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Introduction: In Kampala, Uganda, there is a strong cultural practice for patients to have designated caregivers for the duration of hospitalization. At the same time, nursing support is limited. This quality improvement project aimed to standardize caregiver and nursing perioperative care on the gynecologic oncology wards at the Uganda Cancer Institute and Mulago Specialised Women and Neonatal Hospital. Methods: We developed, implemented, and evaluated a multidisciplinary intervention involving standardization of nursing care, patient education, and family member integration from October 2019 – July 2020. Data were abstracted from medical records and patient interviews pertaining to the following outcomes: 1) pain control; 2) post-operative surgical site infections, urinary tract infections, and pneumonia; 3) nursing documentation of medication administration, pain quality, and vital sign assessments, and 4) patient and caregiver education. Descriptive statistics, Fisher’s exact test, and independent samples t-test were applied. Results: Data were collected from 25 patients undergoing major gynecologic procedures. Pre- (N = 14) and post- (N = 11) intervention comparison demonstrated significant increases in preoperative patient education (0% to 80%, p = 0.001) and utilization of a comprehensive postoperative order form (0% to 45.5%, p = 0.009). Increased frequency in nursing documentation of patient checks (3 to 8, p = 0.266) and intraoperative antibiotic administration (9 to 10, p = 0.180) in patient charts did not reach significance. There was no change in infection rate, pain score utilization, caregiver documentation, or preoperative medication acquisition. Conclusion: Our findings suggest that patient- and family-centered perioperative care can be improved through standardization of nursing care, improved education, and integration of caregivers in a nursing-limited setting.

Background: Gestational diabetes mellitus (GDM) is a pregnancy complication associated with short- and long-term health consequences for mother and child. First line treatment is diet and exercise but there is a recognized knowledge gap as to what diet treatment is optimal. A healthy Nordic diet has been associated with improved health but no studies in women with GDM exist. The New Nordic Diet (NND) is an initiative with the purpose to develop a healthy Nordic diet including foods with the potential to grow in Nordic countries; including fruit, berries, vegetables, whole-grain cereal products, nuts, fish, and rapeseed oil. The purpose of the intervention with new Nordic DIet in women with GestatiOnal diabetes mellitus (iNDIGO) is to test if the NND compared with usual care improves glucose control in women with GDM., Methods: The iNDIGO study is a randomized parallel controlled trial where 50 women with GDM will be randomized to either an NND or usual care for 14 days (30-32 weeks of gestation). Participants in the NND group will receive menus and food bags containing foods to be consumed. Primary outcome is glycemic control (time in target) measured using continuous glucose monitoring. Compliance to the dietary intervention will be tested using dietary biomarkers and adherence questionnaires., Conclusion: Diet treatment represents first line treatment in GDM but it remains unclear what type of diets are effective. iNDIGO is an efficacy study and will provide evidence as to whether a healthy Nordic diet can improve glucose control in women with GDM., Trial Registration: ClinicalTrials.gov registration Number: NCT04169243. Registered 19 November 2019, https://clinicaltrials.gov/ct2/show/NCT04169243., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The insulin family of growth factors plays an important role in development and function of the nervous system. Reduced insulin and insulin-growth-factor signaling (IIS), however, can improve symptoms of neurodegenerative diseases in laboratory model organisms and protect against age-associated decline in neuronal function. Recently, we showed that chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber escape response circuit. Here, we expand our initial findings by demonstrating that reduced functional output in the giant fiber system of aging flies can be prevented by increasing proteasomal activity within the circuit. Manipulations of IIS in neurons can also affect longevity, underscoring the relevance of the nervous system for aging., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Unlabelled: Essentials Mechanism of thrombin-induced inflammation is not fully understood. Thrombin induced monocyte adhesion and barrier loss require Angiopoietin-2 (Ang-2). Ang-2 mediates vessel leakage and monocyte adhesion through SHP-2/p38MAPK pathway. Calcium dependent SHP2/p38MAPK activation regulates Ang-2 expression through a feedback loop., Summary: Background Thrombin imparts an inflammatory phenotype to the endothelium by promoting increased monocyte adhesion and vascular permeability. However, the molecular players that govern these events are incompletely understood. Objective The aim of this study was to determine whether Angiopoietin-2 (Ang-2) has a role, if any, in regulating inflammatory signals initiated by thrombin. Methods Assessment of vascular leakage by Miles assay was performed by intra-dermal injection on the foot paw. Surface levels of intercellular adhesion molecule-1 (ICAM-1) were determined by flow cytometry. Overexpression, knockdown and phosphorylation of proteins were determined by Western blotting. Results In time-course experiments, thrombin-stimulated Ang-2 up-regulation, peaked prior to the expression of adhesion molecule ICAM-1 in human umbilical vein-derived endothelial cells (HUVECs). Knockdown of Ang-2 blocked both thrombin-induced monocyte adhesion and ICAM-1 expression. In addition, Ang-2(-/-) mice displayed defective vascular leakage when treated with thrombin. Introducing Ang-2 protein in Ang-2(-/-) mice failed to recover a wild-type phenotype. Mechanistically, Ang-2 appears to regulate the thrombin-activated calcium spike that is required for tyrosine phosphatase SHP2 and p38 MAPK activation. Further, down-regulation of SHP2 attenuated both thrombin-induced Ang-2 expression and monocyte adhesion. Down-regulation of the adaptor protein Gab1, a co-activator of SHP2, as well as overexpression of the Gab1 mutant incapable of interacting with SHP2 (YFGab1), inhibited thrombin-mediated effects, including downstream activation of p38 MAPK, which in turn was required for Ang-2 expression. Conclusions The data establish an essential role of the Gab1/SHP2/p38MAPK signaling pathway and Ang-2 in regulating thrombin-induced monocyte adhesion and vascular leakage., (© 2016 International Society on Thrombosis and Haemostasis.)

