Neural mechanisms of emotional health in traumatic brain injury patients undergoing rTMS treatment.

Emotional dysregulation such as that seen in depression, are a long-term consequence of mild traumatic brain injury (TBI), that can be improved by using neuromodulation treatments such as repetitive transcranial magnetic stimulation (rTMS). Previous studies provide insights into the changes in functional connectivity related to general emotional health after the application of rTMS procedures in patients with TBI. However, these studies provide little understanding of the underlying neuronal mechanisms that drive the improvement of the emotional health in these patients. The current study focuses on inferring the effective (causal) connectivity changes and their association with emotional health, after rTMS treatment of cognitive problems in TBI patients (N = 32). Specifically, we used resting state functional magnetic resonance imaging (fMRI) together with spectral dynamic causal model (spDCM) to investigate changes in brain effective connectivity, before and after the application of high frequency (10 Hz) rTMS over left dorsolateral prefrontal cortex. We investigated the effective connectivity of the cortico-limbic network comprised of 11 regions of interest (ROIs) which are part of the default mode, salience, and executive control networks, known to be implicated in emotional processing. The results indicate that overall, among extrinsic connections, the strength of excitatory connections decreased while that of inhibitory connections increased after the neuromodulation. The cardinal region in the analysis was dorsal anterior cingulate cortex (dACC) which is considered to be the most influenced during emotional health disorders. Our findings implicate the altered connectivity of dACC with left anterior insula and medial prefrontal cortex, after the application of rTMS, as a potential neural mechanism underlying improvement of emotional health. Our investigation highlights the importance of these brain regions as treatment targets in emotional processing in TBI.

Assessment of rare bleeding disorders in adolescents with heavy menstrual bleeding.

INTRODUCTION: There are a significant number of patients with mucocutaneous bleeding, specifically heavy menstrual bleeding (HMB), who do not have a diagnosed bleeding disorder. These patients receive nontargeted interventions and may have suboptimal treatments. Functional assays, particularly for fibrinolytic and rare platelet function defects, are not robust and not readily available. AIM: We aimed to prospectively evaluate the prevalence of genetic defects associated with rare bleeding disorders and describe alterations of coagulation and fibrinolysis in a cohort of adolescents with HMB. METHODS: We performed a prospective observational cohort study of patients with HMB and unexplained bleeding. The study utilized a next generation sequencing panel and investigational global assays of coagulation and fibrinolysis. Additionally, specific functional assays were performed to help characterize novel variants that were identified. RESULTS: In 10 of the 17 patients (∼59%), genetic variants were identified on molecular testing. Thrombin generation by calibrated thromboelastography was not significantly altered in this patient population. The clot formation and lysis assay showed a trend towards increased fibrinolysis with rapid phase of decline in 23% of the patients. Further corresponding functional assays and study population are described. CONCLUSION: Our study describes a unique correlative model in a homogenous cohort of patients with HMB and unexplained bleeding which may inform future diagnostic algorithms, genotype-phenotype correlations as well as aid in specific targeted treatment approaches. Larger future studies may inform risk stratification of patients and improve health related outcomes in patients with HMB.

Dynamic source credibility and its impacts on knowledge revision.

Corrections to readers' misconceptions should result in higher belief when information sources are of high credibility. However, evaluations of credibility may be malleable, and we do not yet fully understand how changes to a source's credibility influence readers' credibility evaluations and knowledge revision outcomes. Thus, in two experiments, we examined how updating a source's credibility (Experiment 1: initially neutral sources later updated to be high-, low-, or neutral-credibility sources; Experiment 2: initially high- or low-credibility sources later updated to be low- or high-credibility sources) influenced knowledge revision and source credibility evaluations after readers engaged with refutation and non-refutation texts. Results showed that readers revised their credibility judgments from neutral-, high-, and low-credibility initial evaluations, indicating that source judgments are malleable rather than fixed. In addition, refutations from sources that are later revealed to be of high credibility can facilitate revision of both knowledge and initial source credibility evaluations.

Modeling links softening of myelin and spectrin scaffolds of axons after a concussion to increased vulnerability to repeated injuries.

