HIV pre-exposure prophylaxis and buprenorphine at a drug detoxification center during the opioid epidemic: opportunities and challenges

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and buprenorphine decrease HIV acquisition. Between November, 2016 - July, 2017, we surveyed persons (N=200) at a drug detoxification center to assess their interest in PrEP and in buprenorphine, and to examine factors associated with such interests. Participants had a mean [SD] age of 39 [10] years. Over the previous 6 months, 58% (117/200) injected drugs and 50% (85/171) had condomless sex. Only 22% (26/117) of persons who injected drugs were aware of PrEP, yet 74% (86/116) and 72% (84/116) were interested in oral or injectable PrEP, respectively. Thirty-eight percent (47/125) of persons not receiving buprenorphine or methadone expressed interest in buprenorphine. After multivariable adjustment, Latinx ethnicity was associated with interest in PrEP (aOR: 3.80; 95% CI, 1.37-10.53), while male gender (aOR: 2.76; 95% CI, 1.21-6.34) was associated with interest in buprenorphine. Opportunities exist to implement PrEP and buprenorphine within drug detoxification centers.R01 DA046527 - NIDA NIH HHS; R25DA035163, K23DA044085 - National Institute of Drug Abuse; R01DA046527, P30DA040500 - National Institute of Drug Abuse; P30 DA040500 - NIDA NIH HHS; R25 DA035163 - NIDA NIH HHS; K23 DA044085 - NIDA NIH HHS; P30 AI042853 - NIAID NIH HHS; P30AI042853 - National Institute of Allergy and Infectious DiseasesAccepted manuscrip

Cork oak vulnerability to fire: the role of bark harvesting, tree characteristics and abiotic factors

Forest ecosystems where periodical tree bark harvesting is a major economic activity may be particularly vulnerable to disturbances such as fire, since debarking usually reduces tree vigour and protection against external agents. In this paper we asked how cork oak Quercus suber trees respond after wildfires and, in particular, how bark harvesting affects post-fire tree survival and resprouting. We gathered data from 22 wildfires (4585 trees) that occurred in three southern European countries (Portugal, Spain and France), covering a wide range of conditions characteristic of Q. suber ecosystems. Post-fire tree responses (tree mortality, stem mortality and crown resprouting) were examined in relation to management and ecological factors using generalized linear mixed-effects models. Results showed that bark thickness and bark harvesting are major factors affecting resistance of Q. suber to fire. Fire vulnerability was higher for trees with thin bark (young or recently debarked individuals) and decreased with increasing bark thickness until cork was 3–4 cm thick. This bark thickness corresponds to the moment when exploited trees are debarked again, meaning that exploited trees are vulnerable to fire during a longer period. Exploited trees were also more likely to be top-killed than unexploited trees, even for the same bark thickness. Additionally, vulnerability to fire increased with burn severity and with tree diameter, and was higher in trees burned in early summer or located in drier south-facing aspects. We provided tree response models useful to help estimating the impact of fire and to support management decisions. The results suggested that an appropriate management of surface fuels and changes in the bark harvesting regime (e.g. debarking coexisting trees in different years or increasing the harvesting cycle) would decrease vulnerability to fire and contribute to the conservation of cork oak ecosystemsinfo:eu-repo/semantics/publishedVersio

Factors predicting clinically significant fatigue in women following treatment for primary breast cancer

Cancer-related fatigue is common, complex, and distressing. It affects 70–100% of patients receiving chemotherapy and a significant number who have completed their treatments. We assessed a number of variables in women newly diagnosed with primary breast cancer (BrCa) to determine whether biological and/or functional measures are likely to be associated with the development of clinically significant fatigue (CSF). Two hundred twenty-three women participated in a study designed to document the impact of the diagnosis and treatment of primary breast cancer on function. Forty-four had complete data on all variables of interest at the time of confirmed diagnosis but prior to treatment (baseline) and ≥9 months post-diagnosis. Objective measures and descriptive variables included history, physical examination, limb volume, hemoglobin, white blood cell count, and glucose. Patient-reported outcomes included a verbal numerical rating of fatigue (0–10, a score of ≥4 was CSF), five subscales of the SF-36, Physical Activity Survey, and Sleep Questionnaire. At baseline, the entire cohort (n = 223) and the subset (n = 44) were not significantly different for demographic, biological, and self-reported data, except for younger age (p = 0.03) and ER+ (p = 0.01). Forty-five percent had body mass index (BMI) ≥ 25, 52% were post-menopause, and 52% received modified radical mastectomy, 39% lumpectomy, 52% chemotherapy, 68% radiation, and 86% hormonal therapy. Number of patients with CSF increased from 1 at baseline to 11 at ≥9 months of follow-up. CSF at ≥9 months significantly correlated with BMI ≥ 25, abnormal white blood cell count, and increase in limb volume and inversely correlated with vigorous activity and physical function (p < 0.05). Fatigue increases significantly following the treatment of BrCa. Predictors of CSF include high BMI and WBC count, increase in limb volume, and low level of physical activity. These are remediable

Olfactory Ensheathing Cell Transplantation in Experimental Spinal Cord Injury:Effect size and Reporting Bias of 62 Experimental Treatments: A Systematic Review and Meta-Analysis