Background Aims: Endothelial progenitor cells (EPCs) specifically home to sites of malignant growth, rendering them attractive for anti-cancer therapies. Data are conflicting on the phenotype and quantitative contribution toward tumor angiogenesis based on differing culture assays to outgrow EPCs. To evaluate the origin and early phenotype of EPCs and to define a population with enhanced tumor-targeting capacity, we evaluated a hierarchy of cord blood-derived EPCs modeling the multi-step nature of tumor homing., Methods: CD34(+) mononuclear cells were isolated from fresh cord blood and cultured to derive endothelial colony-forming cells (ECFCs). Human umbilical vein endothelial cells (HUVECs) served as control. Using intra-vital microscopy, the recruitment was analyzed in mice bearing C6 xenografts. Adhesion, migration, transmigration and differentiation were further addressed., Results: Within the primary passage, ECFCs underwent a rapid maturation from a CD45(+) and CD31(+) phenotype to a CD45(-) and endothelial marker positive phenotype. Assessing in vivo tumor recruitment, ECFCs had the highest activity in all steps analyzed. In vitro, ECFCs demonstrated significantly higher adhesion under static and flow conditions. Similarly, ECFCs exhibited highest migratory and trans-migratory activity toward tumor-conditioned medium. On subcutaneous implantation, only ECFCs formed blood vessels covered with perivascular cells, similar to HUVECs., Conclusions: Our study indicates that ECFCs emerge from a CD45(+) and CD31(+) progenitor and rapidly mature in culture. ECFCs have a significantly higher potential for tumor targeting than non-cultured CD34(+) cells and HUVECs. They are ideal candidates for future cell-based anti-cancer therapies., (Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: To perform a decision curve analysis (DCA) to compare the Partin Tables 1997, 2001, and 2007 for their clinical applicability., Material and Methods: Clinical and pathologic data of 687 consecutive patients treated with open radical prostatectomy for clinically localized prostate cancer between 2003 and 2008 at a single institution were used. DCA quantified the net benefit relating to specific threshold probabilities of extraprostatic extension (EPE), seminal vesicle involvement (SVI), and lymph node involvement (LNI)., Results: Overall, EPE, SVI, and LNI were recorded in 17.8, 6.0, and 1.2%, respectively. For EPE predictions, the DCA favored the 2007 version vs. 1997 for SVI vs. none of the versions for LNI., Conclusions: DCA indicate that for very low prevalence conditions such as LNI (1.2%), decision models are not useful. For low prevalence rates such as SVI, the use of different versions of the Partin Tables does not translate into meaningful net gains differences. Finally, for intermediate prevalence conditions such as EPE (18%), despite apparent performance differences, the net benefit differences were also marginal. In consequence, the current analysis could not confirm an important benefit from the use of the Partin Tables and it could not identify a clearly better version of any of the 3 available iterations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Dietary restriction (DR) extends lifespan in diverse organisms and, in animal and cellular models, can delay a range of aging-related diseases including Alzheimer's disease (AD). A better understanding of the mechanisms mediating these interactions, however, may reveal novel pathways involved in AD pathogenesis, and potential targets for disease-modifying treatments and biomarkers for disease progression. Drosophila models of AD have recently been developed and, due to their short lifespan and susceptibility to genetic manipulation, we have used the fly to investigate the molecular connections among diet, aging and AD pathology. DR extended lifespan in both Arctic mutant Aβ42 and WT 4R tau over-expressing flies, but the underlying molecular pathology was not altered and neuronal dysfunction was not prevented by dietary manipulation. Our data suggest that DR may alter aging through generalised mechanisms independent of the specific pathways underlying AD pathogenesis in the fly, and hence that lifespan-extending manipulations may have varying effects on aging and functional declines in aging-related diseases. Alternatively, our analysis of the specific effects of DR on neuronal toxicity downstream of Aβ and tau pathologies with negative results may simply confirm that the neuro-protective effects of DR are upstream of the initiating events involved in the pathogenesis of AD., (Copyright © 2009 Elsevier Inc. All rights reserved.)

