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This article discusses the use of Enhanced Recovery After Surgery (ERAS) in minimally invasive cardiac surgery. ERAS is an interdisciplinary approach aimed at improving recovery and reducing complications after major surgery. The study analyzed data from 358 patients who underwent minimally invasive cardiac surgery and perioperative ERAS. The outcomes of interest included major adverse cardiac events, bleeding requiring reoperation, ERAS-associated complications, and the achievement of specific ERAS goals. The results showed that ERAS programs can be successful in cardiac surgery, regardless of patient age and common comorbidities. However, factors such as surgical complexity, preexisting heart failure, and high perioperative risk scores may hinder the success of ERAS. [Extracted from the article]

Linda Veith Sanches,1,* Stephan Greten,1,* Johanna Doll-Lee,1 Sophia Marie Rogozinski,1 Johanne Heine,1 Lea Krey,1 Sarana Ulaganathan,1 Ida Jensen,1,2 Matthias Höllerhage,1 Sam Sadeghi Sani,1 Günter U Höglinger,1– 4 Florian Wegner,1 Martin Klietz1 1Department of Neurology, Hannover Medical School, Hannover, Germany; 2Department of Neurology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany; 3Munich Cluster for Systems Neurology, SyNergy, Munich, Germany; 4German Center for Neurodegenerative Diseases, DZNE, Munich, Germany*These authors contributed equally to this workCorrespondence: Stephan Greten, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Germany, Tel +49 511 532-6462, Fax +49 511 532-6677, Email Greten.stephan@mh-hannover.deIntroduction: Neuropsychiatric symptoms in particular impair health-related quality of life (QoL) of patients with Parkinson’s disease and atypical Parkinsonian syndromes. For this reason, various scales have been developed for detection of neuropsychiatric symptoms, such as the Scale for evaluation of neuropsychiatric disorders in Parkinson’s disease (SEND-PD).Objective: First, the objective of this study was to explore the interrelation between the SEND-PD and clinical parameters in patients with Parkinson’s disease and thus confirm its validity. In addition, the applicability in a well-defined cohort of patients with atypical Parkinsonian syndromes was investigated for the very first time.Methods: A clinically well-defined cohort of 122 patients with Parkinson’s disease (PD), 55 patients with Progressive Supranuclear Palsy (PSP) and 33 patients with Multiple System Atrophy (MSA) were analyzed. First, the SEND-PD was correlated with established disease-specific scores in patients with PD. Next, the results of the SEND-PD were compared between the different Parkinsonian syndromes.Results: The SEND-PD showed a strong significant correlation with several scores, especially the UPDRS I (Rho = 0.655) and GDS-15 (Rho = 0.645). Depressive burden was significantly higher in MSA patients in comparison to the PD patient cohort (PD, 3.8 ± 3.3; MSA, 5.45 ± 3.87), while PSP patients showed significantly less psychotic (PD 1.6 ± 2.1; PSP 0.6 ± 0.9) and impulse control disorders (PD 0.3 ± 1.0; PSP 0.02 ± 0.1).Conclusion: The SEND-PD is a useful, brief and highly applicable screening tool for neuropsychiatric symptoms in PD, but not in atypical Parkinsonism, as their unique neuropsychiatric symptom composition is not fully captured.Keywords: neuropsychiatric symptoms, SEND-PD, Parkinsonian syndromes

Chronic ethanol consumption in rats resulted in a striking fat accumulation in the acinar cells of the parotid gland demonstrated by light microscopy. In addition, a significant decrease in parotid wet weight ( p > 0.02) and in protein content of the gland ( p > 0.02) was observed following alcohol feeding. Wet weight, protein content, and morphology of the submaxillar gland were not affected by ethanol feeding. Alcohol metabolism, similar to that found in the pancreas, via a cytosolic alcohol dehydrogenase could be demonstrated in both the parotid and the submaxillar gland. However, the activity of this enzyme was not affected by chronic ethanol ingestion. Subsequently, chronic ethanol consumption significantly decreased salivary flow rate stimulated by pilocarpine hydrochloride (p > 0.02), salivary a-amylase activity (p > 0.02), and salivary sodium concentration (p > 0.01), whereas potassium concentration of the saliva was increased (p > 0.05). In contrast salivary total protein concentration was not affected by alcohol ingestion. The changes of salivary electrolyte composition observed after chronic ethanol feeding could be due to an altered aldosterone metabolism or to a change in aldosterone receptors of the parotid gland caused by ethanol administration. The reduced salivary flow could play a role in the pathogenesis of oropharyngeal cancer in the alcoholic. [ABSTRACT FROM AUTHOR]

