Fetal CCL2 signaling mediates offspring social behavior and recapitulates effects of prenatal stress.

Maternal stress during pregnancy is prevalent and associated with increased risk of neurodevelopmental disorders in the offspring. Maternal and offspring immune dysfunction has been implicated as a potential mechanism by which prenatal stress shapes offspring neurodevelopment; however, the impact of prenatal stress on the developing immune system has yet to be elucidated. Furthermore, there is evidence that the chemokine C-C motif chemokine ligand 2 (CCL2) plays a key role in mediating the behavioral sequelae of prenatal stress. Here, we use an established model of prenatal restraint stress in mice to investigate alterations in the fetal immune system, with a focus on CCL2. In the placenta, stress led to a reduction in CCL2 and Ccr2 expression with a concomitant decrease in leukocyte number. However, the fetal liver exhibited an inflammatory phenotype, with upregulation of Ccl2, Il6, and Lbp expression, along with an increase in pro-inflammatory Ly6CHi monocytes. Prenatal stress also disrupted chemokine signaling and increased the number of monocytes and microglia in the fetal brain. Furthermore, stress increased Il1b expression by fetal brain CD11b+ microglia and monocytes. Finally, intra-amniotic injections of recombinant mouse CCL2 partially recapitulated the social behavioral deficits in the adult offspring previously observed in the prenatal restraint stress model. Altogether, these data suggest that prenatal stress led to fetal inflammation, and that fetal CCL2 plays a role in shaping offspring social behavior.

Quantifying Amide-Aromatic Interactions at Molecular and Atomic Levels: Experimentally Determined Enthalpic and Entropic Contributions to Interactions of Amide sp2O, N, C and sp3C Unified Atoms with Naphthalene sp2C Atoms in Water.

In addition to amide hydrogen bonds and the hydrophobic effect, interactions involving π-bonded sp2 atoms of amides, aromatics, and other groups occur in protein self-assembly processes including folding, oligomerization, and condensate formation. These interactions also occur in aqueous solutions of amide and aromatic compounds, where they can be quantified. Previous analysis of thermodynamic coefficients quantifying net-favorable interactions of amide compounds with other amides and aromatics revealed that interactions of amide sp2O with amide sp2N unified atoms (presumably C═O···H-N hydrogen bonds) and amide/aromatic sp2C (lone pair π, n-π*) are particularly favorable. Sp3C-sp3C (hydrophobic), sp3C-sp2C (hydrophobic, CH-π), sp2C-sp2C (hydrophobic, π-π), and sp3C-sp2N interactions are favorable, sp2C-sp2N interactions are neutral, while sp2O-sp2O and sp2N-sp2N self-interactions and sp2O-sp3C interactions are unfavorable. Here, from determinations of favorable effects of 14 amides on naphthalene solubility at 10, 25, and 45 °C, we dissect amide-aromatic interaction free energies into enthalpic and entropic contributions and find these vary systematically with amide composition. Analysis of these results yields enthalpic and entropic contributions to intrinsic strengths of interactions of amide sp2O, sp2N, sp2C, and sp3C unified atoms with aromatic sp2C atoms. For each interaction, enthalpic and entropic contributions have the same sign and are much larger in magnitude than the interaction free energy itself. The amide sp2O-aromatic sp2C interaction is enthalpy-driven and entropically unfavorable, consistent with direct chemical interaction (e.g., lone pair-π), while amide sp3C- and sp2C-aromatic sp2C interactions are entropy-driven and enthalpically unfavorable, consistent with hydrophobic effects. These findings are relevant for interactions involving π-bonded sp2 atoms in protein processes.

Transient Receptor Potential (TRP) Channels in Pain, Neuropsychiatric Disorders, and Epilepsy.