We combined reverse and chemical genetics to identify targets and compounds modulating blood vessel development. Through transcript profiling in mice, we identified 150 potentially druggable microvessel-enriched gene products. Orthologs of 50 of these were knocked down in a reverse genetic screen in zebrafish, demonstrating that 16 were necessary for developmental angiogenesis. In parallel, 1280 pharmacologically active compounds were screened in a human cell-based assay, identifying 28 compounds selectively inhibiting endothelial sprouting. Several links were revealed between the results of the reverse and chemical genetic screens, including the serine/threonine (S/T) phosphatases ppp1ca, ppp1cc, and ppp4c and an inhibitor of this gene family; Endothall. Our results suggest that the combination of reverse and chemical genetic screens, in vertebrates, is an efficient strategy for the identification of drug targets and compounds that modulate complex biological systems, such as angiogenesis.

Objectives: The loudness dependency of the auditory evoked potentials (LDAEP) is used as an indicator of the central serotonergic system and predicts clinical response to serotonin agonists. So far, LDAEP has been typically investigated with dipole source analysis, because with this method the primary and secondary auditory cortex (with a high versus low serotonergic innervation) can be separated at least in parts., Methods: We have developed a new analysis procedure that uses an MRI probabilistic map of the primary auditory cortex in Talairach space and analyzed the current density in this region of interest with low resolution electromagnetic tomography (LORETA). LORETA is a tomographic localization method that calculates the current density distribution in Talairach space., Results: In a group of patients with major depression (n=15), this new method can predict the response to an selective serotonin reuptake inhibitor (citalopram) at least to the same degree than the traditional dipole source analysis method (P=0.019 vs. P=0.028). The correlation of the improvement in the Hamilton Scale is significant with the LORETA-LDAEP-values (0.56; P=0.031) but not with the dipole source analysis LDAEP-values (0.43; P=0.11)., Conclusions: The new tomographic LDAEP analysis is a promising tool in the analysis of the central serotonergic system.

Analysis of endothelial cell (EC) chemokine receptor expression by RT-PCR revealed that EC essentially do not express CC-chemokine receptors whereas they express all known CXC-chemokine receptors. Endotheliotropic functions of ligands for CXCR-1, CXCR-2, and CXCR-3 have previously been described. We have consequently performed a detailed analysis of endothelial CXCR-4 expression. CXCR-4 is constitutively expressed by quiescent, resting EC. Cytokine stimulation revealed that bFGF upregulates endothelial CXCR-4 expression, whereas TNF alpha downregulates endothelial CXCR-4 expression. Expression of CXCR-4 mRNA as well as protein is also upregulated in autocrine activated, migrating bovine aortic endothelial cells (BAEC). Furthermore, migrating BAEC preferentially present CXCR-4 on the cell surface as evidenced by cytochemistry and FACS analysis. Lastly, the monospecific CXCR-4 ligand SDF-1 was found to act as a potent inducer of EC chemotaxis. In summary, the data indicate that the CXCR-4/SDF-1 receptor ligand interaction may be an important regulator of activated endothelial cell functions as they occur during vascular remodeling and angiogenesis.

