Co-creation as a new form of citizen engagement:Comparing Danish and Dutch experiences at the local government level

Citizen engagement is a key component of modern liberal democracy, especially at the local level, it is an important tool for generating political input, securing political support, mobilizing societal resources and finding creative solutions to the problems and challenges that governments face. Currently, we are witnessing an interesting shift in citizen engagement towards viewing citizens as co-creators of local governance, thus recognizing that citizens have both knowledge and resources that may help tackling wicked and unruly problems. Local governments increasingly focus on the design of co-creation processes and search for ways to support and enhance this new form of citizen engagement. To explore how processes of co-creation unfold at the level of local government, this article analyzes and compares a Danish and Dutch case of co-creation with local citizens. The comparative case study identifies the different reasons for initiating co-creation. It analyses the processes and outcomes of co-creation and reflects on the role of institutional design and leadership. The conclusion is that co-creation can be a viable strategy in very different situations if supported by the right design and leadership

Maternal determinants and fetal outcome of twin pregnancy: a five-year survey

Background: Study prevalence of twin pregnancy, maternal risk factors and fetal outcome in twin pregnancy.Methods: A retrospective study of mothers with twin pregnancies who delivered during the period of 5 years. There were 109 mothers who gave birth to 218 babies. Maternal details, antenatal complications and fetal outcomes were analysed.Results: There were 5432 deliveries which included 109 twin births. Prevalence of twinning was 20/1000 deliveries. The mean age was 28.11 (±SD 4.89) with 69.7% in the younger age groups. No association with parity, BMI and ovulation induction was found. Most common complication was preterm delivery (64.2%) with mean gestational age being 35.07 (±SD 2.32). Others were diabetes (25.7%), hypertension (22.9%), hypothyroidism (14.6%) and postpartum hemorrhage (13.7%). Cesarean section was the commonest mode of delivery (78.0%) with fetal malpresentation (26.6%), fetal distress (20.2%) and hypertension (12.0%) being the commonest indications for termination. Among the hypertensive mothers, 23 delivered by Cesarean and only 2 delivered vaginally which was statistically significant (p- 0.03 OR 5.20). Dichorionicity was commoner than monochorionicity (66.1% vs. 33.9%). Among 218 fetuses delivered, 214 were live births and 4 still born. There were low birth weight Babies (70.6%), normal weight (15.3%), VLBW babies (11.5%) and 2.7% ELBW babies. Fetal complications were IUGR (11.46%), discordant twins (6.8%), congenital anomalies (1.8%), single fetal demise (1.8%) and Intra uterine death of a twin (0.4%). Perinatal mortality rate was 1.65 per thousand births.Conclusions: Prevalence of twin pregnancy was 20/1000 deliveries. Twin pregnancies were seen to be more in the younger age group. Preterm labor, diabetes and hypertension were the main complications with cesarean the most common mode of delivery. Dichorionicity led to less fetal complications and low perinatal mortality

Congenital anomalies: the spectrum of distribution and associated maternal risk factors in a tertiary teaching hospital

Background: To study the system-wise occurrence of congenital anomalies in newborns admitted in a tertiary hospital and to study the associated maternal factors.Methods: This is a retrospective study of all the mothers and their newborn babies with congenital anomalies who were delivered or referred to the Obstetrical Department / Neonatology unit during a two-year study period. The maternal risk factors and associated Obstetric complications were studied.Results: Among the babies born with congenital anomalies, the systems most involved were Genito-urinary System (28.5%) and Cardiovascular System (20.5%). Among the maternal risk factors, Diabetes (14.01%), previous abortions (12.7%) and hypothyroidism (8.7%) were the most significant associated factors. Intrauterine growth restriction (17.4%) was noted to be more common in these babies.Conclusions: The incidence of anomalies was most involving the Genito-urinary System and Cardiovascular System. The major risk factor identified was maternal Diabetes. Prevention by public awareness during adolescence, pre-conceptional counseling and antenatal screening is stressed. Availability of Pediatric surgery and Rehabilitative facilities to improve the quality of life would be warranted

Simultaneous inhibition of Sirtuin 3 and cholesterol homeostasis targets acute myeloid leukemia stem cells by perturbing fatty acid β-oxidation and inducing lipotoxicity

