injuries. Bone morphogenic protein 12 (BMP-12) possesses tenogenic activity and was proposed as a differentiating factor for stem cells directed to transplantation. However, BMPs belong to pleiotropic TGF-β superfamily and have diverse effect on cells. Therefore, the aim of this study was to determine if BMP-12 induces tenogenic differentiation of human adipose stem cells (hASCs) and how it affects other features of this population. Results: Human ASCs from 6 healthy donors were treated or not with BMP-12 (50 or 100 ng/ml, 7 days) and tested for gene expression (COLL1, SCX, MKH, DCN, TNC, RUNX2), protein expression (COLL1, COLL3, MKH), proliferation, migration, secretory activity, immunomodulatory properties and susceptibility to oxidative stress. RT-PCR revealed up-regulation of SCX, MKH and RUNX2 genes in BMP-12 treated cells (2.05, 2.65 and 1.87 fold in comparison to control, respectively, p < 0.05) and Western Blot revealed significant increase of COLL1 and MHK expression after BMP-12 treatment. Addition of BMP-12 significantly enhanced secretion of VEGF, IL-6, MMP-1 and MPP-8 by hASCs while had no effect on TGF-β, IL-10, EGF and MMP-13. Moreover, BMP-12 presence in medium attenuated inhibitory effect of hASCs on allo-activated lymphocytes proliferation. At the same time BMP-12 displayed no influence on hASCs proliferation, migration and susceptibility to oxidative stress. Conclusion: BMP-12 activates tenogenic pathway in hASCs but also affects secretory activity and impairs immunomodulatory potential of this population that can influence the clinical outcome after cell transplantation. [ABSTRACT FROM AUTHOR]

Background: Longer life expectancy is associated with an increasing prevalence of kidney disease. Aging itself may cause renal damage, but the spectrum of kidney disorders that affect elderly patients is diverse. Few studies, mostly form US, Asia and West Europe found differences in the prevalence of some types of kidney diseases between elderly and younger patients based on renal biopsy findings, with varied proportion between glomerulopathies and arterionephrosclerosis as a dominant injury found. Here, for the first time in Eastern Europe we analyzed native kidney biopsy findings and their relationship to clinical characteristics at the time of biopsy in elderly individuals (aged ≥65) in comparison to younger adults (aged 18-64). Methods: Biopsy and clinical data from 352 patients aged ≥65 were retrospectively identified, analyzed and compared with a control group of 2214 individuals aged 18-64. All kidney biopsies studied were examined at Medical University of Warsaw in years 2009-14. Results: In elderly patients the leading indication for biopsy was nephrotic range proteinuria without hematuria (34.2%) and the most prevalent pathologic diagnoses were: membranous glomerulonephritis (MGN) (18.2%), focal segmental glomerulosclerosis (FSGS) (17.3%) amyloidosis (13.9%) and pauci immune glomerulonephritis (12.8%). Hypertension and age-related lesions very rarely were found an exclusive or dominant finding in a kidney biopsy (1.7%) and a cause of proteinuria (1.1%) in elderly individuals. There were 18.2% diabetics among elderly individuals, and as much as 75% of them had no morphologic signs of diabetic kidney disease in the renal biopsy. Amyloidosis, MGN, pauci immune GN, crescentic GN and light and/or heavy chain deposition disease (LCDD/HCDD) were more frequent whereas IgA nephropathy (IgAN), lupus nephritis (LN) and thin basement membrane disease (TBMD) were less common among elderly than in younger patients. Conclusions: Proteinuria, a dominating manifestation in elderly patients subjected to kidney biopsy was most commonly related to glomerulopathies. The relatively high prevalence of potentially curative kidney diseases in elderly individuals implicates the importance of renal biopsy in these patients. [ABSTRACT FROM AUTHOR]

