Quantifying Psychostimulant-induced Sensitization Effects on Dopamine and Acetylcholine Release across different Timescales

Drug-induced behavioral sensitization describes the phenomenon that behavioral response to a drug of abuse is getting stronger if the same psychostimulant is delivered multiple times which is much more pronounced if done in the same environmental context. A proposed neural basis is the formation of an association between contextual cues and the rewarding drug which is mediated by dopamine. Dopamine operates at different timescales and to fully understand dopamine sensitization, it is necessary to investigate dopamine release at slow (tens of minutes) but also faster (sub-second) timescales. But creating a holistic view has been difficult due to a lack of technology that can measure dopamine across various temporal resolutions. We develop an analysis pipeline to expand fiber photometry to measure tonic dopamine activity. We use genetically encoded neurotransmitter indicators to measure extracellular dopamine and acetylcholine activity in the nucleus accumbens of mice. We show that the method is precise enough to measure dopamine sensitization in response to repeated cocaine and amphetamine injections. We then further characterize how dopamine dynamics change in response to psychostimulants. We see that drug-evoked dopamine rises and decays faster in sensitized mice compared to the first injection and that there are more small but less big transients which leads to a smaller fluctuation at a timescale of tens of seconds. We simultaneously record striatal acetylcholine and observe that the frequency and amplitude of transients decrease during sensitization. We also investigate interaction between dopamine, acetylcholine, and movement and report that the relationship between accumbal activity and locomotion gets stronger and that dopamine and acetylcholine interact closely. In addition, we use DeepLabCut and MoSeq to densely annotate behavior. We show that MoSeq can potentially be used to replace locomotor activity with a better measurement of behavioral sensitization

STNet: Selective Tuning of Convolutional Networks for Object Localization

Visual attention modeling has recently gained momentum in developing visual hierarchies provided by Convolutional Neural Networks. Despite recent successes of feedforward processing on the abstraction of concepts form raw images, the inherent nature of feedback processing has remained computationally controversial. Inspired by the computational models of covert visual attention, we propose the Selective Tuning of Convolutional Networks (STNet). It is composed of both streams of Bottom-Up and Top-Down information processing to selectively tune the visual representation of Convolutional networks. We experimentally evaluate the performance of STNet for the weakly-supervised localization task on the ImageNet benchmark dataset. We demonstrate that STNet not only successfully surpasses the state-of-the-art results but also generates attention-driven class hypothesis maps

Epidemiology, Symptoms, and Treatment Characteristics of Hyponatremic Psychiatric Inpatients

Hyponatremia is a common phenomenon in psychiatry occurring as an adverse effect to drugs or following polydipsia. We performed a retrospective in-depth analysis of hyponatremia cases in a large unselected population of psychiatric inpatients. During a 3-year period, all cases of hyponatremia were identified among patients admitted to a large psychiatric state and university hospital by the institution's electronic laboratory database. Demographic, treatment-related, and laboratory data were obtained by consecutive chart review, respectively. Hyponatremia occurred in 347 (4.9%) of 7113 cases, of which the majority (78%) displayed only a mild manifestation. Symptoms were recorded in 28.8% of cases, already occurred in mild forms, and comprised gait impairment (45%, including falls), confusion (30%), sedation (26%), and dyspepsia (41%). Age, female sex, nonpsychiatric drug polypharmacy-particularly with thiazides and/or angiotensin-converting enzyme inhibitors-and diagnosis of a mood disorder were associated with more severe hyponatremia, respectively. The proportion of hyponatremic patients treated with venlafaxine, trazodone, carbamazepine, oxcarbazepine, and first-generation antipsychotics, respectively, was significantly higher in the hyponatremia sample than in the normonatremic population. This was, surprisingly, not the case with selective serotonin reuptake inhibitors or any other antidepressant drug class. We found prescription with second-generation antipsychotics to be significantly associated with less severe hyponatremia. Hyponatremia may be mainly attributed to the syndrome of inappropriate antidiuretic hormone secretion, as indicated by decreased serum osmolarity in our sample. Besides old age and female sex, treatment with certain drugs-rather than whole drug classes-carries a substantially increased risk