Chronic ethanol consumption significantly increases gastric adenyl-ate cyclase (AC) activity ( p < 0.05) without influencing low Km 3′,5′-cyclic adenosine monophosphate (cAMP) phosphodiesterase (PD) activity in the rat. On the other hand, in the duodenum and upper part of the jejunum, chronic ethanol feeding leads to a significant decrease of adenyiate cyclase activity ( p<0.02) and, again, does not affect low Km cAMP phosphodiesterase activity. In addition, the effect of various hormonal secretagoques on small intestinal adenylate cyclase activity was Investigated. Prostaglandin I2 and D2, as well as glucagon, do not stimulate AC at all. However, small intestinal adenylate cyclase exhibits a lower sensitivity to prostaglandin E2 and vasoactive intestinal peptide (VIP), and a lower efficacy to VIP after chronic ethanol consumption when compared to controls. The decrease of both basal and stimulated AC activity following ethanol ingestion in the upper small intestine may be due to membrane alterations and tissue damage caused by ethanol. The ethanol-induced increase in gastric AC may be of relevance with respect to an increased acid secretion observed after alcohol administration. [ABSTRACT FROM AUTHOR]

Introduction: Enhanced Recovery After Surgery (ERAS) prioritizes faster functional recovery after major surgery. An important aspect of postoperative ERAS is decreasing morbidity and immobility, which can result from prolonged critical care. Using current clinical data, our aim was to analyze whether a six-hour monitoring period after Minimally Invasive Cardiac Surgery (MICS) might be sufficient to recognize major postoperative complications in a future Fast Track pathway. Additionally, we sought to investigate whether it could be possible to deescalate the setting of postoperative monitoring., Methods: 358 patients received MICS and were deemed suitable for an ERAS protocol between 01/2021 and 03/2023 at our institution. Of these, 297 patients could be successfully extubated on-table, were transferred to IMC or ICU in stable condition and therefore served as study cohort. Outcomes of interest were incidence and timing of Major Adverse Cardiac Events (MACE; death, myocardial infarction requiring revascularization, stroke), bleeding requiring reexploration and Fast Track-associated complications (reintubation and readmission to ICU)., Results: Patients' median age was 63 years (IQR 55-70) and 65% were male. 189 (64%) patients received anterolateral mini-thoracotomy, primarily for mitral and/or tricuspid valve surgery ( n  = 177). 108 (36%) patients had partial upper sternotomy, primarily for aortic valve repair/replacement ( n  = 79) and aortic surgery ( n  = 17). 90% of patients were normotensive without need for vasopressors within 6 h postoperatively, 82% of patients were transferred to the general ward on postoperative day 1 (POD). Two (0.7%) MACE events occurred, as well as 4 (1.3%) postoperative bleeding events requiring reexploration. Of these complications, only one event occurred before transfer to the ward - all others took place on or after POD 1. There was one instance of reintubation and two of readmission to ICU., Conclusions: If MICS patients can be successfully extubated on-table and are hemodynamically stable, major postoperative complications were rare in our single-center experience and primarily occurred after transfer to the ward. Therefore, in well selected MICS patients with uncomplicated intraoperative course, monitoring for six hours, possibly outside of an ICU, followed by transfer to the ward appears to be a feasible theoretical concept without negative impact on patient safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Stock, Berger Veith, Holst, Erfani, Pochert, Dumps and Girdauskas.)

