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• Using novel GWAS tools, we studied the genetic link between epilepsy and cognition. • General cognitive ability was estimated to be more polygenic than epilepsies. • We identified 66 epilepsy risk loci shared with general cognitive ability. • Of the 66 shared loci, 38 loci are novel epilepsy associations. • The study informs the shared genetic mechanisms between epilepsy and cognition. Cognitive impairment is prevalent among individuals with epilepsy, and increasing evidence indicates that genetic factors can underlie this relationship. However, the extent to which epilepsy subtypes differ in their genetic relationship with cognitive function, and information about the specific genetic variants involved remain largely unknown. We investigated the genetic relationship between epilepsies and general cognitive ability (COG) using complementary statistical tools, including linkage disequilibrium score (LDSC) regression, MiXeR and conjunctional false discovery rate (conjFDR). We analyzed genome-wide association study data on COG (n = 269,867) and common epilepsies (n = 27,559 cases, 42,436 controls), including the broad phenotypes 'all epilepsy', focal epilepsies and genetic generalized epilepsies (GGE), as well as specific subtypes. We functionally annotated the identified loci using several biological resources and validated the results in independent samples. Using MiXeR, COG (11.2k variants) was estimated to be almost four times more polygenic than 'all epilepsy', GGE, juvenile myoclonic epilepsy (JME), and childhood absence epilepsy (CAE) (2.5k – 2.9k variants). The other epilepsy phenotypes were insufficiently powered for MiXeR analysis. We quantified extensive genetic overlap between COG and epilepsy types, but with varying negative genetic correlations (-0.23 to -0.04). COG was estimated to share 2.9k variants with both GGE and 'all epilepsy', and 2.3k variants with both JME and CAE. Using conjFDR, we identified 66 distinct loci shared between COG and epilepsies, including novel associations for GGE (27), 'all epilepsy' (5), JME (5) and CAE (5). The implicated genes were significantly expressed in multiple brain regions. The results were validated in independent samples (COG: p = 3.62 × 10–7; 'all epilepsy': p = 2.58 × 10–3). Our study further dissects the substantial genetic basis shared between epilepsies and COG and identifies novel shared loci. An improved understanding of the genetic relationship between epilepsies and COG may lead to the development of novel comorbidity-targeted epilepsy treatments. [ABSTRACT FROM AUTHOR]

[Display omitted] Plant leaves have to deal with various environmental influences. While the mechanical properties of petiole and lamina are generally well studied, only few studies focused on the properties of the transition zone joining petiole and lamina. Especially in peltate leaves, characterised by the attachment of the petiole to the abaxial side of the lamina, the 3D leaf architecture imposes specific mechanical stresses on the petiole and petiole-lamina transition zone. Several principles of internal anatomical organisation have been identified. Since the mechanical characterisation of the transition zone by direct measurements is difficult, we explored the mechanical properties and load-bearing mechanisms by finite-element simulations. We simulate the petiole-lamina transition zone with five different fibre models that were abstracted from CT data. For comparison, three different load cases were defined and tested in the simulation. In the proposed model, the fibres are represented in a smeared sense, where we considered transverse isotropic behavior in elements containing fibres. In a pre-processing step, we determined the fibre content, direction, and dispersion and fed them into our model. The simulations show that initially, matrix and fibres carry the load together. After relaxation of the stresses in the matrix, the fibres carry most of the load. Load dissipation and stiffness differ according to fibre arrangement and depend, among other things, on orientation and cross-linking of the fibres and fibre amount. Even though the presented method is a simplified approach, it is able to show the different load-bearing capacities of the presented fibre arrangements. In plant leaves, the petiole-lamina transition zone is an important structural element facilitating water and nutrient transport, as well as load dissipation from the lamina into the petiole. Especially in peltate leaves, the 3D leaf architecture imposes specific mechanical stresses on the petiole-lamina transition zone. This study aims at investigating its mechanical behavior using finite-element simulations. The proposed continuum mechanical anisotropic viscoelastic material model is able to simulate the transition zone under different loads while also considering different fibre arrangements. The simulations highlight the load-bearing mechanisms of different fibre organisations, show the mechanical significance of the petiole-lamina transition zone and can be used in the design of a future biomimetic junction in construction. [ABSTRACT FROM AUTHOR]

