A neuronal signature for monogamous reunion Scribner, Jennifer L.; Vance, Eric A.; Protter, David S. W. ...
Proceedings of the National Academy of Sciences - PNAS,
05/2020, Letnik:
117, Številka:
20
Journal Article
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Pair-bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using 1-photon in vivo Ca2+ imaging ...in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ activity. Instead, we identified distinct ensembles of neurons in this region that are recruited during approach to either a partner or a novel vole. The partner-approach neuronal ensemble increased in size following bond formation, and differences in the size of approach ensembles for partner and novel voles predict bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength, indicating that ensemble plasticity is specific to partner approach. Furthermore, the neurons comprising partner and novel-approach ensembles are nonoverlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner-approach ensemble and its expansion upon bond formation potentially make it a key neuronal substrate associated with bond formation and maturation.
Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a ...primate model of sepsis may provide a novel molecular signature of clinical sepsis.
To develop a biomarker panel to characterize sepsis in primates and ascertain its relevance to early diagnosis and progression of human sepsis.
Intravenous inoculation of Macaca fascicularis with Escherichia coli produced mild to severe sepsis, lung injury, and death. Plasma samples were obtained before and after 1, 3, and 5 days of E. coli challenge and at the time of killing. At necropsy, blood, lung, kidney, and spleen samples were collected. An integrative analysis of the metabolomic and transcriptomic datasets was performed to identify a panel of sepsis biomarkers.
The extent of E. coli invasion, respiratory distress, lethargy, and mortality was dependent on the bacterial dose. Metabolomic and transcriptomic changes characterized severe infections and death, and indicated impaired mitochondrial, peroxisomal, and liver functions. Analysis of the pulmonary transcriptome and plasma metabolome suggested impaired fatty acid catabolism regulated by peroxisome-proliferator activated receptor signaling. A representative four-metabolite model effectively diagnosed sepsis in primates (area under the curve, 0.966) and in two human sepsis cohorts (area under the curve, 0.78 and 0.82).
A model of sepsis based on reciprocal metabolomic and transcriptomic data was developed in primates and validated in two human patient cohorts. It is anticipated that the identified parameters will facilitate early diagnosis and management of sepsis.
Context: In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and ...safety has not been reported.
Objectives: The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size.
Design: This was a multicenter, open-label, 32-wk trial study.
Setting: The study was performed at outpatient clinics.
Patients: Fifty-three patients with acromegaly previously treated with octreotide long-acting release (LAR) participated in this study.
Intervention: Pegvisomant (10 mg/d) was initiated 4 wk after the last dose of octreotide LAR and was adjusted based on serum IGF-I concentrations at wk 12, 20, and 28.
Main Outcome Measures: The main outcome measures were changes in IGF-I, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, and safety during the first 12 wk after conversion.
Results: At the end of pegvisomant treatment, IGF-I was normalized in 78% of patients. At wk 32, median fasting glucose concentration and HbA1c were reduced (−1.4 mmol/liter and −0.4%, respectively; both P ≤ 0.0001) in the study population. Improvements in glycemic control occurred in patients with normal IGF-I concentrations at wk 4 n = 15; fasting glucose, −1.7 mmol/liter (P ≤ 0.0001); HbA1c −0.2% (P = 0.03). Decreases in fasting glucose and HbA1c levels were observed in patients with and without diabetes. HbA1c was reduced by more than 1.0% in patients with diabetes. Median pituitary tumor volume did not change, although tumor volume increased in two patients with macroadenomas.
Conclusions: Conversion from octreotide LAR to pegvisomant was safe and well tolerated. Improved glycemic control indicates that pegvisomant should be considered in patients with acromegaly and diabetes.