Objectives: Enhanced recovery after surgery (ERAS) is a growing phenomenon in all surgical disciplines and aims to achieve a faster functional recovery after major operations. Minimally invasive cardiac surgery (MICS) therefore integrates well into core ERAS values. Surgical access routes in MICS include right anterolateral mini-thoracotomy (MT) as well as partial upper mini-sternotomy (PS). We seek to compare outcomes in these two cohorts, both of which were enrolled in an ERAS scheme., Methods: 358 consecutive patients underwent MICS and perioperative ERAS at our institution between 01/2021 and 03/2023. Patients age >80 years, with BMI > 35 kg/m², LVEF ≤ 35%, endocarditis or stroke with residuum were excluded. Retrospective cohort analysis and statistical testing was performed on the remaining 291 patients. The primary endpoint was successful ERAS, secondary endpoints were the occurrence of major bleeding, ERAS-associated complications (reintubation, return to ICU) as well as access-related complications (wound infection, pleural and pericardial effusions)., Results: 170 (59%) patients received MT for mitral and/or tricuspid valve surgery ( n  = 162), closure of atrial septal defect ( n  = 4) or resection of left atrial tumor ( n  = 4). The remaining 121 (41%) patients had PS for aortic valve repair/replacement ( n  = 83) or aortic root/ascending surgery ( n  = 22) or both ( n  = 16). MT patients' median age was 63 years (IQR 56-71) and 65% were male, PS patients' median age was 63 years (IQR 51-69) and 74% were male. 251 (MT 88%, PS 83%, p = 0.73) patients passed through the ERAS program successfully. There were three instances of reintubation (2 MT, 1 PS), and three instances of readmission to ICU (2 MT, 1 PS). Bleeding requiring reexploration occurred six times (3 MT, 3 PS). There was one death (PS), one stroke (MT), and one myocardial infarction requiring revascularization (MT). There were no significant differences in any of the post-operative outcomes recorded, except for the incidence of pericardial effusions (MT 0%, PS 3%, p  = 0.03)., Conclusions: Despite different surgical access routes and underlying pathologies, results in both the MT and the PS cohort were generally comparable for the recorded outcomes. ERAS remains safe and feasible in these patient groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TH declared a past co-authorship with the author EG to the handling editor. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Berger Veith, Holst, Erfani, Pochert, Dumps, Girdauskas and Stock.)

In football, the number of days without full participation in training/competition is often used as a surrogate measure for time-loss (TL) caused by injury. However, injury management and return-to-play processes frequently include modified participation, which to date has only been recorded through self-reports. This study aims to demonstrate the differentiation between 'full' (no participation in team football) and 'partial' (reduced/modified participation in team football) burden. Injury and exposure data were collected from 118 male elite footballers (U13-U18) over 3 consecutive seasons according to the Football Consensus Statement. TL injury burden was calculated separately as the number of total, 'full' and 'partial' days lost per 1000 h of exposure. Injury burden (137.2 days lost/1000 h, 95% CI 133.4-141.0) was comprised of 23% (31.9 days lost/1000 h, 95% CI 30.1-33.8) partial TL and 77% (105.3 days lost/1000 h, 95% CI 102.0-108.6) full TL burden. Injuries of moderate severity (8-28 days lost) showed 40% of partial TL. TL injury incidence rate (6.6 injuries/1000 h, 95% CI 5.8-7.5), the number of severe injuries (16%), and the distribution of TL and non-TL injuries (56% and 44%) were comparable to other reports in elite youth footballers. Almost one-quarter of the TL injury burden showed that injured players were still included in some team football activities, which, for injuries with TL >7 days, was likely related to the return to play process. Therefore, reporting on partial TL provides insight into the true impact of injury on participation levels.

