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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.21.537874v1?rss=1 Authors: Ontiveros-Angel, P., Vega-Torres, J. D., Simon, T. B., Williams, V., Inostroza-Nives, Y., Alvarado-Crespo, N., Vega Gonzalez, Y., Pompolius, M., Katzka, W., Lou, J., Sharafeddin, F., De La Pena, I., Dong, T., Gupta, A., Viet, C. T., Febo, M., Obenaus, A., Figueroa, J. D. Abstract: Background: Childhood overweight/obesity is associated with the development of stress-related psychopathology. However, the pathways connecting childhood obesity to stress susceptibility remain poorly understood. Here, we used a systems biology approach to determine linkages underlying obesity-induced stress susceptibility. Methods: Sixty-two (62) adolescent Lewis rats (PND21) were fed for four weeks with a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). Subsequently, a group of rats (n = 32) was exposed to a well-established 31-day model of predator exposures and social instability (PSS). The effects of the WD and PSS were assessed with a comprehensive battery of behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), high throughput 16S ribosomal RNA gene sequencing for gut microbiome profiling, hippocampal microglia morphological and gene analysis, and gene methylation status of the stress marker, FKBP5. Parallel experiments were performed on human microglial cells (HMC3) to examine molecular mechanisms by which palmitic acid primes these cells to aberrant responses to cortisol. Results: Rats exposed to the WD and PSS exhibited deficits in sociability indices and increased fear and anxiety-like behaviors, food consumption, and body weight. WD and PSS interacted to alter indices of microstructural integrity within the hippocampal formation (subiculum) and subfields (CA1). Microbiome diversity and taxa distribution revealed that WD/PSS exposure caused significant shifts in the diversity of gut dominant bacteria and decreased the abundance of various members of the Firmicutes phylum, including Lachnospiracae NK4A136. Interestingly, the WD and PSS synergized to promote hippocampal microglia morphological and gene signatures implicated in neuroinflammation. These alterations were associated with changes in the microbiome, and in the expression and methylation status of the corticosterone receptor chaperone rat gene Fkbp5. HMC3 responses to cortisol were markedly disrupted after incubating cells in palmitate, shown by morphological changes and pro-inflammatory cytokine expression and release. Notably, these effects were partly mediated by the human FKBP5 gene. Conclusions: The combination of psychosocial stress and poor diet during adolescence has a deleterious synergistic impact on brain health. This study enhances our understanding of mechanisms and adaptations by which obesogenic environments shape the maturational trajectories of common neurobiological correlates of resilience. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Purpose: To compare the efficacy and safety of three intravitreal bevacizumab upload injections followed by a dexamethasone implant versus dexamethasone implant monotherapy in eyes with macular edema due to retinal vein occlusion. Methods: Sixty-four eyes of 64 patients were included in this prospective, consecutive, nonrandomized case series: group 1 consisted of 38 patients (22 with central retinal vein occlusion, CRVO, 16 with branch retinal vein occlusion, BRVO) treated using a dexamethasone implant (Ozurdex) alone; group 2 consisted of 26 patients (14 CRVO, 12 BRVO) treated with three consecutive intravitreal bevacizumab injections at monthly intervals followed by a dexamethasone implant. In case of recurrence, both cohorts received further dexamethasone implants. Preoperatively and monthly best corrected visual acuity (BCVA, ETDRS), central retinal thickness (Spectralis-OCT), intraocular pressure, and wide-angle fundus photodocumentation (Optomap) were performed. The primary clinical endpoint was BCVA at 6 months after initiation of therapy. Secondary endpoints were central retinal thickness and safety of the therapy applied. Results: In group 1, an increase in BCVA of 2.5 (+/- 1.6) letters in the CRVO and of 13.0 (+/- 3.2) letters in BRVO patients was seen after 6 months, in group 2 of 5.9 (+/- 0.4) letters (CRVO) and 3.8 (+/- 2.4) letters (BRVO), which was not statistically significant. When comparing the two treatment groups with respect to the type of vein occlusion, there was a significant advantage for BRVO patients for the dexamethasone implant monotherapy (BRVO patients in group 1, p = 0.005). Central retinal thickness showed a significant reduction after 6 months only in patients of group 1, both for CRVO (p = 0.01) and BRVO (p = 0.003). First recurrence after the first dexamethasone implant injection occurred after 3.8 months (mean) in CRVO and 3.5 months in BRVO patients (group 1), versus 3.2 and 3.7 months, respectively, in group 2. In group 1, 63.6% with CRVO and 50% with BRVO showed an increased intraocular pressure after treatment; in group 2, 57.1% with CRVO and 50.0% with BRVO, respectively. Conclusion: In CRVO, there was no difference between the two treatment strategies investigated. However, in BRVO, dexamethasone implant monotherapy was associated with better functional outcome. Copyright (C) 2012 S. Karger AG, Basel

