TAC3/TACR3 System Function in the Catadromous Migration Teleost, .

2022

848808

07/2022

1664-2392

Neurokinin B (NKB), a member of the tachykinin (TAC) family, plays important roles in mammalian neuropeptide secretion in related to reproduction. However, its potential role in spawning migration teleost is less clear. In the present study, Japanese eel () was employed to study the performance of NKB in regulating reproduction. Results showed that two and one genes were identified in Japanese eel. Sequence analysis showed that two transcripts, and , encode four NKBs: NKBa-13, NKBa-10, NKBb-13, and NKBb-10. However, compared with other species, a mutation caused early termination of TACR3 protein was confirmed, leading to the loss of the 35 amino acid (aa) C-terminal of the receptor. Expression analysis in different tissues showed that both and mRNAs were highly expressed in the brain. hybridization localized both and mRNAs to several brain regions, mainly in the telencephalon and hypothalamus. Because of the mutation in TACR3 of Japanese eel, we further analyzed whether it could activate the downstream signaling pathway. Luciferase assay results showed the negative regulation of cAMP Response Element (CRE) and Sterol Response Element (SRE) signal pathways by Japanese eel NKBs. Intraperitoneal injection of four different NKB mature peptides at 100 ng/g had negative effect on either or gene expression. However, the high concentration of NKBa-10 and NKBb-13 (1,000 ng/g) upregulated and or expression level significantly, which may be mediated by other receptors. In general, the NKBs/NK3Rs system has important functions in regulating eel puberty onset.

10.3389/fendo.2022.848808

Front Endocrinol (Lausanne)

35937808

Teaching mode of oral English in the age of artificial intelligence.

2022

953482

07/2022

1664-1078

With the deepening of cultural integration, people's demand for English learning is also increasing rapidly. However, traditional teaching methods have certain limitations, and teaching conditions are limited by the slow development of information technology, oral English courses have been shelved and stopped for a long time. With the rapid development of technology, the era of artificial intelligence has arrived. Learning assistance systems based on artificial intelligence have emerged in an endless stream, which has also innovatively solved the problem of oral language learning. Natural language processing is a computing mode of deep learning by artificial intelligence, which can carry out deep learning and training according to the current goal and finally get the desired result. But relying only on the auxiliary learning system cannot fundamentally solve the problem of oral language learning. Therefore, we aim to update the current spoken English learning methods using natural language processing technology, and propose a natural language processing-based oral English teaching model. In this mode, natural language processing can match different teaching methods according to the spoken language characteristics of different students, and give constructive suggestions. Moreover, the spoken English teaching mode based on natural language processing can be continuously upgraded and adjusted to adapt to the changing and developing era in time. Experiments show that the oral English teaching mode based on natural language processing can improve students' comprehensive ability of oral English. And it increased its comprehension by 19.7% year-on-year, and at the same time it also improved the enthusiasm for learning oral language by 33.3%.

10.3389/fpsyg.2022.953482

Front Psychol

35936279

Model-Informed Drug Development of New Cefoperazone Sodium and Sulbactam Sodium Combination (3:1): Pharmacokinetic/Pharmacodynamic Analysis and Antibacterial Efficacy Against Enterobacteriaceae.

2022

856792

07/2022

1663-9812

Cefoperazone/sulbactam is a commonly used antibiotic combination against the extended-spectrum beta-lactamases (ESBLs)-producing bacteria. The objective of this study was to evaluate the efficacy of a new cefoperazone/sulbactam combination (3:1) for Enterobacteriaceae infection via model-informed drug development (MIDD) approaches. Sulperazon [cefoperazone/sulbactam (2:1)] was used as a control. Pharmacokinetic (PK) data was collected from a clinical phase I trial. Minimum inhibitory concentrations (MICs) were determined using two-fold broth microdilution method. The percent time that the free drug concentration exceeded the minimum inhibitory concentration (%T) was used as the pharmacokinetic/pharmacodynamic indicator correlated with efficacy. Models were developed to characterize the PK profile of cefoperazone and sulbactam. Monte Carlo simulations were employed to determine the investigational regimens of cefoperazone/sulbactam (3:1) for the treatment of infections caused by Enterobacteriaceae based on the probability of target attainment (PTA) against the tested bacteria. Two 2-compartment models were developed to describe the PK profiles of cefoperazone and sulbactam. Simulation results following the single-dose showed that the regimens of cefoperazone/sulbactam combinations in the ratios of 3:1 and 2:1 achieved similar PTA against the tested bacteria. Simulation results from the multiple-dose showed that the dosing regimen of cefoperazone/sulbactam (4 g, TID, 3 g:1 g) showed slightly better antibacterial effect than cefoperazone/sulbactam (6 g, BID, 4 g:2 g) against the (ESBL) and (ESBL). For the other tested bacteria, the above regimens achieved a similar PTA. Cefoperazone/sulbactam (3:1) showed similar bactericidal activity to sulperazon [cefoperazone/sulbactam (2:1)] against the tested bacteria. For the ESBL-producing and cefoperazone-resistant and , Cefoperazone/sulbactam (3:1) did not exhibit advantage as anticipated. Our study indicated that further clinical trials should be carried out cautiously to avoid the potential risks of not achieving the expected target.