Adolescent elite-level footballers are exposed to unique physical and psychological stressors which may increase injury risk, with fluctuating injury prevalence and burden. This study investigates the patterns of injury incidence and burden from 2017 to 2020 within combined pre-, start-of-, mid- and end-of-season and school-holiday phases in U13-U18 Australian male academy players. Injury incidence rate and burden were calculated for medical attention (MA), full and partial time-loss (TL) and non-time-loss (non-TL) injuries. Injury rate ratios (IRR) for injury incidences were assessed using Generalised Linear Mixed Models, and 99% confidence intervals for injury burden differences between phases. MA and non-TL injury incidence rates were higher during pre-season (IRR 1.65, p  = 0.01; IRR 2.08, p  = 0.02, respectively), and mid-season showed a higher non-TL incidence rate (IRR 2.15, p  = 0.02) and burden (69 days with injury/1000 hrs, CI 47-103) compared to end-of-season (25 days with injury/1000 hrs, CI 15-45). MA injury rates and partial TL injury burden were higher during school compared to holiday periods (IRR 0.6, p  = 0.04; 61 partial days lost/1000 hrs, CI 35-104; 13 partial days lost/1000 hrs, CI 8-23). Season phase and return-to-school may increase injury risks for elite academy footballers, and considering these phases may assist in developing injury prevention systems.

Context: Concern is growing among soccer players, coaches, and parents regarding head and neck injuries, including concussion, particularly from heading a ball. Thus, we need to explore soccer-specific head injury risk-reduction initiatives. One such initiative is to condition the neck musculature of young players by adding neuromuscular neck exercises to existing injury-reduction exercise programs., Objective: To investigate the effect of neuromuscular neck exercises completed as part of an injury risk-reduction exercise program on the incidence of soccer-related head and neck injuries in adolescent soccer players., Design: Prospective cohort study., Setting: Two sports high schools and 6 soccer clubs during the 2021 soccer season., Patients or Other Participants: A total of 364 male and female soccer players, aged 12 to 18 years., Intervention(s): Members of 1 sports high school and 2 soccer clubs performed neuromuscular neck exercises as part of an injury-reduction program during training (neck training group). Members of another sports high school and 4 soccer clubs performed an injury-reduction program but without neck exercises (comparison group)., Main Outcome Measure(s): Self-reported injury data were collected from each player at the end of the season and used to calculate incidence rate ratios (IRRs) with 95% CIs., Results: In total, 364 players completed the study, including 146 players in the neck training group and 218 players in the comparison group. Despite players in the neck training group being less likely to self-report a concussion (IRR = 0.23; 95% CI = 0.03, 1.04) and pain on heading a ball (IRR = 0.62; 95% CI = 0.34, 1.07), only a lower incidence of possible concussive events (IRR = 0.38; 95% CI = 0.14, 0.90; P < .05) was significant., Conclusions: Integrating neuromuscular neck exercises into injury-reduction exercise programs has the potential to reduce the risk of adolescent soccer players sustaining a possible concussive event, concussion, or pain on heading a ball., (© by the National Athletic Trainers’ Association, Inc.)

Background: Although the 11+ is known to reduce injuries and improve performance in adolescent footballers, its duration presents a notable barrier to implementation. Hence, this study investigated injury and performance outcomes when 65 elite male academy footballers either performed Part 2 3x/week at training (TG) or at home (HG). Methods: Time to stabilisation (TTS), eccentric hamstring strength (EH-S) and countermovement jump height (CMJ-H) were collected 4 times during the 2019 football season. Linear mixed models were used to evaluate main and interaction effects of group and time. Bonferroni post-hoc tests were used to account for multiple comparisons. Differences in time loss and medical attention injuries were determined using a two-tailed Z test for a comparison of rates. Results: Relative to baseline, EH-S (HG 4.3 kg, 95% CI 3 to 5.7, p < 0.001; TG 5.5 kg, 95% CI 4.3 to 6.6, p < 0.001) and CMJ-H (HG 3.5 cm, 95% CI 2.2 to 4.7, p < 0.001; TG 3.2 cm, 95% CI 2.2 to 4.3, p < 0.001) increased, with no difference between groups observed at the end of the season. All injury outcomes were similar. Conclusion: Rescheduling Part 2 did not affect performance or increased injury risks in academy footballers.