Both myoblasts and mesenchymal stem cells (MSC) take part in the muscle tissue regeneration and have been used as experimental cellular therapy in muscular disorders treatment. It is possible that co-transplantation approach could improve the efficacy of this treatment. However, the relations between those two cell types are not clearly defined. The aim of this study was to determine the reciprocal interactions between myoblasts and MSC in vitro in terms of the features important for the muscle regeneration process. Primary caprine muscle-derived cells (MDC) and bone marrow-derived MSC were analysed in autologous settings. We found that MSC contribute to myotubes formation by fusion with MDC when co-cultured directly, but do not acquire myogenic phenotype if exposed to MDC-derived soluble factors only. Experiments with exposure to hydrogen peroxide showed that MSC are significantly more resistant to oxidative stress than MDC, but a direct co-culture with MSC does not diminish the cytotoxic effect of H2O2 on MDC. Cell migration assay demonstrated that MSC possess significantly greater migration ability than MDC which is further enhanced by MDC-derived soluble factors, whereas the opposite effect was not found. MSC-derived soluble factors significantly enhanced the proliferation of MDC, whereas MDC inhibited the division rate of MSC. To conclude, presented results suggest that myogenic precursors and MSC support each other during muscle regeneration and therefore myoblasts-MSC co-transplantation could be an attractive approach in the treatment of muscular disorders. [ABSTRACT FROM AUTHOR]

We examined the serum levels of IL-6, IL-8, TNF, IL-6R, TNF-R1, and CRP and the dynamics of changes in these levels according to age. The study included healthy individuals of 20-90 years of age. Participants were divided into subgroups based on their decade of life, and into subgroups of ≥65 or <65 years. Serum cytokine levels were assayed by ELISA, and CRP using an immunoturbidimetric method. Serum CRP levels were within the normal range for all subgroups. The 60- to 70-year age group showed higher CRP than the 20- to 30- ( p = 0.003), 30- to 40- ( p = 0.009), and 40- to 50- ( p = 0.030) year age groups. Serum cytokine levels were low. It was greater in the 60- to 70-year age group than in the 20- to 30- ( p = 0.008) and 30- to 40- ( p = 0.040) year groups, and was greater in the 70- to 90-year group than the 20- to 30-year group ( p = 0.043). Serum TNF-R1 level in the 70- to 90-year group was greater than in all other age groups ( p = 0.000 for all comparisons). Other measured parameters did not differ between groups. Serum levels of IL-6, CRP, and TNF-R1 were greater in participants ≥65 than <65 years of age. Healthy older people showed low serum levels of CRP and pro-inflammatory cytokines, but higher than in younger population. Therefore, the adjustment of normal ranges in the elderly should be considered. Serum levels of pro-inflammatory cytokines elevated beyond normal ranges indicate particular diseases. [ABSTRACT FROM AUTHOR]

Objectives. The aim of the study was to evaluate the activity of cathepsin B, collagenases, trypsin, and plasmin and concentration of cystatin C in serum of healthy pregnant women in peripartum period. Study Design. The study group included 45 women in uncomplicated pregnancies. Blood samples were collected in four time points. Enzyme activity was measured by spectrofluorometric method. The level of cystatin C was measured using immunonephelometric method. Results. Mean activity of cathepsin B and the level of serum cystatin C were significantly higher in the study group. Collagenase activity was significantly lower in the study group than the control group. No differences in collagenase, plasmin, and trypsin activity on each day of the peripartum period were found. Conclusion. High activity of cathepsin B and increased level of cystatin C are typical for women in late pregnancy. Those levels significantly decrease after delivery which can be associated with potential role of those markers in placental separation. The insignificant changes of cystatin C level in the peripartum period seem to exclude the possibility of using cystatin C as a marker for renal insufficiency in the peripartum period but additional research is necessary to investigate the matter further. [ABSTRACT FROM AUTHOR]

Hyperglycemia results in the activation of tissue angiotensin II. Angiotensin II stimulates the synthesis of ECM proteins and causes a decrease activity of proteolytic enzymes. The aim of this study was to assess the impact of multilevel blocking of the RAAS, cathepsin B activity, and fibronectin accumulation in the glomerular in the rats diabetes model. Sixty male Wistar rats were initially included. Diabetes was induced by intravenous administration of streptozotocin. The animals were randomized to six groups of ten rats in group. Rats in the four groups were treated with inhibitors of the RAAS: enalapril (EN), losartan (LOS), enalapril plus losartan (EN + LOS), and spironolactone (SPIR); another group received dihydralazine (DIH) and the diabetic rats (DM) did not receive any drug. After six weeks, we evaluated blood pressure, 24 h urine collection, and blood for biochemical parameters and kidneys. In this study, fluorometric, ELISA, and immunohistochemical methods were used. Administration of EN + LOS increased activity of cathepsin B in homogenates of glomeruli compared to DM. Losartan treatment resulted in reduction of the ratio kidney weight/body weight compared to untreated diabetic rats. SPIR resulted in the increase activity of cathepsin B in the homogenate of glomeruli. The values of cathepsin B in the plasma of rats in all studied groups were similar and showed no tendency. [ABSTRACT FROM AUTHOR]

