Maternal Postnatal Depressive Symptoms and Its Effects on Infant Bonding

The objective of this thesis is to gain insight on precipitating factors that increase postpartum mother’s depressive symptoms, including stress and anxiety, and how attachment is influenced. Maternal-infant bonding is defined as the emotional relationship and interaction between mother and infant. Postnatal depressive symptoms typically are under-diagnosed due to a lack of education and the stigma of believing that the effects are “normal” consequences of motherhood. Those affected may not seek professional help. Unrealistic expectations about bonding with their infants can have a negative mental health impact on mothers and influence infants’ behaviors. High expectations of needing to be a perfect mother or not meeting certain goals for their child’s care can make mothers feel unaccomplished, increase stress and frustration, lead to parental burnout, and in severe cases, resentment towards their infant. Many factors impact maternal experiences in the postpartum phase, including economic stressors and marital differences, but most importantly infant behaviors. Mothers who struggle to meet their infant’s needs, such as feeding, diaper changes, or sleeping arrangements may encounter negative infant reactivity emotions, which only deepens their depression. To investigate, primary research articles about mother-infant attachment and bonding and causes of ineffective attachment were examined. A plan for future study will include the Maternal Role Attainment Theory by Ramona Mercer. The study will use a prospective longitudinal mixed methods design. Two hundred pregnant women will be followed until one-year postpartum. Quantitative data collection will include surveys asking about mother’s anxiety on a rating scale. Qualitative data will be gathered on infants’ emotional reactivity when stressed and interventions used by mothers to console them. This research may offer insights that aids nurses in providing effective care for mothers with postpartum depression and their newborns

Collateral sensitivity in clinical mecillinam resistant isolates of Escherichia coli

Background The rapid increase in antimicrobial resistance (AMR) has become a major threat to the successful management of infectious diseases. To counteract this global threat, development of novel treatment strategies is essential. A promising strategy may be exploiting collateral sensitivity; a phenomenon that occurs when a microorganism that has developed resistance to one antimicrobial agent, exhibits increased susceptibility to another antimicrobial agent. In order to develop novel treatment strategies and prevent further resistance development, we aimed to explore the generality of the concept of collateral sensitivity in clinical urinary tract isolates of E. coli. Furthermore, we wanted to investigate the underlying mechanisms of collateral sensitivity. Methods We evolved resistance to mecillinam in a collection of clinical isolates of E. coli. Ten were selected for further determination of possible collateral sensitivity and cross-resistance networks. The IC90-assay with micro broth dilution was used for this purpose, which we tested for eight different antimicrobial agents. The results were displayed in heat maps and graphs showing the distribution of AMR to various agents. PCR and DNA sequencing were performed for the mrdA gene to detect mutations that may confer mecillinam resistance. Results According to our results both collateral sensitivity and cross-resistance occurred in mecillinam resistant isolates. Chloramphenicol presented the highest tendency of collateral sensitivity, while ciprofloxacin presented the highest tendency of cross-resistance. In general, a substantial tendency for collateral sensitivity frequently appeared compared to cross-resistance. Moreover, 13 synonymous point mutations were observed in the mrdA gene, leading to no alteration in the amino acid sequence. Conclusion Based on our in vitro results, we suggest mecillinam could be a good candidate to be employed as the first drug of choice for UTIs caused by E. coli. Mecillinam resistant isolates exhibited a clear tendency for collateral sensitivity, which we believe would occur on the population level as well. Further investigations of the underlying mechanisms of collateral sensitivity are required

The β-blocker Nebivolol Is a GRK/β-arrestin Biased Agonist

Nebivolol, a third generation β-adrenoceptor (β-AR) antagonist (β-blocker), causes vasodilation by inducing nitric oxide (NO) production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK)/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). Due to the pharmacological similarities between nebivolol and carvedilol, we hypothesized that nebivolol is also a GRK/β-arrestin biased agonist. We tested this hypothesis utilizing mouse embryonic fibroblasts (MEFs) that solely express β2-ARs, and HL-1 cardiac myocytes that express β1- and β2-ARs and no detectable β3-ARs. We confirmed previous reports that nebivolol does not significantly alter cAMP levels and thus is not a classical agonist. Moreover, in both cell types, nebivolol induced rapid internalization of β-ARs indicating that nebivolol is also not a classical β-blocker. Furthermore, nebivolol treatment resulted in a time-dependent phosphorylation of ERK that was indistinguishable from carvedilol and similar in duration, but not amplitude, to isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to propranolol (non-selective β-AR-blocker), AG1478 (EGFR inhibitor), indicating that the signaling emanates from β-ARs and involves the EGFR. Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. We conclude that nebivolol is a β2-AR, and likely β1-AR, GRK/β-arrestin biased agonist, which suggests that some of the unique clinically beneficial effects of nebivolol may be due to biased agonism at β1- and/or β2-ARs. © 2013 Erickson et al

Health-related preferences of older patients with multimorbidity: the protocol for an evidence map