Background: Impact of telemedicine with remote patient monitoring (RPM) in implantable cardioverter-defibrillator (ICD) patients on clinical outcomes has been investigated in various clinical settings with divergent results. However, role of RPM on patient-reported-outcomes (PRO) is unclear. The INFRARED-ICD trial aimed to investigate the effect of RPM in addition to standard-of-care on PRO in a mixed ICD patient cohort., Methods and Results: Patients were randomized to RPM (n = 92) or standard in-office-FU (n = 88) serving as control group (CTL). At baseline and on a monthly basis over 1 year, study participants completed the EQ-5D questionnaire for the primary outcome Quality of Life (QoL), the Hospital Anxiety and Depression Scale, and the Florida Patient Acceptance Survey questionnaire for secondary outcomes. Demographic characteristics (82% men, mean age 62.3 years) and PRO at baseline were not different between RPM and CTL. Primary outcome analysis showed that additional RPM was not superior to CTL with respect to QoL over 12 months [+ 1.2 vs. + 3.9 points in CTL and RPM group, respectively (p = 0.24)]. Pre-specified analyses could not identify subgroups with improved QoL by the use of RPM. Neither levels of anxiety (- 0.4 vs. - 0.3, p = 0.88), depression (+ 0.3 vs. ± 0.0, p = 0.38), nor device acceptance (+ 1.1 vs. + 1.6, p = 0.20) were influenced by additional use of RPM., Conclusion: The results of the present study show that PRO were not improved by RPM in addition to standard-of-care FU. Careful evaluation and planning of future trials in selected ICD patients are warranted before implementing RPM in routine practice.

Importance: Up to 80% of patients with head and neck cancer undergoing ablative surgery and neck dissection develop postoperative pain with detrimental effects on quality of life that also contributes to neuropathic and chronic postoperative pain., Objective: To investigate the association of continuous local anesthetic wound infusion with pain management after head and neck surgery., Design, Setting, and Participants: This prospective, longitudinal, nonrandomized clinical study carried out in a single tertiary referral center (December 1, 2015, to July 1, 2017) included 2 groups of 30 patients. Patients were consecutively enrolled and presented for ablative head and neck surgery including selective neck dissection and studied from the preoperative through the fourth postoperative day., Interventions: The control group was treated according to a standardized escalating oral treatment protocol (ibuprofen, metamizole, opioids). The intervention group was treated with an intraoperatively applied pain catheter (InfiltraLong plus FuserPump, Pajunk, ropivacaine, 0.2%, 3 mL/h) that was removed 72 hours after operating., Main Outcomes and Measures: Average and maximum pain intensities on a numeric rating scale; quality of life using the acute version of the validated 36-Item Short Form Survey; and neuropathic pain using the validated 12-Item painDETECT questionnaire. Consumption of opioid and nonopioid analgesics and evaluation of catheter-associated complications., Results: During postoperative days 1 through 4, patients of the intervention group (mean [SD] age, 63.2 [13.3 years; 9 [30%] women) experienced lower mean (SD) (1.6 [1.4] vs 2.7 [1.8]; η2p = 0.09 [0.01-0.21]) and maximum (2.4 [2.2] vs 4.2 [2.0]; η2p = 0.11 [0.01-0.24]) pain intensities compared with the control group (mean [SD] age, 62.5 [13.6] years; 5 [17%] women). The intervention group also reported less neuropathic pain (mean [SD], 5.4 [3.4] vs 7.6 [5.1]; η2p = 0.09 [0.004 - 0.22]) and higher quality of life regarding vitality (56.2 [21.5] vs 43.8 [20.9], r = 0.29; 95% CI, 0.01-0.52) and pain (66.8 [27.3] vs 49.5  [27.7], r = 0.31; 95% CI, 0.04-0.54). Patients from the intervention group requested nonopioid analgesics considerably less often (n = 17 [57% ]vs n = 29 [97%]; ϕ = 0.47; 95% CI, 0.30-0.67) associated with a noticeably lower need to escalate pain treatment (n = 3 [10%] vs n = 9 [30%]; mean [SD] ibuprofen dose: 500 [173] mg vs 1133 [650] mg; r = 0.64; 95% CI, 0.02-0.91). No catheter-associated complications were observed., Conclusions and Relevance: Continuous anesthetic wound infusion is associated with reduced postoperative pain and decreased demand for analgesics. It therefore expands the treatment options for postoperative pain in head and neck cancer., Trial Registration: German Clinical Trials Register: DRKS00009378.

