Explore the vast range of titles available.

Gut microbial production of trimethylamine (TMA) from l-carnitine is directly linked to cardiovascular disease. TMA formation is facilitated by carnitine monooxygenase, which was proposed as a target for the development of new cardioprotective compounds. Therefore, the molecular understanding of the two-component Rieske-type enzyme from Escherichia coli was intended. The redox cofactors of the reductase YeaX (FMN, plant-type [2Fe-2S] cluster) and of the oxygenase YeaW (Rieske-type [2Fe-2S] and mononuclear [Fe] center) were identified. Compounds meldonium and the garlic-derived molecule allicin were recently shown to suppress microbiota-dependent TMA formation. Based on two independent carnitine monooxygenase activity assays, enzyme inhibition by meldonium or allicin was demonstrated. Subsequently, the molecular interplay of the reductase YeaX and the oxygenase YeaW was addressed. Chimeric carnitine monooxygenase activity was efficiently reconstituted by combining YeaX (or YeaW) with the orthologous oxygenase CntA (or reductase CntB) from Acinetobacter baumannii. Partial conservation of the reductase/oxygenase docking interface was concluded. A structure guided mutagenesis approach was used to further investigate the interaction and electron transfer between YeaX and YeaW. Based on AlphaFold structure predictions, a total of 28 site-directed variants of YeaX and YeaW were kinetically analyzed. Functional relevance of YeaX residues Arg271, Lys313 and Asp320 was concluded. Concerning YeaW, a docking surface centered around residues Arg83, Lys104 and Lys117 was hypothesized. The presented results might contribute to the development of TMA-lowering strategies that could reduce the risk for cardiovascular disease.

Background Despite being a common overuse entity in youth soccer, scientific data on risk factors, rehabilitation and return to play for long-standing pubic-related groin pain is still rare. The current prospective cohort study aims to evaluate potential risk-factors, propose a criteria-based conservative rehabilitation protocol and assess return-to-play outcomes among professional youth soccer players suffering from long-standing pubic-related groin pain. Methods Male soccer players with long-standing (> 6 weeks) pubic-related groin pain from a professional soccer club’s youth academy were analyzed for possible risk factors such as age, team (U12 - U23), younger/older age group within the team, position and preinjury Functional movement score. All injured players received a conservative, standardized, supervised, criteria-based, 6-level rehabilitation program. Outcome measures included time to return to play, recurrent groin pain in the follow-up period and clinical results at final follow-up two years after their return to play. Results A total of 14 out of 189 players developed long-standing pubic-related groin pain in the 2017/2018 season (incidence 7.4%). The average age of the players at the time of the injury was 16.1 ± 1.9 years. Risk factor analysis revealed a significant influence of the age group within the team ( p  = .007). Only players in the younger age group were affected by long-standing pubic-related groin pain, mainly in the first part of the season. Injured players successfully returned to play after an average period of 135.3 ± 83.9 days. Only one player experienced a recurrence of nonspecific symptoms (7.1%) within the follow-up period. The outcome at the 24-month follow-up was excellent for all 14 players. Conclusions Long-standing pubic-related groin pain is an overuse entity with a markedly high prevalence in youth soccer players, resulting in a relevant loss of time in training and match play. In particular, the youngest players in each team are at an elevated risk. Applying a criteria-based rehabilitation protocol resulted in an excellent return-to-play rate, with a very low probability of recurrence. Trial registration The trial was retrospectively registered under DRKS00016510 in the German Clinical Trials Register on 19.04.2021.

Background Patients suffering cartilage defects of the medial compartment with underlying varus deformity do benefit from high tibial osteotomy (HTO) even in the long term. Nonetheless, kinematic and geometric changes especially in the patellofemoral joint have been described. Purpose of the present study was to evaluate the influence of patellofemoral cartilage defects detected during the diagnostic arthroscopy and their influence on HTO’s postoperative outcome. Methods Ninety patients with a mean follow-up of 10.08 ± 2.33 years after surgery were included. Patients were divided into four groups according to their cartilage status in the patellofemoral joint (A = no defects, B = isolated lesions of the patella, C = isolated lesions of the trochlea, D = kissing lesions). Functional outcome was evaluated before surgery and about ten years thereafter by relying on the IKDC, Lysholm, and KOOS scores. Radiological parameters were assessed pre- and six weeks postoperatively. Results In groups A to D, the HTO led to significant patellar distalisation in the sagittal view, with the mean indices remaining at or above the limit to a patella baja. All patients in all groups profited significantly from HTO (higher Lysholm score, lower VAS p  < 0.001), patients in group D had the lowest outcome scores. Patella height negatively influenced outcome scores in group C (Blackburne-Peel-Index—VAS p  = 0.033) and D (Caton-Deschamps-Index—Tegner p  = 0.018), a larger valgus correction was associated with lower outcome scores in group D (Lysholm p  = 0.044, KOOSpain 0.028, KOOSQOL p  = 0.004). Conclusion Long-term results of HTO for varus medial compartment osteoarthritis remain good to excellent even in the presence of patellofemoral defects. Overcorrection should be avoided. Distal biplanar HTO should be considered for patients presenting trochlear or kissing lesions of the patellofemoral joint. Trial registration DRKS00015733 in the German Registry of Clinical Studies.