Epidemiology, Symptoms, and Treatment Characteristics of Hyponatremic Psychiatric Inpatients

Hyponatremia is a common phenomenon in psychiatry occurring as an adverse effect to drugs or following polydipsia. We performed a retrospective in-depth analysis of hyponatremia cases in a large unselected population of psychiatric inpatients. During a 3-year period, all cases of hyponatremia were identified among patients admitted to a large psychiatric state and university hospital by the institution's electronic laboratory database. Demographic, treatment-related, and laboratory data were obtained by consecutive chart review, respectively. Hyponatremia occurred in 347 (4.9%) of 7113 cases, of which the majority (78%) displayed only a mild manifestation. Symptoms were recorded in 28.8% of cases, already occurred in mild forms, and comprised gait impairment (45%, including falls), confusion (30%), sedation (26%), and dyspepsia (41%). Age, female sex, nonpsychiatric drug polypharmacy-particularly with thiazides and/or angiotensin-converting enzyme inhibitors-and diagnosis of a mood disorder were associated with more severe hyponatremia, respectively. The proportion of hyponatremic patients treated with venlafaxine, trazodone, carbamazepine, oxcarbazepine, and first-generation antipsychotics, respectively, was significantly higher in the hyponatremia sample than in the normonatremic population. This was, surprisingly, not the case with selective serotonin reuptake inhibitors or any other antidepressant drug class. We found prescription with second-generation antipsychotics to be significantly associated with less severe hyponatremia. Hyponatremia may be mainly attributed to the syndrome of inappropriate antidiuretic hormone secretion, as indicated by decreased serum osmolarity in our sample. Besides old age and female sex, treatment with certain drugs-rather than whole drug classes-carries a substantially increased risk

Enchondromas and atypical cartilaginous tumors at the proximal humerus treated with intralesional resection and bone cement filling with or without osteosynthesis: retrospective analysis of 42 cases with 6 years mean follow-up

Background: Enchondromas and atypical cartilaginous tumors (ACT) are often located at the proximal humerus. Most lesions can be followed conservatively, but surgical resection may alleviate pain, avoid pathological fractures, and prevent transformation into higher grade chondrosarcomas. Rigorous intralesional resection and filling with polymethylmethacrylate bone cement has been proposed for enchondromas but also for ACT, as an alternative for extralesional resection. We intended to analyze radiological, clinical, and functional outcome of this strategy and compare bone cement without osteosynthesis to bone cement compound osteosynthesis, which has not been analyzed so far. Methods: We retrospectively analyzed 42 consecutive patients (mean follow-up 73 months; range 8–224) after curettage and bone cement filling with or without osteosynthesis. Exclusion criteria were Ollier’s disease and cancellous bone filling. Twenty-five patients only received bone cement. Seventeen patients received additional proximal humerus plate for compound osteosynthesis to increase stability after curettage. Demographics and radiological and clinical outcome were analyzed including surgery time, blood loss, hospitalization, recurrences, and complications. An additional telephone interview at the final follow-up assessed postoperative satisfaction, pain, and function in the quick disabilities of the arm, shoulder, and hand (DASH) score and the Musculoskeletal Tumor Society (MSTS) score. Statistics included the Student T tests, Mann-Whitney U tests, and chi-square tests. Results: No osteosynthesis compared to compound osteosynthesis showed smaller tumors (4.2 (± 1.5) cm versus 6.6 (± 3.0) cm; p = 0.005) and smaller bone cement fillings after curettage (5.7 (± 2.1) cm versus 9.6 (± 3.2) cm; p = 0.0001). A score evaluating preoperative scalloping and soft-tissue extension did not significantly differ (1.9 (± 0.9) versus 2.0 (± 1.0); rating scale 0–4; p = 0.7). Both groups showed high satisfaction (9.2 (± 1.5) versus 9.2 (± 0.9); p = 0.5) and low pain (1.0(±1.7) versus 1.9(±1.8); p = 0.1) in a rating scale from 0 to 10. Clinical and functional outcome was excellent for both groups in the DASH score (6.0 (± 11.8) versus 11.0 (± 13.2); rating scale 0–100; p = 0.2) and the MSTS score (29.0 (± 1.7) versus 28.7 (± 1.1); rating scale 0–30; p = 0.3). One enchondroma recurrence was found in the group without osteosynthesis. Complications (one fracture and one intra-articular screw) were only detected after osteosynthesis. Osteosynthesis had longer surgery time (70 (± 21) min versus 127 (± 22) min; p < 0.0001), more blood loss (220 (± 130) ml versus 460 (± 210) ml; p < 0.0001), and longer stay in the hospital (6 (± 2) days versus 8 (± 2) days; p = 0.004). Conclusions: Intralesional tumor resection was oncologically safe and clinically successful with or without osteosynthesis. Osteosynthesis did not reduce the risk for fracture but was more invasive