Introduction: Interaction of conditions and treatments, complicated care needs and substantial treatment burden make patient–physician encounters involving multimorbid older patients highly complex. To optimally integrate patients’ preferences, define and prioritise realistic treatment goals and individualise care, a patient-centred approach is recommended. However, the preferences of older patients, who are especially vulnerable and frequently multimorbid, have not been systematically investigated with regard to their health status. The purpose of this evidence map is to explore current research addressing health-related preferences of older patients with multimorbidity, and to identify the knowledge clusters and research gaps. Methods and analysis: To identify relevant research, we will conduct searches in the electronic databases MEDLINE, EMBASE, PsycINFO, PSYNDEX, CINAHL, Social Science Citation Index, Social Science Citation Index Expanded and the Cochrane library from their inception. We will check reference lists of relevant articles and carry out cited reference research (forward citation tracking). Two independent reviewers will screen titles and abstracts, check full texts for eligibility and extract the data. Any disagreement will be resolved and consensus reached with the help of a third reviewer. We will include both qualitative and quantitative studies, and address preferences from the patients’ perspectives in a multimorbid population of 60 years or older. There will be no restrictions on the publication language. Data extraction tables will present study and patient characteristics, aim of study, methods used to identify preferences and outcomes (ie, type of preferences). We will summarise the data using tables and figures (ie, bubble plot) to present the research landscape and to describe clusters and gaps. Ethics and dissemination: Due to the nature of the proposed evidence map, ethics approval will not be required. Results from our research will be disseminated by means of specifically prepared materials for patients, at relevant (inter)national conferences and via publication in peer-reviewed journals

Buddy Study: Partners for better health in adolescents with type 2 diabetes

AIM: To investigate whether assigning young, healthy and motivated lay volunteer partners (“buddies”) to adolescents with type 2 diabetes improves hemoglobin A1c (HbA1c). METHODS: Adolescents with type 2 diabetes were randomized to partnering with a “buddy” or to conventional treatment. During the initial screening visit, which coincided with a routine outpatient diabetes clinic visit, patients with type 2 diabetes underwent a physical examination, detailed medical history, laboratory measurement of HbA1c, and completed two questionnaires (Pediatric Quality of Life Inventory and Children’s Depression Inventory) to assess their overall quality of life and the presence of depressive symptoms. Patients were then randomized to the intervention (the buddy system) or conventional treatment (standard care). All patients were scheduled to return for follow-up at 3- and 6-mo after their initial visit. HbA1c was determined at all visits (i.e., at screening and at the 3- and 6-mo follow-up visits) and quality of life and depressive symptoms were evaluated at the screening visit and were reassessed at the 6-mo visit. RESULTS: Ten adolescents, recruited from a pool of approximately 200 adolescents, enrolled over a two-year time period, leading to premature termination of the study. In contrast, we easily recruited motivated lay volunteers. We found no change in HbA1c from the initial to the 6-mo visit in either group, yet our small sample size limited systematic assessment of this outcome. Participants repeatedly missed clinic appointments, failed to conduct self-glucose-monitoring and rarely brought their glucometers to clinic visits. Total quality of life scores (72.6 ± 6.06) at screening were similar to previously reported scores in adolescents with type 2 diabetes (75.7 ± 15.0) and lower than scores reported in normal-weight (81.2 ± 0.9), overweight (83.5 ± 1.8), and obese youths without diabetes (78.5 ± 1.8) or in adolescents with type 1 diabetes (80.5 ± 13.1). Among adolescents who returned for their 6-mo visit, there were no differences in total quality of life scores (70.2 ± 9.18) between screening and follow-up. CONCLUSION: Our approach, effective in adults with type 2 diabetes, was unsuccessful among adolescents and emphasizes the need for innovative strategies for diabetes treatment in adolescent patients

Gem1 and ERMES Do Not Directly Affect Phosphatidylserine Transport from ER to Mitochondria or Mitochondrial Inheritance

In yeast, a protein complex termed the ER-Mitochondria Encounter Structure (ERMES) tethers mitochondria to the endoplasmic reticulum. ERMES proteins are implicated in a variety of cellular functions including phospholipid synthesis, mitochondrial protein import, mitochondrial attachment to actin, polarized mitochondrial movement into daughter cells during division, and maintenance of mitochondrial DNA (mtDNA). The mitochondrial-anchored Gem1 GTPase has been proposed to regulate ERMES functions. Here, we show that ERMES and Gem1 have no direct role in the transport of phosphatidylserine (PS) from the ER to mitochondria during the synthesis of phosphatidylethanolamine (PE), as PS to PE conversion is not affected in ERMES or gem1 mutants. In addition, we report that mitochondrial inheritance defects in ERMES mutants are a secondary consequence of mitochondrial morphology defects, arguing against a primary role for ERMES in mitochondrial association with actin and mitochondrial movement. Finally, we show that ERMES complexes are long-lived, and do not depend on the presence of Gem1. Our findings suggest that the ERMES complex may have primarily a structural role in maintaining mitochondrial morphology

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease.

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease

International Circumpolar Surveillance, An Arctic Network for the Surveillance of Infectious Diseases

Hospitals, public health agencies, and reference laboratories work together to detect and control infectious disease in Arctic regions