Damage to the microtubule lattice, which serves as a rigid cytoskeletal backbone for the axon, is a hallmark mechanical initiator of pathophysiology after concussion. Understanding the mechanical stress transfer from the brain tissue to the axonal cytoskeleton is essential to determine the microtubule lattice's vulnerability to mechanical injury. Here, we develop an ultrastructural model of the axon's cytoskeletal architecture to identify the components involved in the dynamic load transfer during injury. Corroborative in vivo studies were performed using a gyrencephalic swine model of concussion via single and repetitive head rotational acceleration. Computational analysis of the load transfer mechanism demonstrates that the myelin sheath and the actin/spectrin cortex play a significant role in effectively shielding the microtubules from tissue stress. We derive failure maps in the space spanned by tissue stress and stress rate to identify physiological conditions in which the microtubule lattice can rupture. We establish that a softer axonal cortex leads to a higher susceptibility of the microtubules to failure. Immunohistochemical examination of tissue from the swine model of single and repetitive concussion confirms the presence of postinjury spectrin degradation, with more extensive pathology observed following repetitive injury. Because the degradation of myelin and spectrin occurs over weeks following the first injury, we show that softening of the myelin layer and axonal cortex exposes the microtubules to higher stress during repeated incidences of traumatic brain injuries. Our predictions explain how mechanical injury predisposes axons to exacerbated responses to repeated injuries, as observed in vitro and in vivo.

The oncogenic transcription factor FUS-CHOP can undergo nuclear liquid-liquid phase separation.

Myxoid liposarcoma is caused by a chromosomal translocation resulting in a fusion protein comprised of the N terminus of FUS (fused in sarcoma) and the full-length transcription factor CHOP (CCAAT/enhancer-binding protein homologous protein, also known as DDIT3). FUS functions in RNA metabolism, and CHOP is a stress-induced transcription factor. The FUS-CHOP fusion protein causes unique gene expression and oncogenic transformation. Although it is clear that the FUS segment is required for oncogenic transformation, the mechanism of FUS-CHOP-induced transcriptional activation is unknown. Recently, some transcription factors and super enhancers have been proposed to undergo liquid-liquid phase separation and form membraneless compartments that recruit transcription machinery to gene promoters. Since phase separation of FUS depends on its N terminus, transcriptional activation by FUS-CHOP could result from the N terminus driving nuclear phase transitions. Here, we characterized FUS-CHOP in cells and in vitro, and observed novel phase-separating properties relative to unmodified CHOP. Our data indicate that FUS-CHOP forms phase-separated condensates that colocalize with BRD4, a marker of super enhancer condensates. We provide evidence that the FUS-CHOP phase transition is a novel oncogenic mechanism and potential therapeutic target for myxoid liposarcoma. This article has an associated First Person interview with the first author of the paper.

Electroanatomic visualization of coronary arteries: a case series to elicit safety, feasibility, and diagnostic value in complex ablation procedures.

AIMS: The goal of this case series was to evaluate the feasibility, safety, and advantages of a wire-based approach for the live visualization of coronary arteries (CAs) in an electroanatomic mapping (EAM) system and to assess its diagnostic information. METHODS AND RESULTS: For this single-centre case series, we included procedures in which close proximity of a possible ablation site to any epicardial vessel was suspected. An uncoated-tip guidewire was introduced into the relevant CAs after exclusion of critical CA stenosis by coronary angiography. By connecting this wire to the EAM system using a clip and pin connection, mapping and live visualization of the wire tip is possible, as well as the assessment of the local electrograms within the respective CAs. Procedural wire insertion and intracoronary mapping was performed by EP specialists and was assisted to judge the relevance of CA disease by an interventional cardiologist. A total of nine procedures in nine patients were included in this case series, four ventricular tachycardia ablation procedures and five procedures for the ablation of premature ventricular contractions. The left CAs were mapped in eight cases and the right CA was mapped in one case. In two cases, epicardial mapping was combined with visualization of the right or left CAs. There were no complications attributed to coronary wiring and mapping in this case. CONCLUSION: We demonstrated the feasibility and safety of CA visualization and integration in an EAM. The live visualization of the CAs added valuable information without the need for preprocedural planning or the purchase of separate software. Electroanatomic visualization was achieved intraprocedurally in a safe and straightforward manner, adding critical diagnostic information without excessive costs or risks.

Examining the Relationship Between Sleep Apnea Diagnosis and Suicide Risk in Veterans With Traumatic Brain Injury: A VA TBI Model Systems Study.

