Current treatments for xerostomia/dry mouth are palliative and largely ineffective. A permanent clinical resolution is being developed to correct hyposalivation using implanted hydrogel-encapsulated ...salivary human stem/progenitor cells (hS/PCs) to restore functional salivary components and increase salivary flow. Pluripotent epithelial cell populations derived from hS/PCs, representing a basal stem cell population in tissue, can differentiate along either secretory acinar or fluid-transporting ductal lineages. To develop tissue-engineered salivary gland replacement tissues, it is critical to reliably identify cells in tissue and as they enter these alternative lineages. The secreted protein α-amylase, the transcription factor MIST1, and aquaporin-5 are typical markers for acinar cells, and K19 is the classical ductal marker in salivary tissue. We found that early ductal progenitors derived from hS/PCs do not express K19, and thus earlier markers were needed to distinguish these cells from acinar progenitors. Salivary ductal cells express distinct polarity complex proteins that we hypothesized could serve as lineage biomarkers to distinguish ductal cells from acinar cells in differentiating hS/PC populations. Based on our studies of primary salivary tissue, both parotid and submandibular glands, and differentiating hS/PCs, we conclude that the apical marker MUC1 along with the polarity markers INADL/PATJ and SCRIB reliably can identify ductal cells in salivary glands and in ductal progenitor populations of hS/PCs being used for salivary tissue engineering. Other markers of epithelial maturation, including E-cadherin, ZO-1, and partition complex component PAR3, are present in both ductal and acinar cells, where they can serve as general markers of differentiation but not lineage markers.
Introduction: The objective of this study was to identify primary health care nurses' competencies when responding to hydrological disasters in rural areas. Methods: A descriptive, exploratory and ...qualitative study was developed. The Critical Incidents Technique was adopted. Twenty public health nurses who worked during the flood season in the years 2014 and 2015 in a rural area in southern Brazil were interviewed. Critical incidents and requirements identified in the data gave rise to the development of the competencies. Results: Thirty competencies were identified and classified in the domains of leadership and management, teamwork, health care, being community-oriented, communication, psychological support, health surveillance and education. Conclusions: Although the competencies could be related to the established international competencies for nurses in disasters, a number were described only in this study. These competencies can contribute to the education and practice of nurses in primary health care, strengthening the capacity of the profession to face flood disaster situations in rural areas.
Patients suffering from bacterial bloodstream infections have an increased risk of developing systematic inflammatory response syndrome (SIRS), which can result in rapid deterioration of the ...patients’ health. Diagnostic methods for bacterial identification and antimicrobial susceptibility tests are time-consuming. The aim of this study was to investigate whether Raman spectroscopy would be able to rapidly provide an antimicrobial susceptibility profile from bacteria isolated directly from positive blood cultures. First, bacterial strains (
n
= 133) were inoculated in tryptic soy broth and incubated in the presence or absence of antibiotics for 5 h. Antimicrobial susceptibility profiles were analyzed by Raman spectroscopy. Subsequently, a selection of strains was isolated from blood cultures and analyzed similarly. VITEK®2 technology and broth dilution were used as the reference methods. Raman spectra from 67 antibiotic-susceptible strains showed discriminatory spectra in the absence or at low concentrations of antibiotics as compared to high antibiotic concentrations. For 66 antibiotic-resistant strains, no antimicrobial effect was observed on the bacterial Raman spectra. Full concordance with VITEK®2 data and broth dilution was obtained for the antibiotic-susceptible strains, 68 % and 98 %, respectively, for the resistant strains. Discriminative antimicrobial susceptibility testing (AST) profiles were obtained for all bacterial strains isolated from blood cultures, resulting in full concordance with the VITEK®2 data. It can be concluded that Raman spectroscopy is able to detect the antimicrobial susceptibility of bacterial species isolated from a positive blood culture bottle within 5 h. Although Raman spectroscopy is cheap and rapid, further optimization is required, to fulfill a great promise for future AST profiling technology development.
. Carrero JJ, Qureshi AR, Axelsson J, Yilmaz MI, Rehnmark S, Witt MR, Bárány P, Heimbürger O, Suliman ME, Alvestrand A, Lindholm B, Stenvinkel P (Karolinska Institutet, Stockholm; and Karo Bio AB, ...Novum, Huddinge; Sweden). Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J Intern Med 2007; 262: 690–701.
Objectives. In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end‐stage renal disease (ESRD).
Design. After exclusion of 23 patients with thyroid‐stimulating hormone (TSH) values outside the normal range (0.1–4.5 mIU L−1), 187 clinically and biochemically euthyroid incident ESRD stage 5 patients starting dialysis were followed for a median of 20 (range 1–60) months. Measurements of total and free forms of thyroid hormones, s‐albumin, hs‐CRP, interleukin (IL)‐6, vascular adhesion molecule (VCAM)‐1 and insulin‐like growth factor 1 (IGF‐1) were performed at baseline.