10.3389/fphar.2022.856792

Front Pharmacol

35924047

Model-Informed Drug Development of New Cefoperazone Sodium and Sulbactam Sodium Combination (3:1): Pharmacokinetic/Pharmacodynamic Analysis and Antibacterial Efficacy Against Enterobacteriaceae.

2022

856792

07/2022

1663-9812

Cefoperazone/sulbactam is a commonly used antibiotic combination against the extended-spectrum beta-lactamases (ESBLs)-producing bacteria. The objective of this study was to evaluate the efficacy of a new cefoperazone/sulbactam combination (3:1) for Enterobacteriaceae infection via model-informed drug development (MIDD) approaches. Sulperazon [cefoperazone/sulbactam (2:1)] was used as a control. Pharmacokinetic (PK) data was collected from a clinical phase I trial. Minimum inhibitory concentrations (MICs) were determined using two-fold broth microdilution method. The percent time that the free drug concentration exceeded the minimum inhibitory concentration (%T) was used as the pharmacokinetic/pharmacodynamic indicator correlated with efficacy. Models were developed to characterize the PK profile of cefoperazone and sulbactam. Monte Carlo simulations were employed to determine the investigational regimens of cefoperazone/sulbactam (3:1) for the treatment of infections caused by Enterobacteriaceae based on the probability of target attainment (PTA) against the tested bacteria. Two 2-compartment models were developed to describe the PK profiles of cefoperazone and sulbactam. Simulation results following the single-dose showed that the regimens of cefoperazone/sulbactam combinations in the ratios of 3:1 and 2:1 achieved similar PTA against the tested bacteria. Simulation results from the multiple-dose showed that the dosing regimen of cefoperazone/sulbactam (4 g, TID, 3 g:1 g) showed slightly better antibacterial effect than cefoperazone/sulbactam (6 g, BID, 4 g:2 g) against the (ESBL) and (ESBL). For the other tested bacteria, the above regimens achieved a similar PTA. Cefoperazone/sulbactam (3:1) showed similar bactericidal activity to sulperazon [cefoperazone/sulbactam (2:1)] against the tested bacteria. For the ESBL-producing and cefoperazone-resistant and , Cefoperazone/sulbactam (3:1) did not exhibit advantage as anticipated. Our study indicated that further clinical trials should be carried out cautiously to avoid the potential risks of not achieving the expected target.

10.3389/fphar.2022.856792

Front Pharmacol

35924047

A Comparation Between Frame-Based and Robot-Assisted in Stereotactic Biopsy.

2022

928070

07/2022

1664-2295

Introduction: Frame-based stereotactic biopsy is well-established to play an essential role in neurosurgery. In recent years, different robotic devices have been introduced in neurosurgery centers. This study aimed to compare the SINO surgical robot-assisted frameless brain biopsy with standard frame-based stereotactic biopsy in terms of efficacy, accuracy and complications.

Methods: A retrospective analysis was performed on 151 consecutive patients who underwent stereotactic biopsy at Chongqing Sanbo Jiangling Hospital between August 2017 and December 2021. All patients were divided into the frame-based group ( = 47) and the SINO surgical robot-assisted group ( = 104). The data collected included clinical characteristics, diagnostic yield, operation times, accuracy, and postoperative complications.

Results: There was no significant difference in diagnostic yield between the frame-based group and the SINO surgical robot-assisted group (95.74 vs. 98.08%, > 0.05). The mean operation time in the SINO surgical robot-assisted group was significantly shorter than in the frame-based group (29.36 ± 13.64 vs. 50.57 ± 41.08 min). The entry point error in the frame-based group was significantly higher than in the robot-assisted group [1.33 ± 0.40 mm (0.47-2.30) vs. 0.92 ± 0.27 mm (0.35-1.65), < 0.001]. The target point error in the frame-based group was also significantly higher than in the robot-assisted group [1.63 ± 0.41 mm (0.74-2.65) vs. 1.10 ± 0.30 mm (0.69-2.03), < 0.001]. Finally, there was no significant difference in postoperative complications between the two groups.