Detecting ongoing inflammation in myocarditis patients has prognostic relevance, but there are limited data on the detection of chronic myocarditis and its differentiation from healed myocarditis. This study sought to assess the performance of cardiac magnetic resonance (CMR) for the detection of ongoing inflammation and the discrimination of chronic myocarditis from healed myocarditis. Consecutive patients with persistent symptoms (>30 days) suggestive of myocarditis were prospectively enrolled from a single tertiary center. All patients underwent a multiparametric 1.5-T CMR protocol including biventricular strain, T 1 /T 2 mapping, and late gadolinium enhancement (LGE). Endomyocardial biopsy was chosen for the reference standard diagnosis. Among 452 consecutive patients, 103 (median age: 50 years; 66 men) had evaluable CMR and cardiopathologic reference diagnosis: 53 (51%) with chronic lymphocytic myocarditis and 50 (49%) with healed myocarditis. T 2 mapping as a single parameter showed the best accuracy in detecting chronic myocarditis, if abnormal in ≥3 segments (92%; 95% CI: 85-97), and provided the best discrimination from healed myocarditis, as defined by the area under the receiver-operating characteristic curve (0.87 [95% CI: 0.79-0.93]; P < 0.001), followed by radial peak systolic strain rate of the left ventricle (0.86) and the right ventricle (0.84); T 1 mapping (0.64), extracellular volume fraction (0.62), and LGE (0.57). Specificity increased when T 2 mapping was combined with elevation of either troponin or C-reactive protein. A multiparametric CMR protocol allows detection of ongoing myocardial inflammation and discrimination of chronic myocarditis from healed myocarditis, with segmental T 2 mapping and biventricular strain analysis showing higher diagnostic accuracy compared with T 1 mapping, extracellular volume fraction, and LGE. The use of biomarkers (troponin or C-reactive protein) may improve specificity. [Display omitted] [ABSTRACT FROM AUTHOR]

To highlight the role of a novel synthetic electrospun fiber matrix in the treatment of high-risk wounds across a range of etiologies. This was a retrospective study of patients at a single institution who underwent complex wound care treatment with at least 1 application of the electrospun fiber matrix from January 2021 to December 2022. Information regarding patient demographics, wound size and etiologies, pertinent medical history, and treatment outcomes was collected. Twenty-one patients with 24 complex wounds who received synthetic electrospun fiber matrix treatment were identified. Nineteen patients (22 wounds) met the inclusion criteria for analysis. Patient mean age was 63.58 ± 15.20 (range 34–90) years. A wide range of wound etiologies was represented, including transmetatarsal amputation secondary to frostbite (n = 1), post-Mohs defect (n = 2), acute trauma (n = 3), surgical dehiscence (n = 3), infected implanted medical device (n = 2), chronic ulcers (n = 3), partial ray resection (n = 1), pilonidal cyst (n = 1), rattlesnake bite (n = 1), necrotizing soft-tissue infection (n = 1), and others (n = 2). A total of 17 of 19 (89.5%) patients were observed to meet their individual clinical goals after application of the wound matrix. Wound ages ranged from 1 to 429 days before initial synthetic electrospun fiber matrix application. The synthetic nature of the matrix limits the risk of inflammatory response and is well tolerated, which demonstrates initial proof of concept of synthetic electrospun fiber matrix treatment in a variety of complex wounds. The positive results observed across this mixed etiology surgical analysis should be replicated in future controlled, single-etiology studies to further confirm the utility of the electrospun fiber matrix in the surgical setting. [ABSTRACT FROM AUTHOR]

