Characterization of long-term motor deficits in the 6-OHDA model of Parkinson's disease in the common marmoset.

Research aimed at developing new therapies for Parkinson's disease (PD) critically depend on valid animal models of the disease that allows for repeated testing of motor disabilities over extended time periods. We here present an extensive characterization of a wide range of motor symptoms in the 6-OHDA marmoset model of PD when tested over several months. The severity of motor deficits was quantified in two ways: (i) through manual scoring protocols appropriately adapted to include species specific motor behavior and (ii) using automated quantitative motion tracking based on image processing of the digital video recordings. We show that the automated methods allow for rapid and reliable characterization of motor dysfunctions, thus complementing the manual scoring procedures, and that robust motor symptoms lasting for several months could be induced when using a two-stage neurotoxic lesioning procedure involving one hemisphere at a time. This non-human primate model of PD should therefore be well suited for long-term evaluation of novel therapies for treatment of PD

Severe breastfeeding difficulties: Existential lostness as a mother—Women's lived experiences of initiating breastfeeding under severe difficulties

A majority of women in Sweden initiate breastfeeding but almost a quarter stop or wean the infant in the first few weeks after birth because of difficulties. In order to develop care that facilitates initiation of breastfeeding and enables mothers to realize their expectations concerning breastfeeding, it is necessary to understand what having severe breastfeeding difficulties means for women who experience them. The aim of this study is to describe the lived experiences of initiating breastfeeding under severe difficulties. A reflective lifeworld research design was used. Eight women, seven primiparous and one multipara, were interviewed within 2 months of giving birth. The essential meaning of the phenomenon is described as “Existential lostness as a mother forcing oneself into a constant fight”. This pattern is further explicated through its constituents; shattered expectations, a lost time for closeness, being of no use to the infant, being forced to expose oneself, and gaining strength through sharing. The results show that mothers with severe breastfeeding difficulties feel alone and exposed because of their suffering and are lost in motherhood. Thus, adequate care for mothers should enhance the forming of a caring relationship through sharing rather than exposing

Ubiquitin Carboxyl-Terminal Esterase LI (UCHLI) SI8Y Polymorphism in Patients with Cataracts

Background: Cataract is characterized by light-scattering protein aggregates. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a de-ubiquitinating enzyme wit

Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy

Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca(2+) handling is a key feature of HF pathophysiology. Restoring the Ca(2+) regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp(−/−)), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF

Computed tomography contrast enhancement pattern of the uterus in premenopausal women in relation to menstrual cycle and hormonal contraception

Background: There are different types of computed tomography (CT) contrast enhancement patterns of the uterus. It is not known whether these are hormonally dependent. Purpose: To assess the relationship between these patterns and the menstrual cycle in non-users of hormonal contraception, and the possible impact of hormonal contraception. Material and Methods: Prospective observational study of abdominal CT scans of 53 premenopausal women of whom 28 were non-users and 25 users of hormonal contraception. The non-users were divided according to menstrual cycle phase: follicular (n = 12); ovulatory (n = 1); and luteal (n = 12). The pattern and intensity of contrast enhancement of the uterine myometrium were assessed. Results: The dominant pattern of contrast enhancement of the myometrium was the diffuse homogeneous type in both non-users and users. The intensity of the enhancement measured in Hounsfield units (HU) was higher in the follicular phase (median 102, range 73–130) compared to the luteal phase in non-users (median 92, range 57–130); however this was not statistically significant (P = 0.2). The HU values observed in users (median 95, range 45–160) were at the same levels compared to those of the luteal phase in non-users. Conclusion: The dominant pattern of contrast enhancement in the portal venous phase of the myometrium in fertile ages is the diffuse homogeneous type and is independent of menstrual cycle phase or the use of hormonal contraception. However, these factors seem to play a role in the intensity of contrast enhancement, with a tendency of higher HU values in the follicular phase of non-users. © The Foundation Acta Radiologica 2020

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