Background: The appraisal of a stressor substantially influences how we adapt to it. We used an experimental paradigm to test and replicate the effects of threat appraisals on subsequent intrusive memories, as well as their moderation by neuroticism. Method : In three studies (total N  = 562), participants were randomly assigned to an aversive or control video and then asked to report their threat appraisals of the video. Intrusive memories were assessed at one, three, five, and seven days. We used a robust framework for testing causal mediational effects and their magnitude, including sensitivity analyses and new effect size metrics. Results: We found that threat appraisals mediated the effect of the video on intrusive memories (studies 1-3), and for people higher in neuroticism, the causal mediational pathway was stronger (study 1 and 2). Conclusions: These findings provide methodologically strong evidence that threat appraisals have causal effects on subsequent intrusive memories and that neuroticism enhances this effect, lending empirical support to appraisal theories of posttraumatic stress disorder.

Brown, GA, Veith, S, Sampson, JA, Whalan, M, and Fullagar, HHK. Influence of training schedules on objective measures of sleep in adolescent academy football players. J Strength Cond Res 34(9): 2515-2521, 2020-Football academy settings may pose risks to adolescent athletes achieving sufficient sleep because of the contextual challenges these players face (e.g., psychosocial pressure, changes in training, competition, and academic stress). Given the importance of sleep to overall health as well as physical athletic development and injury risk, this study aimed to investigate whether differences in training schedules (morning vs. evening training sessions) affected objective measures of sleep in adolescent academy football (soccer) players. Twelve academy players (mean age 14.18 ± 1.36 years) wore an ActiGraph accelerometer on nights before, and nights of, training days in 2 separate weeks where morning (09:00-11:00 hours) and evening (18:00-20:00 hours) training occurred. Objective sleep parameters and training load data were collected. Night-time sleep periods were categorized as sleep preceding morning training, preceding evening training, or after evening training. One-way univariate and multivariate analyses of variance for repeated measures were performed to determine the impact of the training schedule on sleep. Significance levels were set at p < 0.05. The total sleep time was below the recommended guidelines (<8 hours) across conditions. A large significant effect of the training schedule on time attempted to fall asleep (p = 0.004, effect size [ES] = 0.40) and time of sleep (p = 0.003, ES = 0.41) was present, with post-evening sessions resulting in the latest times. Overall, the players' sleep behavior was resilient to changes in training schedules. However, the low sleep durations (and potential risks to physical performance/injury) suggest that sleep education coupled with practical interventions are required in this cohort.

The prime function of nucleoli is ribogenesis, however, several other, non-canonical functions have recently been identified, including a role in genotoxic stress response. Upon DNA damage, numerous proteins shuttle dynamically between the nucleolus and the nucleoplasm, yet the underlying molecular mechanisms are incompletely understood. Here, we demonstrate that PARP1 and PARylation contribute to genotoxic stress-induced nucleolar-nucleoplasmic shuttling of key genome maintenance factors in HeLa cells. Our work revealed that the RECQ helicase, WRN, translocates from nucleoli to the nucleoplasm upon treatment with the oxidizing agent H 2 O 2 , the alkylating agent 2-chloroethyl ethyl sulfide (CEES), and the topoisomerase inhibitor camptothecin (CPT). We show that after treatment with H 2 O 2 and CEES, but not CPT, WRN translocation was dependent on PARP1 protein, yet independent of its enzymatic activity. In contrast, nucleolar-nucleoplasmic translocation of the base excision repair protein, XRCC1, was dependent on both PARP1 protein and its enzymatic activity. Furthermore, gossypol, which inhibits PARP1 activity by disruption of PARP1-protein interactions, abolishes nucleolar-nucleoplasmic shuttling of WRN, XRCC1 and PARP1, indicating the involvement of further upstream factors. In conclusion, this study highlights a prominent role of PARP1 in the DNA damage-induced nucleolar-nucleoplasmic shuttling of genome maintenance factors in HeLa cells in a toxicant and protein-specific manner.