Due to high thermomechanical loads, metal cutting processes generally require cooling and lubrication solutions to minimize friction between tool and workpiece. Nowadays, the standard in industry is the application of mineral-oil-based coolants, which represent a significant share of the CO 2 -footprint in production systems in terms of their extraction, fabrication and disposal. The demand for ecological innovations pushes the manufacturing sector to apply sustainable and health compatible coolant alternatives based on renewable vegetable oils for safer work environments and greener production systems. In this work, both mineral-oil-based cooling lubricants and several water-miscible emulsions based on vegetable oils were prepared and tested regarding their suitability for milling tasks of aircraft stainless steels. Therefore, comprehensive tribological investigations were carried out to determine the friction conditions in the contact zone between the tool cutting edge and the workpiece. Additionally, extensive experimental investigations were carried out to measure the process forces and the resulting tool wear as technical performance indicators of the cooling lubricants during machining. The study shows the significant potential of bio-based cooling lubricants as high-performance alternatives to conventional cooling lubricants when milling aircraft stainless steels, regarding the improvement of the tribological system of machining processes and the work environment. [ABSTRACT FROM AUTHOR]

Violence was a feature of life aboard Royal Navy ships in the 18th century. However, the seemingly identical acts of violence on board had different logics and functions depending on the addressee. Based on the autobiographies of Black sailors and court records, this article traces these logics of violence and arguesthatthere was specific violence against Black sailors inthe Royal Navy. It is true that service at sea represented an opportunity for emancipation for Black sailors, as there was little institutional discrimination. At the same time, however, disciplinary and everyday violence among crew members proved to be highly racialised. For example, physical violence against Black crew members served as a means of humiliation, exclusion and emasculation, while for white crew members, fistfights were a responsetothe emasculating experience of shipboard conditions and became an essential element of maritime masculinity that strengthened social bonds. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a neuromuscular disease, causing progressive muscle weakness due to loss of lower motoneurons. Since 2017, three therapies, two modifying gene transcription and one adding the defective gene, have been approved with comparable efficacy on motor outcome. Data on cognitive outcomes of treated SMA type 1 patients is limited. The aim of this study was to evaluate cognitive function in symptomatic and presymptomatic SMA type 1 patients with two or three SMN2 copies who received SMN-modifying or gene-addition therapy in the first year of life. Cognitive testing was performed in 20 patients, including 19 symptomatic SMA type 1 patients with up to three SMN2 copies and 1 pre-symptomatically treated patient. Children were tested using Bayley Scales of Infant Development (BSID-III) at the age of 2 or 3 years or the Wechsler Preschool and Primary Scale of Intelligence (WPSII-IV) at the of age of 5 years. 11/20 patients showed subnormal cognitive development. Boys had significantly lower cognitive scores. Patients requiring assisted ventilation or feeding support were more likely to have cognitive deficits. Achieving more motor milestones was associated with a better cognitive outcome. Treated patients with SMA type 1 have heterogeneous cognitive function with 55 % of patients showing deficits. Risk factors for cognitive impairment in our cohort were male gender and need for assisted ventilation or feeding support. Therefore, cognitive assessment should be included in the standard of care to allow early identification of deficits and potential therapeutic interventions. • Data on cognitive function in SMA type 1 patients is limited. • 55 % of tested SMA patients showed cognitive impairment. • Boys scored significantly lower than girls. • Cognitive testing should be implemented in standard care of SMA patients. [ABSTRACT FROM AUTHOR]

There has been renewed interest in using mitochondrial uncoupler compounds such as niclosamide and carbonyl cyanide p‐(trifluoromethoxy)phenylhydrazone (FCCP) for the treatment of obesity, hepatosteatosis and diseases where oxidative stress plays a role. However, both FCCP and niclosamide have undesirable effects that are not due to mitochondrial uncoupling, such as inhibition of mitochondrial oxygen consumption by FCCP and induction of DNA damage by niclosamide. Through structure–activity analysis, we identified FCCP analogues that do not inhibit mitochondrial oxygen consumption but still provided good, although less potent, uncoupling activity. We also characterized the functional role of the niclosamide 4′‐nitro group, the phenolic hydroxy group and the anilide amino group in mediating uncoupling activity. Our structural investigations provide important information that will aid further drug development. [ABSTRACT FROM AUTHOR]

