Estradiol regulates responsiveness of the dorsal premammillary nucleus of the hypothalamus and affects fear‐ and anxiety‐like behaviors in female rats

Research suggests a causal link between estrogens and mood. Here, we began by examining the effects of estradiol (E₂) on rat innate and conditioned defensive behaviors in response to cat odor. Second, we utilized whole‐cell patch clamp electrophysiological techniques to assess noradrenergic effects on neurons within the dorsal premammillary nucleus of the hypothalamus (PMd), a nucleus implicated in fear reactivity, and their regulation by E₂. Our results show that E₂ increased general arousal and modified innate defensive reactivity to cat odor. When ovariectomized females treated with E₂ as opposed to oil were exposed to cat odor, they showed elevations in risk assessment and reductions in freezing, indicating a shift from passive to active coping. In addition, animals previously exposed to cat odor showed clear cue + context conditioning 24 h later. However, although E₂ persisted in its effects on general arousal in the conditioning task, its effects on fear disappeared. In the patch clamp experiments noradrenergic compounds that typically induce fear clearly excited PMd neurons, producing depolarizations and action potentials. E₂ treatment shifted some excitatory effects of noradrenergic agonists to inhibitory, possibly by differentially affecting α‐ and β‐adrenoreceptors. In summary, our results implicate E₂ in general arousal and fear reactivity, and suggest these may be governed by changes in noradrenergic responsivity in the PMd. These effects of E₂ may have ethological relevance, serving to promote mate seeking even in contexts of ambiguous threat and shed light on the involvement of estrogen in mood and its associated disorders.     

The True Incidence of Gastric GIST—a Study Based on Morbidly Obese Patients Undergoing Sleeve Gastrectomy

Background

Gastrointestinal stromal tumor (GIST) is a rare neoplasm of the alimentary tract. Previous reports described an incidence of 1 per 100,000. Laparoscopic sleeve gastrectomy (LSG) provides pathological specimens of the majority of the stomach. We examined the pathology from LSG and the incidence and location of GIST. The aim of this study was to study the incidence of asymptomatic GISTs found during LSG at our institution.

Methods

A search was conducted in a prospectively maintained bariatric registry. Data collected included the following: gender, age, body mass index (BMI), and concomitant hypertension or diabetes mellitus. Histopathology reports were reviewed for incidental GIST. We compared the patients with incidental GIST to the rest of the cohort.

Results

Pathology reports of 827 patients that underwent LSG between 2007 and 2014 were reviewed. Five patients had GIST in the resected stomach, an incidence of 0.6 %. The group of patients with GIST had lower BMI and older age compared to the remaining 822 patients. All tumors were located close to the lesser curvature.

Conclusions

The incidence of GIST found in this cohort is significantly higher than previously reported. This may be due to an association between these tumors and obesity or because asymptomatic GISTs are underdiagnosed in the general population. These tumors are particularly common in older patients and special attention must be given when performing LSG on this subpopulation. The stomach should be inspected thoroughly before resection. A tumor on the lesser curvature may necessitate changing the surgical plan or aborting the procedure.     

Outcomes and Predictors of Reintervention in Patients With Pulmonary Atresia and Intact Ventricular Septum Treated With Radiofrequency Perforation and Balloon Pulmonary Valvuloplasty

Radiofrequency perforation and valvuloplasty (RFV) is an effective initial treatment in patients with pulmonary atresia and intact ventricular septum (PA-IVS) and mild to moderate right ventricle and tricuspid valve hypoplasia. Outcomes and risk factors for the need for additional interventions in these patients are poorly defined. All patients with PA-IVS who underwent RFV at our center between January 2000 and July 2011 were reviewed. Twenty-three patients met the inclusion criteria. All patients underwent successful valvuloplasty with no procedural deaths and one major complication. Excluding two patients with limited follow-up, 6 (29 %) patients underwent no subsequent interventions, whereas 9 (42 %) patients underwent surgical right-ventricular outflow tract augmentation. All except one patient with adequate follow-up have a biventricular circulation with saturation >92 %. Patients who did not undergo any right-ventricular outflow tract intervention after valvuloplasty had a significantly lower gradient across the pulmonary valve after valvuloplasty (9.9 mmHg ± 8.4 vs. 19.1 mmHg ± 10.4, p = 0.05). Significantly more patients who received a supplemental source of pulmonary blood flow had a tricuspid valve z-score <?0.7 compared with patients who did not receive supplemental blood flow [2 (15 %) vs. 7 (70 %), p = 0.008]. In our cohort of patients with PA-IVS, radiofrequency perforation with valvuloplasty was an effective and safe first step in establishing a biventricular circulation. Postvalvuloplasty pulmonary valve gradient may be predictive of subsequent outflow tract intervention, and tricuspid hypoplasia may be predictive of the need for a supplemental source of pulmonary blood flow.     