Conclusion: Robot-assisted brain biopsy becomes an increasingly mainstream tool in the neurosurgical procedure. The SINO surgical robot-assisted platform is as efficient, accurate and safe as standard frame-based stereotactic biopsy and provides a reasonable alternative to stereotactic biopsy in neurosurgery.

10.3389/fneur.2022.928070

Front Neurol

35923834

Randomized Control Study on Hemoperfusion Combined with Hemodialysis versus Standard Hemodialysis: Effects on Middle-Molecular-Weight Toxins and Uremic Pruritus.

2022

1-11

08/2022

1421-9735

INTRODUCTION: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients.

METHODS: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (β2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of β2M and PTH, while the secondary outcome was the reduction of the pruritus score.

RESULTS: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of β2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively.

CONCLUSION: The long-term HP + HD can reduce β2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

10.1159/000525225

Blood Purif

35952629

miR-124 regulates early isolation-induced social abnormalities via inhibiting myelinogenesis in the medial prefrontal cortex.

2022

507

09/2022

1420-9071

Patients with autism spectrum disorder (ASD) typically experience substantial social isolation, which may cause secondary adverse effects on their brain development. miR-124 is the most abundant miRNA in the human brain, acting as a pivotal molecule regulating neuronal fate determination. Alterations of miR-124 maturation or expression are observed in various neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. In the present study, we analyzed a panel of brain-enriched microRNAs in serums from 2 to 6 year old boys diagnosed with ASD. The hsa-miR-124 level was found significantly elevated in ASD boys than in age and sex-matched healthy controls. In an isolation-reared weanling mouse model, we evidenced elevated mmu-miR-124 level in the serum and the medial prefrontal cortex (mPFC). These mice displayed significant sociability deficits, as well as myelin abnormality in the mPFC, which was partially rescued by expressing the miR-124 sponge in the bilateral mPFC, ubiquitously or specifically in oligodendroglia. In cultured mouse oligodendrocyte precursor cells, introducing a synthetic mmu-miR-124 inhibited the differentiation process through suppressing expression of nuclear receptor subfamily 4 group A member 1 (Nr4a1). Overexpressing Nr4a1 in the bilateral mPFC also corrected the social behavioral deficits and myelin impairments in the isolation-reared mice. This study revealed an unanticipated role of the miR-124/Nr4a1 signaling in regulating early social experience-dependent mPFC myelination, which may serve as a potential therapy target for social neglect or social isolation-related neuropsychiatric disorders.

10.1007/s00018-022-04533-6

Cell Mol Life Sci

36059036

Factors Associated With Penicillin Allergy Labels in Electronic Health Records of Children in 2 Large US Pediatric Primary Care Networks.

2022

e222117

2022 Mar 01

2574-3805

<p><strong>Importance: </strong>Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking.</p>

<p><strong>Objective: </strong>To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks.</p>

<p><strong>Design, Setting, and Participants: </strong>This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, Texas, Philadelphia, Pennsylvania, and parts of New Jersey. Participants were children born between January 2010 and June 2020 who had a health care visit in the first 14 days of life and at least 2 additional visits in the first year of life at one of 90 primary care pediatric practices. Censoring criteria were additionally applied to exclude data from children no longer seeking health care in the 90 clinics over time. Statistical analysis was performed from February to May 2021.</p>

<p><strong>Exposures: </strong>Basic patient demographics, health care utilization, penicillin exposure, and primary clinic location.</p>

<p><strong>Main Outcomes and Measures: </strong>Addition of penicillin allergy label in the electronic medical record.</p>

<p><strong>Results: </strong>Among 334 465 children in the birth cohort, 164 173 (49.1%) were female; 72 831 (21.8%) were Hispanic, 59 598 (17.8%) were non-Hispanic Black, and 148 534 (44.4%) were non-Hispanic White; the median (IQR) age at censoring was 3.8 (1.7-6.6) years; 18 015 (5.4%) were labeled as penicillin allergic, but the prevalence of penicillin allergy labeling ranged from 0.9% to 10.2% across practices. Children were labeled at a median (IQR) age of 1.3 (0.9-2.3) years. Non-Hispanic White children were more likely to be labeled compared with non-Hispanic Black children after controlling for potential confounders (adjusted odds ratio, 1.7 [95% CI, 1.6-1.8]). There were 6797 allergic children (37.7%) labeled after receiving 1 penicillin prescription and 1423 (7.9%) labeled after receiving 0 penicillin prescriptions.</p>

<p><strong>Conclusions and Relevance: </strong>In this cohort study of more than 330 000 children, penicillin allergy labeling was common and varied widely across practices. Children were labeled early in life, and almost half were labeled after receiving 1 or 0 penicillin prescriptions. These findings raise questions regarding the validity of penicillin allergy labels. Future work exploring the fidelity of and outcomes associated with penicillin allergy-labeling in children is warranted.</p>

10.1001/jamanetworkopen.2022.2117

JAMA Netw Open

35285918

CMV infection and management among pediatric solid organ transplant recipients.