OBJECTIVE: Obstructive sleep apnea (OSA) is a common sleep disorder in people with traumatic brain injury (TBI). Although sleep disturbances have been associated with an increased risk of suicide compared with the general population, the relationship between OSA and suicide risk after TBI is not well documented. In this study, we hypothesized that OSA diagnosis would predict suicide risk in veterans with TBI. SETTING: Five Veterans Affairs (VA) Polytrauma Rehabilitation Centers. PARTICIPANTS: Participants were drawn from the VA TBI Model Systems study, with follow-up interviews at year 1 ( n = 392), year 2 ( n = 444), year 5 ( n = 498), or year 10 ( n = 252) post-TBI (7.8%-14.5% follow-up attrition). DESIGN: This was a retrospective analysis from observational data using logistic regression with repeated measurements. Suicide ideation and suicide attempts were examined as outcomes at each follow-up to evaluate the relationship between OSA and suicide risk after adjusting for other risk factors determined a priori via literature review. MAIN MEASURES: Suicidal ideation (Patient Health Questionnaire-9 item 9), suicide attempt during the past year (self-reported), and OSA diagnosis (self-reported). RESULTS: Contrary to study hypotheses, OSA diagnosis had no statistically significant association with suicide ideation or attempt after accounting for known predictors. However, greater depression symptoms, headache severity, and pre-TBI suicidal ideation and attempts predicted suicide risk at follow-up after accounting for other predictors. CONCLUSIONS: Results of this study did not support a relationship between OSA and suicide risk, possibly due to methodological limitations of OSA measurement. Future research on this topic should include objective measures of OSA severity and OSA treatment including adherence. Although suicide is a low base rate occurrence, the impact is disastrous and further research is needed to mitigate suicide risk.

[Arrhythmias : Update on ablations and devices]. / Rhythmusstörungen : Update Ablationen und Devices.

The field of invasive electrophysiology is technically evolving and especially the catheter ablation treatment of symptomatic atrial fibrillation (AF). The technically innovative method of so-called electroporation (pulsed field ablation, PFA) is characterized by a rapid and effective treatment of AF. The current study data confirm a high success rate for ablation and a good safety profile in the treatment of paroxysmal and persistent AF. In the field of radiofrequency ablation (RF) of AF the modified form of energy transfer, the very high-power short-duration (vHPSD) protocols, show good results and can reduce the procedural time. There are also technical innovations in other single-shot devices. There is a device based on the RF technique that could show good clinical results in an initial study and can combine the targeted delivery of RF energy with the advantages of a single-shot device. For ventricular tachycardia (VT) there are innovations in the diagnostics and clarification in the new European guidelines that were presented in August 2022. These make individual recommendations for different types of cardiomyopathy. There are also technical developments in the field of active rhythm implants. In cardiac pacemaker treatment and specifically for conduction system pacing (CSP) there is evidence for a targeted stimulation of the bundle of His or left bundle branch pacing (LBBP). This form of stimulation is particularly advantageous for patients with heart failure and a broad QRS complex. For leadless pacemakers (leadless pacing) there are now good long-term results and also a two-chamber approach.

Coparenting support in the context of difficult children: Mother and father differences.

While parenting children with difficult behaviors can intensify stress within the entire family system, families may lean on other familial relationships to mitigate that stress. The coparenting relationship is known to play a key role within the family system for child outcomes and familial interactions, but it is not clear whether it eases the stress and challenge of raising a difficult child, nor how that plays out differently for mothers versus fathers. Ninety-six couples (89.7% married) parenting young children (Mean age = 3.22 years) were included in this study. Using cross-sectional and aggregated daily response data, actor-partner interdependence models were used to examine how mothers' and fathers' perceived coparenting support lessened or intensified parenting stress and/or daily problems with their child/children-for themselves or their parenting partner. We found that greater coparenting support reported by mothers coincided with stronger links between the mother's report of child difficulty and daily problems encountered by both mothers and fathers. In contrast, when fathers reported greater coparenting support, the intensity between reported child difficulty and daily problems decreased for mothers, and fathers reported lower parenting stress. Coparenting support also moderated associations between parents' perception of child difficulty and daily problems with their children. These results suggest that mothers incur heightened coparenting support from fathers when experiencing more difficult child behavior and that coparenting support experienced by fathers may alleviate parenting challenges for mothers. These findings further contribute to the literature by emphasizing distinct differences between mothers and fathers in coparenting associations within the family system.