Objectives Monoclonal gammopathy of undetermined significance ( MGUS) occurs without other symptoms, although monoclonal proteins can cause kidney injuries. Here, we assessed kidney function and identified the best follow-up parameters in patients with MGUS without kidney damage symptoms. Methodology Forty-six patients with MGUS were included in the study group. The control group ( CRT, n = 23) consisted of healthy subjects matched for age and sex. Serum cystatin C was determined using an immunonephelometric method, serum and urine neutrophil gelatinase-associated lipocalin ( NGAL) was measured with an immunoenzymatic method, and cathepsin B activity was determined fluorometrically. Results Serum cystatin C and urine NGAL were higher, and serum NGAL was lower in MGUS patients compared with CRT. Neither serum cystatin C, nor serum or urine NGAL, correlated with the biomarkers of MGUS. The serum activity of cathepsin B did not differ between groups and did not correlate with serum cystatin C. Serum cystatin C correlated with serum creatinine, while serum NGAL did not correlate with serum creatinine or cystatin C. The estimated glomerular filtration rates ( eGFRs) in MGUS were within normal range and correlated with serum cystatin C. The strongest correlation was observed for CKD-EPI. Seven patients presented with albuminuria >30 mg/day. There was a correlation between albuminuria in this group and λ free light chains. Conclusions The kidney function in MGUS patients is impaired, although there are no clinical and standard laboratory test manifestations. Cystatin C and urine, but not serum, NGAL should be considered markers for kidney injury. CKD-EPI is recommended for eGFR assessment. [ABSTRACT FROM AUTHOR]

Background Plant microRNAs are short (~21 nt) non-coding molecules that regulate gene expression by targeting the mRNA cleavage or protein translation inhibition. In this manner, they play many important roles in the cells of living organisms. One of the plant species in which the entire set of miRNAs has not been yet completely identified is Brassica oleracea var. capitata (cabbage). For this reason and for the economic and nutritional importance of this food crop, high-throughput small RNAs sequencing has been performed to discover the novel and conserved miRNAs in mature cabbage leaves. Results In this study, raw reads generated from three small RNA libraries were bioinformatically processed and further analyzed to select sequences homologous to known B. oleracea and other plant miRNAs. As a result of this analysis, 261 conserved miRNAs (belonging to 62 families) have been discovered. MIR169, MIR167 and MIR166 were the largest miRNA families, while the highest abundance molecules were miR167, miR166, miR168c and miR157a. Among the generated sequencing reads, miRNAs" were also found, such as the miR162c", miR160a" and miR157a". The unannotated tags were used in the prediction and evaluation of novel miRNAs, which resulted in the 26 potential miRNAs proposal. The expressions of 13 selected miRNAs were analyzed by northern blot hybridization. The target prediction and annotation for identified miRNAs were performed, according to which discovered molecules may target mRNAs encoding several potential proteins - e.g., transcription factors, polypeptides that regulate hormone stimuli and abiotic stress response, and molecules participating in transport and cell communication. Additionally, KEGG maps analysis suggested that the miRNAs in cabbage are involved in important processing pathways, including glycolysis, glycerolipid metabolism, flavonoid biosynthesis and oxidative phosphorylation. Conclusions Conclusively, for the first time, the large set of miRNAs was identified in mature cabbage leaves. Potential targets designation for these miRNAs may suggest their essential role in many plants primary biological processes. Presented study not only supplements the knowledge about B. oleracea miRNAs, but additionally it may be used in other research concerning the improvement of the cabbage cultivation. [ABSTRACT FROM AUTHOR]

Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 µmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors. (Progress in Transplantation. 2012;22:423-426) [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are able to modulate the immune system activity and the regeneration processes mainly through the secretion of multiple soluble factors, including prostaglandin E2 (PGE2). PGE2 is produced as a result of cyclooxygenases (COX) activity. In the present study, we investigated how ibuprofen, a nonselective COX inhibitor, affects the proliferation, migration and secretion of human bone marrow MSCs (hBM-MSCs). For this purpose, six hBM-MSCs populations were treated with ibuprofen at doses which do not differ from maximum serum concentrations during standard pharmacotherapy. Ibuprofen treatment (25 or 50 µg/mL) substantially reduced the secretion of PGE2 in all tested populations. Following ibuprofen administration, MSCs were subjected to proliferation (BrdU), transwell migration, and scratch assays, while its effect on MSCs secretome was evaluated by Proteome Profiler and Luminex immunoassays. Ibuprofen did not cause statistically significant changes in the proliferation rate and migration ability of MSCs (p > 0.05). However, ibuprofen (25 µg/mL for 3 days) significantly decreased mean secretion of: CCL2 (by 44%), HGF (by 31%), IL-6 (by 22%), VEGF (by 20%) and IL-4 (by 8%) compared to secretion of control MSCs (p < 0.05). Our results indicate that ibuprofen at therapeutic concentrations may impair the pro-regenerative properties of hBM-MSCs. [ABSTRACT FROM AUTHOR]

Background and aims: The extracellular matrix (ECM) undergoes constant dynamic changes; proteolytic enzymes, particularly the serine proteases plasmin, trypsin and elastase, catalyze critical functions in these processes. Notably, ECM degradation disorders have been reported in various morbid conditions, including cardiac infarction, atheromatosis, and neoplastic diseases, indicating a physiological requirement for proper ECM maintenance. Here we define the role of proteolytic enzymes in the development of aging by assessing changes in proteolytic enzyme activity in serum during aging in rats. Methods: The activities of trypsin, elastase and plasmin in rat serum were determined by the fluorometric method using AMC-labeled substrates in 34 Wistar rats divided into four age groups: 3 month-olds (n=8), 9 month-olds (n=8), 15 month-olds (n=8) and 24 month-olds (n=10). Results: Analysis of proteolytic enzyme activity in four age-dependent groups revealed that in comparison to their 3, 9, and 24 month-old counterparts, the 15 month-old rats exhibited a statistically significant increase in average elastase activity. In accordance with previous studies, a statistically significant increase in trypsin levels was found in the 3 month-old rats, suggesting that trypsin activity decreases with age. Average plasma plasmin activity in the 24 month-old rats was, moreover, statistically significantly higher than that in the other three age groups. Conclusions: Analysis of combined proteolytic activity indicates that age-dependent patterning of blood serine protease enzyme activity may be related to age-related diseases. [ABSTRACT FROM AUTHOR]

Objective: the aim of this work was to define the influence of the ageing process on the activity of proteolytic enzymes, such as trypsin, elastase, plasmin and active MMP-9 concentration, as well as the inhibitor a 1-antitrypsin. Moreover, we assessed associations between enzyme activity and selected clinical and biochemical parameters. Methods: healthy normotensive volunteers (n = 60, 30 women) aged 20-82 years were split into subgroups: young (aged 20-22), middle-aged (49-52) and elderly (77-82). Serum enzyme activity was assessed using fluorometric methods. Results: overall, active MMP-9 concentration and trypsin activity decreased with age, and α1-antitrypsin concentration and plasmin activity increased. Activity of elastase increased with age when compared to the young age group. An inverse correlation was identified between MMP-9 concentration and BMI and a direct correlation found between BMI and elastase, plasmin activity and α1-antitrypsin concentration. In the middle-aged group, glucose correlated directly with trypsin activity and inversely with MMP-9 concentration. Trypsin activity and MMP-9 concentration correlated inversely with cholesterol concentration and plasmin and elastase activity, and the α1-antitrypsin concentration correlated with cholesterol concentration in the overall group. Conclusions: the results confirm the influence of the ageing process on the activity of serum proteolytic enzymes. The activity of individual proteolytic enzymes in the serum changes with age. [ABSTRACT FROM AUTHOR]

