Infinity: A Prospective Trial for Safety and Accuracy of Navigated Posterior Cervical and Thoracic Instrumentation in long-segment Fusions.

STUDY DESIGN: Unblinded single-arm prospective clinical trial. OBJECTIVE: Evaluate safety and accuracy of navigation for placement of posterior cervicothoracic instrumentation. SUMMARY OF BACKGROUND DATA: Computer assisted stereotactic navigation for placement of spinal instrumentation has been widely studied and implemented in the thoracic and lumbar spine. However less literature exists regarding the use of computer assisted navigation for posterior cervical instrumentation, particularly with lateral mass fixation. Here we present the first prospective study of navigated cervical lateral mass screw placement for cervicothoracic fusion. METHODS: Patients who met indications for posterior cervical fusion were screened, consented, and enrolled preoperatively for instrumentation with Medtronic Infinity Occipital-Cervical-Thoracic implants, with use of intraoperative O-arm and stereotactic Stealth navigation. Postoperative CTs of the instrumented levels were obtained during the same hospital admission. Primary outcome of the trial was safety. Secondary outcomes were screw accuracy assessed by Gertzbein-Robbins grade, neurologic exams, and patient reported outcomes on the PROMIS 29 questionnaire. RESULTS: A total of 50 patients underwent surgery, and 557 screws were placed. There were no adverse events related to the use of navigation or screw malposition. Gertzbein-Robbins grade A or B placement comprised 95% of navigated screws. There was a decrease in positive Hoffmann sign rate postoperatively, and sensory and motor exams remained stable. There was improvement in patient reported pain and sleep domains. CONCLUSIONS: Navigation for cervicothoracic instrumentation is safe overall and leads to high rates of accurately placed screws. Longer term follow up could provide more insight to whether the use of this technology results in durable improvement in spinal alignment parameters and patient reported outcomes. LEVEL OF EVIDENCE: 3.

Tumor-related epilepsy in high-grade glioma: a large series survival analysis.

PURPOSE: Seizures are a common clinical occurrence in high-grade glioma (HGG). While many studies have explored seizure incidence and prevalence in HGG, limited studies have examined the prognostic effect of seizures occurring in the post-diagnosis setting. This study aims to assess the impact of seizure presentation on HGG survival outcomes. METHODS: Single-center retrospective review identified 950 patients with histologically-confirmed high-grade glioma. Seizure presentation was determined by clinical history and classified as early onset (occurring within 30 days of HGG presentation) or late onset (first seizure occurring after beginning HGG treatment). The primary outcome, hazard ratios for overall survival and progression-free survival, was assessed with multivariable Cox proportional-hazards models. IDH1 mutation status (assessed through immunohistochemistry) was only consistently available beginning in 2015; subgroup analyses were performed in the subset of patients with known IDH1 status. RESULTS: Epileptic activity before (HR = 0.81, 95% CI = 0.68-0.96, P = 0.017) or after (HR = 0.74, 95% CI = 0.60-0.91, P = 0.005) HGG diagnosis associated with improved overall survival. Additionally, late seizure onset significantly associated with lower odds of achieving partial (OR = 0.25, 95% CI = 0.12-0.53, P = < 0.001) or complete (OR = 0.30, 95% CI = 0.18-0.50, P < 0.001) seizure control than patients with early seizure onset. CONCLUSIONS: Clinical seizures both at the time of diagnosis and later during the HGG treatment course are associated with improved overall survival. This association potentially persists for both IDH1-wildtype and IDH1-mutant patients, but further study is required.

A Comparative Assessment of Outcomes Following Mandibular Distraction Osteogenesis and Tongue-Lip Adhesion in Pierre Robin Sequence.

The purpose of this study was to assess long-term outcomes of tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) to resolve upper airway obstruction in patients with Robin sequence (RS). A retrospective cohort study was performed of subjects presenting to a tertiary care pediatric center who underwent either primary MDO or TLA for the treatment of RS between 2004 and 2020. N=59 subjects met inclusion criteria (n=34 MDO, n=25 TLA), and there were no significant differences in preoperative patient characteristics other than age at surgery (MDO 31 d vs. TLA 17 d, P=0.049). Preoperative apnea-hypopnea index (AHI) was similar between cohorts (33.9 and 46.7, P=0.38). Subjects who underwent MDO demonstrated improved AHI on initial postoperative polysomnogram performed at 2 weeks (3.4 vs. 11.6, P=0.014), however AHI at the second postoperative timepoint (270 vs. 142 d, P=0.007) was no different between cohorts (2.8 vs. 2.6, P=0.89). No subject in either group required enteral nutrition or supplemental oxygen at last follow-up. In subjects undergoing MDO, 14.7% demonstrated temporary asymmetric marginal mandibular nerve dysfunction. Forty-seven percent of MDO patients had injury to first primary molars. MDO and TLA both ultimately achieved similar long-term resolution of upper airway obstruction and associated feeding difficulties in patients with Robin sequence. MDO offered a more immediate airway improvement, but the procedure carried a potential risk of neurosensory and dental injury when compared with TLA.