Background Tranexamic acid is an established drug in the treatment of bleeding trauma patients. Concerns have been raised over possible complications of tranexamic acid regarding thromboembolic events as serious complications during the treatment of severely injured patients. Methods In our study we retrospectively analyzed data from 2015—2019 of multiply injured patients receiving tranexamic acid during distinguished treatment periods from the TraumaRegister DGU®. We statistically analyzed overall thromboembolic complications during hospital stay in the context of number of single-dose tranexamic acid administrations. Results We report on 37,342 patients, of whom 1,151 (3.1%) suffered from thromboembolic events. Patients without tranexamic acid treatment suffered from thromboembolic events in 2.3%, prehospital and emergency department administration increased the incidence to 4.8% and 5.2%, respectively. Administering tranexamic acid twice or three times was associated with an increased incidence of 8.5% and 8.2%, respectively. In a multivariate logistic regression, we uniquely show an independently associated risk for thromboembolic complications with every consecutive administration of tranexamic acid (one application: odds ratio (OR) 1.56, p  < 0.001; two applications: OR 1.79, p  < 0.001; three applications: OR 1.50, p  = 0.113). Conclusions In our study we report on an associated risk of thromboembolic events in multiply injured patients with every single time tranexamic acid was administered in our study. Thus, before a repetitive dose of tranexamic acid is administered checking for indication is advised and especially in multiply injured patients receiving repeated administrations of TXA starting a thromboprophylaxis, as soon as possible after the traumatic bleeding disorder is controlled, is important.

Background Hemispatial neglect results from unilateral brain damage and represents a disabling unawareness for objects in the hemispace opposite the brain lesion (contralesional). The patients’ attentional bias for ipsilesional hemispace represents a hallmark of neglect, which results from an imbalanced attentional priority map in the brain. The aim of this study was to investigate whether gaze-contingent display (GCD) technology, reducing the visual salience of objects in ipsilesional hemispace, is able to rebalance this map and increase awareness and exploration of objects in the neglected contralesional hemispace. Methods Using remote eye-tracking, we recorded gaze positions in 19 patients with left hemispatial neglect following right-hemisphere stroke and 22 healthy control subjects, while they were watching static naturalistic scenes. There were two task conditions, free viewing (FV) or goal-directed visual search (VS), and four modification conditions including the unmodified original picture, a purely static modification and two differently strong modifications with an additional gaze-contingent mask (GC-LOW, GC-HIGH), that continuously reduced color saturation and contrast of objects in the right hemispace. Results The patients’ median gaze position (Center of Fixation) in the original pictures was markedly deviated to the right in both tasks (FV: 6.8° ± 0.8; VS: 5.5° ± 0.7), reflecting the neglect-typical ipsilesional attention bias. GC modification significantly reduced this bias in FV (GC-HIGH: d = − 3.2 ± 0.4°; p < 0.001). Furthermore, in FV and VS, GC modification increased the likelihood to start visual exploration in the (neglected) left hemifield by about 20%. This alleviation of the ipsilesional fixation bias was not associated with an improvement in detecting left-side targets, in contrast, the GC mask even decreased and slowed the detection of right-side targets. Subjectively, patients found the intervention pleasant and most of the patients did not notice any modification. Conclusions GCD technology can be used to positively influence visual exploration patterns in patients with hemispatial neglect. Despite an alleviation of the neglect-related ipsilesional fixation bias, a concomitant functional benefit (improved detection of contralesional targets) was not achieved. Future studies may investigate individualized GCD-based modifications as augmented reality applications during the activities of daily living.