Abstract Background Rupture of the patellar tendon requires surgical repair to restore function of the knee. The most accepted repair technique utilizes running locking non-absorbable sutures secured ...to the patella through three drill holes. Complications with this repair technique include rerupture, knee stiffness, and extensor lag caused by gap formation at the site of repair. Some surgeons have suggested augmenting the standard repair with local autograft tendon to avoid these complications. It was hypothesized that using a repair technique that included augmentation of the repair with autograft tendons would decrease the gap formation at the repair site under cyclic loading conditions. Methods In this experiment, eight specimens were used to analyze two methods of patellar tendon repair: hamstrings autograft augmentation and a standard repair using three vertical bone tunnels in the patella. Each specimen was then extended with a 2.2 kg weight on the tibia at 0.25 Hz to simulate early motion after surgery. The gap formed at the repair site was then measured at 1, 10, 100, and 250 cycles and both techniques confidence interval compared using a Wilcoxon signed rank test. Findings The mean gap formation for the standard repair after one cycle was 8.9 mm (SD 2.4) and for the augmented repair was 3.6 mm (SD 0.9). At 250 cycles the mean gap formed for the standard repair was 13.2 mm (SD 1.9) and the mean gap for the augmented repair was 7.2 mm (SD 0.9). All gaps for all cycles analyzed had an 88% confidence interval for significance using a Wilcoxon signed rank test. Interpretation The biomechanical results of this study show statistical trend toward decrease gap formation with an augmented tendon at the repair site under a simulated dynamic knee motion.
Data were collected over two separate year-long test periods at the Net-Zero Energy Residential Test Facility, alaboratory designed to evaluate a variety of technologies and operational strategies ...that lead to energy efficient houses with comfortable and healthful indoor environments. In a net-zero energy building, all energy consumption over the course of a year is offset by on-site renewable energy production; this facility attempts to meet that goal through use of a photovoltaic array installed on the roof. Data are presented for one-year test periods over which the research team examined whether the facility would reach net-zero status. In both years, the house was operated in an all-electric configuration, with slight modifications made in the second year related to control schemes and equipment selection. A virtual family of four was simulated to carry out the operations that would typically occur in a home (e.g., appliance usage, lighting usage, hot water usage). Data are being released for the second year of operation at the time of publication of this document, with an expectation that data from the first year will be released at a later date.
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD ...is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Social media websites, such as YouTube, Facebook, MySpace, Twitter, and Second Life are rapidly emerging as popular sources of health information especially for teens and young adults. Social media ...marketing carries the advantages of low cost, rapid transmission through a wide community, and user interaction. Disadvantages include blind authorship, lack of source citation, and presentation of opinion as fact. Dermatologists and other health care providers should recognize the importance of social media websites and their potential usefulness for disseminating health information.
Acromegaly is a chronic debilitating disorder resulting from excessive secretion of growth hormone and a resulting increase in the production of insulin-like growth factor I (IGF-I). It is usually ...caused by somatotroph adenomas of the pituitary gland. The goal of treatment is to reverse the effects of the hypersecretion of growth hormone and normalize production of IGF-I. Effective treatment ameliorates the symptoms and signs of the disease and lowers the mortality rate.
The current treatments for acromegaly are surgical removal of the adenoma, radiation therapy, and drug treatment. Among patients treated surgically, only 60 percent of patients overall and less . . .
Abstract Thromboembolic cerebrovascular accident remains a rare but potentially devastating complication of catheter based atrial fibrillation (AF) ablation. Uninterrupted oral anticoagulant (OAC) ...therapy with warfarin has become the standard of care when performing catheter based AF ablation. Compared with warfarin, apixaban, a factor Xa inhibitor, has been shown to reduce the risk of stroke and major bleeding in non-valvular AF. With an increase in apixaban use for stroke prophylaxis in AF patients there is an increased interest in the safety and efficacy of uninterrupted apixaban therapy during AF ablation. We compared the safety and efficacy of uninterrupted OA therapy with either warfarin or apixaban in all patients who underwent catheter based AF ablation at the University of Alabama at Birmingham and at Augusta University Medical Center between January 7, 2013 and February 25, 2016. All patients underwent a transesophageal echocardiogram (TEE) on the day of their ablation to assess for the presence of intracardiac thrombi. All complications were identified and classified as bleeding, thromboembolic events, or other. A total of 627 patients were analyzed as described above. There were 310 patients in the warfarin group and 317 patients in the apixaban group. There were 8 complications in the warfarin group and 5 complications in the apixaban group (P = 0.38). There were no thromboembolic complications in either group. In conclusion, the use of apixaban is as safe and effective as warfarin for uninterrupted OA therapy during catheter based ablation of AF.
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