A Basomedial Amygdala to Intercalated Cells Microcircuit Expressing PACAP and Its Receptor PAC1 Regulates Contextual Fear

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state.SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.     

Successful use of azithromycin for Escherichia coli–associated renal allograft malakoplakia: a report of two cases

European Journal of Clinical Microbiology & Infectious Diseases - Malakoplakia is a chronic granulomatous disease associated with incomplete clearance of bacterial pathogens. A multimodal...     

Negative workplace behavior and coping strategies among nurses: A cross‐sectional study

Negative workplace behavior affecting nurses is an internationally recognized problem. This study examines the types and extent of negative workplace behavior experienced by nurses in non‐metropolitan, regional acute care settings and their ways of coping when subject to that behavior. A cross‐sectional study was conducted involving 74 nurse participants in four regional hospitals in Australia. The structured questionnaire consisted of four parts: demographic questions, the Negative Acts Questionnaire – Revised, questions on exposure to bullying and/or incivility and policy awareness and use of pathways, and the Ways of Coping Questionnaire. Overall, 34% of participants were exposed to bullying and 49% to incivility over the previous month. The most common type of negative workplace behavior reported was “work‐related bullying,” which included exposure to excessive workloads, unrealistic deadlines, and information being withheld. Nurses reported the use of a variety of coping mechanisms, including problem‐focused coping strategies and seeking social support. The findings imply that negative workplace behaviors occur not only at individual nurses? level but also derive from the broader contexts of organizational management and systemic factors.     

Comparison of catheter tip migration using flexible and stimulating catheters inserted into the adductor canal in a cadaver model

Use of adductor canal blocks and catheters for perioperative pain management following total knee arthroplasty is becoming increasingly common. However, the optimal equipment, timing of catheter insertion, and catheter dislodgement rate remain unknown. A previous study has suggested, but not proven, that non-tunneled stimulating catheters may be at increased risk for catheter migration and dislodgement after knee manipulation. We designed this follow-up study to directly compare tip migration of two catheter types after knee range of motion exercises. In a male unembalmed human cadaver, 30 catheter insertion trials were randomly assigned to one of two catheter types: flexible or stimulating. All catheters were inserted using an ultrasound-guided short-axis in-plane technique. Intraoperative knee manipulation similar to that performed during surgery was simulated by five sequential range of motion exercises. A blinded regional anesthesiologist performed caliper measurements on the ultrasound images before and after exercise. Changes in catheter tip to nerve distance (p = 0.547) and catheter length within the adductor canal (p = 0.498) were not different between groups. Therefore, catheter type may not affect the risk of catheter tip migration when placed prior to knee arthroplasty.     

Prevalence of pertussis antibodies in maternal delivery, cord, and infant serum

BACKGROUND: Passively acquired maternal antibodies protect infants from many pathogens. With increasing reports of infant pertussis, we evaluated pertussis antibodies in maternal-infant paired sera from 1999-2000. METHODS: Antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), and fimbrial proteins (FIM) were measured by validated IgG-specific enzyme-linked immunosorbant assay (ELISA) in 64 maternal-umbilical cord serum pairs and in 61 of 64 infant sera. Geometric mean concentrations (GMCs) of pertussis antibodies and cord : maternal GMC ratios were calculated. RESULTS: Mean maternal age and gestation were 29.7 years (range, 19-42) and 39.3 weeks (range, 35.6-40.9), and 81% of mothers were white. GMCs of maternal antibodies at delivery (ELISA units/mL) were 2.4 for PT, 6.9 for FHA, and 13 for FIM. Cord GMCs were 169%, 178%, and 157% of maternal delivery values for PT, FHA, and FIM, respectively, demonstrating active placental transfer (P<.001). Pertussis-specific IgG values for each antigen decayed to below the threshold of detection by age 2 months. CONCLUSIONS: Despite efficient placental transfer, low maternal pertussis antibody levels and their rapid decay in infant sera leave infants with little humoral protection against pertussis. These data support the rationale for maternal or neonatal immunization, with acellular pertussis vaccines, to prevent life-threatening pertussis in early infancy.