Concussion leads to widespread axonal sodium channel loss and disruption of the node of Ranvier.

Despite being a major health concern, little is known about the pathophysiological changes that underly concussion. Nonetheless, emerging evidence suggests that selective damage to white matter axons, or diffuse axonal injury (DAI), disrupts brain network connectivity and function. While voltage-gated sodium channels (NaChs) and their anchoring proteins at the nodes of Ranvier (NOR) on axons are key elements of the brain's network signaling machinery, changes in their integrity have not been studied in context with DAI. Here, we utilized a clinically relevant swine model of concussion that induces evolving axonal pathology, demonstrated by accumulation of amyloid precursor protein (APP) across the white matter. Over a two-week follow-up post-concussion with this model, we found widespread loss of NaCh isoform 1.6 (Nav1.6), progressive increases in NOR length, the appearance of void and heminodes and loss of ßIV-spectrin, ankyrin G, and neurofascin 186 or their collective diffusion into the paranode. Notably, these changes were in close proximity, yet distinct from APP-immunoreactive swollen axonal profiles, potentially representing a unique, newfound phenotype of axonal pathology in DAI. Since concussion in humans is non-fatal, the clinical relevance of these findings was determined through examination of post-mortem brain tissue from humans with higher levels of acute traumatic brain injury. Here, a similar loss of Nav1.6 and changes in NOR structures in brain white matter were observed as found in the swine model of concussion. Collectively, this widespread and progressive disruption of NaChs and NOR appears to be a form of sodium channelopathy, which may represent an important substrate underlying brain network dysfunction after concussion.

Guideline for Children With Cancer Receiving General Anesthesia for Procedures and Imaging.

Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia. Due to limited literature available, this panel created an expert consensus guideline addressing anesthesia preparation for this population.

Screening for von Willebrand disease does not impact posttonsillectomy bleeding in a low-risk population.

BACKGROUND: Bleeding is an important complication in children following tonsillectomy. Screening with coagulation tests prior to procedure is common to assess bleeding risk in the perioperative period, although ASH/ASPHO Choosing Wisely guidelines recommend against routine PT/PTT testing. Our aim was to compare von Willebrand factor antigen (VWF:Ag) and activity levels among patients with postoperative bleeding following tonsillectomy to evaluate for potential risk for bleeding. PROCEDURE: Eligible subjects were aged 0-18 without significant personal or family history of major bleeding. Postoperative bleeding diaries were collected and symptoms measured using a postoperative bleeding score. Plasma VWF levels were drawn at time of anesthesia administration. RESULTS: Postoperative bleeding occurred in 248 cases out of 1399 total subjects. Median VWF:Ag was 86 in patients with postoperative bleeding scores of 1-2, 86 for scores 3-4, 84 for scores 5-6, and 83 for scores >6, with no significant difference among groups (p = .98). Additionally, no difference was observed for subjects with multiple days of postoperative bleeding as compared to those with only 1 day of postoperative bleeding. Finally, no difference in VWF:Ag was observed for subjects whose first reported bleed occurred early in the postoperative course compared to those whose first reported bleed occurred later. VWF:Ag does not correlate with severity of bleeding, time of onset of first bleeding event, or recurrence of bleeding in healthy children with no personal or family history of bleeding who have postoperative bleeding following tonsillectomy. CONCLUSIONS: This data does not support routine von Willebrand disease screening prior to tonsillectomy.

Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer's disease.

Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease, including chronic traumatic encephalopathy (CTE). Preliminary consensus criteria define the pathognomonic lesion of CTE as patchy tau pathology within neurons and astrocytes at the depths of cortical sulci. However, the specific tau isoform composition and post-translational modifications in CTE remain largely unexplored. Using immunohistochemistry, we performed tau phenotyping of CTE neuropathologies and compared this to a range of tau pathologies, including Alzheimer's disease, primary age-related tauopathy, ageing-related tau astrogliopathy and multiple subtypes of frontotemporal lobar degeneration with tau inclusions. Cases satisfying preliminary consensus diagnostic criteria for CTE neuropathological change (CTE-NC) were identified (athletes, n = 10; long-term survivors of moderate or severe TBI, n = 4) from the Glasgow TBI Archive and Penn Neurodegenerative Disease Brain Bank. In addition, material from a range of autopsy-proven ageing-associated and primary tauopathies in which there was no known history of exposure to TBI was selected as non-injured controls (n = 32). Each case was then stained with a panel of tau antibodies specific for phospho-epitopes (PHF1, CP13, AT100, pS262), microtubule-binding repeat domains (3R, 4R), truncation (Tau-C3) or conformation (GT-7, GT-38) and the extent and distribution of staining assessed. Cell types were confirmed with double immunofluorescent labelling. Results demonstrate that astroglial tau pathology in CTE is composed of 4R-immunoreactive thorn-shaped astrocytes, echoing the morphology and immunophenotype of astrocytes encountered in ageing-related tau astrogliopathy. In contrast, neurofibrillary tangles of CTE contain both 3R and 4R tau, with post-translational modifications and conformations consistent with Alzheimer's disease and primary age-related tauopathy. Our observations establish that the astroglial and neurofibrillary tau pathologies of CTE are phenotypically distinct from each other and recapitulate the tau immunophenotypes encountered in ageing and Alzheimer's disease. As such, the immunohistochemical distinction of CTE neuropathology from other mixed 3R/4R tauopathies of Alzheimer's disease and ageing may rest solely on the pattern and distribution of pathology.

Whose parenting stress is more vulnerable to marital dissatisfaction? A within-couple approach examining gender, cognitive reappraisal, and parental identity.

Conflict and tension in the couple relationship transfers to the parent-child relationship, amplifying the stress parents experience while parenting young children. Pinpointing moderating and individual-level factors that exist in this spillover process may identify both couple and individual areas where spillover might be mitigated. This study used a within-couple approach to test for gender differences in marital-to-parenting spillover and to examine the moderating roles of gender, parental identity, and the emotion regulation strategy cognitive reappraisal in the linkages between marital-parenting spillover. From a larger study of parenting experiences, 96 mother-father couples of young children (mean age = 3.22 years) reported on measures of marital satisfaction, cognitive reappraisal, parenting identity, and parenting stress. Using path model comparisons, we found more similarities than differences between mothers and fathers and, contrary to the hypothesis, that mothers experienced greater spillover between marital satisfaction and parental distress than fathers. Results differed between outcome measures, suggesting that parents experience more spillover from marital satisfaction to parenting in the context of parental distress than in dysfunctional interactions with their child. Importantly, we found that higher parental identity strengthened marital-to-parenting spillover for mothers in contrast to expectations based on theoretical assumptions, whereas cognitive reappraisal weakened marital-to-parenting spillover, supporting the broader emotion regulation literature. These results signify the importance of situating the marriage to parenting transfer in the context of affective experiences and intensified parenting expectations, wherein flexibility in role identity may help alleviate parenting stress.

El conflicto y la tensión en la relación de pareja se traslada a la relación entre padres e hijos, lo cual intensifica el estrés que sufren los padres mientras crían a niños pequeños. La detección de los factores moderadores e individuales que existen en este proceso de desbordamiento puede identificar las áreas tanto a nivel de la pareja como individual donde el desbordamiento podría mitigarse. En este estudio se usó un enfoque dentro de la pareja para examinar las diferencias de género en el desbordamiento del matrimonio hacia la crianza de los niños y para analizar los roles moderadores del género, la identidad parental y la revaluación cognitiva de la estrategia de regulación emocional en las asociaciones entre el desbordamiento desde el matrimonio hacia la crianza. De un estudio más extenso de experiencias de crianza, 96 parejas de madres y padres de niños pequeños (edad promedio = 3.22 años) informaron medidas de satisfacción conyugal, revaluación cognitiva, identidad parental y estrés por la crianza. Utilizando comparaciones del modelo de pautas, encontramos más similitudes que diferencias entre las madres y los padres, y, contrariamente a la hipótesis, las madres experimentaron un mayor desbordamiento entre la satisfacción conyugal y el distrés parental que los padres. Los resultados variaron entre los criterios de valoración, lo cual indica que los padres experimentan más desbordamiento desde la satisfacción conyugal hacia la crianza en el contexto del distrés parental que en las interacciones disfuncionales con su hijo. Cabe destacar que descubrimos que una mayor identidad parental fortaleció el desbordamiento del matrimonio hacia la crianza en las madres en contraste con las expectativas basadas en supuestos teóricos, mientras que la revaluación cognitiva debilitó el desbordamiento desde el matrimonio hacia la crianza, lo cual respalda la bibliografía más amplia sobre regulación emocional. Estos resultados indican la importancia de ubicar el traslado desde el matrimonio a la crianza en el contexto de las experiencias afectivas y las expectativas de crianza intensificadas, donde la flexibilidad en la identidad de roles puede contribuir a aliviar el estrés por la crianza.