• The prevalence of high levels of posttraumatic stress symptoms is greatest 12 months after ICU admission. • Posttraumatic stress symptoms at 6 months were associated with ICU patient characteristics being males with longer hospital stay. • Posttraumatic stress symp 3, 6, and 12 months were associated with ICU patient characteristics being ≥ 70 years old, a lower educational level, a higher SAPS II score, and being mechanically ventilated in ICU. • Healthcare professionals can be aware that specific groups of patients may have different follow-up needs, implying that the follow-up period should exceed on year. Intensive care unit (ICU) patients are at risk of suffering from posttraumatic stress symptoms (PTSS) after ICU survival. To describe the prevalence of high levels of PTSS the first year after ICU admission. Further, to identify specific combinations of patient characteristics (latent classes based on pre-ICU data, demographics, and clinical characteristics), and to investigate possible associations among these classes and PTSS at 3, 6, and 12 months after ICU admission. Self-reported PTSS were measured with Impact of Event Scale-Revised (IES-R). PTSS and possible predictive factors (pre-ICU data, demographics, and clinical characteristics) were analyzed using descriptive statistics, latent class analysis, and linear mixed model for repeated measures. High PTSS levels (IES- R ≥ 33) were reported by 14.9 % (95 % confidence interval [CI] [10.0; 21.1]), 16.7 % (95 % CI [11.5; 23.1]), and 18.4 % (95 % CI [12.9; 25.0]) of patients (sample 1, n = 174) at 3, 6, and 12 months, respectively. Three latent classes were identified (sample 2, n = 417). PTSS were significantly associated with class 2 (male with longer hospital stay) at 6 months and class 3 (age≥70, lower level of education, higher Simplified Acute Physiology Score, being mechanically ventilated) at all three measurement times. The prevalence of high levels of PTSS is the greatest 12 months after ICU admission. Health professionals can use this information to be aware of specific groups of ICU patients reporting PTSS during the first year and follow up on these. [ABSTRACT FROM AUTHOR]

Pediatric regional anesthesia has been in existence for over 125 years, but significant progress and widespread use has occurred in the last few decades, with the increasing availability of ultrasound guidance. Evidence supporting the safety of regional anesthesia when performed under general anesthesia has also allowed the field to flourish. Newer techniques allow for more precise nerve blockade and in general this has resulted in more peripheral blocks replacing central blocks, such as caudal epidurals and spinal anesthesia. Current controversial topics in the field include the method of obtaining loss of resistance when placing epidural catheters, the role of regional anesthesia in compartment syndrome and post-hypospadias repair complications, and utility of test doses. [ABSTRACT FROM AUTHOR]

To describe the current organization and implementation of formalized, multi-disciplinary hospital-based antimicrobial stewardship (AMS) structures in Denmark, the Faroe Islands and Greenland. A structured electronic questionnaire was sent to all trainees and specialists in clinical microbiology (N =207) and infectious diseases (N =260), as well as clinical pharmacists (N =20) and paediatricians (N =10) with expertise in infectious diseases. The survey had 30 multiple-choice, rating-scale, and open-ended questions based on an international consensus checklist for hospital AMS, adapted to a Danish context. Overall, 145 individual responses representing 20 hospitals were received. Nine hospitals (45%) reported a formal AMS strategy, eight (40%) a formal organizational multi-disciplinary structure and a multi-disciplinary AMS team, and six (30%) a designated professional as a leader of the AMS team. A majority of hospitals reported access to updated guidelines (80%) and regularly monitored and reported the quantity of antibiotics prescribed (70% and 65%, respectively). Only one hospital (5%) reported a dedicated, sustainable and sufficient AMS budget, three hospitals (15%) audited courses of therapy for specific agents/clinical conditions and four hospitals (20%) had a document clearly defining roles, procedures of collaboration and responsibilities for AMS. A total of 42% of all individual respondents had received formal AMS training. Main barriers were a lack of financial resources (52%), a lack of mandate from the hospital management (30%) and AMS not being a priority (18%). Core elements important for multi-disciplinary hospital-based AMS can be strengthened in Danish hospitals. Funding, clear mandates, prioritization from the hospital management and the implementation of multi-disciplinary AMS structures may help close the identified gaps. [ABSTRACT FROM AUTHOR]