Patient Radiation Exposure in a Modern,Large-Volume,Pediatric Cardiac Catheterization Laboratory

Radiation exposure from pediatric cardiac catheterization may be substantial, although published estimates vary. We sought to report patient radiation dose across a range of diagnostic and interventional cases in a modern, high-volume pediatric catheterization laboratory. We retrospectively reviewed diagnostic and interventional cases performed in our pediatric catheterization laboratory from 1 April 2009 to 30 September 2011 for which radiation usage data were available as reported by the Artis Zee^® (Siemens Medical Solutions) system. Electrophysiology cases were excluded. Radiation dose was quantified as air kerma dose (mGy) and dose-area product (DAP; μGy m²). The DAP was converted to an effective dose millisievert (mSv) using the Monte Carlo method. Radiation usage data were available from 2,265 diagnostic and interventional cases with an overall median air kerma dose of 135 mGy [interquartile range (IQR) 59–433], median DAP of 760 μGy m² (IQR 281–2,810), of which 75 % (IQR 59–90 %) was derived from fluoroscopy, and median effective dose of 6.2 mSv (IQR 2.7–14.1). Air kerma dose from a single camera >2,000 mGy occurred in 1.8 % of cases. Significant differences in all measures of radiation exposure existed based on procedural and interventional types (p = 0.0001), with interventional cases associated with the highest effective dose after adjusting for patient weight category (p < 0.001). Patient weight, age, fluoroscopy time, and proportional use of digital acquisition were independent predictors of exposure (p ≤ 0.001; R ² = 0.59–0.64). In a modern, large-volume pediatric catheterization laboratory, the median effective dose is 6.2 mSv with a wide range of exposure based on patient- and procedure-specific factors. Radiation monitoring is an important component of a pediatric laboratory and further dose reduction strategies are warranted.     

Characterization of TEM-1 β-Lactamase-Producing Kingella kingae Clinical Isolates

Kingella kingae is a human pathogen that causes pediatric osteoarticular infections and infective endocarditis in children and adults. The bacterium is usually susceptible to β-lactam antibiotics, although β-lactam resistance has been reported in rare isolates. This study was conducted to identify β-lactam-resistant strains and to characterize the resistance mechanism. Screening of a set of 90 K. kingae clinical isolates obtained from different geographic locations revealed high-level resistance to penicillins among 25% of the strains isolated from Minnesota and Iceland. These strains produced TEM-1 β-lactamase and were shown to contain additional ≥50-kb plasmids. Ion Torrent sequencing of extrachromosomal DNA from a β-lactamase-producing strain confirmed the plasmid location of the bla_TEM gene. An identical plasmid pattern was demonstrated by multiplex PCR in all β-lactamase producers. The porin gene''s fragments were analyzed to investigate the relatedness of bacterial strains. Phylogenetic analysis revealed 27 single-nucleotide polymorphisms (SNPs) in the por gene fragment, resulting in two major clusters with 11 allele types forming bacterial-strain subclusters. β-Lactamase producers were grouped together based on por genotyping. Our results suggest that the β-lactamase-producing strains likely originate from a single plasmid-bearing K. kingae isolate that traveled from Europe to the United States, or vice versa. This study highlights the prevalence of penicillin resistance among K. kingae strains in some regions and emphasizes the importance of surveillance for antibiotic resistance of the pathogen.