Satisfaction with a Vacuum Constriction Device for Erectile Dysfunction among Middle-Aged and Older Veterans.

OBJECTIVES: To investigate satisfaction with a vacuum constriction device for middle-aged and older male Veterans with erectile dysfunction and their female partners. METHODS: Patients (N = 57; mean age = 64.28 years; SD = 8.7) received comprehensive education and training and ongoing follow-up of device use, which included a semi-structured interview. Female partners (n = 41) also rated their satisfaction with the device. RESULTS: Over 96% of patients (n = 53/56 responses) endorsed the ability to maintain an erection with the device and 100% (n = 56/56 responses) indicated they would recommend the device to others. Female partners generally rated sex as better with the device (83.8%; n = 31/37 responses). Physical discomfort using the device was reported among 23% of patients (n = 16), and often due to difficulty or pain with the constriction bands. Difficulty obtaining erections with the device, though infrequently reported, was more common with older age. CONCLUSIONS: The majority of male patients and their female partners receiving comprehensive training for vacuum constriction device use reported satisfaction with the device. CLINICAL IMPLICATIONS: Vacuum constriction devices can be highly effective in improving the sexual health and intimacy of Veterans of all ages experiencing erectile dysfunction.

Mechanisms of Local Stress Amplification in Axons near the Gray-White Matter Interface.

Diffuse axonal injury is a primary neuropathological feature of concussion and is thought to greatly contribute to the classical symptoms of decreased processing speed and memory dysfunction. Although previous studies have investigated the injury biomechanics at the micro- and mesoscale of concussion, few have addressed the multiscale transmission of mechanical loading at thresholds that can induce diffuse axonal injury. Because it has been recognized that axonal pathology is commonly found at anatomic interfaces across all severities of traumatic brain injury, we combined computational, analytical, and experimental approaches to investigate the potential mechanical vulnerability of axons that span the gray-white tissue interface. Our computational models predict that material heterogeneities at the gray-white interface lead to a highly nonuniform distribution of stress in axons, which was most amplified in axonal regions near the interface. This mechanism was confirmed using an analytical model of an individual fiber in a strained bimaterial interface. Comparisons of these collective data with histopathological evaluation of a swine model of concussion demonstrated a notably similar pattern of axonal damage adjacent to the gray-white interface. The results suggest that the tissue property mismatch at the gray-white matter interface places axons crossing this region at greater risk of mechanical damage during brain tissue deformation from traumatic brain injury.

Mossy cell hypertrophy and synaptic changes in the hilus following mild diffuse traumatic brain injury in pigs.