Outcomes for patients with acute myeloid leukemia (AML) remain poor due to the inability of current therapeutic regimens to fully eradicate disease-initiating leukemia stem cells (LSC). Previous studies have demonstrated that oxidative phosphorylation (OXPHOS) is an essential process that is targetable in LSC. Sirtuin 3 (SIRT3), a mitochondrial deacetylase with a multi-faceted role in metabolic regulation, has been shown to regulate OXPHOS in cancer models; however, it has not yet been studied in the context of LSC. Thus, we sought to identify if SIRT3 is important for LSC function. Using RNAi and a SIRT3 inhibitor (YC8-02), we demonstrate that SIRT3 is a critical target for the survival of primary human LSC but is not essential for normal human hematopoietic stem and progenitor cell function. In order to elucidate the molecular mechanisms by which SIRT3 is essential in LSC we combined transcriptomic, proteomic, and lipidomic approaches, showing that SIRT3 is important for LSC function through the regulation of fatty acid oxidation (FAO) which is required to support OXPHOS and ATP production in human LSC. Further, we discovered two approaches to further sensitize LSC to SIRT3 inhibition. First, we found that LSC tolerate the toxic effects of fatty acid accumulation induced by SIRT3 inhibition by upregulating cholesterol esterification. Disruption of cholesterol homeostasis sensitizes LSC to YC8-02 and potentiates LSC death. Second, SIRT3 inhibition sensitizes LSC to the BCL-2 inhibitor venetoclax. Together, these findings establish SIRT3 as a regulator of lipid metabolism and potential therapeutic target in primitive AML cells

Cutaneous manifestations of juvenile onset lupus erythematosus: A clinical study

Introduction: Juvenile-onset systemic lupus erythematosus (SLE) is one of the most common systemic autoimmune connective tissue disorders in children. Studies focusing on the mucocutaneous manifestations of childhood lupus are scanty in literature. Objectives: This study was an attempt to describe the cutaneous changes seen in Pediatric Lupus and to correlate with the histopathological and immunofluoresecence findings. Methods: This was a retrospective study. All children under the age of 18 years who were diagnosed to have SLE according to the ACR criteria and presented to the dermatology outpatient department during a period of 1 year were included in the study. Details including clinical features, investigation findings including immunological tests and skin biopsy findings were noted. The analysis was performed using descriptive statistical tools such as percentage and frequency. Results: A total of 14 cases, average age at presentation was 10.14 years. Among the cutaneous manifestations, the most common presenting feature was urticarial vasculitis. Malar rash was seen in 57% of cases. Other cutaneous features seen were diffuse alopecia, oral ulcers. Antinuclear antibody was positive in all cases. Conclusion: Pediatric lupus tends to have a more aggressive course than adult lupus. Early diagnosis and treatment is necessary to prevent progression and development of complications

Akt and ERK1/2 pathways are components of the vasopressin signaling network in rat native IMCD

Vasopressin regulates water excretion through effects on the renal collecting duct. Vasopressin signaling in the inner medullary collecting duct (IMCD) is mediated by V2 receptor occupation coupled to the generation of cyclic AMP. Here, we employ a “systems” approach to analysis of vasopressin signaling. The objective is to investigate roles of activation of the Akt and ERK1/2 MAP kinase pathways, as well as Ca2+ mobilization, in IMCD cells isolated from rat kidney. The V2 receptor-selective vasopressin analog dDAVP increased the state of Akt activation (increased phosphorylation at T308 and S473) and decreased the state of ERK1/2 activation (decreased phosphorylation at T202 and Y204). Akt activation was blocked by an inhibitor of PI3K, LY294002. In microdissected IMCD segments, nonperiodic spike-like increases in intracellular Ca2+ (FLUO-4) were accelerated by vasopressin. Chelation of Ca2+ or calmodulin inhibition markedly decreased Akt phosphorylation. Decreased ERK1/2 phosphorylation was associated with a decrease in MEK1/2 phosphorylation and an increase in c-Raf phosphorylation at S259 (an inhibitory site). Based on the current findings integrated with previous findings in the IMCD, we now report a 33-node vasopressin signaling network involved in vasopressin regulation of IMCD function