Abstract This retrospective series reviews risk factors for chronic allograft nephropathy (CAN) based on the 10-year experience of a single institution. One thousand one hundred and twelve primary cadaveric renal transplant recipients whose graft survived for more than 6 months were followed for a mean of 4.6 years. The data were analyzed using the multivariate Cox proportional hazards model. CAN was defined as an irreversible rise of serum creatinine (SCr) by 30% in the absence of other causes and occurred in 42% of the patients. The risk of CAN was significantly increased in patients who experienced late [ABSTRACT FROM AUTHOR]

Despite intensive clinical research on the use of mesenchymal stromal cells (MSCs), further basic research in this field is still required. Herein, we compared human bone marrow MSCs (BM-MSCs, n = 6) and Wharton's jelly MSCs (WJ-MSCs, n = 6) in their ability to interact with human primary macrophages. Evaluation of secretory potential revealed that under pro-inflammatory stimulation, WJ-MSCs secreted significantly more IL-6 than BM-MSCs (2-fold). This difference did not translate into the effect of MSCs on macrophages: both types of MSCs significantly directed M1-like macrophages toward the M2 phenotype (based on CD206 expression) to a similar extent. This observation was consistent both in flow cytometry analysis and immunocytochemical assessment. The effect of MSCs on macrophages was sustained when IL-6 signaling was blocked with Tocilizumab. Macrophages, regardless of polarization status, enhanced chemotaxis of both BM-MSCs and WJ-MSCs (p < 0.01; trans-well assay), with WJ-MSCs being significantly more responsive to M1-derived chemotactic signals than BM-MSCs. Furthermore, WJ-MSCs increased their motility (scratch assay) when exposed to macrophage-conditioned medium while BM-MSCs did not. These results indicate that although both BM-MSCs and WJ-MSCs have the ability to reciprocally interact with macrophages, the source of MSCs could slightly but significantly modify the response under clinical settings. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cell (MSC) therapy is making its way into clinical practice, accompanied by research into strategies improving their therapeutic potential. Preconditioning MSCs with hypoxia-inducible factors-α (HIFα) stabilizers is an alternative to hypoxic priming, but there remains insufficient data evaluating its transcriptomic effect. Herein, we determined the gene expression profile of 6 human bone marrow-derived MSCs preconditioned for 6 h in 2% O2 (hypoxia) or with 40 μM Vadadustat, compared to control cells and each other. RNA-Sequencing was performed using the Illumina platform, quality control with FastQC and adapter-trimming with BBDUK2. Transcripts were mapped to the Homo_sapiens. GRCh37 genome and converted to relative expression using Salmon. Differentially expressed genes (DEGs) were generated using DESeq2 while functional enrichment was performed in GSEA and g:Profiler. Comparison of hypoxia versus control resulted in 250 DEGs, Vadadustat versus control 1071, and Vadadustat versus hypoxia 1770. The terms enriched in both phenotypes referred mainly to metabolism, in Vadadustat additionally to vesicular transport, chromatin modifications and interaction with extracellular matrix. Compared with hypoxia, Vadadustat upregulated autophagic, phospholipid metabolism, and TLR cascade genes, downregulated those of cytoskeleton and GG-NER pathway and regulated 74 secretory factor genes. Our results provide valuable insight into the transcriptomic effects of these two methods of MSCs preconditioning. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) belongs to systemic autoinflammatory diseases (AIDs). Many of these syndromes are genetically conditioned and can be inherited. Diagnosis relies on clinical symptoms and should be confirmed by genetic testing. One of the most serious complications is AA amyloidosis. We present the diagnostic route of a 33-year-old male with AA amyloidosis and his children, leading to diagnosis of monogenic autoinflammatory syndrome, confirmed by genetic analysis. A novel variant of the in-frame insertion type in one allele of TNFRSF1A gene was found by whole exome sequencing and confirmed by Sanger sequencing, which allowed a diagnosis of TRAPS. Three-dimensional modeling was used to assess the structural changes introduced into TNFR1 molecule by the insertion. The analysis of the 3D model revealed that accommodation of the 4AA insert induces misalignment of three cysteine bridges (especially the C70-C96 bridge) in the extracellular domain, leading to putatively misfolded and improperly functioning TNFR1. Three of the patient's daughters inherited the same variant of the TNFRSF1A gene and presented TRAPS symptoms. TRAPS is a very rare disease, but in the presence of suggestive symptoms the genetic diagnostic workout should be undertaken. Early diagnosis followed by appropriate clinical management can prevent irreversible complications. [ABSTRACT FROM AUTHOR]

The article presents an obituary for Tadeusz Orlowski, professor and pioneer of European nephrology and transplantation.