Pharmacomodulation of membrane channels is an essential topic in the study of physiological conditions and disease status. Transient receptor potential (TRP) channels are one such family of nonselective cation channels that have an important influence. In mammals, TRP channels consist of seven subfamilies with a total of twenty-eight members. Evidence shows that TRP channels mediate cation transduction in neuronal signaling, but the full implication and potential therapeutic applications of this are not entirely clear. In this review, we aim to highlight several TRP channels which have been shown to mediate pain sensation, neuropsychiatric disorders, and epilepsy. Recent findings suggest that TRPM (melastatin), TRPV (vanilloid), and TRPC (canonical) are of particular relevance to these phenomena. The research reviewed in this paper validates these TRP channels as potential targets of future clinical treatment and offers patients hope for more effective care.

Permafrost thaw with warming reduces microbial metabolic capacities in subsurface soils.

Microorganisms are major constituents of the total biomass in permafrost regions, whose underlain soils are frozen for at least two consecutive years. To understand potential microbial responses to climate change, here we examined microbial community compositions and functional capacities across four soil depths in an Alaska tundra site. We showed that a 5-year warming treatment increased soil thaw depth by 25.7% (p = .011) within the deep organic layer (15-25 cm). Concurrently, warming reduced 37% of bacterial abundance and 64% of fungal abundances in the deep organic layer, while it did not affect microbial abundance in other soil layers (i.e., 0-5, 5-15, and 45-55 cm). Warming treatment altered fungal community composition and microbial functional structure (p < .050), but not bacterial community composition. Using a functional gene array, we found that the relative abundances of a variety of carbon (C)-decomposing, iron-reducing, and sulphate-reducing genes in the deep organic layer were decreased, which was not observed by the shotgun sequencing-based metagenomics analysis of those samples. To explain the reduced metabolic capacities, we found that warming treatment elicited higher deterministic environmental filtering, which could be linked to water-saturated time, soil moisture, and soil thaw duration. In contrast, plant factors showed little influence on microbial communities in subsurface soils below 15 cm, despite a 25.2% higher (p < .05) aboveground plant biomass by warming treatment. Collectively, we demonstrate that microbial metabolic capacities in subsurface soils are reduced, probably arising from enhanced thaw by warming.

Catheter-driven His bundle pacemaker lead implantation.

Delivery of leads to the His bundle pacing region is most commonly performed with non-deflectable or deflectable sheaths and a His lead with an exposed helix. We present a technique where any pacing lead may be delivered to the His region utilizing a catheter- and snare-delivered approach.

Dizziness spells: Should one suspect the pacemaker?

A 52-year-old lady presented to the emergency department with recurrent episodes of dizziness and near-syncope on awakening up or swinging her left arm. Initial rhythm strips demonstrated intermittently non-conducted p waves corresponding to inappropriate pacemaker inhibition and oversensing malfunction. Pacemaker was interrogated in the ED showing ventricular lead noise and decreased lead impedance over a one year period. The patient was diagnosed with pacemaker lead failure supported by correlating pacemaker lead variation with homolateral arm movement. The patient was referred to an electrophysiologist and underwent new right ventricular lead placement with the resolution of symptoms.

Reoperation of decompression alone or decompression plus fusion surgeries for degenerative lumbar diseases: a systematic review.

PURPOSE: The objective of this paper was to compare the reoperation rates, timing and causes between decompression alone and decompression plus fusion surgeries for degenerative lumbar diseases through a systematic review of the published data. METHODS: A search of the literature was conducted on PubMed/MEDLINE, EMBASE and the Cochrane Collaboration Library. Reports that included reoperations after decompression alone and/or decompression plus fusion surgeries were selected using designed eligibility criteria. Comparative analysis of reoperation rates, timing and causes between the two surgeries was conducted. RESULTS: Thirty-two retrospective and three prospective studies were selected from 6401 papers of the literature search. The analysis of data reported in these studies revealed that both surgeries resulted in similar reoperation rates after the primary surgery. However, majority of reoperations following the fusion surgeries were due to adjacent-segment diseases, and following the decompression alone surgeries were due to the same-segment diseases. Reoperation rates were not found to decrease in patients operated more recently than those operated in early times. CONCLUSIONS: Reoperation rates were similar following decompression alone or plus fusion surgeries for degenerative lumbar diseases. However, different underlying major causes exist between the two surgeries. There is no evidence showing that the reoperation rate has a trend to decline with newer surgical techniques used. The exact mechanisms of reoperation after both surgeries are still unclear. Further researches are necessary to investigate the mechanisms of reoperation for improvement of surgical techniques that aim to delay or prevent reoperation after lumbar surgery. These slides can be retrieved under Electronic Supplementary Material.