Background and Aims: Patients with advanced liver cirrhosis who develop renal dysfunction have a poor prognosis. Elevated intrarenal resistance indices (RIs) due to renal vascular constriction have been described before in cirrhotic patients. In the current study, we prospectively investigated the course of intrarenal RIs and compared their prognostic impact with those of the Model for End-Stage Liver Disease (MELD) and the Child-Pugh scores. Methods: Sixty-three patients with liver cirrhosis underwent a baseline visit which included a sonographic examination and laboratory tests. Forty-four patients were prospectively monitored. The end points were death or survival at the day of the follow-up visit. Results: In 28 patients, a follow-up visit was performed after 22 8 months (group 1). Sixteen patients died during follow-up after 12 8 months (group 2). Group 2 patients showed a significantly higher baseline RI (0.76 +/- 0.05) than group 1 patients (RI = 0.72 +/- 0.06; p < 0.05). As shown by receiver operating characteristic analysis, the RI and the MELD score achieved similar sensitivity and specificity {[}area under the curve (AUC): 0.722; 95% confidence interval (95% CI): 0.575-0.873 vs. AUC: 0.724; 95% CI: 0.575-0.873, z = 0.029, n.s.] in predicting survival and were superior to the Child-Pugh score (AUC: 0.677; 96% Cl: 0.518-0.837). Conclusion: The RI is not inferior in sensitivity and specificity to the MELD score. Cirrhotic patients with elevated RIs have impaired short- and long-term survival. The RI may help identify high-risk patients that require special therapeutic care. Copyright (C) 2012 S. Karger AG, Basel

Background: The impact of infraglenoidal scapular notching in reversed total shoulder arthroplasty (RTSA) is still controversially discussed. Our goal was to evaluate its potential influence on subjective shoulder stability and clinical outcome. We hypothesized that subjective instability and clinical outcome after implantation of RTSA correlates with objective scapular notching. Methods: Sixty shoulders were assessed preoperatively and at minimum 2-year follow-up for active range of motion and by use of the Oxford instability score, Rowe score for instability, Constant score for pain, Constant shoulder score, DASH score. All shoulders were evaluated on anterior-posterior and axillary lateral radiographic views. These X-ray scans were classified twice by two orthopaedic surgeons with respect to infraglenoidal scapular notching according to the classification of Nerot. Notching was tested for correlation with clinical outcome scores to the evaluated notching. Results: We found no significant correlation between infraglenoidal scapular notching and clinical outcomes after a mid-term follow-up from 24 to 60 months, but at the final follow-up of 60 months and more, we did see statistically significant, positive correlations between infraglenoidal scapular notching and the Constant pain score as well as active range of motion. At mean follow-up of 42 months (range from 24 to 96 months) we found no significant correlation between subjective instability and infraglenoidal scapular notching. Conclusions: We conclude that patients' subjective impression on their shoulders' stability is not correlating with radiological signs of infraglenoidal scapular notching. Nevertheless clinical parameters are affected by infraglenoidal scapular notching, at least in the long term

Aims: The decrease in uterine resistance during normal pregnancy is known to be related to invading trophoblast cells which derive from placental tissue. Uterine and peripheral resistance is elevated in preeclampsia. The aim of the present study was to prospectively examine uterine and peripheral resistance in pregnancies complicated by preeclampsia (PE), fetal intrauterine growth restriction (IUGR) and pregnancy induced hypertension (PIH). Methods: Sixty-seven women with normal pregnancies, 17 with PE, 12 with IUGR underwent Doppler sonographic investigation of the uterine and the cubital arteries. The Pulsatility Index (PI) was calculated for each vessel. Statistical analysis was performed and a P-value < 0.05 was considered significant. Results: Patients with preeclampsia and IUGR showed a significant higher resistance at the placental (mean PI 1.267 and 1.063), nonplacental (mean PI 1.631 and 1.124) and cubital artery (mean PI 3,777 and 3.995) compared to the normal pregnancy group (mean PI 0.678; 0.859 and 2.95 respectively). Mean birth weight in the PE group was 1409 g, in the IUGR group 1649 g and 3419 g in the normal pregnancy group. Conclusions: Pregnancies with IUGR are associated with elevated peripheral resistance in the maternal arterial system as seen in pregnancies with preeclampsia. Our findings encourage to further investigate the maternal vascular system in high risk pregnancies.

Purpose: To introduce the scanning laser ophthalmoscope-evoked mfERG (SLO-mfERG) as a new method to measure focal retinal function. Methods: Sixty-two healthy individuals and 12 patients with Best's disease were examined. mfERGs were recorded using a scanning laser ophthalmoscope as a stimulator and trigger device (He-Neon 632.8 nm) as well as a fundus-monitoring system (infrared 730 nm). Results: Amplitudes in the central concentric area were found to be significantly lower in patients with Best's disease than in healthy controls, while no significant differences were found for the more peripheral areas. Conclusion: SLO-mfERG is a reliable new technique for topographic mapping of retinal function under simultaneous control of fixation.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.18.036368v1?rss=1 Authors: Ekhtiari, H., Kuplicki, R., Aupperle, R., Paulus, M. P. Abstract: Introduction: The brain response to drug-related cues is an important marker in addiction-medicine, however, the temporal dynamics of this response in repeated exposure to the cues are not well known yet. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations. Methods: Sixty-five male participants (35.8+-8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD and 22 male with opioid use disorder). The second replication-sample was re-tested within two weeks. Results: In the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both significant condition and condition-by-time interaction with a habituation response for the drug-related cues but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed consistent lack of drug>neutral and habituation response within all selected clusters in the second cue-exposure session. Conclusions: VMPFC, amygdala and ventral striatum show a habituation in response to drug-related cues which is consistent among different clinical populations. Habituation in response in the first session of cue-exposure and lack of reactivity in the second session of exposure provide foundations for development of cue-desensitization interventions. Copy rights belong to original authors. Visit the link for more info