Objective: The aim of the current study was to determine levels of circulating endothelial cell adhesion molecules during preeclampsia and to assess their predictive value as diagnostic markers for the early identification of pregnant women at risk of developing preeclampsia., Study Design: Plasma samples were obtained from women with preeclampsia; the syndrome of hemolysis, elevated liver enzymes, and low platelets; uncomplicated pregnancy-induced hypertension; and women with normal pregnancy. In addition, longitudinal plasma profiles of pregnant women were randomly collected to determine individual profiles of circulating endothelial cell adhesion molecules. A sandwich enzyme-linked immunosorbent assay technique was used to quantitate concentrations of soluble intercellular adhesion molecule-1 (CD54), vascular cell adhesion molecule-1 (CD106), E-selectin (CD62E), platelet endothelial cell adhesion molecule (CD31), and P-selectin (CD62P)., Results: Plasma levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and platelet endothelial cell adhesion molecule-1 were significantly elevated in women with preeclampsia compared with healthy control pregnant women. Longitudinal analysis of soluble plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels during pregnancy revealed that these molecules (1) show little variation in healthy pregnant women, (2) do not vary during normal pregnancy, and (3) are significantly elevated in women with preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets compared with control pregnant women and those with uncomplicated pregnancy-induced hypertension. Analysis of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels in longitudinal profiles of pregnant women identified significantly elevated levels of these molecules in the plasma of preeclampsia-prone women 3 to 15 weeks before the onset of clinical symptoms., Conclusion: Elevated soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 measurements during pregnancy can be considered as major risk factors. Elevated levels of these substances in the plasma of pregnant women with preeclampsia support the concept of a primary endothelial cell involvement in the pathogenesis of preeclampsia. Although currently based on a limited database, significantly elevated levels of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the plasma of otherwise healthy pregnant women suggest a very high predictive value of these molecules for the earliest identification of women at risk of developing preeclampsia.

Angiogenesis occurs during embryogenesis and is a down-regulated process in the healthy adult that is almost exclusively linked to pathological conditions such as tumor growth, wound healing, and inflammation. Physiological angiogenic processes in the adult are restricted to the female reproductive system where they occur cyclically during the ovarian and uterine cycle as well as during pregnancy. By systematically analyzing the phenotypic changes of endothelial cells during bovine corpus luteum (CL) formation and regression, we have established a physiological model of blood vessel growth and regression. Quantitation of vessel density, percentage of vessels with lumen, and ratio of Bandeiraea simplicifolia-I to von Willebrand Factor-positive endothelial cells were established as parameters of angiogenesis. Sprouting endothelial cells invade the growing CL and continue to grow throughout the first third of the ovarian cycle. Thereafter the mature CL is characterized by a dense network of vessels with gradually decreasing vessel density. During luteolysis and for several weeks thereafter (regressing and residual CL) all newly formed vessels regress, which is accompanied by gradual foreshortening and rounding of endothelial cells and subsequent detachment. Based on histochemical detection of nucleosomal fragmentation products physiological blood vessel regression in the cyclic CL does not appear to involve endothelial cell apoptosis. Lectin histochemical analysis revealed a distinct alteration of endothelial cell glycoconjugate expression during ovarian angiogenesis comparable with the distinct pattern of hyperglycosylation of cultured migrating endothelial cells (up-regulation of binding sites for Lycopersicon esculentum lectin, wheat germ agglutinin, neuraminidase-treated peanut agglutinin, and Ricinus communis agglutinin-I on sprouting ECs). Northern blot analysis of glycosyltransferases during the different stages of angiogenesis revealed an up-regulation of beta-galactoside alpha 2,6-sialyltransferase and alpha 1,3-galactosyltransferase mRNA expression during the angiogenic stages of CL formation. These data establish the ovarian angiogenesis model as a suitable experimental system to study the functional and phenotypic properties of endothelial cells in sprouting and regressing blood vessels and provide additional evidence for the importance of endothelial cell surface glycoconjugates during angiogenesis.

Endothelial cells line the inside of all blood vessels forming a structurally and functionally highly heterogenous population of cells. Here we describe the application of the differential RNA display technique to the analysis of the heterogeneity of endothelial cells. Multiple fragment cDNAs from quiescent resting and from activated migrating endothelial cells were amplified by RT-PCR using random 10mer 5' primers and T11XY 3' primers. Labelled amplification products were displayed on a sequencing gel. Expression patterns of more than 5000 bands of the two cell populations were approximately 98% identical. Of the differentially expressed bands, 26 fragment cDNAs were reamplified, sequenced, and used as probes for Northern blots. Approximately 50% of the analyzed fragment cDNAs could be confirmed as being differentially expressed by Northern blot analysis. Among the differentially expressed cDNAs was follistatin, which was exclusively expressed by migrating and not by quiescent arrested endothelial cells. Stimulation by exogenous bFGF, however, induced follistatin expression in arrested endothelial cells. These experiments support the use of the differential RNA display technique as a rapid cloning strategy for the identification of differentially expressed genes and suggest a role of the follistatin/activin system in the autocrine control of endothelial cell growth and differentiation.