Atypical monocyte dynamics in healthy humans in response to fasting and refeeding are distinguished by fasting HDL and postprandial cortisol.

Monocytes are innate immune cells that are continuously produced in bone marrow which enter and circulate the vasculature. In response to nutrient scarcity, monocytes migrate back to bone marrow, where, upon refeeding, they are rereleased back into the bloodstream to replenish the circulation. In humans, the variability in monocyte behavior in response to fasting and refeeding has not been characterized. To investigate monocyte dynamics in humans, we measured blood monocyte fluctuations in 354 clinically healthy individuals after a 12-h overnight fast and at 3 and 6 h after consuming a mixed macronutrient challenge meal. Using cluster analysis, we identified three distinct monocyte behaviors. Group 1 was characterized by relatively low fasting monocyte counts that markedly increased after consuming the test meal. Group 2 was characterized by relatively high fasting monocyte counts that decreased after meal consumption. Group 3, like Group 1, was characterized by lower fasting monocyte counts but increased to a lesser extent after consuming the meal. Although monocyte fluctuations observed in Groups 1 and 3 align with the current paradigm of monocyte dynamics in response to fasting and refeeding, the atypical dynamic observed in Group 2 does not. Although generally younger in age, Group 2 subjects had lower whole body carbohydrate oxidation rates, lower HDL-cholesterol levels, delayed postprandial declines in salivary cortisol, and reduced postprandial peripheral microvascular endothelial function. These unique characteristics were not explained by group differences in age, sex, or body mass index (BMI). Taken together, these results highlight distinct patterns of monocyte responsiveness to natural fluctuations in dietary fuel availability.NEW & NOTEWORTHY Our study composed of adult volunteers revealed that monocyte dynamics exhibit a high degree of individual variation in response to fasting and refeeding. Although circulating monocytes in most volunteers behaved in ways that align with previous reports, many exhibited atypical dynamics demonstrated by elevated fasting blood monocyte counts that sharply decreased after meal consumption. This group was also distinguished by lower HDL levels, reduced postprandial endothelial function, and a delayed postprandial decline in salivary cortisol.

Association between help-seeking and motivation for completing a couple relationship education program across service modality.

Levels of motivation and help-seeking impact the effectiveness of couple relationship education (CRE), as those with greater help-seeking and motivation are more likely to attend more sessions and remain engaged. Less is known about what impacts the association between motivation and help-seeking between partners in a couple engaging in CRE. The current study aims to examine (a) the effect of couples' self-stigma for help-seeking on their own or partner's motivation to complete the relationship education program and (b) whether the effects differ between service modality (i.e., online and in-person). We sampled 276 heterosexual couples who participated in a relationship education program. A multiple-group actor-partner interdependence model analysis revealed that women and men with higher self-stigma for seeking help exhibited lower motivation to complete the program in both settings. Higher self-stigma in men for help-seeking significantly enhanced the motivation of their female partners to complete the online relationship education program.

Innate and Adaptive Immune Responses in Intestinal Transplant Rejection: Through the Lens of Inflammatory Bowel and Intestinal Graft-Versus-Host Diseases.

Intestinal transplantation is a life-saving procedure utilized for patients failing total parenteral nutrition. However, intestinal transplantattion remains plagued with low survival rates and high risk of allograft rejection. The authors explore roles of innate (macrophages, natural killer cells, innate lymphoid cells) and adaptive immune cells (Th1, Th2, Th17, Tregs) in inflammatory responses, particularly inflammatory bowel disease and graft versus host disease, and correlate these findings to intestinal allograft rejection, highlighting which effectors exacerbate or suppress intestinal rejection. Better understanding of this immunology can open further investigation into potential biomolecular targets to develop improved therapeutic treatment options and immunomonitoring techniques to combat allograft rejection and enhance patient lives.

