Individual and social network correlates of recent treatment for substance use disorders

Substance use disorders (SUDs) result in numerous negative outcomes, with only a minority of those with a SUD ever seeking treatment. A more complete understanding is needed of the factors that impact treatment enrollment. The purpose of this analysis was to identify individual and social network correlates of treatment enrollment for substance use disorders among a sample of 330 persons who used drugs and resided in Baltimore, MD between 2014 and 2017. Models were built using multivariable logistic regression and sub-analyses were performed among subsets of individuals based on type of drug use and available treatment options for that type. In the overall sample, the number of network members currently enrolled in drug treatment was positively associated with treatment enrollment, with an increase in odds of treatment enrollment of 122% for each additional network member currently enrolled in treatment (95% CI: 1.48, 3.34). The number of network members who used heroin, cocaine, and/or crack was not associated with treatment enrollment (OR: 1.07, 95% CI: 0.88, 1.37); however, the number of network members who used drugs and provided emotional, financial, instrumental or material support (i.e., network members he/she could talk to, socialize with, who pitched in to help him/her, who were willing to provide financial support, or who he/she stayed with) reduced the odds of treatment enrollment by 38% for each additional person who used drugs in the could support network (95% CI: 0.42, 0.92). It appears to be the nature, rather than the number, of ties with other people who use drugs (PWUD) that impacts an individual’s probability of treatment enrollment. The implication may be that, rather than encouraging PWUD to distance themselves from all PWUD in their network, that they focus on fostering close relationships with sober individuals, and that they attempt to transfer sources of emotional and financial support to people who do not use drugs.2021-02-28T00:00:00

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases

Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Nonetheless, more often than not mouse models do not reproduce the pathophysiology of the human conditions they are designed to mimic. Naturally occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. In particular, numerous models have been discovered in dogs and have a fundamental role in bridging proof of concept studies in mice to human clinical trials. The present article is a review that highlights current canine models of human diseases, including Alzheimer\u27s disease, degenerative myelopathy, neuronal ceroid lipofuscinosis, globoid cell leukodystrophy, Duchenne muscular dystrophy, mucopolysaccharidosis, and fucosidosis. The goal of the review is to discuss canine and human neurodegenerative pathophysiologic similarities, introduce the animal models, and shed light on the ability of canine models to facilitate current and future treatment trials

Sexueller Missbrauch Minderjähriger durch katholische Geistliche in Deutschland

"In this anthology, empirical findings on sexual abuse by Catholic clerics in Germany are presented for the first time. The results are based on data of two samples of victims and thereby provide in-depth knowledge about background, characteristics and consequences of sexual abuse within the Catholic Church: a quantitative questionnaire study and a qualitative interview study. The analyses of the quantitative survey emphasize the central characteristics of the abuse and their psychosocial effects on the victims. Additionally, reactions of the public authorities and the Catholic Church regarding the victims’ disclosure of the sexual abuse are taken into account. The qualitative research focusses on victims’ different biographical ways of handling the sexual abuse. Particularly the recourse to Catholic beliefs in dealing with the experienced sexual violence is revealed.

Volume and Infusion Rate Dynamics of Intraparenchymal Central Nervous System Infusion in a Large Animal Model

Thalamic infusion of adeno-associated viral (AAV) vectors has been shown to have therapeutic effects in neuronopathic lysosomal storage diseases. Preclinical studies in sheep model of Tay-Sachs disease demonstrated that bilateral thalamic injections of AAV gene therapy are required for maximal benefit. Translation of thalamic injection to patients carries risks in that (1) it has never been done in humans, and (2) dosing scale-up based on brain weight from animals to humans requires injection of larger volumes. To increase the safety margin of this infusion, a flexible cannula was selected to enable simultaneous bilateral thalamic infusion in infants while monitoring by imaging and/or to enable awake infusions for injection of large volumes at low infusion rates. In this study, we tested various infusion volumes (200-800 muL) and rates (0.5-5 muL/min) to determine the maximum tolerated combination of injection parameters. Animals were followed for approximately 1 month postinjection with magnetic resonance imaging (MRI) performed at 14 and 28 days. T1-weighted MRI was used to quantify thalamic damage followed by histopathological assessment of the brain. Trends in data show that infusion volumes of 800 muL (2 x the volume required in sheep based on thalamic size) resulted in larger lesions than lower volumes, where the long infusion times (between 13 and 26 h) could have contributed to the generation of larger lesions. The target volume (400 muL, projected to be sufficient to cover most of the sheep thalamus) created the smallest lesion size. Cannula placement alone did result in damage, but this is likely associated with an inherent limitation of its use in a small brain due to the length of the distal rigid portion and lack of stable fixation. An injection rate of 5 muL/min at a volume approximately 1/3 of the thalamus (400-600 muL) appears to be well tolerated in sheep both clinically and histopathologically

A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna

Global gene delivery to the CNS has therapeutic importance for the treatment of neurological disorders that affect the entire CNS. Due to direct contact with the CNS, cerebrospinal fluid (CSF) is an attractive route for CNS gene delivery. A safe and effective route to achieve global gene distribution in the CNS is needed, and administration of genes through the cisterna magna (CM) via a suboccipital puncture results in broad distribution in the brain and spinal cord. However, translation of this technique to clinical practice is challenging due to the risk of serious and potentially fatal complications in patients. Herein, we report development of a gene therapy delivery method to the CM through adaptation of an intravascular microcatheter, which can be safely navigated intrathecally under fluoroscopic guidance. We examined the safety, reproducibility, and distribution/transduction of this method in sheep using a self-complementary adeno-associated virus 9 (scAAV9)-GFP vector. This technique was used to treat two Tay-Sachs disease patients (30 months old and 7 months old) with AAV gene therapy. No adverse effects were observed during infusion or post-treatment. This delivery technique is a safe and minimally invasive alternative to direct infusion into the CM, achieving broad distribution of AAV gene transfer to the CNS