BACKGROUND: Each year in the USA, over 2.4 million people experience mild traumatic brain injury (TBI), which can induce long-term neurological deficits. The dentate gyrus of the hippocampus is notably susceptible to damage following TBI, as hilar mossy cell changes in particular may contribute to post-TBI dysfunction. Moreover, microglial activation after TBI may play a role in hippocampal circuit and/or synaptic remodeling; however, the potential effects of chronic microglial changes are currently unknown. The objective of the current study was to assess neuropathological and neuroinflammatory changes in subregions of the dentate gyrus at acute to chronic time points following mild TBI using an established model of closed-head rotational acceleration induced TBI in pigs. METHODS: This study utilized archival tissue of pigs which were subjected to sham conditions or rapid head rotation in the coronal plane to generate mild TBI. A quantitative assessment of neuropathological changes in the hippocampus was performed via immunohistochemical labeling of whole coronal tissue sections at 3 days post-injury (DPI), 7 DPI, 30 DPI, and 1 year post-injury (YPI), with a focus on mossy cell atrophy and synaptic reorganization, in context with microglial alterations (e.g., density, proximity to mossy cells) in the dentate gyrus. RESULTS: There were no changes in mossy cell density between sham and injured animals, indicating no frank loss of mossy cells at the mild injury level evaluated. However, we found significant mossy cell hypertrophy at 7 DPI and 30 DPI in anterior (> 16% increase in mean cell area at each time; p = <  0.001 each) and 30 DPI in posterior (8.3% increase; p = <  0.0001) hippocampus. We also found dramatic increases in synapsin staining around mossy cells at 7 DPI in both anterior (74.7% increase in synapsin labeling; p = <  0.0001) and posterior (82.7% increase; p = < 0.0001) hippocampus. Interestingly, these morphological and synaptic alterations correlated with a significant change in microglia in proximity to mossy cells at 7 DPI in anterior and at 30 DPI in the posterior hippocampus. For broader context, while we found that there were significant increases in microglia density in the granule cell layer at 30 DPI (anterior and posterior) and 1 YPI (posterior only) and in the molecular layer at 1 YPI (anterior only), we found no significant changes in overall microglial density in the hilus at any of the time points evaluated post-injury. CONCLUSIONS: The alterations of mossy cell size and synaptic inputs paired with changes in microglia density around the cells demonstrate the susceptibility of hilar mossy cells after even mild TBI. This subtle hilar mossy cell pathology may play a role in aberrant hippocampal function post-TBI, although additional studies are needed to characterize potential physiological and cognitive alterations.

Photophysical and Chiroptical Properties of the Enantiomers of N,N'-Bis(1-phenylpropyl)-2,6-pyridinecarboxamide and their Chiral 9-Coordinate Ln3+ Complexes.

The R,R and S,S enantiomers of N,N'-bis(1-phenylpropyl)-2,6-pyridinedicarboxamide, L(Et), react with Ln3+ ions (Ln = La, Eu, Gd, and Tb) to give stable [Ln((R,R)- and (S,S)-L(Et))3]3+ in anhydrous acetonitrile solution, as evidenced by various spectroscopic measurements, including NMR and luminescence titrations. In addition to the characteristic Eu3+ and Tb3+ luminescence bands, the steady-state and time-resolved luminescence spectra of the aforementioned complexes show the residual ligand-centered emission of the 1ππ* to 3ππ* states, indicating an incomplete intersystem crossing (ISC) transfer from the 1ππ* to 3ππ* and ligand-to-Ln3+ energy transfer, respectively. The high circularly polarized luminescence (CPL) activity of [Eu(L(Et))3]3+ confirms that using a single enantiomer of L(Et) induces the preferential formation of one chiral [Eu(L(Et))3]3+ complex, consistent with the [EuL 3]3+ complexes formed with other ligands derived from a 2,6-pyridine dicarboxamide moiety. Furthermore, the CPL sign patterns of complexes with (R,R) or (S,S) enantiomer of L(Et) are consistent with the CPL sign pattern of related [LnL 3]3+ complexes with the (R,R) or (S,S) enantiomer of the respective ligands in this family.

CT characteristics of primary splenic torsion in eight dogs.

Splenic torsion is a rare potentially life-threatening condition characterized by rotation of the spleen around the gastrosplenic and phrenosplenic ligaments leading to occlusion of venous drainage and arterial supply. This retrospective study describes the CT characteristics for dogs with surgically confirmed splenic torsion from 2013 to 2018 using the submissions to a large multinational teleradiology database. Eight dogs had the splenic torsion confirmed with surgery. Seven of eight cases had histology confirming congestion, hemorrhage, and necrosis, and one had concurrent myelolipoma infiltration. The CT characteristics included an enlarged (8/8), rounded (7/8), folded C-shaped spleen (8/8) with a difference of median parenchymal attenuation between pre- and postcontrast of +1.15 HU (Hounsfield units). Other common features included a mainly homogeneous parenchyma on pre- and post-contrast images (6/8), lack of subjective and objective vascular and parenchymal contrast enhancement (6/8) and free peritoneal fluid (6/8). A "whirl sign" was seen in the majority of cases (7/8) alongside a strongly hyperattenuating center (95-416 HU) on the precontrast images (5/7), which has not been previously described in the veterinary literature. Gastric position was normal in all cases. More variable CT characteristics of the confirmed torsions were attributable to suspected partial torsion and myelolipomatous infiltration. Overall, primary splenic torsion confirmed with surgery showed consistent characteristics on CT.