A reversal of fate : unravelling the role of central 5-HT in cardiorespiratory control in neonatal and adult rodents

We seek to address the extent to which a specific loss of 5-hydroxytryptamine (5-HT) affects the control of respiration, arterial blood pressure (ABP) and heart rate (HR) across vigilance-states based on existing evidence suggesting that 5-HT defects increase the risk for Sudden Infant Death Syndrome (SIDS) and neurogenic hypertension. SIDS is the leading cause of infant mortality between 1 month and 1 year of age, occurs during sleep, and up to 70% of all SIDS cases have at least one 5-HT system abnormality. Neonatal rodents lacking central 5-HT exhibit severe apneas, and a reduced ABP and HR. Central 5-HT has been implicated in the etiology of neurogenic hypertension, presumably due to projections of 5-HT neurons within the midline raphe to vagal and presympathetic regions of the brain. However, data from studies examining the specific role of central 5-HT function is conflicting or inconclusive. Neurogenic hypertension accounts for more than 90% of all hypertensive cases and the normal fall in ABP that occurs during non-rapid eye movement sleep is absent in some patients with hypertension. Understanding the mechanisms associated with the development of hypertension is critical not only to lower blood pressure, but to lower its associated cardiovascular events. The purpose of this dissertation is to examine the role of central 5-HT in the control of ABP during sleep and reveal, mechanistically, the physiological role of 5-HT in the autonomic control of ABP in neonatal and adult rodents. The overarching hypothesis for this dissertation is that central 5-HT is required for the maintenance of ABP and autonomic tone at rest in both neonatal and adult rodents.Includes bibliographical reference

Elementary Principal and Assistant Principal Instructional Leadership Practices Influencing Student Literacy

AbstractThe problem of a rural school district’s declining reading scores for students in Grades 3 through 8 was a significant concern because effective reading skills are of paramount importance to student success in school and life. Evidence suggests that principal instructional leadership practices influence student achievement; therefore, the purpose of this basic qualitative study was to examine the district’s elementary principals’ and assistant principals’ instructional leadership practices that influenced student literacy. Murphy’s model of instructional leadership served as the conceptual framework. The research question for this study addressed how these elementary administrators implemented instructional leadership practices at their schools to influence student literacy. Eleven elementary principals and assistant principals from this rural school district in the southern United States were interviewed using semistructured, predetermined questions. The interviews were transcribed verbatim, followed by provisional and open pattern coding with thematic analysis. Three major themes arose from the data analysis: (a) literacy-focused instructional leadership practices supporting teachers, (b) literacy-focused instructional leadership practices to support student literacy, and (c) instructional leadership practices supporting literacy schoolwide. This study may foster positive social change by positively influencing student literacy and improving the reading skills and abilities of the students within the school district as principals and assistant principals evaluate the instructional leadership practices they have employed or are considering for future use in their schools

Age at first intercourse and subsequent sexual partnering among adult women in the United States, a cross-sectional study

BACKGROUND: Concurrency and serial monogamy may increase risk for STIs when gaps fall within the infectious period. This study examined the association between early sexual debut and concurrent or serial sexual partnering among heterosexual adult women. METHODS: We identified 6,791 heterosexually active women, ages 21-44, from the 2006-2010 National Survey of Family Growth, a multi-stage probability sample of women in the United States. Self-reported age at first intercourse was categorized as \u3c 15, 15-17 and \u3e /=18 years (referent). Sexual partnering was defined as concurrency (within the same month), serial monogamy with either a 1-3 month, or \u3e /=4 month gap between partners, or monogamy (referent) in the year prior to interview. Polytomous logistic models provided adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: Concurrent partnerships in the year prior to interview were reported by 5.2% of women. Serial monogamy with a 1-3 month gap was reported by 2.5% of women. Compared with women whose sexual debut was \u3e /=18 years, those \u3c 15 years at sexual initiation had 3.7 times the odds of reporting concurrent partnerships (aOR: 3.72; 95% CI: 2.46-5.62). Women \u3c 15 years of age at sexual debut had twice the odds of serial monogamy with gap lengths of 1-3 months between partners (aOR1-3 months: 2.13; 95% CI 1.15-3.94) as compared to women \u3e /=18 years at sexual debut. CONCLUSIONS: Sexual debut at \u3c 15 years is associated with both concurrency and serial monogamy with 1-3 month gaps between partners in U.S. women aged 21-44

Inhibition of PTP1B disrupts cell-cell adhesion and induces anoikis in breast epithelial cells.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesProtein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492. In normal breast tissue and primary breast cells, PTP1B is widely expressed in both epithelial and stromal cells, with highest expression in myoepithelial cells and fibroblasts. PTP1B is widely expressed in branching structures generated by D492 when cultured in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and another mammary epithelial cell line HMLE resulted in reduced cell proliferation and induction of anoikis. These changes were seen when cells were cultured both in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression of cell adhesion proteins and actin polymerization. Moreover, epithelial to mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells and fibroblasts. Inhibition of PTP1B in D492 and HMLE affects cell-cell adhesion and induces anoikis-like effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B inhibitors making PTP1B a potential candidate for further studies as a target for drug development in cancer involving the EMT phenotype.Landspitali University Hospital Science Fund University of Iceland Research Fund Icelandic Science and Technology Policy Council Research Fund Icelandic Science and Technology Policy - Grant of Excellence Gongum sama