Mapping the unmappable: local vector mapping.

Arrhythmias are commonly mapped using a timing reference signal. There are a number of situations where mapping may be difficult or even impossible using conventional reference-based mapping. Wobbling arrhythmias or those who do not maintain a 1:1 relationship with the reference signal are problematic. Local vector mapping may be performed in these situations to map arrhythmias without the use of a reference signal.

Change in P wave morphology after convergent atrial fibrillation ablation.

Convergent atrial fibrillation ablation involves extensive epicardial as well as endocardial ablation of the left atrium. We examined whether it changes the morphology of the surface P wave. We reviewed electrocardiograms of 29 patients who underwent convergent ablation for atrial fibrillation. In leads V1, II and III, we measured P wave duration, area and amplitude before ablation, and at 1, 3 and 6 months from ablation. After ablation, there were no significant changes in P wave amplitude, area, or duration in leads II and III. There was a significant reduction in the area of the terminal negative deflection of the P wave in V1 from 0.38 mm(2) to 0.13 mm(2) (p = 0.03). There is also an acute increase in the amplitude and duration of the positive component of the P wave in V1 followed by a reduction in both by 6 months. Before ablation, 62.5% of the patients had biphasic P waves in V1. In 6 months, only 39.2% of them had biphasic P waves. Hybrid ablation causes a reduction of the terminal negative deflection of the P wave in V1 as well as temporal changes in the duration and amplitude of the positive component of the P wave in V1. This likely reflects the reduced electrical contribution of the posterior left atrium after ablation as well as anatomical and autonomic remodeling. Recognition of this altered sinus P wave morphology is useful in the diagnosis of atrial arrhythmias in this patient population.

A new trick to a routine procedure: taking the fear out of the axillary vein stick using the 35° caudal view.

AIMS: The axillary vein is frequently used to implant pacemaker and defibrillator leads. We describe a technique utilizing the caudal fluoroscopic view to facilitate axillary venous access without contrast. METHODS AND RESULTS: Outcomes of device implants or upgrades utilizing this technique were examined during a 1-year period at our institution. Of 229 consecutive implants, only 9 patients required an alternate technique for lead implantation. There were zero cases of pneumothorax. CONCLUSIONS: The caudal view allows for optimal appreciation of the anterior border of the lung and the first rib. This simple technique increases the implanter's appreciation of and control over the access needle depth relative to the lung and first rib, thereby reducing pneumothorax risk.

Labial Necrotizing Fasciitis Caused by Pelvic Eggerthia catenaformis Infection.

A patient with comorbid diabetes mellitus, obesity, and hypertension acutely presented to the ED due to labial cellulitis with rapidly progressing symptoms of systemic inflammation. Clinical examination revealed fever and groin pain that was tender to palpation. Initial contrast-enhanced CT scans showed labial cellulitis extending to the inguinal canal, with later CT imaging findings of subcutaneous air indicative of necrotizing fasciitis (NF). Antimicrobial therapy was initiated empirically and later tailored to culture antibiogram. The patient underwent acute surgical abscess drainage and tissue debridement but was transferred to the surgical intensive care unit (SICU) due to postoperative blood loss and hypotension. Two additional surgical procedures were needed before sufficient drainage was achieved, and Eggerthia catenaformis (E. catenaformis) was isolated from all samples. Due to the extent of the infection, the patient was admitted for a total of 16 days, with five days spent in the SICU. They recovered completely due to adequate surgery and antimicrobial therapy for a total of 24 days. Here, we present the third reported case of NF due to E. catenaformiswhile emphasizing timely treatment with empiric antibiotics and surgical intervention.