The therapeutic potential of mesenchymal stromal cells (MSCs) is largely attributed to their immunomodulatory properties, which can be further improved by hypoxia priming. In this study, we investigated the immunomodulatory properties of MSCs preconditioned with hypoxia-mimetic Vadadustat (AKB-6548, Akebia). Gene expression analysis of immunomodulatory factors was performed by real-time polymerase chain reaction (real-time PCR) on RNA isolated from six human bone-marrow derived MSCs populations preconditioned for 6 h with 40 μM Vadadustat compared to control MSCs. The effect of Vadadustat preconditioning on MSCs secretome was determined using Proteome Profiler and Luminex, while their immunomodulatory activity was assessed by mixed lymphocyte reaction (MLR) and Culturex transwell migration assays. Real-time PCR revealed that Vadadustat downregulated genes related to immune system: IL24, IL1B, CXCL8, PDCD1LG1, PDCD1LG2, HIF1A, CCL2 and IL6, and upregulated IL17RD, CCL28 and LEP. Vadadustat caused a marked decrease in the secretion of IL6 (by 51%), HGF (by 47%), CCL7 (MCP3) (by 42%) and CXCL8 (by 40%). Vadadustat potentiated the inhibitory effect of MSCs on the proliferation of alloactivated human peripheral blood mononuclear cells (PBMCs), and reduced monocytes-enriched PBMCs chemotaxis towards the MSCs secretome. Preconditioning with Vadadustat may constitute a valuable approach to improve the therapeutic properties of MSCs. [ABSTRACT FROM AUTHOR]

Background: Cell therapy constitutes an attractive alternative to treat stress urinary incontinence. Although promising results have been demonstrated in this field, the procedure requires further optimization. The most commonly proposed cell types for intraurethral injections are muscle derived cells (MDCs) and mesenchymal stem/stromal cell (MSCs). The aim of this study was to evaluate the effects of MDC-MSC co-transplantation into the urethra. Methods: Autologous transplantation of labeled MDCs, bone marrow MSCs or co-transplantation of MDC-MSC were performed in aged multiparous female goats (n = 6 in each group). The mean number of cells injected per animal was 29.6 × 106(± 4.3 × 106). PBS-injected animals constituted the control group (n = 5). Each animal underwent urethral pressure profile (UPP) measurements before and after the injection procedure. The maximal urethral closure pressure (MUCP) and functional area (FA) of UPPs were calculated. The urethras were collected at the 28th or the 84th day after transplantation. The marker fluorochrome (DID) was visualized and quantified using in vivo imaging system in whole explants. Myogenic differentiation of the graft was immunohistochemically evaluated. Results: The grafted cells were identified in all urethras collected at day 28 regardless of injected cell type. At this time point the strongest DID-derived signal (normalized to the number of injected cells) was noted in the co-transplanted group. There was a distinct decline in signal intensity between day 28 and day 84 in all types of transplantation. Both MSCs and MDCs contributed to striated muscle formation if transplanted directly to the external urethral sphincter. In the MSC group those events were rare. If cells were injected into the submucosal region they remained undifferentiated usually packed in clearly distinguishable depots. The mean increase in MUCP after transplantation in comparison to the pre-transplantation state in the MDC, MSC and MDC-MSC groups was 12.3% (± 11.2%, not significant (ns)), 8.2% (± 9.6%, ns) and 24.1% (± 3.1%, p = 0.02), respectively. The mean increase in FA after transplantation in the MDC, MSC and MDC-MSC groups amounted to 17.8% (± 15.4%, ns), 15.2% (± 12.9%, ns) and 17.8% (± 2.5%, p = 0.04), respectively. Conclusions: The results suggest that MDC-MSC co-transplantation provides a greater chance of improvement in urethral closure than transplantation of each population alone. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Hypophosphatemia as a key factor in sudden infant death syndrome (SIDS)?" by Van Kempen and colleagues that was published in a previous issue is presented.