Olfactory ensheathing cell (OEC) transplantation is a candidate cellular treatment approach for human spinal cord injury (SCI) due to their unique regenerative potential and autologous origin. The objective of this study was, through a meta-epidemiologic approach, (i) to assess the efficacy of OEC transplantation on locomotor recovery after traumatic experimental SCI and (ii) to estimate the likelihood of reporting bias and/or missing data. A study protocol was finalized before data collection. Embedded into a systematic review and meta-analysis, we conducted a literature research of databases including PubMed, EMBASE, and ISI Web of Science from 1949/01 to 2014/10 with no language restrictions, screened by two independent investigators. Studies were included if they assessed neurobehavioral improvement after traumatic experimental SCI, administrated no combined interventions, and reported the number of animals in the treatment and control group. Individual effect sizes were pooled using a random effects model. Details regarding the study design were extracted and impact of these on locomotor outcome was assessed by meta-regression. Missing data (reporting bias) was determined by Egger regression and Funnel-plotting. The primary study outcome assessed was improvement in locomotor function at the final time point of measurement. We included 49 studies (62 experiments, 1,164 animals) in the final analysis. The overall improvement in locomotor function after OEC transplantation, measured using the Basso, Beattie, and Bresnahan (BBB) score, was 20.3% (95% CI 17.8-29.5). One missing study was imputed by trim and fill analysis, suggesting only slight publication bias and reducing the overall effect to a 19.2% improvement of locomotor activity. Dose-response ratio supports neurobiological plausibility. Studies were assessed using a 9-point item quality score, resulting in a median score of 5 (interquartile range [IQR] 3-5). In conclusion, OEC transplantation exerts considerable beneficial effects on neurobehavioral recovery after traumatic experimental SCI. Publication bias was minimal and affirms the translational potential of efficacy, but safety cannot be adequately assessed. The data justify OECs as a cellular substrate to develop and optimize minimally invasive and safe cellular transplantation paradigms for the lesioned spinal cord embedded into state-of-the-art Phase I/II clinical trial design studies for human SCI

Impacts of soil conditions and light availability on natural regeneration of Norway spruce Picea abies (L.) H. Karst. in low-elevation mountain forests

& Key message Natural regeneration of P. abies (L.) H. Karst. may reach high densities in lower mountain elevations. The highest densities were found in sites with moderate light availability, with low pH, and not near the riverbank. However, age-height classes differed in the predicted magnitude of response, but were consistent in response directions. Mosses and understory species typical of coniferous forests were positively correlated with regeneration density. & Context Norway spruce Picea abies (L.) H. Karst. in Central Europe is at risk under climate change scenarios, particularly in mountain regions. Little is known about the impact of environmental factors on the natural regeneration of P. abies in lowelevation mountain forests. & Aims We aimed to assess impacts of distance from the riverbank, soil pH, and light availability on natural P. abies regeneration. We hypothesized that (1) natural P. abiesregeneration would depend on light availability and soil pH and (2) there are understory plant species which may indicate the microsites suitable for natural regeneration of P. abies. & Methods The study was conducted in the Stołowe Mountains National Park (SW Poland, 600–800 m a.s.l.). We established 160 study plots (25 m2 ) for natural regeneration, light availability, soil pH, and understory vegetation assessment

Differentiation of human adipose-derived stem cells into neuron/motoneuron-like cells for cell replacement therapy of spinal cord injury

Human adipose-derived stem cells (hADSCs) are increasingly presumed to be a prospective stem cell source for cell replacement therapy in various degenerative and/or traumatic diseases. The potential of trans-differentiating hADSCs into motor neuron cells indisputably provides an alternative way for spinal cord injury (SCI) treatment. In the present study, a stepwise and efficient hADSC trans-differentiation protocol with retinoic acid (RA), sonic hedgehog (SHH), and neurotrophic factors were developed. With this protocol hADSCs could be converted into electrophysiologically active motoneuron-like cells (hADSC-MNs), which expressed both a cohort of pan neuronal markers and motor neuron specific markers. Moreover, after being primed for neuronal differentiation with RA/SHH, hADSCs were transplanted into SCI mouse model and they survived, migrated, and integrated into injured site and led to partial functional recovery of SCI mice. When ablating the transplanted hADSC-MNs harboring HSV-TK-mCherry overexpression system with antivirial Ganciclovir (GCV), functional relapse was detected by motor-evoked potential (MEP) and BMS assays, implying that transplanted hADSC-MNs participated in rebuilding the neural circuits, which was further confirmed by retrograde neuronal tracing system (WGA). GFP-labeled hADSC-MNs were subjected to whole-cell patch-clamp recording in acute spinal cord slice preparation and both action potentials and synaptic activities were recorded, which further confirmed that those pre-conditioned hADSCs indeed became functionally active neurons in vivo. As well, transplanted hADSC-MNs largely prevented the formation of injury-induced cavities and exerted obvious immune-suppression effect as revealed by preventing astrocyte reactivation and favoring the secretion of a spectrum of anti-inflammatory cytokines and chemokines. Our work suggests that hADSCs can be readily transformed into MNs in vitro, and stay viable in spinal cord of the SCI mouse and exert multi-therapeutic effects by rebuilding the broken circuitry and optimizing the microenvironment through immunosuppression