From trenches to technology: a narrative review of sleep medicine in the military.

Diagnoses of military-relevant sleep disorders have increased substantially since the terrorist attacks of September 11, 2001. The cause of this increase appears to be complicated and multifactorial, with military and civilian populations clearly differing with respect to both the nature and distribution of sleep disorders diagnoses. In part, these differences may be attributable to the fact that a majority of service members are chronically sleep-restricted-an unavoidable consequence of continuous and sustained military operations that "set the stage" for development of specific sleep disorders. The purpose of this narrative review is to describe the military relevance of several common sleep disorders, assess the extent to which these disorders currently constitute a burden on the military health care system, and suggest strategies to alleviate that burden. The military health care system does not have enough sleep medicine providers to address the immediate and long-term consequences of sleep disorders in military personnel. Digital technologies and education packages can be leveraged to improve access to care. CITATION: Thomas CL, Carr K, Yang F, et al. From trenches to technology: a narrative review of sleep medicine in the military. J Clin Sleep Med. 2024;20(6):973-981.

Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis.

Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2-4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed "committed pre-adipocytes" from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling, and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.

Atrial fibrillation symptom reduction and improved quality of life following the hybrid convergent procedure: a CONVERGE trial subanalysis.

Background: CONVERGE was a prospective, multicenter, randomized controlled trial that evaluated the safety of Hybrid Atrial Fibrillation Convergent (HC) and compared its effectiveness to endocardial catheter ablation (CA) for the treatment of persistent atrial fibrillation (PersAF) and longstanding PersAF (LSPAF). In 2020, we reported that CONVERGE met its primary safety and effectiveness endpoints. The primary objective of the present study is to report CONVERGE trial results for quality of life (QOL) and Class I/III anti-arrhythmic drug (AAD) utilization following HC. Methods: Eligible patients had drug-refractory symptomatic PersAF or LSPAF and a left atrium diameter ≤6.0 cm. Enrolled patients were randomized 2:1 to receive HC or CA. Atrial Fibrillation Severity Scale (AFSS) and the 36-Item Short Form Health Survey (SF-36) were assessed at baseline and 12 months; statistical comparison was performed using paired t-tests. AAD utilization at baseline through 12 and 18 months post-procedure was evaluated; statistical comparison was performed using McNemar's tests. Results: A total of 153 patients were treated with either HC (n=102) or CA (n=51). Of the 102 HC patients, 38 had LSPAF. AFSS and SF-36 Mental and Physical Component scores were significantly improved at 12 months versus baseline with HC overall and for the subset of LSPAF patients treated with either HC or CA. The proportion of HC patients (n=102) who used Class I /III AADs at 12 and 18 months was significantly less (33.3% and 36.3%, respectively) than baseline (84.3%; P<0.001). In LSPAF patients who underwent HC (n=38), AADs use was 29.0% through 18 months follow-up versus 71.1% at baseline (P<0.001). Conclusions: HC reduced AF symptoms, significantly improved QOL, and reduced AAD use in patients with PersAF and LSPAF. ClinicalTrialsgov Identifier: NCT01984346.

Differences and trends in stroke prevention anticoagulation in primary care vs cardiology specialty management of new atrial fibrillation: The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study.