Current efforts on microplastic monitoring in Arctic fish and how to proceed

In this review, we investigated published data on the occurrence of microplastic in Arctic fish, and the suitability of the data and species for risk assessment and monitoring. As of 11.11.2021, we found nine studies in the peer-reviewed literature, one thesis and one report, confirming the occurrence of microplastic in fishes from multiple Arctic regions. The studies varied in methodology, detection and quantification limitations, reported categories of size, shape, and chemical identity. All these factors influence the numbers of microplastic reported, thus limiting comparability and hindering integrative analysis. The physiological impacts of the reported microplastic contamination cannot be determined, as all studies targeted stomach/intestine contents and did not use methods with limits of detection low enough to determine particle translocation from the intestine to other organs, tissues or body fluids within the fish. Furthermore, there is a fundamental lack of understanding the transfer and the effects of plastic additives to Arctic fishes. In addition to discussing methodological challenges and knowledge gaps, we consider ecosystem needs, commercial interests, Indigenous people’s subsistence, food safety and food sovereignty concerns, and developed a framework to harmonize and facilitate pan-Arctic microplastic monitoring.Current efforts on microplastic monitoring in Arctic fish and how to proceedacceptedVersio

Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults

Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance training. Thirty-six individuals were randomly assigned to a placebo (67 ± 2 yr old), acetaminophen (64 ± 1 yr old; 4,000 mg/day), or ibuprofen (64 ± 1 yr old; 1,200 mg/day) group in a double-blind manner and completed 12 wk of knee extensor resistance training. Before and after training in vivo patellar tendon properties were assessed with MRI [cross-sectional area (CSA) and signal intensity] and ultrasonography of patellar tendon deformation coupled with force measurements to obtain stiffness, modulus, stress, and strain. Mean patellar tendon CSA was unchanged (P > 0.05) with training in the placebo group, and this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the acetaminophen group (3%, P < 0.05), primarily due to increases in the mid (7%, P < 0.05) and distal (8%, P < 0.05) tendon regions. Correspondingly, tendon signal intensity increased with training in the acetaminophen group at the mid (13%, P < 0.05) and distal (15%, P = 0.07) regions. When normalized to pretraining force levels, patellar tendon deformation and strain decreased 11% (P < 0.05) and stiffness, modulus, and stress were unchanged (P > 0.05) with training in the placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the acetaminophen group, tendon deformation and strain increased 20% (P < 0.05) and stiffness (−17%, P < 0.05) and modulus (−20%, P < 0.05) decreased with training. These data suggest that 3 mo of knee extensor resistance training in older adults induces modest changes in the mechanical properties of the patellar tendon. Over-the-counter doses of acetaminophen, but not ibuprofen, have a strong influence on tendon mechanical and material property adaptations to resistance training. These findings add to a growing body of evidence that acetaminophen has profound effects on peripheral tissues in humans

The power of multi-matrix monitoring in the Pan-Arctic region: plastics in water and sediment

Litter and microplastic assessments are being carried out worldwide. Arctic ecosystems are no exception and plastic pollution is high on the Arctic Council's agenda. Water and sediment have been identified as two of the priority compartments for monitoring plastics under the Arctic Monitoring and Assessment Programme (AMAP). Recommendations for monitoring both compartments are presented in this publication. Alone, such samples can provide information on presence, fate, and potential impacts to ecosystems. Together, the quantification of microplastics in sediment and water from the same region produce a three-dimensional picture of plastics, not only a snapshot of floating or buoyant plastics in the surface water or water column but also a picture of the plastics reaching the shoreline or benthic sediments, in lakes, rivers, and the ocean. Assessment methodologies must be adapted to the ecosystems of interest to generate reliable data. In its current form, published data on plastic pollution in the Arctic is sporadic and collected using a wide spectrum of methods which limits the extent to which data can be compared. A harmonised and coordinated effort is needed to gather data on plastic pollution for the Pan-Arctic. Such information will aid in identifying priority regions and focusing mitigation efforts.publishedVersio

ICON 2019: International Scientific Tendinopathy Symposium Consensus: Clinical Terminology

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.Background Persistent tendon pain that impairs function has inconsistent medical terms that can influence choice of treatment.1 When a person is told they have tendinopathy by clinician A or tendinitis by clinician B, they might feel confused or be alarmed at receiving what they might perceive as two different diagnoses. This may lead to loss of confidence in their health professional and likely adds to uncertainty if they were to search for information about their condition. Clear and uniform terminology also assists inter-professional communication. Inconsistency in terminology for painful tendon disorders is a problem at numerous anatomical sites. Historically, the term ‘tendinitis’ was first used to describe tendon pain, thickening and impaired function (online supplementary figure S1). The term ‘tendinosis’ has also been used in a small number of publications, some of which were very influential.2 3 Subsequently, ‘tendinopathy’ emerged as the most common term for persistent tendon pain.4 5 To our knowledge, experts (clinicians and researchers) or patients have never engaged in a formal process to discuss the terminology we use. We believe that health professionals have not yet agreed on the appropriate terminology for painful tendon conditions.Peer reviewedFinal Accepted Versio