The purpose of this study is to assess the trends in operative management of geriatric (≥65 years) proximal humerus fractures during a 6-year period (2015-2020) within an insurance claims database. This retrospective database cohort study used data gathered from the 2015-2020 IBM Truven MarketScan Commercial and IBM Truven MarketScan Medicare Supplemental databases. The International Statistical Classification of Disease and Related Health Problems, Tenth Revision, data was correlated to the Current Procedural Terminology code for shoulder arthroplasty (proximal humeral prosthetic replacement: 23616, shoulder hemiarthroplasty [HA]: 23470, reverse total shoulder arthroplasty [rTSA]: 23472) or open reduction internal fixation (ORIF; open treatment of proximal humerus fracture with internal fixation: 23615, open treatment of proximal humerus fracture-dislocation with internal fixation: 23680). We investigated the number of proximal humerus fracture operative cases per year, percentage arthroplasty used per year, rTSA and HA per year, hospital cost information, as well as percentage arthroplasty per US geographic region. A total of 8057 operative proximal humerus fractures cases were identified in 7697 patients aged >65 years, with 0.45% (360 of 8057) being bilateral. There was a 40.8% decrease in the rate of operative management of proximal humerus fractures between the first half (2015-2017, 1687.3 ± 146.6) and the second half of the study period (2018-2020, 998.3 ± 258.7). Arthroplasty accounted for 78.7% of all surgeries, 91% of those being rTSA. The total number of cases of rTSA and ORIF performed decreased per year (P =.01). The downward trend of percentage ORIF per year approached significance (P =.054). Arthroplasty was a more expensive option of payment for total case by almost $850.00 (P =.001). There was a larger percentage of arthroplasty performed in the Northeast and North Central US geographic regions. Despite the rise of both the elderly population and related geriatric proximal humerus fractures, they were less operatively represented in this insurance claims database across the 6-year period. There may be a trend to use less ORIF when addressing these fractures. Although it incurred a higher in-hospital cost, arthroplasty was being performed at a higher percentage in the Northeast and North Central regions of the United States. [ABSTRACT FROM AUTHOR]

Chronic oral mucosal diseases (COMDs) represent a significant challenge for clinicians and patients. They are commonly associated with chronic pain and negative effects on healing and patient's quality of life. Regenerative medicine including the use of biological autologous blood-derived substances (e.g., platelet concentrates [PCs]), has been reported to improve healing and reduce pain in orthopedic and maxillofacial surgeries as well as chronic oral mucosal diseases. In this review, we aim to describe the different types of PCs and their applications in the management of COMDs such as lichen planus, mucositis, pemphigus vulgaris, mucous membrane pemphigoid, and plasma cell mucositis, in terms of healing potential, pain control, and quality of life. Overall, PC applications seem to enhance healing and reduce pain in patients with COMDs. However, due to the small sample size and the lack of standardized clinical trials, further research is required to support these findings. [Display omitted] [ABSTRACT FROM AUTHOR]

Women with symptomatic pelvic organ prolapse are offered a choice of conservative and surgical treatment options. Two thirds of women choose a vaginal pessary, a support device inserted in the vagina. This article reports the finding of a randomized controlled trial published in 2023 evaluating the cost-effectiveness of self-management of pessary compared to clinic-based care. Women were recruited in 21 centres across the UK and 340 women were randomized to pessary self-management or clinic-based care. The primary outcome measure was prolapse-specific quality of life and secondary outcomes were generic quality of life, pelvic floor symptoms, sexual function, self-efficacy, pessary complications, pessary use and pessary confidence. Participants' health care resource use was measured. The trial showed that at 18 month follow-up self-management was not associated with better or worse quality of life than clinic-based care. Women in the self-management group reported fewer pessary complications and lower healthcare resource use. [ABSTRACT FROM AUTHOR]