2-Substituted (N)-Methanocarba A3 Adenosine Receptor Agonists: In Silico, In Vitro, and In Vivo Characterization.

2-Arylethynyl (N)-methanocarba adenosine 5'-methylamides are selective A3 adenosine receptor (AR) agonists containing a preestablished receptor-preferred pseudoribose conformation. Here, we compare analogues having bulky 2-substitution, either containing or lacking an ethynyl spacer between adenine and a cyclic group. 2-Aryl compounds 9-11, 13, 14, 19, 22, 23, 27, 29, 31, and 34, lacking a spacer, had human (h) A3AR K i values of 2-30 nM, and others displayed lower affinity. Mouse (m) A3AR affinity varied, with 2-arylethynyl having a higher affinity than 2-aryl analogues (7, 8 > 3c, 3d > 3b). However, 2-aryl-4'-truncated derivatives had greatly reduced hA3AR affinity, even containing affinity-enhancing N 6-dopamine-derived substituents. Molecular modeling, including molecular dynamics simulation, predicted stable poses in the canonical A3AR agonist binding site, but 2-aryl (ECL2 interactions) and 2-arylethynyl (TM2 interactions) substituents have different conformations and environments. In a hA3AR miniGαi recruitment assay, 31 (MRS8062) was (slightly) more potent compared to a ß-arrestin2 recruitment assay, both in engineered HEK293T cells, and its maximal efficacy (E max) was much higher (165%) than reference agonist NECA's. Thus, in the 2-aryl series, A3AR affinity and selectivity were variable and generally reduced compared to the 2-arylethynyl series, with a greater dependence on the specific aryl group present. Selected compounds were studied in vivo in an ischemic model of peripheral artery disease (PAD). Rigidified 2-arylethynyl analogues 3a-3c were protective in this model of skeletal muscle ischemia-reperfusion injury/claudication, as previously shown only for moderately A3AR-selective ribosides or (N)-methanocarba derivatives. Thus, we have expanded the A3AR agonist SAR for (N)-methanocarba adenosines.

Microbial etiology of vertebral osteomyelitis/discitis amid the opioid epidemic.

OBJECTIVE: The primary goal of this study was to establish the current microbial trends in vertebral osteomyelitis/discitis (VOD) amid the opioid epidemic and to determine if intravenous drug use (IVDU) predisposes one to a unique microbial profile of infection. METHODS: The authors performed a retrospective cohort study consisting of 1175 adult patients diagnosed with VOD between 2011 and 2022 at a single quaternary center. Data were acquired through retrospective chart review, with pertinent demographic and clinical information collected. RESULTS: Staphylococcus aureus was the most cultured organism in both the IVDU and non-IVDU groups at 56.1% and 40.7%, respectively. In the IVDU cohort, Serratia marcescens was the next most prevalently cultured organism at 13.9%. CONCLUSIONS: The present study demonstrates that in the IVDU population S. marcescens is an organism of high concern. The potential for Serratia spp. infection should be accounted for when selecting empirical antimicrobial therapy in VOD patients.

History of biological, mechanistic, and clinical understanding of concussion.

The history behind the biological, mechanistic, and clinical insights into concussion provides awareness of the current understanding and future areas for study. Although the initial description of concussion appeared in the 10th century, the potential long-term structural consequences were first defined by Harrison Martland, M.D., who performed a postmortem study of former boxers in 1928. He found evidence of perivascular microhemorrhage that he believed eventually evolved into a "replacement gliosis" underlying a clinical syndrome that he named "punch drunk," which was characterized by acute confusion with chronic cognitive and physical symptoms developing in those with prolonged exposure. Further research into the potential long-term consequences of repetitive concussions, particularly in athletics and the military, led to an understanding of chronic traumatic encephalopathy. To ameliorate possible long-term risks, research has been focused on preventative and therapeutic measures for concussion. In this review article, the authors present the history of concussion and the long-term sequelae of repeated head injury. Specifically, they consider how the understanding of concussion has evolved from antiquity into the modern era, and how this change in understanding of head injury has led to an appreciation of the fact that its long-term implications sometimes manifest as the clinical and histopathological entity of chronic traumatic encephalopathy.

Phenotype-driven assessment of the ancestral trajectory of sulfur biooxidation in the thermoacidophilic archaea Sulfolobaceae.