Background Severe thoracic trauma in children is rare and often underestimated. While standardized protocols exist, the rarity of polytrauma in children may lead to uncertainties in their application. Thus, we aim to characterize severely injured children with significant thoracic trauma and identify age-dependent differences in prehospital and early clinical management. Methods Patients documented by German hospitals between 2008 and 2023 in the TraumaRegister DGU ® , aged ≤ 20 years and sustaining at least serious chest injury (AIS Thorax ≥ 3) were analyzed. Patients were grouped by age: 0–5 years, 6–12 years and 13–16 years and statistically compared; additional data from patients aged 17–20 years is provided. Demographic, clinical characteristics and treatment comparing the aforementioned groups were evaluated using descriptive statistics. In the group of 0–16 years old independent risk factors for mortality were scrutinized applying multiple logistic regression analysis. Results A total of 5,040 severely injured patients were analyzed (310 patients aged 0–5 years, 475 aged 6–12 years, 984 aged 13–16 years and 3,271 in group 17–20 years). With increasing age, significantly more males were injured and mechanism of injury was significantly different between the age groups. During prehospital management significant age dependent differences were seen regarding helicopter emergency medical service treatment, intubation, chest tube placement, application of catecholamines or tranexamic acid. Significant differences were found in terms of injured body regions, where the youngest suffered most from leading thoracic injury and injury to the head while abdominal injury and injury to extremities happened significantly more often in the 13–16 years old. During treatment the 13–16 years old received more blood products, were more likely to undergo thoracic surgery and stayed longer on the respective wards. Multivariate logistic regression showed an independent association with a significant mortality risk for MAIS ≥ 4 (OR = 2.87; p  = 0.03), polytrauma (OR = 3.09; p  < 0.001) and the need for blood transfusion before admission to the intensive care unit (OR = 2.46; p  < 0.001). Conclusions Treating severely injured children is always challenging, even more so when they have suffered critical trauma to the chest. With our results we offer starting points for age-dependent injury prevention and provide information to analyze and question current (pre-) hospital management protocols.

Thoracic trauma has decisive influence on the outcome of multiply-injured patients and is often associated with clavicle fractures. The affected patients are prone to lung dysfunction and multiple organ failure. A multi-center, retrospective analysis of patient records documented in the TraumaRegister DGU was performed to assess the influence of surgical stabilization of clavicle fractures in patients with thoracic trauma. A total of 3,209 patients were included in the analysis. In 1362 patients (42%) the clavicle fracture was treated operatively after 7.1 ± 5.3 days. Surgically treated patients had a significant reduction in lung failure (p = 0.013, OR = 0.74), multiple organ failure (p = 0.001, OR = 0.64), intubation time (p = 0.004; −1.81 days) and length of hospital stay (p = 0.014; −1.51 days) compared to non-operative treatment. Moreover, surgical fixation of the clavicle within five days following hospital admission significantly reduced the rates of lung failure (p = 0.01, OR = 0.62), multiple organ failure (p = 0.01, OR = 0.59) and length of hospital stay (p = 0.01; −2.1 days). Based on our results, multiply-injured patients with thoracic trauma and concomitant clavicle fracture may benefit significantly from surgical stabilization of a clavicle fracture, especially when surgery is performed within the first five days after hospital admission.

The 2010s were perhaps the most tumultuous decade since the 1960s. The effects of the Great Recession continued to be felt. The administration of Barack Obama, the first African-American president, encouraged many to think that America was now 'post-racial', an illusion broken by the election of Donald Trump. Polarisation reigned, communicated on social media. Netflix and Amazon jumped into production. By 2019, Netflix produced more feature films than the traditional studios combined. Cinema's move from film to digital, in production and in exhibition, was complete by mid-decade. `MeToo and `Oscarssowhite signaled a reckoning with gross gender and racial inequalities in the media, matched by that in the wider culture. The essays of this book explore the blockbusters, low-budget sleepers, and films in between.

This paper offers a historical inquiry into industry worries about incredulous viewers, prompted by the persistence of claims by prominent contemporary film industry figures that computer-generated imagery (CGI) is intrinsically detrimental to cinematic realism and is eroding viewer immersion in screen fiction. Examining a range of fan and trade magazines from the 1910s and 1920s, I find evidence of an earlier anxiety in the film industry about incredulous viewers. This anxiety, however, was blamed not on the intrinsic unreality of cinematic tricks but a broader film culture, including fake actuality films and journalistic revelations of filmmaking secrets. I show that the industry made a concerted effort to manage such viewership by cultivating uncertainty about the reality or artifice of what appeared on the screen. Finally, moving back to the present, I argue that CGI is not inherently less real. Rather, a broader viewing culture of incredulity has reemerged due to a combination of production publicity, cult viewing of bad cinema, online forums, editorial photoshopping, and image hoaxes.