The post-translational modification poly(ADP-ribosyl)ation (PARylation) plays key roles in genome maintenance and transcription. Both non-covalent poly(ADP-ribose) binding and covalent PARylation control protein functions, however, it is unknown how the two modes of modification crosstalk mechanistically. Employing the tumor suppressor p53 as a model substrate, this study provides detailed insights into the interplay between non-covalent and covalent PARylation and unravels its functional significance in the regulation of p53. We reveal that the multifunctional C-terminal domain (CTD) of p53 acts as the central hub in the PARylation-dependent regulation of p53. Specifically, p53 bound to auto-PARylated PARP1 via highly specific non-covalent PAR-CTD interaction, which conveyed target specificity for its covalent PARylation by PARP1. Strikingly, fusing the p53-CTD to a protein that is normally not PARylated, renders this a target for covalent PARylation as well. Functional studies revealed that the p53-PAR interaction had substantial implications on molecular and cellular levels. Thus, PAR significantly influenced the complex p53-DNA binding properties and controlled p53 functions, with major implications on the p53-dependent interactome, transcription, and replication-associated recombination. Remarkably, this mechanism potentially also applies to other PARylation targets, since a bioinformatics analysis revealed that CTD-like regions are highly enriched in the PARylated proteome., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure-function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\L713F mutant is constitutively active in cells. Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser-induced DNA damage, which can potentially be attributed to non-covalent PARP1-PAR interaction via several PAR binding motifs. Thirdly, both mutants had distinct functional consequences in cellular patho-physiology, i.e. PARP1\L713F expression triggered apoptosis, whereas PARP1\E988K reconstitution caused a DNA-damage-induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor treatment, indicating distinct cellular consequences of constitutive PARylation and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation (F304L\V762A) present in a patient with pediatric colorectal carcinoma exhibit altered biochemical and cellular properties, thereby potentially supporting human carcinogenesis. Together, we establish a novel cellular model for PARylation research, by revealing strong structure-function relationships of natural and artificial PARP1 variants., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: To retrospectively determine the effectiveness and accuracy of CT-guided percutaneous biopsy of malignant and inflammatory bone lesions of the spine and to assess the reliability of pre-biopsy CT and MRI. Materials and Methods: 214 patients with lesions of the spine, which were suspicious either for being malignant or inflammatory, underwent CT-guided biopsy for pathological and/or microbiological detection. Biopsy samples were sent for histological examination in 128/214 patients, for microbiological analysis in 17/214 patients and for both analyses in 69/214 patients. Retrospectively, the diagnostic accuracy and sensitivity/specificity of the pre-interventional imaging (CT and MRI) were determined. In addition, the influence of the biopsy on subsequent patient management was assessed. Results: The accuracy was 94.4 % for histopathological analysis and 97.7 % for microbiological analysis. In 25 % of cases the microbiological analysis revealed an underlying pathogen that was not significantly affected by pre-biopsy antibiotic therapy. The sensitivity/specificity of the pre-biopsy cross-sectional imaging concerning suspected malignancy was 69 %/78 %. For suspected infection, the sensitivity/specificity of pre-biopsy imaging was 81 %/44 %. In 52 % of all cases, the biopsy result changed subsequent patient management. Conclusion: Percutaneous CT-guided spine biopsy is a useful and reliable diagnostic procedure to establish a definitive diagnosis but with a relatively low yield of microorganisms in the case of infection. Key Points: • CT-guided spine biopsy is an accurate and reliable procedure in case of infection and tumour.• The results of the CT-guided spine biopsy have a significant influence on the subsequent patient management.• Pathogen recovery-rate in case of infection is moderate but not significantly affected by prebiopsy antibiotic therapy. Citation Format: • Rehm J, Veith S, Akbar M et al. CT-Guided Percutaneous Spine Biopsy in Suspected Infection or Malignancy: A Study of 214 Patients. Fortschr Röntgenstr 2016; 188: 1156 - 1162., (© Georg Thieme Verlag KG Stuttgart · New York.)