BACKGROUND: Atrial fibrillation and flutter (AF, collectively) cause stroke. We evaluated whether treating specialty influences warfarin prescription in patients with newly diagnosed AF. METHODS: In the TREAT-AF study, we used Veterans Health Administration health record and claims data to identify patients with newly diagnosed AF between October 2004 and November 2008 and at least 1 internal medicine/primary care or cardiology outpatient encounter within 90 days after diagnosis. The primary outcome was prescription of warfarin. RESULTS: In 141,642 patients meeting the inclusion criteria, the mean age was 72.3 ± 10.2 years, 1.48% were women, and 25.8% had cardiology outpatient care. Cardiology-treated patients had more comorbidities and higher mean CHADS2 scores (1.8 vs 1.6, P < .0001). Warfarin use was higher in cardiology-treated vs primary care only-treated patients (68.6% vs 48.9%, P < .0001). After covariate and site-level adjustment, cardiology care was significantly associated with warfarin use (odds ratio [OR] 2.05, 95% CI 1.99-2.11). These findings were consistent across a series of adjusted models (OR 2.05-2.20), propensity matching (OR 1.98), and subgroup analyses (OR 1.58-2.11). Warfarin use in primary-care-only patients declined from 2004 to 2008 (51.6%-44.0%, P < .0001), whereas the adjusted odds of warfarin receipt with cardiology care (vs primary care) increased from 2004 to 2008 (1.88-2.24, P < .0001). CONCLUSION: In patients with newly diagnosed AF, we found large differences in anticoagulation use by treating specialty. A divergent 5-year trend of risk-adjusted warfarin use was observed. Treating specialty influences stroke prevention care and may impact clinical outcomes.

Quantifying Amide-Aromatic Interactions at Molecular and Atomic Levels: Experimentally-determined Enthalpic and Entropic Contributions to Interactions of Amide sp 2 O, N, C and sp 3 C Unified Atoms with Naphthalene sp 2 C Atoms in Water.

In addition to amide hydrogen bonds and the hydrophobic effect, interactions involving π-bonded sp 2 atoms of amides, aromatics and other groups occur in protein self-assembly processes including folding, oligomerization and condensate formation. These interactions also occur in aqueous solutions of amide and aromatic compounds, where they can be quantified. Previous analysis of thermodynamic coefficients quantifying net-favorable interactions of amide compounds with other amides and aromatics revealed that interactions of amide sp 2 O with amide sp 2 N unified atoms (presumably C=O···H-N hydrogen bonds) and amide/aromatic sp 2 C (lone pair-π, n-π * ) are particularly favorable. Sp 3 C-sp 3 C (hydrophobic), sp 3 C-sp 2 C (hydrophobic, CH-π), sp 2 C-sp 2 C (hydrophobic, π-π) and sp 3 C-sp 2 N interactions are favorable, sp 2 C-sp 2 N interactions are neutral, while sp 2 O-sp 2 O and sp 2 N-sp 2 N self-interactions and sp 2 O-sp 3 C interactions are unfavorable. Here, from determinations of favorable effects of fourteen amides on naphthalene solubility at 10, 25 and 45 °C, we dissect amide-aromatic interaction free energies into enthalpic and entropic contributions and find these vary systematically with amide composition. Analysis of these results yields enthalpic and entropic contributions to intrinsic strengths of interactions of amide sp 2 O, sp 2 N, sp 2 C and sp 3 C unified atoms with aromatic sp 2 C atoms. For each interaction, enthalpic and entropic contributions have the same sign and are much larger in magnitude than the interaction free energy itself. The amide sp 2 O-aromatic sp 2 C interaction is enthalpy-driven and entropically unfavorable, consistent with direct chemical interaction (e.g. lone pair-π) while amide sp 3 C- and sp 2 C-aromatic sp 2 C interactions are entropy-driven and enthalpically unfavorable, consistent with hydrophobic effects. These findings are relevant for interactions involving π-bonded sp 2 atoms in protein processes.

Hybrid epicardial-endocardial ablation for long-standing persistent atrial fibrillation: A subanalysis of the CONVERGE Trial.