Certain members of the family Sulfolobaceae represent the only archaea known to oxidize elemental sulfur, and their evolutionary history provides a framework to understand the development of chemolithotrophic growth by sulfur oxidation. Here, we evaluate the sulfur oxidation phenotype of Sulfolobaceae species and leverage comparative genomic and transcriptomic analysis to identify the key genes linked to sulfur oxidation. Metabolic engineering of the obligate heterotroph Sulfolobus acidocaldarius revealed that the known cytoplasmic components of sulfur oxidation alone are not sufficient to drive prolific sulfur oxidation. Imaging analysis showed that Sulfolobaceae species maintain proximity to the sulfur surface but do not necessarily contact the substrate directly. This indicates that a soluble form of sulfur must be transported to initiate cytoplasmic sulfur oxidation. Conservation patterns and transcriptomic response implicate an extracellular tetrathionate hydrolase and putative thiosulfate transporter in a newly proposed mechanism of sulfur acquisition in the Sulfolobaceae.IMPORTANCESulfur is one of the most abundant elements on earth (2.9% by mass), so it makes sense that the earliest biology found a way to use sulfur to create and sustain life. However, beyond evolutionary significance, sulfur and the molecules it comprises have important technological significance, not only in chemicals such as sulfuric acid and in pyritic ores containing critical metals but also as a waste product from oil and gas production. The thermoacidophilic Sulfolobaceae are unique among the archaea as sulfur oxidizers. The trajectory for how sulfur biooxidation arose and evolved can be traced using experimental and bioinformatic analyses of the available genomic data set. Such analysis can also inform the process by which extracellular sulfur is acquired and transported by thermoacidophilic archaea, a phenomenon that is critical to these microorganisms but has yet to be elucidated.

Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the HTT gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin. We find that HTT interacts directly with ubiquitin in vitro. Tandem affinity purification was used to identify ubiquitinated and ubiquitin-associated proteins that copurify with a HTT N-terminal fragment under basal conditions. Copurification is enhanced by HTT polyQ expansion and reduced by mimicking HTT serine 421 phosphorylation. The identified HTT-interacting proteins include RNA-binding proteins (RBPs) involved in mRNA translation, proteins enriched in stress granules, the nuclear proteome, the defective ribosomal products (DRiPs) proteome and the brain-derived autophagosomal proteome. To determine whether the proteins interacting with HTT are autophagic targets, HTT knockout (KO) cells and immunoprecipitation of lysosomes were used to investigate autophagy in the absence of HTT. HTT KO was associated with reduced abundance of mitochondrial proteins in the lysosome, indicating a potential compromise in basal mitophagy, and increased lysosomal abundance of RBPs which may result from compensatory up-regulation of starvation-induced macroautophagy. We suggest HTT is critical for appropriate basal clearance of mitochondrial proteins and RBPs, hence reduced HTT proteostatic function with mutation may contribute to the neuropathology of HD.

Primary caregiver employment status is associated with traumatic brain injury in children in the USA.

BACKGROUND: Traumatic brain injury (TBI) is a common injury in children. Previous literature has demonstrated that TBI may be associated with supervision level. We hypothesised that primary caregiver employment would be associated with child TBI. METHODS: A retrospective cross-sectional study was performed for children aged 0-17 using the National Survey of Children's Health (NSCH) 2018-2019. The NSCH contains survey data on children's health completed by adult caregivers from randomly selected households across the USA. We compared current TBI prevalence between children from households of different employment statuses. Current TBI was defined by survey responses indicating a healthcare provider diagnosed TBI or concussion for the child and the condition was present at the time of survey completion. Household employment status was categorised as two caregivers employed, two caregivers unemployed, one of two caregivers unemployed, single caregiver employed and single caregiver unemployed. Multivariable logistic regression was performed, controlling for sociodemographic factors. RESULTS: Of 56 865 children, median age was 10 years (IQR: 5-14), and 0.6% (n=332) had a current TBI. Children with TBI were older than children without TBI (median 12 years vs 10 years, p<0.001). On multivariable regression, children with at least one caregiver unemployed had increased odds of current TBI compared with children with both caregivers employed. CONCLUSIONS: Children with at least one caregiver unemployed had increased TBI odds compared with children with both caregivers employed. These findings highlight a population of families that may benefit from injury prevention education and intervention.

Contribution of Electrostatic CH3-π Interactions to Recognition of Histone Asymmetric Dimethylarginine by the SPIN1 Triple Tudor Domain.