Drought Reduces Release of Plant Matter Into Dissolved Organic Matter Potentially Restraining Ecosystem Recovery

Future climate scenarios indicate increasing drought intensity that threatens ecosystem functioning. However, the behavior of ecosystems during intense drought, such as the 2018 drought in Northern Europe, and their respective response following rewetting is not fully understood. We investigated the effect of drought on four different vegetation types in a temperate climate by analyzing dissolved organic matter (DOM) concentration and composition present in soil leachate, and compared it to two accompanying years. DOM is known to play an important role in ecosystem recovery and holds information on matter flows between plants, soil microorganisms and soil organic matter. Knowledge about DOM opens the possibility to better disentangle the role of plants and microorganisms in ecosystem recovery. We found that the average annual DOM concentration significantly decreased during the 2018 drought year compared to the normal year. This suggests a stimulation of DOM release under normal conditions, which include a summer drought followed by a rewetting period. The rewetting period, which holds high DOM concentrations, was suppressed under more intense drought. Our detailed molecular analysis of DOM using ultrahigh resolution mass spectrometry showed that DOM present at the beginning of the rewetting period resembles plant matter, whereas in later phases the DOM molecular composition was modified by microorganisms. We observed this pattern in all four vegetation types analyzed, although vegetation types differed in DOM concentration and composition. Our results suggest that plant matter drives ecosystem recovery and that increasing drought intensity may lower the potential for ecosystem recovery

Risk factors for sporadic domestically acquired Campylobacter infections in Norway 2010–2011: A national prospective case-control study

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: https://creativecommons.org/licenses/by/4.0/"Background: Campylobacteriosis is the most frequently reported food- and waterborne infection in Norway. We investigated the risk factors for sporadic Campylobacter infections in Norway in order to identify areas where control and prevention measures could be improved."Funds were provided for the preparation of data collection materials by the Norwegian Food Safety Authority and the Norwegian Veterinary Institut

The diagnostic value of a treadmill test in predicting lumbar spinal stenosis

Lumbar spinal stenosis is a frequent indication for spinal surgery. The predictive quality of treadmill testing and MRI for diagnostic verification is not yet clearly defined. Aim of the current study was to assess correlations between treadmill testing and MRI findings in the lumbar spine. Twenty-five patients with lumbar spinal stenosis were prospectively examined. Treadmill tests were performed and the area of the dural sac and neuroforamina was examined with MRI for the narrowest spinal segment. VAS and ODI were used for clinical assessment. The median age of the patients was 67years. In the narrowest spinal segment the median area of the dural sac was 91mm2. The median ODI was 66 per cent. The median walking distance in the treadmill test was 70m. The distance reached in the treadmill test correlated with the area of the dural sac (Spearman's ρ=0.53) and ODI (ρ=−0.51), but not with the area of the neuroforamina and VAS. The distance reached in the treadmill test predicts the grade of stenosis in MRI but has a limited diagnostic importance for the level of clinical symptoms in lumbar spinal stenosi