Background: Favorable clinical outcomes are difficult to achieve in long-standing persistent atrial fibrillation (LSPAF) with catheter ablation (CA). The CONVERGE (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent Atrial FIbrillation) trial evaluated the effectiveness of hybrid convergent (HC) ablation vs endocardial CA. Objective: The study sought to evaluate the safety and effectiveness of HC vs CA in the LSPAF subgroup from the CONVERGE trial. Methods: The CONVERGE trial was a prospective, multicenter, randomized trial that enrolled 153 patients at 27 sites. A post hoc analysis was performed on LSPAF patients. The primary effectiveness was freedom from atrial arrhythmias off new or increased dose of previously failed or intolerant antiarrhythmic drugs (AADs) through 12 months. The primary safety endpoint was major adverse event incidence through 30 days with HC. Key secondary effectiveness measures included (1) percent of patients achieving ≥90% AF burden reduction vs baseline and (2) AF freedom. Results: Sixty-five patients (42.5% of total enrollment) had LSPAF; 38 in HC and 27 in CA. Primary effectiveness was 65.8% (95% confidence interval [CI] 50.7%-80.9%) with HC vs 37.0% (95% CI 5.1%-52.4%) with CA (P = .022). Through 18 months, these rates were 60.5% (95% CI 50.0%-76.1%) with HC vs 25.9% (95% CI 9.4%-42.5%) with CA (P = .006). Secondary effectiveness rates were higher than CA with HC at 12 and 18 months. Freedom from atrial arrhythmias off AADs was 52.6% (95% CI 36.8%-68.5%) and 47.4% (95% CI 31.5%-63.2%) with HC at 12 and 18 months vs 25.9% (95% CI 9.4%-42.5%) and 22.2% (95% CI 6.5%-37.9%) with CA, respectively (12 months: P = .031; 18 months: P = .038). Three (7.9%) major adverse events occurred within 30 days of HC. Conclusion: Post hoc analysis demonstrated effectiveness and acceptable safety of HC compared with CA in LSPAF.

Batokines: Mediators of Inter-Tissue Communication (a Mini-Review).

PURPOSE OF REVIEW: This review highlights aspects of brown adipose tissue (BAT) communication with other organ systems and how BAT-to-tissue cross-talk could help elucidate future obesity treatments. RECENT FINDINGS: Until recently, research on BAT has focused mainly on its thermogenic activity. New research has identified an endocrine/paracrine function of BAT and determined that many BAT-derived molecules, termed "batokines," affect the physiology of a variety of organ systems and cell types. Batokines encompass a variety of signaling molecules including peptides, metabolites, lipids, or microRNAs. Recent studies have noted significant effects of batokines on physiology as it relates whole-body metabolism and cardiac function. This review will discuss batokines and other BAT processes that affect the liver, cardiovascular system, skeletal muscle, immune cells, and brown and white adipose tissue. Brown adipose tissue has a crucial secretory function that plays a key role in systemic physiology.

Acid-Sensing Ion Channel 2: Function and Modulation.

Acid-sensing ion channels (ASICs) have an important influence on human physiology and pathology. They are members of the degenerin/epithelial sodium channel family. Four genes encode at least six subunits, which combine to form a variety of homotrimers and heterotrimers. Of these, ASIC1a homotrimers and ASIC1a/2 heterotrimers are most widely expressed in the central nervous system (CNS). Investigations into the function of ASIC1a in the CNS have revealed a wealth of information, culminating in multiple contemporary reviews. The lesser-studied ASIC2 subunits are in need of examination. This review will focus on ASIC2 in health and disease, with discussions of its role in modulating ASIC function, synaptic targeting, cardiovascular responses, and pharmacology, while exploring evidence of its influence in pathologies such as ischemic brain injury, multiple sclerosis, epilepsy, migraines, drug addiction, etc. This information substantiates the ASIC2 protein as a potential therapeutic target for various neurological, psychological, and cerebrovascular diseases.