Methylation of arginine (Arg) residues on histones creates a new binding epitope, enabling recognition by aromatic cage binding pockets in Tudor domains; these protein-protein interactions (PPIs) govern gene expression. Despite their biological importance, the molecular details of methylated Arg recognition are poorly understood. While the desolvation, hydrogen bonding, and guanidinium stacking of methylated Arg have been explored in model systems and proposed to contribute to binding, direct interactions between the methyl groups and the aromatic residues in the binding pocket have not previously been investigated. Herein, we mechanistically study the CH3-π interactions between the SPIN1 triple Tudor domain and histone asymmetric dimethylarginine. We find that these CH3-π interactions are electrostatically tunable, exhibiting cation-π character, albeit attenuated relative to cation-π interactions with quaternary ammonium ions, offering key insight into how methylation of Arg alters its binding epitope to enable new PPIs.

Osseous Triceps Avulsion in a 12-Year-Old Girl: A Case Report.

CASE: A 12-year-old girl presented with significant right elbow pain following a fall during soccer which caused an osseous triceps avulsion injury and nondisplaced type II Salter-Harris radial neck fracture. The patient was treated with successful open repair utilizing suture anchor fixation, resulting in full return of function and return to previous activities. CONCLUSION: Timely and accurate diagnosis and treatment of displaced triceps sleeve avulsion injuries is critical and can result in excellent patient outcomes and return to previous functional level. This unique case contributes to the diagnosis and management of this rare condition in pediatric populations.

Mid-Life Household Food Insecurity and Subsequent Memory Function and Rate of Decline in Rural South Africa, 2004-2022.

INTRODUCTION: We aimed to investigate mid-life food insecurity over time in relation to subsequent memory function and rate of decline in Agincourt, rural South Africa. METHODS: Data from the longitudinal Agincourt Health and Socio-Demographic Surveillance System (Agincourt HDSS) were linked to the population-representative Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI). Food insecurity (yes vs. no) and food insecurity intensity (never/rarely/sometimes vs. often/very often) in the past month were assessed every 3 years from 2004 to 2013 in Agincourt HDSS. Cumulative exposure to each food insecurity measure was operationalized as 0, 1, and ≥2 time points. Episodic memory was assessed from 2014/15 to 2021/22 in HAALSI. Mixed-effects linear regression models were fitted to investigate the associations of each food insecurity measure with memory function and rate of decline over time. RESULTS: A total of 3,186 participants (mean age [SD] in 2004: 53 [12.87]; range: 30-96) were included and 1,173 (36%) participants experienced food insecurity in 2004, while this figure decreased to 490 (15%) in 2007, 489 (15%) in 2010, and 150 (5%) in 2013. Experiencing food insecurity at one time point (vs. never) from 2004 to 2013 was associated with lower baseline memory function (ß = -0.095; 95% CI: -0.159 to -0.032) in 2014/15 but not rate of memory decline. Higher intensity of food insecurity at ≥2 time points (vs. never) was associated with lower baseline memory function (ß = -0.154, 95% CI: -0.338 to 0.028), although the estimate was imprecise. Other frequencies of food insecurity and food insecurity intensity were not associated with memory function or decline in the fully adjusted models. CONCLUSION: In this setting, mid-life food insecurity may be a risk factor for lower later-life memory function, but not decline.

High-throughput volumetric mapping of synaptic transmission.

Volumetric imaging of synaptic transmission in vivo requires high spatial and high temporal resolution. Shaping the wavefront of two-photon fluorescence excitation light, we developed Bessel-droplet foci for high-contrast and high-resolution volumetric imaging of synapses. Applying our method to imaging glutamate release, we demonstrated high-throughput mapping of excitatory inputs at >1,000 synapses per volume and >500 dendritic spines per neuron in vivo and unveiled previously unseen features of functional synaptic organization in the mouse primary visual cortex.

Explorative Characterization of GI Complaints, General Physical and Mental Wellbeing, and Gut Microbiota in Trained Recreative and Competitive Athletes with or without Self-Reported Gastrointestinal Symptoms.