2022

e14220

2022 Jan 06

1399-3046

<p><strong>BACKGROUND: </strong>Cytomegalovirus (CMV) is an important cause of morbidity and mortality in pediatric solid organ transplant (SOT) recipients. However, the impact of asymptomatic CMV infections (ie, DNAemia) on clinical outcomes is not well established.</p>

<p><strong>METHODS: </strong>We performed a retrospective cohort study of children undergoing first SOT at our institution from January 2012 to June 2018. We evaluated the epidemiology of CMV infections and performed multivariable Cox regression to assess the association between CMV DNAemia without disease or CMV disease (syndrome or end-organ disease) on negative outcomes (death, re-transplantation, or moderate/severe rejection) within the first year after SOT.</p>

<p><strong>RESULTS: </strong>Among 271 individuals, 43 (15.9%) developed ≥1 CMV infection during the first year after SOT. There were 56 unique CMV infections including 14 episodes of CMV disease. In 167 patients offered CMV prophylaxis, only 8 (4.8%) developed their first CMV DNAemia episode while on prophylaxis 32 developed CMV DNAemia after prophylaxis completion; only 1 episode of CMV disease occurred while on antiviral prophylaxis. When accounting for receipt of ATG, oral steroids, and number of immunosuppressives on a given day, CMV disease was more strongly associated with negative outcomes (Hazard Ratio (HR): 3.28, 95% CI: 0.73-14.64; p&nbsp;=&nbsp;.12) than CMV DNAemia without disease (HR 1.42, 95% CI: 0.19- 10.79; p&nbsp;=&nbsp;.74), although not to a statistically significant degree.</p>

<p><strong>CONCLUSIONS: </strong>Most CMV infections occurred after completion of antiviral prophylaxis. CMV disease was more strongly associated with negative outcomes than asymptomatic CMV DNAemia and should be the focus of CMV prevention practices.</p>

10.1111/petr.14220

Pediatr Transplant

34994041

COVID-19 and Antibiotic Prescribing in Pediatric Primary Care.

2022

2022 02 01

1098-4275

<p><strong>BACKGROUND AND OBJECTIVES: </strong>With the onset of the coronavirus disease 2019 (COVID-19) pandemic, pediatric ambulatory encounter volume and antibiotic prescribing both decreased; however, the durability of these reductions in pediatric primary care in the United States has not been assessed.</p>

<p><strong>METHODS: </strong>We conducted a retrospective observational study to assess the impact of the COVID-19 pandemic and associated public health measures on antibiotic prescribing in 27 pediatric primary care practices. Encounters from January 1, 2018, through June 30, 2021, were included. The primary outcome was monthly antibiotic prescriptions per 1000 patients. Interrupted time series analysis was performed.</p>

<p><strong>RESULTS: </strong>There were 69 327 total antibiotic prescriptions from April through December in 2019 and 18 935 antibiotic prescriptions during the same months in 2020, a 72.7% reduction. The reduction in prescriptions at visits for respiratory tract infection (RTI) accounted for 87.3% of this decrease. Using interrupted time series analysis, overall antibiotic prescriptions decreased from 31.6 to 6.4 prescriptions per 1000 patients in April 2020 (difference of -25.2 prescriptions per 1000 patients; 95% CI: -32.9 to -17.5). This was followed by a nonsignificant monthly increase in antibiotic prescriptions, with prescribing beginning to rebound from April to June 2021. Encounter volume also immediately decreased, and while overall encounter volume quickly started to recover, RTI encounter volume returned more slowly.</p>

<p><strong>CONCLUSIONS: </strong>Reductions in antibiotic prescribing in pediatric primary care during the COVID-19 pandemic were sustained, only beginning to rise in 2021, primarily driven by reductions in RTI encounters. Reductions in viral RTI transmission likely played a substantial role in reduced RTI visits and antibiotic prescriptions.</p>

10.1542/peds.2021-053079

Pediatrics

35102416