Results. In this population, 17 out of 210 patients (8%) were defined as subclinically hypothyroid. Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3). When using the cut‐off levels derived from ROC, low T3 levels were associated with increased inflammation (higher hs‐CRP, IL‐6 and VCAM‐1) and lower concentration of both s‐albumin and IGF‐1. Finally, low T3 but not low free triiodothyronine was associated with worse all‐cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors.
Conclusion. This study showed that low T3 levels are independent predictors of all‐cause and also cardiovascular disease mortality in biochemically euthyroid patients, perhaps due to an intimate association with inflammation. Based on these results, the use of T3 levels in studies assessing the relationship between thyroid dysfunction and mortality risk is recommended.
Despite many preventive measures, including prophylactic antibiotics, periprosthetic joint infection (PJI) remains a devastating complication following arthroplasty, leading to pain, suffering, ...morbidity and substantial economic burden. Humans have a powerful innate immune system that can effectively control infections, if alerted quickly. Unfortunately, pathogens use many mechanisms to dampen innate immune responses. The study hypothesis was that immunomodulators that can jumpstart and direct innate immune responses (particularly neutrophils) at the surgical site of implant placement would boost immune responses and reduce PJI, even in the absence of antibiotics. To test this hypothesis, N-formyl-methionyl-leucyl-phenylalanine (fMLP) (a potent chemoattractant for phagocytic leukocytes including neutrophils) was used in a mouse model of PJI with Staphylococcus aureus (S. aureus). Mice receiving intramedullary femoral implants were divided into three groups: i) implant alone; ii) implant + S. aureus; iii) implant + fMLP + S. aureus. fMLP treatment reduced S. aureus infection levels by ~ 2-Log orders at day 3. Moreover, fMLP therapy reduced infection-induced peri-implant periosteal reaction, focal cortical loss and areas of inflammatory infiltrate in mice distal femora at day 10. Finally, fMLP treatment reduced pain behaviour and increased weight-bearing at the implant leg in infected mice at day 10. Data indicated that fMLP therapy is a promising novel approach for reducing PJI, if administered locally at surgical sites. Future work will be toward further enhancement and optimisation of an fMLP-based therapeutic approach through combination with antibiotics and/or implant coating with fMLP.
To determine if attempts to maximize oocyte yield during ovarian stimulation translates into improved outcome of in vitro fertilization (IVF) cycles.
Retrospective study.
Academic tertiary care IVF ...center.
806 de-identified nondonor IVF cycles.
Evaluation of fresh nondonor IVF cycles (n = 806) for the period January 1, 1999, to December 30, 2001.
Cycle cancellation, clinical pregnancy, spontaneous miscarriage, and live birth after IVF.
Advancing age, independent of ovarian reserve status (reflected by early follicular phase FSH and estradiol) augured a worse prognosis for all outcomes. Higher gonadotropin use lowered cycle cancellations but was associated with a statistically significantly reduced likelihood of clinical pregnancy and live birth and a trend toward a higher likelihood for spontaneous miscarriage after IVF.
Our data add to the accruing literature suggesting adverse influences of excess gonadotropin use on IVF outcomes. Although an aggressive approach to controlled ovarian hyperstimulation results in a statistically significant reduction in cycle cancellations, the excessive use of gonadotropins detrimentally influences live birth after IVF.
•Interleukin-27 expression increases in neonatal dendritic cells in response to BCG.•The BCG vaccine is currently the only licensed vaccine available for tuberculosis.•BCG is commonly administered to ...neonates in TB endemic areas.•IL-27 limits BCG clearance by DCs and restricts interleukin-12 production.•IL-27 opposes T cell stimulation by neonatal dendritic cells.
Bacille Calmette Guérin (BCG) is a live-attenuated vaccine for protection against Mycobacterium tuberculosis. Despite high disease protection in infancy and early childhood, it generates poor long-term protection against pulmonary tuberculosis. We hypothesized that the unique immune profile that includes elevated interleukin (IL)-27, contributes to insufficient protection from routine neonatal BCG administration. Using a novel method to obtain neonatal progenitors, we showed that neonatal bone marrow-derived dendritic cells (BMDCs) increase production of IL-27 following BCG stimulation. To study the effect of IL-27 on BMDCs, we utilized mice deficient for IL-27 receptor-α (KO). We observed greater BCG clearance and elevated IL-12 production in the neonatal KO BMDCs compared to WT. BMDCs from KO neonates in turn stimulated more interferon-γ production from CD4+ T cells isolated from BCG-vaccinated mice than WT counterparts. To further confirm the importance of these findings, C57BL/6 mice were vaccinated as neonates in line with the approach to human vaccination in high TB burden regions. IL-27 levels progressively increased through 5 weeks and were significantly elevated in mice vaccinated with BCG compared to controls. The impact of IL-27 production on clearance of BCG was significant as KO mice cleared BCG from peripheral tissues that persisted in WT mice 5 weeks post-vaccination. These results are the first to highlight the suppressive role of IL-27 on DCs in the neonatal period and the impact on neonatal immune responses to BCG.
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Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have ...been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide–polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the
ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation.
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