The current state of the literature lacks a clear characterization of gastrointestinal (GI) symptoms, gut microbiota composition, and general physical and mental wellbeing in well-trained athletes. Therefore, this study aimed to characterize differences in self-reported symptoms, gut microbiota composition, and wellbeing (i.e., sleep quality, mood, and physical (PHQ) and mental wellbeing) between athletes with and without GI symptoms. In addition, we assessed the potential impact of a 3-week multi-ingredient fermented whey supplement in the GI complaints group, without a control group, on the gut microbiota and self-reported GI symptoms and wellbeing. A total of 50 athletes (24.7 ± 4.5 years) with GI issues (GI group at baseline, GI-B) and 21 athletes (25.4 ± 5.3 years) without GI issues (non-GI group, NGI) were included. At baseline, there was a significant difference in the total gastrointestinal symptom rating scale (GSRS) score (24.1 ± 8.48 vs. 30.3 ± 8.82, p = 0.008) and a trend difference in PHQ (33.9 ± 10.7 vs. 30.3 ± 8.82, p = 0.081), but no differences (p > 0.05) were seen for other outcomes, including gut microbiota metrics, between groups. After 3-week supplementation, the GI group (GI-S) showed increased Bifidobacterium relative abundance (p < 0.05), reported a lower number of severe GI complaints (from 72% to 54%, p < 0.001), and PHQ declined (p = 0.010). In conclusion, well-trained athletes with GI complaints reported more severe GI symptoms than an athletic reference group, without showing clear differences in wellbeing or microbiota composition. Future controlled research should further investigate the impact of such multi-ingredient supplements on GI complaints and the associated changes in gut health-related markers.

Identifying dysregulated regions in amyotrophic lateral sclerosis through chromatin accessibility outliers.

The high heritability of amyotrophic lateral sclerosis (ALS) contrasts with its low molecular diagnosis rate post-genetic testing, pointing to potential undiscovered genetic factors. To aid the exploration of these factors, we introduced EpiOut, an algorithm to identify chromatin accessibility outliers that are regions exhibiting divergent accessibility from the population baseline in a single or few samples. Annotation of accessible regions with histone chromatin immunoprecipitation sequencing and Hi-C indicates that outliers are concentrated in functional loci, especially among promoters interacting with active enhancers. Across different omics levels, outliers are robustly replicated, and chromatin accessibility outliers are reliable predictors of gene expression outliers and aberrant protein levels. When promoter accessibility does not align with gene expression, our results indicate that molecular aberrations are more likely to be linked to post-transcriptional regulation rather than transcriptional regulation. Our findings demonstrate that the outlier detection paradigm can uncover dysregulated regions in rare diseases. EpiOut is available at github.com/uci-cbcl/EpiOut.

Mechanisms of Photoredox Catalysis Featuring Nickel-Bipyridine Complexes.

Metallaphotoredox catalysis can unlock useful pathways for transforming organic reactants into desirable products, largely due to the conversion of photon energy into chemical potential to drive redox and bond transformation processes. Despite the importance of these processes for cross-coupling reactions and other transformations, their mechanistic details are only superficially understood. In this review, we have provided a detailed summary of various photoredox mechanisms that have been proposed to date for Ni-bipyridine (bpy) complexes, focusing separately on photosensitized and direct excitation reaction processes. By highlighting multiple bond transformation pathways and key findings, we depict how photoredox reaction mechanisms, which ultimately define substrate scope, are themselves defined by the ground- and excited-state geometric and electronic structures of key Ni-based intermediates. We further identify knowledge gaps to motivate future mechanistic studies and the development of synergistic research approaches spanning the physical, organic, and inorganic chemistry communities.

Sex and the facilitation of cued fear by prior contextual fear conditioning in rats.

Previous studies have shown that the formation of new memories can be influenced by prior experience. This includes work using pavlovian fear conditioning in rodents that have shown that an initial fear conditioning experience can become associated with and facilitate the acquisition of new fear memories, especially when they occur close together in time. However, most of the prior studies used only males as subjects resulting in questions about the generalizability of the findings from this work. Here we tested whether prior contextual fear conditioning would facilitate later learning of cued fear conditioning in both male and female rats, and if there were differences based on the interval between the two conditioning episodes. Our results showed that levels of cued fear were not influenced by prior contextual fear conditioning or by the interval between training, however, females showed lower levels of cued fear. Freezing behavior in the initial training context differed by sex, with females showing lower levels of contextual fear, and by the type of initial training, with rats given delayed shock showing higher levels of fear than rats given immediate shock during contextual fear conditioning. These results indicate that contextual fear conditioning does not prime subsequent cued fear conditioning and that female rats express lower levels of cued and contextual fear conditioning than males.